Psychotropic Monitoring Guidelines 2010 · Further monitoring as clinically indicated. Also see notes on the effect of antiepileptic drugs on bone. Therapeutic Drug Monitoring No

Psychotropic Monitoring

Guidelines

2010

Update prepared by: Rachel Brown, Clinical Lead Pharmacist, Medicines Information & Evidence Based Medicine Approved by: OBMH Drug & Therapeutics Committee 2010

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Contents Page Foreword and “using the guidelines”______________________________________________ 2 Table of psychotropic drugs - recommended monitoring, notes, and evidence:

Carbamazepine 3 Lamotrigine 4 Lithium 5 Valproate/valproic acid 7 SSRIs 8 MAOIs 10 TCAs 10 Agomelatine 10 Duloxetine 11 Mianserin 11 Mirtazapine 12 Reboxetine 12 Trazodone 12 Tryptophan 13 Venlafaxine 13 All antipsychotic drugs 14 Amisulpride 15 Aripiprazole 16 Clozapine 16 Olanzapine 17 Quetiapine 17 Risperidone 18 Typical antipsychotics (except haloperidol and pimozide –see separate entries) 19 Haloperidol (oral, IM and depot) 19 Pimozide 20 Acetylcholinesterase inhibitors 20 Memantine 21 Atomoxetine 21 Clonidine 23 Dexamfetamine 23 Methylphenidate 24

Appendix 1 Metabolic Management Guidelines & Weight Management Options 26 Appendix 2 General Psychotropic Medication Monitoring 28 Appendix 3 Antidepressant-induced hyponatraemia 29 Appendix 4 Serotonin syndrome 31 Appendix 5 Neuroleptic Malignant Syndrome 33 Appendix 6 Drug treatments for serotonin syndrome and neuroleptic malignant syndrome

(for hospital practitioners and for in-patients only) – for information only 34

Appendix 7 Hyperprolactinaemia guidelines 35 Appendix 8 Cardiovascular disease – assessing risk and recommendations for primary

prevention management (lipid modification) 38

Appendix 9 Abnormal glucose levels – recommendations for further monitoring 42 Appendix 10 Anorexia nervosa – cardiac complications and medication 46 Appendix 11 Side effect rating scales (GASS, LUNSERS) 47 Appendix 12 Oxfordshire PCT/OBMH Good practice monitoring guidelines for SMI patients 51

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Foreword These guidelines are an update to those previously developed in 2006. Their aim is to continue to provide evidence-based, pragmatic advice on the clinical parameters that should be monitored in order to ensure continued good physical health in patients with severe enduring mental illness. The guidelines are not intended to function as a prescriptive protocol for clinical care and clinical expertise should be used in their application. The update includes the latest advice from the MHRA, the CSM and the NPSA as well as monitoring recommendations from the most recent national guidelines (eg NICE). There remains a relative paucity of specific published data, so we have continued to use literature where pragmatic recommendations were stated or could be derived, as well as information from the manufacturer’s literature, where it was available, and from personal communication with company medical information departments when appropriate. This update also includes a number of additional appendices, including summaries of Trust guidance on the monitoring and management of patients with hyperprolactinaemia, hyperlipidaemia and diabetes. One appendix highlights the increased cardiac risk from medication used in patients with anorexia nervosa and another includes some side effect rating scales. These guidelines are not intended to be used in isolation, rather that they should be used adjunctively to a patient’s own familial history and individual risk factors and with the knowledge that patients with severe enduring mental illness are already at an increased risk for conditions such as diabetes and cardiovascular disorders. The guidelines are intended primarily for use within Oxfordshire & Buckinghamshire Mental Health Partnership NHS Foundation Trust. “Good Practice Monitoring Guidelines for SMI patients” are being developed for use by Primary Care that are based on these guidelines. Primary care has a large role to play in the continued treatment of patients with severe enduring mental illness, so we hope that these guidelines will be a useful tool for healthcare professionals working in the primary care sector to use in tandem with the “Good Practice Monitoring Guidelines”. Using the guidelines A section on “General Psychotropic Medication Monitoring” can be found in appendix 2 and includes a number of monitoring parameters that ideally apply to all psychotropic medicines. When a prescriber is considering which parameters to monitor, the recommendations made within appendix 2 should be considered in conjunction with the monitoring that is specifically recommended for each individual drug or group of drugs listed in the tables on the following pages. In addition, recommended guidelines for managing weight gain and metabolic side effects can be found in appendix 1 and, when it is appropriate, a referral is made from the individual drug in the tables to these guidelines.

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Drug

Recommended monitoring Notes Evidence

Carbamazepine Recommended according to risk: Baseline: • FBC including platelets • Renal function • LFTs • U&Es (particularly in the elderly [increased risk of

hyponatraemia]) • Pregnancy test Follow-up at 6 months: • FBC including platelets • LFTs • U&Es Then every 6 months • U&Es (particularly in the elderly) • Plasma level (see below) Further monitoring as clinically indicated. Also see notes on the effect of antiepileptic drugs on bone. Therapeutic Drug Monitoring No therapeutic levels have been established for use in psychiatry so plasma levels are of limited value in assessing efficacy, however they are recommended as a tool for checking compliance or toxicity. Therapeutic levels and toxic levels are close so it’s recommended that levels are measured every 6 months to exclude toxicity.

• LFTs/FBCs. Whilst the risk of altered LFTs and FBCs is greatest in the first few months of treatment monitoring is less important than continued clinical vigilance throughout treatment. Advise patients to report signs of liver dysfunction immediately.

• Infections & rashes. Advise patients to

report signs of infection, especially influenza-like illness, or rashes immediately.

• Suicidal risk. The CSM issued a warning in

2008 that antiepileptic treatment is associated with a small (rare) risk of suicidal thoughts and behaviour. They state that available data suggest that the increased risk applies to all antiepileptic drugs and is seen as early as 1 week after starting treatment. The CSM recommends the following: • Patients should be alert to any mood changes, distressing thoughts, or feelings about suicide or harming themselves at any point during treatment and should be advised to seek medical advice if they develop such thoughts or behaviour, and should be referred for appropriate treatment if necessary. A study published in 2009 aiming to determine whether antiepileptic drugs (AEDs) increase the risk of suicide attempts specifically in bipolar patients, relative to no AED or to lithium treatment, concluded that they do not. In addition the authors concluded that there may be a possible protective effect of AED on suicidality. One of the exceptions to this was with carbamazepine, where the rates of post-treatment suicide attempt were not significantly different to pre-treatment rates and they were higher than the no-treatment or lithium rates. However the author suggests that there is no evidence that carbamazepine increased the rate of suicide attempt.

Goodwin GM et al. Evidence-based guidelines for treating bipolar disorder: revised second edition – recommendations from the British Association of Psychopharmacology (BAP). Journal of Psychopharmacology 2009;23(4):346-388 Novartis Pharmaceuticals UK Ltd. Tegretol Summary of Product Characteristics. Date of most recent revision of the text: 11.2.09

National Institute for Health and Clinical Excellence. Bipolar Disorder – the management of bipolar disorder in adults, children and adolescents, primary and secondary care. NICE clinical guideline 38, July 2006

Drug safety advice: Antiepileptics: risk of suicidal thoughts and behaviour. Drug Safety Update 2008;2(1):2 (accessed online at http://www.mhra.gov.uk)

Gibbons RD, Hur K, Brown H & Mann JJ. Relationship between antiepileptic drugs and suicide attempts in patients with bipolar disorder. Arch Gen Psych 2009:66(12):1354-1360

Antiepileptics: adverse effects on bone Drug Safety Update: Volume 2 Issue 9, April 2009:2

http://www.mhra.gov.uk/

http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON043810&RevisionSelectionMethod=LatestReleased



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Drug


(Carbamazepine continued)

• Therapeutic Drug Monitoring. Where TDM levels are requested they should be taken immediately before a dose. Therapeutic levels are generally felt to be in the range 4-12 mg/L or 17-50 micromols/L

• Weight gain may occur during

carbamazepine treatment. If this becomes a problem refer to the Trust’s Weight Management Guideline.

• Antiepileptic effects on bone.

Carbamazepine is known to cause osteomalacia. Long term use is also associated with decreased bone mineral density that may lead to osteopenia, osteoporosis, and increased fractures in at-risk patients. The following patients are considered to be at risk: • those who are immobilised for long periods • those who have inadequate sun exposure • those with inadequate dietary calcium intake and Vitamin D supplementation should be considered for these patients. For patients with no renal impairment, Adcal-D3 2 tabs daily provides an appropriate amount of Vitamin D. If advice is required for prescribing in patients with renal impairment please contact: [email protected].

Lamotrigine There are no specific recommended monitoring parameters for lamotrigine however as with all of the psychotropic medicines the General Psychotropic Medication Monitoring (see appendix 2) should be considered.

Further monitoring as clinically indicated (see notes)

• Bone marrow failure. The CSM has advised prescribers to be alert for symptoms and signs suggestive of bone-marrow failure such as anaemia, bruising, or infection. Aplastic anaemia, bone-marrow depression and pancytopenia have been associated rarely with lamotrigine.

• Skin reactions. There have been reports of adverse skin reactions that have generally occurred within the first 8 weeks after initiation of lamotrigine. The majority of rashes are mild and self-limiting, however rarely, serious potentially life-threatening skin rashes

Evidence GlaxoSmithKline UK Lamictal. Summary of Product Characteristics, date of most recent revision of the text: 1/3/07 Personal communication with GlaxoSmithKline Medical Information Officer 4/2007 Drug safety advice: Antiepileptics: risk of suicidal thoughts and behaviour. Drug Safety Update 2008;2(1):2 (accessed online at:

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Drug


(Lamotrigine continued)

including Stevens Johnson Syndrome and Toxic Epidermal Necrolysis have been reported. Additionally the overall risk of rash appears to be strongly associated with: ⇒ High initial doses of lamotrigine and

escalating doses more quickly than advised in the product literature.

⇒ Concomitant use of valproic acid/valproate.


2008 that antiepileptic treatment is associated with a small (rare) risk of suicidal thoughts and behaviour. They state that available data suggest that the increased risk applies to all antiepileptic drugs and is seen as early as 1 week after starting treatment. The CSM recommends the following: • Patients should be alert to any mood changes, distressing thoughts, or feelings about suicide or harming themselves at any point during treatment and should be advised to seek medical advice if they develop such thoughts or behaviour, and should be referred for appropriate treatment if necessary. A study published in 2009 aiming to determine whether antiepileptic drugs (AEDs) increase the risk of suicide attempts specifically in bipolar patients, relative to no AED or to lithium treatment, concluded that they do not. In addition the authors concluded that there may be a possible protective effect of AED on suicidality.

http://www.mhra.gov.uk) Gibbons RD, Hur K, Brown H & Mann JJ. Relationship between antiepileptic drugs and suicide attempts in patients with bipolar disorder. Arch Gen Psych 2009:66(12):1354-1360

Lithium Recommended according to risk: Baseline: • Renal function tests (request eGFR) • Pregnancy test • TSH • Where practical a baseline ECG may be performed but it

should always be performed where there are known cardiac disease risk factors or other high risk medications and at annual intervals whilst on treatment

• Plasma levels - timing. Based on the pharmacokinetics of the controlled release product used in OBMH (Priadel®) an interval of five to seven days is felt to be more suitable than the BNF recommended four to seven days for taking a plasma level.

• Fluid balance. Plasma levels can be severely

affected by changes in fluid and salt intake.

Sanofi Aventis. Priadel Summary of Product Characteristics, date of most revision of the text: 27/1/09. Goodwin GM et al. Evidence-cased guidelines for treating bipolar disorder: revised second edition – recommendations from the British Association of Psychopharmacology


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Drug


(Lithium continued)

At 3 months: Repeat renal function tests (request eGFR) & TFTs. If tests are within normal parameters and the regimen is stable repeat these tests every 6 months.

Every 6 months: • Repeat renal function tests (request eGFR) & TFTs Dose Change: Perform renal function test (request eGFR) & TSH after 3 months. Therapeutic Drug Monitoring: All samples should be taken 12 hours post-dose (for twice daily dosing regimens withhold the morning dose until after the blood sample is taken). Take a plasma level five to seven days after initiation of treatment and following dose changes, then take weekly levels until the dosage has remained constant for four weeks. Once the routine is stable take levels every 3 months.

Patients should be advised accordingly particularly if travelling to hot countries where dehydration may be a risk.

• Target plasma levels. o For bipolar disorder aim for 0.6 – 0.8

mmol/L normally, or 0.8-1.0 if the patient has relapsed previously on lithium or has subsyndromal symptoms.

o For recurrent unipolar depression there is a lack of good evidence or consensus about what level to aim for. However, as a guide, aim for a minimum level of 0.5mmol/L. Some people may require higher levels in the range of 0.5-1.0mol/L. Assess lithium levels in conjunction with clinical response and tolerability and adjust the dose accordingly.

• Weight gain may occur during lithium

treatment. If this becomes a problem refer to the Trust’s Weight Management Guideline.

• Patient information. At the start of therapy

and throughout their treatment patients should receive appropriate ongoing verbal and written information and a record book to track lithium blood levels and clinical tests. It is particularly important that patients know the signs or symptoms of toxicity. Information and record books are produced by the NPSA and are available through pharmacy.

(BAP). Journal of Psychopharmacology 2009;23(4):346-388 Joint Formulary Committee. British National Formulary No 57. London: British Medical Association & Royal Pharmaceutical Society of Great Britain March 2009

National Institute for Health and Clinical Excellence. Bipolar Disorder – the management of bipolar disorder in adults, children and adolescents, primary and secondary care. NICE clinical guideline 38, July 2006 NICE CG90&92 Depression: treatment and management of depression in adults, including adults with a chronic physical health problem. October 2009 Price LH, Carpenter LL, Tyrka AR. Lithium augmentation for refractory depression: a critical reappraisal Primary Psychiatry 2008;15(11):35-42 Stein G.,Bernadt M. Lithium augmentation therapy in tricyclic-resistant depression - a controlled trial using lithium in low and normal doses. B J Psych 1993;162:634-640 Bauer M and Dopfmer S. Lithium augmentation in treatment-resistant depression - meta analysis of placebo-controlled studies. Journal of Clinical Psychopharmacology 1999;19(5):427-434 NPSA patient safety alert. Safer lithium therapy. NPSA 2009/PSA005, December 2009

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Drug


Valproate / Valproic acid

Recommended according to risk: Baseline: • FBC including PTT • LFTs • Weight • Pregnancy test Follow-up within 6 months: • Repeat LFTs • Repeat FBC including PTT • Repeat weight and refer to OBMH weight management

guidelines if increased weight occurs (see appendix1) Other further monitoring as clinically indicated. Also see notes on the effect of antiepileptic drugs on bone. Therapeutic Drug Monitoring: No therapeutic levels have been established for use in psychiatry and therefore these are of limited value and are recommended only as a tool for checking compliance. However, please note that these tests cannot be processed locally or routinely.

• Weight gain may occur during valproate treatment. If this becomes a problem refer to the Trust’s Weight Management Guideline.

• LFTs. Increased liver enzymes are common,

particularly at the beginning of therapy; they are also usually transient. Severe liver damage, including hepatic failure sometimes resulting in fatalities, is very rare. Whilst the risk of altered LFTs and FBCs is greatest in the first six months of treatment this can happen throughout treatment and therefore increased clinical vigilance is important. Advise patients to report signs of liver dysfunction immediately.

• Infections. Advise patient to report signs of

infection immediately. • Therapeutic Drug Monitoring. Where TDM

levels are requested they should be taken 12 hours post dose. Therapeutic levels are generally felt to be in the range 50-100mg/L, however some patients with acute mania may require levels of 125mg/L for response. A linear relationship between valproate levels and efficacy in mania has been shown in a recent analysis of pooled data from 3 RCTs. The analysis indicates that a valproate level towards the higher end of the range (range specified above) may be the most optimal when treating acute mania.

• Antiepileptic effects on bone. Long term

use of sodium valproate is associated with decreased bone mineral density that may lead to osteopenia, osteoporosis, and increased fractures in at-risk patients. The following patients are considered to be at risk: • those who are immobilised for long periods • those who have inadequate sun exposure • those with inadequate dietary calcium intake and Vitamin D supplementation should be

Sanofi Aventis Summary of Product Characteristics Depakote, date of most recent revision of the text: 24/3/09 Goodwin GM et al. Evidence-based guidelines for treating bipolar disorder: revised second edition – recommendations from the British Association of Psychopharmacology (BAP). Journal of Psychopharmacology 2009;23(4):346-388 Allen MH et al. Linear relationship of valproate serum concentration to response and optimal serum levels for acute mania. American Journal of Psychiatry 2006;163:272-275 National Institute for Health and Clinical Excellence. Bipolar Disorder – the management of bipolar disorder in adults, children and adolescents, primary and secondary care. NICE clinical guideline 38, July 2006 Antiepileptics: adverse effects on bone Drug Safety Update: Volume 2 Issue 9, April 2009:2 Drug safety advice: Antiepileptics: risk of suicidal thoughts and behaviour. Drug Safety Update 2008;2(1):2 (accessed online at http://www.mhra.gov.uk) Gibbons RD, Hur K, Brown H & Mann JJ. Relationship between antiepileptic drugs and suicide attempts in patients with bipolar disorder. Arch Gen Psych 2009:66(12):1354-1360





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Drug


(Valproate / valproic acid continued)

considered for these patients. For patients with no renal impairment, Adcal-D3 2 tabs daily provides an appropriate amount of Vitamin D. If advice is required for prescribing in patients with renal impairment please contact: [email protected].


2008 that antiepileptic treatment is associated with a small (rare) risk of suicidal thoughts and behaviour. They state that available data suggest that the increased risk applies to all antiepileptic drugs and is seen as early as 1 week after starting treatment. The CSM recommends the following: • Patients should be alert to any mood changes, distressing thoughts, or feelings about suicide or harming themselves at any point during treatment and should be advised to seek medical advice if they develop such thoughts or behaviour, and should be referred for appropriate treatment if necessary. A study published in 2009 aiming to determine whether antiepileptic drugs (AEDs) increase the risk of suicide attempts specifically in bipolar patients, relative to no AED or to lithium treatment, concluded that they do not. In addition the authors concluded that there may be a possible protective effect of AED on suicidality.

SSRIs ⇒ Fluoxetine ⇒ Paroxetine ⇒ Sertraline ⇒ Citalopram ⇒ Escitalopram ⇒ Fluvoxamine

There are no specific recommended monitoring parameters for this group of antidepressants however as with all of the psychotropic medicines the General Psychotropic Medication Monitoring (see appendix 2) should be considered. The following should also be considered:

• There is an increased risk of hyponatraemia (sodium

below the normal range of 135-145 mmol/L) in elderly, females, those with a previous history of hyponatraemia, or with concurrent diuretic therapy. Symptoms include confusion, fatigue, syncope, dizziness, delirium, agitation, and some alteration in pulse or blood pressure may occur. If sodium level rapidly decreases then muscle twitching or

• Serotonergic antidepressants may cause serotonin syndrome – see appendix 4 for further information.

• Citalopram & ECG: “Consideration should be

given to factors which may affect the disposition of a minor metabolite of citalopram (didemethylcitalopram) since increased levels of this metabolite could theoretically prolong the QTc interval in susceptible individuals. However, in ECG monitoring of 2500 patients in clinical trials, including 277 patients with pre-existing cardiac conditions,

1. Do SSRIs cause gastrointestinal bleeding? DTB 2004;42(3):17-18

2. Paton C and Ferrier IN. SRIs and

gastrointestinal bleeding – gastroprotection may be justified in some patients. BMJ 2005;331:529-530

3. Lundbeck Ltd. Cipramil tablets,

Summary of Product Characteristics. Date of most recent revision of the text: 18/9/09

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Drug


(SSRIs continued)

convulsions can occur. Symptoms do not generally occur until the sodium level falls below 125mmol/L – see appendix 3 for further information.

• SSRIs and bleeding risk SSRIs rarely cause bleeding disorders such as bruising, nose-bleeds, GI-bleeds, and prolonged bleeding time. Evidence suggests that the risk of upper GI bleeding is three times greater than in those not taking SSRIs.1 However, the absolute risk still remains very small and is comparable to the relative risk seen in patients taking aspirin or another NSAID.1 Risk of bleeding is further increased in elderly patients, those with a prior history of GI bleeding, or if anticoagulants or drugs that affect platelet function are taken concurrently. It has been suggested that on current evidence SSRIs should be avoided if possible or used with caution in patients aged over 80 years, those with prior upper GI bleeding or those also taking aspirin or another NSAID.1

Routine monitoring of prothrombin time, clotting factors, and platelets is unlikely to be necessary, but it may be worth considering in higher risk patients. It may also be worth considering the use of gastroprotective agents in patients who are taking SSRIs and aspirin or NSAIDS concurrently.2

• Suicide/suicidal thoughts - Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old. Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

no clinically significant changes were noted.”3

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Drug


MAOIs/RIMAs ⇒ Moclobemide ⇒ Phenelzine ⇒ Tranylcypromine ⇒ Isocarboxazid

There are no specific recommended monitoring parameters for this group of antidepressants, however, as with all psychotropic medicines, the General Psychotropic Medication Monitoring (see appendix 2) should be considered.There have been reports of inappropriate appetite and associated weight gain with the MAOIs. If weight gain becomes a problem refer to the Trust’s Weight Management Guideline.

• All antidepressants have the potential to cause hypnotraemia – see SSRIs above and appendix 3 for further information

Serotonergic antidepressants may cause serotonin syndrome – see appendix 4 for further information.

TCAs ⇒ Amitriptyline ⇒ Clomipramine ⇒ Dosulepin ⇒ Doxepin ⇒ Imipramine ⇒ Lofepramine ⇒ Nortriptyline ⇒ Trimipramine

• Due to the cardiovascular adverse effect profile of this group of antidepressants, consideration should be given to carrying out a pre-treatment baseline ECG and blood pressure measurement along with subsequent monitoring of these parameters, particularly in those at greater risk such as the elderly.


• Serotonergic antidepressants may cause

serotonin syndrome – see appendix 4 for further information.

NICE CG90&92 Depression: treatment and management of depression in adults, including adults with a chronic physical health problem. October 2009 Rosemont Pharmaceuticals Lts. Amitriptyline oral solution 25mg/5ml. SPC 4/3/08 Novartis Pharmaceuticals UK Ltd. Anafranil (clomipramine) SPC 25 March 2008 Marlborough Pharmaceuticals Ltd. Sinepin (doxepin) SPC 28th April 2008 Rosemont Pharmaceuticals. Imipramine 25mg/5ml oral solution. SPC 3rd August 2009 Merck Serono Lofepramine SPC 14 July 2008 King Pharmaceuticals Allegron (nortriptyline) SPC March 2008

Sanofi-Aventis Surmontil (trimipramine) tablets SPC 5 March 2008

Agomelatine Recommended monitoring Recommended according to risk: Baseline: LFTs

LFTs. Liver function tests should be performed in all patients. Baseline LFTs should be obtained prior to initiation of treatment, and then at 6, 12 and 24 weeks. Further LFT monitoring is only necessary if clinically indicated. Elevations >3xupper limit of normal (ULN) in all

Servier Laboratories Ltd. Valdoxan Summary of Product Characteristics February 2009 Vol 7 No 1 Agomelatine OBMH Medicines Information Bulletin August

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Drug


(Agomelatine continued)

Further monitoring: Repeat LFTs at weeks 6, 12, and 24 and then if clinically indicated.

patients (i.e. regardless of their transaminase values at baseline) has been classed as a common occurrence. In trials 1.1% of patients taking agomelatine 25mg and 0.72% of patients taking placebo had levels >3xULN, however the difference was not statistically significant. Hepatitis and transaminase elevations >10xULN have been reported rarely (>/=1/10,000 to <1/1000). If transaminases are elevated, the advice is to repeat LFTs within 48 hours, however if transaminases are >3x ULN, agomelatine should be discontinued and LFTs performed regularly until they return to normal.

2009 (available on the Trust intranet)

Duloxetine Recommended according to risk: Baseline in patients with known hypertension and/or other cardiac disease: • Blood pressure Further monitoring: • BP should be closely monitored particularly during the first

month of treatment in patients with known hypertension and/or cardiovascular disease

• Hypertension. Duloxetine is contraindicated in patients with uncontrolled hypertension.

• Bleeding risk – see SRIs and bleeding risk

above • All antidepressants have the potential to

cause hypnotraemia – see SSRIs above and appendix 3 for further information



Eli Lilly and Company Limited. Cymbalta Summary of Product Characteristics, date of revision of the text: 9/2009

Mianserin Recommended according to risk: Baseline: • FBC Further monitoring: • FBC monthly for 1st three months • Thereafter, further monitoring as clinically indicated by

symptoms – stop treatment and take a FBC if fever, sore throat, stomatitis or other signs of infection develop.

• White cell disorders. Mianserin can cause white blood cell disorders including agranulocytosis and neutropenia. Data indicate that the risk is greatest during the first 3 months, and that elderly patients may be more at risk.

• Infections. Treatment should be stopped and

a FBC obtained if there is fever, sore throat, stomatitis, or if other signs of infection develop.

• All antidepressants have the potential to

cause hypnotraemia – see SSRIs above and

Joint Formulary Committee. British National Formulary No 58. London: British Medical Association & Royal Pharmaceutical Society of Great Britain 9/2009 Generics UK Ltd. Mianserin Summary of Product Characteristics. Date of most recent revision of the text: 2 June 2009 NICE CG90&92 Depression: treatment and management of depression in adults, including adults with a chronic physical health problem. October 2009

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(Mianserin continued)

appendix 3 for further information • Serotonergic antidepressants may cause


Mirtazapine There are no specific recommended monitoring parameters for this antidepressant however, as with all psychotropic medicines, the General Psychotropic Medication Monitoring (see appendix 2) should be considered as should the following:

• Bone marrow depression, usually presenting as granulocytopenia or agranulocytosis, has been reported during treatment with Mirtazapine. Reversible agranulocytosis has been reported as a rare occurrence in clinical studies with mirtazapine. In the postmarketing period with mirtazapine very rare cases of agranulocytosis have been reported, mostly reversible, but in some cases fatal. Fatal cases mostly concerned patients with an age above 65.

• Infections. Treatment should be stopped and a FBC obtained if there is fever, sore throat, stomatitis, or if other signs of infection develop.

• Weight gain may occur. If this becomes a problem refer to the Trust’s Weight Management Guideline.




Organon Laboratories Limited Zispin Soltab Summary of Product Characteristics, date of most recent revision of the text: 17 February 2009

Reboxetine There are no specific recommended monitoring parameters for this antidepressant however, as with all psychotropic medicines, the General Psychotropic Medication Monitoring (see appendix 2) should be considered, as should the following: • Orthostatic hypotension has been reported. • Blood pressure should be monitored if reboxetine is given

concomitantly with other drugs known to lower blood pressure.


Pharmacia Limited. Edronax Summary of Product Characteristics, date of most recent revision of the text: July 2008

Trazodone There are no specific recommended monitoring parameters for this antidepressant however, as with all psychotropic medicines, the General Psychotropic Medication Monitoring (see appendix 2) should be considered.

• Blood dyscrasias, including agranulocytosis, thrombocytopenia and anaemia, have been reported on rare occasions. Treatment should be stopped immediately and a FBC obtained if there is fever, sore throat, stomatitis, or if other signs of infection develop.

• Adverse effects on hepatic function, including

Sanofi-Aventis. Molipaxin tablets Summary of Product Characteristics. Date of revision of the text: 16/9/08

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(Trazodone continued)

jaundice and hepatocellular damage, sometimes severe, have been rarely reported. Should such effects occur, trazodone should be discontinued immediately.





Tryptophan There are no specific recommended monitoring parameters for this antidepressant however, as with all psychotropic medicines, the General Psychotropic Medication Monitoring (see appendix 2) should be considered.

There is no longer a requirement to register the patient and prescriber with the Optimax Information and Clinical Support (OPTICS) Unit, however the initial prescription has to be made by a consultant psychiatrist or specialist working in the field. After the initial prescription further prescriptions can be written by the GP. The information that has been collected by the OPTICS unit over the past 10 years has been reviewed by the CSM and this has shown no increase in risk of Eosinophilia Myalgia Syndrome.

Personal communication with Merck Pharmaceuticals Medical Information Officer, 8/8/05 Letter received from Merck Serono Medical Information Department, 18th June 2009

Venlafaxine Recommended according to risk: Baseline: • Blood pressure Further monitoring: Consideration should be given to: • monitoring blood pressure at 6 monthly intervals unless

clinically indicated otherwise. • conducting an ECG and/or U&Es if indicated by clinical

symptoms • measuring serum cholesterol levels during long term

treatment (see notes)

• Hypertension. Pre-existing hypertension should be controlled before initiating treatment with venlafaxine.

• Cardiac disease. Venlafaxine should be used

with caution in patients with established cardiac disease that may increase the risk of ventricular arrhythmias (e.g. recent MI)

• Cholesterol levels. Clinically relevant

increases in serum cholesterol were recorded in 5.3% of venlafaxine-treated patients and 0.0% of placebo-treated patients treated for at least 3 months in placebo-controlled trials.

• Bleeding risk – see SSRIs and bleeding risk

above

Wyeth Pharmaceuticals Efexor XL Summary of Product Characteristics, date of most recent revision of the text: 22 March 2010 MHRA Drug Alert: Updated prescribing advice for venlafaxine (Efexor/Efexor XL) Message from Professor G Duff, Chairman, Commission on Human Medicines, 31 May 2006 NICE CG90&92 Depression: treatment and management of depression in adults, including adults with a chronic physical health problem. October 2009

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(Venlafaxine continued)

• Serotonergic antidepressants may cause serotonin syndrome – see appendix 4 for further information.



All antipsychotic drugs

Give consideration to the General Psychotropic Medication Monitoring (see appendix 2). Consider the need for additional blood glucose monitoring (see notes section). The NICE clinical guideline for schizophrenia recommends that an ECG should be conducted prior to the initiation of an antipsychotic in all inpatients. Patients who are not inpatients should be offered an ECG if it is specified in the manufacturers literature (SPC) – see individual drugs below, or if a physical examination shows specific cardiovascular risk (such as a diagnosis of high BP), or if there is a personal history of cardiovascular disease. Patients should be monitored for the development of side effects (GASS and LUNSERS are examples side effect rating scales that may be useful. Copies of these can be found in appendix 11 and on the Trust intranet).

• Neuroleptic malignant syndrome (NMS) is a risk with all antipsychotics – for further information see appendix 5

• High dose prescribing. When doses above

the BNF max. are used please also refer to the High Dose Monitoring policy (available on the Trust intranet)

• Hyperprolactinaemia. All antipsychotics

have the potential to raise prolactin. Please refer to the Trust’s Hyperprolactinaemia Guideline &/or the prolactin monitoring algorithm in appendix 7 for further information. Specific antipsychotics that require routine monitoring are indicated in the relevant sections below.

• Stroke risk. There is a clear increased risk of

stroke and a small increased risk of death when antipsychotics (typical or atypical) are used in elderly people with dementia. The mechanism for this increased risk is not known and an increased risk cannot be excluded for other patient populations. Antipsychotics should be used with caution in patients with risk factors for stroke.

• Thromboembolism. Antipsychotic use may

be associated with an increased risk of venous thromboembolism (VTE). At present there are insufficient data available to determine any difference in risk between atypical and conventional antipsychotics or between individual drugs. All possible risk

Antipsychotics: use in elderly patients with dementia. Drug Safety Update March 2009;2(8):5 (accessed at www.mhra.gov.uk)

Antipsychotics: risk of venous thromboembolic events. Drug Safety Update June 2009;2(11):2 (accessed at www.mhra.gov.uk) Cohen D and Correll CU. Second-generation antipsychotic-associated diabetes mellitus and diabetic ketoacidosis: mechanisms, predictors, and screening need. Journal of Clinical Psychiatry 2009;70(5):765-766


15

Drug


(All antipsychotic drugs continued)

factors for VTE should be identified before and during antipsychotic treatment and preventive measures undertaken

• Glucose dysregulation. Consideration

should be given to more frequent monitoring of blood glucose than is suggested in the metabolic management guidelines (appendix 1) - ie monthly for 1st 3 months in the following patients:

o Those prescribed olanzapine and clozapine.

o Those prescribed any antipsychotic and who have risk factors for diabetes mellitus

All patients receiving antipsychotics should be screened at each visit for symptoms and signs of new-onset diabetes. Refer to appendix 9 for information and recommendations on managing abnormal glucose results.

Amisulpride • See “all antipsychotic drugs” above Plus: Recommended according to risk: Baseline:

• ECG (see notes) • Prolactin level (see appendix 7 for prolactin monitoring

algorithm) Further monitoring: • Prolactin level (follow the algorithm in appendix 7)

The manufacturers of Solian recently added the recommendation that a baseline ECG should be completed prior to treatment in all patients especially in the elderly and patients with a positive personal or family history of cardiac disease or abnormal findings on cardiac clinical examination. They suggest that during therapy, the need for ECG monitoring (e.g. at dose escalation) should be assessed on an individual patient basis.

Solian SPC Sanofi Aventis Date of most recent revision of the text: 7 February 2009

16

Drug


Aripiprazole • See “all antipsychotic drugs” above

Clozapine • See “all antipsychotic drugs” above Plus: • The Metabolic Management guidelines (see appendix 1)

should be followed (see also notes under “all antipsychotic drugs” above about additional glucose monitoring recommendations).

Recommended according to risk: Baseline: • FBC (compulsory) • Temperature, blood pressure, and pulse • Consideration should be given to conducting a baseline

ECG Further FBC monitoring (compulsory): • Week 1 to 18: weekly • Week 18 to 52: fortnightly • Week 52 onwards: monthly The above is at the discretion of the manufacturer – additional monitoring may be required. BP, temperature, and pulse monitoring: • Day 1: Hourly for 1st six hours post dose, and then pm • Day 2 and until titration is complete: Twice daily • Once titration is complete: If parameters are abnormal

continue with close monitoring. If parameters are normal, the patient should still be monitored, but the frequency will be determined on an individual patient basis.

Therapeutic Drug Monitoring: There is no established therapeutic range but generally a plasma level of > 0.35mg/L clozapine is felt to be clinically therapeutic. Samples should be taken immediately before a dose for BD regimes (i.e. a trough level) or 12 hours post-dose if on a once daily regimen.

• Neutropenia / agranulocytosis is more common during 1st 18 weeks, but can occur at any time. It is unpredictable, with 3-4% patients affected. However, the risk is well-managed by clozapine-monitoring service. o Advise patients to report signs of

infection immediately, especially influenza-like illness.

• Hypotension is common, especially during 1st

four weeks. Slow the titration schedule &/or reduce the dose. Advise the patient to stand slowly.

• Hypertension may occur during 1st 4 weeks,

sometimes longer. Slow the titration schedule &/or reduce the dose. An antihypertensive may sometimes be necessary.

• Tachycardia is very common in early stages,

especially first 4 weeks, but usually benign.** Slow the titration schedule &/or reduce the dose. A beta-blocker may sometimes be necessary.

• Fever – may occur during the first ~3 weeks.

It is unlikely to be related to blood dyscrasias and is usually clinically insignificant. However, check FBC and give paracetamol, but also consider myocarditis.**

• Clozapine concentrations above 0.6mg/L

increase the risk of seizures. ** Tachycardia, if persistent at rest and associated with fever, hypotension, or chest pain, may indicate myocarditis. Other symptoms include flu-like symptoms, fatigue, dyspnoea, arrhythmias. If myocarditis is suspected stop clozapine

Denlfeet Pharma Ltd. Denzapine Summary of Product Characteristics. Date of first authorisation: 16/05/08

17

Drug


(Clozapine continued)

immediately. Myocarditis is rare and the greatest risk is during the first 6-8 weeks. Therefore, closely monitor for signs especially during 1st few months. Cardiomyopathy may occur later on.

Olanzapine • See “all antipsychotic drugs” above

Plus:

• The Metabolic Management guidelines (see appendix 1) should be followed (see also notes under “all antipsychotic drugs” above about additional glucose monitoring recommendations).

• LFTs. Transient, asymptomatic elevations of hepatic transaminases (ALT, AST), especially in early treatment, are common (1-10%). There is no requirement for routine monitoring however further monitoring will be dictated by baseline result or clinical symptoms.

Eli Lilly and Company. Zyprexa Summary of Product Characteristics. Date of revision of the text: 3 July 2009

Quetiapine • See “all antipsychotic drugs” above Plus: Recommended according to risk: Baseline: • Blood pressure (sitting and standing) Further monitoring • BP (sitting and standing) daily for the first 4 days and then

as clinically indicated.

• Orthostatic hypotension may occur particularly during the initial dose titration period. This is more common in elderly patients. Use quetiapine with caution in patients who have known cardiovascular disease, cerebrovascular disease or other conditions predisposing to hypotension.

• LFTs. Asymptomatic elevations of AST & ALT

are common (1-10%) and elevations of GGT are uncommon (0.1-1%). There is no requirement to routinely monitor LFTs whilst on treatment – need should be dictated by clinical symptoms.

• White cell abnormalities. Leukopenia occurs

commonly (1-10%) and eosinophilia occurs uncommonly (0.1-1%). There were no cases of persistent severe neutropenia or agranulocytosis reported in controlled clinical trials with Seroquel. During post-marketing experience, resolution of leukopenia and/or neutropenia has followed cessation of therapy with Seroquel. Possible risk factors for leukopenia and/or neutropenia include pre-existing low white cell count and history of drug induced leukopenia and/or neutropenia.

• Thyroid function tests. Quetiapine can

Astra Zeneca UK Limited. Quetiapine Summary of Product Characteristics. Date of revision of the text: 9 September 2009

18

Drug


(Quetiapine continued)

cause dose-related decreases in thyroid hormone levels, particularly total T4 and free T4 with a maximal effect at 2-4 weeks. There is no indication that quetiapine causes clinically relevant hypothyroidism.

Risperidone • See “all antipsychotic drugs” above Plus: Recommended according to risk: Baseline: • Prolactin level (see appendix 7 for prolactin monitoring

algorithm) Further monitoring: • Prolactin level (follow the algorithm in appendix 7)

• Stroke risk. See “all antipsychotics” above regarding the risks of stroke and death associated with the use of antipsychotics in patients with dementia. The balance of risks and benefits associated with risperidone treatment should be carefully assessed for every patient, taking into consideration the known increased mortality rate associated with antipsychotic treatment in the elderly. Prescribers should carefully consider the risk of cerebrovascular events before treating with risperidone ▼ any patient who has a previous history of stroke or transient ischaemic attack. Consideration should also be given to other risk factors for cerebrovascular disease including hypertension, diabetes, smoking, and atrial fibrillation

• Dementia-related behavioural disturbance.

Risperidone is the only antipsychotic that is licensed for the treatment of dementia-related behavioural disturbances. It should only be used for the specific indication of short term (up to 6 weeks) treatment of persistent aggression in Alzheimer’s dementia unresponsive to non-pharmacological approaches and where there is risk of harm to the patient or others.

Risperidone ▼ has been added to the list of black triangle medicines after the granting of the new narrow indication in Alzheimer’s dementia. The Black Triangle Scheme identifies medicines whose safety profiles are monitored intensively by MHRA and CHM. All

Janssen-Cilag Ltd. Risperdal Summary of Product Characteristics. Date of most recent revision of the text: 8/12/08

Antipsychotics: use in elderly patients with dementia. Drug Safety Update March 2009;2(8):5 (accessed at www.mhra.gov.uk)

19

Drug


(RIsperidone continued)

suspected side-effects to risperidone that occur when it is used to treat elderly people with dementia should be reported via the Yellow Card Scheme:(www.yellowcard.gov.uk)

• Psychosis treatment in patients with

dementia. Treatment of acute psychoses in patients with a history of dementia should be limited to short term only and should be under specialist advice.

Typical antipsychotics (for haloperidol and pimozide – see separate entries below)

• See “all antipsychotic drugs” above Plus: Recommended according to risk: Baseline: • Prolactin level (see appendix 7 for prolactin monitoring algorithm) Further monitoring: • Prolactin level (follow the algorithm in appendix 7)

• Photosensitisation may occur with chlorpromazine – patients should be advised to avoid direct sunlight

Haloperidol (intramuscular injection, oral and depot)

• See “all antipsychotic drugs” above Plus: Recommended according to risk: Baseline: • ECG • Electrolytes • Prolactin level (see appendix 7 for prolactin monitoring

algorithm) Further monitoring:

• ECGs should be conducted after all dose increases and then yearly, unless clinically indicated earlier.

• Electrolyte monitoring should be conducted yearly or more frequently if clinically indicated (see notes section).

• Prolactin level (follow the algorithm in appendix 7)

ECGs. A baseline ECG is recommended prior to treatment in all patients, especially in the elderly and patients with a positive personal or family history of cardiac disease or abnormal findings on cardiac clinical examination. During therapy, the need for ECG monitoring (e.g. at dose escalation) should be assessed on an individual basis. Whilst on therapy, the dose should be reduced if QT is prolonged, and haloperidol injection should be discontinued if the QTc exceeds 500 ms. Electrolytes. Electrolyte imbalance, particularly hypokalaemia, can cause ECG changes. Patients with no risk factors for altered electrolytes should be monitored yearly. However, more frequent monitoring should be carried out: ⇒ in patients taking medicines that affect fluid

balance eg diuretics, ACEIs, steroids, beta-blockers,

Janssen-Cilag Ltd. Haldol injection. Summary of Product Characteristics. Date of revision of the text: April 2009

Janssen-Cilag Ltd. Haldol tablets Summary of Product Characteristics. Date of revision of the text: April 2009 Janssen-Cilag Ltd. Haldol decanoate. Summary of Product Characteristics. Date of revision of the text: 5 June 2009

http://www.yellowcard.gov.uk/

20

Drug


(Haloperidol (intramuscular injection, oral and depot) continued)

⇒ during intercurrent illness, particularly conditions that may affect fluid balance eg where vomiting or diarrhoea are present,

⇒ in changing renal function, ⇒ in the elderly.

Pimozide • See “all antipsychotic drugs” above Plus: Recommended according to risk: Baseline: • ECG • Electrolytes • Prolactin level (see appendix 7 for prolactin monitoring

algorithm) Further monitoring

• ECGs should be conducted after all dose increases and then yearly, unless clinically indicated earlier.

• Electrolyte monitoring should be conducted yearly or more frequently if clinically indicated (see notes section).

• Prolactin level (follow the algorithm in appendix 7)

QT interval prolongation risks. Do not give with other antipsychotics, with TCAs, or with other drugs that prolong the QT interval. Concurrent use with drugs that cause electrolyte disturbances (especially diuretics) is also not recommended. Electrolytes. Electrolyte imbalance, particularly hypokalaemia, can cause ECG changes. Patients with no risk factors for altered electrolytes should be monitored yearly. However, more frequent monitoring should be carried out: ⇒ in patients taking medicines that affect fluid

balance eg diuretics, ACEIs, steroids, beta-blockers (but see notes above, as they are not generally recommended),

⇒ during intercurrent illness, particularly conditions that may affect fluid balance eg where vomiting or diarrhoea are present,

⇒ in changing renal function, ⇒ in the elderly, ⇒ If repolarization changes (prolongation of QT

interval, T-wave changes or U-wave development) appear or arrhythmias develop, the need for treatment with pimozide in these patients should be reviewed. They should be closely monitored and their dose of pimozide should be reduced or the drug discontinued. If QT or QTc exceeds 500 msec, pimozide should be discontinued.

Janssen-Cilag Ltd. Orap Summary of Product Characteristics. Date of revision of the text: 11/2/09

Acetyl-cholinesterase inhibitors ⇒ Donepezil ⇒ Galantamine ⇒ Rivastigmine

The General Psychotropic Medication Monitoring (see appendix 2) should be considered. Recommended according to risk: Baseline: • Weight • Pulse

• Weight loss may occur with acetylcholinesterase inhibitor treatment so a pre-treatment baseline weight is recommended and consideration should be given to measuring weight periodically during treatment – for example, every 6 to 12 months unless indicated earlier.

Shire Pharmaceuticals Limited. Reminyl tablets. Date of revision of the text: September 2007 Novartis Pharmaceuticals UK Limited. Exelon Summary of Product Characteristics. Date of revision of the

21

Drug


(Acetyl-cholinesterase inhibitors continued)

Further monitoring: • Weight (see notes) • Pulse (see notes)

• Bradycardia can occur with AChEI treatment. A recent large cohort study identified that the risk compared with no treatment in patients with dementia was an adjusted hazard ratio of 1.4, 95%CI =1.1 to 1.6. Patients with bradycardia were more likely to fall, experience syncope or need a pacemaker implantation. Pulse should be monitored at each clinic visit or more frequently if symptoms indicate a need or there are other risk factors for bradycardia (eg patients taking beta-blockers, a history of falls since diagnosis, those with a history of MI, heart failure or hypertension).

text: 30/1/09 Hernandez RK et al. Cholinesterase inhibitors and incidence of bradycardia in patients with dementia in the veterans affairs New England healthcare system. J Am Geriatr Soc 2009;57:1997-2003

Memantine There are no specific recommended monitoring parameters for memantine however, the General Psychotropic Medication Monitoring (see appendix 2) should be considered.

Lundbeck Limited Ebixa Summary of Product Characteristics. Date of revision of the text: 02/12/2008

Atomoxetine Recommended according to risk: Baseline: • Height (children and young people) • Weight • Blood pressure • Pulse • LFTs • ECG - consideration should be given to conducting an ECG

if indicated by past medical history or by the use of concomitant medication that may affect the ECG

Further monitoring: Before and after each dose adjustment: • Blood pressure • Pulse • Appetite At 3 months: • Weight • Blood pressure • Pulse • Appetite

• Weight. o For children and young people, height

and weight should be plotted on growth charts and reviewed regularly.

o For adults consider monitoring body mass index (BMI) if weight loss occurs.

• Cardiac effects. Sustained resting

tachycardia, arrhythmia or sBP >95th percentile (or a clinically significant increase) measured on 2 occasions should prompt dose reduction and referral to paediatrician or physician. In February 2006 the Committee on Safety of Medicines advised prescribers that there had been reports of QT interval prolongation. Therefore Strattera should be used with caution in those with congenital or acquired long QT or a family history of QT prolongation.

• Seizures – if exacerbated in a child with

epilepsy or de novo seizures emerge, discontinue immediately

Eli Lilly and Company. Strattera Summary of Product Characteristics. Date of revision on the text: 22 October 2008 Strattera – risk of hepatic disorders. Letter from Prof G Duff, Chairman of commission on human Medicines, Committee on Safety of Medicines. 2nd February 2005 Strattera – conclusions of risk:benefit review. Letter from Prof G Duff, Chairman of commission on human Medicines, Committee on Safety of Medicines. 16th February 2006.

Atomoxetine: risk of psychotic or manic symptoms. Drug Safety Update March 2009;2(8):4 (accessed at www.mhra.gov.uk) NICE CG72. Attention Deficit hyperactivity disorder. September 2008


22

Drug


(Atomoxetine continued)

At 6 months: • Height (children and young people) • Weight • Blood pressure • Pulse • Appetite Subsequent regular monitoring: Every 3 months: • Blood pressure • Pulse Every 6 months: • Height (children and young people) • Weight • Appetite Additional monitoring only if symptoms indicate a need: • LFTs (see notes on hepatic disorders) • ECG (see notes on cardiac effects)

• Hepatic disorders. In February 2005 the Committee on Safety of Medicines advised all prescribers about the risk of rare, but sometimes severe, hepatic disorders in association with atomoxetine. The risk is estimated to be <1/50,000 patients treated. There is no clear pattern in terms of onset time, the reactions may occur after several months of treatment, and there appears to be no dose relationship. The CSM has therefore advised the following:

⇒ Routine monitoring of liver function is not recommended. The reactions are seemingly idiosyncratic in nature therefore routine monitoring is unlikely to be helpful in minimising the risk.

⇒ All suspected hepatic reactions should be investigated.

⇒ Atomoxetine should be discontinued in patients with jaundice or laboratory evidence of hepatic injury and should not be restarted.

• Psychotic/manic symptoms. At normal

doses, atomoxetine can be associated with treatment emergent psychotic or manic symptoms (eg, hallucinations, delusional thinking, mania, or agitation) in children and adolescents without a history of psychotic illness or mania. If such symptoms occur, consideration should be given to a possible causal role of atomoxetine and discontinuation of treatment. It remains possible that atomoxetine might exacerbate pre-existing psychotic or manic symptoms.

• Agitation, irritability, suicidal thinking and

self-harm (children, young people and adults) - closely observe especially during the initial months of treatment or after a change in dose.

• Other monitoring. Monitor for erectile dysfunction, ejaculatory dysfunction and dysmenorrhoea (young people and adults).

23

Drug


Clonidine Recommended according to risk: Baseline: • Blood pressure • Pulse • ECG - consideration should be given to conducting an ECG


Further monitoring following dose adjustments and then every 6 months: • Blood pressure • Pulse • ECG (if indicated by symptoms)

• Orthostatic hypotension is very common (>1/10).

• Cardiac arrhythmias are rare (> 1/10000,

<1/1000) but potentially serious.

Taylor E, Dopfner M, Sergeant J et al. European clinical guidelines for hyperkinetic disorder – fist upgrade. European Child and Adolescent Psychiatry 2004;13(S1):7-30

Boehringer Ingelheim Limited. Catapress tablets Summary of Product Characteristics. Date of revision of the text: March 2009

Dexamfetamine Recommended according to risk: Baseline: • Height (children and young people) • Weight • Blood pressure • Pulse • ECG - consideration should be given to conducting an ECG


Further monitoring: Before and after each dose adjustment: • Blood pressure • Pulse • Appetite At 3 months: • Weight • Blood pressure • Pulse • Appetite At 6 months: • Weight • Blood pressure • Pulse • Appetite

• Weight o For children and young people, height




tachycardia, arrhythmia or sBP >95th percentile (or a clinically significant increase) measured on 2 occasions should prompt dose reduction and referral to paediatrician or physician.

• Tics. If tics occur, consider whether they are stimulant related and whether tic-related impairment outweighs the benefits of ADHD treatment.

• Psychotic/manic symptoms. Treatment

emergent psychotic or manic symptoms (e.g. hallucinations, delusional thinking or mania) without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. Drug treatment should be withdrawn, a full psychiatric assessment carried out, and atomoxetine considered instead.

UCB Pharma Limited. Dexedrin tablets Summary of Product Characteristics. Date of revision of the text: September 2008 NICE CG72. Attention Deficit hyperactivity disorder. September 2008

24

Drug


(Dexamphetamine continued)

• Height (children and young people) Subsequent regular monitoring: Every 3 months: • Blood pressure • Pulse Every 6 months: • Height (children and young people) • Weight • Appetite Additional monitoring only if symptoms indicate a need: ECG (see notes on cardiac effects)

• Aggressive behaviour. Patients beginning treatment with stimulants for ADHD should be monitored for the appearance, or worsening of, aggressive behaviour or hostility.

• Anxiety. If anxiety symptoms (including

panic) are precipitated by stimulants, particularly in adults with a history of coexisting anxiety, use lower doses and/or combine treatment with an antidepressant used to treat anxiety or consider switching to atomoxetine.

Methylphenidate Recommended according to risk: Baseline: • Height (children and young people) • Weight • Blood pressure • Pulse ECG - consideration should be given to conducting an ECG if indicated by past medical history or by the use of concomitant medication that may affect the ECG Further monitoring: Before and after each dose adjustment: • Blood pressure • Pulse • Appetite • Development of psychiatric symptoms (see notes) At 3 months: • Weight • Blood pressure • Pulse • Appetite • Development of psychiatric symptoms (see notes) At 6 months: • Height (children and young people) • Weight

• Weight. o For children and young people, height




tachycardia, arrhythmia or sBP >95th percentile (or a clinically significant increase) measured on 2 occasions or the development of symptoms such as palpitations, exertional chest pain, unexplained syncope, dyspnoea, or other symptoms suggestive of heart disease should prompt dose reduction and referral to paediatrician or physician.

• Tics. If tics occur, consider whether they are

stimulant related and whether tic-related impairment outweighs the benefits of ADHD treatment.

• Seizures – if exacerbated in a child with

epilepsy or de novo seizures emerge, discontinue immediately.

Novartis Pharmacueticals UK Limited. Ritalin Summary of Product Characteristics. Date of revision of the text: 3 March 2008 Janssen-Cilag Limited. Concerta XL Summary of Product Characteristics. Date of revision of the text: 29th July 2008

25

Drug


(Methylphenidate continued)

• Blood pressure • Pulse • Appetite • Development of psychiatric symptoms (see notes) Subsequent regular monitoring: Every 3 months: • Blood pressure • Pulse Every 6 months: • Height (children and young people) • Weight • Appetite • Development of psychiatric symptoms (see notes) Additional monitoring only if symptoms indicate a need: • ECG (see notes on cardiac symptoms)

• Psychiatric symptoms. Methylphenidate could cause or worsen some psychiatric disorders such as depression, suicidal thoughts, hostility, anxiety, agitation, psychosis, and mania. Development of new, or worsening of pre-existing, psychiatric symptoms should be monitored at every dose adjustment and then at least every 6 months, and at every visit.

• Blood tests. Manufacturers recommend

periodic blood tests to detect any haematological abnormality but recent European clinical guidelines for hyperkinetic disorder suggest that there is no evidence for this practice and that the remote chance of benefit is usually outweighed by the unpleasantness for the child.

Shire Pharmaceuticals Limited. Equasym Summary of Product Characteristics. Date of revision of the text: 17 June 2009 Flynn Pharma Ltd. Medikinet Summary of Product Characteristics. Date of revision on the text: 22.02.2007 Methylphenidate: updated guidance on safe and effective use in ADHD. Drug Safety Update March 2009;2(8):2-3 (accessed at www.mhra.gov.uk) NICE CG72. Attention Deficit hyperactivity disorder. September 2008 Taylor E, Dopfner M, Sergeant J et al. European clinical guidelines for hyperkinetic disorder – fist upgrade. European Child and Adolescent Psychiatry 2004;13(S1):7-30


26

Appendix 1: Metabolic Management Guidelines Baseline:

• Weight • Height • BMI (calculated by dividing body weight [kg] by the square of the height [metres]) • Waist circumference (measured only if BMI between 25-35.5kg/m2. Locate the upper hipbone & place

measure around abdomen horizontally) • Lipid profile:

o HDL-C and LDL-C fasting (or random if fasting not possible) o TG fasting only

• Fasting glucose (random if not possible) • HbA1c – ONLY if fasting glucose levels raised on 2 occasions (refer to NICE diabetes guideline where

indicated) • Blood pressure & pulse

Suggested monitoring for the first year Regularly during 1st 3 months then at 3 monthly intervals: • Weight • Height • BMI • Waist circumference (only if BMI between 25-35.5kg/m2) • BP • Pulse At months 3 & 6 • Lipid profile:


• Fasting glucose (random if not possible) During maintenance treatment- Yearly: • Weight • Height • BMI • Waist circumference (only if BMI between 25-35.5kg/m2) • BP • Pulse • Lipid profile:


• Fasting glucose (random if not possible) Follow up abnormal results and refer to appropriate guidance (eg NICE guidelines on obesity, hypertension, lipid modification and diabetes). OBMH Weight Management Guidelines can be found on the Trust intranet and refer to appendix X (lipid modification), and Y (abnormal glucose results) within these guidelines for further guidance.

References: American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, and North American

Association for the study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care 2004;27(2:596601

Chue P, Jovacs CS Bipolar Disorder 2003;(S2):62-79 Schizophrenia & diabetes 2003 Expert Consensus Meeting, Straker D, Correll CU, Kramer-Ginsberg E et al. Cost effective screening for the metabolic syndrome in patients treated with second-

generation antipsychotic medications. American Journal of Psychiatry 2005;162(6):1217-1221 Yusuf S, Hawken S, Ounpuu S et al. Obesity and the risk of myocardial infarction in 27000 participants from 52 countries: a case-control

study. The Lancet 2005;366:1640-1649 OBMH Weight management guidelines for clinicians prescribing and monitoring patients treated with psychotropic medication. DTC

approved October 2008

Weight management options -see following page

27

Weight management options (appendix 1 continued)

The purpose of this section is to signpost some of the options that are available within the Trust, which may be used to form part of a weight and metabolic management plan. There are likely to be other services and options available. If anyone is aware of a service that should be included please let the Drugs and Therapeutics Committee know so that it can be included in future updates of these guidelines.

OBMH Weight management guidelines for clinicians prescribing and monitoring patients treated with psychotropic medication are available on the Trust intranet. They are a comprehensive guide that includes monitoring recommendations, interpretation of results (eg BMI, waist circumference) guidance on when drug treatment is appropriate, dietary advice and referral forms to the dietetic service, physiotherapy referral guidance, exercise interventions and details of local leisure/activity facilities In addition, the following may also be useful: In-patients The catering department can accommodate almost any diet that is required. General diet areas include:

• Diabetic • Weight reducing • Healthy eating • Low fat • Vegetarian • Vegan • Low potassium • Low sodium • MAOI suitable

In-patients/out-patients Occupational therapists can help with the following areas:

• Activities of Daily Living o Look at healthy living e.g. diet, cooking, exercise o Budgeting e.g. how to use money appropriately for a healthy diet o Domestic activities e.g. house keeping as exercise

• Accessing sports centres/facilities • Gardening – some wards run gardening groups. Allotments may become available in the future.

Occupational therapists work closely with dieticians and physiotherapists and, when appropriate, can make referrals to link into these services.

28

Appendix 2: General Psychotropic Medication Monitoring Baseline Observations:

• BP and pulse • FBC • Urea & electrolytes, including serum creatinine (and request eGFR) • LFTs • Basic urine screen • TSH • Weight • Height (calculate BMI) • Waist circumference (if BMI between 25-35.5kg/m2) [measured midway between lower margin of the ribs

and the top of the iliac crest laterally] • Fasting lipid profile including triglycerides • Fasting glucose (random if not possible) • HbA1c – ONLY if fasting glucose levels raised on 2 occasions (refer to NICE diabetes guideline where

indicated) • Pregnancy test • Urine drug screen • Enquire about alcohol intake

and where indicated by individual risk factors:

• ECG Yearly monitoring • BMI • Waist circumference (if BMI between 25-35.5 Kg/m2) • BP and pulse • Fasting lipids (random if not possible) including triglycerides (TG), HDL-C and Cholesterol ratio • Fasting glucose (random if not possible) • Smoking and alcohol intake Further monitoring

• Repeat as clinical need dictates or as specified in the individual drug monograph in the tables on the following pages

• Mental state should be closely monitored during treatment - consideration should be given to the possibility that some medicines may adversely affect mental state e.g. antidepressants causing manic or hypomanic episodes, the appearance or worsening of suicide-related behaviours with drugs such as atomoxetine and the SSRIs.

29

Appendix 3: Antidepressant induced hyponatraemia Background Hyponatraemia is a relatively uncommon but potentially serious condition which can occur as a result of drug treatment. Drug induced hyponatraemia can occur through several mechanisms either directly by increased excretion of sodium, as with thiazides, or indirectly via water intoxication, as seen with drug induced polydipsia. Another cause of drug-induced hyponatraemia is Syndrome of Inappropriate ADH secretion (SIADH). This is characterised by a sustained release of AntiDiuretic Hormone (ADH) from the pituitary resulting in a reduced ability to excrete water. SIADH is a recognised adverse effect of several different medicines. It was first reported with antipsychotics and antidepressants in 19741. As yet it is not understood why certain psychotropic drugs have this effect, although it is known that both noradrenaline and serotonin can induce the release of ADH. Animal studies have also shown that dopamine antagonists facilitate ADH release2. In addition it is possible that antidepressants, such as SSRIs, could increase the responsiveness of the kidney to ADH3. Therefore a variety of mechanisms could be involved. Antidepressant induced SIADH does not appear to be dose related4, however it does appear to be more common with serotonergic agents5,6. A review in 2002, which examined case reports taken from Medline (1966-2000) and the FDA regulatory body (1996-1999), identified 70 cases related to SSRIs and only 42 related to other antidepressants5. There is an established link between carbamazepine and SIADH, however there are important differences between carbamazepine-induced SIADH and that linked to SSRI treatment. It is thought that carbamazepine causes the syndrome through potentiation of ADH action and in contrast to the antidepressants it is not age or gender related, but it is dose related5. Diagnosis Diagnosis of SIADH can be difficult. It usually involves a process of elimination to rule out other causes of hyponatraemia. Often the first indication of a problem will be an abnormal blood result, as many patients remain asymptomatic until the sodium levels are severely reduced. Even with sodium levels <125mmol/L up to 50% of patients will remain asymptomatic.7 However symptoms are likely to be severe if hyponatraemia has developed acutely rather than chronically.7 Some of the symptoms which may occur are listed in the box on the right. In contrast to other causes of hyponatraemia, oedema, hypotension and dehydration do not occur with SIADH.3,4

The following clinical features can be indicative of SIADH:8

1. hyponatraemia (serum sodium concentration < 135mmol/L) 2. urine osmolality > 100mOsm/kg water (especially noted if urine is hypertonic

relative to plasma.) 3. hypo-osmolality of the serum and ECF (osmolality <280mOsm/kg water) 4. absence of clinical evidence of fluid depletion 5. normal renal function 6. normal adrenal function

While making the diagnosis it is important to rule out other causes of hyponatraemia, such as ADH secreting neoplasms, hypothyroidism, lung disorders, CNS damage, nephritis, adrenal insufficiency, infectious processes, self-induced water intoxication and severe hyperglycaemia.2,7,9 SIADH has also been reported as a component of mood disorders in patients not receiving psychotropic treatment3. Suggested initial investigations of patients with suspected SIADH may include:7

Blood tests: U&Es, FBC, ESR, glucose, LFTs, plasma osmolality, TFTs, morning cortisol. Urine tests: sodium, glucose, osmolality, specific gravity Other: chest X-ray At risk populations Although SIADH is relatively rare, it occurs more commonly in certain populations. Risk factors include being elderly, female, and being a smoker5. In 1996 a systematic review identified 736 cases of hyponatraemia and SIADH associated with the use of SSRIs, and reported that 83% of the published cases involved patients who were 65 years or older2. Prescribers should consider monitoring serum sodium levels in these high risk patients. They should also be alert for poly- pharmacy, especially concomitant treatment with other medicines, which may cause hyponatraemia (see box on the right).

Symptoms of SIADH 7

1. Often absent 2. Early/mild/chronic a. weakness; lethargy, weight gain; without oedema; muscle cramps b. headache; vomiting anorexia 3. Late/severe/acute confusion; convulsions; coma; death

Medicines which may cause hyponatraemia

3,4,9

SSRIs Carbamazepine Tricyclic Antidepressants MAOIs Anti-psychotics:

-phenothiazines -butyrophenones

Thiazides (usually hypokalaemia is also present when this is the cause) Narcotics Nicotine Oral hypoglycaemic agents Anti-cancer agents Analgesics e.g. NSAIDS Valproate Oxytocin

30

Treatment Management of SIADH depends on the severity of the hyponatraemia. If the sodium level is >125mmol/L the causative agent should be withdrawn and serum sodium levels monitored daily until they return to normal. Usually sodium levels will normalise within a week of discontinuing an antidepressant,10 however the time necessary for this to happen has ranged from 48 hours to 6 weeks3. If hyponatraemia is mild it can usually be managed with fluid restriction (restrict to 1000ml per day or less)1,7. Sodium chloride tablets (Slow Sodium®) are not normally used for the treatment of SIADH. There are some reports in the literature of asymptomatic patients with sodium levels >125mmol/L whose sodium levels normalised despite continuing with antidepressant treatment. This appears to suggest that hyponatraemia may be a transient adverse event, which corrects itself over time4. Risks and benefits of this approach should be carefully weighed up and very close monitoring of sodium levels ensured. If the patient is symptomatic or the sodium level is <125mmol/L, it is recommended that the causative agent is withdrawn immediately and the patient referred for urgent specialist medical care.10 Often there is a temporal relationship between the patient starting the drug and developing the syndrome, which simplifies the task of identifying this agent. Onset of SIADH can occur within a couple of days of starting a new medicine, however it may also emerge after many months of treatment. Some reports suggest that it tends to develop earlier (during the first few weeks of treatment) with antidepressants, and may take longer to develop with antipsychotics5,11. Subsequent antidepressant use Withdrawal of the offending antidepressant may leave the patient’s condition untreated, yet prescribers must take care when choosing an alternative as most antidepressants have been associated with SIADH. It is generally recommended that if hyponatraemia occurs with a particular drug, then an antidepressant from a different class should be tried next, however there are also some reports of successful rechallenge with the same drug.12 If hyponatraemia occurs with an SSRI, a TCA or an MAOI could be considered next. There is some suggestion that antidepressants that predominantly affect noradrenaline are less likely than those affecting serotonin to cause hyponatraemia (eg lofepramine and reboxetine), however this is still yet to be confirmed. Hyponatraemia is not listed in the manufacturer’s product literature (SPC) for reboxetine however there are 3 case reports in the literature and 3 Yellow Card reports.10 As there are no placebo-controlled studies in elderly patients the manufacturer of reboxetine sates that it cannot be recommended for use in this particular age group.13 Hyponatraemia (SIADH) is listed as a recognised but rare side effect in the SPC for lofepramine.14 The SPC for tryptophan does not list hyponatraemia and there also no reports in the literature or Yellow Card reports.10 However tryptophan should only be initiated by a hospital specialist for treatment resistant depression as an adjunct to other antidepressant treatment. There are cases reported of SIADH reoccurring when patients have been rechallenged with a different antidepressant,1,8 so it is recommended that sodium levels are monitored closely (e.g. weekly)10 for at least the first few weeks of treatment.

In extreme cases, where an alternative antidepressant cannot be used or where SIADH reoccurs despite trying different antidepressants demeclocycline has been used to help manage the problem and to allow continuation of antidepressant treatment.7 Demeclocyline is a tetracycline derivative, which inhibits the effect of ADH on the kidney. The usual recommended dose for treatment of SIADH is 900 to 1200mg daily in divided doses initially, reduced to 600 to 900mg daily for maintenance.15 Tolvaptan, the first oral vasopressin receptor antagonist, was recently launched for the treatment of hyponatraemia secondary to SIADH however only very small numbers of patients in the clinical trials of this drug had iatrogenic causes of SIADH.16

The advice and support of a nephrologist should be sought in all instances where drug treatment of SIADH is being considered. References: 1. Woo M.H. et al. Association of SIADH with Selective Serotonin Reuptake Inhibitors. The Annals of Pharmacotherapy 1997;31:108-110 2. Liu B. et al. Hyponatraemia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective

serotonin reuptake inhibitors: a review of spontaneous reports Canadian Medical Association 1996;155(5):519-527 3. Goldberg R.J. Selective Serotonin Reuptake Inhibitors. Archives of Family Medicine. 1998;7:78-84 4. Finfgeld D. L. SSRI-related hyponatraemia among aging adults. Journal of Psychosocial Nursing & Mental Health Services

2003;41(4):12-19 5. Madhusoodanan S. et al. Hyponatraemia associated with psychotropic medications. Adv Drug React Toxicol Rev 2002;21(1-2):17-29 6. Settle E. Antidepressant drugs: disturbing and potentially dangerous adverse effects. J. Clin. Psychiatry 1998;59(suppl 16):25-30 7. Haddad P, Dursun S and Deakin B. Adverse syndromes and psychiatric drugs – a clinical guide. Oxford University Press 2004 8. Kirby D. Hyponatraemia and selective serotonin re-uptake inhibitors in elderly patients. Int K Geriatr Pscyhiatry 2001;16:484-493 9. Belton K et al. Drug-induced syndrome of inappropriate antidiuretic hormone secretion. Postgrad Med J 1999;75:509-510 10. UKMI Medicines Q&A: If antidepressant-induced hyponatraemia has been diagnosed, how should depression be treated? Q&A 137.2,

expiry 8/2010 11. Spigset O. et al. Hyponatraemia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by psychotropic

drugs Drug Safety 1995;12(3):209-225. 12. Taylor D, Paton C, Kerwin R. The South London and Maudsley NHS Foundation Trust & Oxleas NHS Foundation Trust Prescribing

Guidelines. 10th Edition. Martin Dunitz Taylor & Francis Group 2009. 13. Pharmacia Ltd. Edronax Summary of Product Characteristics. Date of revision of the text: July 2009 14. Merck Serono. Lofepramine Summary of Product Characteristics. Date of revision of the text: 22 February 2010 15. Goldshield Plc. Demeclocycline Summary of Product Characteristics. Date of revision of the text: May 2009 16. Personal communication with Otsuka Pharmaceuticals Medical Information Officer, 4th June 2010

31

Appendix 4: Serotonin Syndrome

Serotonin Syndrome is a potentially life threatening adverse drug reaction that can be caused by a multitude of different substances ranging from prescribed medicines through OTC medications to herbal or homeopathic substances (Table 1). The feature common to all of these substances is that they all increase serotonergic agonism; either alone, as a result of monotherapy or overdose; or in combination, whether that combination is intended or inadvertent. Unlike Neuroleptic Malignant Syndrome, Serotonin Syndrome is not an idiopathic reaction but a predictable response to the overstimulation of serotonin receptors1. Serotonin syndrome can occur in all age groups from newborn infants and children through to the elderly1. The presentation of the syndrome varies with the severity of the syndrome (Table 2). Often the signs of mild serotonin syndrome, such as tremor and diarrhoea, are overlooked but the syndrome can quickly escalate to life-threatening delirium, neuromuscular rigidity and hyperthermia1. Due to the syndromes’ insidious presentation and ensuing difficult diagnosis, an accurate figure for prevalence of the syndrome is difficult to make but it is not felt to be rare. An incidence of serotonin syndrome of 14 to 16% in cases of SSRI overdose has been reported1. No laboratory test confirms the diagnosis of serotonin syndrome however there have been prior attempts to produce some diagnostic criteria that, whilst useful, have been found in clinical practice to overlook early, mild presentations of the syndrome (Table 3). However a recent review of the clinical and toxicological signs in over 2000 cases of self-poisoning with serotonergic drugs revealed statistically significant associations between certain neuromuscular and autonomic signs and a diagnosis of serotonin syndrome. From this range of signs the presence of clonus, whether inducible, spontaneous or ocular, seems to be the most significant in establishing a diagnosis of serotonin syndrome1.

Table 1: Drugs which can potentially cause serotonin syndrome1,2

Prescribed medications SSRI’s: sertraline, fluoxetine, paroxetine, citalopram and fluvoxamine

Other antidepressants: trazodone, TCA’s particularly clomipramine, venlafaxine, buspirone.

MAOI’s: phenelzine, moclobemide and isocarboxazid

Anticonvulsants: Valproate

Antimanic: Lithium

Analgesics: fentanyl, tramadol and pentazocine

Anti-emetics: ondansetron, granisetron and metoclopramide

Antimigraine: sumatriptan

Miscellaneous: sibutramine, linezolide & ritonavir

OTC medications & Herbal Cough & cold remedies containing dextromethorphan

Herbal: tryptophan, Hypericum perforatum (St John’s Wort) & ginseng.

Drugs of Misuse MDMA/ecstasy, LSD, 5-methoxydiisopropyltryptamine, Syrian rue

Table 2 : Signs & Symptoms of Serotonin Syndrome1

Mild

Tachycardia, shivering, diaphoresis, mydriasis, tremor or myoclonus, hyperreflexia

Moderate

Tachycardia, hypertension and hyperthermia (core temp of 40οC is not uncommon).

Mydriasis, hyperactive bowel sounds, diaphoresis and normal skin colour will be

found on physical examination. Hyperreflexia and clonus may be considerably

greater in lower extremities. Changes in mental state include mild agitation and

hypervigilance as well as slightly pressured speech.

Severe

May have severe hypertension and tachycardia that may deteriorate into frank

shock. May have agitated delirium, muscular rigidity and hypertonicity. Muscle

hyperactivity may produce core temperature of more than 41οC.

Complications arising, possibly from poorly treated hyperthermia, include metabolic

acidosis, rhabdomyolsis, elevated serum aminotransferase and creatinine, seizures,

renal failure and disseminated intravascular coagulation (DIC).

This appendix is for information only – if there is any doubt about a diagnosis the patient should be refered to A&E

32

Table 3: Diagnostic Criteria, Sternbach 1991

a) Coincident with the addition of or an increase in dosage of a known serotonergic agent to an

established medication regimen. At least three of the following clinical features must be present:

i) Mental status changes e.g.

confusion, hypomania

ii) Agitation

iii) Myoclonus

iv) Hyperreflexia

v) Diaphoresis

vi) Shivering

vii) Tremor

viii) Diarrhoea

ix) Incoordination

x) Fever

b) Other aetiologies e.g. infections, metabolic, substance misuse or withdrawal have been ruled out.

c) An antipsychotic drug has not been started or increased in dosage prior to the onset of symptoms.

Recommendations for Diagnosis1

Interview: ask about prescription and OTC medications, illicit substances, herbal/dietary supplements, caffeine, and alcohol.

Physical examination: include focussed assessment of deep tendon reflexes, clonus and muscle rigidity. Assess size & reactivity

of the pupils, dryness of oral mucosa, intensity of bowel sounds, skin colour and presence or absence of diaphoresis. Take a core

temperature, blood pressure and pulse to assess for hyperthermia, hypertension and tachycardia.

Differential Diagnosis1 Anticholinergic poisoning: these patients have normal reflexes and show the “toxidrome” of mydriasis; agitated delirium; dry oral

mucosa; hot,dry, erythematous skin; urinary retention; and absence of bowel sounds. (Serotonin syndrome patients have

hyperactive bowel sounds and normal skin colour).

Malignant Hyperthermia: characterized by increasing concentrations of end-tidal CO2, hypertonicity, hyperthermia and metabolic

acidosis. This event usually occurs minutes after exposure to inhalational anaesthetic agents. Examination reveals skin to be

mottled with cyanotic areas that contrast with patches of bright red flushing. Skeletal muscles exhibit rigidity and hyporeflexia.

Neuroleptic Malignant Syndrome: defined by slow onset, bradykinesia or akinesia, “lead pipe” muscular rigidity, hyperthermia,

fluctuating consciousness and autonomic instability. These signs and symptoms evolve over several days in contrast to the rapid

onset and hyperkinesia of serotonin syndrome.

Management 1,2

1. Removal of precipitating drugs; Serotonin syndrome is usually self-resolving within 24 hours after the removal of the

precipitating agent/s.

2. Refer to A&E

References 1. Boyer E, Shannon M. The Serotonin Syndrome. NEJM 2005; 352:1112-20. 2. Mir S, Taylor D. Serotonin Syndrome. Psychiatric Bulletin 1999; 23:742-747.

33

Appendix 5: Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome is a potentially life-threatening problem associated with the use of antipsychotic medication. It

occurs with an incidence of approximately 0.2%.1 NMS can occur in females and males of all age groups who are treated with

antipsychotics for various psychiatric illnesses as well as in medical patients who receive antiemetics or sedatives with

neuroleptic properties (e.g. metoclopramide, prochlorperazine, promethazine).1, 2 Patients that may be at greater risk for

developing NMS include those with other conditions affecting deep brain structures, those with pre-existing catatonia, and those

with low serum iron, agitation, exhaustion, or dehydration. 1, 2 NMS usually occurs within the therapeutic range however it has

been suggested that people who do develop NMS are more likely to have received higher doses, more rapid titration, and more

parenteral neuroleptic injections.1

NMS has a variable onset and can sometime develop very quickly. Early features, which occur in about 80% of cases, include

rigidity and altered mental status. These features are then followed by autonomic changes and hyperthermia.1,3 A typical patient

with NMS appears awake but dazed, stuporous, and mute,1 however mental state changes range from stupor to coma. Table 1: Common clinical features of NMS1

• Altered level of consciousness • Catatonia • Diaphoresis • Dysarthria

• Dysphagia • Elevated temperature • Incontinence • Labile blood pressure

• Muscle rigidity • Mutism • Myoclonus • Rigidity

• Sialorrhoea • Tachycardia • Tachypnoea • Tremor

Unfortunately there are no laboratory tests that are specific in aiding a diagnosis of NMS, however a full laboratory evaluation is

essential in order to exclude other causes of hyperthermia.1

Table 2: Common laboratory findings1, 2

• Raised serum creatine kinase • Metabolic acidosis • Leukocytosis • Hypoxia

• Low serum iron • Serum catecholamine elevations • Electrolyte abnormalities • Coagulopathies

Disease states and conditions that are often confused with NMS that should be excluded include infections, midbrain structural

lesions, benign extrapyramidal side effects, malignant catatonia or delirious mania secondary to psychotic disorders, autoimmune

disorders, environmental heatstroke, serotonin syndrome, and withdrawal from dopamine agonists, other drugs or alcohol.2

Early recognition of NMS with exclusion of other possible causes should be followed quickly by the discontinuation of the

suspected causative drug.

Management

1. Removal of precipitating drugs.

2. Refer to A&E

References:

1. Caroff SN, Mann SC, Campbell EC. Neurolpetic Malignant Syndrome. Adverse Drug Reaction Bulletin 2001;209:799-802 2. Caroff SN. Nueroleptic Malignant Syndrome. Still a risk, but which patients may be in danger? Current Psychiatry 2003;12(2):36-42 3. Proctor and Gamble Pharmaceuticals Limited. Dantrium intravenous Summary of Product Characteristics. Date of revision of the text:

October 2002

This appendix is for information only – if there is any doubt about a diagnosis the patient should be refered to A&E

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Appendix 6: For hospital practitioners & for in-patients only Drug treatments for serotonin syndrome and NMS

This appendix is for information only – treatment will be conducted in an A&E environment

Drug treatments for Serotonin Syndrome:

Treatment Drug Comments

Sedatives (agitation) Lorazepam, diazepam To control agitation and may blunt the hyperadrenergic response. Physical restraint not advised as may contribute to severe lactic acidosis and hyperthermia.

Cyproheptadine Recognised as a treatment for serotonin syndrome but efficacy has not been clearly established.

Olanzapine Sublingual administration has been found to be beneficial but again efficacy has not been rigorously determined

5HT2A antagonist

Propranolol

Hyperthermia

Diazepam, lorazepam Vecuronium

Antipyretics e.g. paracetamol, ibuprofen

Control of hyperthermia involves eliminating excessive muscle activity. Benzodiazepines may be beneficial in moderate cases but in severe cases (temp >41C) paralysis should be induced using non-depolarizing agents e.g. vecuronium. Have no role as the hyperthermia is not related to an alteration in the hypothalamic temperature set point.

Drug treatments and interventions for Neuroleptic Malignant Syndrome: Early recognition of NMS with exclusion of other possible causes should be followed quickly by the discontinuation of the

suspected causative drug.

Intensive supportive care should be given to reduce temperature, ensure fluid balance, and to detect complications.2 In some

cases this management will be adequate until recovery occurs.1

However the following interventions may be useful in some cases. They should be chosen empirically, based on the character,

severity and duration of symptoms in a given case.2

Drug and indication Dose and notes Benzodiazepines For sedation, reversal of catatonia.

Parenteral lorazepam 1 to 2mg or higher, moving to oral treatment to maintain the effect when appropriate

Dopamine agonists For reversal of parkinsonism and dopamine agonist properties. NB can worsen psychosis and cause hypotension and emesis.

Bromocriptine 2.5mg every 8 hours or amantadine 100mg every 8 hours. Monitor psychosis, BP, and nausea. Newer drugs such as ropinorole and pramipexole may also be useful.

Dantrolene For reducing hyperthermia related to skeletal muscle hypermetabolism.

1 to 2.5mg/kg IV every 6 hours. If response is obtained oral dantrolene can be used to maintain the effect. Monitor respiratory function and hepatic function. Avoid calcium channel blockers.3

ECT For patients who fail to respond to drug therapy or supportive care, or for patients with residual catatonic symptoms.

ECT may be preferred if idiopathic lethal catatonia cannot be excluded and in patients who remain psychotic after NMS has resolved.1 Non-depolarizing muscle relaxants should be used instead of succinylcholine in patients with rhabdomyolysis to avoid the risk of hyperkalaemia.

References:

1. Caroff SN, Mann SC, Campbell EC. Neurolpetic Malignant Syndrome. Adverse Drug Reaction Bulletin 2001;209:799-802 2. Caroff SN. Nueroleptic Malignant Syndrome. Still a risk, but which patients may be in danger? Current Psychiatry 2003;12(2):36-42

35

Appendix 7: Antipsychotic-induced hyperprolactinaemia

- guidelines for identification, monitoring, and management

The normal range of prolactin is:

Males 45 – 375 mU/L Females 60 – 620 mU/L There are many physiological, pharmacological and pathological causes of hyperprolactinaemia – see main guideline for more details.

Which antipsychotics are associated with hyperprolactinaemia? All antipsychotics have the potential to raise prolactin. The antipsychotics associated with the highest prevalence of hyperprolactinaemia are risperidone and amisulpride.3 Risperidone appears to cause a bigger elevation in prolactin and more frequently than with haloperidol,3 however all the typical antipsychotics are associated with hyperprolactinaemia to varying degrees. The lowest prevalence rate reported with the typicals is 33% and the highest is 87%.3 The effect of antipsychotics on prolactin is dose-related. Comparison of the approximate extent to which antipsychotics raise prolactin4,5,6

Antipsychotic Prolactin elevation Conventional (typical) ↑↑ to ↑↑↑ Amisulpride ↑↑ to ↑↑↑ Aripiprazole ←→ Clozapine ←→ Risperidone ↑↑ to ↑↑↑ Quetiapine ←→ Olanzapine ←→ to ↑(usually transient) What are the effects of hyperprolactinaemia? Common symptoms Some people with a raised prolactin may display no symptoms. Others may experience problems such as amenorrhoea, breast enlargement, galactorrhoea, reduced libido, erectile dysfunction, oligospermia, and anorgasmia. Sexual dysfunction is reported by 30-93% of people receiving antipsychotics. Although there are various mechanisms by which antipsychotics can affect sexual function, it is more commonly reported in patients taking antipsychotics that cause hyperprolactinaemia.7

Long term complications - osteoporosis Osteoporosis leads to skeletal fragility and fracture, particularly common are fractures of the hip, spine and wrist. Age related osteoporosis is the commonest reason for fractures, however hyperprolactinaemia is an important secondary cause.8 Women with amenorrhoea and men with sexual dysfunction plus low testosterone that has been present for 3 to 6 months or more should be referred further investigation into the adverse effect of raised prolactin on bone (see the management algorithms on the following pages for more detailed information about which patients require referral)

Long term complications – cancer Although there are conflicting reports about the rates of cancer in those receiving antipsychotics, recent evidence suggests that hyperprolactinaemia is associated with breast cancer. Evidence also suggests that rates of prostate cancer may be increased in patients with hyperprolactinaemia, but further research in this area is required. The implications for patients receiving antipsychotics is unclear, however it would seem prudent to avoid prolactin-raising antipsychotics in patients with a history of breast cancer and probably prostate cancer.10

A note about baseline prolactin levels Blood should be taken prior to any doses of antipsychotic because even a single dose can raise prolactin. If a baseline level is raised (and the patient was not being switched from another antipsychotic that could explain the level)

and it is confirmed that no dose of the prolactin-raising antipsychotic was taken prior to the blood being taken this could be explained by stress.

Stress may cause slight increases in prolactin to levels of up to 1000mU/L. Levels higher than those explained by stress (ie >1000mU/L), taken prior to the initiation of any antipsychotic, warrant

referral to the endocrinology team at the Churchill Hospital for further investigation.

For the purpose of this appendix to the Psychotropic Monitoring Guideline only limited background detail and the management algorithms have been included. The full guideline includes more detailed background about hyperprolactinaemia, its causes and complications, along with the forms that are required to make referrals to the JR and the to the NOC for those patients who meet the criteria for further investigation into the effects of raised prolactin on their bones.

***The full guideline is available on the Trust Intranet and should be referred to for more detail.***

←→ = no or minimal elevation ↑ = mild elevation ↑↑ = moderate elevation ↑↑↑ = marked elevation

For a comprehensive guide on how to identify and manage antipsychotic-induced hyperprolactinaemia please follow the algorithm on the following two pages

36

Antipsychotic-induced hyperprolactinaemia – guidelines for identification, monitoring, and management (appendix 7 continued)

Are you initiating an antipsychotic known to cause a sustained rise in prolactin for the first time in your patient?

If you are following these guidelines for the 1st time in your patient: ⇒ Start at A if you are initiating an antipsychotic ⇒ Start at B if your patient is currently taking an antipsychotic

Is your patient currently receiving an antipsychotic known to cause a sustained rise in prolactin?

There is no need to take a baseline prolactin level. Check prolactin only if symptoms of hyperprolactinaemia develop (see appendix 1 in the full guideline for screening tool).

A B

Are there any symptoms that might indicate hyperprolactinaemia? (see appendix 1 in the full guideline for screening tool)

There is no need for prolactin levels to be monitored unless symptoms indicate otherwise (see appendix 1 in the full guideline for screening tool).

Recheck prolactin after 3 months on a stable dose (or before if indicated by symptoms)

For information about interpretation and management of raised baseline levels see previous page

Take a prolactin level as soon as possible.

Take a prolactin level before giving any doses of the antipsychotic. The level can be taken when blood is drawn for all other required baseline measurements (see OBMH Psychotropic Monitoring Guideline)

A prolactin level should be included when the patient’s next blood test is due (eg physical health check), or sooner if symptoms indicate a more urgent need

Prolactin normal. Continue antipsychotic. Further prolactin level monitoring is not necessary unless there has been a dose increase (re-check 3 months after any dose increase) or if symptoms indicate a need.

Prolactin raised (males >375mIU/L, females >620mIU/L) See next page for further guidance

Yes No Yes No

NoYes

37

1. Consider dose reduction or a switch to an antipsychotic with a lower potential to elevate prolactin (but see NOTES section below and notes for primary care) 2. In addition, follow the recommendations below to identify which patients require further investigation into the adverse effect of raised prolactin on bone: MALES In males without a history of >1 fragility fracture# who have had sexual symptoms present for 3-6 months (or longer) Take a testosterone level (take at 9 am). If the testosterone level is less than 8.4nmol/L, follow the instructions in box 1. In males with a history of >1 fragility fracture# Follow the advice in box 1. NB there is no need to take a testosterone level. FEMALES In females with a history of >1 fragility fracture# follow the advice in box 1. In females without a history of >1 fragility fracture# but who have had amenorrhoea present for 3-6 months (or longer) refer all females, except those who are receiving combined oral contraception (COC) (the COC provides enough oestrogen to protect bones), for further assessment to Prof Margaret Rees’ clinic at the JR using the referral form in appendix 3 [NB. referral includes women who use progesterone-only methods of contraception and women who are peri- or post-menopausal].

Prolactin >3000mIU/L

Consider prolactinoma – refer to endocrinologist (at the Churchill Hospital) for further investigation

Asymptomatic

Symptomatic (see appendix 1 in the

full guideline)

Prolactin <3000mIU/L

Continue antipsychotic and monitor for symptoms (see appendix 1 in the full guideline). Recheck prolactin only if indicated by symptoms.

BOX 1 Conduct the following blood tests: FBC, ESR, U&Es, Cr, Ca, PO4, Albumin, ALP, ALT, and TSH. Then refer for further assessment and DXA scanning to Dr Javaid’s clinic at the Nuffield Orthopaedic Centre using the referral form in appendix 2.

NB. For patients who do not meet the referral criteria above and continue to have a raised prolactin (eg if antipsychotic dose reduction is not possible/does not result in normalisation of prolactin &/or a switch is not possible), consideration should be given to the following: men - repeat testosterone level at 6-monthly intervals, women - establish whether amenorrhoeic at 6 monthly intervals and follow referral criteria as above, if appropriate.

consider repeating prolactin level under ideal conditions ie in the morning at least 1 hour after waking and before eating consider the effects of stress on prolactin levels (see page 2) rule out pregnancy in female patients assess for any symptoms of hyperprolactinaemia (see screening tool in appendix 1 in the full guideline), if not already done

Notes for primary care GPs should refer patients to OBMH for a review of their antipsychotic medication if a dose reduction or switch is indicated. If appropriate, the Psychiatrist will also initiate referral for further investigation of bone risk, liaising with the GP about blood tests.

Prolactin raised

Continued from previous page (appendix 7 continued)

NOTES 1. Side effects must be balanced against the benefits of treatment. 2. Other risk factors for osteoporosis should be addressed eg smoking

(see OBMH smoking cessation guideline), sedentary lifestyle (see OBMH weight management guideline), and alcohol intake.

3. A normalisation in prolactin may result in the return of fertility. And contraceptive advice may need to be offered.

4. Prolactin levels should fall fairly quickly after dose reductions or switches, but a return to normal may take several weeks. Recheck prolactin monthly until normal.

5. Dopamine agonists to treat hyperprolactinaemia should only be considered in exceptional circumstances due to the serious risk of worsening the psychosis.

6. There are a handful of case reports and 1 RCT of aripiprazole being used as “add-on” therapy to reduce prolactin when switching antipsychotics is not possible (see full guideline for further details).

# Fragility fracture definition: A type of (pathological) fracture occurring as a result of a trauma – typically from a fall. Exclusions are major RTAs, falls from more than 10 feet, and the following fracture sites: fingers, toes, scaphoid and skull.

38

Appendix 8: Cardiovascular Disease (CVD) – guidance for assessing risk and recommendations for primary prevention management (lipid modification)

Background Several medicines used in the treatment of mental health problems can cause adverse effects that may indirectly contribute to poor cardiovascular health for example lipid alterations, weight gain, hyperglycaemia and diabetes (see OBMH psychotropic monitoring guidelines). These effects alone or in combination with other factors frequently seen in this patient population, such as smoking, poor dietary intake and lack of physical exercise, all increase a person’s overall cardiovascular risk. NICE guidelines for lipid modification recommend that, for the primary prevention of cardiovascular disease (CVD), a systematic strategy should be used in primary care to identify people who are likely to be at high risk. These people should then be prioritised on the basis of an estimate of their CVD risk before a full formal risk assessment. Aim of this guideline The purpose of this guideline is to provide OBMH staff with the tools to calculate CVD risk. This may be particularly important for longer stay inpatients who may miss routine CVD risk assessments that are conducted in primary care. It could also be useful in decision making where choice of psychotropic treatment may be influenced by existing CVD risk. We hope that it may identify an unmet need in some patients who could benefit from statin therapy. Depending on a patient’s circumstance, it may be appropriate for OBMH clinicians to either initiate this treatment or to include details of calculated risks in the GP discharge summary so that statin treatment can be started in primary care. Calculating CVD risk Use the algorithm and the CVD risk prediction charts on the following pages. Assessment for lipid modification therapy If the calculated CVD risk suggests that lipid modification therapy is indicated (10 year CVD risk estimate >/=20%) consider the following: 1. Before offering lipid modification therapy for primary prevention, carry out the following tests/assessments

and optimise the management of any modifiable risk factors if possible: Smoking status Refer to OBMH NRT guideline Alcohol consumption Offer advice on recommended intake and encourage patients to cut down if they drink excessively.

Recommendations are that men should not regularly drink more than 3 to 4 units of alcohol/day and women should not regularly drink more than 2 to 3 units of alcohol/day.

Blood pressure Target blood pressure = sBP <140 and dBP<90. Refer to NICE hypertension guideline for further information.

BMI / waist circumference

Refer to OBMH weight management guideline.

Fasting TC, LDLC, HDLC, and TGs (if not already available)

NICE state that there is no target level for total or LDLC for primary prevention. Repeat lipid profiles are stated as being not necessary but management should be reviewed according to clinical judgement.

Fasting blood glucose (non-fasting if fasting is not possible)

If non-fasting glucose is <6.1 there is no need to repeat. If non-fasting level is >/=11.1mmol/L and symptoms are present (ie polyuria, polydipsia, unexplained weight loss) a diagnosis of diabetes should be made. If non-fasting level is >6.1 but <11.1 or if level is >11.1 with no symptoms, take a fasting level (FPG). If FPG >/= 7.0mmol/L AND symptoms present a diagnosis of diabetes should be made. If FPG >/= 7.0mmol/L without symptoms repeat FPG. If diagnosis remains unclear, consider conducting an OGTT. A FPG of 6.1-6.9mmol/L may indicate either Impaired Glucose Tolerance (IGT) or Impaired Fasting Glucose (IFG) but does not necessarily exclude diabetes. The practical approach to managing a FPG of 6.1-6.9mmol/L is to offer lifestyle advice and then recheck FPG in 3 to 6 months time. For further information see OBMH guideline “abnormal glucose levels – recommendations for further monitoring” in appendix 9 below (or on the Trust intranet).

LFTs (transaminases)

Do not routinely exclude from statin therapy people with transaminases that are raised but less than 3 times the upper limit of normal (ULN).

TSH if dyslipidaemia present

Hypothyroidism can raise plasma lipid levels

Creatine kinase (CK) level

It is not necessary to routinely measure CK levels prior to initiation of statin therapy in all patients. However, patients with existing risk factors for myopathy/rhabdomyolysis should be treated with caution and the risks and benefits carefully weighed up before considering treatment and in the following situations abaseline CK level should be taken: elderly (age > 70 years), renal impairment, uncontrolled hypothyroidism, personal or familial history of hereditary muscular disorders, previous history of muscular toxicity with a statin or fibrate, alcohol abuse. If CK levels are significantly elevated (> 5 x ULN) at baseline, treatment should not be started and the results should be re-measured after 5 7 days. All patients should be advised of the risk of myopathy with statins and told to report promptly any unexplained muscle pain, tenderness or weakness. The risk of myopathy is dose-related.

39

(appendix 8 continued) 2. Offer 40mg simvastatin (or include a copy of the CVD risk calculation in the discharge summary to the

GP). If there are potential drug interactions consider a lower dose of simvastatin or use pravastatin 40mg (pravastatin is not metabolised via CYP3A4 so is devoid of some of the interactions common to simvastatin). It may be preferable to use pravastatin in patients with pre-existing muscle disease (pravastatin is hydrophilic and may be less likely to cause muscle effects). See below for additional information relating to the contraindications and interactions for simvastatin. For further information or advice about drug interactions or cautions/contraindications with statin therapy please contact the Trust’s Medicines Information Service on 01865 455716.

3. Continue 40mg simvastatin. It is not necessary to escalate the dose to achieve a target cholesterol level (see further monitoring below). If the patient experiences intolerable side effects consider simvastatin 20mg or pravastatin 40mg, if appropriate.

4. Further monitoring:

• LFTs: Repeat LFTs within 3 months and at again 12 months, unless alterations in LFTs or the presence of symptoms indicate testing is required sooner. Only carry out further LFTs if clinically indicated.

• CK level: If muscle pain, weakness or cramps occur whilst a patient is receiving treatment with a statin, their

CK levels should be measured. If these levels are found, in the absence of strenuous exercise, to be significantly elevated (> 5 x ULN), treatment should be stopped. If muscular symptoms are severe and cause daily discomfort, even if CK levels are < 5 x ULN, treatment discontinuation may be considered. If myopathy is suspected for any other reason, treatment should be discontinued. If symptoms resolve and CK levels return to normal, then re-introduction of the statin or introduction of an alternative statin may be considered at the lowest dose and with close monitoring.

• LIPIDS: Repeat lipid profile is not necessary (NICE guidelines state that there is no target level for total or LDL

cholesterol for primary prevention. Repeat lipid profiles are stated as being not necessary but management should be reviewed according to clinical judgement and patient preference.)

Simvastatin

Contraindications • Active liver disease or unexplained persistent elevations of serum transaminases

• Pregnancy and lactation (see section 4.6) • Concomitant administration of potent CYP3A4 inhibitors (see below) Potent CYP3A4 inhibitors: Itraconazole Ketoconazole Erythromycin Clarithromycin Telithromycin HIV protease inhibitors Nefazodone

Contraindicated – do not co-prescribe

Gemfibrozil

Avoid, but if necessary do not exceed 10 mg simvastatin daily

Ciclosporin Danazol Other fibrates (except fenofibrate)

Do not exceed 10 mg simvastatin daily

Amiodarone Verapamil


Diltiazem


Fusidic acid

Patients should be closely monitored. Temporary suspension of simvastatin treatment may be considered.

Grapefruit juice

Avoid grapefruit juice when taking simvastatin

Interactions

Warfarin Enhanced anticoagulant effect – monitor INR more closely References JBS2: Joint British Societies’ guidelines on prevention of cardiovascular disease in clinical practice. Heart 2005:91;v51-v52. NICE Clinical Guideline 67. Lipid modification. May 2008. NICE Clinical Guideline 34. Hypertension: management of hypertension in adults in primary care. June 2006. NICE Clinical Guideline 66. Type 2 diabetes. May 2008. BMS Pharmaceuticals Ltd. Zocor. Summary of Product Characteristics. Date of revision of the text: 23 July 2009 MSD Ltd. Lipostat. Summary of Product Characteristics. Date of revision of the text: October 2009.

40

Calculating CVD risk

Does your patient have: • CHD or other major artherosclerotic disease? • Familial hypercholesterolemia or other inherited

dyslipidaemias? • Renal dysfunction including diabetic nephropathy? • Type 1 or 2 diabetes mellitus? • High BP (dBP >100mmHg or sBP >160mmHg)? • Lesser degrees of raised BP that has caused target organ

damage (eg retinopathy, renal impairment, left ventricular hypertrophy on ECG or echo)?

• TC:HDLC >/= 6.0?

Is your patient • >75 years?

Calculate CVD risk using the charts on following page

You will need: • Age* • Smoking history** • sBP*** • Total cholesterol (fasting if possible – random if

not)

Is your patient aged 40 to 74?

If less than 40 but with a family history of premature CHD in a 1st degree relative (premature = male relative <55 years, female relative <65 years) continue with CVD risk assessment. If less than 40 with no risk factors for CVD – review risk on an ongoing basis eg yearly. If less than 40 but with one or more risk factor present (eg smoking history**, hypertensive, raised lipids, obese, centrally obese, raised TG, low HDL, IFG, IGT, low socioeconomic group, chronic kidney disease, RA, SLE, HIV Tx, antipsychotic Tx, premature menopause) continue with risk assessment, project risk forward to age 49, and make a clinical judgement, as their CVD risk will be higher than that shown on the chart by the time they reach 49. Consider potential life-years gained by treating someone earlier who is on track to become high risk in later life.

YES

Your patient is already at high risk of CVD and should be offered lifestyle intervention and appropriate use of antithrombotic, antihypertensive, and lipid lowering therapy.

NO YES

Consider to be at increased risk of CVD and likely to benefit from statin treatment, particularly if they smoke or have high BP. Consider co-morbidities, benefits and risks of treatment, and person’s preference

NO NO

YES

Is the CVD risk estimate >/=20%?

Is the CVD risk estimate approaching 20%?

If your patient is a male with South Asian background - ↑ the calculated risk by a factor of 1.4 If your patient has one 1st degree relative with a history of premature CHD (premature = male relative <55 years, female

relative <65 years) - ↑ the calculated risk by a factor of 1.5 If your patient has more than one 1st degree relative with a history of premature CHD - ↑ the risk by a factor of 2.0

NO Review risk on an ongoing basis e.g. yearly NO

Offer information about absolute risk of CVD and the absolute benefits & harms of an intervention over a 10 year period Discuss lifestyle changes for primary prevention (see NICE CG67 Lipid modification, OBMH weight management

guidelines, and OBMH smoking cessation guideline) Optimise management of other modifiable risk factors (see previous pages) Offer statin treatment (see previous pages)

YES

Consider other risk factors that are not included in the chart (see above in red) and make a clinical judgement about the need for intervention

YES

* Charts are for 3 age ranges: <50, 50-59, and >/=60. Risks given are actually for age 49, 59, and 69. So, charts will overestimate risk in the 2 younger age bands unless aged exactly 49 or 59 and overestimate risk for those aged <69 and underestimate risk for >70 ** An assessment of lifetime tobacco exposure is required. Classifying someone as a smoker or non-smoker is not sufficiently precise. Those who have given up smoking within the previous 5 years should be classed as smokers. A judgement should be made for other ex-smokers – for example a current smoker who smokes 5/day for the last 8 years has a lower exposure than an ex-smoker who smoked 40 per day for 20 years until 6 years ago. To classify the 40/day smoker as a non-smoker would under-estimate the real CVD risk. *** CVD risk estimation is more complicated for people already on drug treatment for hypertension. Using the risk estimate based on treated BP could lead to a decision not to use statins, whereas using a pre-treatment BP could result in an estimate of risk >/=20%. It is important, if possible, to estimate CVD risk retrospectively by using a pre-treatment BP whenever this can be found in the notes. If there is no record, as a rule of thumb, assume sBP was at least 160mmHg.

Appendix 8 continued

41

Appendix 8 continued Joint British Societies’ cardiovascular disease risk prediction charts:

42

Appendix 9: Abnormal glucose levels – recommendations for further monitoring Background Several medicines used in the treatment of mental health problems can cause adverse effects that may indirectly contribute to the development of Type 2 diabetes for example weight gain, alterations in glucose regulation and the “metabolic syndrome” (see OBMH psychotropic monitoring guidelines). These effects alone or in combination with other factors frequently seen in this patient population, such as poor dietary intake and lack of physical exercise, all increase a person’s overall risk of developing diabetes. Untreated or poorly controlled diabetes increases a person’s risk of developing problems such as high blood pressure, cardiovascular disease, stroke, retinopathy, nephropathy and diabetic foot problems. It has been estimated that 7 million people in the UK have a condition termed “pre-diabetes”. Pre-diabetes is where there is impaired glucose regulation but levels of glucose are not high enough for a diagnosis of diabetes. Patients with pre-diabetes have an increased risk of heart disease and stroke and are 15 times more likely to develop Type 2 diabetes than those without it; however lifestyle modifications can delay or prevent the progression to diabetes in up to 60% of cases. Aim of these recommendations The purpose of these recommendations is to provide guidance for OBMH staff on what to do if abnormal glucose levels are identified during the routine psychotropic medication monitoring that is recommended in the Psychotropic Monitoring Guidelines. Glucose level testing Ideally, plasma glucose levels should be taken in the fasting state, however, for many of our patients this may not be practical. Therefore a non-fasting level is adequate as an initial test. The flow chart on the following page may be useful to help identify what should be done with an abnormal non-fasting plasma glucose level. Patients identified as having Impaired Glucose Tolerance (IGT) or Impaired Fasting Glycaemia (IFG) IGT and IFG are not clinical entities in their own right, but rather risk categories for cardiovascular disease and / or future diabetes. Consideration should be given to switching psychotropic medication to a lower risk alternative where possible. For IFG and IGT the aim is to prevent progression to diabetes through lifestyle intervention and drug management (if appropriate). Patients should be offered diet, exercise, and other lifestyle advice and should be followed up at 6 months and then annually with repeat fasting glucose level tests (or more frequently if psychotropic medication cannot be switched). Patients identified as having Type 2 Diabetes: Consideration should be given by the psychiatric team to switching psychotropic medication to a lower risk alternative where possible. Inpatients who are likely to only be in hospital for a short time should have the details of all glucose level findings communicated to the GP in the discharge letter and the patient should be advised to make an appointment with their GP as soon as possible in order that an appropriate care plan can be put in place. For longer-stay inpatients, appropriate management of diabetes should be initiated as soon as possible. The psychiatrist should consult the NICE Type 2 Diabetes guideline &/or the Clinical Knowledge Summary guidance on Type 2 Diabetes management and they may wish to liaise with appropriate specialists for advice if appropriate (the diabetes nurse specialists and registrars at OCDEM [Oxford Centre for Diabetes Endocrinology and Metabolism 01865 857371] are happy to offer phone advice about our OBMH inpatients if necessary). A brief summary of the current UK guidance and recommendations is included on the following pages for information including links to other OBMH guidelines if relevant. For longer-stay patients who are eventually discharged back to primary care, detailed information about what treatment plan has been put in place including any referrals made (eg for retinal screening) should be communicated to the GP. Please note that monitoring blood glucose using finger prick testing sticks in patients with Type 2 Diabetes who are not on insulin is not usually recommended. However Oxfordshire PCT allow the use of finger prick testing in special circumstances – please see “Self-Monitoring of Blood Glucose in Type 2 Diabetes” on the PCT intranet by clicking here or see link in bibliography below.

http://opct.oxnet.nhs.uk/GeneralPractice/Document Library/Prescribing/Prescribing Guidelines/Self Monitoring Blood Glucose in TII Diabetes.pdf

43

If an OGTT is carried out: Diagnose diabetes if 2 hour OGTT >/= 11.1mmol/L Diagnose Impaired Glucose Tolerance (IGT) if 2 hour OGTT >/= 7.8 and <11.1mmol/L Diagnose Impaired Fasting Glucose (IFG) if 2 hour OGTT <7.8mmol/L

Appendix 9 continued Managing abnormal blood glucose levels: Bibliography • Diabetes type 2. Clinical Knowledge Summary. V 2.3. Accessed online at http://www.cks.nhs.uk/diabetes_type_2# • Type 2 diabetes. NICE Clinical Guideline 66, May 2008. Accessed online at http://www.nice.org.uk/ • WHO, World Health Organisation / International Diabetes Federation, Definition & Diagnosis of Diabetes Mellitus & Intermediate Hyperglycaemia,

2006 • Hackett E & Jacques N. Type 2 diabetes – pathophysiology and clinical features. Clinical Pharmacist 2009;1:475-478 • Self-Monitoring of Blood Glucose in Type 2 Diabetes

http://opct.oxnet.nhs.uk/GeneralPractice/Document%20Library/Prescribing/Prescribing%20Guidelines/Self%20Monitoring%20Blood%20Glucose%20in%20TII%20Diabetes.pdf

Acknowledgements With thanks to Nicola Middleton (Diabetes Research Nurse, OCDEM), Dr Michael Robertson (GP), Dr Margaret Denman (GP), and Dr Jonathan Bickford (GP) for their comments and input in the production of these guidelines.

*Oral Glucose Tolerance Test (OGTT) ⇒ The test involves giving anhydrous glucose 75g after an overnight fast

of at least 8 hours. ⇒ During the 3 days prior to the test the patient should consume a

normal carbohydrate diet. ⇒ The patient should not eat or smoke on the morning of the test or

during the test. ⇒ The glucose load should be prescribed as Polycal liquid 113mL to be

given with water to administer a total volume of 200mL (shake well to mix). This should be consumed over a 5 minute period followed by a further 100mls of plain water.

⇒ A blood sample is drawn exactly 2 hours later to measure the glucose level.

Non-fasting plasma glucose

level

No need to repeat

<6.1 mmol/L

Take a fasting plasma glucose level (FPG)

>6.1 but <11.1mmol/L

FPG >/= 7.0mmol/L AND symptoms present (ie polyuria, polydipsia, unexplained weight loss) = DIAGNOSIS of DIABETES

FPG >/= 7.0mmol/L WITHOUT symptoms

FPG = 6.1-6.9mmol/L

Repeat FPG

If repeat FPG >/= 7.0 = DIAGNOSIS of DIABETES

A FPG of 6.1-6.9mmol/L may indicate either Impaired Glucose Tolerance (IGT) or Impaired Fasting Glucose (IFG) but does not necessarily exclude diabetes. The practical approach to managing a FPG of 6.1-6.9mmol/L is to offer lifestyle advice and then recheck FPG in 3 to 6 months time. However, the only way to confirm the presence of IGT, IFG or diabetes in this group of patents is to carry out an OGTT.*

If repeat FPG does not confirm a diagnosis of diabetes, consider the need to carry out an OGTT* NB. FPG alone will fail to diagnose 30% of cases of diabetes

If symptoms are present (ie polyuria, polydipsia, unexplained weight loss) = DIAGNOSIS of DIA ETES

>/=11.1mmol/L

If no symptoms present

If 2 hour OGTT glucose level >/= 11.1mmol/L = DIAGNOSIS of DIABETES

http://www.cks.nhs.uk/diabetes_type_2

http://www.nice.org.uk/



44

1. Diet / lifestyle / non-pharmacological interventions

Offer nutritional advice

Offer advice about weight loss

Encourage a reduction in alcohol

intake

Encourage smoking cessation

Encourage regular exercise

Refer to dieticians

See OBMH weight management guidelines

See OBMH smoking cessation guideline

See OBMH weight management guideline appendix C for referral guidance to physiotherapy, appendix D for exercise interventions and appendix E for local leisure facilities

2. Set HbA1c target level

6.5% (4.8mmol/mol) if managed by diet alone or by one drug

7.5% (5.9mmol/mol) if more intensive treatment is required

Measure HbA1c at 2-6 month intervals until HbA1c is stable on unchanging therapy

Measure 6 monthly once HbA1c and drug therapy is stable(NB GPs currently only get paid to do this yearly)

3. Start oral antidiabetic medication if blood glucose remains inadequately controlled after 3 to 6 months of lifestyle intervention.

If the person is overweight or obese (BMI >25kg/m2) start metformin

If a rapid response is required due to hyperglycaemic symptoms a sulphonylurea may be preferred

If the person is not overweight start either metformin or a sulphonylurea

If inadequate blood glucose control despite lifestyle interventions and monotherapy with an antidiabetic medicine, refer to NICE/CKS guidelines for further recommendations on drug management.

4. Set blood pressure target and monitor

<140/80mmHg for all people except those below

<130/80mmHg for people with kidney, eye or cerebrovascular damage

Monitor BP yearly in people without previously diagnosed hypertension or renal disease. If BP is above target, offer lifestyle advice and repeat measurement within: – 1 month if BP >150/90mmHg – 2 months if BP >140/80mmHg – 2 months if BP >130/80mmHg

and there is kidney, eye or cerebrovascular damage

If BP remains above target, reinforce lifestyle advice and repeat BP within the specified time frames. If BP continues to remain high offer drug treatment – see below.

Appendix 9 continued Guidance on managing Type 2 Diabetes

Consult BNF or manufacturer’s literature for information on doses. NB – metformin should be taken with food and titrated slowly to minimise the risk of nausea.

45

5. Treat blood pressure that remains above target (see 4 above)

1st line treatment = once-daily generic ACEI EXCEPTIONS: If of African-Caribbean descent start ACEI + thiazide or CCB If pregnant or planning a pregnancy start CCB If intolerant of ACEI (other than renal deterioration or hyperkalaemia) – start angiotensin II receptor antagonist

Monitor BP every 1 – 2 months and intensify therapy until consistently below target

If BP continues to be above target, despite maximum licensed or tolerated doses, add in a CCB or a thiazide. If the patient is already taking both of these, add an alpha-blocker, beta-blocker, or potassium sparing diuretic (serum potassium levels will need very close monitoring if the latter is chosen and the patient is taking and ACEI or AIIRA Continue to monitor BP every 1-2 months. If BP continues to be above target, consider referral to a specialist.

6. Offer lipid modifying therapy

In patients of any age with cardiovascular disease (ie secondary prevention)

In those aged >40 years (unless the person is not a high CV risk – see NICE/CKS guideline for more details)

Aged <40 years and the CV risk profile seems to be particularly poor (see NICE/CKS guideline for more details)

Start simvastatin 40mg daily. Aim for a target total cholesterol <4mmol/L or LDL-C <2mmol/L by reinforcing lifestyle advice and increasing the dose to a maximum of 80mg simvastatin daily. If there is cardiovascular disease or microalbuminuria consider switch to atorvastatin or adding ezetimibe to simvastatin 40mg.

Fibrates:

Fibrates are usually recommended in patients of any age with a triglyceride (TG) level >4.5mmol/L. They may also be recommended in patients at high CV risk whose TG level remains raised despite statin treatment. For further details about starting fibrates and what to do if TG levels remain raised see NICE/CKS guidance

7. Consider the need for antithrombotic treatment

All patients with pre-existing cardiovascular disease (eg previous MI, TIA or stroke, angina, or peripheral vascular disease) should be offered aspirin 75mg daily (ie as secondary prevention). (Clopidogrel should only be offered to people with a clear intolerance to aspirin)

Aspirin as primary prevention in patients with diabetes The balance of risks and benefits of aspirin is less clear in patients without pre-existing cardiovascular disease. Recent advice from the Scottish Intercollegiate Guidelines Network (SIGN) guideline on Management of Diabetes is that aspirin should not be used for primary prevention in people with diabetes. The MHRA recently reminded prescribers that if aspirin is used for primary prevention, the balance of benefits and risks should be considered for each individual (particularly the presence of risk factors for vascular disease) and the risk of gastrointestinal bleeding.

8. Assess at diagnosis and annually for renal disease

Measure albumin:creatinine ratio (ACR) ideally with a first pass morning urine (FPMU) sample. If obtaining FPMU is not practical, a spot sample can be used, but would need repeating using FPMU if the result is abnormal. Measure creatinine and calculate eGRF.

Diabetic nephropathy Diabetic nephropathy is diagnosed if there is persistent albuminuria. See NICE/CKS guidelines for further details on confirming the diagnosis, for recommendations on treating with an ACEI and for further monitoring.

9. Additional monitoring at diagnosis and then annually

Retinal screening refer for retinal screening. NB screening can be done on the unit for detained patients. Foot problems refer to podiatry at the Warneford for annual assessment. Neuropathy see NICE/CKS guideline for further details.

Appendix 9 continued

46

Appendix 10: Anorexia Nervosa – cardiac complications and medication The following cardiac findings have been noted in patients with Anorexic Nervosa:

• smaller volume left atria and left ventricles and decreased left ventricular muscle mass • associated systolic dysfunction in the form of decreased ejection fraction, heart rate and stroke volume. • increased vagal activity leading to greater variability in heart rate, bradycardia and hypotension • increase in QTC interval on the electrocardiogram, which tends to normalize with weight gain.

Electrolyte disturbances commonly seen in this population (hypokalaemia, hypophosphataemia and hypomagnesaemia) can exacerbate the cardiac risk and precipitate arrhythmias. Mortality from Cardiac problems A two-fold increased risk of death from cardiovascular causes was estimated from a large nationwide cohort of people with Anorexia Nervosa (Standardised Mortality Ratio (SMR) = 2.3 [95%CI 1.1-4.1]). Psychotropic medication in Anorexia Nervosa Patients with Anorexia Nervosa are particularly vulnerable to psychotropic medicines that adversely affect the heart. There is very little information in the published literature to help determine or quantify cardiac risks from specific medicines used in these patients. NICE guidelines make the following recommendations:

There is a very limited evidence base for the pharmacological treatment of Anorexia nervosa and medication should not be used as the sole or primary treatment. A range of medicines may be used in the treatment of co-morbid conditions. Carefully consider the side effects of drug treatment (in particular, cardiac side effects). Avoid prescribing drugs with side effects that may compromise cardiac functioning (e.g. antipsychotics, tricyclic antidepressants, macrolide antibiotics and some antihistamines). If the prescription of medication that may compromise cardiac functioning is essential, ECG monitoring should be undertaken. All patients with a diagnosis of anorexia nervosa should have an alert placed in their prescribing record concerning the risk of side effects.

OBMH guidelines for prescribing and monitoring medicines that may affect the heart in patients with anorexia nervosa: ⇒ On each drug chart, place the following alert sticker: ⇒ Discuss the risks and benefits and the reasons for selecting a medicine that has cardiac

side effects with the patient. Document the discussion and the decision in the patient’s notes.

⇒ Conduct a baseline ECG prior to starting any medicine that is known to affect the heart – see individual drug monographs in this guideline.

⇒ Start with low doses and increase gradually. Repeat the ECG 7 days after starting the medicine and then annually unless indicated otherwise by symptoms or by a reduction in body weight. ECGs should also be carried out 7 days after any dose increase, or sooner if indicated. References: National Institute for Clinical Excellence. Eating Disorders. Clinical Guideline 9, January 2004 Ryan LJM, Targosz S, and Brown R. An audit on the use of medication affecting cardiac function in anorexia nervosa. Cotswold House Eating Disorders Unit, Warneford Hospital, Oxford, June 2009

Patient at increased cardiac risk – take care when prescribing medicines that affect the heart.

See OBMH Psychotropic Monitoring Guideline for more information.

47

Appendix 11: Antipsychotic side effect rating scales – GASS and LUNSERS Please note that copies of these rating scales are also available on the Trust intranet

GASS – information for staff:

1. Allow the patient to fill in the questionnaire themselves. Questions 1-20 relate to the previous week. 2. Scoring

⇒ For questions 1-20 award 1 point for the answer “once”, 2 points for the answer “a few times” and 3 points for the answer “everyday”. Please note zero points are awarded for an answer of “never”.

⇒ For questions 21 and 22 award 3 points for a “yes” answer and 0 points for a “no”.

3. Calculated total score a. For male and female patients a total score of:

i. 0-21 = absent/mild side effects ii. 22-42 = moderate side effects iii. 43-63 = severe side effects

4. Side effects covered include: 1-2 sedation and CNS side effects

3-4 cardiovascular side effects 5-10 extra pyramidal side effects 11-13 anticholinergic side effects 14 gastro-intestinal side effects 15 genitourinary side effects 16 screening question for diabetes mellitus 17-21 prolactinaemic side effects 22 weight gain

NB. The column relating to the distress experienced with a particular side effect is not scored, but is intended to inform the clinician of the service user’s views and condition.

LUNSERS – information for staff: LUNSERS is intended to be completed by the patient. It contains 51 side effects – 41 that are known side effects of antipsychotics and 10 that are “red herrings” which are not known side effects of antipsychotics. The red herrings are included but scored separately and may indicate patients who over-score generally on the scale.

LUNSERS – side effects by group Extrapyramidal side effects Questions: 19, 29, 34, 37, 40, 43, 48 Possible range of scores: 0-28

Psychiatric side effects Question: 2, 4, 9, 14, 18, 21, 23, 26, 31, 41 Possible range of scores: 0-40

Anticholinergic side effects Questions: 6, 10, 32, 38, 51 Possible range of scores: 0-20

Other autonomic Questions: 15, 16, 20, 27, 36 Possible range of scores: 0-20

Allergic reaction Questions: 1, 35, 47, 49 Possible range of scores: 0-16

Hormonal side effects Questions: 7, 13, 17, 24, 46, 50 Possible range of scores: women: 0-24

Miscellaneous Questions: 5, 22, 39, 44 Possible range of scores: 0-16

“Red Herrings” Questions: 3, 8, 11, 12, 25, 28, 30, 33, 42, 45 Possible range of scores: 0-40

Possible range for total scores: Antipsychotic side effects only (41 items): women 0-164, men 0-156 Lunsers all 51 items: women 0-204, men 0-196

48

Glasgow Antipsychotic Side-effect Scale (GASS)

(Reference: Waddell and Taylor. Journal of Pyschopharmacology 2008;22:238-243)

Name: Age: Sex: M / F Please list current medication and total daily doses below:

This questionnaire is about how you have been recently. It is being used to determine if you are suffering from excessive side effects from your antipsychotic medication. Please place a tick in the column which best indicates the degree to which you have experienced the following side effects. Also tick the end or last box if you found that the side effect was distressing for you.

Over the past week: Never

Once A few times

Everyday

Tick this box if distressing

1. I felt sleepy during the day

2. I felt drugged or like a zombie

3. I felt dizzy when I stood up and/or have fainted

4. I have felt my heart beating irregularly or unusually fast

5. My muscles have been tense or jerky

6. My hands or arms have been shaky

7. My legs have felt restless and/or I couldn’t sit still

8. I have been drooling

9. My movements or walking have been slower than usual

10. I have had uncontrollable movements of my face or body

11. My vision has been blurry

12. My mouth has been dry

13. I have had difficulty passing urine

14. I have felt like I am going to be sick or have vomited

15. I have wet the bed

16. I have been very thirsty and/or passing urine frequently

17. The areas around my nipples have been sore and swollen

18. I have noticed fluid coming from my nipples

19. I have had problems enjoying sex

20. Men only: I have had problems getting an erection

Tick yes or no for the last three months No Yes Tick this box if distressing

21. Women only: I have noticed a change in my periods

22. Men and women: I have been gaining weight

49

THE LIVERPOOL UNIVERSITY NEUROLEPTIC SIDE EFFECT RATING SCALE (LUNSERS)

(Reference: Day JC, Wood G, Dewey M and Bentall RP. British Journal of Psychiatry 2005;166:650-653)

The following scale is intended to be self-administered. Please indicate how much you have experienced each of the following symptoms in the last month by ticking a box for each of the 51 items. Name: ................................................................................. Date: ......................

Not at all (0)

Very little (1)

A little (2)

Quite a lot (3)

Very much (4)

1. Rash

2. Difficulty staying awake during the day

3. Runny nose

4. Increased dreaming

5. Headaches

6. Dry mouth

7. Swollen or tender chest

8. Chilblains

9. Difficulty in concentrating

10. Constipation

11. Hair loss

12. Urine darker than usual

13. Period problems

14. Tension

15. Dizziness

16. Feeling sick

17. Increased sex drive

18. Tiredness

19. Muscle stiffness

20. Palpitations

21. Difficulty in remembering things

22. Losing weight

23. Lack of emotions

24. Difficulty in achieving climax

25. Weak fingernails

26. Depression

27. Increased sweating

50

Not at all (0)

Very little (1)

A little (2)

Quite a lot (3)

Very much (4)

28. Mouth ulcers

29. Slowing of movements

30. Greasy skin

31. Sleeping too much

32. Difficulty passing water

33. Flushing of face

34. Muscle spasms

35. Sensitivity to sun

36. Diarrhoea

37. Over-wet or drooling mouth

38. blurred vision

39. Putting weight on

40. Restlessness

41. Difficulty getting to sleep

42. Neck and muscles aching

43. Shakiness

44. Pins and needles

45. Painful joints

46. Reduced sex drive

47. New or unusual skin marks

48. Parts of body moving on their own

accord eg. Foot moving up and down

49. Itchy skin

50. periods less frequent

51. Passing a lot of water

51

Appendix 12: Oxfordshire Primary Care Trust and Oxfordshire & Buckinghamshire Mental Health NHS Foundation Trust Good Practice Monitoring Guidelines for Severe Mental Illness

patients – Version 2, Jan 2010 (also available on Oxfordshire PCT intranet via OXWEB)

These guidelines provide information and guidance relating to the monitoring of patients diagnosed with Severe Mental Illness (SMI) – for example, Schizophrenia, Bipolar Disorder or treatment resistant depression. They have been developed on the principles of clinical safety, patient choice and social inclusion. BACKGROUND SMI patients have greater risks of diabetes & cardiovascular disease than the general population. Antipsychotics, especially atypical antipsychotics, may compound this through potential side effects of weight gain, dyslipidaemia, impaired glucose tolerance & diabetes. Adults of African-American, Asian or Hispanic race have higher cardiovascular and diabetes risk factors at lower BMIs and waist circumferences than western populations. Most weight gain occurs in the first few months of treatment. Some antipsychotics may cause hyperprolactinaemia, prolongation of the cardiac QT interval, muscular rigidity (raised CK levels) and neuroleptic malignant syndrome and monitoring may be necessary as clinically indicated. GUIDANCE 1. When referring patients to Secondary care GPs should send a print out of the clinical summary including current treatment and latest blood tests and monitoring results. 2. Secondary care clinicians should include specific requests for the necessary monitoring in outpatient letters and results of these communicated to them on a regular basis to enable relevant care planning. Discharge summaries should include monitoring results and request follow up of abnormal results 3. Service users should be given a psychotropic monitoring record card to be completed and brought to appointments BASELINE MONITORING YEARLY MONITORING BMI Blood pressure & pulse Fasting lipids(random if not possible) including Triglycerides, HDL-C and Cholesterol ratio Fasting glucose(random if not possible) TFT U+E LFT FBC Drug specific monitoring as outlined in table below

BMI Blood pressure & pulse Fasting lipids(random if not possible) including Triglycerides(TG),HDL-C and Cholesterol ratio Fasting glucose(random if not possible) Smoking and alcohol intake Illicit drug use Check status of other annual health checks Drug specific monitoring as outlined in table below

Calculate Framingham cardiovascular risk score for patients > 40yrs or with raised BP or lipid profile

DRUG SPECIFIC MONITORING: (Treat abnormal results as per NICE guidance – refer to CMHT if risks outweigh benefits of treatment)

Drug/Drug group

Baseline after 1 month

after 3 months

after 6months

6 monthly Yearly Repeat test

Antidepressants U&E Typical

antipsychotic Risperidone,

Sulpiride

Prolactin Prolactin if symptoms

Amisulpiride Prolactin , ECG

Prolactin if symptoms

Carbamazepine (CBZ)

LFT +FBC U+E & CBZ-level

Clozapine BMI BMI Fasting

glucose, TG & cholesterol

BMI

Haloperidol Prolactin, ECG

Prolactin if symptoms

Lithium Lithium level (and then every 3 months)

TFT,U+E, Lithium- level

Levels-5-7 days after

dose ↑

Olanzapine BMI LFT,BMI, Fasting

glucose, TG & cholesterol,

BMI

Quetiapine Fasting, TG & cholesterol

Valproate BMI,LFT,FBC (incl ptt)

Venlafaxine BP

References: Summary of Product Characteristics (SPC), NICE guidelines, OBMH Psychotropic Monitoring Guidelines, Maudsley Guidelines. [TFT= thyroid function test U+E= renal function and electrolyte test]

Documents

Psychotropic Monitoring Guidelines 2010 · Further monitoring as clinically indicated. Also see notes on the effect of antiepileptic drugs on bone. Therapeutic Drug Monitoring No