MANAGEMENT OF SCHIZOPHRENIA

BY

Dr. Parvaiz Ahmad KhanNIMS HOSPITAL JAIPUR

PSYCHIATRIC MANAGEMENT APA

Formulate and implement a treatment plan

Assess symptoms and establish a diagnosis....

Develop therapeutic alliance & promote Rx adherence

Provide patient and family education and therapies

Treat comorbid conditions

Attend to the patient’s social circumstances & functioning

Integrate treatments from multiple clinicians

Carefully document the treatment

Assess symptoms and establish a diagnosis.

• Establish an accurate diagnosis, major implications for short- and long-term treatment planning

• Reevaluate diagnosis and update the treatment plan as new information about the patient & symptoms becomes available.

• Identify the targets of each treatment, have realistic expectations about the degrees of improvement that constitute successful treatment

• Consider the use of rating scales to monitor clinical status (e.g., [AIMS], [SCID], [BPRS], [PANSS]).

Formulate & implement a treatment plan.

Develop a therapeutic alliance and promote treatment adherence.

• Assess factors contributing to incomplete adherence which include:

patient’s lack of insight. patient’s perceptions about lack of treatment benefits and risks. cognitive impairment. breakdown of the therapeutic alliance. barriers ‘financial concerns or lack of transportation’ cultural beliefs. lack of family or social support.

• Identify patient’s goals & aspirations.

• Consider assertive outreach (telephone calls and home visits)

Provide patient and family education and therapies.

• Educate family & patient - nature of the illness & coping strategies to improve quality of life of patients.

• Educate family & patients to recognize early symptoms of relapse.

• Prevent full-blown illness exacerbations.

Treat comorbid conditions • Especially major depression,

• Substance use disorders & posttraumatic stress disorder.

Attend to the patient’s social circumstances and functioning.

• Work with patient and family to ensure

• Coordinated services & appropriate referrals

Integrate treatments from multiple clinicians.

Carefully document the treatment.

• Since patients may have different practitioners over their course of illness.

History 1920s Barbiturates were

introduced.

1930s Insulin coma treatment was introduced.

1935 Prefrontal lobotomy was proposed by Moniz.

1950s Reserpine, a rauwolfia alkaloid, was introduced.

1950s Chlorpromazine.

1958 Haloperidol /Clozapine

1994 Risperidone.

1996 Olanzapine.

1997 Quetiapine.

2001 Ziprasidone.

2002 Aripiprazole.

2007 Paliperidone.

Treatment of Schizophrenia

Somatic treatment

Psychosocial treatment and Rehabilitation

Pharmacological Treatment ECT

Pharmacological treatment Outpatient or Inpatient

• Indications of Hospitalization

1. Danger to self and others

2. Poor treatment adherence

3. Neglect of food and water intake

4. Significant neglect of self care

5. Lack of social support

PHASES OF TRETMENT

ACUTE PHASE

STABILISATION PHASE

MANTAINANCEPHASE

ACUTE PHASE• Acute psychotic symptoms -delusions, hallucination,

disorganized thinking, behavioral disturbance.

• This phase lasts from 4 to 8 weeks.

1. ASSESSMENT 2. SELECTION OF ANTIPSYCHOTICS

3. STARTING ANTIPSYCHOTICS 4. DOSAGE SELECTION

5. SIDE EFFECT MANAGEMENT 6. HEALTH MONITORING

• 1. ASSESSMENT

A mental status examination A physical examination A neurological examination A laboratory evaluation

AP’s can be started before lab results except clozapine.

Should be delayed several days for thorough evaluation, R/O substance abuse, extreme stress, medical/psychiatric illness.

• 2. SELECTION OF ANTIPSYCHOTICS FIRST GENERATION ANTIPSYCHOTICS:• Dopamine 2 antagonist- mesolimbic dopamine pathway -reducing activity known to cause

positive symptoms.

1) PHENOTHIAZINES: Chlorpromazine Triflupromazine

Thioridazine Trifluperazine Fluphenazine

2) THIOXANTHIENES:

Chlorprothixene Zuclopenthixol Flupenthixol

3) BUTYROPHENONES: 4) DIPHENYLBUTYLPIPERIDINE:

Haloperidol Pimozide

5) DIBENZOXAZEPINES: Loxapine

• Low potency Chlorpromazine Mesoridazine Thioridazine• Medium potency Loxapine Perphenazine Thiothixene• High potency Droperidol Flupentixol Fluphenazine Haloperidol Prochlorperazine Trifluoperazine

• High potency- greater affinity for D2- greater tendency to cause EPS

• Low potency- other neuroreceptors- postural hypotension, sedation, anticholinergic effect.

SECOND GENERATION ANTIPSYCHOTICS

• serotonin 2A— dopamine 2 antagonist

1) DIBENZODIAZEPINES 5) DIBENZOTHIAZEPINES

Clozapine Quetiapine

2) SUBSTITUTED BENZAMIDES 6) PARTIAL AGONISTS Sulpride Amisulpride Aripiprazole

3) BENZISOXALES 7) BENZISOTHIZOLYL

Risperidone Ziprasidone

4) THIOBENZODIAZEPINES Olanzapine

• Comparison studies All AP’s – similar effectiveness - different side effect profile - except clozapine (more effective)

• Some meta analytic studies- Olanzapine & Risperidone – greter response than other AP’s but

• CATIE in USA & CUtLASS in UK - clozapine advatageous for refractory symptoms- People tend to take olanzapine for longer periods- With Olanzapine having no substatial advantage over others- Clozapine, Olanzapine, Quetiapine – weight gain & sr. lipid

abnormalities.

• 3. STARTING ANTIPSYCHOTICS & DOSAGE SELECTION

• Provide information-benefits and side-effects of drugs.

• Necessary to take verbal or written consent in some settings.

• Be familiar about local/state laws about patient’s right to refuse or accept treatment.

• Meta-analyses - in a 4 to 6 week treatment course, greatest reduction in symptoms - within the first week.

• Little or no response during the first week or two is a powerful predictor of subsequent poor response.

• Best dose for an antipsychotic is both difficult and important.

• Some recent findings suggest doses effective – occupy 60 to 70 % of receptors.

NICE GUIDELINES• Newly diagnosed schizophrenia –oral antipsychotic medication.

• Provide information-benefits and side-effects of drugs.

• Choice of drug – patient and doctor. considering:

– EPS, metabolic and other side-effects.– the views of the carer where the service user agrees.

• Offer the person an ECG if:

– a physical examination reveals any CVS risk eg. HT.– there is personal history of cardiovascular disease.– the service user is being admitted as an inpatient.

• Treatment with antipsychotics- considered an explicit individual therapeutic trial. For each patient:

– record- indications, expected benefits, risks of oral antipsychotics, expected time for a change in symptoms , appearance of side-effects.

– starting dose- at lower end of licensed range and slowly titrate upwards within the dose range.

– justify and record reasons for dosages given outside the range.

• Monitor and record regularly especially during titration:

– efficacy – side-effects– adherence– physical health.– rationale for continuing, changing or stopping medication, and

the effects of such changes.

• Carry out a trial of the medication at optimum dosage for 4–6 weeks.

• Do not initiate regular combined antipsychotic, except for short periods (eg., when changing medication).

• For chlorpromazine, warn of its potential skin photosensitivity. Advise using sunscreen if necessary.

• Consider depot/long-acting injectable antipsychotics to people with schizophrenia:

– who would prefer such treatment after an acute episode– where non-adherence to antipsychotics is a clinical priority.

• Offer clozapine where

- illness has not responded adequately

- despite the use of adequate doses of at least two antipsychotic drugs.

- at least one of the drugs should be a nonclozapine second-generation antipsychotic

-we recommend that one of the drugs should be Olanzapine.

• For people not responding adequately to clozapine• before adding a second antipsychotic to augment treatment

with clozapine.

• establish prior compliance• measuring plasma drug levels• psychological treatment

• An adequate trial of such an augmentation may need to be up to 8–10 weeks.

• Choosen drug- does not have common side-effects of clozapine.

1

Min & Max effective daily dose of antipsychotics• Antipsychotic First episode Relapse/Exc. Max.• Dose (mg) Dose (mg) dosage

• 1st-generation• Chlorpromazine 200 300 1000• Haloperidol 2 >4 30• Sulpiride 400 800 2400• Trifluoperazine 10 15 30

• 2nd-generation• Amisulpride 400 800 1200• Aripiprazole 10 10 30• Asenapine 10 10 20• Iloperidone 4 8• Olanzapine 5 10 20• Quetiapine 150 300 800• Risperidone 2 3 16• Ziprasidone 80 80 160

SIDE EFFECT MANAGEMENT

Relative adverse effects of antipsychotic drugs: a rough guide

Drug Sedation Weight Diabetes Extrapyramidal Anticholinergic Hypotension Prolactin gain symptoms effect

• Amisulpride − + + + − − +++• Aripiprazole − +/− - +/− − − −• Asenapine + + +/- +/− − − +/−• Chlorpromazine +++ ++ ++ ++ ++ +++ +++• Clozapine +++ +++ +++ − +++ +++ −• Flupentixol + ++ + ++ ++ + ++• Fluphenazine + + + +++ ++ + +++• Haloperidol + + +/- +++ + + +++• Iloperidone − ++ + + − + −• Loxapine ++ + + +++ + ++ +++• Olanzapine ++ +++ +++ + + + +• Quetiapine ++ ++ ++ − + ++ −• Risperidone + ++ + + + ++ +• Trifluoperazine + + +/- +++ +/− + +++• Ziprasidone + +/ - +/− − + +/−

ACUTE DYSTONIA

• Parenteral (intramuscular [IM] or IV) benztropine (2 mg) or diphenhydramine (50 mg) typically produce rapid relief.

• Prophylactic use of oral anticholinergic medication.

Medication Induced Parkinsonism

• First line: Anticholinergic/Antiparkinsonian eg. Trihexyphenidyl, procyclidine, benzhexol.

• Second line: Antihistaminics, Amantadine

AKATHISIA • Reduce dose of antipsychotic (if possible) Effective continue on reduced dose or slow rate of increase Ineffective/not appropriate

• Switch to quetiapine/olanzapine (lower doses) Effective Continue (clozapine also possible if treatment resistant)

Ineffective/not appropriate

• Consider an antimuscarinic drug Effective Continue, but attempt (e.g. benzatropine 6 mg/day) where other parkinsonian symptoms are present withdrawal after several months

Ineffective/no other parkinsonian symptoms

• Try propranolol 30–80 mg/day(start 10mg tds) Effective Continue if no contraindications• Note contraindications (asthma, bradycardia, etc.)

Ineffective/contraindicated/not tolerated

• Try cyproheptadine16 mg/day(other serotonin Effective Continue, if no contraindications antagonists [e.g. mianserin 15–30 mg mirtazapine 15 mg )

• Try benzodiazepine (e.g. diazepam up to Effective Effective Continue, but attempt slow 15 mg/day, clonazepam 0.5–3 mg/day) withdrawal after 2–4 weeks

(danger of dependence) • Try clonidine 0.2–0.8 mg/day2 Effective Continue if tolerated; withdraw very slowly

TARDIVE DYSKINESIA

• APA task force on TD recommended a number of steps for the prevention and management of the disorder, including:

(1) establishing objective evidence that antipsychotic medications are effective;

(2) using the minimum effective dosage for long-term treatment; (3) exercising caution with children, the elderly, and patients with mood

disorders; (4) examining patients on a regular basis for evidence of dyskinesia and

noting the results of the examination in the medical record; (5) if TD is diagnosed, considering alternatives to antipsychotics,

obtaining informed consent, and considering dosage reduction; and (6) if the dyskinesia worsens, considering the discontinuation of the

antipsychotic, switching to a different drug, or considering a trial of clozapine.

• substantial data indicates that clozapine and other SGAs are less likely to cause TD.

Neuroleptic malignant syndrome

• Withdraw antipsychotics; monitor temperature, pulse, blood pressure.

• Rehydration, bromocriptine + dantrolene, sedation with benzodiazepines, artificial ventilation if required.

• Dantrolene- 0.8 - 2.5 mg/kg 6 hrly iv untill patient takes orally.

• Then Dantrolene- 100 – 200 mg/day plus Bromocriptine – 20 – 30 mg/day in divided doses for 7 – 10 days.

• Consider ECT for treatment of psychosis.

• Allow symptoms and signs of NMS to resolve completely.

• Begin with very small dose of SGA’s & increase very slowly with close monitoring of temperature, pulse and blood pressure.

• Consider using an antipsychotic structurally unrelated to that associated with NMS or a drug with low dopamine affinity (quetiapine or clozapine).

• Avoid depots (of any kind) and high-potency FGA’s

CATATONIA

Lorazepam up to 4 mg/day , Start with 1 mg and give a further 1 mg if no effect after 3 h.Use IM route from then on

if no respose after 1 to 2 days Lorazepam high dose 8–24 mg/day

if no respose after 3 to 4 days

ECT

Health monitoring

• Monitor BMI, fasting blood glucose, & lipid profiles, blood pressure & waist circumference.

• ECG monitoring of patients prescribed antipsychotics• Measure QTc in all patientas on admission (NICE guideline)• at yearly check-up (abnormality or additional risk factors).

• Measurement and interpretation of prolactin concentration• Take blood sample at least 1 h after waking or eating.• Minimise stress during venepuncture (stress elevates plasma prolactin).

• Normal Women 0–25 ng/ml ( 0–530 mIU/L)∼

• Men 0–20 ng/ml ( 0–424 mlU/L)∼

• Re-test if prolactin concentration 25–118 ng/ml (530–2500 mIU/l)

• Rule out prolactinoma if prolactin concentration 118 ng/ml (2500 mIU/l)

• Monitoring diabetes in patients receiving AP’s

• Time Ideal test Minimum test• Baseline OGTT or FPG HbA1C if fasting Urine glucose not possible (+ RPG) RPG

• Continuation All drugs: OGTT or Urinary glucose or RPG

• FPGor HbA1C every 12 months with• every 12 months (+ RPG) symptom monitoring

• For clozapine and OGTT or FPG after 1 Olanzapine or if other month, then every risk factors present: 4 - 6 months

• Monitoring lipid concentrations in patients on AP drugs

• Antipsychotic drug Suggested monitoring

• Clozapine Fasting lipids at baseline, then every 3 months Olanzapine for a year, then annually• Other antipsychotics Fasting lipids at baseline and at 3 months, then annually

STABILISATION PHASE

• acute symptoms have been controlled, but

• patients remain at risk for relapse if treatment is interrupted • if the patients are exposed to stress.

• treatment focuses on consolidating therapeutic gains,

• similar treatments as those used in the acute stage.

• last as long as 6 months following recovery from acute symptoms.

Stable or maintenance phase • Illness is either in a relative stage of remission or symptomatically

stable.

• Goal during this phase is to prevent psychotic relapse or exacerbation and

• Assist patients in improving their level of functioning.

• 15 to 25 % will experience a relapse while receiving medications in a year.

• 50 to 75 % will relapse without medications.

• patients who have had only one episode have a four in five chance of relapsing at least once over the next 5 years.

• Single episode- maintenance for 1 – 2 years might not be adequate.

• multiepisode patients receive maintenance treatment for at least 5 years.

• large meta-analysis, SGAs are more effective in preventing relapse than the FGA’s drugs.

• 40 to 50 % of patients become at least partially noncompliant within 1 or 2 years.

• high rates of relapse following discontinuation has potentially severe consequences (loss of job, interference with school, family burden, suicidality, homelessness, aggressive or violent behavior)

• attempts to enhance adherence are critical.

• importance of combining psychosocial treatments, family therapy, rehabilitation, and pharmacologic management.

• Psychosocial treatments may also improve the response to pharmacotherapy by improving medication compliance.

• Psychosocial treatments & long acting injectable AP’s improve compliance.

• advantages of long-acting injectable

- First in case of noncompliance we have some time to initiate appropriate interventions before the medication effect dissipates.

- Second, there is less day-to-day variability in blood levels, making it easier to establish minimum effective doses.

- Third, many patients who have had experience with such treatment often prefer it.

Psychosocial approaches• wide range of interventions

• designed to help people with schizophrenia

• cope with their illnesses and

• improve their functioning and quality of life

• by enabling them to acquire the skills and supports • necessary for their role in the environment of their

choice

HISTORY• 19th century: “Moral treatment” Recognized that participation in education, work, social activities and other normal roles was not harmful and could in fact have a beneficial effect

• 1950: Deinstitutionalization From hospital to community

Patient Outcomes Research team(PORT) Psychosocial Treatment Recommendations:• Family Interventions

• Supported Employment

• Assertive Community Treatment

• Skills Training

• Cognitive Behaviorally oriented Psychotherapy

• Token Economy Interventions

Psychosocial Treatment1. Social skill Training

2. Cognitive behavior therapy

3. Family Oriented Therapy

4. Case Management

5. Assertive Community treatment

6. Group therapy

7. Individual Psychotherapy

8. Token economy programs

9. Vocational Rehabilitation

Social skill Training• People with Schizophrenia have difficulty fulfilling

social roles, such as worker, spouse and friend and they have difficulty meeting their own needs when social interactions is required.

• Social Competence is based on 3 component skills:

1. Social Perception or receiving skills2. Social Cognition or Processing skills3. Behavioral Response or Expressive skills

Cognitive Behavior Therapy

• Psychological approach focused on the interrelationship between thoughts, behaviors and feelings

• CBT model purports that persons feelings and actions are determined by his interpretations and attributions about a situation and

• that emotional stress is related to faulty assumptions ,that , if modified will lead to reductions in stress

Family oriented Therapy

• Brief and intensive course of family therapy

• Therapist must help both family and patient understand and learn about schizophrenia

• Effective in reducing relapses

Case Management

• Variety of professionals with specialized skills such as psychiatrist , social workers and occupational therapist are involved in treatment program

• Case manager is appointed , who can coordinate their efforts

Assertive Community Treatment• Was originally developed by researchers in Madison,

Winconsin in 1970, for delivery of services with chronic mental illness

• Patients are assigned to one multidisciplinary team(case manager, psychiatrist, nurse, general physicians etc.)

• Mobile intensive intervention that provides treatment, rehabilitation and support activities

• Home delivery of medications• Monitoring mental and physical health• In vivo social skills• Frequent contact with family members• Decrease the risk of re hospitalization for persons with

schizophrenia

Group Therapy

• Focuses on real life plans, problems and relationship

• Helps in reducing social isolation, increasing sense of cohesiveness and improving reality testing for patients with schizophrenia

Individual Psychotherapy

• Therapeutic alliance with therapist

• Persons with Schizophrenia are desperately lonely, yet defend against closeness and trust, also suspicious, anxious and hostile

Token Economy Programs• Behavioral reinforcement programs based on the principles

of social learning• Employed in patient or residential settings with dual goal of:1.Managing patients behavior while they are in the hospital2.Preparing them to able to function better in other less restrictive settings

• Key elements:1. Identification of target behaviors, desirable2. Earning points or tokens for engaging in these behaviors3. Redeeming the points in exchange for material items or

privileges4. Participation by all patients in treatment settings

Vocational Rehabilitation

• Impairment of vocational role function is a common complication related to schizophrenia

• Less than 15%of patients with schizophrenia are employed

• Train – then –place models

• Extensive Pre employment assessment

• Prevocational training

• Sheltered workshops

• Disadvantage :It did not improved the rate of employment

Supported Employment

• Supported employment emphasizes individualized placement

• Rapid job search

• No extensive pre employment assessment or training

• After being placed in jobs of their choice, pts. are helped to learn skills and provided with support needed to be successful

• Individual placement and support model(IPS)of supported employment

Primary goal of IPS is to assist those with schizophrenia in obtaining and maintaining competitive employment in a job of their choice Major components of IPS model are:

• Competitive employment in community• Rapid search for a job• Integration of vocational and mental health

services• Patient preference• Ongoing support, assessment and training

• Contradictions to supported employment

• Cognitive deficits

• Negative symptoms

• Economic factors

• ETHICAL ISSUES Disclosure of mental health

Integrating Pharmacotherapy and Psychosocial treatment

• Overall outcome of Schizophrenia can be improved if patients receive optimal form of both treatments at the appropriate stage of their illness.

• Psychosocial treatments are most likely to be effective when patient have been adequately stabilized on drugs.

THANK YOU