Concurrent Disorders; Pharmacotherapy

Addiction Day—CSAMNovember 12, 2015

Banff Alberta

Tashi Kinjo MD, PhD, FRCPC Psychiatrist

Conflicts of InterestPharmaceutical Disclosure;

I introduced a speaker at an event sponsored by Otsuka once.

Alberta Health Services� Foothills Medical Centre Addiction Centre

� Addiction Network Hospital Consults

� Claresholm Centre for Mental Health and Addiction

� Sunridge Mental Health Clinic

� Claresholm Mental Health Clinic

Personal Disclosure� I was more confused at the end of this talk, than

before I started it.

Outline� Background

� Major Depressive Disorder

� Anxiety Disorders

� Bipolar Disorder

� Schizophrenia

� Summary

What is meant by the term ‘Concurrent Disorders’?

Concurrent Disorder

Persistent mental Illness + Substance Use Disorder or Gambling Addicion

Concurrent Disorders� suicide and violence

� medication compliance

� Homelessness

� medical problems

� psychiatric Hospitalization

� Health Care Costs

Prevalence of Substance Use Disorders in Psychiatric

Disorders

� Antisocial PD 84%

� Bipolar Disorder (I and II) 56%

� Schizophrenia 47%

� Affective Disorders 32%

� Major Depressive Disorder 27%

Is it due to the substance?� Family History of Psychiatric Disorders

� Temporal association

� Psychiatric symptoms are in excess of what would be expected for a type of amount of substance use.

Concurrent Disorders Treatment models

� Sequential- treat one and then the other

� Parallel- same time, but two different treatment teams

� Integrated- both types of disorders treated at the same time by the same team.

Health Canada Best Practice Guidelines (2002)

Sequential Intergrated/parallel

Depression Severe and Persistent

Anxiety Disorders PTSD

Antisocial PD Eating Disorders

Borderline PD (DBT)

Canadian Guidelines?

Depression and Substance Use

Disorders

MDD and Opiate Use Disorder

-Buprenorphine vs Methadone

-TCAs- Desipramine + BUP or MMTà level 2 negative Imipramine + MMTàLevel 2 (CANMAT 3rd choice)

-SSRI- Fluoxetine or Setraline + MMT (level 2 negative), Escitalopram + BUP showed no advantage for depression nor opiate outcomes.

Antidepressant + MMT can improve depressive symptoms, however, robust effects on mood are not usual. Nor is improvement in opiate outcomes.

Antidepressants not robustly superior for mood or substance use than placebo (meta-analysis of 14 studies Nunes 2004)

-Naltrexone- not found to worsen mood in newly abstinent Heroin addicts

MDD and Alcohol Use Disorder: Antidepressants

� More likely to respond to antidepressants than for other drug addictions.

� Level 2 for TCAs (CANMAT)

� Level 2 for Escitalopram, Fluoxetine

� Some suggestion that TCA’s > SSRI for mood (OR=4.16 vs OR=1.85) and alcohol (OR=1.99 vs OR=0.93) (Torrens 2005).

� Small DB RCT; Mirtazapine = Amitriptyline for mood and alcohol and better tolerated (Altintoprak 2008) (CANMAT 1st choice)

MDD and Alcohol Use Disorder: Relapse prevention meds

� Sertraline + Naltrexone; some evidence, better than either alone for mood and decreased alcohol use (Pettinati 2010).

� Naltrexone and Disulfiram can be use safely in this population with similar efficacy as non-depressed. (Petrakis 2005, 2007)

� Acamprosate

CANMAT recommendations for MDD and SUD

� Alcohol; 1st choice = Mirtazapine, Naltrexone add on or alone Sertraline add on Naltrexone

� Opiate; 3rd choice = MMT, add on imipramine

� Cocaine; 3rd choice = Risperidone add on or alone (open label study N=6)

� THC, Stimulants, polysubstance- no choices.

MDD and Substance Use Disorders

� Antidepressants may improve mood, but not necessarily substance use.

� Antidepressant use is recommended with emphasis on the concurrent treatment of the substance use disorder.

� TCAs not recommended

� Consider antidepressants with mixed serotonergic and noradrenergic pharmacology.

� Consider Naltrexone, Disulfiram, Acamprosate.

� Caution with SSRI in Babor type B/Cloninger type 2

Anxiety and Substance Use

Disorders

Anxiety and Substance Use Disorders; Antidepressants

� Sequential (except PTSD)

� Studies have primarily looked at alcohol.

� GAD; Buspirone decreased anxiety but NOT alcohol (Malec 1996)

� SAD; Paroxetine decreased anxiety but NOT alcohol (Book 2008, Thomas 2008)

� PTSD- Setraline à Yes and No (Brady 2005)

Anxiety Disorders and Substance Use Disorders; Relapse Prevention meds

� Naltrexone

� Disulfiram

Petrakis et al. 93 veterans with Alcohol Use Disorder and PTSD. Treatment with Naltrexone, Disulfiram or combo

àDecreased drinking and PTSD symptoms

àDisulfiram better for PTSD symptoms

So what do we do?� Not everyone gets Mirtazapine!

� Consider pain- Duloxetine (no in liver disease) 1st line for GAD, 3rd line for Panic, SAD, OCD (off label)

� Gabapentin- Anxiety (off label) 2ndline SAD,3rd line Panic, adjunctive 3rd line PTSD

� Pregabalin- Anxiety (off label)1st line SAD, GAD2nd line adjunctive GAD3rd line adjunctive OCD, PTSD

Canadian Clinical Practice Guidelines of Anxiety, Posttraumatic Stress and Obsessive Compulsive Disorders. BMC Psychiatry 2014

Bipolar Disorder and SUD� CANMAT 2005 guidelines for management of patients

with Bipolar Disorder àcomorbid substance abuse is a positive predictor for response to Epival.

� CANMAT 2012 task force; alcohol à1st choice Add Naltrexone

� Growing evidence for the addition of Epival to Lithium for SUD and BP

Cannabisà 1st choice Add Epival to Li Cocaine à 1st choice Add Epival to Li

� No other 1st choice recommendations.

Schizophrenia and SUD:Antipsychotics

� SGA suggested to be more effective.

� Clozapine (alcohol)

� Olanzapine (alcohol)

� Quetiapine (alcohol)

� Flupenthixol Depot (alcohol)

� Aripiprazole (cocaine)

Schizophrenia and SUD:relapse prevention meds

� Naltrexone à effective for alcohol � Does not worsen psychosis.

� Disulfiram à effective for alcohol� Does not worsen psychosis

Canadian Journal of Psychiatry, Vol 57, No 6.June 2012

Summary� Overall, more data is needed.

� There is no definitive evidence for a specific medication in the concurrent disorder population.

� Available data suggests that Naltrexone and Disulfiram are safe in this population.

� Pharmacotherapy is not a substitute for psychosocial and rehabilitation programs.

References� Lev-Ran, Balchand, Lefebvre, Araki, Le Foll. Pharmacotherapy of Alcohol Use Disorders and

Concurrent Psychiatric Disorders. Canadian Journal of Psychiatry, June 2012, Vol 57, No 6. 342-349.

� Lingford-Hughes, Welch, Peters, Nutt. BAP updated guidelines: evidence-based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP. Journal of Psychopharmacol. 2012 Jul;26(7):899-952.

� Pettinati, O’Brien, Dudon. Current Status of Co-Occurring Mood and Substance Use Disorders: A New Therapeutic Target. Am J Psychiatry. 2013 Jan 1;170(1):23-30

� Beaulieu, Saury, Sareen, Tremblay, Schutz, McIntyre, Schaffer. The Canadian Network for Mood and Anxiety Treatments (CANMAT) task force recommendations for the management of patients with mood disorders and comorbid substance use disorders. Annals of Clinical Psychiatry2012;24(1):38-55.

� Torrens M, Fonseca F, Mateu G, et al. (2005) Efficacy of antidepressants in substance use disorders with and without comorbid depression. A systematic review and meta-analysis. Drug Alcohol Depend 78: 1–22.

� Altintoprak AE, Zorlu N, Coskunol H, et al. (2008) Effectiveness and tol- erability of mirtazapine and amitriptyline in alcoholic patients with co-morbid depressive disorder: a randomized, double-blind study. Hum Psychopharmacol 23: 313–319.

References� Yatham, Kennedy, O’Donovan, Parikh, MacQueen, McIntyre, Sharma, Silverstone, Alda, Baruch, Beaulieu,

Daigneault, Milev, Young, Ravindran, Schaffer, Connolly, Gorman. Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the management of patients with bipolar disorder:consensus and controversies. Bipolar Disord 2005:7 (Suppl. 3.)5-69.

� Katzman, Bleau, Blier, Chokka, Kjernisted, Van Amerigen. Canadian Clinical Practice guidelines for the management of anxiety, posttraumatic stress and obsessive compulsive disorders. BMC Psychiatry 2014, 14 (Suppl 1);S1

� Nunes, EV, Hasin, D.S., Weiss, R.D., (2015) Co-Occurring Mood and Substance Use Disorders. El-Guebaly, N, Carra, G., Galanter, M., Textbook of Addiction Treatment: International Perspectives. (Vol. 4, pp.1937-1958). Verlag Italia:vSpringer.

� Nunes EV, Sullivan MA and Levin FR (2004) Treatment of depression in patients with opiate dependence. Biol Psychiatry 56: 793–802.

� Charney D., E.K. Koryani Review Course in Psychiatry. Substance Abuse and Concurrent Disorders. February 2015.

� Health Canada Best Practices; Concurrent Mental Health and Substance Use Disorders (2002).

� Dean AJ, Bell J, Christie MJ, et al. (2004) Depressive symptoms during buprenorphine vs. methadone maintenance: findings from a randomised, controlled trial in opioid dependence. Eur Psychiatry 19: 510–513.

� Diagnostic and Statistical Manual of Mental Disorders- IV TR.

Questions, Comments? � "Psychiatry should

be outlawed. You don't know the history of psychiatry, I do." Tom Cruise to Matt Lauer, Today Show, June 25th, 2005

� tashi.kinjo@ahs.ca