Evidence-Based Reviews

Comorbid bipolar disorder and substance abuse: Evidence-based options

Current Psychiatry. 2011 April;10(4):57-67

References

1. Regier DA, Farmer ME, Rae DS, et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) Study. JAMA. 1990;264(19):2511-2518.

2. Kessler RC, Crum RM, Warner LA, et al. Lifetime cooccurrence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey. Arch Gen Psychiatry. 1997;54(4):313-321.

3. Grant BF, Stinson FS, Hasin DS, et al. Prevalence, correlates, and comorbidity of bipolar I disorder and axis I and II disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 2005;66(10):1205-1215.

4. Feinman JA, Dunner DL. The effect of alcohol and substance abuse on the course of bipolar affective disorder. J Affect Disord. 1996;37(1):43-49.

5. Cassidy F, Ahearn EP, Carroll BJ. Substance abuse in bipolar disorder. Bipolar Disord. 2001;3(4):181-188.

6. Frye MA, Altshuler LL, McElroy SL, et al. Gender differences in prevalence, risk, and clinical correlates of alcoholism comorbidity in bipolar disorder. Am J Psychiatry. 2003;160(5):883-889.

7. Khalsa HM, Salvatore P, Hennen J, et al. Suicidal events and accidents in 215 first-episode bipolar I disorder patients: predictive factors. J Affect Disord. 2008;106(1-2):179-184.

8. Baldessarini RJ, Perry R, Pike J. Factors associated with treatment nonadherence among US bipolar disorder patients. Hum Psychopharmacol. 2008;23(2):95-105.

9. Cardoso BM, Kauer Sant’Anna M, Dias VV, et al. The impact of co-morbid alcohol use disorder in bipolar patients. Alcohol. 2008;42(6):451-457.

10. Schuckit MA. Alcohol-use disorders. Lancet. 2009;373 (9662):492-501.

11. Goldberg JF, Whiteside JE. The association between substance abuse and antidepressant-induced mania in bipolar disorder: a preliminary study. J Clin Psychiatry. 2002;63:791-795.

12. Weiss RD, Griffin ML, Kolodziej ME, et al. A randomized trial of integrated group therapy versus group drug counseling for patients with bipolar disorder and substance dependence. Am J Psychiatry. 2007;164(1):100-107.

13. Geller B, Cooper TB, Sun K, et al. Double-blind and placebo-controlled study of lithium for adolescent bipolar disorders with secondary substance dependency. J Am Acad Child Adolesc Psychiatry. 1998;37:171-178.

14. Nunes EV, McGrath PJ, Wager S, et al. Lithium treatment for cocaine abusers with bipolar spectrum disorders. Am J Psychiatry. 1990;147:655-657.

15. Weiss RD, Greenfield SF, Najavits LM, et al. Medication compliance among patients with bipolar disorder and substance use disorder. J Clin Psychiatry. 1998;59:172-174.

16. Salloum IM, Cornelius JR, Daley DC, et al. Efficacy of valproate maintenance in patients with bipolar disorder and alcoholism: a double-blind placebo-controlled study. Arch Gen Psychiatry. 2005;62(1):37-45.

17. Salloum IM, Douaihy A, Cornelius JR, et al. Divalproex utility in bipolar disorder with co-occurring cocaine dependence: a pilot study. Addict Behav. 2007;32(2):410-405.

18. Brady KT, Sonne SC, Malcolm RJ, et al. Carbamazepine in the treatment of cocaine dependence: subtyping by affective disorder. Exp Clin Psychopharmacol. 2002;10:276-285.

19. Brown ES, Perantie DC, Dhanani N, et al. Lamotrigine for bipolar disorder and comorbid cocaine dependence: a replication and extension study. J Affect Disord. 2006;93(1-3):219-222.

20. Martinotti G, Andreoli S, Di Nicola M, et al. Quetiapine decreases alcohol consumption, craving, and psychiatric symptoms in dually diagnosed alcoholics. Hum Psychopharmacol. 2008;23(5):417-424.

21. Brown ES, Garza M, Carmody TJ. A randomized double-blind, placebo-controlled add-on trial of quetiapine in outpatients with bipolar disorder and alcohol use disorders. J Clin Psychiatry. 2008;69(5):701-705.

22. Brown ES, Nejtek VA, Perantie DC, et al. Quetiapine in bipolar disorder and cocaine dependence. Bipolar Disord. 2002;4(6):406-411.

23. Nejtek VA, Avila M, Chen LA, et al. Do atypical antipsychotics effectively treat co-occurring bipolar disorder and stimulant dependence? A randomized, double-blind trial. J Clin Psychiatry. 2008;69(8):1257-1266.

24. Brown ES, Jeffress J, Liggin JD, et al. Switching outpatients with bipolar or schizoaffective disorders and substance abuse from their current antipsychotic to aripiprazole. J Clin Psychiatry. 2005;66:756-760.

25. Sattar SP, Grant K, Bhatia S, et al. Potential use of olanzapine in treatment of substance dependence disorders. J Clin Psychopharmacol. 2003;23:413-415.

26. Brown ES, Beard L, Dobbs L, et al. Naltrexone in patients with bipolar disorder and alcohol dependence. Depress Anxiety. 2006;23(8):492-495.

27. Brown ES, Carmody TJ, Schmitz JM, et al. A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with bipolar disorder and alcohol dependence. Alcohol Clin Exp Res. 2009;33:1863-1869.

28. Petrakis IL, Poling J, Levinson C, et al. and the VA New England VISN I MIRECC Study Group. Naltrexone and disulfiram in patients with alcohol dependence and comorbid psychiatric disorders. Biol Psychiatry. 2005;57(10):1128-1137.

29. Petrakis I, Ralevski E, Nich C, et al. and the VA VISN I MIRECC Study Group. Naltrexone and disulfiram in patients with alcohol dependence and current depression. J Clin Psychopharmacol. 2007;27(2):160-165.

30. Sullivan MA, Nunes EV. New-onset mania and psychosis following heroin detoxification and naltrexone maintenance. Am J Addict. 2005;14(5):486-487.

31. Sonne SC, Brady KT. Naltrexone for individuals with comorbid bipolar disorder and alcohol dependence. J Clin Psychopharmacol. 2000;20(1):114-115.

32. Ceylan ME, Turkcan A, Mutlu E, et al. Manic episode with psychotic symptoms associated with high dose of disulfiram: a case report. J Clin Psychopharmacol. 2007;27(2):224-225.

33. Li MY, Shen YC. Manic episode with psychosis following a lower than recommended dosage regimen of disulfiram. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(1):311-312.

Quetiapine may be effective for treating BD patients with comorbid cocaine dependence. In an open-label study, 12 weeks of quetiapine augmentation in 17 cocaine-dependent BD patients was associated with decreased cocaine craving and improvement in depressive symptoms.²² In another open-label study, 80 BD patients with comorbid cocaine or amphetamine dependence were randomly assigned to receive quetiapine or risperidone as adjunctive therapy or monotherapy for 20 weeks.²³ Both groups showed significantly decreased drug use and drug craving and improved mood. This study suggests that risperidone also may be an option for BD patients with comorbid cocaine or stimulant dependence.

Clinical Point

Open-label studies suggest quetiapine may be effective for treating cocaine-dependent BD patients

A 20-week, open-label study of 20 BD-SUD patients found that switching patients from their previous antipsychotic to aripiprazole resulted in less cocaine craving, less alcohol craving, and less money spent on alcohol.²⁴

Olanzapine has not been systematically studied in BD-SUD patients. Some case reports suggest that olanzapine may decrease cocaine craving and use in patients with schizoaffective disorder (bipolar type) and alcohol craving and use in BD patients with comorbid alcohol dependence.²⁵

Table 3

Evidence of efficacy for antipsychotics for BD patients with SUDs

Study	Intervention	Design	Substance use disorder	Results
*Martinotti et al, 2008²⁰**	Quetiapine	Open label	Alcohol dependence	Decreased alcohol consumption and alcohol craving
Brown et al, 2008²¹	Quetiapine vs placebo	Double-blind, placebo-controlled	Alcohol dependence	No difference between quetiapine and placebo in decreasing alcohol use and alcohol craving
Brown et al, 2002²²	Quetiapine	Open label	Cocaine dependence	Decreased cocaine use and cocaine craving
Nejtek et al, 2008²³	Risperidone vs quetiapine	Open label	Cocaine dependence and amphetamine dependence	Decreased drug use and drug craving
Brown et al, 2005²⁴	Aripiprazole	Open label	Alcohol and cocaine dependence	Decreased alcohol and cocaine craving and money spent on alcohol
*Sample included, but was not limited to, patients with BD BD: bipolar disorder; SUDs: substance use disorders

SUD medications. Little evidence guides using medications indicated for treating SUDs—such as naltrexone, acamprosate, and disulfiram—as treatment for BD patients (Table 4).^26-29 In an open-label trial of 34 BD patients with alcohol dependence, naltrexone was well tolerated and associated with decreased alcohol craving and use and modest improvement in manic and depressive symptoms.²⁶

Clinical Point

In 2 trials, naltrexone and disulfiram reduced drinking in patients with mood disorders

In a double-blind, placebo-controlled study, 50 alcohol-dependent BD patients treated with standard mood-stabilizing therapy and cognitive-behavioral therapy were randomized to receive add-on naltrexone, 50 mg/d, or placebo.²⁷ Patients receiving naltrexone showed decreased alcohol consumption, although no measures were statistically significant. Effect sizes of alcohol use decrease and alcohol craving were moderate to large compared with placebo, which suggests that naltrexone may be effective for treating alcoholism in these patients.

Two other studies evaluated naltrexone and disulfiram in patients with BD or other mood disorders.^28,29 Naltrexone was well tolerated, caused no serious adverse side effects, and was significantly more effective than placebo in decreasing drinking rates and increasing the number of abstinent days.^28,29 Disulfiram was as effective as naltrexone, but the combination of both offered no advantage over use of either drug separately.

Clinical Point

In case reports, naltrexone triggered mania in BD patients who were alcohol- or cocaine-dependent

There are reports of a new-onset manic episode associated with naltrexone use in a patient with opioid dependence, and a manic episode triggered by naltrexone in a patient with BD with comorbid alcohol dependence.^30,31 At both low and high doses, disulfiram is associated with induction of psychotic mania in alcoholic patients without a personal or family history of BD.^32,33

We found no studies that evaluated treating BD patients who abused other substances, such as cannabis or opiates. We recommend that BD patients with these substance use disorders should be referred to treatment modalities that are condition-specific, such as psychotherapy for cannabis use disorders or methadone or naltrexone treatment for opiate dependence. More severe cases of comorbid SUD probably would benefit from a referral to or consultation with a SUD specialist.

Table 4

Naltrexone and disulfiram for BD patients with alcohol dependence

Study	Intervention	Design	Substance use disorder	Results
Brown et al, 2006²⁶	Naltrexone	Open label	Alcohol dependence	Decreased alcohol use and craving
Brown et al, 2009²⁷	Naltrexone vs placebo	Double-blind, placebo-controlled	Alcohol dependence	Nonsignificant decrease in alcohol consumption
Petrakis et al, 2005²⁸ and 2007²⁹	Naltrexone alone vs disulfiram alone vs naltrexone plus disulfiram	Double-blind, randomized, placebo-controlled	Alcohol dependence	More time in abstinence and decreased craving for both compounds
BD: bipolar disorder

Related Resource

Tolliver BK. Bipolar disorder and substance abuse: Overcome the challenges of ‘dual diagnosis’ patients. Current Psychiatry. 2010; 9(8): 32-38.

Drug Brand Names

Acamprosate • Campral
Aripiprazole • Abilify
Carbamazepine • Carbatrol, Equetro, others
Disulfiram • Antabuse
Divalproex sodium • Depakote,
Depakote ER Lamotrigine • Lamictal
Lithium • Eskalith, Lithobid
Methadone • Dolophine
Naltrexone • ReVia, Vivitrol
Quetiapine • Seroquel
Risperidone • Risperdal
Topiramate • Topamax
Valproate • Depacon