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.

Lithium. Given its well-documented mood stabilizing effect, lithium would seem to be a reasonable option to treat BD-SUD patients, but scant evidence supports its role as an anti-alcohol or anti-drug medication (Table 1).^13,14 Lithium’s efficacy was evaluated in a study of 25 adolescents suffering from mood disorders (mostly BD) and comorbid SUDs (mostly alcohol and cannabis) randomized to receive lithium or placebo for 6 weeks.¹³ Lithium was well tolerated and improved psychiatric symptoms. At week 3, patients receiving lithium produced fewer positive results on randomly administered urine drug screens than those receiving placebo.

Clinical Point

In alcohol-dependent BD patients, lithium plus divalproex sodium increased abstinence

However, lithium seems to have little efficacy in reducing cocaine use in cocaine-dependent patients with bipolar spectrum disorders.¹⁴ In an open-label study, 10 patients with a history of hypomania or cyclothymia received lithium monotherapy for 12 weeks. Although patients experienced improved mood symptoms and decreased cocaine use, the mean decrease was transitory and not statistically significant. Another factor that may limit lithium’s use for BD-SUD patients is that these patients are more likely to comply with valproate treatment than with lithium.¹⁵

Table 1

Lithium for BD patients with substance use disorders

Study	Intervention	Design	Substance use disorder	Results
Geller et al, 1998¹³	Lithium vs placebo	Double-blind, placebo-controlled	Alcohol and cannabis use disorders	Decreased positive drug screen results
Nunes et al, 1990¹⁴	Lithium	Open label	Cocaine abuse	Nonsignificant decrease in cocaine use
BD: bipolar disorder

Anticonvulsants. In a double-blind, placebo-controlled study of 59 alcohol-dependent bipolar I disorder patients, lithium plus divalproex sodium was superior to lithium plus placebo in decreasing number of drinking days and number of drinks per day and in increasing periods of abstinence (Table 2).^16-19 Divalproex sodium was well tolerated and liver function improved in the divalproex sodium group compared with the placebo group, which probably was a benefit of decreased alcohol consumption. In addition, there was a strong association between mood symptoms and alcohol use, which suggests that maximizing mood symptom treatment may decrease alcohol use. However, the divalproex sodium and placebo groups did not differ in measures of mood symptoms, which implies that divalproex sodium might exhibit a positive effect on drinking regardless of its mood-stabilizing properties.

Divalproex sodium also has been used to treat BD comorbid with cocaine dependence. In a small open-label study, 15 patients receiving divalproex sodium plus counseling for mood and substance use disorders were followed for 6 weeks.¹⁷ The 7 patients who completed the trial had significantly more cocaine-abstinent days, spent less money on cocaine, and experienced fewer manic and depressive symptoms. However, divalproex sodium’s effect on cocaine use cannot be determined solely from this study because there was no placebo control group.

Clinical Point

In a placebo-controlled trial, carbamazepine modestly reduced positive drug screens in cocaine-dependent BD patients

Despite its widespread use as a mood stabilizer and potential use in alcohol detoxification, carbamazepine scarcely has been studied in BD-SUD patients. A double-blind, placebo-controlled study of 139 cocaine-dependent patients with BD or other affective disorders found that patients taking carbamazepine for 12 weeks experienced modest reductions in positive urine drug screens and increased time to cocaine use.¹⁸ They also reported less cocaine craving than patients taking placebo, and mood symptoms (mostly depressive) improved.

An open-label study used lamotrigine as adjunctive therapy or monotherapy for 62 cocaine-dependent BD patients followed for 36 weeks.¹⁹ There was some decrease in cocaine craving, money spent on cocaine, and rate of depressive and manic symptoms, but no effect on cocaine use. A placebo-controlled trial is necessary to confirm these modest effects.

No studies have evaluated the potential role of topiramate in treating BD-SUD, despite its FDA-approved indication for alcoholism treatment. Topiramate’s well-known safety and tolerability profile in BD patients make it an interesting option for those with co-occurring alcohol dependence.

Table 2

Studies suggest anticonvulsants may reduce alcohol, cocaine use in BD patients

Study	Intervention	Design	Substance use disorder	Results
Salloum et al, 2005¹⁶	Divalproex sodium plus lithium vs placebo plus lithium	Double-blind, placebo-controlled	Alcohol dependence	Decreased number of drinking days and number of drinks per day and increased time of abstinence
Salloum et al, 2007¹⁷	Divalproex sodium	Open label	Cocaine dependence	Increased cocaine-abstinent days and decreased money spent on cocaine and cocaine use severity index
*Brady et al, 2002¹⁸**	Carbamazepine vs placebo	Double-blind, placebo-controlled	Cocaine dependence	Decreased cocaine craving and cocaine use
Brown et al, 2006¹⁹	Lamotrigine	Open label	Cocaine dependence	Decreased cocaine craving and money spent on cocaine
*Sample included, but was not limited to, patients with BD BD: bipolar disorder

Atypical antipsychotics. In an open-label study, 16 weeks of quetiapine monotherapy effectively decreased alcohol consumption, alcohol craving, and psychotic and affective symptoms in 28 alcoholics with a variety of psychiatric diagnoses, including BD, schizoaffective disorder, and borderline personality disorder (Table 3).^20-24 However, in a double-blind study of augmentation with quetiapine or placebo for 102 alcohol-dependent BD patients, no significant differences in alcohol use were found between groups.²¹