Bipolar disorder and substance abuse: Overcome the challenges of ‘dual diagnosis’ patients
Research underscores the difficulty in keeping dual diagnosis patients in treatment. Salloum et al24 reported that only one-third of randomized subjects completed the 24-week study. In the Kemp study,28 79% of 149 recruited subjects failed to complete the lead-in stabilization phase. Of the 31 remaining subjects who were randomized to lithium or lithium/divalproex combination, only 8 (26% of those randomized, 5% of those recruited) completed the 6-month trial.
Substance abuse is associated with significantly decreased treatment adherence in persons with BD20 and may affect medication choice. For example, caution may be warranted in the use of lamotrigine in substance-abusing patients with poor adherence because re-titration from the starting dose is recommended if the medicine has been missed for a consecutive period exceeding 5 half-lives of the drug.30
Notable progress has been made in developing psychosocial treatments for comorbid SUDs and BD. Integrated group therapy has been designed to address the 2 disorders simultaneously by emphasizing the relationship between the disorders and highlighting similarities in cognitive and behavioral change that promote recovery in both.31 In a recent well-controlled RCT, this approach reduced alcohol and other drug use to approximately one-half the levels observed in those who received only group drug counseling.31
Research suggests that an integrated approach that encompasses psychiatric, medical, psychosocial, and legal dimensions simultaneously may be most effective. For patients such as Mr. M, this would include aggressively treating mood symptoms while employing motivational interviewing techniques to improve engagement in substance dependence treatment. If possible, involving family members, parole officials, housing agencies, and other public assistance workers in the treatment plan may increase treatment adherence and reduce loss of contact during illness exacerbations. Stabilization of substance use and psychiatric morbidity should be accompanied by timely evaluation of HCV and other medical comorbidities in order to improve long-term prognosis.
Table 2
Assessing patients you suspect have comorbid BD and SUDs
| Initial assessment |
|---|
Thorough substance use history in all patients with known or suspected bipolar disorder:
|
Thorough evaluation of any history of hypomania/mania and depression in all patients with known or suspected SUDs:
|
| Assess risk factors, screening status for hepatitis C, HIV |
| Obtain collateral information from family and significant others if feasible and appropriate |
| Detailed assessment of suicide risk |
| Follow-up assessments |
| Substance use since last visit by self-report |
| Consider UDS, CDT, GGT |
| Medication adherence |
| Detailed assessment of suicide risk |
| BD: bipolar disorder; CDT: carbohydrate-deficient transferrin; GGT: gamma-glutamyltransferase; HIV: human immunodeficiency virus; SUDs: substance use disorders; UDS: urine drug screen |
Table 3
Pharmacotherapy for bipolar disorder and co-occurring SUDs
| Study | Diagnoses/N* | Medications | Outcome |
|---|---|---|---|
| Salloum et al, 200524 | BD I, alcohol dependence. N=59 [20] | Divalproex + lithium vs lithium, 24 weeks | Decreased number of heavy drinking days, fewer drinks per heavy drinking day |
| Geller et al, 199825 | BD I, BP II, MDD (adolescents); alcohol, cannabis abuse. N=25 [21] | Lithium, 6 weeks | Decreased cannabis-positive urine drug screen (lithium > placebo) |
| Brady et al, 200226 | BD I, BD II, cyclothymia; cocaine dependence. N=57 | Carbamazepine, 12 weeks | Trend toward longer time to cocaine use |
| Brown et al, 200827 | BD I, BD II; N=102 | Quetiapine, 12 weeks | Decreased HAM-D scores (quetiapine > placebo) |
| Kemp et al, 200928 | BD I, BD II, rapid cycling; alcohol, cannabis, cocaine abuse or dependence. N=31 [8] | Divalproex + lithium vs lithium, 6 months | No group differences |
| Brown et al, 200929 | BD I, BD II; alcohol dependence. N=50 [26] | Naltrexone, 12 weeks | Trend toward increased probability of no drinking days |
| * N=number of subjects randomized to double-blind treatment. Numbers in brackets indicate the number of subjects who completed all study visits (when reported) | |||
| BD: bipolar disorder; HAM-D: 17-item Hamilton Rating Scale for Depression; MDD: major depressive disorder; SUDs: substance use disorders | |||
Related Resources
- International Society for Bipolar Disorders. www.isbd.org.
- National Institute on Alcohol Abuse and Alcoholism. www.niaaa.nih.gov.
- National Institute on Drug Abuse. www.nida.nih.gov.
Drug Brand Names
- Carbamazepine • Tegretol
- Divalproex/valproic acid • Depakote
- Lamotrigine • Lamictal
- Lithium • Lithobid
- Naltrexone • ReVia
- Quetiapine • Seroquel
Disclosure
Dr. Tolliver receives research grant funding from Forest Laboratories and the National Institute on Alcohol Abuse and Alcoholism. Neither source influenced the content or submission of this manuscript.
A recent analysis of data from >65,000 veterans found bipolar patients with comorbid substance use disorders (SUDs) were 7 times more likely to have hepatitis C virus (HCV) than patients with no serious mental illness.a Matthews and colleagues found that 29.6% of persons diagnosed with bipolar disorder (BD) and SUDs tested positive for HCV—roughly 5 times the relative risk of patients without either diagnosis.b The high prevalence of HCV in patients with comorbid BD and SUDs may be the result of injection drug use, increased risky sexual behavior while manic or intoxicated, or both.
HCV has multiple treatment implications for these patients. Alcohol abuse and dependence are the most common SUDs that co-occur with BD,c-e and patients with HCV who drink alcohol excessively have more severe hepatic fibrosis, accelerated disease progression, and higher rates of cirrhosis and hepatocellular carcinoma than HCV patients who do not drink.f Medications commonly used to treat BD or alcohol dependence may have adverse effects on the liver and require more careful monitoring in the presence of HCV infection. For example, valproic acid has been reported to improve drinking outcomes in alcohol-dependent patients with BDg but has been associated with higher rates of marked hepatic transaminase elevation in patients with HCV infection compared with those without HCV.h Marked elevation of hepatic transaminases may be observed in HCV-infected individuals treated with other medications such as lithium or antidepressants,h and valproic acid use is not an absolute contraindication in HCV patients. Nevertheless, the effects of valproic acid in HCV-infected BD patients who drink alcohol are unknown and therefore cautious and frequent monitoring of hepatic enzymes are warranted in this population.
Finally, both SUDs and BD complicate HCV treatment. In a database review of >113,000 veterans with HCV infection, Butt and colleagues found that individuals with BD accounted for 10.4% of the HCV-infected sample but only 5% of those who received HCV treatment.i Similarly, patients with alcohol abuse or dependence made up 44.3% of the HCV-infected sample but only 28.9% of those who received HCV treatment.
Because the rate of liver biopsy in untreated patients was low, the decision not to treat appeared to be based more often on other criteria. This is not surprising; pegylated interferon-alfa—the most effective treatment for chronic HCV—has been associated with multiple neuropsychiatric symptoms observed in BD, including depression, mania, psychosis, and suicidal ideation.j Emergence of severe psychiatric complications usually results in permanent discontinuation of interferon treatment. Likewise, the presence of alcohol abuse or other SUDs is a strong negative predictor of interferon treatment response and retention and generally has been considered a relative contraindication for interferon initiation.f
References
a. Himelhoch S, McCarthy JF, Ganoczy D, et al. Understanding associations between serious mental illness and hepatitis C virus among veterans: a national multivariate analysis. Psychosomatics. 2009;50:30-37.
b. Matthews AM, Huckans MS, Blackwell AD, et al. Hepatitis C testing and infection rates in bipolar patients with and without comorbid substance use disorders. Bipolar Disord. 2008;10:266-270.
c. Grant BF, Stinson FS, Dawson DA, et al. Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders. Results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2004;61:807-816.
d. Hasin DS, Stinson FS, Ogburn E, et al. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States. Results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2007;64:830-842.
e. Merikangas KR, Akiskal HS, Angst J, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2007;64:543-552.
f. Bhattacharya R, Shuhart M. Hepatitis C and alcohol. J Clin Gastroenterol. 2003;36:242-252.
g. 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;62:37-45.
h. Felker BL, Sloan KL, Dominitz JA, et al. The safety of valproic acid use for patients with hepatitis C infection. Am J Psychiatry. 2003;160:174-178.
i. Butt AA, Justice AC, Skanderson M, et al. Rate and predictors of treatment prescription for hepatitis C. Gut. 2006;56:385-389.
j. Onyike CU, Bonner JO, Lyketsos CG, et al. Mania during treatment of chronic hepatitis C with pegylated interferon and ribavirin. Am J Psychiatry. 2004;161:429-435.
