Evidence-Based Reviews

Pharmacotherapy for comorbid depression and alcohol dependence

Current Psychiatry. 2013 January;12(1):24-33

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The atypical antipsychotic quetiapine acts as a serotonin (5-HT1A and 5-HT2) and dopamine (D1 and D2) antagonist, and reports suggest it reduces alcohol craving and affective symptoms in patients with AUDs.^34,35 In a 16-week, open-label study, quetiapine decreased alcohol consumption, alcohol craving, and intensity of some psychiatric symptoms in 28 alcohol-dependent patients with bipolar disorder, schizoaffective disorder, or borderline personality disorder.³⁶

See the Box for a description of the role CRF₁ antagonists may play in treating patients with concurrent MDD and AUDs. See Table 4 for studies of memantine and quetiapine in treating depression with AUDs.

Box

CRF₁ receptor antagonists for concurrent depression and AUDs: For which patients might they work best?

Corticotropin-releasing factor (CRF) has a well-established role in stress and has been implicated for treating anxiety and depressive disorders. Evidence also suggests that CRF receptor 1 (CRF₁) may be a treatment target for alcohol use disorders (AUDs). Acute alcohol withdrawal and prolonged alcohol use are associated with elevated levels of extrahypothalamic CRF and correlated anxiety. CRF antagonists can reduce the anxiogenic effects of alcohol withdrawal and reduce some symptoms of alcohol dependence, including excessive alcohol self-administration and stress-induced relapse to alcohol use in rats with alcohol dependence, but not in those without dependence. Therefore, CRF₁ receptor antagonists may be especially helpful for individuals who use alcohol to reduce negative emotional states such as anxiety or dysphoria, including those with concurrent major depressive disorder and AUDs.

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Table 4

Other agents may play a role in treating depression with AUDs

Study	Sample	Results
Muhonen et al, 2008³²	Outpatients with MDD and AD 1. Memantine (20 mg/d; n = 40) 2. Escitalopram (20 mg/d; n = 40)	Both treatments reduced depressive and anxiety symptoms. No significant differences between groups. Study did not examine alcohol-related outcomes
Martinotti et al, 2008³³	Outpatients with comorbid AD and either bipolar disorder, schizoaffective disorder or borderline personality disorder. Open-label study 1. Quetiapine (300 to 800 mg/d; n = 28)	Quetiapine was associated with reduced alcohol consumption, alcohol craving, and intensity of psychiatric symptoms
AD: alcohol dependence; AUDs: alcohol use disorders; MDD: major depressive disorder

Interpreting the evidence

Clinical Point

Research on using a combination of antidepressants and medications that target alcohol use have been disappointing

The co-occurrence of MDD and AUDs is a common and difficult clinical problem. Although FDA-approved medications targeting depression and AUD are effective when these conditions occur alone, their efficacy when these conditions co-occur is still under investigation. Antidepressants have modest efficacy in reducing depressive symptoms but are less effective in reducing alcohol consumption, which suggests that their action on mood has little direct impact on alcohol consumption. Evidence for the efficacy of medications to treat alcohol consumption is less robust. Results from studies of using a combination of antidepressants and medications that directly target alcohol use have been conflicting and disappointing.

Clinical Point

SSRIs probably should be the first choice for depressed patients with comorbid alcohol use disorders

These findings underscore the importance of thorough evaluations. SSRIs are a first-line treatment for depression and as such probably should be the first choice for patients with comorbid AUDs. Drinking should be monitored closely and abstinence encouraged. Using medications that target AUDs is safe and modestly effective in patients with comorbid depression. Evidence suggests that treating both disorders simultaneously is more effective than treating either alone. Medications should be prescribed as part of a comprehensive treatment plan that also includes psychotherapy.

Related Resources

Pettinati H. Antidepressant treatment of co-occurring depression and alcohol dependence. Biol Psychiatry. 2004;56(10):785-792.
Nunes EV, Levin FR. Treatment of depression in patients with alcohol or other drug dependence: a meta-analysis. JAMA. 2004;291(15):1887-1896.

Drug Brand Names

Acamprosate • Campral
Amitriptyline • Elavil
Desipramine • Norpramin
Disulfiram • Antabuse
Escitalopram • Lexapro
Fluoxetine • Prozac
Imipramine • Tofranil
Ketamine • Ketalar
Memantine • Namenda
Mirtazapine • Remeron
Naltrexone • Revia, Vivitrol
Nefazodone • Serzone
Quetiapine • Seroquel
Sertraline • Zoloft

Disclosures

The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Petrakis receives research or grant support from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, the U.S. Department of Defense, and the U.S. Department of Veterans Affairs.