Preferred Antidepressant in Alcoholism
Sertraline or mirtazapine are the preferred antidepressants for adults with alcohol dependence and depression, based on their favorable efficacy for both depressive symptoms and alcohol use outcomes, combined with better tolerability profiles compared to other agents. 1, 2, 3
Primary Evidence Supporting Sertraline and Mirtazapine
Sertraline
- Sertraline is specifically recommended as a preferred agent in American Family Physician guidelines for depression treatment due to its favorable adverse effect profile 1
- FDA-approved for major depressive disorder in adults 4
- Demonstrated efficacy in reducing both depressive symptoms AND alcohol consumption in systematic reviews of patients with co-occurring depression and alcohol dependence 3
- Low-quality but consistent evidence shows antidepressants (particularly SSRIs like sertraline) increase abstinence rates (RR 1.71,95% CI 1.22 to 2.39) and reduce drinks per drinking day (MD -1.13 drinks, 95% CI -1.79 to -0.46) 3
Mirtazapine
- Also listed as a preferred agent in the same American Family Physician guidelines 1
- FDA-approved for major depressive disorder 5
- Open-label trial specifically in comorbid MDD/alcohol dependence showed 74% reduction in depressive symptoms (p<0.001) and 60.8% reduction in weekly drinking (p<0.05) 2
- Well-tolerated in this treatment population with unique pharmacological profile unrelated to SSRIs or tricyclics 2
- Associated with weight gain, which may be beneficial in malnourished alcoholic patients 1
Why These Over Other Antidepressants
Avoid These Agents
- Paroxetine should be avoided due to higher anticholinergic effects and increased sexual dysfunction compared to other SSRIs 1
- Fluoxetine should be avoided due to greater risk of agitation and overstimulation 1
- While fluoxetine showed efficacy in one double-blind trial for comorbid depression/alcoholism, it is not a preferred first-line agent based on current guidelines 6
Other Considerations
- Bupropion is associated with lower sexual adverse events than fluoxetine and sertraline, making it an alternative option 1
- However, bupropion carries seizure risk, which may be elevated in alcohol withdrawal 1
- Tricyclic antidepressants (TCAs) are effective but have higher discontinuation rates due to adverse effects and are potentially dangerous in overdose—a critical concern in this population 1
Treatment Algorithm
Step 1: Initiate sertraline (50-200 mg daily) as first-line treatment 4, 3
- Start at 50 mg daily and titrate based on response
- Provides dual benefit for depression and alcohol use reduction
- Monitor for nausea (most common reason for discontinuation) 1
Step 2: If sertraline not tolerated or sexual side effects problematic, switch to mirtazapine (15-45 mg at bedtime) 1, 5, 2
- Particularly useful if insomnia is prominent (sedating effect)
- May improve appetite in malnourished patients
- Monitor for weight gain and sedation 1
Step 3: If sexual dysfunction is primary concern, consider bupropion SR (100-400 mg daily) 1
- Screen carefully for seizure history and ensure patient is not in acute alcohol withdrawal
- Requires dose adjustment in hepatic impairment 1
Critical Caveats
- Antidepressants alone are insufficient—must be combined with alcohol dependence treatment and psychosocial interventions 3
- Treatment duration should be at least 4-12 months after first depressive episode; longer for recurrent depression 1
- SSRIs do not offer significant advantages over tricyclics in substance use disorders, but have superior safety profiles 7
- Antidepressants are NOT effective for alcohol dependence without comorbid depression—the evidence only supports their use when both conditions are present 7, 3
- Monitor for serotonin syndrome if combining with other serotonergic medications 1
- Discontinuation rates are similar between antidepressants and placebo (RR 0.98,95% CI 0.79 to 1.22), suggesting good overall tolerability 3