Can mirtazapine (an antidepressant medication) reduce alcohol cravings as a side effect?

Mirtazapine and Alcohol Cravings

Mirtazapine does reduce alcohol cravings in patients with comorbid depression and alcohol dependence, but this is a therapeutic effect rather than a side effect, and it should not be used solely for craving reduction without concurrent depression.

Evidence for Craving Reduction

The research demonstrates that mirtazapine significantly reduces alcohol cravings when used to treat depression in patients with alcohol use disorder:

• In a multicentre open-label study of 143 patients with alcohol dependence and comorbid depression, mirtazapine reduced craving scores by 42.3% on the Obsessive Compulsive Drinking Scale and 53.2% on the Visual Analog Scale for Craving over 8 weeks 1

• A pilot study of 12 patients with major depression and alcohol dependence showed drinking decreased from 33.9 to 13.3 drinks per week (60.8% reduction) over 8 weeks of mirtazapine treatment 2

• The craving reduction occurred alongside significant improvements in depression scores, with 72% of patients achieving a 50% or greater reduction in Hamilton Depression Rating Scale scores 1

Critical Clinical Context

This is NOT a side effect—it is a potential therapeutic benefit that occurs specifically in patients with comorbid depression and alcohol dependence:

• Guidelines for alcoholic liver disease management list baclofen, acamprosate, naltrexone, and disulfiram as pharmacologic treatments for alcohol abstinence, but do not include mirtazapine 3

• The European Association for the Study of the Liver specifically states that in patients with advanced alcoholic liver disease, baclofen is the recommended medication for preventing alcohol relapse, with no mention of mirtazapine for this indication 3

• Mirtazapine should only be used when both depression and alcohol dependence are present—not as a standalone anti-craving agent 4

Mechanism of Action

The craving reduction likely occurs through multiple pathways:

• Mirtazapine blocks central α2-adrenergic receptors and enhances both noradrenergic and serotonergic neurotransmission, which may affect reward pathways involved in alcohol craving 5

• The drug's antagonism of 5-HT2 and 5-HT3 receptors may contribute to reduced craving and improved mood 5

• The craving reduction appears to be secondary to improvement in depressive symptoms rather than a direct anti-craving effect 4

Important Limitations and Caveats

The evidence base has significant weaknesses:

• All published studies are open-label or naturalistic without placebo controls, limiting the strength of conclusions 1, 2, 4

• A comprehensive literature review concluded that while mirtazapine shows promise for decreasing depression in MDD/AUD, there is no clear evidence of effectiveness for decreasing alcohol ingestion independent of depression improvement 4

• Large-scale double-blind, placebo-controlled studies are still needed to definitively establish efficacy 4

Clinical Algorithm for Use

Use mirtazapine for alcohol cravings ONLY when:

1. The patient has diagnosed major depressive disorder or depressive disorder comorbid with alcohol dependence 1, 2

2. Depression treatment is clinically indicated as the primary goal 4

3. The patient does not have advanced alcoholic liver disease where baclofen would be preferred 3

4. Weight gain and sedation (common mirtazapine effects occurring in 10% and 23% of patients respectively) would not be detrimental 6

Dosing for this indication:

• Start at 15 mg nightly for 4 days, then increase to 30 mg daily 5

• Monitor depression scores, craving levels, and alcohol consumption weekly initially 1

• Continue for at least 8 weeks to assess full therapeutic response 1, 2