What are the side effects of combining sertraline (selective serotonin reuptake inhibitor) with alcohol?

Side Effects of Combining Sertraline and Alcohol

The FDA explicitly states that concomitant use of sertraline and alcohol is not recommended, even though sertraline does not potentiate the cognitive and psychomotor effects of alcohol in laboratory studies with normal subjects. 1

Key Safety Considerations

No Pharmacological Interaction in Controlled Studies

• Multiple controlled studies in both young and elderly volunteers demonstrate that sertraline does not potentiate alcohol's effects on cognitive or psychomotor performance, including simulated car driving tasks. 2, 3
• In elderly volunteers specifically, sertraline (up to 200 mg/day) combined with moderate alcohol (0.5 g/kg body weight) showed no additive depressant effects on objective performance measures. 3
• The drug maintains a neutral psychomotor profile even when combined with alcohol in experimental settings. 2

FDA Warning Despite Lack of Interaction

• Despite the absence of demonstrated pharmacological interaction, the FDA drug label explicitly advises against combining sertraline with alcohol. 1
• This precautionary stance reflects the general principle that drugs acting on the central nervous system may affect individuals adversely, even when laboratory studies show no interaction. 1

Common Side Effects of Sertraline (Relevant to Alcohol Use)

Central Nervous System Effects

• Drowsiness and sedation can occur with sertraline, particularly at doses ≥100 mg/day, though the drug is generally neither stimulating nor sedating. 2
• Patients may experience impaired ability to make decisions, think clearly, or react quickly—effects that could theoretically be compounded by alcohol despite lack of formal interaction data. 1
• Dizziness and feeling tired or fatigued are common side effects. 1

Gastrointestinal Effects

• Nausea, loss of appetite, diarrhea, and indigestion are common with sertraline. 1
• These effects could be exacerbated by alcohol's own gastrointestinal irritant properties.

Bleeding Risk

• Sertraline increases bleeding risk, particularly when combined with NSAIDs or aspirin, due to effects on platelet serotonin release. 1
• Alcohol also impairs hemostasis, creating a theoretical additive bleeding risk, though this specific combination has not been formally studied. 1

Special Considerations for Alcohol-Dependent Patients

Therapeutic Context

• In alcohol-dependent patients with co-occurring depression, sertraline (200 mg/day) has been studied and shows modest benefit in reducing drinks per drinking day. 4
• When combined with naltrexone, sertraline demonstrates superior outcomes for both alcohol abstinence (53.7% vs 23-27% for monotherapy) and depression remission in alcohol-dependent patients. 5
• However, stress may reduce sertraline's effectiveness in decreasing alcohol consumption, as demonstrated in primate models. 6

Clinical Recommendations

Patient Counseling

• Advise patients to avoid alcohol while taking sertraline, following FDA guidance. 1
• Warn patients that until they understand how sertraline affects them individually, they should exercise caution with activities requiring alertness (driving, operating machinery). 1
• Explain that while laboratory studies show no interaction, individual responses may vary and the combination is not recommended. 1

Monitoring

• If patients consume alcohol despite recommendations, monitor for:
  • Excessive sedation or drowsiness beyond expected sertraline effects 1
  • Increased bleeding tendency, particularly if taking NSAIDs or aspirin 1
  • Worsening depression or emergence of suicidal ideation 1

Common Pitfall

• Do not assume safety based on lack of pharmacokinetic interaction—the FDA's recommendation against combining these substances is based on the unpredictable nature of CNS-active drugs in real-world settings, not laboratory findings. 1