Which selective serotonin reuptake inhibitor (SSRI) has the lowest incidence of drug‑induced sweating?

SSRI with Lowest Sweating Risk

Sertraline (Zoloft) appears to be the SSRI with the lowest incidence of drug-induced sweating, based on its favorable tolerability profile and minimal effect on metabolism compared to other SSRIs. 1

Evidence-Based Ranking of SSRIs by Sweating Risk

Lower Risk Options

• Sertraline (Zoloft) is described as "well tolerated" with less effect on metabolism of other medications compared to other SSRIs, suggesting a more favorable side effect profile overall 1
• Start at 25-50 mg daily, maximum 200 mg daily 1

Moderate to Higher Risk Options

• Paroxetine (Paxil) has been specifically implicated in case reports of excessive sweating requiring discontinuation 2

• In one documented case, paroxetine-induced sweating took 5 weeks to resolve after discontinuation, with a "probable" causal relationship on the Naranjo scale 2

• Escitalopram (Lexapro) has been associated with "increased sweating" as a notable side effect 3

• A case report documented escitalopram-induced excessive sweating that required additional treatment with mirtazapine for symptom control 4

• Fluoxetine (Prozac) is the most activating SSRI, which may correlate with higher sweating rates given the association between activation and autonomic side effects 5

• Citalopram (Celexa) commonly causes sweating (listed among nausea, headache, dry mouth, and tremor as frequent adverse effects) 5

General Context on SSRI-Induced Sweating

• Approximately 63% of patients on second-generation antidepressants experience at least one adverse effect, with sweating being commonly reported alongside diarrhea, dizziness, dry mouth, fatigue, headache, sexual dysfunction, tremor, and weight gain 1

• All SSRIs as a class can cause sweating, tremors, nervousness, insomnia or somnolence, dizziness, and gastrointestinal disturbances 1

Management Algorithm if Sweating Occurs

Step 1: Dose Reduction

• Attempt to reduce the SSRI dose while maintaining therapeutic efficacy 2

Step 2: Switch to Alternative SSRI

• If dose reduction is ineffective or inappropriate, switch to sertraline as the best-tolerated option 1, 2

Step 3: Add Adjunctive Agent

• If sweating persists despite switching, consider adding:
  • Benztropine (anticholinergic agent) 2
  • Cyproheptadine (serotonin antagonist) 2
  • Mirtazapine (has demonstrated dose-dependent reduction of SSRI-induced sweating through its serotonin antagonistic properties) 4

Step 4: Discontinuation

• If all above measures fail and sweating significantly impacts quality of life, consider discontinuing the SSRI entirely 2

Important Clinical Caveats

• Venlafaxine (SNRI) can paradoxically both cause and reduce sweating depending on dose: at ≤75 mg daily, the serotonergic effect may reduce sweating, while higher doses increase noradrenergic activity and worsen sweating 6

• Sweating symptoms may take several weeks to resolve after discontinuation (up to 5 weeks documented) 2

• The mechanism involves complex interactions between serotonergic and noradrenergic pathways in central thermoregulation, with peripheral sympathetic nervous system involvement 6