What selective serotonin reuptake inhibitors (SSRIs) are less likely to cause sweating?

SSRIs with Lower Risk of Sweating

Based on the available evidence, citalopram (Celexa) and escitalopram (Lexapro) appear to be the SSRIs least likely to cause sweating, while paroxetine (Paxil) and sertraline (Zoloft) are associated with higher rates of this adverse effect. 1, 2

Evidence-Based Ranking of SSRIs by Sweating Risk

Lower Risk Options:

• Citalopram (Celexa): Well tolerated with some patients experiencing nausea and sleep disturbances, but sweating is not prominently listed among its common adverse effects 1
• Escitalopram (Lexapro): Has minimal affinity for receptors associated with anticholinergic and adrenergic side effects, which may contribute to a lower sweating profile 3

Higher Risk Options:

• Paroxetine (Paxil): Associated with higher incidences of sweating, sexual dysfunction, and discontinuation reactions compared to other SSRIs 2
• Sertraline (Zoloft): FDA labeling data shows increased sweating occurred in 8% of patients with major depression (vs 3% placebo), 15% with OCD (vs 1% placebo), and 11% with social anxiety disorder (vs 2% placebo) 4
• Fluoxetine (Prozac): While activating properties are prominent, sweating is listed among typical SSRI side effects 1, 5

Clinical Context from Guidelines

All SSRIs as a class can cause sweating as a common adverse effect, along with tremors, nervousness, insomnia or somnolence, dizziness, and gastrointestinal disturbances 1. Approximately 63% of patients receiving second-generation antidepressants experience at least one adverse effect, with sweating being commonly reported 1.

Practical Selection Algorithm

Step 1: If sweating is a primary concern, start with citalopram 10 mg daily (maximum 40 mg) or escitalopram 10 mg daily (maximum 20 mg) 1

Step 2: Avoid paroxetine and sertraline as first-line options if the patient has a history of problematic sweating or heat intolerance 2

Step 3: For elderly patients specifically, citalopram, escitalopram, and sertraline are generally preferred, though sertraline carries higher sweating risk; paroxetine and fluoxetine should be avoided due to higher rates of adverse effects 1

Management if Sweating Develops

If excessive sweating occurs despite choosing a lower-risk SSRI:

• First approach: Consider dose reduction if clinically appropriate 6
• Second approach: Switch to an alternative SSRI with lower sweating risk (citalopram or escitalopram if not already tried) 6
• Third approach: Consider switching to a non-SSRI antidepressant such as bupropion, which is not associated with sweating and may promote weight loss 1
• Adjunctive treatment: If switching is not feasible, terazosin (1-6 mg/day) has shown effectiveness in treating antidepressant-induced excessive sweating, with 22 of 23 patients responding in an open-label trial 7
• Alternative adjunctive options: Benztropine or cyproheptadine have been reported successful, though evidence is limited 6

Important Caveats

Drug interactions: When prescribing SSRIs to patients on tamoxifen for breast cancer, avoid paroxetine and fluoxetine as they are potent CYP2D6 inhibitors; citalopram, escitalopram, sertraline, and venlafaxine have minimal effect on tamoxifen metabolism 1

Discontinuation symptoms: Shorter-acting SSRIs (paroxetine, fluvoxamine, sertraline) are associated with more discontinuation symptoms than longer-acting ones like fluoxetine 5

Serotonin syndrome risk: All SSRIs can potentially cause serotonin syndrome when combined with other serotonergic medications 1, 5