Incidence of Fatigue and Dry Mouth with Zoloft (Sertraline)
Based on FDA-approved labeling data from over 4,000 adult patients, fatigue occurs in approximately 12% of sertraline-treated patients versus 8% on placebo, while dry mouth affects 14% versus 8% on placebo. 1
Fatigue Incidence Rates
Fatigue is a common but relatively mild side effect of sertraline, occurring at rates that vary by indication:
- In pooled data across all indications (major depression, OCD, panic disorder, PTSD, PMDD, social anxiety disorder), fatigue occurred in 12% of sertraline patients compared to 7% on placebo 1
- In major depressive disorder specifically, fatigue affected 11% of sertraline patients versus 8% on placebo 1
- In OCD trials, fatigue rates were 14% with sertraline versus 10% on placebo 1
- In panic disorder, 11% experienced fatigue on sertraline versus 6% on placebo 1
- In PTSD patients, 10% reported fatigue with sertraline versus 5% on placebo 1
The absolute increase in fatigue risk with sertraline is approximately 4-5% above placebo rates across most indications. 1
Dry Mouth Incidence Rates
Dry mouth (xerostomia) is one of the most common side effects of sertraline, though it remains less problematic than with tricyclic antidepressants:
- Across all pooled indications, dry mouth occurred in 14% of sertraline patients versus 8% on placebo 1
- In major depressive disorder, 16% experienced dry mouth with sertraline compared to 9% on placebo 1
- In OCD trials, dry mouth affected 14% on sertraline versus 9% on placebo 1
- In panic disorder, 15% reported dry mouth with sertraline versus 10% on placebo 1
- In PTSD, 11% experienced dry mouth on sertraline versus 6% on placebo 1
- In social anxiety disorder, 12% had dry mouth with sertraline versus 4% on placebo 1
Meta-analytic data confirms that SSRIs like sertraline carry a 1.65-fold increased risk of dry mouth compared to placebo (95% CI: 1.39-1.95), which is significantly lower than the 2.24-fold risk seen with SNRIs. 2
Clinical Context and Comparative Risk
Sertraline's side effect profile is considerably more favorable than older antidepressants:
- Tricyclic antidepressants cause significantly more severe dry mouth than sertraline, both objectively and subjectively 3
- SSRIs as a class, including sertraline, are generally associated with less severe dry mouth symptoms compared to tricyclics 3
- The American Family Physician guidelines note that approximately 63% of patients on second-generation antidepressants experience at least one adverse effect, with dry mouth, fatigue, dizziness, and headache being commonly reported 4
In elderly patients (≥60 years), sertraline is specifically preferred over paroxetine and fluoxetine due to better tolerability and lower anticholinergic effects, with the most frequently reported adverse events being dry mouth, headache, diarrhea, nausea, insomnia, somnolence, constipation, dizziness, and sweating. 4, 5
Important Clinical Considerations
Both fatigue and dry mouth typically emerge within the first few weeks of treatment and often decrease in frequency with continued use:
- Most adverse effects appear within the first few weeks of SSRI treatment 4
- These side effects are usually mild and transient, decreasing with continued treatment 6
- The American Academy of Child and Adolescent Psychiatry notes that dry mouth, nausea, diarrhea, heartburn, fatigue, and diaphoresis are common adverse events during extended sertraline use 4, 7
Discontinuation rates due to fatigue or dry mouth are low:
- Fatigue led to discontinuation in approximately 2% of social anxiety disorder patients on sertraline versus <1% on placebo 1
- Dry mouth alone rarely causes treatment discontinuation, as it was not listed among the most common reasons for stopping sertraline in FDA trials 1
The risk-benefit ratio remains favorable, as the number needed to treat for response is only 3, while the number needed to harm for serious adverse events is 143. 4