Among the common adverse effects associated with sertraline and listed in the prescribing information, the effects with the greatest difference from placebo are nausea (25% vs 11% for placebo), ejaculation failure (14% vs 1% for placebo), insomnia (21% vs 11% for placebo), diarrhea (20% vs 10% for placebo), dry mouth (14% vs 8% for placebo), somnolence (13% vs 7% for placebo), dizziness (12% vs 7% for placebo), tremor (8% vs 2% for placebo) and decreased libido (6% vs 1% for placebo). Those that most often resulted in interruption of the treatment were nausea (3%), diarrhea (2%) and insomnia (2%). Sertraline appears to be associated with microscopic colitis, a rare condition of unknown etiology.

Akathisia, that is "inner tension, restlessness, and the inability to stay still", caused by sertraline was observed in 16% of patients in a case series.This and other reports note that akathisia begins soon after the initiation of treatment or increase of the dose, often, several hours after taking the medication. Akathisia usually disappears within several days after sertraline is stopped or its dose is decreased. In some cases, clinicians confused akathisia with anxiety, and increased the dose of sertraline causing further worsening of the patients' symptoms. The experts note that because of the possible link of akathisia with suicide and the distress it causes to the patient, "it is of vital importance to increase awareness amongst staff and patients of the symptoms this relatively common condition".

Over more than six months of sertraline therapy for depression, patients showed an insignificant weight increase of 0.1%. Similarly, a 30 months-long treatment with sertraline for OCD, resulted in a mean weight gain of 1.5% (1 kg). Although the difference did not reach statistical significance, the weight gain was lower for fluoxetine (Prozac) (1%) but higher for citalopram (Celexa), fluvoxamine (Luvox) and paroxetine (Paxil) (2.5%). Only 4.5% of the sertraline group gained a large amount of weight (defined as more than 7% gain). This result compares favorably with placebo, where, according to the literature, 3,6% of patients gained more than 7% of their initial weight. The large weight gain was observed only among female members of the sertraline group; the significance of this finding is unclear because of the small size of the group.

Over a two-week treatment of healthy volunteers, sertraline slightly improved verbal fluency and did not affect word learning, short-term memory, vigilance, flicker fusion time, choice reaction time, memory span, and psychomotor coordination. In spite of lower subjective rating, no clinically relevant differences were observed in the objective cognitive performance in a group of people treated for depression with sertraline for 1.5 year as compared to healthy controls.

Birth defects and effects on breast-fed infants

The studies comparing the levels of sertraline and its principal metabolite, desmethylsertraline, in mother's blood to their concentration in umbilical cord blood at delivery indicated that the fetus's exposure to sertraline and its metabolite is approximately a third of the maternal exposure. The use of sertraline during the first trimester of pregnancy was associated with the increased odds of the following birth defects: omphalocele—six-fold, septal defects—two-fold, anal atresia and limb reduction defects—four-fold. Concentration of sertraline and desmethylsertraline in the breast milk is highly variable and, on average, is of the same order of magnitude as their concentration in the blood plasma of the mother. As a result, more than half of the breast-fed babies receive less than 2 mg/day of sertraline and desmethylsertraline combined, and in most cases these substances are undetectable in their blood. No changes in the serotonin uptake by the platelets of breast-fed infants were found, as measured by their blood serotonin levels before and after their mothers began sertraline treatment.

Sexual side effects

The observed frequency of the sexual side effects depends greatly on whether they are reported by patients spontaneously, as in the manufacturer's trials, or actively solicited by the physicians. There have been several double-blind studies of the sexual side effects comparing sertraline with placebo or other antidepressants. While nefazodone (Serzone) and bupropion did not have negative effect on sexual functioning, 67% of men on sertraline experienced ejaculation difficulties vs. 18% before the treatment (or 61% vs 0% according to another paper). Similarly, in a group of women who initially had not have difficulties achieving orgasm, 41% acquired this problem during treatment with sertraline. The 40% rate of orgasm dysfunction (vs 9% for placebo) on sertraline was observed in a mixed group in another study. Sexual arousal disorder defined as "inadequate lubrication and swelling for women and erectile difficulties for men" occurred in 12% of sertraline patients as compared with 1% of patients on placebo. At the same time, sexual desire and overall satisfaction with sex stayed the same, as in the beginning of the sertraline treatment, and slightly below the placebo.

Suicidality

The FDA requires all antidepressants, including sertraline, to carry a black box warning stating that antidepressants may increase the risk of suicide in persons younger than 25. This warning is based on statistical analyses conducted by two independent groups of the FDA experts that found a 2-fold increase of the suicidal ideation and behavior in children and adolescents, and 1.5-fold increase of suicidality in the 18-24 age group.

Suicidality in adults

Suicidal ideation and behavior in clinical trials are not rare. For the above analysis, the FDA combined the results of 295 trials of 11 antidepressants for psychiatric indications in order to obtain statistically significant results. Considered separately, sertraline use in adults decreased the odds of suicidality with a marginal statistical significance by 37%or 50% depending of the statistical technique used. The authors of the FDA analysis note that "given the large number of comparisons made in this review, chance is a very plausible explanation for this difference". The more complete data submitted later by the sertraline manufacturer Pfizer indicated increased suicidality. Similarly, the analysis conducted by the UK MHRA found a 50% increase of odds of suicide-related events, not reaching statistical significance, in the patients on sertraline as compared to the ones on placebo.

Discontinuation syndrome

Main article: SSRI discontinuation syndrome

Abrupt interruption of sertraline may result in withdrawal or discontinuation syndrome. This syndrome occurred in 60% of the sertraline subjects in a blind discontinuation study, as compared to 14% of fluoxetine and 66% of paroxetine subjects. During the 5-8 days of the sertraline discontinuation, the most frequent symptoms reported by more than a quarter of patients were irritability, agitation, dizziness, headache, nervousness, crying, emotional lability, bad dreaming and anger. Approximately one third of the subjects experienced mood worsening to the level generally associated with a major depressive episode.