[11] Although also having approval for post-traumatic stress disorder (PTSD), findings indicate it leads to only modest improvements in symptoms associated with this condition.

Similar to other antidepressants, the use of sertraline for depression may be associated with a mildly elevated rate of suicidal thoughts in people under the age of 25 years old.

[24][25] A major study of sertraline in a broad primary care population found improvements in general mental health, quality of life, and anxiety.

[27][28] In several double-blind studies, sertraline was consistently more effective than placebo for dysthymia, a more chronic variety of depression, and comparable to imipramine in that respect.

[32] For example, a meta-analysis of 12 new-generation antidepressants showed that sertraline and escitalopram are the best in terms of efficacy and acceptability in the acute-phase treatment of adults with depression.

[33] Comparative clinical trials demonstrated that sertraline is similar in efficacy against depression to moclobemide,[34] nefazodone,[35] escitalopram, bupropion,[36] citalopram, fluvoxamine, paroxetine,[33] venlafaxine,[37] and mirtazapine.

[37] Sertraline appears to work better in melancholic depression than fluoxetine, paroxetine, and mianserin and is similar to the tricyclic antidepressants such as amitriptyline and clomipramine.

[32] Sertraline used for the treatment of depression in elderly (older than 60) patients is superior to placebo and comparable to another SSRI fluoxetine, and tricyclic antidepressants (TCAs) amitriptyline, nortriptyline and imipramine.

[64] Sertraline has not been approved for the treatment of generalized anxiety disorder; however, several guidelines recommend it as a first-line medication referring to good quality controlled clinical trials.

[71] There are both negative and positive clinical trial results for sertraline, which may be explained by the types of psychological traumas, symptoms, and comorbidities included in the various studies.

[50] Positive results were obtained in trials that included predominantly women (75%) with a majority (60%) having physical or sexual assault as the traumatic event.

[21] Nausea, ejaculation failure, insomnia, diarrhea, dry mouth, somnolence, dizziness, tremor, headache, excessive sweating, fatigue, restless legs syndrome and decreased libido are the common adverse effects associated with sertraline with the greatest difference from placebo.

[77] Although the difference did not reach statistical significance, the average weight gain was lower for fluoxetine (1%) but higher for citalopram, fluvoxamine and paroxetine (2.5%).

[80] In children and adolescents taking sertraline for six weeks for anxiety disorders, 18 out of 20 measures of memory, attention, and alertness stayed unchanged.

[82][83] Sertraline has a low level of exposure of an infant through the breast milk and is recommended as the preferred option for the antidepressant therapy of breast-feeding mothers.

While nefazodone and bupropion do not have negative effects on sexual functioning, 67% of men on sertraline experienced ejaculation difficulties versus 18% before the treatment.

[92] Sexual arousal disorder, defined as "inadequate lubrication and swelling for women and erectile difficulties for men", occurred in 12% of people on sertraline as compared with 1% of patients on placebo.

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".

[101] 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.

Plasma, serum or blood concentrations of sertraline and norsertraline, its major active metabolite, may be measured to confirm a diagnosis of poisoning in hospitalized patients or to aid in the medicolegal investigation of fatalities.

[21] Over time, this leads to a downregulation of pre-synaptic 5-HT1A receptors, which is associated with an improvement in passive stress tolerance, and delayed downstream increase in expression of brain-derived neurotrophic factor (BDNF), which may contribute to a reduction in negative affective biases.

[5][124][136] Based on in vitro studies, sertraline is metabolized by multiple cytochrome 450 isoforms;[9][137] however, it appears that in the human body CYP2C19 plays the most important role, followed by CYP2B6.

[138] In addition to the cytochrome P450 system, sertraline can be oxidatively deaminated in vitro by monoamine oxidases;[5] however, this metabolic pathway has never been studied in vivo.

[138] The history of sertraline dates back to the early 1970s when Pfizer chemist Reinhard Sarges invented a novel series of psychoactive compounds, including lometraline, based on the structures of the neuroleptics thiothixene and pinoxepin.

A few years later, in 1977, pharmacologist Kenneth Koe, after comparing the structural features of a variety of reuptake inhibitors, became interested in the tametraline series.

Weissman and Koe recalled that the group did not set up to produce an antidepressant of the SSRI type—in that sense their inquiry was not "very goal driven", and the invention of the sertraline molecule was serendipitous.

The group had to overcome initial bureaucratic reluctance to pursue sertraline development, as Pfizer was considering licensing an antidepressant candidate from another company.

During the discussion, Paul Leber, the director of the FDA Division of Neuropharmacological Drug Products, noted that granting approval was a "tough decision", since the treatment effect on outpatients with depression had been "modest to minimal".

Other experts emphasized that the drug's effect on inpatients had not differed from placebo and criticized the poor design of the clinical trials by Pfizer.

In 2003, the UK Medicines and Healthcare products Regulatory Agency issued guidance that, apart from fluoxetine (Prozac), SSRIs are not suitable for the treatment of depression in patients under 18.