Depression

The original clinical trials demonstrated only moderate efficacy of sertraline for depression (see History). Nevertheless, later research firmly established sertraline as one of the drugs of choice for the treatment of depression in outpatients. In addition, sertraline is effective for dysthymia and comparable to imipramine in that respect. In the treatment of depression accompanied by OCD, sertraline performed significantly better than desipramine (Norpramine) on the measures of both OCD and depression.

Comparison with tricyclic antidepressants

Sertraline has a similar effect on the core depressive symptoms as the tricyclic antidepressants (TCAs); however, it is better tolerated and results in a better quality of life.

For example, similar improvement of depression scores was in comparative studies of sertraline versus clomipramine (Anafranil) and amitriptyline (Elavil). At the same time, sertraline resulted in a much lower rate of side effects than amitriptyline (49% vs 72% vs 32% for placebo), particularly dry mouth, somnolence, constipation and increased appetite. However, there were more cases of nausea and sexual dysfunction in the sertraline group. Furthermore, sertraline patients showed a greater improvement of the subjective quality of life on such measures as work satisfaction, subjective feeling, perceptions of health and cognitive function.

A large and thorough double-blind study compared sertraline, prescribed for chronic (longer than 2 years) depression or depression with dysthymia, to the "gold standard" of depression treatment TCA imipramine (Tofranil). Sertraline was equivalent to imipramine for both of these indications during the first 12 weeks of the study and the 16 weeks continuation phase. Only 11% of patients on sertraline suffered severe side effects vs. 24% on imipramine. Constipation, dizziness, tremor, dry mouth, micturition disorder and sweating adverse effects were observed more often with imipramine, and diarrhea and insomnia with sertraline. Sertraline patients also reported significantly better social and physical functioning. Interestingly, the patients who achieved a remission during the trial (30% of the sample) did not differ from the healthy population on the measures of marital, parental, physical and work functioning and were close to normal on social adjustment and other measures of interpersonal functioning.

Comparison with other antidepressants

Comparative clinical trials demonstrated that sertraline's efficacy in depression is similar to moclobemide (Aurorix), nefazodone (Serzone),, escitalopram (Lexapro), bupropion (Wellbutrin), citalopram (Celexa), fluvoxamine (Luvox), paroxetine (Paxil) and mirtazapine (Remeron). Remarkably, the patients on sertraline had much higher rate of sexual dysfunction (61% vs 10% for men and 41% vs 7% for women), nausea, diarrhea, somnolence and sweating as well as rate of discontinuation due to the side effects (13% vs 3%) than the patients on bupropion. Meta-analysis by the independent Cochrane Collaboration indicated that sertraline is more effective for the treatment of depression than fluoxetine (Prozac) (probability of response 1.4 times higher) and, possibly, is better tolerated. Three comparative studies of sertraline and venlafaxine (Effexor) has been conducted. In the first study supported by the venlafaxine manufacturer Wyeth and in the second — by the sertraline manufacturer Pfizer, sertraline performed marginally worse on some psychiatric scales and similarly to venlafaxine on others. However, the former study was criticized for the methodology shortcomings. A third study, funded by Pfizer, found no differences between sertraline and venlafaxine.

Depression in elderly

Sertraline used for the treatment of depression in elderly (older than 60) was superior to placebo and comparable to another SSRI fluoxetine, and TCAs amitriptyline, nortriptyline (Pamelor) and imipramine. Sertraline had much lower rate of adverse effects than these TCAs, for the exception of nausea, which occurred more frequently with sertraline. In addition, sertraline appeared to be more effective than fluoxetine or nortriptyline in the older than 70 subgroup. A more recent trial of sertraline vs placebo in elderly showed a statistically significant, that is unlikely to occur by chance, but clinically very modest improvement in depression and no improvement in quality of life. The authors were sharply criticized by Bernard Carroll, a one time chairman of the FDA Psychopharmacological Drugs Advisory Committee, for presenting these results as positive: "The study has all hallmarks of an experimercial, a cost-no-object exercise driven by a corporate sponsor to create a positive publicity for its product in a market niche... Thus does the corporate mandate to put lipstick on the pig prevail over the academic duty to communicate independent analysis of the data."

Obsessive-compulsive disorder

Placebo-controlled studies have demonstrated sertraline to be efficacious for the treatment of OCD in adults and children. It was better tolerated and, based on intention to treat analysis, performed better than the gold standard of OCD treatment clomipramine. Sertraline was also marginally more efficacious than fluoxetine (Prozac). If the patient did not respond to sertraline, increasing the dose to 250-400 mg, that is higher than the maximum recommended, did not bring any additional benefits. The patients who responded to sertraline during a short-term trial sustained their improvement when the treatment continued for a year and longer. At the same time, the prolonged treatment may not be necessary for everyone. In a double-blind study, half of the subjects who had been successfully treated for a year were discontinued from sertraline. The rate of relapse among them was the same as in the control group who continued taking sertraline. The withdrawal syndrome may, at least partially, account for the fact that more subjects in the discontinuation group dropped off from the study due to the side effects and worsening of the OCD symptoms. Overall, the 48% of the discontinuation group who were able to complete the study fared as well as the subjects who continued taking sertraline. CBT alone was superior to sertraline in both adults and children; however, the best results were achieved using combination of these treatments.

Posttraumatic stress disorder

Two double-blind placebo-controlled studies confirmed the efficacy of sertraline for a severe chronic PTSD in civilians, with the mean duration of the illness more than 10 years. Physical or sexual assault was the traumatic event for more than 60% the subjects, and 75% of them were women. Over the 12-week period, 53-60% of the patients treated with sertraline were much or very much improved vs 32-38% for placebo. The treatment was continued for another year with some participants from both trials. The condition of the responders further improved; some of the patients who did not respond to the initial 12-week trial slowly improved as well, so that about half of them were classified as responders by the end of the following 24 weeks. The authors note that the medication worked slower for those with more severe symptoms. Discontinuation of the successful treatment after six months, resulted in the return of the PTSD symptoms in 52% of the patients vs 16% in those who continued taking sertraline. Longer term treatment has been advocated in such cases.

Three-way (placebo-sertraline-third antidepressant) comparison trials of sertraline for PTSD found it to be better than placebo and equivalent to venlafaxine (Effexor) or citalopram (Celexa), and in a two-way comparison it has the same efficacy as nefazodone (Serzone). Sertraline was not effective for veterans with combat-related PTSD.

Other indications

Sertraline can also be used in the treatment of general anxiety disorder, binge eating disorder, and premature ejaculation.

There is also evidence that sertraline may be effective in the treatment of refractory neurocardiogenic syncope in children and adolescents.

A study has shown that sertraline is an effective treatment for impulsive aggressive behavior in personality disordered patients.

It has also been used to treat Tourettes Syndrome.