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Antidepressant (SSRI class) medication

Sertraline shares the common side effects and contraindications of other SSRIs, with high rates of diarrhea, nausea, insomnia, and sexual dysfunction, but it appears not to lead to much weight gain, and its effects on cognitive performance are mild. 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. It should not be used together with monoamine oxidase inhibitors (MAOIs): this combination may cause serotonin syndrome, which can be life threatening in some cases. Sertraline taken during pregnancy is associated with an increase in congenital heart defects in newborns. It is available as a generic medication. In 2016, sertraline was the most commonly prescribed psychotropic medication in the United States. In 2021, it was the eleventh most commonly prescribed medication in the United States, with over 39million prescriptions.

Sertraline has been approved for major depressive disorder (MDD), obsessive–compulsive disorder (OCD), post traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), panic disorder, and social anxiety disorder (SAD). Sertraline is approved for use in children with OCD.

In meta analyses, sertraline displays similar efficacy to other SSRI antidepressants, with an odds ratio for response in clinical depression of between 1.44 and 1.67. However, as with other antidepressants, the nature and clinical significance of this effect remain disputed. A major study of sertraline in a broad primary care population found improvements in general mental health, quality of life, and anxiety. However, it failed to find significant effects on depression in either the mildly or severely depressed, and the clinical relevance and accuracy of the positive effects found have been questioned. 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. Sertraline also improves the functional impairments of dysthymia to a similar degree whether group Cognitive Behavioural Therapy is undergone or not. Limited pediatric data also demonstrates reduction in depressive symptoms in the pediatric population though remains a second line therapy after fluoxetine.

In general, sertraline efficacy is similar to that of other antidepressants. 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. Comparative clinical trials demonstrated that sertraline is similar in efficacy against depression to moclobemide, nefazodone, escitalopram, bupropion, citalopram, fluvoxamine, paroxetine, Sertraline may be more efficacious for the treatment of depression in the acute phase (first four weeks) than fluoxetine. There are differences between sertraline and some other antidepressants in their efficacy in the treatment of different subtypes of depression and in their adverse effects. For severe depression, sertraline is as good as clomipramine but is better tolerated. 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. Sertraline is equivalent to imipramine for the treatment of depression with co morbid panic disorder, but it is better tolerated. Compared with amitriptyline, sertraline offered a greater overall improvement in quality of life of depressed patients. Accordingly, a meta analysis of antidepressants in older adults found that sertraline, paroxetine and duloxetine were better than placebo. On the other hand, in a 2003 trial the effect size was modest, and there was no improvement in quality of life as compared to placebo. With depression in dementia, there is no benefit of sertraline treatment compared to either placebo or mirtazapine.

Sertraline is effective for the treatment of OCD in adults, It was better tolerated and, based on intention to treat analysis, performed better than the gold standard of OCD treatment clomipramine. Continuing sertraline treatment helps prevent relapses of OCD with long term data supporting its use for up to 24 months. The sertraline dosages necessary for the effective treatment of OCD are higher than the usual dosage for depression. The onset of action is also slower for OCD than for depression. The treatment recommendation is to start treatment with a half of maximal recommended dose for at least two months. After that, the dose can be raised to the maximal recommended in the cases of unsatisfactory response. Cognitive behavioral therapy alone is not more effective than sertraline in adolescents and children; however, a combination of these treatments is effective. Sertraline is equally effective for men and women, Previous unsuccessful treatment with benzodiazepines does not diminish its efficacy. However, the response rate was lower for the patients with more severe panic. Double blind comparative studies found sertraline to have the same effect on panic disorder as paroxetine or imipramine. While imprecise, comparison of the results of trials of sertraline with separate trials of other anti panic agents (clomipramine, imipramine, clonazepam, alprazolam, and fluvoxamine) indicates approximate equivalence of these medications. All three major domains of the disorder (fear, avoidance, and physiological symptoms) respond to sertraline. The improvement is greater among the patients with later, adult onset of the disorder. In a comparison trial, sertraline was superior to exposure therapy, but patients treated with the psychological intervention continued to improve during a year long follow up, while those treated with sertraline deteriorated after treatment termination. The combination of sertraline and cognitive behavioral therapy appears to be more effective in children and young people than either treatment alone. 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. Significant improvement was observed in 50–60% of cases treated with sertraline vs. 20–30% of cases on placebo. The improvement began during the first week of treatment, and in addition to mood, irritability, and anxiety, improvement was reflected in better family functioning, social activity and general quality of life. Work functioning and physical symptoms, such as swelling, bloating and breast tenderness, were less responsive to sertraline. Taking sertraline only during the luteal phase, that is, the 12–14 days before menses, was shown to work as well as continuous treatment.

Sertraline is approved for the treatment of post traumatic stress disorder (PTSD). Other guidelines also suggest sertraline as a first line option for pharmacological therapy. 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. Another meta analysis relegated sertraline to the second line, proposing trauma focused psychotherapy as a first line intervention. The authors noted that Pfizer had declined to submit the results of a negative trial for the inclusion into the meta analysis making the results unreliable. Sertraline when taken daily can be useful for the treatment of premature ejaculation. A disadvantage of sertraline is that it requires continuous daily treatment to delay ejaculation significantly. A 2019 systematic review suggested that sertraline may be a good way to control anger, irritability and hostility in depressed patients and patients with other comorbidities.

Sertraline is contraindicated in individuals taking monoamine oxidase inhibitors or the antipsychotic pimozide. Sertraline concentrate contains alcohol and is therefore contraindicated with disulfiram. The prescribing information recommends that treatment of the elderly and patients with liver impairment "must be approached with caution". Due to the slower elimination of sertraline in these groups, their exposure to sertraline may be as high as three times the average exposure for the same dose. Over more than six months of sertraline therapy for depression, people showed no significant weight increase. A 30 month long treatment with sertraline for OCD also resulted in no significant weight gain. 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%). Of the sertraline group, 4.5% 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. In spite of lower subjective rating, that is, feeling that they performed worse, no clinically relevant differences were observed in the objective cognitive performance in a group of people treated for depression with sertraline for 1.5 years as compared to healthy controls. In children and adolescents taking sertraline for six weeks for anxiety disorders, 18 out of 20 measures of memory, attention and alertness stayed unchanged. Divided attention was improved and verbal memory under interference conditions decreased marginally. Because of the large number of measures taken, it is possible that these changes were still due to chance. The unique effect of sertraline on dopaminergic neurotransmission may be related to these effects on cognition and vigilance. 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. There is 29–42% increase in congenital heart defects among children whose mothers were prescribed sertraline during pregnancy, with sertraline use in the first trimester associated with 2.7 fold increase in septal heart defects. Abrupt interruption of sertraline treatment may result in withdrawal or discontinuation syndrome. Dizziness, insomnia, anxiety, agitation, and irritability are its common symptoms. It typically occurs within a few days from drug discontinuation and lasts a few weeks. In most cases symptoms are mild, short lived, and resolve without treatment. More severe cases are often successfully treated by temporary reintroduction of the drug with a slower tapering off rate. Sertraline and SSRI antidepressants in general may be associated with bruxism and other movement disorders. Sertraline appears to be associated with microscopic colitis, a rare condition of unknown etiology.

Like other SSRIs, sertraline is associated with sexual side effects, including sexual arousal disorder, erectile dysfunction and difficulty achieving orgasm. 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. 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 mood improvement resulting from the treatment with sertraline sometimes counteracted these side effects, so that sexual desire and overall satisfaction with sex stayed the same as before the sertraline treatment. However, under the action of placebo the desire and satisfaction slightly improved. Some people continue experiencing sexual side effects after they stop taking SSRIs.

The US Food and Drug Administration (FDA) requires all antidepressants, including sertraline, to carry a boxed warning stating that antidepressants increase the risk of suicide in persons younger than 25 years. This warning is based on statistical analyses conducted by two independent groups of FDA experts that found a 100% increase of suicidal thoughts and behavior in children and adolescents, and a 50% increase in the 18–24 age group. Suicidal ideation and behavior in clinical trials are 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 suicidal behavior with a marginal statistical significance by 37% 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.

Acute overdosage is often manifested by emesis, lethargy, ataxia, tachycardia and seizures. 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. As with most other SSRIs its toxicity in overdose is considered relatively low.

The US patent for Zoloft expired in 2006, and sertraline is available in generic form and is marketed under many brand names worldwide. In May 2020, the FDA placed Zoloft on the list of drugs currently facing a shortage.

Sertraline has been the most sought after antidepressant worldwide before, during, and after the COVID 19 pandemic, according to Google Trends data. The pandemic has led to an increase in searches for antidepressants, with sertraline, fluoxetine, duloxetine, and venlafaxine showing the highest search volumes, whereas searches of citalopram decreased during the pandemic.

Sertraline may be useful to treat murine Zaire ebolavirus (murine EBOV). Lass Flörl et al., 2003 finds it significantly inhibits phospholipase B in the fungal genus Candida, reducing virulence. Sertraline is also a very effective leishmanicide. It is also known to act as a photosensitizer of bacterial surfaces. Lass Flörl et al., 2003 finds this compound acts as a fungicide against Candida parapsilosis. Sertraline is a promising trypanocide.