Sertraline
Sertraline, sold under the brand name Zoloft among others, is an antidepressant medication of the selective serotonin reuptake inhibitor class used to treat major depressive disorder, generalized anxiety disorder, social anxiety disorder, obsessive–compulsive disorder, panic disorder, and premenstrual dysphoric disorder. Although also having approval for post-traumatic stress disorder, findings indicate it leads to only modest improvements in symptoms associated with this condition.
The drug shares the common side effects and contraindications of other SSRIs, with high rates of nausea, diarrhea, headache, insomnia, mild sedation, dry mouth, 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 : 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.
Sertraline was developed by scientists at Pfizer and approved for medical use in the United States in 1991. It is on the World Health Organization's List of Essential Medicines and available as a generic medication. In 2016, sertraline was the most commonly prescribed psychotropic medication in the United States. It was also the eleventh most commonly prescribed medication in the United States, with more than 42million prescriptions in 2023, and sertraline ranks among the top 10 most prescribed medications in Australia between 2017 and 2023.
Sertraline's effectiveness is similar to that of other antidepressants in its class, such as fluoxetine and paroxetine, which are also considered first-line treatments and are better tolerated than the older tricyclic antidepressants.
Medical uses
Sertraline has been approved for major depressive disorder, obsessive–compulsive disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, panic disorder, social anxiety disorder, and generalized anxiety disorder. Sertraline is approved for use in children with OCD.Depression
In meta-analyses, sertraline efficacy is similar to that of 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-Behavioral Therapy is undergone or not.
Limited pediatric data also demonstrates a reduction in depressive symptoms in the pediatric population though remains a second-line therapy after fluoxetine.
Comparison with other antidepressants
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, venlafaxine, and mirtazapine. Sertraline may be more efficacious for the treatment of depression in the acute phase 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. In the treatment of depression accompanied by OCD, sertraline performs significantly better than desipramine on the measures of both OCD and depression. 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.
Depression in elderly
Sertraline used for the treatment of depression in elderly patients is superior to placebo and comparable to another SSRI fluoxetine, and tricyclic antidepressants amitriptyline, nortriptyline and imipramine. Sertraline has much lower rates of adverse effects than these TCAs, with the exception of nausea, which occurs more frequently with sertraline. In addition, sertraline appears to be more effective than fluoxetine or nortriptyline in the older-than-70 subgroup. Accordingly, a meta-analysis of antidepressants in older adults found that sertraline, paroxetine and duloxetine were better than placebo. However, 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.Obsessive–compulsive disorder
Sertraline is effective for the treatment of OCD in adults, adolescents and children. 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 half of the 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.
Panic disorder
Sertraline is superior to placebo for the treatment of panic disorder. The response rate was independent of the dose. In addition to decreasing the frequency of panic attacks by about 80% and decreasing general anxiety, sertraline resulted in an improvement in quality of life on most parameters. The patients rated as "improved" on sertraline reported better quality of life than the ones who "improved" on placebo. The authors of the study argued that the improvement achieved with sertraline is different and of a better quality than the improvement achieved with a placebo. Sertraline is equally effective for men and women, and for patients with or without agoraphobia. Previous unsuccessful treatment with benzodiazepines does not diminish its efficacy. However, the response rate was lower for the patients with more severe panic. Starting treatment simultaneously with sertraline and clonazepam, with subsequent gradual discontinuation of clonazepam, may accelerate the response.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 indicates approximate equivalence of these medications.
Other anxiety disorders
Sertraline has been successfully used for the treatment of social anxiety disorder. All three major domains of the disorder respond to sertraline. Maintenance treatment, after the response is achieved, prevents the return of the symptoms. 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.
Premenstrual dysphoric disorder
Sertraline is effective in alleviating the symptoms of premenstrual dysphoric disorder, a severe form of premenstrual syndrome. 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 is not as effective as continuous treatment. Continuous treatment with sub-therapeutic doses of sertraline is also effective.Other indications
Sertraline is approved for the treatment of post-traumatic stress disorder. The National Institute for Clinical Excellence recommends it for patients who prefer drug treatment to a psychological one. Other guidelines also suggest sertraline as a first-line option for pharmacological therapy. When necessary, long-term pharmacotherapy can be beneficial. 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. Positive results were obtained in trials that included predominantly women with a majority having physical or sexual assault as the traumatic event. Somewhat contrary to the above suggestions, a meta-analysis of sertraline clinical trials for PTSD found it to be statistically superior to placebo in the reduction of PTSD symptoms but the effect size was small. 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 inclusion in 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.