America's favourite psychiatric drug works about as well as its rivals
Sertraline, best known as Zoloft, was the most prescribed psychotropic medicine in the United States in 2016, and in 2023 it filled more than 42 million American prescriptions. Developed at Pfizer and approved in 1991, it performs roughly on par with other drugs of its class, with the size of that benefit still debated.
It belongs to the selective serotonin reuptake inhibitors, or SSRIs, alongside fluoxetine and paroxetine, all considered first-line options and easier to tolerate than older tricyclic antidepressants. Approved uses include major depression, obsessive-compulsive disorder, panic disorder, social anxiety, premenstrual dysphoric disorder and post-traumatic stress disorder, though for PTSD the gains appear modest. The World Health Organization lists it as an essential medicine, and generic versions are available.
Head-to-head comparisons produce a mixed picture. A meta-analysis of 12 newer antidepressants placed sertraline and escitalopram at the top for combining effectiveness with acceptability in the early treatment of adult depression. On the other hand, a large study in general practice found better anxiety scores and quality of life but no significant effect on depression itself in either mild or severe cases. With depression in dementia, it showed no advantage over placebo.
Some results are striking. In panic disorder, attack frequency fell by about 80%, against 45% on placebo. In premenstrual dysphoric disorder, 50 to 60% of patients improved compared with 20 to 30% on dummy pills, often within the first week. For obsessive-compulsive disorder it outperformed clomipramine, long regarded as the benchmark, though higher doses and more patience are needed. In social anxiety it beat exposure therapy in one trial, yet people who had therapy kept improving over the following year while those on the drug slipped back after stopping.
Side effects mirror the class: nausea, diarrhoea, headache, insomnia, dry mouth and sexual problems, which in some people persist after the drug is stopped; European and Canadian regulators want labels to warn of this. It causes little weight gain. Combining it with MAO inhibitors risks serotonin syndrome, and use in pregnancy has been associated with more heart defects in newborns. One PTSD meta-analysis warned its conclusions were shaky because Pfizer declined to share a negative trial.
Source: Sertraline
