Long-term study finds some antidepressants work better than others, with important limits

What the review found

The review, published in The Lancet Psychiatry, examined randomised trials involving more than 30,000 people. Researchers defined long-term use as six months or longer and combined results from 35 trials that directly compared medicines.

Compared with fluoxetine, three medicines—escitalopram, duloxetine and agomelatine—were associated with a greater likelihood of maintaining improvement. Participants taking escitalopram or duloxetine were also less likely to leave trials than those taking fluoxetine.

Why long-term treatment matters

About one in seven Australians experience depression during their lifetime. In 2024–25, 3.8 million Australians received a dispensed prescription for an antidepressant. Guidelines advise adults who respond adequately to treatment to continue antidepressants for at least six months, and preferably 12 months. If depression has resolved after six to 12 months, reducing and stopping medication may be appropriate; this should happen gradually with a doctor's guidance because symptoms can arise during withdrawal.

Australian studies indicate that many people use these medicines for longer. One study found nearly a quarter of people prescribed antidepressants still received them two years later, while another reported an average use of four years.

Limits to the evidence

The review's findings are not definitive: more than half the trials in its main analysis were judged to have a high risk of bias. Some medicines were represented by only a small number of studies, adding uncertainty to comparisons.

Most direct comparisons tracked participants for about six months after they began medication, and only six trials lasted longer. The evidence therefore offers limited insight into how the medicines compare over the longer periods many people use them.

Trial dropouts served as the researchers' measure of acceptability, but leaving a study may not capture the full experience of taking a medicine. Responses and preferences differ among individuals, so group averages cannot identify the best option for a particular person.

Medicines in Australia

Escitalopram, also sold as Lexapro, was Australia's most commonly prescribed antidepressant and ranked 13th among PBS-dispensed prescriptions in 2024–25. Duloxetine, sold as Cymbalta, ranked 45th. Agomelatine, sold as Valdoxan, is not available on the PBS. These prescribing details provide context for the review's findings, but do not establish which treatment is right for any one person.