Source: The Conversation (Au and NZ)
A new review has found some antidepressants may be more effective than others at helping people reduce the severity of their symptoms of depression over the long term.
The research, published in The Lancet Psychiatry, found people taking escitalopram (commonly sold as Lexapro), duloxetine (Cymbalta) and agomelatine (Valdoxan) were more likely to report improved symptoms over the long term than those taking fluoxetine (Prozac). For those taking Lexapro and Cymbalta, they were also more likely to stay on their medications.
But does that mean these are the best antidepressants?
Why do people take antidepressants long term?
Around one in seven Australians will experience depression during their lifetime.
Treatment can involve psychological therapies, social support and lifestyle changes, such as doing more exercise. For some people, these approaches may be enough to support recovery. For others, adding an antidepressant can be an important part of treatment.
In 2024-2025, 3.8 million Australians were dispensed a prescription for an antidepressant.
For adults with depression, clinical guidelines recommend continuing antidepressants for at least six months, and preferably 12 months, after an acceptable response to treatment is achieved.
If, after six to 12 months, the depressive episode has resolved, it may be appropriate to reduce, and eventually stop the antidepressant. But symptoms can occur when discontinuing antidepressants so it’s important this is done gradually, in consultation with a doctor.
Studies of real world antidepressant prescribing patterns in Australia suggest many people take antidepressants for longer than this. One 2022 study found nearly a quarter of those prescribed antidepressants were still receiving prescriptions for them two years later.
Another Australian study found people take antidepressants for an average of four years.
What did the researchers find?
The new review set out to compare how well different antidepressants help people maintain improvements in depression. The researchers also compared how acceptable the medicines were to the people taking them. They measured this by looking at the proportion of people who stopped treatment for any reason during the study period.
The researchers identified and reviewed 115 randomised controlled trials, involving more than 30,000 people. The researchers classified long-term use as six months or more. Their main analysis combined the results of 35 trials that directly compared one antidepressant with another.
They found that three antidepressants – escitalopram, duloxetine and agomelatine – were associated with a greater likelihood of sustained response than fluoxetine.
People taking escitalopram or duloxetine were also less likely to drop out of the trials than those taking fluoxetine.
How reliable are the findings?
The findings are interesting as escitalopram (Lexapro) is the most commonly prescribed antidepressant in Australia. It ranked number 13 out of all PBS-dispensed prescriptions in 2024–25. Duloxetine was number 45, but agomelatine isn’t available on the PBS.
The findings suggest some antidepressants may be more effective than others at sustaining a response to treatment, but the results are far from definitive. More than half of the studies included in the main analysis were assessed as having a high risk of bias.
This means some of the differences between antidepressants may reflect limitations in the original studies rather than genuine differences between the medicines. Some medicines were also supported by very few studies, making comparisons less certain.
Another aspect to keep in mind when considering these results is what is meant by “long term”. The trials directly comparing antidepressants typically followed participants for around six months after they first started taking the medication. Only six followed people for longer than six months.
This means we still know relatively little about how the effectiveness of different antidepressants compares over longer periods. This is important given the average time people take them is much longer.
What this research can’t tell us
Importantly, these findings reflect average outcomes across groups of people. They can’t tell us which antidepressant will work best for any particular person.
People respond differently to antidepressants, and what makes a medicine acceptable to one person may not be acceptable to another. While the researchers used trial drop-out rates as a measure of acceptability, this doesn’t necessarily capture people’s experiences of taking these medicines.
For someone taking an antidepressant, acceptability might not be so binary. It may involve a trade-off between how the medication improves symptoms, its side effects, and how the medicine affects their everyday life.
Continuing to take an antidepressant doesn’t necessarily mean someone finds it acceptable. Some people experience withdrawal symptoms when trying to stop, which can make discontinuation difficult.
What’s the best fit for you?
Ultimately, determining if an antidepressant is right for you, and which is the best fit, depends on many factors. These include your symptoms, other health conditions, previous experiences with medicines, potential side effects and what matters most to you.
If you’re taking an antidepressant that’s working well for you, the findings of this study aren’t a reason to switch.
And if you’re considering starting, changing or stopping an antidepressant, discuss your options with your doctor.
The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.
Original source: https://analysis1.mil-osi.com/2026/11/11/some-antidepressants-may-work-better-than-others-long-term-new-study/