Some antidepressants may be more effective than others in the long term
A review published in The Lancet Psychiatry shows that some antidepressants, such as escitalopram and duloxetine, may be more effective than fluoxetine at helping people with depression to improve and to remain on treatment in the long term — typically for around six months. The study, which pooled the results of 115 randomised controlled trials on 21 antidepressants involving more than 30,000 people, is the first to compare the long-term efficacy — over more than 12 weeks — of different antidepressants.
Eduard Vieta - antidepresivos
Eduard Vieta
Director of the Institute of Neurosciences at Hospital Clínic, Professor of Psychiatry at the University of Barcelona and researcher at IDIBAPS and CIBERSAM
In my opinion the article has serious methodological flaws. The main problem is "confounding by indication", which is characteristic of observational studies, especially if they are retrospective.
By comparing the cohort of medicated and non-medicated depressed patients, and by not controlling for the severity of the cases (an unforgivable error), the results of the comparison cannot be attributed to the treatment, but to the characteristics of the patient, which is what determines whether they are treated or not.
In other words, the lack of differences between the two groups cannot be attributed to the antidepressants, as the treated patients were most likely more severe than the untreated ones.
It is like comparing patients with covid-19 treated with corticosteroids and without: mortality is higher in patients treated with corticosteroids, but corticosteroids are given to the most severe patients precisely to save their lives.
I believe that there is still a long way to go for depression treatments to solve all the problems associated with depression, but today's treatments are saving lives and helping millions of people to regain their previous life, work and family. They can be improved and should be combined with psychotherapy, but this study does not provide valid or reliable information to help improve patient care.
Eduard Vieta has collaborated with companies producing antidepressants such as Angelini, Janssen and Lundbeck on aspects of research and clinical trial design. Most of the resulting funds have gone to the institutions he works with, such as the Hospital Clínic and its Foundation
Jauhar - antidepresivos
Sameer Jauhar
This is a comprehensive systematic review and network meta-analysis, addressing an important clinical question: whether antidepressants differ in their ability to achieve and maintain improvement in depression over the longer term.
The authors have undertaken a substantial amount of work, including sensitivity analyses examining different study designs, and the findings suggest that there may be differences between individual antidepressants. The press release broadly reflects the findings of the study.
One finding is that continuing antidepressants is associated with a greater likelihood of maintaining improvement compared with discontinuing treatment. Around 62% of those continuing antidepressants maintained improvement, compared with 45% of those switched to placebo. This is broadly consistent with findings from the large ANTLER trial, published in the New England Journal of Medicine, which also found lower rates of relapse in those continuing antidepressants.
However, there are some important qualifications.
Although the review includes over 30,000 participants, the primary analysis comparing individual antidepressants was based on 35 trials involving approximately 10,000 people. Over half of these trials were judged to be at high risk of bias, and the typical duration of follow-up was around six months. We should therefore be cautious about interpreting these findings as evidence of differences in effectiveness over several years.
A further issue is that the evidence for some individual antidepressants is relatively limited. For example, although bupropion performed less well than several other antidepressants in the network meta-analysis, the primary analysis did not demonstrate a statistically significant difference from fluoxetine, and the evidence for bupropion was based on relatively few participants. The secondary analysis, incorporating additional study designs, suggested a larger difference, but this involves additional assumptions. This illustrates why we should be cautious about translating differences between individual drugs in network meta-analyses into clinical recommendations.
The authors acknowledge these limitations, and the additional analyses provide some reassurance about the overall findings. Nevertheless, network meta-analysis relies partly on indirect comparisons, and the reliability of individual drug rankings depends on the amount and quality of the underlying evidence.
The study provides useful information to inform treatment decisions, but it cannot tell us which antidepressant will work best for an individual patient. I would not interpret these findings as a reason for someone who is responding well to their current antidepressant to change treatment.
Overall, this is a valuable contribution to the literature, but the findings concerning the relative effectiveness of individual antidepressants should be interpreted cautiously.
Conflict of interest: Sameer Jauhar has received personal fees from Recordati, LB Pharmaceuticals, Boehringer Ingelheim, Accord Pharmaceuticals, Wellcome Trust, Lundbeck, Janssen and Sunovion, and non-financial support from the National Institute for Health and Care Excellence, the British Association for Psychopharmacology and the Royal College of Psychiatrists. He was also one of the reviewers of this paper.
van Haaren et al.
- Review
- Peer reviewed
- Systematic review
- Meta-analysis