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Efficacy of antidepressants in adults

Posted by shutah on January 16, 2011

Paper written by Joanna Moncrieff, Irving Kirsch and published in the British Medical Journal (BMJ) 16/07/2005

Summary points

  • Recent meta-analyses show selective serotonin reuptake inhibitors have no clinically meaningful advantage over placebo.
  • Claims that antidepressants are more effective in more severe conditions have little evidence to support them.
  • Methodological artefacts may account for the small degree of superiority shown over placebo.  Antidepressants have not been convincingly shown to affect the long term outcome of depression or suicide rates.
  • Given doubt about their benefits and concern about their risks, current recommendations for prescribing antidepressants should be reconsidered.

Effect of antidepressants

Longitudinal follow-up studies show very poor outcomes for people treated for depression both in hospital and in the community, and the overall prevalence of depression is rising despite increased useof antidepressants.

Two studies that prospectively assessed outcome in depressed patients treated naturalistically by general practitioners and psychiatrists found that people prescribed antidepressants had a slightly worse outcome than those not prescribed them, even after baseline severity had been taken into account.

No comparable studies could be found that showed a better outcome in people prescribed antidepressants.  Some authors have suggested a causal association between increased antidepressant prescribing since 1990 and reduction of overall suicide rates observed insome countries.

However, others have pointed out that falls in overall suicide rates started long before this period and suicide rates have increased in some age groups and some countries despite increased antidepressant prescribing.

Meta-analyses of data from controlled trials have not found reduced rates of suicide or suicidal behaviour in drug arms compared with placebo arms.


The NICE review data suggest that selective serotonin reuptake inhibitors do not have a clinically meaningful advantage over placebo, which is consistent with other recent meta-analyses.

In addition, methodological artefacts may account for the small effect seen. Evidence that antidepressants are more effective in more severe conditions is not strong, and data on long term outcome of depression and suicide do not provide convincing evidence of benefit.

In children, the balance of benefits to risks is now recognised as unfavourable. We suggest this may also be the case for adults, given the continuing uncertainty about the possible risk of increased suicidality as well as other known adverse effects.

This conclusion implies the need for a thorough re-evaluation of current approaches to depression and further development of alternatives to drug treatment. Since antidepressants have become society’s main response to distress, expectations raised by decades of their use will also need to be addressed.

We thank other members of the Critical Psychiatry Network who contributed to the response to the NICE depression review and especially Duncan Double, who coordinated the response. Contributors and sources: Both authors have conducted separate meta-analyses of antidepressant trials and reviews of antidepressant literature. JM has recently obtained an MD in antidepressant research methodology.  The article draws on these sources,  as well as the data contained in the NICE review. JM and IK contributed to the response to the NICE review. JMhad the idea to write the paper. JM and IK drafted and revised the current manuscript. JM will act as guarantor.
Competing interests: IK has received consulting fees fromSquibb and Pfizer. JM is co-chair of the Critical Psychiatry Network

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