Antidepressant drugs may be associated with an increased risk of suicidal behaviour, particularly in the early stages of treatment, shows new evidence in this week's BMJ.
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressant, yet concerns have arisen that these drugs may induce or worsen suicidal feelings in vulnerable patients.
Three studies published in this issue shed new light on the benefits and harms of these drugs.
In the first study, researchers analysed 702 trials involving over 87,000 patients with depression and other clinical conditions to establish whether a link exists between use of SSRIs and suicide attempts.
They found that patients taking SSRIs were twice as likely to attempt suicide compared with patients taking placebo. However, no increase in risk was seen when only fatal suicidal attempts were compared between SSRIs and placebo. Finally, they found no difference between patients taking SSRIs and those taking other drugs, known as tricyclic antidepressants.
The authors point out that, while the absolute risk of suicide is low, the widespread use of SSRIs makes this a population health concern. They also warn that major limitations in the published trials may have led to underestimates of the risk of suicide attempts.
The second study reviewed 477 trials submitted by drug companies to the safety review of the Medicines and Healthcare products Regulatory Agency (MHRA). These trials compared SSRIs with placebo in adults with depression and other clinical conditions.
The research team found no evidence that SSRIs increased the risk of suicide. They found weak evidence of an increased risk of self harm, but no evidence of an increased risk of suicidal thoughts.
Increased risks of suicide and self harm caused by SSRIs cannot be ruled out, say the authors, but larger trials with longer monitoring periods are needed to assess the balance of risks and benefits fully. They recommend that patients should be warned of the potential hazard and monitored closely in the early weeks of treatment.
The final study was based on information from the General Practice Research Database and analysed the risk of self harm and suicide in over 146,000 patients taking SSRIs and tricyclic antidepressants for the first time.
Risks of self harm and suicide were no different in patients prescribed SSRIs compared with those prescribe tricyclics. However, under 18s prescribed SSRIs seemed to be at increased risk of self harm.
The finding that SSRIs and tricyclic antidepressants have a similar risk profile with respect to suicide and self harm is reassuring, say the authors. They call for further research to assess the short and long term risks and benefits of antidepressants.
Despite several limitations, these studies provide some useful insights for clinical practice, write experts in an accompanying editorial. For instance, they should make doctors aware that SSRIs and tricyclics may induce or worsen suicidal behaviour during the early phases of treatment and encourage them to monitor patients closely. They should also discourage the routine prescribing of antidepressant drugs in children and adolescents.
"The debate is not yet done, but these papers crystallise arguments that have been drifting in the ether these past months," says Kamran Abbasi, BMJ Acting Editor. "How many people who turned to 'happy pills' would not have done so if they had been fully aware of the potential harms?"
Materials provided by British Medical Journal. Note: Content may be edited for style and length.
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