Three new studies published in the British Medical Journal on the use of popular antidepressants and suicide risk in adults reach conflicting conclusions.
One study reviewed data from 702 randomized controlled clinical trials (87,650 patients) that compared selective serotonin reuptake inhibitors with placebos or other treatments in patients with various conditions, including depression, bulimia, panic disorder, and sexual dysfunction. The authors found that suicide attempts were twice as likely among patients taking the SSRIs than among those taking a placebo or receiving interventions other than tricyclics (BMJ 2005;330:396–9).
That finding suggests that patients who take antidepressants are more likely to talk about their suicidal thoughts or tell someone about their suicidal attempts—and in doing so, hopefully get help, David Fassler, M.D., a trustee of the American Psychiatric Association, told FAMILY PRACTICE NEWS.
When asked about his reaction to the BMJ studies, Rodrigo Muñoz, M.D., a psychiatrist who practices in San Diego, agreed that SSRIs could have the effect of increasing communications about suicide among patients. In addition, Dr. Muñoz also pointed to a recently published study of county-level suicide rates among adults (Arch. Gen. Psychiatr. 2005;62:165–72), in which SSRIs and other newer antidepressants were associated with lower suicide rates.
SSRIs have been under scrutiny over the last year amid concerns about an increased risk of suicidality among adolescents while on the drugs. Ultimately, those concerns prompted the Food and Drug Administration to order a black box warning for the medications, noting the potential risks in children and adolescents.
The findings published in BMJ did not show an increase in overall suicide attempts among SSRI users, compared with patients taking tricyclics. And an increased risk was not observed between SSRI use and placebo when only fatal suicides were considered.
“We documented a difference in absolute risk of 5.6 suicide attempts per 1,000 patient years of SSRI exposure, compared with placebo,” wrote Dean Fergusson, Ph.D., of the Ottawa Health Research Institute and his colleagues. “Although small, the incremental risk remains an important population health issue because of the widespread use of SSRIs.” This information should be relayed to physicians and patients, as long as the risk is kept in perspective relative to the benefits of the drugs, the authors stated.
Methodologic limitations among the published trials considered in this analysis may compromise the findings. For example, the risk of suicide attempts may be underestimated, the authors said. “We were unable to find documentation confirming or refuting suicide attempts in 51,205 of the 87,650 patients.”
Additionally, many of the trials only reported adverse events that occurred in excess of a prespecified threshold, leaving open the possibility of rare but lethal complications going unreported or underreported, the authors noted. And many of the randomized control trials considered small patient populations for short time periods, and as such were not designed to identify completed or attempted suicides, thus making it impossible to infer long-term risks and treatment benefits.
In fact, although pooling the data from hundreds of trials increased the overall numbers, the absolute numbers of patients attempting and committing suicide remained very low, according to the authors of an accompanying editorial. This means that “reporting or not reporting a few cases could have completely changed the overall outcome,” wrote Andrea Cipriani, M.D., of the University of Verona (Italy) and her colleagues in an accompanying editorial (BMJ 2005;330:373–4).
Dr. Fassler said one of the problems with interpreting these findings is that it is difficult to tease out the methodologic details. “The current findings do not demonstrate that antidepressants are associated with an increased risk of suicide. This result is consistent with previous studies and should be reassuring to physicians and patients,” said Dr. Fassler, a clinical associate professor of psychiatry at the University of Vermont at Burlington.
The largest of the three new investigations was a nested case-control study based on the British general practice research database that assessed the risk of nonfatal self harm and suicide among 146,095 patients newly diagnosed with depression who received SSRIs or tricyclics (BMJ 2005;330:389–93).
“We found no evidence that the risk of suicide or nonfatal self harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants,” reported Carlos Martinez, M.D., of the Medicines and Healthcare Products Regulatory Agency in London and his colleagues in the review.
The results of the third study—a metaanalysis of published and unpublished randomized control trials of SSRIs, compared with placebo, in about 40,000 adults submitted by drug companies to the safety review arm of the Medicines and Healthcare Products Regulatory Agency—are similarly vague and inconclusive. The authors determined that because of the low incidence of suicide, “it is not possible to rule out either a threefold increase or a decrease in its occurrence among people treated with SSRIs.” To detect an important effect on risk, an analysis would require large trials randomizing “around 2 million individuals,” according to David Gunnell, M.D., of the University of Bristol (England) and his colleagues in the study (BMJ 2005; 330:385–8).