Acknowledging such limitations, Simon and associates sought to distinguish events occurring in patients receiving the tricyclic antidepressants (TCAs) from those occurring in patients receiving 1 of the 10 newer agents cited in a March 2004 FDA advisory for possible worsening of depression and or emergence of suicidality in adults and children.5 The incidence of attempted suicide in their study was 129 and 76 per 100,000 persons for old and new agents, respectively. The incidence of death from suicide was also higher with the old than the new agents: 51 versus 34 per 100,000.
Acknowledging such limitations, Simon and associates sought to distinguish events occurring in patients receiving the tricyclic antidepressants (TCAs) from those occurring in patients receiving 1 of the 10 newer agents cited in a March 2004 FDA advisory for possible worsening of depression and or emergence of suicidality in adults and children.5 The incidence of attempted suicide in their study was 129 and 76 per 100,000 persons for old and new agents, respectively. The incidence of death from suicide was also higher with the old than the new agents: 51 versus 34 per 100,000.
The investigators determined that the highest rate of suicide attempts occurred in the 7 days preceding antidepressant treatment. The frequency of suicide attempts was relatively consistent throughout the month after treatment was started. During this period, the investigators found an increased risk with the older antidepressants, but they suggested that this could reflect the longer dose escalation period needed to attain therapeutic but tolerated amounts of these more discomforting agents. They concluded that “the results of the month-by-month comparison of newer and older drugs certainly argue against any increase in risk specific to newer antidepressants.”
In this study, the time pattern of suicide attempts was similar for adolescents and adults, although the rate in the teens was substantially higher. Adolescents constituted too small a portion of the sample size to enable their risk-benefit balance to be analyzed, however, and any increase in suicide attempts after receiving antidepressants was too small to separate statistically from the general decline.
Simon and colleagues could not exclude the possibility that antidepressants exacerbate or precipitate suicidality in a subgroup of vulnerable individuals. “Our data contribute nothing to the debate regarding the efficacy or clinical appropriateness of antidepressant treatment for adolescents,” they added.
The Simon study follows 2 casecontrol observational studies that used the General Practice Research Database (GPRD) in the United Kingdom. One identified approximately 160,000 patients receiving 1 of either 2 TCAs or 2 selective serotonin reuptake inhibitors (SSRIs) between 1993 and 1999.6 The match control design distinguished between persons with and those without suicidal behavior before index antidepressant treatment.
The antidepressants did not differ significantly in terms of patients' risk for suicidal behavior. The investigators did find a 4-fold greater risk of suicide within the first 9 days of antidepressant treatment than after 90 days of maintenance therapy, but this could have reflected the lag before medication onset. As in the Simon study, the data were insufficient to provide an answer to the question of increased risk in adolescents.
Another case-control study with GPRD data compared nonfatal selfharm and suicide in patients receiving TCAs and those receiving SSRIs between 1995 and 2001.7 Again, there was no statistically significant difference in risk between the newer agents and the TCAs, although there was a weak suggestion of increased risk in patients younger than 18 years who were taking an SSRI. The investigators noted that patients at higher risk for suicidal behavior might have preferentially received SSRIs, but a different drug response in this age group could not be ruled out.
