Increased Antidepressant Suicide Risk Not Found for Adults

NEW YORK, Aug 8 -- Severely depressed adults do not seem susceptible to an additional suicide risk from antidepressants as do children and adolescents, a case-control study here suggested.

The study confirmed the increased suicide risk with antidepressants in younger patients reported by other researchers, said Mark Olfson, M.D., M.P.H., of the Columbia College of Physicians and Surgeons.

The current study went beyond those upon which the FDA based its "black box" warning for antidepressants by examining actual suicide attempts and successful suicides rather than suicidal thinking and behavior, Dr. Olfson and colleagues said in the August issue of Archives of General Psychiatry.

As a whole, antidepressants increased the risk for suicide attempts in severely depressed children and adolescents by more than 50%. However, some individual drugs were associated with much higher risk while others appeared to have no effect, the investigators said.

The researchers analyzed the medical records of nearly 5,500 Medicaid patients who were hospitalized for depression at least once in 1999 or 2000. The researchers selected all cases of completed suicides (eight children and adolescents and 86 adults) and suicide attempts (263 children and adolescents, 521 adults). They then matched each case with up to five controls.

Patients with comorbid conditions known to increase suicide risk, such as bipolar disorder or schizophrenia, were excluded from the study.

However, in children and adolescents (ages six to 18), antidepressants were significantly associated with suicide attempts (OR=1.52; 95% CI=1.12 to 2.07).

The increased risk for suicide deaths in younger patients was especially large (OR=15.62; 95% CI=1.65 to infinity). However, "because this finding is based on only eight suicide deaths and we cannot preclude the possibility that more severely ill patients tend to be treated with antidepressant drugs, the association should be interpreted with caution," the scientists said.

Not all classes of antidepressants or specific drugs included in the study were linked with a significant effect on suicide risk. In fact, the effect varied greatly:

• Any SSRI: OR=1.24; 95% CI=0.86 to 1.79
• Prozac (fluoxetine): OR=0.69; 95% CI=0.35 to 1.37
• Paxil (paroxetine): OR=1.36; 95% CI=0.80 to 2.30
• Zoloft (sertraline): OR=1.88; 95% CI=1.15 to 3.06
• Celexa (citalopram): OR=0.68; 95% CI=0.28 to 1.67
• Luvox (fluvoxamine): OR=0.91; 95% CI=0.09 to 8.93
• Tricyclic agents: OR=3.09; 95% CI=1.32 to 7.22
• Effexor (venlafaxine): OR=2.33; 95% CI=1.25 to 4.33
• Remeron (mirtazapine): OR=1.64; 95% CI=0.68 to 3.94
• Wellbutrin (bupropion:) OR=1.07; 95% CI=0.53 to 2.19
• Desyrel (trazodone): OR=0.86; 95% CI=0.35 to 2.42
• Serzone (nefazodone): OR=1.62; 95% CI=0.58 to 4.53

As two why antidepressants appeared to increase suicide risk in children and adolescents but not adults, one possibility is the underlying neurobiological differences between adults and children, speculated Dr. Olfson in an interview.

In general, young people tend to be more irritable and impulsive, and depression is not as stable and predictable in this patient population as it is in adults, he said.

In fact, the study authors said that "it is possible that the association between antidepressant drug use and suicide in youths in the present analyses is confined to a relatively narrow band of high-risk or clinically unstable young people after hospitalization for depression and that in the general youth population, antidepressant drugs have a net protective effect on risk of suicide."

"With these caveats in mind," they continued, "the present findings are consistent with recommendations for careful clinical monitoring during the treatment of depressed children and adolescents with antidepressant medications."

"In practice, physicians face the difficult challenge of balancing safety concerns against evidence that depression is a key risk factor for adult and adolescent suicide and that antidepressant agents are effective for adult and adolescent depression," the authors concluded.

In October of 2004, the FDA issued so-called black box warnings for all antidepressants, cautioning physicians about increased risk of suicidal thinking and behavior in children and adolescents. The warnings were based on analysis of 24 pediatric trials of various antidepressants involving more than 4,400 patients. The analysis showed a greater risk of suicidal thinking and behavior during the first few months of treatment in those receiving antidepressants (4%) compared with placebo (2%). No actual suicides occurred.

The authors noted a number of limitations to their study:

• It is possible that antidepressant drugs are selectively prescribed to more severely depressed children and adolescents and that these more severely depressed youths are also at increased risk for suicidal behavior.
• No matching was performed on several important but unavailable factors related to suicide risk, such as family history of suicide.
• Although pharmacy claims measure psychotropic medication use with reasonable accuracy, pill counts or electronic monitoring might have yielded more accurate information.
• The accuracy of the death category "suicide" has been questioned.
• The study is limited to depressed Medicaid beneficiaries who likely differ from depressed privately insured patients in their pharmacologic treatment.
• The study included no adults older than 64; therefore, the results cannot be safely generalized to older adults.
• Even among nonelderly individuals, the cases are only a small and highly selected sample of total suicide attempts and deaths. It is not known whether similar findings would be observed in a larger and more representative sample of depressed patients.