Antidepressant Adherence and Suicide Risk in Depressed Youth

Abstract

The lack of adequate data on treatment adherence may be what is hampering full understanding of relationship between use of selective serotonin reuptake inhibitor (SSRI) or newer-generation antidepressants and risk of suicide in depressed children/adolescents. The clinical trial data have been analyzed and reanalyzed to answer following question: do depressed children/adolescents treated with SSRIs and newer-generation antidepressants have a greater risk of suicide than those treated with placebo? However, adequate data do not exist to examine whether adherence mediates relationship between antidepressant use and risk of suicide. This suggested mediating role of adherence is supported by an examination of correlation between multiple-dose plasma elimination half-lives of various antidepressants (venlafaxine, fluvoxamine, paroxetine, sertraline, mirtazapine, citalopram, and fluoxetine) and risk ratio for suicide. There is a significant negative correlation between multiple-dose plasma elimination half-life and risk ratio (Spearmanâ??s rho, rs=â??0.929, p<0.01). The risk ratio data used in this analysis are from Columbia University Outcome 3 (Food and Drug Administrationâ??s Division of Neuropharmacological Drug Products analysis PID number D040495). The significant negative correlation between plasma half-life and risk of suicide strongly suggests that it is effects of symptoms due to acute discontinuation from SSRIs and newer-generation antidepressants in children/adolescents, as opposed to effective use of these medications by children/adolescents, that is related to risk of suicide. We hypothesize that children/adolescents are less likely than adults to adequately articulate discontinuation symptoms and are more likely to react to these symptoms impulsively. Dr. T. Hammad, senior medical reviewer at Food and Drug Administration, presented his analysis of suicidality in pediatric trials of newer antidepressants to Psychopharmacologic Drugs Advisory Committee and Pediatric Advisory Committee on Sept. 13, 2004. He found that although medication compliance may have influenced occurrence of events of interest (i.e., suicidal behavior or ideation), the determination of noncompliance was There is a paucity of research on treatment adherence in depressed children or adolescents. Most of research on adherence in youth has investigated adherence to treatment of medical disorders (e.g., asthma, arthritis, diabetes). Although rates of adherence are suboptimal at all ages, Staples and Bravender found that nonadherence reaches a nadir during adolescent years (p. 504). Based on data presented, we strongly advocate for more sophisticated and systematic assessment of adherence in clinical trials of SSRIs and newer-generation antidepressants in depressed children or adolescents. We strongly encourage clinicians to assess adherence of their child/adolescent patients taking antidepressants and to intervene with children/adolescents and their caregivers to improve adherence when it is suboptimal.