Suicidal Events in the Treatment for Adolescents With Depression Study (TADS)

Abstract

Objectives-We analyzed the Treatment for Adolescents with Depression Study (TADS) database to determine whether suicidal events (attempts and ideation) occurred early in treatment, could be predicted by severity of depression or other clinical characteristics, and were preceded by clinical deterioration or symptoms of increased irritability, akathisia, sleep disruption, or mania.Methods-TADS was a 36-week randomized controlled clinical trial of pharmacological and psychotherapeutic treatments involving 439 youths with major depressive disorder. Suicidal events were defined according to the Columbia Classification Algorithm of Suicidal Assessment.Results-Forty-four patients (10.0%) had at least one suicidal event (no suicide occurred). Events occurred 0.4-31.1 weeks (mean 11.9 ± 8.2) after starting TADS treatment, with no difference in event timing for patients receiving medication versus those not on medication. Severity of self-rated pre-treatment suicidal ideation (Suicidal Ideation Questionnaire for Adolescents score ≥ 31) and depressive symptoms (Reynolds Adolescent Depression Scale score ≥91), predicted occurrence of suicidal events during treatment (p<0.05). Patients with suicidal event were on average still moderately ill prior to the event (Clinical Global Impression-severity score 4.0 ± 1.3), and only minimally improved (Clinical Global Impression-improvement score 3.2 ± 1.1). Events were not preceded by increased irritability, akathisia, sleep disturbance, or manic signs. Specific inter-personal stressors were identified in 73% of cases. Of the events, 55% resulted in overnight hospitalization.Address correspondence to: Dr. Benedetto Vitiello, NIMH Room 7147, 6001 Executive Blvd., Bethesda, MD 20892-9633; e-mail: Email: bvitiell@mail.nih.gov. Financial Disclosure: Susan Silva is a consultant with Pfizer. Christopher Kratochvil receives research support from Eli Lilly, Somerset, Abbott, Shire, McNeil, and Cephalon, is a consultant for Eli Lilly, Pfizer, Cephalon, AstraZeneca, Organon, and Shire, and is on the Speaker's Bureau of Eli Lilly. Dr. Posner has been consultant and/or received research support from GlaxoSmithKline, Forest, Eisai, AstraZeneca, Johnson&Johnson, Abbott, Wyeth, Organon, Bristol-Myers Squibb, Sanofi-Aventis, Cephalon, Novartis, Shire, and UCB Pharma. John March is a consultant or scientific advisor to Pfizer, Lilly, Wyeth, GSK, Jazz, and MedAvante and holds stock in MedAvante; he receives research support from Lilly and study drug for an NIMH-funded study from Lilly and Pfizer. The other authors have no financial relationships to disclose. Conclusions-Most suicidal events occurred in the context of persistent depression and insufficient improvement, without evidence of medication-induced behavioral activation as a precursor. Severity of self-rated suicidal ideation and depressive symptoms predicted emergence of suicidality during treatment. Risk for suicidal events did not decrease after the first month of treatment, suggesting the need for careful clinical monitoring for se...

Is it valid to measure suicidal ideation by depression rating scales?

“…Subjects in out-patient clinical trials may well deny stigmatized suicidal ideas and behaviors causing Type II error (false negatives). This difference between clinician and self-report assessments regarding suicidality has been found across many years with higher levels of false negatives in clinician ratings than in self-report assessments (Greist et al, 1973;Levine et al, 1989;Vitiello et al, 2009). Clinician raters in clinical trials may also be biased against finding suicidality if suicidality is an exclusion criterion for participation in a clinical trial.…”

Treatment of adolescent depression: what we have come to know

“…An analysis of all the suicidal events in TADS, however, did not support this hypothesis, as suicidality was not preceded by signs of behavioral activation, but rather occurred in a context of persistent depression and lack of adequate improvement. [13] In addition, the rate of suicidal events was not highest in the first few weeks of treatment, as it would be expected based on a behavioral activation hypothesis. Clearly, more research is needed to understand the probably multiple pathways mediating treatment emergent suicidal behavior in adolescent depression.…”

“…[3] For antidepressants, the response rate after acute treatment averages 61 versus 50% for placebo. The difference translates into a number needed to treat of 10 (95% CI, [7][8][9][10][11][12][13][14][15]. This relatively modest effect, however, is not specific to adolescent depression but it is observed also in adults.…”

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