A Randomized, Double-blind, Placebo-controlled Study of Citalopram in Adolescents With Major Depressive Disorder

Abstract

In a European, multicenter, double-blind study, 244 adolescents, 13 to 18 years old, with major depression were randomized to treatment with citalopram (n = 124) or placebo (n = 120). One third of the patients in both groups withdrew from the study. No significant differences in improvement of scores from baseline to week 12 between citalopram and placebo were found. The response rate was 59% to 61% in both groups according to the Schedule for Affective Disorders and Schizophrenia for school-aged children-Present episode version (Kiddie-SADS-P) (depression and anhedonia scores < or =2) and Montgomery Asberg Depression Rating Scale (MADRS) (> or =50% reduction). Remission (MADRS score < or =12) was achieved by 51% of patients with citalopram and 53% with placebo. A post hoc analysis revealed that more than two thirds of all patients received psychotherapy during this study. For those patients not receiving psychotherapy, there was a higher percentage of Kiddie-SADS-P responders with citalopram (41%) versus placebo (25%) and a significantly higher percentage of MADRS responders and remitters with citalopram (52% and 45%, respectively) versus placebo (22% and 19%, respectively). Mild to moderate treatment-emergent adverse events were reported in 75% citalopram and 71% of placebo patients, most commonly headache, nausea, and insomnia. Serious adverse events occurred in 14% to 15% in both groups. Suicide attempts, including suicidal thoughts and tendencies, were reported by 5 patients in the placebo group and by 14 patients in the citalopram group (not significant) with no pattern with respect to duration of treatment, time of onset, or dosage. In contrast, the suicidal ideation (Kiddie-SADS-P) single item showed worsening more frequently in the placebo (18%) than in the citalopram group (8%).

The citalopram CIT-MD-18 pediatric depression trial: Deconstruction of medical ghostwriting, data mischaracterisation and academic malfeasance

“…However, concerns about suicidal risk were prevalent before the Wagner et al article was written and published [27]. In fact, undisclosed in both the published article and Wagner's letter-to-the-editor, the 2001 negative Lundbeck study had raised concern over heightened suicide risk [10,20,21].…”

“…Even though the results of a prior European citalopram pediatric registration trial (i.e., Lundbeck study 94404) were not published until 2006 [21], as early as July 16, 2001, Forest was aware that the Lundbeck study had failed to demonstrate efficacy for citalopram in adolescents [22]. However, Wagner et al omitted this fact in their published article, leading the editors of the American Journal of Psychiatry to publish a correction, acknowledging that Forest had failed to disclose the result that the Lundbeck trial was negative and had shown an increase in suicidality in both children and adolescents [19].…”

The Efficacy of Antidepressants on Overall Well-Being and Self-Reported Depression Symptom Severity in Youth: A Meta-Analysis

“…We did not use data from either the Hamilton Depression Rating Scale [19] or the Montgomery-Asberg Depression Rating Scale [20] because these measures were designed for use in adults and may not be ideal to assess depressive severity in youth. Data reporting in one study was quite minimal [21]. For this study, we extracted mean change data on the Kiddie Schedule for Affective Disorders and Schizophrenia from a figure in the paper, in which it was clear that the mean difference between groups was zero.…”

“…For the Beck Depression Inventory (BDI), we calculated the standard deviation in von Knorring et al [21] as the sample size-weighted standard deviation from Berard et al [22] and Emslie et al [58]. For the Kiddie Schedule for Affective Disorders and Schizophrenia, we calculated the standard deviation in von Knorring et al [21] as the sample size-weighted standard deviation from Berard et al [22] and Keller et al [23]. …”

Escitalopram in the Treatment of Adolescent Depression: A Randomized, Double-Blind, Placebo-Controlled Extension Trial

“…In an 8-week, flexible-dose, placebo-controlled study of MDD in children and adolescents (7-17 years of age), racemic citalopram 20-40 mg/day demonstrated significant improvement in depressive symptoms versus placebo within 1 week . In subsequent clinical trials of citalopram (age range, 13-18 years) (von Knorring et al 2006) and escitalopram (age range, 6-17 years) (Wagner et al 2006), active treatment failed to separate from placebo. However, age-group adjusted post-hoc analyses of the escitalopram trial (Wagner et al 2006) revealed significant differences in favor of escitalopram compared with placebo in the adolescent subgroup (age range, 12-17 years).…”