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

Abstract

Objective: The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Methods: Adolescents (12-17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10-20 mg versus placebo could enroll in a 16-24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the leadin study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Results: Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo ( p = 0.005, LOCF; p = 0.014; MMRM). Response rates (CDRS-R ‡ 40% reduction from baseline [adjusted and unadjusted] and CGI-I £ 2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R £ 28) were 50.6% for escitalopram and 35.7% for placebo ( p = 0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs ( ‡ 5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were mild/ moderate and not related to the study drug. AEs suggestive of self-harm occurred in 5.7% and 7.1% of placebo and escitalopram patients. Occurrence of suicidal behavior and/or suicidal ideation assessed by C-SSRS was 10.9% (14/128) for placebo and 14.5% (19/131) for escitalopram. Conclusions: Extended use of escitalopram was generally safe and resulted in modest improvement in efficacy in adolescents with MDD.

Safety of 80 antidepressants, antipsychotics, anti‐attention‐deficit/hyperactivity medications and mood stabilizers in children and adolescents with psychiatric disorders: a large scale systematic meta‐review of 78 adverse effects

“…For antidepressants, we included four NMAs 40,48‐50 , 15 MAs 36,51‐64 , 27 individual RCTs 65‐91 also covered in those NMA/MAs, six additional RCTs 92‐97 , and three cohort studies 98‐100 . There were 120,637 youth on antidepressants, including 24,659 across 139 RCTs after eliminating duplicated RCTs in multiple NMA/MAs (22,704 in NMA/MAs, 1,955 in additional RCTs), and 95,978 in three cohort studies.…”

Influence of CYP2C19 Metabolizer Status on Escitalopram/Citalopram Tolerability and Response in Youth With Anxiety and Depressive Disorders

“…The efficacy and tolerability of es/citalopram has been extensively evaluated in the pediatric population (Wagner et al, 2004, 2006; Findling et al, 2006, 2013; Isolan et al, 2007; Emslie et al, 2009), but pharmacogenetic studies are lacking. In adults, faster CYP2C19 metabolizers have lower serum es/citalopram concentrations at equivalent doses, compared with normal metabolizers (NMs), while slower CYP2C19 metabolizers have increased serum concentrations (Altar et al, 2013; Chang et al, 2014; Jukic et al, 2018).…”

Effects of Exercise Training on Restless Legs Syndrome, Depression, Sleep Quality, and Fatigue Among Hemodialysis Patients: A Systematic Review and Meta-analysis

“…4 Despite the encouraging effects of pharmacological treatment, chemical drugs are costly and associated with adverse effects. 5 Meanwhile, people with ESRD usually take several drugs, and renal impairment could lead to a higher risk of adverse effects, drug interactions, or other drug-related problems. 6 Hence, health providers are actively seeking an effective treatment with few side effects to reduce the symptom burden of patients receiving HD.…”