A double-blind, placebo-controlled study of selegiline transdermal system in depressed adolescents.

OBJECTIVE: A randomized, double-blind, placebo-controlled flexible-dose, parallel group trial was conducted at 26 clinical investigational sites in the United States to examine the safety and efficacy of the selegiline transdermal system (STS) (EMSAM®) in adolescents (ages 12-17 years) meeting American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for moderate to severe major depressive disorder (MDD) without psychotic features. METHODS: Adolescents (n=308) with moderate to severe MDD were randomized to either STS (n=152) or placebo (n=156). Two hundred and fifteen (69.8%) subjects completed the study and 17 (5.5%) reported discontinuation because of adverse events (AEs). The primary efficacy outcome measure was the mean change from baseline to end of study (week 12 last observation carried forward [LOCF]) in the Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary outcome measures included end-point Clinical Global Impressions - Severity (CGI-S) and Clinical Global Impressions - Improvement (CGI-I). RESULTS: Patients on STS or placebo had a significant decline from baseline (p<0.001) on their CDRS-R total score with mean reductions±SD as follows: STS 21.4±16.6; placebo 21.5±16.5. Both groups had similar response rates (58.6% vs. 59.3%) defined as CGI-I of 1 or 2 at study end. However, these between-group efficacy findings were without statistical significance. The overall incidence of reported AEs was 62.5% for STS-treated patients and 57.7% for placebo-treated patients. Most commonly reported AEs in STS or placebo groups were application site reactions (STS=24.3%; placebo=21.8%), headache (STS=17.1%; placebo=16.7%), and nausea (STS=7.2%; placebo=7.7%). Treatment groups did not differ on any laboratory parameters, vital signs, or electrocardiogram (ECG) findings. No suspected hypertensive crises were reported in the trial. CONCLUSIONS: These data demonstrated that the STS was safe and well tolerated in this adolescent sample. However, both STS-treated and placebo-treated subjects demonstrated a decline from baseline in depressive symptoms (CDRS-R total score) over the length of the study, without statistical superiority by either group.

Placing transdermal selegiline for major depressive disorder into clinical context: number needed to treat, number needed to harm, and likelihood to be helped or harmed.

BACKGROUND: This is a quantitative review of existing studies of transdermal selegiline for major depressive disorder. METHODS: Data for dichotomous outcomes were extracted from the five 6-8 week studies of transdermal selegiline. Number needed to treat (NNT) vs. placebo was calculated for response and remission using standard definitions. Number needed to harm (NNH) vs. placebo for commonly encountered adverse events (AEs), AEs associated with sexual function, incidence of weight gain ≥5% from baseline, and discontinuation due to an AE, were also calculated. Data was pooled as appropriate and likelihood to be helped or harmed (LHH) ratios contrasting remission with selected tolerability outcomes were determined. RESULTS: When pooling together the two pivotal trials as identified in product labeling, NNT for response was 11 (95% CI 6-109) and for remission, 9 (95% CI 6-28). Pooling all trials, NNH for application site reaction was 7 (95% CI 6-10) and for insomnia, 19 (95% CI 12-41). There were no clinically relevant differences from placebo regarding weight gain or impairment in sexual functioning. NNH for discontinuation due to an AE was 32 (95% CI 19-132). LHH for remission vs. discontinuation from treatment due to an AE was 3.6. LIMITATIONS: The studies included were not identical in design. The studies were registrational in nature and thus not necessarily generalizable. CONCLUSIONS: NNT for transdermal selegiline for efficacy is similar to that for other antidepressant regimens for which similar analyses have been published. There appear to be no clinically relevant effects of selegiline on weight or sexual functioning.

Selegiline transdermal system: use pattern and adherence in patients with major depressive disorder.

OBJECTIVE: To discern the pattern of use of selegiline transdermal system as well as the level of adherence relative to other pharmacotherapies for treatment of major depressive disorder. METHOD: Deidentified patient-level data (2010-2011; N = 2,985) were abstracted from US longitudinal archives (Medicaid, Medicare, managed care) in this retrospective exploratory claims-based analysis. Major depressive disorder was defined as ICD-9-CM codes 292.2, 296.3, 300.4, or 311. Antidepressant treatment failure was defined as receipt of < 90 days of initial antidepressant. RESULTS: Most patients received selegiline transdermal system as a second or third treatment option following treatment failure, and only 71 patients received it as first-line therapy. Patients were more likely to receive selegiline transdermal system for 60, 90, or 180 days compared to other therapies irrespective of treatment failure (P < .05). Among patients who did not fail treatment in the first 90 days, selegiline transdermal system was associated with a greater probability of receipt compared to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors at 120 days (odds ratio [OR] = 1.21; 95% CI, 1.14-1.47) and 180 days (OR = 1.09; 95% CI, 1.01-1.28). CONCLUSION: Although limited by the small sample size of patients receiving selegiline transdermal system versus other pharmacotherapies, the results suggest that after antidepressant treatment failure, earlier use of selegiline transdermal system may be warranted.

Safety of selegiline transdermal system in clinical practice: analysis of adverse events from postmarketing exposures.

OBJECTIVE: The objective of this analysis is to present the safety profile of selegiline transdermal system (STS) in clinical practice after US Food and Drug Administration approval by analyzing reported postmarketing adverse events (AEs). METHOD: Deidentified data were obtained on AEs, regardless of causality, as collected and compiled in the pharmaceutical company's adverse event collection systems/databases after the launch of STS in the United States. All reports of hypertensive crisis, suicide attempts, and STS overdoses were carefully examined to independently determine relation of the AE to STS. RESULTS: From April 2006 to October 2010, a total of 3,155 AEs in 1,516 patients were reported (5.2% of the total exposures; N = 29,141), regardless of causality. The most frequently reported categories of AEs were general disorders (no. of AEs = 1,037, 3.6%) and central nervous system (CNS) disorders (no. of AEs = 574, 2.0%). A total of 266 reports (0.9%) were classified as serious AEs; CNS disorders (no. of AEs = 71, 26.7%) and cardiac and vascular disorders (no. of AEs = 44, 16.5%) were most common. There were 13 self-reports of possible hypertensive events or hypertension, although objective clinical data were not submitted in any of these cases. Thirteen drug-drug interactions (0.04%) were reported, and 5 were classified as serious. CONCLUSIONS: The most commonly reported AEs were application site reactions and insomnia. Very few patients reported a hypertensive event, and there were no objectively confirmed reports of hypertensive crisis with food at any STS dose. Therapeutic doses of STS appear to have a safety profile in clinical practice that is consistent with that observed in clinical trials. However, given the relatively modest exposure numbers, continued safety monitoring is recommended.