Long-term augmentation therapy with lisdexamfetamine for adults with major depressive disorder who are unresponsive or inadequately responsive to antidepressant monotherapy is no more effective than placebo, according to a study published in Journal of Clinical Psychopharmacology1.
The study followed up on similar previous short-term studies2-4 that produced mixed results with a 12-month open-label extension trial. Study participants were adult men and women at 207 study sites in 17 countries who had completed 1 of 3 short-term antecedent studies, and had major depressive disorder that did not adequately respond to antidepressant monotherapy.
The study began with a 4-week phase of dose optimization, followed by 48-weeks of dose-maintenance, then concluded with a follow-up visit between 7 and 9 days after final dose. Although 300 patients did complete all 52 weeks of the study, 1270 did not, because the trial was discontinued early due to a failure to meet the primary study end points.
After 12-months of treatment the safety and tolerability of lisdexamfetamine dimesylate was consistent with antecedent studies. With no statistically significant differences between lisdexamfetamine treatment and placebo, study investigators conclude that lisdexamfetamine is no more effective than placebo in reducing depressive symptoms for adults with major depressive disorder who do not respond adequately to antidepressant monotherapy.
They conclude, “[m]ost [treatment-emergent adverse events] were mild or moderate in severity, and the most frequently reported [treatment-emergent adverse events] were those known to be associated with [lisdexamfetamine] or with commonly occurring intercurrent illnesses. Treatment with [lisdexamfetamine] was associated with increased blood pressure and pulse in some individuals, so it is important for clinicians to regularly monitor vital signs when treating patients with [lisdexamfetamine], as is recommended in the product labeling for [lisdexamfetamine].”
This study was supported by Shire Development LLC (Lexington, MA). Please refer to reference for a complete list of authors’ disclosures.
- Richards C, Iosifescu DV, Mago R, et al. A 12-month open-label extension study of the safety and tolerability of lisdexamfetamine dimesylate for major depressive disorder in adults. J Clin Psychopharmacol. 2018; 38(4):336-343. doi: 10.1097/JCP.0000000000000897
- Trivedi MH, Cutler AJ, Richards C, et al. A randomized controlled trial of the efficacy and safety of lisdexamfetamine dimesylate as augmentation therapy in adults with residual symptoms of major depressive disorder after treatment with escitalopram. J Clin Psychiatry. 2013;74:802–809.
- Madhoo M, Keefe RS, Roth RM, et al. Lisdexamfetamine dimesylate augmentation in adults with persistent executive dysfunction after partial or full remission of major depressive disorder. Neuropsychopharmacology. 2014;39:1388–1398.
- Richards C, McIntyre RS, Weisler R, et al. Lisdexamfetamine dimesylate augmentation for adults with major depressive disorder and inadequate response to antidepressant monotherapy: results from 2 phase 3, multicenter, randomized, double-blind, placebo-controlled studies. J Affect Disord. 2016;206:151–160.