General Information

Aplenzin is an orally-active enhanced-absorption salt of bupropion. It belongs to the class of antidepressants known as aminoketones.

Aplenzin is specifically indicated for the treatment of major depresive disorder.

Aplenzin is supplied as a tablet designed for oral administration. The tablets come in 174 mg, 348 mg and 522 mg strengths. The recommended initial dose of the drug is 348 mg/day, given once daily in the morning. Dosing with Aplenzin should begin at 174-mg/day given as a single daily dose in the morning. If the 174 mg initial dose is adequately tolerated, an increase to the 348-mg/day target dose, given as once daily, may be made as early as day 4 of dosing. There should be an interval of at least 24 hours between successive doses. The full antidepressant effect of Aplenzin may not be evident until 4 weeks of treatment or longer. An increase in dosage to the maximum of 522 mg/day, given as a single dose, may be considered for patients in whom no clinical improvement is noted after several weeks of treatment at 348 mg/day.

Caution should be taken in patients with hepatic impairment; the dose should not exceed 174 mg every other day, as well as in subjects with renal impairment.

Clinical Results

FDA Approval
FDA approval of Aplenzin was based on the results of two 4-week, placebo-controlled trials and one 6-week, placebo-controlled trial. In the first study, subjects were titrated in a bupropion hydrochloride dose range of 300 to 600 mg/day of the immediate-release formulation on a three times daily schedule; 78% of patients received maximum doses of 450 mg/day or less. This trial demonstrated the effectiveness of bupropion on the Hamilton Depression Rating Scale (HDRS) total score, the depressed mood item (item 1) from that scale, and the Clinical Global Impressions (CGI) severity score. A second study included 2 fixed doses of the immediate-release formulation of bupropion hydrochloride (300 and 450 mg/day) and placebo. This trial demonstrated the effectiveness of bupropion, but only at the 450mg/ day dose of the immediate-release formulation; the results were positive for the HDRS total score and the CGI severity score, but not for HDRS item 1. In the third study, outpatients received 300 mg/day of the immediate-release formulation of bupropion hydrochloride. This study demonstrated the effectiveness of bupropion on the HDRS total score, HDRS item 1, the Montgomery-Asberg Depression Rating Scale, the CGI severity score, and the CGI improvement score.

In a longer-term study, outpatients meeting DSM-IV criteria for major depressive disorder, recurrent type, who had responded during an 8-week open trial on bupropion hydrochloride (150 mg twice daily of the sustained-release formulation) were randomized to continuation of their same dose of bupropion or placebo, for up to 44 weeks of observation for relapse. Response during the open phase was defined as CGI Improvement score of 1 (very much improved) or 2 (much improved) for each of the final 3 weeks. Relapse during the double-blind phase was defined as the investigator’s judgment that drug treatment was needed for worsening depressive symptoms. Patients receiving continued bupropion treatment experienced significantly lower relapse rates over the subsequent 44 weeks compared to those receiving placebo.

Ongoing Study Commitments

Biovail has agreed to a deferred pediatric study under PREA for the treatment of Major Depressive Disorder in pediatric patients ages 7 to 17.
Final Report Submission: 5 years from the date of approval

Mechanism of Action

Aplenzin is an orally-active enhanced-absorption salt of bupropion. It belongs to the class of antidepressants known as aminoketones. Aplenzin is chemically unrelated to tricyclic, tetracyclic, selective serotonin re-uptake inhibitor, or other known antidepressant agents. The mechanism of action of bupropion is unknown, however it is presumed that the action is mediated by noradrenergic and/or dopaminergic mechanisms.

Literature References

Herrera-Guzmán I, Gudayol-Ferré E, Lira-Mandujano J, Herrera-Abarca J, Herrera-Guzmán D, Montoya-Pérez K, Guardia-Olmos J Cognitive predictors of treatment response to bupropion and cognitive effects of bupropion in patients with major depressive disorder. Psychiatry Research 2008 May 22

Robertson B, Wang L, Diaz MT, Aiello M, Gersing K, Beyer J, Mukundan S Jr, McCarthy G, Doraiswamy PM Effect of bupropion extended release on negative emotion processing in major depressive disorder: a pilot functional magnetic resonance imaging study. The Journal of Clinical Psychiatry 2007 Feb;68(2):261-7

Jefferson JW, Rush AJ, Nelson JC, VanMeter SA, Krishen A, Hampton KD, Wightman DS, Modell JG Extended-release bupropion for patients with major depressive disorder presenting with symptoms of reduced energy, pleasure, and interest: findings from a randomized, double-blind, placebo-controlled study. The Journal of Clinical Psychiatry 2006 Jun;67(6):865-73

DeBattista C, Solvason HB, Poirier J, Kendrick E, Schatzberg AF A prospective trial of bupropion SR augmentation of partial and non-responders to serotonergic antidepressants. Journal of Clinical Psychopharmacology 2003 Feb;23(1):27-30

Dunner DL, Kwong WJ, Houser TL, Richard NE, Donahue RM, Khan ZM Improved Health-Related Quality of Life and Reduced Productivity Loss After Treatment With Bupropion Sustained Release: A Study in Patients With Major Depression. Primary Care Companion to the Journal of Clinical Psychiatry 2001 Feb;3(1):10-16