Pharmacy & Therapeutics - April 2008 - (Page 213) DRUG FORECAST • the 17-item Hamilton Rating Scale for Depression (HAM-D-17) (–8.7 ± 7.5 vs. –6.1 ± 6.7; P = 0.01). • the 28-item HAM-D Scale (–11.2 ± 9.8 vs. –7.6 ± 8.6; P = 0.004). • the Montgomery–Åsberg Depression Rating Scale (MADRS) (–9.8 ± 11.5 vs. –5.7 ± 9.1; P = 0.005). Greater reductions in mean scores occurred as early as the first week of STS treatment, compared with placebo.22 In addition, significantly more STS patients achieved a reduction of 50% or more in both total HAM-D-17 scores (37.5% vs. 22.7%; P = 0.04) and HAM-D-28 scores (37.5% vs. 22.7%; P = 0.03) at the study’s endpoint than the placebo group. Moreover, more patients scored below 8 on the HAM-D-17 with the STS, compared with placebo (22.7 vs. 11.4%; P = 0.04). Efficacy was also evaluated with the Clinical Global Impression (CGI) Severity of Illness and Improvement measures. Greater global improvement was observed with the STS than with placebo (42% vs. 27%; P = 0.03). Feiger et al.23 In a second, short-term, eight-week study (n = 265), patients with moderateto-severe depression received a flexible STS dose of 6 to 12 mg/24 hours or placebo once daily with no dietary tyramine restrictions. Patients receiving the STS experienced greater reductions at the endpoint (eight weeks) in: • HAM-D-28 scores (STS baseline = 28.3 ± 3.7, mean change = –11.1 ± 8.6; placebo baseline = 28.6 ± 4.0, mean change = –8.9 ± 9.1; P = 0.03). • MADRS scores (STS baseline = 29.3 ± 4.2, mean change = –11.6 ± 9.8; placebo baseline = 29.3 ± 4.2, mean change = –8.6 ± 10.3; P = 0.02). • Inventory for Depressive Symptomatology-Self Rated scores (STS baseline = 37.3 ± 8.8, mean change = –13.9 ± 12.1; placebo baseline = 37.6 ± 9.4, mean change = –10.6 ± 12.5; P = 0.03), compared with placebo. In this study, patients receiving the STS also showed significant improvements from baseline, compared with placebo, for the secondary outcome of HAM-D Bech-6 scores (representing core depressive symptoms) (STS baseline = 12.4 ± 1.3, mean change = –5.5 ± 4.3; placebo baseline = 8.5 ± 4.3, mean change = –4.1 ± 4.2; P = 0.01). Amsterdam24 In a fur ther shor t-term study, 289 patients received either the STS 6 mg/24 hours (n = 145) or placebo (n = 144) once daily for eight weeks. Patients did not need to follow a tyramine-restricted diet. At the study’s endpoint, the STS group experienced significantly greater reductions in HAM-D-28 scores (18.6 ± 9.4 vs. 21.2 ± 9.3; P = 0.39) and in MADRS scores (18.0 ± 10.0 vs. 21.7 ± 9.9; P = 0.03). HAMD-17 scores were also better at the endpoint but not significantly (STS = 14.7 ± 7.2 vs. placebo = 16.3 ± 7.1; P = 0.06). Amsterdam and Bodkin25 In a long-term, double-blind, placebocontrolled relapse-prevention study, 322 patients who had responded to 10 weeks of open-label STS 6 mg/24 hours were randomly selected to receive either transdermal selegiline 6 mg/24 hours or placebo once daily for up to 52 weeks. No dietary tyramine restrictions were required. Relapse was defined as meeting these criteria on two consecutive visits: • a HAM-D-17 score of 14 or higher • a CGI score of 3 or higher with a two-point increase from the baseline score • criteria for MDD, as defined in the Diagnostic Statistical Manual of Mental Disorders (DSM-IV) At week 26, significantly fewer STStreated patients (16.8%) than placebotreated patients (29.4%) experienced a relapse (P = 0.005). STS efficacy was maintained throughout the study, with significantly fewer STS patients experiencing relapse at week 52 (17%), compared with placebo patients (30.7%; P = 0.003). Patients who completed the study also experienced a significantly longer time to relapse over 52 weeks, compared with those receiving placebo (P = 0.005). significant differences in treatment withdrawal rates between STS and placebo groups. The most common adverse events that occurred with the long-term STS use included application-site re actions, infection, insomnia, and headache.25 The occurrence rate of adverse events with the STS was similar to that seen in the placebo patients except for reactions at the application site. In a 52-week study,25 a trend toward an increased incidence of insomnia in STStreated patients was also observed. Application-site reactions, which generally consisted of mild-to-moderate itching, redness, and swelling, were the most problematic adverse events associated with STS patches. However, these reactions were usually transient, of short duration, and mild to moderate in intensity, and they usually resolved within several hours after patch removal. The patch should not be applied to an area of skin that is irritated, broken, scarred, or calloused, and a new application site should be selected with each new patch to avoid a reaction at the site. Cases of persistent irritation should be referred to a physician. No cases of hypertensive crisis were reported in any of the controlled clinical trials. CLINICAL APPLICATIONS: ADDRESSING UNMET NEEDS For the substantial number of patients with depression, including those who do not respond adequately to, or who are intolerant of, existing antidepressant therapy, alternative options are needed. The clinical data regarding the STS patch demonstrate both its acute and long-term safety and efficacy in patients with MDD. In particular, as the first antidepressant available for transdermal administration, STS offers the benefits of an effective MAOI without the need for dietary modifications at the lowest effective dose (6 mg/24 hours). The STS may therefore offer a promising alternative therapeutic option for patients with only partial or no response to initial MDD therapy. Although the STS provides several advantages over oral MAOIs (i.e., minimal interaction with dietary tyramine and possibly a more rapid onset of therapeutic action), additional studies are needed in order to further evaluate this Safety and Tolerability of the STS Patch In the acute22–24 and long-term25 studies already outlined, transdermal selegiline was well tolerated, and there were no Vol. 33 No. 4 • April 2008 • P&T® 213
For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.