A Randomized, Double-Blind Comparison of Olanzapine/Fluoxetine Combination, Olanzapine, and Fluoxetine in Treatment-Resistant Major Depressive Disorder

A randomized, placebo-controlled trial of risperidone augmentation for patients with difficult-to-treat unipolar, non-psychotic major depression

“…We explicitly broadened our inclusion criteria, however, in order to increase generalizability and to address the needs of the significant numbers of depressed patients who have less than an optimal response to first line treatment. We do not yet know if difficult-to-treat depression represents a unique subtype (Kupfer and Charney, 2003), or if it is one part of a wide spectrum of depressions that characterize the staging systems (Thase et al, 2007). Findings from the STAR*D study suggest that two treatment failures are likely to signify a TRD Trivedi et al, 2006).…”

“…In two large double-blind studies using a combination of medications (i.e., not augmentation trials per se), patients reported a rapid response to the combined use of olanzapine and an antidepressant, though the treatment effect was not sustained at the study endpoints of 8 and 12 weeks (Corya et al, 2006;Shelton et al, 2005). A more recent report of parallel studies of patients with Treatment Resistant Depression (TRD) found that one study showed no treatment differences using an olanzapine/fluoxetine combination while the second study, and the pooled data, did find significant improvement in patients who received the combination therapy (Thase et al, 2007). Aripiprazole has been shown to have positive results when used as adjunctive therapy for patients diagnosed with major depression (Berman et al, 2007) and a meta-analysis concluded that augmenting antidepressant medications with atypical antipsychotics (olanzapine, risperidone, and quitiapine) resulted in significantly stronger remission and response rates (Papakostas et al, 2007).…”

“…Of interest, study designs often differ in the lack of a standard definition of the study population (e.g., differences between difficult-to-treat and treatment resistant depressions, Thase, 2002;Kupfer and Charney, 2003;Shelton et al, 2005), the variation in lead-in trial time (4-8 weeks, Appelberg et al, 2001;Licht and Qvitzau, 2002;Bouhours et al, 2004;Papakostas et al, 2005;Corya et al, 2006;Berman et al, 2007;Alexopoulos et al, 2008), differences in study length and the range of cut-offs and instruments defining remission (e.g., ≤8-10 on MADRS) (Nemeroff, 2005;Shelton et al, 2005;Berman et al, 2007;Papakostas et al, 2007;Thase et al, 2007).…”

“…The primary objective was to compare the efficacy of augmentation with risperidone vs. placebo in patients with difficult-to-treat depression, defined as patients who failed to respond or only partially responded to antidepressant monotherapy. We focused on difficultto-treat depression as a useful concept that may have more generalizability than TRD and, according to a recent STAR*D report, may be part of a continuum that leads to TRD (Thase et al, 2007;Rush et al, 2006). We selected 5 weeks as a lead-in period as it met the higher range of duration (3-5 weeks) defining an adequate treatment trial (Keller, 1988;Sackheim, 2001).…”

Augmentation Treatments with Second-generation Antipsychotics to Antidepressants in Treatment-resistant Depression

“…The mean weight change was significantly greater with adjunctive aripiprazole compared with placebo (1.73 kg versus 0.38 kg), and more patients (5.2 %) receiving The data in a meta-analysis by Nelson et al [5] and the Cochran data [6] were referred. Thase et al [18] includes two trials (study 1 and study 2). Response was defined as an improvement of C50% from baseline to endpoint on the HAM-D or the MADRS, and remission was defined as a MADRS total score of B10 and C50% reduction in MADRS total score in the trials except trials by Shelton et al [15] and Corya et al [17] (two subsequent MADRS total score B8), McIntyre and Gendron [22] and Mahmoud et al [24] (HAM-D-17 score B7), Bauer et al [20], El-Khalili et al [21] and Keitner et al [26] (MADRS total score B8), trial by Reeves et al [25] aripiprazole than receiving placebo (0.6 %) had a weight gain of 7 % or more [13].…”