Olanzapine/Fluoxetine Combination for Treatment-Resistant Depression

Shelton, Richard C.; Williamson, D.S.; Corya, S.; Sanger, T.M.; Campen, Luann E. Van; Case, Michael; Briggs, Susan D.; Tollefson, Gary D.

doi:10.4088/jcp.v66n1012

Cited by 149 publications

(207 citation statements)

References 22 publications

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“…The fact that 21% of the placebo group dropped from the study (vs. 12.9% of the risperidone group) may be due to inadequate response to medication. Rapid response to an adjunctive atypical followed by convergence with a control group was found in the recent study by Berman et al (2007) and the combination studies also reported a quick response followed by a leveling off after a few weeks (Shelton et al, 2005;Corya et al, 2006).…”

Section: Discussionmentioning

confidence: 63%

“…In a double-blind, randomized risperidone augmentation trial, patients improved after 4 weeks and maintained the improvement at the 6-week endpoint (Gharabawi 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).…”

Section: Introductionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Keitner

Garlow

Ryan

et al. 2009

Journal of Psychiatric Research

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Objective-Patients (30-50%) with non-psychotic major depression will not respond despite an adequate trial of antidepressant medication. This study evaluated risperidone as an augmenting agent for patients who failed or only partially responded to an adequate trial of an antidepressant medication.Method-Ninety-seven patients with unipolar non-psychotic major depression who were not responsive to antidepressant monotherapy were randomized to risperidone (0.5-3 mg/day) or placebo augmentation in a four-week, double-blind, placebo controlled treatment trial. The primary outcome measure was remission defined by a score of ≤10 on the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes measures were the Hamilton Rating Scale for Depression, the Clinician Global Impression of Severity scale and the overall satisfaction item of the Quality of Life and Enjoyment Questionnaire.Results-Subjects in both treatment groups improved significantly over time. The odds of remitting were significantly better for patients in the risperidone vs. placebo arm (OR = 3.33, p = . 011). At the end of 4 weeks of treatment 52% of the risperidone augmentation group remitted (MADRS ≤ 10) compared to 24% of the placebo augmentation group (CMH(1) = 6.48, p = .011), but the two groups were converging. Patients in the risperidone group also reported significantly more improvement in quality-of-life than patients in the placebo group. There were no betweengroup differences in the number of adverse events reported, however, weight gain was significantly higher in the group receiving risperidone. Conclusion-Augmentation of an antidepressant with risperidone for patients with difficult-totreat depression leads to more rapid response and a higher remission rate and better quality-of-life.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Keitner

Garlow

Ryan

et al. 2009

Journal of Psychiatric Research

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“…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]. The difference in weight gain with SGA adjunctive therapy was small, and no other adverse event related to metabolic function, such as changes in mean waist circumference, total cholesterol, high or low-density lipoprotein cholesterol, triglycerides, fasting plasma glucose, or haemoglobin A1C, was associated with aripiprazole augmentation in short-term trials.…”

Section: Aripiprazolementioning

confidence: 99%

“…Five trials were performed to evaluate the efficacy of OFC compared with fluoxetine monotherapy in patients with TRD by Shelton and colleagues [15,16], Corya et al [17] and Thase et al [18] ( Table 2). Olanzapine was initiated at either 5 or 6 mg/day, and doses were titrated up to a maximum of 12, 18, or 20 mg/day, with a modal dose of 8-13 mg/day at the end of those studies.…”

Section: Olanzapinementioning

confidence: 99%

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

Kato

Chang

2013

CNS Drugs

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Various classes of antidepressants have been used in the treatment of major depressive disorder (MDD); however, the efficacy of these treatments remains uncertain. A number of well-controlled clinical trials, meta-analyses and practical clinical studies have found that approximately 30 % of MDD patients remit following antidepressant treatment, leaving approximately 70 % of patients with significant residual symptoms. In these latter patients with what is considered treatment-resistant MDD, typical antipsychotics have sometimes been administered in order to augment the antidepressant effects but safety and tolerability concerns significantly reduce their usage in MDD patients. The advent of second-generation antipsychotics (SGAs), which have diverse pharmacodynamic profiles relative to antidepressants, has dramatically increased the usage of such drugs for patients with MDD. Recently, SGAs such as aripiprazole, quetiapine and olanzapine in combination with fluoxetine have been approved for the treatment of MDD, especially in the case of treatment resistance. This article reviews the efficacy and tolerability of SGA augmentation when added to antidepressant therapy for treatment-resistant MDD patients in acute phase studies published to date.

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