The Efficacy and Safety of Aripiprazole as Adjunctive Therapy in Major Depressive Disorder

Berman, R.; Marcus, Ronald N.; Swanink, René; McQuade, Robert D.; Carson, William H.; Corey‐Lisle, Patricia K.; Khan, Arif

doi:10.4088/jcp.v68n0604

Cited by 371 publications

(328 citation statements)

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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%

“…Finally, the small to moderate treatment effect may indicate that the study was underpowered. That other studies testing atypical antipsychotics as augmenting agents (Berman et al, 2007;Ostroff and Nelson, 1999;Shelton et al, 2001) and those with larger samples (Corya et al, 2006;Shelton, 2006) report a similar pattern (i.e., rapid response followed by convergence of treatment groups), suggests otherwise. In fact, a compelling reason to initiate an atypical antipsychotic augmenting agent sooner rather than later may be because several studies, including this one, have reported a significant response as early as 1 week into treatment (Barbee et al, 2004;Bouhours et al, 2004;Ostroff and Nelson, 1999;Shelton et al, 2001).…”

Section: Discussionmentioning

confidence: 87%

“…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).…”

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: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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show abstract

“…Three 6-week, double-blind RCTs by Berman and colleagues [7,8] and Marcus et al [9] presented data on aripiprazole augmentation in conjunction with selective serotonin reuptake inhibitors (SSRIs) and selective serotonin/norepinephrine reuptake inhibitors (SNRIs) compared with adjunctive placebos for TRD (Table 2). In those trials, aripiprazole therapy was initiated at 5 mg/day, with the possibility of decreasing to 2 mg/day if not tolerated, and the dose was titrated up to a maximum of 20 mg/day, with a mean dose of approximately 11 mg/kg at the end of the studies.…”

Section: Aripiprazolementioning

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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Magnitude of the Placebo Response Across Treatment Modalities Used for Treatment-Resistant Depression in Adults

et al. 2021

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IMPORTANCEThe placebo effect in depression clinical trials is a substantial factor associated with failure to establish efficacy of novel and repurposed treatments. However, the magnitude of the placebo effect and whether it differs across treatment modalities in treatment-resistant depression (TRD) is unclear.OBJECTIVE To examine the magnitude of the placebo effect in patients with TRD across different treatment modalities and its possible moderators. DATA SOURCESSearches were conducted on MEDLINE, Web of Science, and PsychInfo from inception to June 21, 2021. STUDY SELECTION Randomized clinical trials (RCTs) were included if they recruited patients with TRD and randomized them to a placebo or sham arm and a pharmacotherapy, brain stimulation, or psychotherapy arm. DATA EXTRACTION AND SYNTHESIS Independent reviewers used standard forms for data extraction and quality assessment. Random-effects analyses and standard pairwise meta-analyses were performed. MAIN OUTCOMES AND MEASURES The primary outcome was the Hedges g value for the reported depression scales. Secondary outcomes included moderators assessed via meta-regression and response and remission rates. Heterogeneity was assessed with the I 2 test, and publication bias was evaluated using the Egger test and a funnel plot. Cochrane Risk of Bias Tool was used to estimate risks. RESULTS Fifty RCTs were included involving various types of placebo or sham interventions with a total of 3228 participants (mean [SD] age, 45.8 [6.0] years; 1769 [54.8%] female). The pooledplacebo effect size for all modalities was large (g = 1.05; 95% CI, 0.91-1.1); the placebo effect size in RCTs of specific treatment modalities did not significantly differ. Similarly, response and remission rates associated with placebo were comparable across modalities. Heterogeneity was large. Three variables were associated with a larger placebo effect size: open-label prospective treatment before double-blind placebo randomization (β = 0.35; 95% CI, 0.11 to 0.59; P = .004), later year of publication (β = 0.03; 95% CI, 0.003 to 0.05; P = .03), and industry-sponsored trials (β = 0.34; 95% CI, 0.09 to 0.58; P = .007). The number of failed interventions was associated with the probability a smaller placebo effect size (β = −0.12; 95% CI, −0.23 to −0.01, P = .03). The Egger test result was not significant for small studies' effects. (continued) Key Points Question What is the placebo effect magnitude in different treatment modalities used for management of patients with treatment-resistant depression? Findings In this systematic review and meta-analysis of 3228 patients with treatment-resistant depression in 50 randomized clinical trials, the placebo effect size was large and consistent across treatment modalities. Response and remission rates associated with placebo effect were comparable across modalities.Meaning The findings of this study suggest a placebo effect size benchmark may be used to interpret the findings of past and future clinical trials.

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The Efficacy and Safety of Aripiprazole as Adjunctive Therapy in Major Depressive Disorder

Cited by 371 publications

References 0 publications

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

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

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

Magnitude of the Placebo Response Across Treatment Modalities Used for Treatment-Resistant Depression in Adults

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