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Efficacy of dose increase among nonresponders to low-dose aripiprazole augmentation in patients with inadequate response to antidepressant treatment: a randomized, double-blind, placebo-controlled, efficacy trial.
J Clin Psychiatry 2012; 73(3):353-7JC

Abstract

OBJECTIVE

To examine the efficacy of a dose increase of aripiprazole to 5 mg/d in subjects with major depressive disorder (MDD) who did not respond to 4 weeks of treatment with aripiprazole 2 mg/d in a randomized, double-blind, placebo-controlled, parent study.

METHOD

221 Subjects with Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition-diagnosed DSM-IV-TR MDD (mean ± SD age, 45 ± 11 years; 64% women) with inadequate antidepressant response were recruited from September 2008-July 2009 and randomized to 60 days of double-blind augmentation with either aripiprazole or placebo in two 30-day phases. The study was performed across 8 academic hospital sites and 14 nonacademic (private clinic) sites throughout the United States. Randomization in a 2:3:3 ratio per sequential parallel comparison design was drug/drug (aripiprazole 2 mg/d in phase 1 and 5 mg/d in phase 2), placebo/placebo (placebo in both phases), and placebo/drug (placebo in phase 1 and aripiprazole 2 mg/d in phase 2). In phase 2, we examined efficacy of an aripiprazole dose increase to 5 mg/d in nonresponders to 2 mg/d by assessing response rates (≥ 50% reduction in Montgomery-Asberg Depression Rating Scale [MADRS] score [primary outcome measure]) and score changes in MADRS, Quick Inventory of Depressive Symptomatology-Self-Report, 9-item Patient Health Questionnaire (PHQ-9), the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, and patient-rated versions of the CGI-I and CGI-S scales.

RESULTS

Response rate for aripiprazole 2 mg/d in phase 1 was 18.5% (n/n = 10/54). Among 39 nonresponders who increased their dose to 5 mg/d, response rate was 12.8% (95% CI, 4.30%-27.43%), with significant overall mean ± SD reductions in MADRS scores (-9.46 ± 7.83 [95% CI, -12.00 to -6.92]; P < .0001), Symptoms Questionnaire Distress scores (19.51 ± 17.73 [95% CI, 13.60 to 25.43]; P < .0001), PHQ-9 scores (-7.92 ± 5.92 [95% CI, -9.89 to -5.94]; P < .0001), and CGI-S scores (-0.86 ± 0.86 [95% CI, -1.15 to -0.58]; P < .0001). Differences in efficacy between drug and placebo groups were nonsignificant, however. Aripiprazole and placebo were well tolerated.

CONCLUSIONS

Augmentation with aripiprazole 5 mg/d may provide only a modest additional benefit in patients who do not benefit from lower doses.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT00683852.

Authors+Show Affiliations

Depression Clinical and Research Program, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. dmischoulon@partners.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21939613

Citation

Mischoulon, David, et al. "Efficacy of Dose Increase Among Nonresponders to Low-dose Aripiprazole Augmentation in Patients With Inadequate Response to Antidepressant Treatment: a Randomized, Double-blind, Placebo-controlled, Efficacy Trial." The Journal of Clinical Psychiatry, vol. 73, no. 3, 2012, pp. 353-7.
Mischoulon D, Witte J, Levy M, et al. Efficacy of dose increase among nonresponders to low-dose aripiprazole augmentation in patients with inadequate response to antidepressant treatment: a randomized, double-blind, placebo-controlled, efficacy trial. J Clin Psychiatry. 2012;73(3):353-7.
Mischoulon, D., Witte, J., Levy, M., Papakostas, G. I., Pet, L. R., Hsieh, W. H., ... Fava, M. (2012). Efficacy of dose increase among nonresponders to low-dose aripiprazole augmentation in patients with inadequate response to antidepressant treatment: a randomized, double-blind, placebo-controlled, efficacy trial. The Journal of Clinical Psychiatry, 73(3), pp. 353-7. doi:10.4088/JCP.10m06541.
Mischoulon D, et al. Efficacy of Dose Increase Among Nonresponders to Low-dose Aripiprazole Augmentation in Patients With Inadequate Response to Antidepressant Treatment: a Randomized, Double-blind, Placebo-controlled, Efficacy Trial. J Clin Psychiatry. 2012;73(3):353-7. PubMed PMID: 21939613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of dose increase among nonresponders to low-dose aripiprazole augmentation in patients with inadequate response to antidepressant treatment: a randomized, double-blind, placebo-controlled, efficacy trial. AU - Mischoulon,David, AU - Witte,Janet, AU - Levy,Michael, AU - Papakostas,George I, AU - Pet,L Russell, AU - Hsieh,Wen-hua, AU - Pencina,Michael J, AU - Ward,Sean, AU - Pollack,Mark H, AU - Fava,Maurizio, Y1 - 2011/09/20/ PY - 2010/08/30/received PY - 2010/11/03/accepted PY - 2011/9/24/entrez PY - 2011/9/24/pubmed PY - 2012/6/29/medline SP - 353 EP - 7 JF - The Journal of clinical psychiatry JO - J Clin Psychiatry VL - 73 IS - 3 N2 - OBJECTIVE: To examine the efficacy of a dose increase of aripiprazole to 5 mg/d in subjects with major depressive disorder (MDD) who did not respond to 4 weeks of treatment with aripiprazole 2 mg/d in a randomized, double-blind, placebo-controlled, parent study. METHOD: 221 Subjects with Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition-diagnosed DSM-IV-TR MDD (mean ± SD age, 45 ± 11 years; 64% women) with inadequate antidepressant response were recruited from September 2008-July 2009 and randomized to 60 days of double-blind augmentation with either aripiprazole or placebo in two 30-day phases. The study was performed across 8 academic hospital sites and 14 nonacademic (private clinic) sites throughout the United States. Randomization in a 2:3:3 ratio per sequential parallel comparison design was drug/drug (aripiprazole 2 mg/d in phase 1 and 5 mg/d in phase 2), placebo/placebo (placebo in both phases), and placebo/drug (placebo in phase 1 and aripiprazole 2 mg/d in phase 2). In phase 2, we examined efficacy of an aripiprazole dose increase to 5 mg/d in nonresponders to 2 mg/d by assessing response rates (≥ 50% reduction in Montgomery-Asberg Depression Rating Scale [MADRS] score [primary outcome measure]) and score changes in MADRS, Quick Inventory of Depressive Symptomatology-Self-Report, 9-item Patient Health Questionnaire (PHQ-9), the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, and patient-rated versions of the CGI-I and CGI-S scales. RESULTS: Response rate for aripiprazole 2 mg/d in phase 1 was 18.5% (n/n = 10/54). Among 39 nonresponders who increased their dose to 5 mg/d, response rate was 12.8% (95% CI, 4.30%-27.43%), with significant overall mean ± SD reductions in MADRS scores (-9.46 ± 7.83 [95% CI, -12.00 to -6.92]; P < .0001), Symptoms Questionnaire Distress scores (19.51 ± 17.73 [95% CI, 13.60 to 25.43]; P < .0001), PHQ-9 scores (-7.92 ± 5.92 [95% CI, -9.89 to -5.94]; P < .0001), and CGI-S scores (-0.86 ± 0.86 [95% CI, -1.15 to -0.58]; P < .0001). Differences in efficacy between drug and placebo groups were nonsignificant, however. Aripiprazole and placebo were well tolerated. CONCLUSIONS: Augmentation with aripiprazole 5 mg/d may provide only a modest additional benefit in patients who do not benefit from lower doses. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00683852. SN - 1555-2101 UR - https://www.unboundmedicine.com/medline/citation/21939613/Efficacy_of_dose_increase_among_nonresponders_to_low_dose_aripiprazole_augmentation_in_patients_with_inadequate_response_to_antidepressant_treatment:_a_randomized_double_blind_placebo_controlled_efficacy_trial_ L2 - http://www.psychiatrist.com/jcp/article/pages/2012/v73n03/v73n0311.aspx DB - PRIME DP - Unbound Medicine ER -