Efficacy and safety of adjunctive armodafinil in adults with major depressive episodes associated with bipolar I disorder

a randomized, double-blind, placebo-controlled, multicenter trial

Armodafinil Treatment Trial Study Network

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

OBJECTIVE: To examine the efficacy and safety of adjunctive armodafinil for major depressive episodes associated with bipolar I disorder.

METHOD: Adults meeting DSM-IV-TR criteria for bipolar I disorder and currently experiencing a major depressive episode while taking at least 4 weeks of conventional maintenance medication were enrolled in a placebo-controlled evaluation of adjunctive armodafinil 150 or 200 mg (conducted January 2010-March 2012). The primary efficacy measure was change from baseline to week 8 on the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) total score in the 150-mg armodafinil group versus placebo.

RESULTS: Of 786 patients screened, 433 were randomized (placebo, n = 199; armodafinil 150 mg, n = 201; armodafinil 200 mg, n = 33). The 200-mg armodafinil group was discontinued by protocol amendment due to lower than expected patient enrollment. For the 150-mg armodafinil group versus placebo, there was a significantly greater decrease in least squares mean (standard error of mean [SEM]) IDS-C30 total score at week 8 (-21.7 [1.1] vs -17.9 [1.1]; P = .0097; Cohen d therapeutic effect size = 0.28). The proportion of IDS-C30 responders (≥ 50% decrease from baseline) was significantly higher for the 150-mg armodafinil group versus placebo at final visit (46% [91/197] vs 34% [67/196]; P = .0147). The proportion of IDS-C30 remitters (total score ≤ 11) was 21% (42/197) for armodafinil 150 mg versus 17% (34/196) for placebo (P = .3343) at final visit. Adverse events (AEs) observed in > 5% of either the armodafinil 150 mg or placebo groups and more frequently with 150 mg armodafinil were diarrhea (9% [17/198] vs 7% [13/199]), and nausea (6% [11/198] vs 5% [9/199]), respectively. In the 200-mg armodafinil group, there were 2 serious AEs (n = 1, hepatic failure leading to death; n = 1, acute hepatitis). The death was not considered related to study treatment.

CONCLUSIONS: Adjunctive armodafinil 150 mg significantly improved symptoms of major depressive episodes associated with bipolar I disorder versus placebo and was generally well tolerated.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01072929.

Original languageEnglish (US)
Pages (from-to)1054-1061
Number of pages8
JournalThe Journal of clinical psychiatry
Volume75
Issue number10
DOIs
StatePublished - Oct 1 2014

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Bipolar Disorder
Multicenter Studies
Placebos
Safety
armodafinil
Liver Failure
Therapeutic Uses
Least-Squares Analysis
Diagnostic and Statistical Manual of Mental Disorders
Nausea
Hepatitis
Diarrhea
Maintenance
Depression

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{e93533623bf649349cf3ac0263a14333,
title = "Efficacy and safety of adjunctive armodafinil in adults with major depressive episodes associated with bipolar I disorder: a randomized, double-blind, placebo-controlled, multicenter trial",
abstract = "OBJECTIVE: To examine the efficacy and safety of adjunctive armodafinil for major depressive episodes associated with bipolar I disorder.METHOD: Adults meeting DSM-IV-TR criteria for bipolar I disorder and currently experiencing a major depressive episode while taking at least 4 weeks of conventional maintenance medication were enrolled in a placebo-controlled evaluation of adjunctive armodafinil 150 or 200 mg (conducted January 2010-March 2012). The primary efficacy measure was change from baseline to week 8 on the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) total score in the 150-mg armodafinil group versus placebo.RESULTS: Of 786 patients screened, 433 were randomized (placebo, n = 199; armodafinil 150 mg, n = 201; armodafinil 200 mg, n = 33). The 200-mg armodafinil group was discontinued by protocol amendment due to lower than expected patient enrollment. For the 150-mg armodafinil group versus placebo, there was a significantly greater decrease in least squares mean (standard error of mean [SEM]) IDS-C30 total score at week 8 (-21.7 [1.1] vs -17.9 [1.1]; P = .0097; Cohen d therapeutic effect size = 0.28). The proportion of IDS-C30 responders (≥ 50{\%} decrease from baseline) was significantly higher for the 150-mg armodafinil group versus placebo at final visit (46{\%} [91/197] vs 34{\%} [67/196]; P = .0147). The proportion of IDS-C30 remitters (total score ≤ 11) was 21{\%} (42/197) for armodafinil 150 mg versus 17{\%} (34/196) for placebo (P = .3343) at final visit. Adverse events (AEs) observed in > 5{\%} of either the armodafinil 150 mg or placebo groups and more frequently with 150 mg armodafinil were diarrhea (9{\%} [17/198] vs 7{\%} [13/199]), and nausea (6{\%} [11/198] vs 5{\%} [9/199]), respectively. In the 200-mg armodafinil group, there were 2 serious AEs (n = 1, hepatic failure leading to death; n = 1, acute hepatitis). The death was not considered related to study treatment.CONCLUSIONS: Adjunctive armodafinil 150 mg significantly improved symptoms of major depressive episodes associated with bipolar I disorder versus placebo and was generally well tolerated.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01072929.",
author = "{Armodafinil Treatment Trial Study Network} and Calabrese, {Joseph R.} and Frye, {Mark A} and Ronghua Yang and Ketter, {Terence A.}",
year = "2014",
month = "10",
day = "1",
doi = "10.4088/JCP.13m08951",
language = "English (US)",
volume = "75",
pages = "1054--1061",
journal = "Journal of Clinical Psychiatry",
issn = "0160-6689",
publisher = "Physicians Postgraduate Press Inc.",
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TY - JOUR

T1 - Efficacy and safety of adjunctive armodafinil in adults with major depressive episodes associated with bipolar I disorder

T2 - a randomized, double-blind, placebo-controlled, multicenter trial

AU - Armodafinil Treatment Trial Study Network

AU - Calabrese, Joseph R.

AU - Frye, Mark A

AU - Yang, Ronghua

AU - Ketter, Terence A.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - OBJECTIVE: To examine the efficacy and safety of adjunctive armodafinil for major depressive episodes associated with bipolar I disorder.METHOD: Adults meeting DSM-IV-TR criteria for bipolar I disorder and currently experiencing a major depressive episode while taking at least 4 weeks of conventional maintenance medication were enrolled in a placebo-controlled evaluation of adjunctive armodafinil 150 or 200 mg (conducted January 2010-March 2012). The primary efficacy measure was change from baseline to week 8 on the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) total score in the 150-mg armodafinil group versus placebo.RESULTS: Of 786 patients screened, 433 were randomized (placebo, n = 199; armodafinil 150 mg, n = 201; armodafinil 200 mg, n = 33). The 200-mg armodafinil group was discontinued by protocol amendment due to lower than expected patient enrollment. For the 150-mg armodafinil group versus placebo, there was a significantly greater decrease in least squares mean (standard error of mean [SEM]) IDS-C30 total score at week 8 (-21.7 [1.1] vs -17.9 [1.1]; P = .0097; Cohen d therapeutic effect size = 0.28). The proportion of IDS-C30 responders (≥ 50% decrease from baseline) was significantly higher for the 150-mg armodafinil group versus placebo at final visit (46% [91/197] vs 34% [67/196]; P = .0147). The proportion of IDS-C30 remitters (total score ≤ 11) was 21% (42/197) for armodafinil 150 mg versus 17% (34/196) for placebo (P = .3343) at final visit. Adverse events (AEs) observed in > 5% of either the armodafinil 150 mg or placebo groups and more frequently with 150 mg armodafinil were diarrhea (9% [17/198] vs 7% [13/199]), and nausea (6% [11/198] vs 5% [9/199]), respectively. In the 200-mg armodafinil group, there were 2 serious AEs (n = 1, hepatic failure leading to death; n = 1, acute hepatitis). The death was not considered related to study treatment.CONCLUSIONS: Adjunctive armodafinil 150 mg significantly improved symptoms of major depressive episodes associated with bipolar I disorder versus placebo and was generally well tolerated.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01072929.

AB - OBJECTIVE: To examine the efficacy and safety of adjunctive armodafinil for major depressive episodes associated with bipolar I disorder.METHOD: Adults meeting DSM-IV-TR criteria for bipolar I disorder and currently experiencing a major depressive episode while taking at least 4 weeks of conventional maintenance medication were enrolled in a placebo-controlled evaluation of adjunctive armodafinil 150 or 200 mg (conducted January 2010-March 2012). The primary efficacy measure was change from baseline to week 8 on the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30) total score in the 150-mg armodafinil group versus placebo.RESULTS: Of 786 patients screened, 433 were randomized (placebo, n = 199; armodafinil 150 mg, n = 201; armodafinil 200 mg, n = 33). The 200-mg armodafinil group was discontinued by protocol amendment due to lower than expected patient enrollment. For the 150-mg armodafinil group versus placebo, there was a significantly greater decrease in least squares mean (standard error of mean [SEM]) IDS-C30 total score at week 8 (-21.7 [1.1] vs -17.9 [1.1]; P = .0097; Cohen d therapeutic effect size = 0.28). The proportion of IDS-C30 responders (≥ 50% decrease from baseline) was significantly higher for the 150-mg armodafinil group versus placebo at final visit (46% [91/197] vs 34% [67/196]; P = .0147). The proportion of IDS-C30 remitters (total score ≤ 11) was 21% (42/197) for armodafinil 150 mg versus 17% (34/196) for placebo (P = .3343) at final visit. Adverse events (AEs) observed in > 5% of either the armodafinil 150 mg or placebo groups and more frequently with 150 mg armodafinil were diarrhea (9% [17/198] vs 7% [13/199]), and nausea (6% [11/198] vs 5% [9/199]), respectively. In the 200-mg armodafinil group, there were 2 serious AEs (n = 1, hepatic failure leading to death; n = 1, acute hepatitis). The death was not considered related to study treatment.CONCLUSIONS: Adjunctive armodafinil 150 mg significantly improved symptoms of major depressive episodes associated with bipolar I disorder versus placebo and was generally well tolerated.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01072929.

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DO - 10.4088/JCP.13m08951

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