Randomized, placebo-controlled, adjunctive study of armodafinil for bipolar I depression: implications of novel drug design and heterogeneity of concurrent bipolar maintenance treatments

Mark A Frye, Jess Amchin, Michael Bauer, Caleb Adler, Ronghua Yang, Terence A. Ketter

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Some, but not all, prior investigations suggest armodafinil may have utility as an adjunctive treatment in bipolar I depression. Methods: Multicenter, randomized, double-blind study in patients aged 18 to 65 years experiencing a depressive episode despite maintenance therapy for bipolar I disorder. Patients were randomized to receive adjunctive armodafinil 150 mg/day or adjunctive placebo for 8 weeks. Primary efficacy outcome was change from baseline in 30-Item Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30) total score at week 8. Safety and tolerability were monitored. Results: Of 656 patients screened, 399 were randomized, of whom 308 (77 %) were taking a protocol-allowed mood stabilizer as monotherapy. The primary efficacy outcome did not reach statistical significance; however, several secondary efficacy outcomes demonstrated statistically significant advantages for adjunctive armodafinil (n = 197) over adjunctive placebo (n = 196), including Clinical Global Impression of Severity of Illness for depression (weeks 6, 8, and endpoint; all P < 0.05), Global Assessment of Functioning (weeks 4, 8, and endpoint; all P < 0.02), IDS-C30 remitter rates (week 8 and endpoint; both P < 0.02), and mean change from baseline in IDS-C30 total score at week 7 (P < 0.05). Adjunctive armodafinil and adjunctive placebo were generally well tolerated. Although adjunctive armodafinil compared with adjunctive placebo yielded a higher headache rate (15 vs 8 %), it yielded similar (generally favorably low) rates of all-cause discontinuation (16 vs 16 %), adverse event discontinuation (4 vs 5 %), nausea (6 vs 4 %), ≥7 % weight gain (2 vs 5 %), anxiety (4 vs 3 %), insomnia (3 vs 2 %), sedation/somnolence (1 vs 1 %), and hypomania (0 vs <1 %). Conclusions: In this study, adjunctive armodafinil compared with adjunctive placebo in bipolar I depression did not separate in the primary efficacy outcome but demonstrated advantages for several secondary efficacy outcomes and was generally well tolerated. Additional research is warranted and necessary to better identify clinical predictors (e.g., atypical depressive symptoms, specific anti-manic/mood-stabilizing agents used) that would provide optimized, individualized therapeutics for bipolar depression. Trial registration: ClinicalTrials.gov: NCT01305408

Original languageEnglish (US)
Article number18
JournalInternational Journal of Bipolar Disorders
Volume3
Issue number1
DOIs
StatePublished - Dec 7 2015

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Drug Design
Bipolar Disorder
Placebos
Therapeutics
Depression
Excipients
Sleep Initiation and Maintenance Disorders
Double-Blind Method
Nausea
Weight Gain
Headache
armodafinil
Anxiety
Safety
Equipment and Supplies
Research

Keywords

  • Armodafinil
  • Bipolar I disorder
  • Major depressive episode

ASJC Scopus subject areas

  • Biological Psychiatry
  • Psychiatry and Mental health

Cite this

Randomized, placebo-controlled, adjunctive study of armodafinil for bipolar I depression : implications of novel drug design and heterogeneity of concurrent bipolar maintenance treatments. / Frye, Mark A; Amchin, Jess; Bauer, Michael; Adler, Caleb; Yang, Ronghua; Ketter, Terence A.

In: International Journal of Bipolar Disorders, Vol. 3, No. 1, 18, 07.12.2015.

Research output: Contribution to journalArticle

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abstract = "Background: Some, but not all, prior investigations suggest armodafinil may have utility as an adjunctive treatment in bipolar I depression. Methods: Multicenter, randomized, double-blind study in patients aged 18 to 65 years experiencing a depressive episode despite maintenance therapy for bipolar I disorder. Patients were randomized to receive adjunctive armodafinil 150 mg/day or adjunctive placebo for 8 weeks. Primary efficacy outcome was change from baseline in 30-Item Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30) total score at week 8. Safety and tolerability were monitored. Results: Of 656 patients screened, 399 were randomized, of whom 308 (77 {\%}) were taking a protocol-allowed mood stabilizer as monotherapy. The primary efficacy outcome did not reach statistical significance; however, several secondary efficacy outcomes demonstrated statistically significant advantages for adjunctive armodafinil (n = 197) over adjunctive placebo (n = 196), including Clinical Global Impression of Severity of Illness for depression (weeks 6, 8, and endpoint; all P < 0.05), Global Assessment of Functioning (weeks 4, 8, and endpoint; all P < 0.02), IDS-C30 remitter rates (week 8 and endpoint; both P < 0.02), and mean change from baseline in IDS-C30 total score at week 7 (P < 0.05). Adjunctive armodafinil and adjunctive placebo were generally well tolerated. Although adjunctive armodafinil compared with adjunctive placebo yielded a higher headache rate (15 vs 8 {\%}), it yielded similar (generally favorably low) rates of all-cause discontinuation (16 vs 16 {\%}), adverse event discontinuation (4 vs 5 {\%}), nausea (6 vs 4 {\%}), ≥7 {\%} weight gain (2 vs 5 {\%}), anxiety (4 vs 3 {\%}), insomnia (3 vs 2 {\%}), sedation/somnolence (1 vs 1 {\%}), and hypomania (0 vs <1 {\%}). Conclusions: In this study, adjunctive armodafinil compared with adjunctive placebo in bipolar I depression did not separate in the primary efficacy outcome but demonstrated advantages for several secondary efficacy outcomes and was generally well tolerated. Additional research is warranted and necessary to better identify clinical predictors (e.g., atypical depressive symptoms, specific anti-manic/mood-stabilizing agents used) that would provide optimized, individualized therapeutics for bipolar depression. Trial registration: ClinicalTrials.gov: NCT01305408",
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N2 - Background: Some, but not all, prior investigations suggest armodafinil may have utility as an adjunctive treatment in bipolar I depression. Methods: Multicenter, randomized, double-blind study in patients aged 18 to 65 years experiencing a depressive episode despite maintenance therapy for bipolar I disorder. Patients were randomized to receive adjunctive armodafinil 150 mg/day or adjunctive placebo for 8 weeks. Primary efficacy outcome was change from baseline in 30-Item Inventory of Depressive Symptomatology–Clinician-Rated (IDS-C30) total score at week 8. Safety and tolerability were monitored. Results: Of 656 patients screened, 399 were randomized, of whom 308 (77 %) were taking a protocol-allowed mood stabilizer as monotherapy. The primary efficacy outcome did not reach statistical significance; however, several secondary efficacy outcomes demonstrated statistically significant advantages for adjunctive armodafinil (n = 197) over adjunctive placebo (n = 196), including Clinical Global Impression of Severity of Illness for depression (weeks 6, 8, and endpoint; all P < 0.05), Global Assessment of Functioning (weeks 4, 8, and endpoint; all P < 0.02), IDS-C30 remitter rates (week 8 and endpoint; both P < 0.02), and mean change from baseline in IDS-C30 total score at week 7 (P < 0.05). Adjunctive armodafinil and adjunctive placebo were generally well tolerated. Although adjunctive armodafinil compared with adjunctive placebo yielded a higher headache rate (15 vs 8 %), it yielded similar (generally favorably low) rates of all-cause discontinuation (16 vs 16 %), adverse event discontinuation (4 vs 5 %), nausea (6 vs 4 %), ≥7 % weight gain (2 vs 5 %), anxiety (4 vs 3 %), insomnia (3 vs 2 %), sedation/somnolence (1 vs 1 %), and hypomania (0 vs <1 %). Conclusions: In this study, adjunctive armodafinil compared with adjunctive placebo in bipolar I depression did not separate in the primary efficacy outcome but demonstrated advantages for several secondary efficacy outcomes and was generally well tolerated. Additional research is warranted and necessary to better identify clinical predictors (e.g., atypical depressive symptoms, specific anti-manic/mood-stabilizing agents used) that would provide optimized, individualized therapeutics for bipolar depression. Trial registration: ClinicalTrials.gov: NCT01305408

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KW - Bipolar I disorder

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