Long-term safety and tolerability of open-label aripiprazole augmentation of antidepressant therapy in major depressive disorder

Robert M. Berman, Michael E. Thase, Madhukar H. Trivedi, James A. Hazel, Sabrina Vogel Marler, Robert D. McQuade, William Carson, Ross A. Baker, Ronald N. Marcus

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background: Effective management of major depressive disorder often includes the long-term use of multiple medications, and the longer-term utility and safety of adjunctive aripiprazole has not been evaluated in a controlled setting. Patients and methods: Patients (n = 706) completing one of two 14-week double-blind studies of aripiprazole augmentation, as well as de novo patients (n = 296) nonresponsive to current antidepressant therapy, were enrolled in this open-label study. Patients received openlabel aripiprazole for up to 52 weeks. Results: Open-label treatment was completed by 323 patients (32.2%). At endpoint (n = 987), the mean dose of aripiprazole was 10.1 mg/day. Common (>15% of patients) spontaneously reported adverse events were akathisia (26.2%), fatigue (18.0%), and weight gain (17.1%). The incidence of serious adverse events was 4.0%. Four spontaneous reports of possible tardive dyskinesia were submitted (0.4%); all resolved within 45 days of drug discontinuation. Mean weight change was 4.4 kg; 36.6% experienced ≥7% increase in weight from baseline (observed case analysis, n = 303). No clinically relevant changes in other metabolic parameters were seen. At the end of open-label treatment, 221 patients (69.7%) had a Clinical Global Impression- Severity of Illness score of 1 (not at all ill) or 2 (borderline ill). Conclusion: Long-term adjunctive aripiprazole therapy was well tolerated with an acceptable long-term safety and tolerability profile in patients with major depressive disorder who had not responded to treatment with one or more antidepressant therapies. Clinically significant weight gain was observed in about one-third of patients. Overall, the adverse event profile was consistent with that reported in the short-term trials and readily managed clinically.

Original languageEnglish (US)
Pages (from-to)303-312
Number of pages10
JournalNeuropsychiatric Disease and Treatment
Volume7
Issue number1
DOIs
StatePublished - 2011

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Major Depressive Disorder
Antidepressive Agents
Safety
Therapeutics
Weight Gain
Aripiprazole
Weights and Measures
Psychomotor Agitation
Double-Blind Method
Fatigue
Incidence

Keywords

  • Adjunctive aripiprazole
  • Antidepressant therapy
  • Longterm safety and tolerability
  • Major depressive disorder

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Long-term safety and tolerability of open-label aripiprazole augmentation of antidepressant therapy in major depressive disorder. / Berman, Robert M.; Thase, Michael E.; Trivedi, Madhukar H.; Hazel, James A.; Marler, Sabrina Vogel; McQuade, Robert D.; Carson, William; Baker, Ross A.; Marcus, Ronald N.

In: Neuropsychiatric Disease and Treatment, Vol. 7, No. 1, 2011, p. 303-312.

Research output: Contribution to journalArticle

Berman, Robert M. ; Thase, Michael E. ; Trivedi, Madhukar H. ; Hazel, James A. ; Marler, Sabrina Vogel ; McQuade, Robert D. ; Carson, William ; Baker, Ross A. ; Marcus, Ronald N. / Long-term safety and tolerability of open-label aripiprazole augmentation of antidepressant therapy in major depressive disorder. In: Neuropsychiatric Disease and Treatment. 2011 ; Vol. 7, No. 1. pp. 303-312.
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abstract = "Background: Effective management of major depressive disorder often includes the long-term use of multiple medications, and the longer-term utility and safety of adjunctive aripiprazole has not been evaluated in a controlled setting. Patients and methods: Patients (n = 706) completing one of two 14-week double-blind studies of aripiprazole augmentation, as well as de novo patients (n = 296) nonresponsive to current antidepressant therapy, were enrolled in this open-label study. Patients received openlabel aripiprazole for up to 52 weeks. Results: Open-label treatment was completed by 323 patients (32.2{\%}). At endpoint (n = 987), the mean dose of aripiprazole was 10.1 mg/day. Common (>15{\%} of patients) spontaneously reported adverse events were akathisia (26.2{\%}), fatigue (18.0{\%}), and weight gain (17.1{\%}). The incidence of serious adverse events was 4.0{\%}. Four spontaneous reports of possible tardive dyskinesia were submitted (0.4{\%}); all resolved within 45 days of drug discontinuation. Mean weight change was 4.4 kg; 36.6{\%} experienced ≥7{\%} increase in weight from baseline (observed case analysis, n = 303). No clinically relevant changes in other metabolic parameters were seen. At the end of open-label treatment, 221 patients (69.7{\%}) had a Clinical Global Impression- Severity of Illness score of 1 (not at all ill) or 2 (borderline ill). Conclusion: Long-term adjunctive aripiprazole therapy was well tolerated with an acceptable long-term safety and tolerability profile in patients with major depressive disorder who had not responded to treatment with one or more antidepressant therapies. Clinically significant weight gain was observed in about one-third of patients. Overall, the adverse event profile was consistent with that reported in the short-term trials and readily managed clinically.",
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AU - Berman, Robert M.

AU - Thase, Michael E.

AU - Trivedi, Madhukar H.

AU - Hazel, James A.

AU - Marler, Sabrina Vogel

AU - McQuade, Robert D.

AU - Carson, William

AU - Baker, Ross A.

AU - Marcus, Ronald N.

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N2 - Background: Effective management of major depressive disorder often includes the long-term use of multiple medications, and the longer-term utility and safety of adjunctive aripiprazole has not been evaluated in a controlled setting. Patients and methods: Patients (n = 706) completing one of two 14-week double-blind studies of aripiprazole augmentation, as well as de novo patients (n = 296) nonresponsive to current antidepressant therapy, were enrolled in this open-label study. Patients received openlabel aripiprazole for up to 52 weeks. Results: Open-label treatment was completed by 323 patients (32.2%). At endpoint (n = 987), the mean dose of aripiprazole was 10.1 mg/day. Common (>15% of patients) spontaneously reported adverse events were akathisia (26.2%), fatigue (18.0%), and weight gain (17.1%). The incidence of serious adverse events was 4.0%. Four spontaneous reports of possible tardive dyskinesia were submitted (0.4%); all resolved within 45 days of drug discontinuation. Mean weight change was 4.4 kg; 36.6% experienced ≥7% increase in weight from baseline (observed case analysis, n = 303). No clinically relevant changes in other metabolic parameters were seen. At the end of open-label treatment, 221 patients (69.7%) had a Clinical Global Impression- Severity of Illness score of 1 (not at all ill) or 2 (borderline ill). Conclusion: Long-term adjunctive aripiprazole therapy was well tolerated with an acceptable long-term safety and tolerability profile in patients with major depressive disorder who had not responded to treatment with one or more antidepressant therapies. Clinically significant weight gain was observed in about one-third of patients. Overall, the adverse event profile was consistent with that reported in the short-term trials and readily managed clinically.

AB - Background: Effective management of major depressive disorder often includes the long-term use of multiple medications, and the longer-term utility and safety of adjunctive aripiprazole has not been evaluated in a controlled setting. Patients and methods: Patients (n = 706) completing one of two 14-week double-blind studies of aripiprazole augmentation, as well as de novo patients (n = 296) nonresponsive to current antidepressant therapy, were enrolled in this open-label study. Patients received openlabel aripiprazole for up to 52 weeks. Results: Open-label treatment was completed by 323 patients (32.2%). At endpoint (n = 987), the mean dose of aripiprazole was 10.1 mg/day. Common (>15% of patients) spontaneously reported adverse events were akathisia (26.2%), fatigue (18.0%), and weight gain (17.1%). The incidence of serious adverse events was 4.0%. Four spontaneous reports of possible tardive dyskinesia were submitted (0.4%); all resolved within 45 days of drug discontinuation. Mean weight change was 4.4 kg; 36.6% experienced ≥7% increase in weight from baseline (observed case analysis, n = 303). No clinically relevant changes in other metabolic parameters were seen. At the end of open-label treatment, 221 patients (69.7%) had a Clinical Global Impression- Severity of Illness score of 1 (not at all ill) or 2 (borderline ill). Conclusion: Long-term adjunctive aripiprazole therapy was well tolerated with an acceptable long-term safety and tolerability profile in patients with major depressive disorder who had not responded to treatment with one or more antidepressant therapies. Clinically significant weight gain was observed in about one-third of patients. Overall, the adverse event profile was consistent with that reported in the short-term trials and readily managed clinically.

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