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

Berman RM, Thase ME, Trivedi MH, Hazel JA, Marler SV, McQuade RD, Carson W, Baker RA, Marcus RN - Neuropsychiatr Dis Treat (2011)

Bottom Line: 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%.Clinically significant weight gain was observed in about one-third of patients.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Global Clinical Research Bristol-Myers Squibb, Wallingford, CT, USA;

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 open-label 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.

No MeSH data available.


Related in: MedlinePlus

Time-course of fasting metabolic mean changes from baseline (observed case analysis).Notes: Mean (SE) baseline values: fasting total cholesterol (n = 773), 214.6 (1.5) mg/dL; fasting HDL cholesterol (n = 773), 57.8 (0.6) mg/dL; fasting LDL cholesterol (n = 773), 125.8 (1.3) mg/dL; fasting triglycerides (n = 773), 156.5 (3.9) mg/dL; fasting glucose (n = 769), 93.5 (0.6) mg/dL. Dashed line and arrows represents abnormal lipid values (NCEP-defined criteria) and glucose levels (ADA criteria). Laboratory evaluations were performed at weeks 6, 14, 32, 44, and 58 for aripiprazole rollover patients, and weeks 8, 26, 38, and 52 for placebo rollover/de novo patients. For patients who had received aripiprazole in the previous double-blind study (aripiprazole rollover patients), baseline refers to week 8 scores from double-blind treatment.Abbreviations: SE, standard error; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NCEP, National Cholesterol Education Program; ADA, American Diabetes Association.
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f3-ndt-7-303: Time-course of fasting metabolic mean changes from baseline (observed case analysis).Notes: Mean (SE) baseline values: fasting total cholesterol (n = 773), 214.6 (1.5) mg/dL; fasting HDL cholesterol (n = 773), 57.8 (0.6) mg/dL; fasting LDL cholesterol (n = 773), 125.8 (1.3) mg/dL; fasting triglycerides (n = 773), 156.5 (3.9) mg/dL; fasting glucose (n = 769), 93.5 (0.6) mg/dL. Dashed line and arrows represents abnormal lipid values (NCEP-defined criteria) and glucose levels (ADA criteria). Laboratory evaluations were performed at weeks 6, 14, 32, 44, and 58 for aripiprazole rollover patients, and weeks 8, 26, 38, and 52 for placebo rollover/de novo patients. For patients who had received aripiprazole in the previous double-blind study (aripiprazole rollover patients), baseline refers to week 8 scores from double-blind treatment.Abbreviations: SE, standard error; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NCEP, National Cholesterol Education Program; ADA, American Diabetes Association.

Mentions: Figure 3 shows the mean change in fasting metabolic parameters from adjunctive aripiprazole baseline, by treatment period, for patients who continued to receive treatment (observed case analysis). National Cholesterol Education Program (NCEP)-defined cut-offs (see Figure 3) show that, on average, LDL, HDL, and glucose levels remained within normal limits. Baseline levels of cholesterol were higher, but tended to decrease over the 52-week exposure to aripiprazole. Baseline triglyceride levels were also above the normal 150 mg/dL criterion and remained above baseline throughout the course of aripiprazole treatment. Overall, there were no clinically important findings in the mean changes from baseline in fasting cholesterol, HDL, LDL, triglycerides, or glucose. For adjunctive aripiprazole exposure >46 weeks, the median change (range) in fasting metabolic parameters from adjunctive aripiprazole baseline were as follows: fasting cholesterol (n = 264), −4.0 (−154.0 to 90.0) mg/dL; fasting HDL (n = 264), −5.0 (−85.0 to 24.0) mg/dL; fasting LDL (n = 264), 1.0 (−117.0 to 94.0) mg/dL; fasting triglycerides (n = 264), 8.0 (−385.0 to 354.0) mg/dL, and fasting glucose (n = 262), 2.5 (−128.0 to 151.0) mg/dL.


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

Berman RM, Thase ME, Trivedi MH, Hazel JA, Marler SV, McQuade RD, Carson W, Baker RA, Marcus RN - Neuropsychiatr Dis Treat (2011)

Time-course of fasting metabolic mean changes from baseline (observed case analysis).Notes: Mean (SE) baseline values: fasting total cholesterol (n = 773), 214.6 (1.5) mg/dL; fasting HDL cholesterol (n = 773), 57.8 (0.6) mg/dL; fasting LDL cholesterol (n = 773), 125.8 (1.3) mg/dL; fasting triglycerides (n = 773), 156.5 (3.9) mg/dL; fasting glucose (n = 769), 93.5 (0.6) mg/dL. Dashed line and arrows represents abnormal lipid values (NCEP-defined criteria) and glucose levels (ADA criteria). Laboratory evaluations were performed at weeks 6, 14, 32, 44, and 58 for aripiprazole rollover patients, and weeks 8, 26, 38, and 52 for placebo rollover/de novo patients. For patients who had received aripiprazole in the previous double-blind study (aripiprazole rollover patients), baseline refers to week 8 scores from double-blind treatment.Abbreviations: SE, standard error; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NCEP, National Cholesterol Education Program; ADA, American Diabetes Association.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3104689&req=5

f3-ndt-7-303: Time-course of fasting metabolic mean changes from baseline (observed case analysis).Notes: Mean (SE) baseline values: fasting total cholesterol (n = 773), 214.6 (1.5) mg/dL; fasting HDL cholesterol (n = 773), 57.8 (0.6) mg/dL; fasting LDL cholesterol (n = 773), 125.8 (1.3) mg/dL; fasting triglycerides (n = 773), 156.5 (3.9) mg/dL; fasting glucose (n = 769), 93.5 (0.6) mg/dL. Dashed line and arrows represents abnormal lipid values (NCEP-defined criteria) and glucose levels (ADA criteria). Laboratory evaluations were performed at weeks 6, 14, 32, 44, and 58 for aripiprazole rollover patients, and weeks 8, 26, 38, and 52 for placebo rollover/de novo patients. For patients who had received aripiprazole in the previous double-blind study (aripiprazole rollover patients), baseline refers to week 8 scores from double-blind treatment.Abbreviations: SE, standard error; HDL, high-density lipoprotein; LDL, low-density lipoprotein; NCEP, National Cholesterol Education Program; ADA, American Diabetes Association.
Mentions: Figure 3 shows the mean change in fasting metabolic parameters from adjunctive aripiprazole baseline, by treatment period, for patients who continued to receive treatment (observed case analysis). National Cholesterol Education Program (NCEP)-defined cut-offs (see Figure 3) show that, on average, LDL, HDL, and glucose levels remained within normal limits. Baseline levels of cholesterol were higher, but tended to decrease over the 52-week exposure to aripiprazole. Baseline triglyceride levels were also above the normal 150 mg/dL criterion and remained above baseline throughout the course of aripiprazole treatment. Overall, there were no clinically important findings in the mean changes from baseline in fasting cholesterol, HDL, LDL, triglycerides, or glucose. For adjunctive aripiprazole exposure >46 weeks, the median change (range) in fasting metabolic parameters from adjunctive aripiprazole baseline were as follows: fasting cholesterol (n = 264), −4.0 (−154.0 to 90.0) mg/dL; fasting HDL (n = 264), −5.0 (−85.0 to 24.0) mg/dL; fasting LDL (n = 264), 1.0 (−117.0 to 94.0) mg/dL; fasting triglycerides (n = 264), 8.0 (−385.0 to 354.0) mg/dL, and fasting glucose (n = 262), 2.5 (−128.0 to 151.0) mg/dL.

Bottom Line: 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%.Clinically significant weight gain was observed in about one-third of patients.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Global Clinical Research Bristol-Myers Squibb, Wallingford, CT, USA;

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 open-label 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.

No MeSH data available.


Related in: MedlinePlus