Metabolic assessment of aripiprazole as adjunctive therapy in major depressive disorder: a pooled analysis of 2 studies.
In 2 identical multicenter, double-blind, placebo-controlled trials, an 8-week prospective treatment phase to ensure inadequate response to standard antidepressants was followed with 6 weeks of aripiprazole (2-20 mg/d) or placebo, plus a standard antidepressant. This pooled analysis involving 737 patients across the 2 studies evaluated the metabolic effects of adjunctive aripiprazole in patients with major depressive disorder. Outcomes included mean change from end of prospective treatment phase to endpoint in body weight, waist circumference, fasting levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides (TG), fasting plasma glucose, and glycosylated hemoglobin (hemoglobin A1C). Logistic regression determined whether baseline variables were associated with weight gain or whether weight change was associated with clinical outcome. Statistically significant increases occurred in mean body weight (adjunctive aripiprazole, +1.73 kg, vs adjunctive placebo, +0.38 kg; P < 0.001). Significantly more subjects receiving adjunctive aripiprazole had clinically relevant (> or = 7%) weight gain versus placebo (5.2% vs 0.6%; P < 0.001). More patients treated with adjunctive aripiprazole shifted body mass index category group from normal to overweight and from overweight to obese than those treated with adjunctive placebo. Body mass index, sex, age, Montgomery-Asberg Depression Rating Scale score, fasting TG, fasting glucose, and standard antidepressants were not clinically meaningful predictors of weight gain with adjunctive aripiprazole, and change in weight had no correlation with clinical outcome. Adjunctive aripiprazole produced no significant changes versus placebo in mean waist circumference, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, TG, fasting plasma glucose, or hemoglobin A1C. Also, there was no apparent change in the incidence of National Cholesterol Education Program-defined abnormal metabolic measures after treatment with aripiprazole.
Fava
Maurizio
M
Depression Clinical and Research Program, Massachusetts General Hospital, Boston, MA 02114-2696, USA. mfava@partners.org
Wisniewski
Stephen R
SR
Thase
Michael E
ME
Baker
Ross A
RA
Tran
Quynh-Van
QV
Pikalov
Andrei
A
Yang
Huyuan
H
Marcus
Ronald N
RN
Berman
Robert M
RM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000009:adverse effects*; D000068180:Aripiprazole; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects; D015992:Body Mass Index; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D016015:Logistic Models; D008297:Male; D008659:Metabolic Diseases / Q000097:blood / Q000139:chemically induced*; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009765:Obesity / Q000097:blood / Q000139:chemically induced*; D010879:Piperazines / Q000009:adverse effects*; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D015363:Quinolones / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D055105:Waist Circumference; D015430:Weight Gain; D055815:Young Adult
D000928:Antidepressive Agents; D000068180:Aripiprazole; D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D008055:Lipids; D010879:Piperazines; D015363:Quinolones; C517652:hemoglobin A1c protein, human