The pharmacokinetics of standard antidepressants with aripiprazole as adjunctive therapy: studies in healthy subjects and in patients with major depressive disorder.
Possible effects of the atypical antipsychotic aripiprazole on the pharmacokinetics of standard antidepressant therapies (ADTs) were assessed in two open-label, non-randomised studies in healthy subjects (Studies 1 and 2) and two placebo-controlled studies in patients with major depressive disorder (MDD) (Studies 3 and 4). Healthy subjects received venlafaxine 75 mg/day (Study 1; N = 38) or escitalopram 10 mg/ day (Study 2; N = 25) with the addition of aripiprazole 10-20 mg/day (10 mg/day fixed dose in Study 2) for 14 days. Patients with MDD (N = 498; Studies 3 and 4) received escitalopram (10-20 mg/day), fluoxetine (20-40 mg/day), paroxetine controlled-release (37.5-50 mg/day), sertraline (100-150 mg/day) or venlafaxine extended-release (150-225 mg/day) for 8 weeks plus placebo. Incomplete responders were randomised (1:1) to placebo or adjunctive aripiprazole 2-20 mg/day. Blood samples were collected for pharmacokinetic analysis of ADTs. Plasma concentration-time data from Studies 3 and 4 were combined for statistical analysis. In healthy subjects, point estimates [90% CI] for the ratios of geometric means of C( max) (venlafaxine 1.148 [1.083-1.217]; escitalopram 1.04 [0.99-1.09]) and AUC(TAU) (venlafaxine 1.183 [1.130-1.238]; escitalopram 1.07 [1.04-1.11]) indicated no meaningful increase in ADT exposure in the presence of aripiprazole. In patients, point estimates for mean plasma concentration ratios indicated no substantial effect of aripiprazole on any ADT escitalopram 0.970 [0.911-1.033], fluoxetine 1.177 [1.049-1.321], paroxetine 0.730 [0.598-0.892], sertraline 0.958 [0.887-1.035] or venlafaxine 0.966 [0.887-1.051]. Aripiprazole had no meaningful effects on the pharmacokinetics of standard ADTs in either healthy subjects or patients with MDD.
Boulton
D W
DW
Bristol-Myers Squibb, Princeton, NJ 08543, USA. david.boulton@bms.com
Balch
A H
AH
Royzman
K
K
Patel
C G
CG
Berman
R M
RM
Mallikaarjun
S
S
Reeves
R A
RA
D000328:Adult; D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000068180:Aripiprazole; D015283:Citalopram / Q000493:pharmacokinetics; D003511:Cyclohexanols / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005473:Fluoxetine / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015363:Quinolones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D020280:Sertraline / Q000493:pharmacokinetics; D016896:Treatment Outcome; D014481:United States; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003511:Cyclohexanols; D003692:Delayed-Action Preparations; D010879:Piperazines; D015363:Quinolones; D005473:Fluoxetine; D015283:Citalopram; D000069470:Venlafaxine Hydrochloride; D000068180:Aripiprazole; D020280:Sertraline