Early dose augmentation with aripiprazole useful in major depression
Aripiprazole augmentation early in treatment is useful for inducing response in major depressive disorder (MDD), although caution should be exercised when increasing the dose to >6 mg/day, a study has shown.
The study randomized 31 MDD patients with inadequate response to antidepressants to receive adjunctive treatment with aripiprazole at either a fixed low dose (3 mg/day; n=17) or at increasing dose (high-dose, from 3 to 12 mg/day; n=14) for 6 weeks.
The main outcome of Montgomery–Åsberg Depression Rating Scale (MADRS) score significantly improved from baseline to week 6 in both the low- and high-dose groups (p<0.001 for both). Changes in mean MADRS scores did not significantly differ between the two groups (p=0.061), but the high-dose group showed a much greater improvement at week 2 (p=0.015).
Plasma homovanillic acid (pHVA) levels during treatment remained unchanged, from 12.5 ng/ml at baseline to 12.6 ng/ml after 6 weeks (p=0.95). No significant difference in mean pHVA changes was seen between the low- and high-dose groups at both week 2 (p=0.51) and week 6 (p=0.58). However, between responders (n=11) and nonresponders (n=20), pHVA decreased significantly in the former at week 2 (p=0.044).
Six of 31 patients (19.4 percent) withdrew from the study due to side effects such as headache, drowsiness, akathisia, loss of motivation or tremor. Dropout rates were significantly higher in the high- vs low-dose group (five vs one), and these patients discontinued from week 2 to study conclusion (after increasing the dose to >6 mg/day).
According to researchers, the possible risk of increased side effects from increasing doses may have contributed to the relatively high dropout rate, suggesting that caution is needed when increasing the dose of aripiprazole to >6 mg/day.