Home Clinical Psychology & Psychotherapy Aripiprazole Discontinuation Does Not Significantly Increase Major Depressive Disorder Recurrence Risk, Reveals New Study

Aripiprazole Discontinuation Does Not Significantly Increase Major Depressive Disorder Recurrence Risk, Reveals New Study

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A recent study investigates the effects of discontinuing aripiprazole augmentation therapy (AATA) in patients with major depressive disorder (MDD) who have achieved remission. This 24-week, multicenter, placebo-controlled, double-blind, randomised trial offers new insights into the recurrence risk of MDD post-AATA discontinuation, highlighting the need for further research in this area. The findings were published in the journal Psychopharmacology.

Aripiprazole, an atypical antipsychotic, is commonly used as an augmentation therapy for MDD, particularly in cases resistant to traditional antidepressants. Previous studies have established its efficacy and safety in augmenting antidepressant treatment, resulting in increased remission and response rates. However, the long-term effects of continuing or discontinuing aripiprazole after achieving remission have not been thoroughly examined.

The study, conducted at two sites in Akita Prefecture, Japan, involved 23 adult participants aged 20 years and older who met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD. Participants had achieved full remission and maintained it for a period ranging from 20 weeks to two years after receiving AATA. Exclusion criteria included a history or current diagnosis of psychotic disorders, bipolar disorder, borderline personality disorder, eating disorders, or substance abuse disorders. The primary goal was to compare the recurrence risk of MDD between those who continued aripiprazole and those who were switched to a placebo.

The trial results indicated no significant difference in the recurrence of MDD between the aripiprazole and placebo groups. Specifically, 18.2% of participants in the aripiprazole group and 25.0% in the placebo group experienced recurrence. The Kaplan–Meier analysis, used to evaluate time-to-recurrence, showed no significant difference between the two groups. Furthermore, there were no notable differences in the severity of depressive symptoms or social functioning between the groups, as assessed by the 17-item Hamilton Depression Rating Scale (HAM-D17) and the Social and Occupational Functioning Assessment Scale (SOFAS).

In terms of safety, no participants developed extrapyramidal symptoms, akathisia, tardive dyskinesia, or dystonia during the study period. This is noteworthy, as these side effects are often associated with long-term antipsychotic use. The low dose and relatively short duration of aripiprazole treatment in this study may explain the absence of such adverse effects​.

Despite its contributions, the study had several limitations. Firstly, it was a small exploratory study with a limited sample size, which restricted its statistical power. Secondly, the participant pool was primarily older adults, a demographic at higher risk for MDD recurrence, thus not representative of the general population. Thirdly, the study’s 24-week duration precluded long-term evaluation of the effects of aripiprazole discontinuation. Fourthly, all participants had been in remission for at least 20 weeks, making it unclear whether the results apply to those in shorter remission periods. Finally, the study did not assess the cost-effectiveness of continuing AATA, an important consideration given the economic burden of long-term depression treatment.

The findings suggest that patients with MDD in remission after AATA do not face a significantly increased risk of recurrence upon discontinuing the therapy. However, the small sample size and other study limitations mean that definitive conclusions cannot be drawn. As such, there is a need for larger, more representative studies with longer follow-up periods to better understand the long-term effects of aripiprazole discontinuation in this patient population.

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