Differentiated strategies for antidepressant augmentation: focus on aripiprazole

Unipolar depression is highly prevalent in the population and has a significant impact on quality of life and somatic health. Despite the high efficacy of antidepressants, a substantial proportion of patients demonstrate an incomplete response to first-line therapy. One of the most evidence-based augmentation strategies is the addition of atypical antipsychotics. This review examines the pharmacological properties, efficacy, and tolerability of aripiprazole compared with quetiapine in unipolar depression. Partial agonism at D2 receptors and activity at serotonin receptors make aripiprazole particularly effective not only in anhedonia, apathy, reduced motivation, and cognitive impairment, but also in comorbid obsessive-compulsive and hyperkinetic disorders. Quetiapine, by contrast, may be preferable when anxiety and sleep disturbances predominate. When selecting a drug, it is essential to consider differences in adverse event profiles, including cardiometabolic effects, akathisia, weight gain, and the risk of restless legs syndrome. A differentiated choice of antipsychotic based on the clinical structure of depression allows optimization of the augmentation strategy and increases the likelihood of therapeutic response.

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Publication Details

Journal
Neurology neuropsychiatry Psychosomatics
Published
2026-10-30
DOI
https://doi.org/10.14412/2074-2711-2026-5-156-161
Primary Topic
Treatment of Major Depression
Type
article
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article

Differentiated strategies for antidepressant augmentation: focus on aripiprazole

Yu. V. Dolgopolova, D. S. Petelin, E. I. Konovalov
Neurology neuropsychiatry Psychosomatics
Treatment of Major Depression
article

Differentiated strategies for antidepressant augmentation: focus on aripiprazole

Yu. V. Dolgopolova, D. S. Petelin, E. I. Konovalov
article en

Abstract

Unipolar depression is highly prevalent in the population and has a significant impact on quality of life and somatic health. Despite the high efficacy of antidepressants, a substantial proportion of patients demonstrate an incomplete response to first-line therapy. One of the most evidence-based augmentation strategies is the addition of atypical antipsychotics. This review examines the pharmacological properties, efficacy, and tolerability of aripiprazole compared with quetiapine in unipolar depression. Partial agonism at D2 receptors and activity at serotonin receptors make aripiprazole particularly effective not only in anhedonia, apathy, reduced motivation, and cognitive impairment, but also in comorbid obsessive-compulsive and hyperkinetic disorders. Quetiapine, by contrast, may be preferable when anxiety and sleep disturbances predominate. When selecting a drug, it is essential to consider differences in adverse event profiles, including cardiometabolic effects, akathisia, weight gain, and the risk of restless legs syndrome. A differentiated choice of antipsychotic based on the clinical structure of depression allows optimization of the augmentation strategy and increases the likelihood of therapeutic response.

Neurology neuropsychiatry PsychosomaticsVol. 18(5)
Sechenov University (RU)
Good health and well-being
Openalex Percentile: Top 13%
Treatment of Major Depression
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