Antipsychotic-Induced Neurological Adverse Drug Reactions: Frequency, Hypotheses, and Management (Review)

INTRODUCTION. The widespread use of antipsychotics (APs) makes the issue of antipsychotic-induced neurological adverse drug reactions clinically significant, as these reactions can limit the effectiveness of therapy for schi­zophrenia spectrum disorders and impair patients’ quality of life.

AIM. To critically evaluate current evidence on the frequency, underlying hypotheses, and strategies for the prevention and management of antipsychotic-induced neurological adverse drug reactions to optimize the treatment of schizophrenia spectrum disorders.

DISCUSSION. A review of the scientific literature was conducted using the PubMed, eLIBRARY.RU, Google Scholar, Cochrane Library, and Lens.org databases for the period 2020–2025. The frequency of neurological adverse drug reactions was found to vary among patients taking first-generation (AP1s), second-generation (AP2s), and third-generation (AP3s) antipsychotics. AP1s are characterized by a high incidence of acute extrapyramidal symptoms, including akathisia (14–35%), parkinsonism (18.5–51.3%), acute dystonia (1.4–60%), and hyperprolactinemia (40–70%). A key advantage of AP2s and AP3s is a significantly reduced risk of extrapyramidal syndrome, although the frequency of tardive dyskinesia and acute akathisia remains comparable to that observed with AP1s. Due to their affinity for cholinergic receptors, AP2s and AP3s may exert a greater negative impact on higher cortical functions compared to AP1s, potentially contributing to cognitive impairment.

CONCLUSIONS. Research from the last decade indicates a trend toward a changing profile of antipsychotic-induced neurological adverse reactions, coinciding with the increasingly widespread use of AP2s and AP3s in clinical psychiatry. A personalized approach to the choice of AP and its dose, including assessment of anticholinergic burden, therapeutic drug monitoring, and pharmacogenetic testing, can help achieve an optimal balance between the effectiveness and safety of psychopharmacotherapy.

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