Sedating, Activating Effects of Second-Generation Antipsychotics Compared

All first-line, oral, second-generation antipsychotics available in the U.S. were assessed in the study
All first-line, oral, second-generation antipsychotics available in the U.S. were assessed in the study

Second-generation antipsychotic agents, used for the treatment of schizophrenia and major depressive disorder (MDD), are associated with varying degrees of activating or sedating adverse effects (AEs), with some agents having both properties. These are the findings of a new quantitative study published in the Journal of Clinical Pharmacology. 

Researchers analyzed product labeling (and the studies that contributed to the labeling) for antipsychotic-associated activating (akathisia, restlessness, agitation, anxiety, insomnia) and sedating (somnolence, sedation, fatigue) AEs in the acute treatment of schizophrenia and for adjunctive use in major depressive disorder. All first-line, oral, second-generation antipsychotics available in the U.S. were assessed. 

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Heterogeneity with regards to activation or sedation was found among the different antipsychotics. Among agents indicated for schizophrenia treatment, lurasidone and cariprazine were found to be predominately activating, while olanzapine, quetiapine (both immediate and extended-release), ziprasidone, asenapine, and iloperidone were predominately sedating. Risperidone and aripiprazole were similarly activating and sedating, while paliperidone and brexipiprazole were found to be neither activating nor sedating. Similar findings were seen with agents indicated for the treatment of MDD.

These adverse effects can be a major obstacle to treatment, therefore knowing the differences in tolerability profiles among these agents may help with selecting optimal therapy. “Despite the availability of numerous antipsychotics, after appraising patient characteristics at the time of treatment selection, physicians may quickly run out of tolerable treatment options,"the authors concluded.

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