Objective: To review evidence on the risk of drug-induced movement disorders (DIMDs) with newer antipsychotic (AP) drugs.

Background: DIMDs, both acute/subacute “extrapyramidal symptoms” and chronic tardive syndromes, are common and associated with poor compliance and neurologic morbidity [1]. Within the last ten years, six novel antipsychotics (brexpiprazole, cariprazine, lurasidone, lumateperone, pimavanserin, olanzapine-samidorphan) and five novel formulations (long-acting injectable [LAI] risperidone, LAI aripiprazole, LAI paliperidone, transdermal asenapine, and inhaled loxapine) of antipsychotics have received FDA approval [2]. There has not been a comprehensive relative risk assessment of DIMDs of these novel medications to each other or to older second-generation antipsychotics.

Method: Primary research articles and review articles were obtained through PUBMED searches in February 2022 for generic drug names in combination with “extrapyramidal” and “tardive”. Studies that did not discuss DIMDs or tardive syndromes, were not available in the English language, or were not available through institutional subscription or open-access were excluded. We also reviewed the literature related to DIMDs in experimental drug targets for psychosis including trace amine-associated receptor 1 agonists, 5-HT_2A/sigma2R antagonists, and M1/M4 muscarinic receptor agonists.

Results: Of the novel APs, brexipiprazole and cariprazine showed increased rates of akathisia relative to other SGAs with comparable rates of other DIMDs and tardive syndromes. Lurasidone and olanzapine-samidorphan had comparable rates of these adverse effects while lumateperone and pimavanserin had significantly reduced rates. Except for LAI paliperidone which potentially has reduced risk of DIMDs, other LAI and non-oral formulations of antipsychotics have a similar risk profile to oral formulations.

Conclusion: Several novel APs, such as lumateperone and pimavanserin, show minimal risk of DIMDs and tardive syndromes. Compared to oral paliperidone, the LAI may decrease risk of DIMDs while LAI risperidone and aripiprazole have equal risk compared to oral formulations. Furthermore, new experimental drug targets that do not use dopamine receptor blockade show promise in reducing incidence of DIMDs.

References: 1. Caroff, S. N. & Campbell, E. C. Drug-Induced Extrapyramidal Syndromes: Implications for Contemporary Practice. Psychiatr. Clin. North Am. 39, 391–411 (2016).
2. Pahwa M, Sleem A, Elsayed OH, Good ME, El-Mallakh RS. New Antipsychotic Medications in the Last Decade. Curr Psychiatry Rep. 2021 Nov 29;23(12):87. doi: 10.1007/s11920-021-01298-w. PMID: 34843030.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-antipsychotics-and-risk-of-drug-induced-movement-disorders-and-tardive-syndromes/