Risk of Drug-induced Movement Disorders with Newer Antipsychotic Agents

Abstract

Background: The last decade has seen development of numerous novel antipsychotic drugs with unique mechanisms including long-acting formulations for clinical use. A comparative assessment of these new drugs with each other and previous antipsychotics have not been performed with regards to risk for drug-induced movement disorders (DIMD). Methods: Medline was searched from January 2010 to February 2022 for primary research articles and review articles in English using the search terms “extrapyramidal” and “tardive” with individual drug names of novel antipsychotics. Results: We identified articles describing the risk of DIMD with 6 novel antipsychotics, 4 novel formulations, and 3 experimental antipsychotics. Both short- and long-term data generally showed comparable to lower risk of DIMD with novel antipsychotics and recent long-acting formulations compared to previously marketed antipsychotics. Discussion: Several novel antipsychotics, particularly lumateperone and pimavanserin, show promise in being able to treat psychosis while reducing the risk of DIMD. Long-acting paliperidone may reduce risk of DIMD while other long-acting injectable formulations of SGA have similar risk of DIMD compared to oral formulations. New drug targets for treating psychosis without dopamine blockade also show promise.

Early Onset of Tardive Dyskinesia in an Antipsychotic-Naive Patient Treated With Low-Dose Cariprazine

“…Interestingly, in our case, there is a lack most of the risk factors, with the exception of the early appearance of akathisia. Although cariprazine has comparable rates of drug-induced movement disorders relative to previous SGAs, it may be more prone to causing akathisia, particularly early in treatment, relative to aripiprazole and risperidone 17 . Akathisia constitutes a risk factor for later development of TD; this seems to be relevant in our case, where our patient developed akathisia early in treatment along with an early onset of TD symptoms.…”

A Comprehensive Review of Secondary Movement Disorders

“…However, one of the significant side effects associated with these medications is the development of movement disorders, known as antipsychotic-induced movement disorders (AIMDs). These AIMDs can range from acute and reversible to chronic and irreversible conditions, posing significant challenges in the management of patients receiving antipsychotic treatment [24].…”

A new era in the diagnosis and treatment of tardive dyskinesia

“…69,77 The relative risk of long-acting injectable antipsychotics compared to oral agents is unclear but likely similar, with newer SGAs less likely than FGAs to cause TD in some but not all studies. [78][79][80][81] Studies of long-acting injectable agents have suggested that guaranteed continuous administration of antipsychotics may actually decrease the risk of TD compared with intermittent treatment resulting from "drug holidays," symptom-driven administration or patient nonadherence. [82][83][84][85] The effect of other prescription drugs or substance abuse on the risk of TD is less clear.…”

“…In addition, research and development of antipsychotics that target novel brain targets (trace amine-associated receptor 1 agonists, serotonin agonists and serotonin/opioid antagonists, muscarinic receptor agonists) that lack dopamine receptor affinity may offer promise as effective antipsychotics without movement disorder liability. 78 Meanwhile, VMAT2 inhibitors are likely to transform the treatment of TD and renew interest in TD research. 172 Although trials of VMAT2 inhibitors offer clear evidence of efficacy and tolerability in suppressing TD, their impact on real-world outcomes merits additional investigation.…”

“…There is a compelling need for education among practitioners about conservative use of antipsychotics, the risks of TD, and screening and monitoring policies and instruments. In addition, research and development of antipsychotics that target novel brain targets (trace amine-associated receptor 1 agonists, serotonin agonists and serotonin/opioid antagonists, muscarinic receptor agonists) that lack dopamine receptor affinity may offer promise as effective antipsychotics without movement disorder liability 78 …”