Second-Generation Antipsychotics and Extrapyramidal Adverse Effects

Abstract

Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability.

Pharmacogenetic-based risk assessment of antipsychotic-induced extrapyramidal symptoms

“…Таким образом, антипсихотики второго поколения не вполне оправдали ожидания клиницистов относительно их безопасности, и осложнения психотропной терапии экстрапирамидного спектра остаются клинически важ-ными в эпоху их применения [24].…”

Extrapyramidal Symptoms in Patients Treated with Antipsychotic Drugs

“…Schizophrenic patients are treated with Second-Generation Antipsychotic Drugs (SGAs) such as risperidone, olanzapine, quetiapine and aripiprazole and, in some cases, with First-Generation Antipsychotic Drugs (FGAs) such as haloperidol [3]. Adverse effects of the FGAs and to a lesser extent of the SGAs are Extrapyramidal Symptoms (EPS), for example Parkinsonism, dystonia, dyskinesia or oculogyric crises [4]. These adverse effects are due to the blockade of D2 dopaminergic receptors in the extrapyramidal system.…”

“…These adverse effects are due to the blockade of D2 dopaminergic receptors in the extrapyramidal system. It has been reported that recent developed antipsychotic drugs exert a mechanism of action different from the blockade of the D2 receptor and cause less often EPS [4].…”

Electrophysiological evidence showing muscarinic agonist–antagonist activities of N-desmethylclozapine using hippocampal excitatory and inhibitory neurons

“…Clozapine improves positive and negative symptoms, while inducing minimal extrapyramidal side effects (Divac et al, 2014). Clozapine and its predominant active metabolite, N-desmethylclozapine (NDMC), have complex pharmacological profiles, and interact with a wide range of neurotransmitter receptors including dopamine, serotonin, norepinephrine, histamine and acetylcholine receptors (Correll, 2010;Lameh et al, 2007;Mendoza and Lindenmayer, 2009;Weiner et al, 2004).…”