Extrapyramidal Side Effects of Antipsychotic Treatment: Scope of Problem and Impact on Outcome

Abstract

Previously, clinicians worked with antipsychotic drugs (conventional or typical) that almost invariably caused extrapyramidal symptoms (EPS) at clinically effective doses. This led to the false impression that all antipsychotics were the same, and that EPS were an unavoidable consequence of effective antipsychotic therapy. EPS adversely impact several aspects of antipsychotic efficacy and tolerability, thereby worsening outcome of afflicted individuals. EPS reduce beneficial effects of antipsychotic treatment on the negative, cognitive, and mood symptom domains, while increasing the risk of tardive dyskinesia and reducing compliance. By definition, the newer generation of "atypical" antipsychotic agents are significantly better than conventional agents with regard to EPS (i.e., they are clinically effective at doses at which they do not cause EPS). Pharmacologically, this difference is expressed in the greater degree of separation between respective dose response curves for antipsychotic and EPS effects observed for "atypical" in contrast to conventional agents. Clinically, this EPS advantage of atypical antipsychotics translates into several important benefits, including better negative symptom efficacy, less dysphoria, less impaired cognition, a lower risk of TD, and better overall outcome.

Progressive ratio performance following challenge with antipsychotics, amphetamine, or NMDA antagonists in adult rats treated perinatally with phencyclidine

“…The well-documented motor effects of typical antipsychotics (e.g. Tandon and Jibson 2002) most likely contribute to these reductions, as well as to the observed reductions in response rates. Given that haloperidol-induced breakpoint decreases were observed in the present study in all rats that responded and at a dose (0.1 mg/kg) that did not significantly affect response rates, however, it is likely that a decrease in incentive motivation also played a role in this effect.…”

A Controlled, Evidence-Based Trial of Paliperidone Palmitate, A Long-Acting Injectable Antipsychotic, in Schizophrenia

“…These agents are generally viewed as having efficacy at least equivalent to that of older neuroleptics, with a lower risk for extrapyramidal symptoms (EPSs) and associated anhedonia and apathy, impaired cognition, and dysphoria (Lieberman et al, 2005;Tandon and Jibson, 2002). Although considered a significant advancement over older drugs, atypical antipsychotics still have limited efficacy in many patients (Stroup et al, 2006), particularly with respect to negative and cognitive symptoms.…”

Safety profiles of atypical antipsychotics in the elderly

“…It is not unusual for intolerability to play a major role in a physician's decision to discontinue a conventional antipsychotic, or to interfere with a patient's adherence to his or her prescribed treatment. In contrast, atypical antipsychotics as a class are generally better tolerated, with reduced occurrence of the aforementioned side effects, particularly with regard to EPS [1].…”