All first-generation antipsychotic drugs are associated with adverse effects, such as sedation, dystonia and muscle stiffness, tremors, elevated prolactin levels, and weight gain. Akathisia (motor restlessness) is particularly unpleasant and is often associated with drug refusal and outpatient noncompliance. Cogwheeling, a shuffling gait, pacing, agitation, and excessive leg-swinging may be indications of acute extrapyramidal side effects. These acute side effects of antipsychotic agents are usually dose related. In addition to acute motor side effects, with long-term administration antipsychotic drugs may also cause tardive dyskinesia, an involuntary movement disorder most often characterized by puckering of the lips and tongue and/or writhing of the arms or legs. The incidence of tardive dyskinesia is about 5% per year of drug exposure among patients taking first-generation antipsychotic drugs (Kane et al. 1984). In about 2% of cases, tardive dyskinesia is severely disfiguring. In some patients, tardive dyskinesia persists indefinitely, even after the drug is discontinued. Because of the risk of tardive dyskinesia, patients receiving long-term maintenance therapy should be evaluated for abnormal involuntary movements at least every 6 months. Rating instruments such as the Abnormal Involuntary Movement Scale may be used (Table 20–2). Neuroleptic malignant syndrome, a rare but potentially fatal adverse effect, is characterized by rigidity, fever, autonomic instability, and elevated creatinine phosphokinase.