Biological Perspectives

Abstract

He's gone country Everybody's gone country Yeah we've gone country The whole world's gone country --Alan Jackson Psychotropic drugs are in. Even psychiatric nurses who once considered psychotropic drugs a necessary evil or a treatment of last resort, now embrace the inevitability of the times--the fusion of public expectations, third-party considerations, and time constraints. As a result, psychotropic medications have become firstline options in treatment. However, several serious and potentially fatal side effects are related to these agents--for example, neuroleptic malignant syndrome, serotonin syndrome, and agranulocytosis. All these adverse responses were discovered the fact: that is, these effects were not anticipated but were described after patients had developed symptoms or had died. With careful assessments demanded by unacceptable levels of morbidity and mortality, both incidence and death rates have dropped significantly in recent years. Rather than risk allowing these catastrophic consequences to drift to the periphery of practice, we attempt in the following pages to bring the discussions up to date. Neuroleptic Malignant Syndrome Neuroleptic malignant syndrome (NMS) is a potentially fatal reaction to dopamine blockade caused by antipsychotic and other medications. The majority of these medications are prescribed in the treatment of schizophrenia and work by antagonizing dopamine D2 receptors (Keltner & McIntyre, 1985). Although uncommon, NMS may be fatal if left untreated. Estimates of the incidence of NMS range from 0.5% to 2.4%, and the mortality rate may be as high as 20% in those who are not treated (Reeves, Mack, & Torres, 2001). Persing (1994) identified four cardinal symptoms of NMS: hyperthermia, muscle rigidity, mental status changes, and autonomic instability. NMS most often occurs with high potency antipsychotics, and was first described during clinical trials with haloperidol in 1960 (Reeves, Torres, Liberto, & Hart, 2002). Although haloperidol has been most often implicated, cases also are reported with atypical antipsychotic and other dopamine receptor-blocking medications (Beauchemin, Millaud, & Nguyen, 2002; Harradine, Williams, & Doherty, 2001; Philibert, Adam, Frank, & Carney-Doebbeling, 2001; Solomons, 2002). Ninety-six percent of NMS cases occur within the first 30 days of treatment (Persing), with a duration of 5 to 10 days after antipsychotic medications are discontinued (Lappa et al., 2002). Dopamine and NMS. Dopamine is a catecholamine. It has as its immediate precursor levodopa and is itself a precursor to norepinephrine. Dopamine is synthesized from the amino acid tyrosine, which crosses the blood brain barrier and is converted to levodopa in dopaminergic and noradrenergic neurons. Dopamine's metabolic pathway, then, may be summarized as: tyrosine [right arrow] levodopa [right arrow] dopamine [right arrow] norepinephrine (Keltner, Hogan, & Guy, 2001). Pathophysiology of NMS. Central nervous system dopamine is localized in four specific pathways. Altered functioning in two of these pathways is thought to induce the positive and negative symptoms of schizophrenia. Treatment strategies aimed at manipulating dopamine affect all four tracts. Chemical manipulation of three of these pathways may contribute to NMS (Table 1). Some of these symptoms of NMS are interrelated. For example, high temperatures may develop and can be exacerbated by massive muscle contraction and hypermetabolism (Lappa et al., 2002). Rigidity also may cause rhabdomyolysis, which can lead to acute renal failure when kidneys are flooded with myoglobin. Severity is assessed by measurement of creatine phosphokinase (CPK). Renal failure is the most common cause of death in NMS (Persing, 1994). Mental status changes can be an early sign of NMS and may progress to coma. Changes in mental status may be characterized by delirium, catatonia, and agitation. …