Clozapine-associated extrapyramidal reaction.

OBJECTIVE: To report a case of extrapyramidal reaction associated with a dosage increase of clozapine. CASE SUMMARY: A 44-year-old white man with a 20-year history of chronic paranoid schizophrenia was admitted to an inpatient psychiatric facility. His prior medications restarted on admission were clozapine 650 mg at bedtime, haloperidol 10 mg at bedtime, clonazepam 2 mg/d, and aspirin 325 mg/d. Two days after admission (hospital day 3), clozapine and clonazepam were discontinued, and he was prescribed haloperidol 5 mg every morning and 10 mg every evening. Stabilization occurred over the following 24 days, with progressively lower dosages of haloperidol and increasing dosages of clozapine. Haloperidol was discontinued on day 24. On day 47, the patient was agitated and making bizarre statements; thus, the morning dose of clozapine was increased by 50 mg (total 450 mg/d). On day 48 at 2200, a dystonic reaction was diagnosed; he received intramuscular diphenhydramine 50 mg, which caused the reaction to subside. At the time of the adverse reaction, he was prescribed clozapine 450 mg/d, vitamin E 400 IU three times daily, aspirin 325 mg/d, and acetaminophen, milk of magnesia, and Maalox as needed. DISCUSSION: Although the risk of extrapyramidal symptoms (EPS) is significantly lower with clozapine than with conventional agents, elevated clozapine blood concentrations have been reported to cause EPS; other reports have cited severe dystonias and dyskinesias on abrupt clozapine withdrawal. Considering the medications prescribed at the time and the discontinuation of haloperidol 24 days before the event, clozapine was the most likely cause of the extrapyramidal reaction. CONCLUSIONS: Regardless of anticipated safety associated with novel antipsychotics such as clozapine, reports of dystonic reactions must be taken into account and patients monitored appropriately.

Phenobarbital dosing and pharmacokinetics in a neonate receiving extracorporeal membrane oxygenation.

OBJECTIVE: To describe the dosing and pharmacokinetics of phenobarbital in a neonate receiving extracorporeal membrane oxygenation (ECMO). CASE SUMMARY: The treatment of a 2.6 kg, 38-week gestational age boy with congenital diaphragmatic hernia who developed seizures while receiving ECMO support is described. A loading dose of 20 mg/kg resulted in concentrations of 16.4 and 12.9 micrograms/mL at 3 and 24 hours, respectively. A maintenance dose of 5 mg/kg/d provided a peak concentration of 19.7 micrograms/mL and trough concentration of 16.7 micrograms/mL after four doses. The calculated volume of distribution was 1.2 L/kg and the estimated elimination half-life was 92 hours. Serum concentrations decreased after circuit changes unless the new circuit was redosed. DISCUSSION: The reported incidence of seizures in neonates while receiving ECMO support is 18%. Despite this frequency, there are no clinical reports describing anticonvulsant use in this population. This case demonstrates the use of standard phenobarbital doses to achieve low, but therapeutic, serum concentrations. Pharmacokinetic analysis revealed a volume of distribution slightly larger than expected in neonates and an elimination half-life similar to published values. Altering circulating blood volumes resulted in significant reductions in serum concentrations. CONCLUSIONS: Neonates on ECMO may have a larger volume of distribution than neonates not receiving ECMO and may require larger phenobarbital doses to achieve desired serum concentrations. This may result from the presence of large exogenous blood volumes for priming, as well as loss of drug during circuit changes, extraction by the circuit, or hemofiltration. Further work is needed to better define the pharmacokinetics and pharmacodynamics of phenobarbital in the neonatal ECMO population.

Goals: an approach to motivation and achievement.

This study tested a framework in which goals are proposed to be central determinants of achievement patterns. Learning goals, in which individuals seek to increase their competence, were predicted to promote challenge-seeking and a mastery-oriented response to failure regardless of perceived ability. Performance goals, in which individuals seek to gain favorable judgments of their competence or avoid negative judgments, were predicted to produce challenge-avoidance and learned helplessness when perceived ability was low and to promote certain forms of risk-avoidance even when perceived ability was high. Manipulations of relative goal value (learning vs. performance) and perceived ability (high vs. low) resulted in the predicted differences on measures of task choice, performance during difficulty, and spontaneous verbalizations during difficulty. Particularly striking was the way in which the performance goal-low perceived ability condition produced the same pattern of strategy deterioration, failure attribution, and negative affect found in naturally occurring learned helplessness. Implications for theories of motivation and achievement are discussed.