First approved for marketing by the FDA in 1991, transdermal fentanyl provides continuous delivery of the drug for about 3 days. After application of the patch, a depot of fentanyl forms in the upper layers of the skin. Serum concentrations of the drug increase gradually, reaching a peak (Cmax) in 24-72 hours. According to a pharmacokinetic model mentioned in the labeling, an increase in body temperature to 40°C (104°F) could increase fentanyl serum concentrations by 33%. Local application of heat near or on a fentanyl transdermal patch also increases systemic absorption; in one study, heating the patch during the first 4 hours after application increased maximum serum concentrations nearly three-fold. Unintentional increases in systemic fentanyl absorption caused by a heating pad, a warming blanket used during surgery and strenuous exertion have led to respiratory depression in 3 patients. No reports of clinical overdosage caused by fever have been published.

Second-generation drugs are less likely than first generation drugs to cause extrapyramidal symptoms, tardive dyskinesia and neuroleptic malignant syndrome, but more likely to cause weight gain and other metabolic abnormalities. Aripiprazole (Abilify) is least likely to prolong the QT interval, which is one of the mechanisms that could be responsible for the small increase in theabsolute risk of sudden death among patients who take antipsychotic drugs.

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