Lack of Enhanced Response to Repeated d-Amphetamine Challenge in First-Episode Psychosis: Implications for a Sensitization Model of Psychosis in Humans

Behavioral sensitization is the process whereby intermittent stimulant exposure produces a time-dependent, enduring, and progressively more robust behavioral response. This process serves as a model for the development of psychosis, but has been little studied in humans. The authors report results from a double-blind, placebo-controlled study of repeated d-amphetamine challenges in 13 patients with first-episode manic or schizophrenic psychosis. Each patient received two daily doses of d-amphetamine (0.25 mg/kg) separated by 48 hours that alternated with two daily doses of matched placebo. Symptoms (activity/energy level, mood, rate and amount of speech, and severity of psychosis) and eye-blink rates were measured hourly for 5 hours following drug administration. In contrast to results from previous work in normal volunteers, none of the measures demonstrated the progressive increase following the second amphetamine dose as compared to the first dose that characterizes sensitization. These results suggest that patients with psychosis are already maximally sensitized, so cannot exhibit progressive behavioral enhancement following repeated stimulant challenges, or that patients with psychosis do not sensitize.