Understanding the Relationship Between Amphetamines and Psychosis

Use of amphetamine and methamphetamine (hereafter amphetamines) can cause acute psychotic symptoms and may also contribute to persistent psychotic conditions such as schizophrenia. Still, much remains uncertain about the mechanisms and nature of this relationship. In this paper, we review certain aspects of this relationship, with particular emphasis on papers published during the past 3 years. A review of the literature reveals that, in addition to the established knowledge that amphetamines can cause acute psychotic symptoms, more evidence has emerged that amphetamines may play a role also in the pathogenesis of schizophrenia. Determining causality for the amphetamine-psychosis association has, however, proven complicated. Reversed causality may be the case, as may be the notion that both use of amphetamines and psychosis reciprocally affect each other with deteriorating effects on both conditions. Clinical features like sensitization to amphetamines precipitating psychosis, that even amphetamine-induced psychosis may persist, and diagnostic transition from amphetamine-induced to primary psychosis suggest a continuous and mutual interaction between individual vulnerability, amphetamine exposure, and psychosis. The high transition rates also point to amphetamine-induced psychosis as a major risk factor for primary psychosis. Mortality rates are high for both psychosis and use of amphetamines, and we lack high-quality treatment guidelines to apply when these two conditions occur together. Amphetamine-induced psychosis may be more affiliated with primary psychosis than previously assumed. Some clinical implications are suggested.