The Mechanism of Drug-induced Akathisia

Akathisia is a movement disorder character-
ized by an inner sense of unease, unrest, and dys-
phoria. It can result in an inability to stand, sit, or
lie still, and an intense urge to move around. It is
a common side effect of drugs, such as antipsy-
chotics and serotonin selective reuptake inhibi-
tors (SSRIs), but it also occurs spontaneously in
patients with Parkinson’s disease. Several lines of
evidence suggest that akathisia can be attributed
to low activity of dopaminergic projections from
the midbrain to the ventral striatum. However,
the exact pathophysiological mechanism of this
extrapyramidal symptom remains unclear. This
article describes a possible mechanism for drug-
induced akathisia based on the differential func-
tions of the core and shell portions of the nucleus
accumbens. These ideas arise from contemporary
concepts regarding the mechanisms of compul-
sion, impulsivity, and depression.