Pathophysiology of Akathisia
Although there are many possible hypotheses for the pathophysiology of acute akathisia, none is completely satisfactory. So far the most attractive hypothesis is dopamine receptor blockade in the mesocortical and mesolimbic regions of the brain. It is unlikely that a single neurotransmitter hypothesis will explain all the complex features of the disorder, and the interaction of several neurotransmitters may be involved. There have been some recent imaging, genetic, and neurotransmitter depletion studies that have looked at the pathophysiology of akathisia. Striatal dopamine-2 (D2) receptor occupancy by antipsychotics has been implicated in the pathophysiology of EPSEs. In this regard, a recent study using single photon emission computed tomography (SPECT) and ligand iodobenzamide showed that bipolar patients receiving 5-45 mg/day of olanzapine for 2 weeks did not show any EPSEs at a D2 occupancy level of 28-80%, suggesting that, at clinically relevant doses, it is unlikely that bipolar patients would develop EPSEs.[46] In a recent study,[47] dopamine depletion using the administration of alphamethyl paratyrosine (AMPT) resulted in subjective changes in a group of patients with schizophrenia, including dysphoria, social withdrawal, and personal distress followed by akathisia, akinesia, and rigidity.
In a single case study,[48] olanzapine-induced akathisia was studied using 18F-fluoro-deoxyglucose-positron emission tomography (FDG-PET) during akathisia and after recovery. Results showed that akathisia was associated with reduced metabolic activity in the thalamus and cerebellum. More importantly, the metabolic activity recovered when akathisia disappeared after discontinuation of olanzapine. The role of the serotonin system was also explored in a study on the role of serotonin transporter promoter genotypes in acute antipsychotic efficacy and side effects in schizophrenia.[49] The authors used the SAS, BAS, and abnormal involuntary movement scale for assessment of EPSEs. There was no significant association between EPSEs and the serotonin transporter promoter gene polymorphism.
Curr Opin Psychiatry. 2009;22(3):293-299. © 2009 Lippincott Williams & Wilkins
Comments