Measurement of the serotonin 1A receptor availability in patients with schizophrenia during treatment with the antipsychotic medication ziprasidone

The aim of this study was to compare 5-HT_1A availability in vivo in individuals with schizophrenia before and during treatment with the atypical antipsychotic ziprasidone. Six individuals with schizophrenia underwent two PET scans with [¹¹C]WAY 100635; the first while medication-free (baseline) and the second while taking the atypical antipsychotic ziprasidone (on-medication). Regional volumes of distribution (V _T, mL g⁻¹) were derived using a two-tissue compartment kinetic model. Outcome measures included binding potential relative to the plasma (BP _P, mL g⁻¹) and the binding potential relative to the nonspecific distribution volume (BP _ND, unitless). No significant differences were observed in regional BP _P or BP _ND with ziprasidone treatment. A significant correlation was noted between BP _P measured in the orbitofrontal cortex during the on-medication condition and degree of improvement in negative symptoms with treatment (r = 0.96, p = 0.004). Consistent with the published literature of changes in 5-HT_1A binding during treatment with 5-HT_1A receptor agonists, this study did not detect a significant reduction in 5-HT_1A binding with ziprasidone. The finding of a relationship between 5-HT_1A binding and the degree of improvement in negative symptoms provides further support for the role of the 5-HT_1A receptor in the pathophysiology and treatment of this symptom domain.