P.2.024 Clozapine efficacy on suicidal behavior across two main psychiatric disorders

Abstract

[123I]Iodobenzamide (IBZM) is an iodine-labeled dopamine receptor ligand and can be used to visualize brain D2 receptors in humans with single photon emission computerized tomography (SPECT). The ratio of striatal IBZM uptake to uptake in frontal cortex (ST/FC ratio) represents a semiquantitative measure of D2 receptor binding in the striatum. Our study sample included six patients treated with haloperidol (3.0–8.0 mg/day orally; one patient with an average of 0.9 mg/day intramuscularly), five patients with benperidol (9.0–15.0 mg/day orally) and nine patients treated with clozapine (200.0–600.0 mg/day orally). Typical neuroleptics (TNs) and atypical neuroleptics (ANs) were significantly different in their ST/FC ratios. The ST/FC ratios indicated that patients treated with benperidol exhibited the lowest ST/FC ratios, with increasingly higher ratios in patients on haloperidol or clozapine. We found a curvilinear relationship between the ST/FC ratios and the dose/kg body wt. of TNs and ANs on the basis of a dose-normalization according to Ki-values of the neuroleptic at D2 receptors and a weaker, but also curvilinear relationship between ST/FC ratios and normalized dosages according to clinically defined chlorpromazine equivalents. The specific uptake of IBZM did not correlate with the plasma levels of the TN haloperidol at the present dose range (0–12.4 ng/ml). For clozapine, a meaningful negative correlation between plasma levels and ST/FC ratio could be established. There was a negative continuous correlation between uptake of IBZM and extrapyramidal side effects, which is different from the threshold-based relationship between extrapyramidal side effects and IBZM uptake reported previously.