Hiroyuki Uchida

When nonpharmacological strategies alone are insufficient, and switching antipsychotics to relatively weight-neutral agents is not feasible, the literature supports the use of concomitant metformin as first choice among pharmacological interventions to counteract antipsychotic-induced weight gain and other metabolic adversities in schizophrenia.

While clinicians conclusively hold that patients become more sensitive to antipsychotics as they become older, this proposition has only modest empirical support and warrants further investigation. Age-related functional decline in the dopaminergic system predicts lower antipsychotic doses for older patients. We propose a hierarchical series of testable hypotheses to address the relative contribution of age-related pharmacokinetic and pharmacodynamic changes to antipsychotic drug sensitivity.

Positron emission tomography (PET) studies proposed a therapeutic window of D2 receptor occupancy (65%-80%) of antipsychotics for the treatment of schizophrenia in young adults. However, this conclusion has been drawn from clinical PET studies using small sample sizes (<20). Prospective PET studies that measured D2 occupancy levels and assessed extrapyramidal side effects (EPS) and/or treatment response induced by antipsychotics (excluding partial agonists) were identified, using MEDLINE and EMB

These findings suggest a nonlinear relationship between prescribed antipsychotic doses and overall neurocognitive function and vigilance. This study shows that D2 occupancy above approximately 80% not only increases the risk for extrapyramidal side effects as consistently reported in the literature but also increases the risk for cognitive impairment.

Although antipsychotic treatment with ≥50% to <1 DDD may be as effective as standard-dose therapy, there are insufficient clinical trial data to draw firm conclusions on standard- vs low-dose maintenance antipsychotic therapy for schizophrenia.

Measuring dopamine D₂ receptor occupancy levels using positron emission tomography (PET) is still widely unavailable. The objective of this study was to evaluate the accuracy of predicting D2 occupancy from the antipsychotic plasma level in patients with schizophrenia. Positron emission tomographic studies that measured plasma levels of antipsychotics and their corresponding D₂ occupancy levels were identified, using MEDLINE and EMBASE (last search: March 2010). Antipsychotics that were investig

The primary objective of this study was to evaluate the magnitude and variability of concentration exposure to clozapine and norclozapine in a real-world clinical setting, with a focus on smoking status, using population pharmacokinetic methodologies. A retrospective review of plasma clozapine and norclozapine concentrations taken from inpatients at the Centre for Addiction and Mental Health, Toronto, from 2001 to 2007 was conducted. A nonlinear mixed-effects model was developed using NONMEM, in