D₂receptor occupancy following lurasidone treatment in patients with schizophrenia or schizoaffective disorder

Abstract

Positron emission tomography (PET) occupancy data suggest that greater than 65% occupancy can be achieved across the dose range of 80-160 mg/day and that some patients require higher doses to achieve antipsychotic efficacy; this finding supports prior randomized clinical trial results.

Lurasidone Dose Escalation in Early Nonresponding Patients With Schizophrenia

“…schizophrenia randomly assigned to receive lurasidone 80, 120, or 160 mg/d for 1 week indicated that doses greater than 80 mg/d may be necessary to achieve therapeutic threshold levels of D 2 receptor occupancy in some patients. 28 In support of these observations, in this study, serum lurasidone concentration increased in a dose-related fashion, with an approximately 2-fold increase observed in patients treated with lurasidone 160 mg/d compared with patients continued on 80 mg/d. Notably, serum lurasidone concentration in patients receiving lurasidone 80 mg/d did not differentiate treatment responders from nonresponders at week 2.…”

“…Imaging studies have shown a strong relationship between serum lurasidone concentration and D 2 receptor occupancy. 27,28 A PET study of patients with It is illegal to post this copyrighted PDF on any website. schizophrenia randomly assigned to receive lurasidone 80, 120, or 160 mg/d for 1 week indicated that doses greater than 80 mg/d may be necessary to achieve therapeutic threshold levels of D 2 receptor occupancy in some patients.…”

Association between ANKK1 (rs1800497) polymorphism of DRD2 gene and attention deficit hyperactivity disorder: A meta-analysis

“…Among the five dopamine receptor subtypes, DRD2 seems to be the cardinal type that regulate the firing rate, synthesis and release of dopamine in presynaptic membrane [18]. Signal transduction through DRD2 controls substance abuse, locomotor behavior and antipsychiatric drug treatment response in ADHD patients [19][20][21]. Thus, it is not unexpected that rs1800497 variance is associated with the occurrence of ADHD.…”

Positron Emission Tomography in CNS Drug Discovery and Drug Monitoring

“…127 Another PET investigation of lurasidone in a large group of schizophrenia patients, however, showed that daily doses only modestly correlate with receptor occupancies, which were, however, predicted by plasma levels of the compound, along with its active metabolites. 128 It is well-known in therapeutic drug monitoring (TDM) that daily doses may fail to reliably predict plasma levels, clinical response, or side effects. 129 PET investigations, however, also uncovered that some agents, notably the AP quetiapine, fail to even reveal plasma concentration vs occupancy relationships, which calls into question the validity of simple daily dose suggestions for this compound.…”