METHODS: A systematic review of published and unpublished studies were carried out. Included studies described the development of explicit criteria for PIM use in older adults and provided a list of medications that should be considered inappropriate. PubMed, Medline, EMBASE, Cochrane CENTRAL, CINAHL, PsycINFO, and Scopus searches were conducted. The PIMs were analyzed according to the general conditions, disease-specific conditions, and drug-drug interaction classes. The qualities of the included studies were assessed using a nine-point evaluation tool. The kappa agreement index was used to evaluate the level of agreement between the identified explicit PIM tools.

RESULTS: The search yielded 1206 articles, and 15 studies were included in our analysis. Thirteen criteria were identified in East Asia and two in South Asia. Twelve out of the 15 criteria were developed using the Delphi method. We identified 283 PIMs independent of medical conditions and 465 disease-specific PIMs. Antipsychotics were included in most of the criteria (14/15), followed by tricyclic antidepressants (TCAs) (13/15), antihistamines (13/15), sulfonylureas (12/15), benzodiazepines (11/15), and nonsteroidal anti-inflammatory drug (NSAIDs) (11/15). Only one study fulfilled all the quality components. There was a low kappa agreement (k = 0.230) between the included studies.

MATERIALS AND METHODS: A randomized, 2-treatment, 2-period, 2-sequence, single dose, crossover with a washout period of 2 weeks, was conducted in 24 healthy Thai male volunteers. Blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h following drug administration. Plasma concentrations of risperidone and 9-hydroxyrisperidone were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of risperidone and 9-hydroxyrisperidone were determined using a non-compartmental model.

RESULTS: The geometric means ratios (%) and 90% confidence interval (CI) of the test and reference products for the log-transformed pharmacokinetic parameters, Cmax, AUC0-t and AUC0-inf of risperidone were 104.49 % (92.79% - 117.66%), 100.96 % (92.15% - 110.61 %) and 97.99 % (90.72% - 105.85%). The 90% CI of geometric means ratios of the test and reference products for the log-transformed pharmacokinetic parameters, Cmax, AUC0-t and AUC0-inf of 9-hydroxyrisperidone were 97.00%, 96.97% and 97.49%.

METHODS: Patients (N = 281) with schizophrenia who had completed a randomized, double-blind (DB), 6-week comparison of lurasidone (40 and 80 mg/day) and placebo were enrolled in a 26-week extension study in which all patients received open-label (OL), flexible doses of lurasidone (40 or 80 mg/day). Effectiveness was measured using the Positive and Negative Syndrome Scale (PANSS) scale.

RESULTS: Fifty-seven percent of patients completed the OL extension study; 16.7% discontinued early due to lack of effectiveness; and 10.3% due to adverse events. The most common adverse events were insomnia (11.3%), akathisia (11.0%), and nasopharyngitis (10.6%). Adverse events related to weight gain, metabolic parameters, prolactin, and ECG measures were uncommon. Mean change in the PANSS total score from the DB baseline to OL endpoint was -28.4, with mean improvement of -7.5 observed from baseline to OL endpoint, and with a PANSS responder rate of 73.7%.