OBJECTIVE To examine the impact of medication nonadherence on treatment outcome in schizophrenia and potential risk factors for nonadherence. METHOD A post hoc analysis of a randomized, double-blind, 8-week, fixed-dose study comparing olanzapine 10, 20, and 40 mg/day for patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) with suboptimal response to current treatment (N = 599) was conducted between September 12, 2003, and November 3, 2005, at 55 study centers in the United States. Nonadherence was defined as not taking medication as prescribed based on daily pill counts. Because there was no significant difference in nonadherence between dose groups, effects of nonadherence on efficacy and safety outcomes were examined using all 3 groups combined. Baseline demographics and symptom severity were investigated as potential risk factors for nonadherence. RESULTS During the 8-week study, 34.5% of patients were nonadherent at least once. Nonadherent patients had significantly less improvement compared to adherent patients as measured by change in Positive and Negative Syndrome Scale total score (-22.57 vs. -26.84, p = .002). Longer duration of nonadherence was associated with reduced likelihood of treatment response (odds ratio = 0.94, 95% CI = 0.90 to 0.99, p = .008). The early treatment discontinuation rate was higher in nonadherent compared to adherent patients (40.8% vs. 24.5%, p < .001). Adherent and nonadherent patients had comparable outcomes in most safety measures, except for weight change, for which adherent patients had greater weight gain than nonadherent patients (2.63 kg vs. 1.96 kg, p = .02). Greater depression severity at baseline (p = .01) and greater hostility level during the study were significant risk factors for nonadherence (p = .02). CONCLUSIONS Medication nonadherence had a significantly negative impact on treatment response, highlighting the importance of adherence to achieve satisfactory treatment outcome. Findings may also help clinicians identify patients at risk for nonadherence and utilize interventions to improve adherence. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00100776.

OBJECTIVE:We present a post-hoc analysis of the safety and efficacy of duloxetine, a selective serotonin/norepinephrine reuptake inhibitor, for treatment of diabetic peripheral neuropathic pain (DPNP) in older patients. METHODS:Data from three double-blind, placebo-controlled trials in adult patients with DPNP were pooled and stratified by age (<65, >or=65 years). Patients were randomized to duloxetine (DLX) 60 mg once-daily, 60 mg twice-daily, or placebo for 12 weeks, followed by a 52-week extension phase (re-randomization to routine care or DLX 120 mg/day). Intent-to-treat analyses were used for safety and efficacy assessment. RESULTS:In the acute phase, overall TEAE rates did not differ significantly by age. A greater percentage of older patients discontinued due to TEAEs (P<0.001), regardless of treatment group. Duloxetine improved weekly mean 24-hour average pain scores versus placebo in both age groups (P<0.01). In the extension phase, a significant therapy-by-age interaction (P<0.05) was observed in overall TEAE rate; with routine care, 86.6% of older patients had >or=1 TEAE versus 74.6% of younger patients. CONCLUSIONS:Although TEAEs more frequently lead to discontinuation in older patients, duloxetine was well tolerated and efficacious for treatment of DPNP regardless of age. These data suggest duloxetine may be beneficial for treatment of DPNP in patients>or=65.

We examined the potential risks and benefits of switching from olanzapine to quetiapine in mentally stable, obese, or overweight patients with schizophrenia or schizoaffective disorder. Patients receiving olanzapine were randomized to continuing olanzapine treatment (N =68; 7.5-20 mg/day) or switching to quetiapine (N =65; 300-800 mg/day). Time to relapse was the primary study objective; secondary objectives included changes in weight, metabolic parameters, and psychiatric symptoms, and discontinuation rates. No significant difference in time to relapse was observed (p =0.293), but significantly more patients remained on treatment in the olanzapine group compared with the quetiapine group (70.6% vs 43.1%; p =0.002). Olanzapine-treated patients had significantly lower rates of study discontinuation for lack of efficacy and psychiatric adverse events (AEs) compared to quetiapine (2.94% vs 15.38%, p =0.015). Significantly more patients in the olanzapine group experienced an increase in BMI ≥1 kg/m(2). Olanzapine-treated patients experienced significantly greater increases in weight from Weeks 2 through 13. Switching patients with stable disease from olanzapine to quetiapine did not significantly shorten time to relapse, but produced more frequent study discontinuations due to lack of efficacy or psychiatric AEs with moderate but variable improvement in weight and no significant between-group differences in mean changes in metabolic laboratory parameters.