Lower social participation and physical activity in patients with craniopharyngioma or CNS germ cell tumor: Their association with apathy.

Guidelines recommend second-generation antipsychotics as first-line treatment for schizophrenia. Olanzapine is a second-generation antipsychotic with a manufacturer’s recommended maximum of 20 mg/day, though treatment guidelines recommend doses up to 30 mg/day., In the Clinical Antipsychotic Trials of Intervention Effectiveness study, olanzapine at doses of 7.5 to 30 mg/day (mean modal dose 20.1 mg/day) was associated with more discontinuation due to weight gain or metabolic effects among second-generation antipsychotics received by patients diagnosed with chronic schizophrenia. In other studies, off-label doses above 30 mg/day have been associated with a higher incidence of adverse effects. “High-dose olanzapine” (HD-olanzapine; generally doses >20 mg/day) has been documented in literature as an alternative therapeutic option for patients unable to tolerate clozapine. At doses of 25 to 45 mg/day, olanzapine has demonstrated comparable efficacy to 100 to 600 mg/day of clozapine, as well as few safety concerns, in at least 3 double-blinded, randomized controlled trials conducted in adult patients with treatment-resistant schizophrenia (TRS) or treatment-resistant schizoaffective disorder, ranging from 18 to 24 weeks of treatment. In 1 double-blinded, randomized controlled trial, the efficacy and safety of olanzapine, risperidone, and clozapine were compared to each other and with haloperidol in patients with TRS or treatment-resistant schizoaffective disorder. HD-olanzapine (mean dose during last 6 weeks of study of 30.4, SD = 6.6 mg/day) was associated with improvements in baseline Positive and Negative Syndrome Scale total scores, as well as positive symptoms and general psychopathology subscales, at 14 weeks of treatment, as compared with relatively lower doses of olanzapine (mean dose achieved during first period of study was 19.6, SD = 2.1 mg/day). Olanzapine dosages in the setting of TRS or treatment-resistant schizoaffective disorder have been compared in a few open-label trials in recent years. The relatively small sample sizes of participants who completed these studies (ranging from 4-43) included 13- to 24-week time horizons in both inpatient and outpatient settings for olanzapine doses up to 40 mg. A 20% reduction from baseline in total Positive and Negative Syndrome Scale scores was not found to be statistically significant in 2 of these studies in which subjects received olanzapine doses over 20 mg/day., Significant improvements in positive and negative symptoms were observed in 1 study, where response was defined as at least 20% reduction in Brief Psychiatric Rating Scale scores; 39.2% of olanzapine-treated patients responded to 10 to 25 mg/day, with associated EPS at these doses reported as mild. Available case reports show favorable benefit-risk ratios for up to 60-mg/day olanzapine administration to patients., The risk of adverse effects with HD-olanzapine has also been specifically studied in several randomized trials, often with clozapine or other antipsychotic comparator groups.,,,, Common adverse effects with olanzapine include postural hypotension, constipation, weight gain, dizziness, and akathisia. In a 2023 systematic review of studies of adult patients with TRS or related disorders treated with “high-dose” or “low-dose” olanzapine (≤20 mg/day) compared with placebo or other antipsychotics, the most significant adverse effects observed in the HD-olanzapine treatment groups in 5 of these studies were weight gain (mean weight gain 2.1-7.2 kg), sedation, or drowsiness; EPS incidence was relatively low. In the double-blind crossover trial where HD-olanzapine was defined as 25 mg/day, only headache was observed at a higher prevalence than in the control group. In the open-label studies, olanzapine doses up to 40 mg/day were not associated with any serious events.