Paliperidone

Observational studies

Paliperidone palmitate, an injectable atypical antipsychotic drug, has been assessed in a 1-year open extension of a double-blind study in 288 patients with schizophrenia [ ]. The median duration of exposure was 338 (range 10–390) days. The most frequent adverse events were insomnia (7%) and worsening of schizophrenia, nasopharyngitis, headache, weight gain, and extrapyramidal symptoms (6% each). Potentially prolactin-related adverse events occurred in 13 patients, mostly women. Tremor occurred in eight patients.

Placebo-controlled studies

Paliperidone modified-release, quetiapine, and placebo have been compared in patients with recently exacerbated schizophrenia requiring hospitalization in a 6-week double-blind study [ ]. In-patients were randomly assigned to paliperidone modified-release (n = 160), quetiapine (n = 159), or placebo (n = 80). A 2-week monotherapy phase was followed by a 4-week additive-therapy phase; target doses were at the upper end of the recommended ranges: paliperidone modified-release, 9 or 12 mg/day, and quetiapine, 600 or 800 mg/day. Six-week completion rates were 78% with paliperidone modified-release, 67% with quetiapine, and 64% with placebo. Improvement in mean PANSS total change score was greater with paliperidone modified-release than with quetiapine from day 5 (− 11 versus − 8.2) to the monotherapy phase end-point (− 23.4 versus − 17.1). At the 6-week end-point, there was significantly greater improvement with paliperidone than quetiapine or placebo, despite similar use of additive therapy (predominantly other antipsychotic drugs). Over the entire study period, serious adverse events were reported by 13 (8.2%) patients taking paliperidone, 7 (4.4%) taking quetiapine, and 2 (2.5%) taking placebo; the most common adverse event was schizophrenia (3.8%, 1.9%, and 0.0% respectively). There were significantly higher values for changes in prolactin with paliperidone; the values at end-point were 32, − 6.7, and − 4.5 ng/ml respectively.

Elderly patients with schizophrenia (mean age 70 years; n = 114) who took paliperidone in a 6-week double-blind, placebo-controlled study followed by a 24-week open extension with paliperidone (mean doses 7.4 and 8.5 mg/day respectively) treatment-emergent adverse events were similar (71% with placebo and 67% with paliperidone), as were withdrawal rates because of adverse events (8% and 7% respectively) [ ]. There were serious adverse events in three patients taking placebo and in two taking paliperidone (acute coronary syndrome and mania, n = 1 each); there was also an age-related increase in the incidence of somnolence. There was a higher incidence of tachycardia with paliperidone in both phases, increases being more pronounced in patients aged 70–75 years compared with those aged 64–69. There was prolongation of the QT _c interval to over 500 ms in the first phase, leading to discontinuation (n = 2), and in the second phase (n = 1); these three patients had histories of QT interval prolongation. In the double-blind phase, there were raised prolactin concentrations in 45% of the men and 49% of the women taking paliperidone, but they returned to normal at the end of the study; prolactin concentrations also rose in patients taking paliperidone who had previously taken placebo. The incidence of extrapyramidal symptoms was low throughout the study; during the second phase, medication for treatment of this effect was used in 27% and 22% respectively.

aIn a re-analysis of different short-term studies, the efficacy and tolerability of modified-release paliperidone have been assessed in patients with acute schizophrenia [ ]. Patients were randomly allocated to paliperidone 3 mg/day (n = 123), 6 mg/day (n = 234), 9 mg/day (n = 245), 12 mg/day (n = 240), 15 mg/day (n = 113), or placebo (n = 351); mean ages were 36–39 years. All doses of paliperidone were significantly better than placebo. There were treatment-emergent adverse events in 66–77% in those who took paliperidone and in 6% of those who took placebo; serious adverse events occurred in 5–6% of patients in all groups, the most common being exacerbation of psychotic symptoms. Orthostatic hypotension occurred from 1% at 6 mg/day to 4% at 12 mg/day. A higher proportion of patients assigned to paliperidone above 6 mg/day had extrapyramidal symptoms; one patient with a previous history of tardive dyskinesia with clozapine had an episode after taking paliperidone for 4 days. Glucose-related adverse events were reported in both groups (paliperidone, 1%; placebo, 1%). Mean body weight increased by 0.6 kg with paliperidone 3 mg/day and 1.9 kg with 15 mg/day, and fell by 0.4 kg with placebo. Median prolactin concentration increases were larger among women (81 ng/ml) than men (24 ng/ml) when all paliperidone groups were combined; the magnitude of this effect increased with increasing drug doses and there were prolactin-related adverse events in 1–2% of patients taking paliperidone 3–12 mg and 4% of those taking 15 mg. There were no deaths, cases of neuroleptic malignant syndrome, or other severe symptoms.