Medication satisfaction in schizophrenia: a blinded-initiation study of paliperidone extended release in patients suboptimally responsive to risperidone.

Patient-reported outcomes, including treatment satisfaction, are now recognized as important and valid measures in assessment of therapeutic interventions. This randomized, 6-week, prospective, blinded-initiation study evaluated medication satisfaction as a primary outcome measure in a schizophrenia trial. Participants with suboptimal response to oral risperidone were randomized to paliperidone extended release (ER) immediate or delayed (week 2) initiation. Primary endpoint was change in Medication Satisfaction Questionnaire (MSQ; ratings from 1=extremely dissatisfied to 7=extremely satisfied) score at endpoint (last observation carried forward) for the overall population (all randomized participants). In total, 201 participants were randomized to immediate (n=100) or delayed (n=101) initiation of paliperidone ER. In the overall population, the mean + or - standard deviation MSQ score improved from 2.7 + or - 0.8 (very to somewhat dissatisfied) at baseline to 5.1 + or - 1.2 (somewhat satisfied) at endpoint (P<0.001). On the basis of dichotomized analysis of the MSQ scale (score 1-4=dissatisfied, 5-7=satisfied), 82.7% of participants were satisfied with their medication at endpoint. At the 2-week time point, significantly more participants in the immediate initiation group reported satisfaction (67.7%) compared with those in the delayed initiation group (45.3%) (P=0.002), who were still receiving risperidone at this time. Positive And Negative Syndrome Scale total scores also improved from baseline to endpoint (-12.9 + or - 13.1; P<0.001). Most common adverse events were insomnia (9.1%), constipation (7.6%), headache (7.6%) and somnolence (6.6%). Participants with schizophrenia who were suboptimally responsive to risperidone reported improved medication satisfaction after initiation of paliperidone ER.

The cognitive benefits of galantamine are sustained for at least 36 months: a long-term extension trial.

BACKGROUND: Alzheimer disease (AD) causes progressive cognitive and functional decline over years. Although cholinesterase inhibitors have demonstrated efficacy in studies lasting 3 to 6 months, little is known about long-term therapy. OBJECTIVE: To report the long-term cognitive effects of galantamine hydrobromide given continuously for 36 months in AD patients. PARTICIPANTS: Subjects were 194 US patients with mild to moderate AD who had been randomized to continuous galantamine therapy in either of 2 double-blind placebo-controlled trials. Subjects subsequently received open-label continuous galantamine therapy for up to 36 months. MAIN OUTCOME MEASURES: Effects on cognition were analyzed as change from study enrollment baseline in scores on the Alzheimer's Disease Assessment Scale-11-item cognitive subscale. Cognitive decline in galantamine-treated subjects was compared with that in a clinically similar historical control sample of AD patients who had received placebo for 12 months and with the mathematically predicted decline of untreated patients over 36 months. The rate of cognitive decline of patients who completed the entire 36-month trial (n = 119) was compared with that of patients who withdrew for any reason during the long-term open-label extension (n = 75). An inverted responder analysis was also performed in 36-month completers. RESULTS: Patients treated continuously with galantamine for 36 months increased a mean +/- SE of 10.2 +/- 0.9 points on the Alzheimer's Disease Assessment Scale-11-item cognitive subscale-a substantially smaller cognitive decline (approximately 50%) than that predicted for untreated patients. Patients discontinuing galantamine therapy before 36 months had declined at a similar rate before discontinuation as those completing 36 months of treatment. Almost 80% of patients who received galantamine continuously for up to 36 months seemed to demonstrate cognitive benefits compared with those predicted for untreated patients. CONCLUSIONS: Cognitive decline over 36 months of continuous galantamine treatment was substantially less than the predicted cognitive decline of untreated patients with mild to moderate dementia. Thus, the cognitive benefits of galantamine seemed to be sustained for at least 36 months. These findings suggest that galantamine slows the clinical progression of AD.

Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial.

BACKGROUND: Vascular dementia is the second commonest form of dementia, and vascular factors contribute to the development of dementia in many patients with Alzheimer's disease. Galantamine amplifies the acetylcholine response by inhibiting acetylcholinesterase and modulating nicotinic receptors. It has shown broad, sustained benefits in patients with Alzheimer's disease. We investigated the effects of galantamine in patients with a diagnosis of probable vascular dementia or Alzheimer's disease combined with cerebrovascular disease. METHODS: Eligible patients were randomly assigned galantamine 24 mg/day (n=396) or placebo (n=196) in a multicentre, double-blind, 6-month trial. Primary endpoints were cognition (Alzheimer's disease assessment scale, cognitive subscale [ADAS-cog]) and global functioning (clinician's interview-based impression of change plus caregiver input [CIBIC-plus]). Secondary endpoints included assessments of activities of daily living and behavioural symptoms. Patients were monitored for adverse events. Analyses were on the basis of observed case or last observation carried forward. FINDINGS: Galantamine showed greater efficacy than placebo on ADAS-cog (galantamine change -1.7 [SE 0.4] vs placebo 1.0 [0.5]; treatment effect 2.7 points; p<0.0001) and CIBIC-plus (213 [74%] vs 95 [59%] patients remained stable or improved, p=0.0001). Activities of daily living and behavioural symptoms were also significantly improved compared with placebo (p=0.002 and p=0.016, respectively). Galantamine was well tolerated. INTERPRETATION: Galantamine showed a therapeutic effect on all key areas of cognitive and non-cognitive abilities in this group of dementia patients.