Effect of paliperidone palmitate on hospitalisation in a naturalistic cohort - a four-year mirror image study.

BACKGROUND: Clinical trial outcomes are heavily influenced by the non-naturalistic clinical trial process. Observations of outcomes in clinical practice are a valuable adjunct to clinical trial results. HYPOTHESIS: Our null hypothesis was that clinically indicated switching to paliperidone palmitate had no effect on hospital admissions or hospital bed days. METHOD: This was a part-prospective mirror image study examining outcomes 2years before starting paliperidone palmitate and 2years after. Sensitivity analyses examined the effect of different placings of the mirror in the mirror image design. RESULTS: We prospectively followed-up 225 patients prescribed paliperidone palmitate in clinical practice. At 2years, 41.8% of patients were still receiving paliperidone palmitate. In the primary analysis, the mean number of admissions fell from 1.80 in the two years before starting paliperidone palmitate to 0.81 in two years following the drug's initiation (outpatients) or two years following hospital discharge (inpatients) (P<0.001). More than half of patients were not admitted to hospital during two years follow-up. Mean total bed days was reduced from 79.6 in the two years before to 46.2 in the two years after paliperidone palmitate initiation or discharge (P<0.001). Sensitivity analyses gave broadly similar outcomes. Continuers demonstrated better outcomes than discontinuers in sensitivity analyses but not in the primary analysis. CONCLUSION: Paliperidone palmitate initiation is associated with a substantial reduction in hospital admissions and days spent in hospital. The reduction in costs associated with reduced use of health care facilities is likely to exceed the purchase and administration costs of the drug.

A naturalistic evaluation and audit database of agomelatine: clinical outcome at 12 weeks.

OBJECTIVE: To determine the effectiveness of agomelatine in routine clinical practice and explore factors associated with response and continuation. METHOD: Consecutive patients prescribed agomelatine in participating psychiatric services were included. Patient demographic and outcome data were collected at treatment initiation and then at weeks 4, 8 and 12. Outcomes were analysed with respect to clinical and demographic factors. RESULTS: A total of 110 patients from nine NHS trusts were followed through 12 weeks of treatment. Agomelatine was largely used in difficult-to-treat or refractory patients: 83 (75%) had failed to respond to, or relapsed on, prior antidepressants. There were high rates of physical (54.5%) and psychiatric (50.0%) comorbidity. At 12 weeks of treatment, 68 (62%) continued agomelatine treatment. Overall, 69 subjects (62.7%) improved by at least one point of the Clinical Global Impression (severity) scale. Of 42 who discontinued, 23 (56%) discontinued because of lack of efficacy and 10 (24%) due to an adverse event. Of all variables examined, only a history of more than five episodes of depression significantly predicted discontinuation of treatment (OR continuation - 0.36, 95% CI 0.14, 0.95). CONCLUSION: Agomelatine was effective and generally well tolerated in a cohort of difficult-to-treat patients in clinical practice.

Amisulpride - dose, plasma concentration, occupancy and response: implications for therapeutic drug monitoring.

OBJECTIVE: To evaluate the relationships between dose, plasma concentration, pharmacological activity and clinical outcome to evaluate the appropriateness of therapeutic drug monitoring (TDM) in patients receiving amisulpride. METHOD: Literature search of Embase, Medline and PubMed databases. RESULTS: Amisulpride plasma concentration is closely correlated with dose (r(2) = 0.96, P < 0.0001), dopamine occupancy, response and with extra-pyramidal symptoms (EPS). Dose is correlated with response, dopamine occupancy and EPS. Optimal clinical response was found at doses of 400-800 mg/day, corresponding to plasma levels of approximately 200-500 ng/ml. EPS appears to be more reliably predicted by a plasma level above 320 ng/ml than by a particular dose. CONCLUSION: The effects and safety of amisulpride in the treatment of schizophrenia and schizoaffective disorder are predicted by daily dose. The plasma concentration threshold for response appears to be approximately 200 ng/ml. EPS are more reliably predicted by plasma level than by dose. TDM for patients prescribed amisulpride is thus of some clinical value.

Risperidone long-acting injection: a 6-year mirror-image study of healthcare resource use.

OBJECTIVE: To evaluate naturalistic use of risperidone long-acting injection (RLAI) and its effect on healthcare resource use. METHOD: Mirror-image comparison of healthcare resource use for 3 years before RLAI initiation and 3 years after. RESULTS: In total, 211 of 277 patients consecutively prescribed RLAI were evaluable over the full 6-year study period. Median days in hospital/patient increased significantly in the 3 years after RLAI initiation [87 days (inter-quartile range 25-236) before vs. 192 days (47-426) after; P < 0.001]. Those 34 patients who continued RLAI for 3 years showed no change in median bed days [64 days (6.5-182) before vs. 64 days (12-180) after] and median number of admissions was decreased [1.5 (1-2.25) before vs. 1.00 (0-1.25) after; P = 0.001]. Healthcare costs more than doubled for the whole cohort (P < 0.001) and discontinuers (P < 0.001) and increased significantly for continuers (P = 0.010). CONCLUSION: RLAI did not decrease either time spent in hospital or overall healthcare costs in this patient cohort.

A prospective 6-month analysis of the naturalistic use of aripiprazole - factors predicting favourable outcome.

OBJECTIVE: To evaluate the effectiveness of aripiprazole in clinical practice. METHOD: Prospective follow-up of patients consecutively prescribed aripiprazole in an acute mental health unit. Retrospective analysis of outcome from casenotes. RESULTS: Data were available on 228 patients. Fifty-one per cent discontinued aripiprazole over 6-month follow-up. Continuation with treatment was more likely in out-patients [relative risk (RR) 1.50; 95% CI: 1.13-2.00], those never before considered for clozapine treatment (RR 1.61, 95% CI: 1.06-2.44) and older patients [RR 1.05, 95% CI: 1.01-1.09 (per 5-year increase)]. The main reason for early discontinuation was the occurrence of minor adverse effects. CONCLUSION: Aripiprazole is effective in practice. Outcome is likely to be improved by careful patient selection and by attending to adverse effects experienced early in treatment.