Effectiveness of antipsychotic treatments in a nationwide cohort of patients in community care after first hospitalisation due to schizophrenia and schizoaffective disorder: observational follow-up study.
To study the association between prescribed antipsychotic drugs and outcome in schizophrenia or schizoaffective disorder in the community.
Prospective cohort study using national central registers.
Community care in Finland.
Nationwide cohort of 2230 consecutive adults hospitalised in Finland for the first time because of schizophrenia or schizoaffective disorder, January 1995 to December 2001.
Rates of discontinuation of drugs (all causes), rates of rehospitalisation, and mortality associated with monotherapy with the 10 most commonly used antipsychotic drugs. Multivariate models and propensity score methods were used to adjust estimates of effectiveness.
Initial use of clozapine (adjusted relative risk 0.17, 95% confidence interval 0.10 to 0.29), perphenazine depot (0.24, 0.13 to 0.47), and olanzapine (0.35, 0.18 to 0.71) were associated with the lowest rates of discontinuation for any reason when compared with oral haloperidol. During an average follow-up of 3.6 years, 4640 cases of rehospitalisation were recorded. Current use of perphenazine depot (0.32, 0.22 to 0.49), olanzapine (0.54, 0.41 to 0.71), and clozapine (0.64, 0.48 to 0.85) were associated with the lowest risk of rehospitalisation. Use of haloperidol was associated with a poor outcome among women. Mortality was markedly raised in patients not taking antipsychotics (12.3, 6.0 to 24.1) and the risk of suicide was high (37.4, 5.1 to 276).
The effectiveness of first and second generation antipsychotics varies greatly in the community. Patients treated with perphenazine depot, clozapine, or olanzapine have a substantially lower risk of rehospitalisation or discontinuation (for any reason) of their initial treatment than do patients treated with haloperidol. Excess mortality is seen mostly in patients not using antipsychotic drugs.
Cites: N Engl J Med. 2000 Jun 22;342(25):1887-9210861325
Cites: N Engl J Med. 2000 Jun 22;342(25):1878-8610861324
Mental disorders are associated with premature mortality, and the magnitudes of risk have commonly been estimated using hospital data. However, psychiatric patients who are hospitalized have more severe illness and do not adequately represent mental disorders in the general population. We conducted a national cohort study using outpatient and inpatient diagnoses for the entire Swedish adult population (N = 7,253,516) to examine the extent to which mortality risks are overestimated using inpatient diagnoses only. Outcomes were all-cause and suicide mortality during 8 years of follow-up (2001-2008). There were 377,339 (5.2%) persons with any inpatient psychiatric diagnosis, vs. 680,596 (9.4%) with any inpatient or outpatient diagnosis, hence 44.6% of diagnoses were missed using inpatient data only. When including and accounting for prevalent psychiatric cases, all-cause mortality risk among persons with any mental disorder was overestimated by 15.3% using only inpatient diagnoses (adjusted hazard ratio [aHR], 5.89; 95% CI, 5.85-5.92) vs. both inpatient and outpatient diagnoses (aHR, 5.11; 95% CI, 5.08-5.14). Suicide risk was overestimated by 18.5% (aHRs, 23.91 vs. 20.18), but this varied widely by specific disorders, from 4.4% for substance use to 49.1% for anxiety disorders. The sole use of inpatient diagnoses resulted in even greater overestimation of all-cause or suicide mortality risks when prevalent cases were unidentified (~20-30%) or excluded (~25-40%). However, different methods for handling prevalent cases resulted in only modest variation in risk estimates when using both inpatient and outpatient diagnoses. These findings have important implications for the interpretation of hospital-based studies and the design of future studies.
Optimal treatment decisions in children require sufficient evidence on the safety and efficacy of pharmaceuticals in pediatric patients. However, there is concern that not enough trials are conducted in children and that pediatric trials differ from those performed in adults. Our objective was to measure the prevalence of pediatric studies among clinical drug trials and compare trial characteristics and quality indicators between pediatric and adult drug trials.
For conditions representing a high burden of pediatric disease, we identified all drug trials registered in ClinicalTrials.gov with start dates between 2006 and 2011 and tracked the resulting publications. We measured the proportion of pediatric trials and subjects for each condition and compared pediatric and adult trial characteristics and quality indicators.
For the conditions selected, 59.9% of the disease burden was attributable to children, but only 12.0% (292/2440) of trials were pediatric (P