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Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29?823 Patients With Schizophrenia.

ABSTRACT: It has remained unclear whether there are clinically meaningful differences between antipsychotic treatments with regard to preventing relapse of schizophrenia, owing to the impossibility of including large unselected patient populations in randomized clinical trials, as well as residual confounding from selection biases in observational studies.To study the comparative real-world effectiveness of antipsychotic treatments for patients with schizophrenia.Prospectively gathered nationwide databases were linked to study the risk of rehospitalization and treatment failure from July 1, 2006, to December 31, 2013, among all patients in Sweden with a schizophrenia diagnosis who were 16 to 64 years of age in 2006 (29?823 patients in the total prevalent cohort; 4603 in the incident cohort of newly diagnosed patients). Within-individual analyses were used for primary analyses, in which each individual was used as his or her own control to eliminate selection bias. Traditional Cox proportional hazards multivariate regression was used for secondary analyses.Risk of rehospitalization and treatment failure (defined as psychiatric rehospitalization, suicide attempt, discontinuation or switch to other medication, or death).There were 29?823 patients (12?822 women and 17?001 men; mean [SD] age, 44.9 [12.0] years). During follow-up, 13?042 of 29?823 patients (43.7%) were rehospitalized, and 20?225 of 28?189 patients (71.7%) experienced treatment failure. The risk of psychiatric rehospitalization was the lowest during monotherapy with once-monthly long-acting injectable paliperidone (hazard ratio [HR], 0.51; 95% CI, 0.41-0.64), long-acting injectable zuclopenthixol (HR, 0.53; 95% CI, 0.48-0.57), clozapine (HR, 0.53; 95% CI, 0.48-0.58), long-acting injectable perphenazine (HR, 0.58; 95% CI, 0.52-0.65), and long-acting injectable olanzapine (HR, 0.58; 95% CI, 0.44-0.77) compared with no use of antipsychotic medication. Oral flupentixol (HR, 0.92; 95% CI, 0.74-1.14), quetiapine (HR, 0.91; 95% CI, 0.83-1.00), and oral perphenazine (HR, 0.86; 95% CI, 0.77-0.97) were associated with the highest risk of rehospitalization. Long-acting injectable antipsychotic medications were associated with substantially lower risk of rehospitalization compared with equivalent oral formulations (HR, 0.78; 95% CI, 0.72-0.84 in the total cohort; HR, 0.68; 95% CI, 0.53-0.86 in the incident cohort). Clozapine (HR, 0.58; 95% CI, 0.53-0.63) and all long-acting injectable antipsychotic medications (HRs 0.65-0.80) were associated with the lowest rates of treatment failure compared with the most widely used medication, oral olanzapine. The results of several sensitivity analyses were consistent with those of the primary analyses.Clozapine and long-acting injectable antipsychotic medications were the pharmacologic treatments with the highest rates of prevention of relapse in schizophrenia. The risk of rehospitalization is about 20% to 30% lower during long-acting injectable treatments compared with equivalent oral formulations.

SUBMITTER: Tiihonen J

PROVIDER: S-EPMC5710250 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia.

Tiihonen Jari J Mittendorfer-Rutz Ellenor E Majak Maila M Mehtälä Juha J Hoti Fabian F Jedenius Erik E Enkusson Dana D Leval Amy A Sermon Jan J Tanskanen Antti A Taipale Heidi H

JAMA psychiatry 20170701 7

<h4>Importance</h4>It has remained unclear whether there are clinically meaningful differences between antipsychotic treatments with regard to preventing relapse of schizophrenia, owing to the impossibility of including large unselected patient populations in randomized clinical trials, as well as residual confounding from selection biases in observational studies.<h4>Objective</h4>To study the comparative real-world effectiveness of antipsychotic treatments for patients with schizophrenia.<h4>D ...[more]

PMID: 28593216

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Project description:Importance:Mood stabilizers and antipsychotics are the main maintenance treatments for bipolar disorder. Lithium is considered to be the most effective mood stabilizer, but very little is known about overall health outcomes associated with specific treatments and the comparative long-term effectiveness of specific psychotropics or routes of administration in the prevention of rehospitalizations. Objective:To study the comparative effectiveness of pharmacologic treatments in the prevention of rehospitalization in a nationwide cohort of patients with bipolar disorder. Design, Setting, and Participants:This cohort study examined the risk of psychiatric, cardiovascular, and all-cause hospitalization from January 1, 1987, to December 31, 2012, among all patients in Finland who had been hospitalized for bipolar disorder (N?=?18?018; mean follow-up time, 7.2 years) using prospectively gathered nationwide databases for hospitalization and dispensed medications. The primary analysis was within-individual analysis, in which each individual was used as his or her own control to eliminate selection bias. The study adjusted for the effect of concomitant psychotropic medications, duration of illness, and the temporal orders of exposure and nonexposure periods. Statistical analysis was conducted from January 1, 1996, to December 31, 2012. Main Outcomes and Measures:Adjusted hazard ratios (HRs) for rehospitalization were calculated. Results:Among the cohort (9558 women and 8460 men; mean [SD] age, 46.6 [17.0] years), 9721 patients (54.0%) had at least 1 psychiatric rehospitalization. In comparison between use and no use among specific agents reaching nominal statistical significance, risperidone long-acting injection (HR, 0.58 [95% CI, 0.34-1.00]), gabapentin (HR, 0.58 [95% CI, 0.44-0.77]), perphenazine long-acting injection (HR, 0.60 [95% CI, 0.41-0.88]), and lithium carbonate (HR, 0.67 [95% CI, 0.60-0.73]) were associated with the lowest risk of psychiatric rehospitalization. Concerning all-cause hospitalization, lithium (HR, 0.71 [95% CI, 0.66-0.76]) was associated with the lowest risk. The most frequently used antipsychotic treatment, quetiapine fumarate, showed only modest effectiveness (risk of psychiatric rehospitalization: HR, 0.92 [95% CI, 0.85-0.98]; risk of all-cause hospitalization: HR, 0.93 [95% CI, 0.88-0.98]). Long-acting injections were associated with substantially better outcomes compared with identical oral antipsychotics (risk of psychiatric rehospitalization: HR, 0.70 [95% CI, 0.55-0.90]; risk of all-cause hospitalization: HR, 0.70 [95% CI, 0.57-0.86]). Results from sensitivity analyses showed consistent beneficial effects only for lithium and for long-acting injections compared with their oral counterparts. Conclusions and Relevance:Lithium was the most effective mood stabilizer, and long-acting injections the most effective antipsychotics, in preventing hospitalization due to mental or physical illness.

Project description:AimTo investigate the real-world effectiveness of pharmacological treatments (buprenorphine, methadone) of opioid use disorder (OUD).DesignA nation-wide, register-based cohort study.SettingSweden.ParticipantsAll residents aged 16-64 years living in Sweden using OUD medication from July 2005 to December 2016 (n = 5757, 71.8% men) were identified from registers of prescriptions, inpatient and specialized outpatient care, causes of death, sickness absence and disability pensions.MeasurementsMain outcome: hospitalization due to OUD.Secondary outcomeshospitalization due to any cause; death due to all, natural and external causes. Mortality was analyzed with between-individual multivariate-adjusted Cox hazards regression model. Recurrent outcomes, such as hospitalizations, were analyzed with within-individual analyses to eliminate selection bias. OUD medication use versus non-use was modelled with PRE2DUP (from prescription drug purchases to drug use periods) method.FindingsBuprenorphine [hazard ratio (HR) = 0.73, 95% confidence interval (CI) = 0.54-0.97] and methadone (HR = 0.74, 95% CI = 0.59-0.93) use were associated with significantly lower risk of OUD hospitalization, but not any-cause hospitalizations, compared with the time-periods when the same individual did not use OUD medication. The use of buprenorphine and methadone were both associated with significantly lower risk of all-cause mortality (HR = 0.45, 95% CI = 0.34-0.59; HR = 0.51, 95% CI = 0.41-0.63, respectively), compared with non-use of both medications. Similar results were found for risk of mortality due to external causes (HR = 0.39; 95% CI = 0.27-0.54; HR = 0.40; 95% CI = 0.29-0.53, respectively), but not for mortality due to natural causes. The risk of OUD hospitalization and all-cause mortality was decreased in all duration categories of studied medications (< 30, 31-180, 181-365 and >365 days), except for methadone use less than 30 days.ConclusionsThe use of buprenorphine and methadone are both associated with a significantly lower risk of hospitalization due to opioid use disorder and death due to all and external causes, when compared with non-use.

Project description:Background and aimPharmacotherapy for alcohol use disorder (AUD) is recommendable, but under-used, possibly due to deficient knowledge of medications. This study aimed to investigate the real-world effectiveness of approved pharmacological treatments (disulfiram, acamprosate, naltrexone and nalmefene) of AUD.DesignA nation-wide, register-based cohort study.SettingSweden.ParticipantsAll residents aged 16-64 years living in Sweden with registered first-time treatment contact due to AUD from July 2006 to December 2016 (n = 125 556, 62.5% men) were identified from nation-wide registers.MeasurementsThe main outcome was hospitalization due to AUD. The secondary outcomes were hospitalization due to any cause, alcohol-related somatic causes, as well as work disability (sickness absence or disability pension), and death. Mortality was analysed with between-individual analysis using a traditional multivariate-adjusted Cox hazards regression model. Recurrent outcomes, such as hospitalization-based events and work disability, were analysed with within-individual analyses to eliminate selection bias.FindingsNaltrexone combined with acamprosate [hazard ratio (HR) = 0.74; 95% confidence interval (CI) = 0.61-0.89], combined with disulfiram (HR = 0.76, 95% CI = 0.60-0.96) and as monotherapy (HR = 0.89, 95% CI = 0.81-0.97) was associated with a significantly lower risk of AUD-hospitalization compared with no use of AUD medication. Similar results were found for risk of hospitalization due to any cause. Benzodiazepine use and acamprosate monotherapy were associated with an increased risk of AUD-hospitalization (HR = 1.18, 95% CI = 1.14-1.22 and HR = 1.10, 95% CI = 1.04-1.17, respectively). No statistically significant effects were found for work disability or mortality.ConclusionsNaltrexone as monotherapy and when combined with disulfiram and acamprosate appears to be associated with lower risk of hospitalization due to any and alcohol-related causes, compared with no use of alcohol use disorder (AUD) medication. Acamprosate monotherapy and benzodiazepine use appear to be associated with increased risk of AUD-associated hospitalization.

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Dataset Information

Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29?823 Patients With Schizophrenia.

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Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia.

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Real-World Effectiveness of Antipsychotic Treatments in a Nationwide Cohort of 29 823 Patients With Schizophrenia.