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Although clozapine is often discontinued, there is a paucity of guidelines and evidence on treatment options after clozapine discontinuation. Moreover, it is currently unknown whether reinstating clozapine in patients formerly using clozapine should be avoided.
To compare the real-world effectiveness of antipsychotics after clozapine cessation.
From Finnish registry data (1995–2017), we identified 2250 patients with schizophrenia who had been using clozapine for ≥1 year before treatment cessation. The primary analysis consisted of adjusted within-individual analyses of psychiatric ward readmission owing to psychosis and treatment failure. Secondary analyses concerned between-individual mortality differences.
Compared with no use of antipsychotics, risk of psychiatric ward readmission was lowest for reinitiation of clozapine (adjusted hazard ratio (aHR) 0.49; 95% CI 0.40–0.61; P < 0.0001), oral olanzapine (aHR 0.58; 95% CI 0.48–0.71; P < 0.0001) and antipsychotic polypharmacy (aHR 0.62; 95% CI 0.53–0.72; P < 0.0001). Risk of treatment failure was lowest for aripiprazole long acting injectable (aHR 0.42; 95% CI 0.27–0.65; P < 0.0001), reinitiation of clozapine (aHR 0.49; 95% CI 0.43–0.57; P < 0.0001) and oral olanzapine (aHR 0.69; 95% CI 0.61–0.77; P < 0.0001). Mortality risk was lowest for reinitiation of clozapine (aHR 0.18; 95% CI 0.09–0.36; P < 0.0001) and oral olanzapine (aHR 0.26; 95% CI 0.17–0.40; P < 0.0001).
Clozapine and olanzapine are the most effective and safest treatment options in those discontinuing clozapine for undefined reasons. Clozapine should therefore be reconsidered in patients with schizophrenia who previously discontinued this compound.
There is uncertainty about the incidence of breakthrough psychosis in treatment adherent patients, and the role that factors, such as cumulative antipsychotic exposure, play in this phenomenon.
In a nationwide cohort of individuals treated for schizophrenia-spectrum disorders in Finland between 1 January 1996 and 31 December 2015, ‘Breakthrough Psychosis on Antipsychotic Maintenance Medication’ (BAMM) was defined as hospitalization for psychosis despite ongoing continuous treatment with long-acting injectable antipsychotics (LAIs) or oral antipsychotics (OAPs) for ⩾8 weeks. Incidence rates, survival curves, and risk factors were presented.
In a cohort of 16 031 continuous LAI treatment episodes with virtually assured adherence [median duration = 441 days, interquartile range (IQR) = 155–1277], BAMM incidence was 31.5%. For 42 867 OAPs treatment episodes (median duration = 483 days, IQR = 167–1491), for whom adherence was modeled by the PRE2DUP method, BAMM incidence was 31.1%. Factors related to illness instability at treatment onset were associated with BAMM, although median time to BAMM was 291 days (IQR = 121–876) for LAIs and 344 days (IQR = 142–989) for OAPs, and 27.4% (N = 1386) of the BAMM events in the LAI, and 32.9% (N = 4378) in the OAP group occurred despite >1 year since last hospitalization at treatment onset. Cumulative antipsychotic exposure was not a consistent risk factor.
BAMM was relatively common even when adherence was confirmed with LAIs. Illness instability at treatment onset accounted for most cases, but relapse after years of continuous treatment was still prevalent. There was insufficient evidence to support causality between cumulative antipsychotic exposure and BAMM. Future research needs to address the role of symptom severity and neurobiology in BAMM.
We analyzed the impact of opioid initiation on the prevalence of antipsychotic and benzodiazepine and related drug (BZDR) use among community-dwelling persons with Alzheimer's disease (AD).
We utilized the register-based Medication use and Alzheimer's disease (MEDALZ) cohort for this study. We included all community-dwelling persons diagnosed with AD during 2010–2011 in Finland initiating opioid use (n = 3,327) and a matched cohort of persons not initiating opioids (n = 3,325). Interrupted time series analyses were conducted to compare the prevalence of antipsychotic and BZDR use in 30-day periods within six months before opioid initiation to 30-day periods six months later.
Before opioid initiation, prevalence of antipsychotic use among opioid initiators was 13.3%, 18.3% at opioid initiation, and 17.3% six months later. Prevalences of BZDR use were 27.1% six months prior, 28.9% at opioid initiation, and 26.9% six months later. After opioid initiation, antipsychotic and BZDR use declined by 0.3 percentage points (pps, 95% confidence interval 0.1–0.5) and 0.4 pps (0.2–0.7) per month, respectively, until the end of the follow-up. Compared to persons not initiating opioid use, opioid initiation immediately resulted in an increase in prevalence of 1.9 pps (0.9–2.8) for antipsychotics and of 1.6 pps (0.9–2.2) for BZDR use. However, in total there was a comparative decrease of 0.5 pps (0.3–0.8) per month for antipsychotics and of 0.4 pps (0.2–0.6) for BZDR use until the end of the follow-up.
Our results suggest that opioid initiation may reduce antipsychotic and BZDR use among persons with AD.
Behavioural and psychological symptoms of dementia are frequently treated
To determine the incidence of antipsychotic use in relation to diagnosis
of Alzheimer's disease.
Cohort of all community-dwellers in Finland diagnosed with Alzheimer's
disease in 2005 and matched controls. All antipsychotics dispensed
between 1995 and 2009 were extracted from the Finnish National
Altogether 1996/6087 (32.8%) persons with Alzheimer's disease initiated
antipsychotic use. The incidence of antipsychotic use was fivefold among
persons with Alzheimer's disease compared with controls, started to
increase 2–3 years before diagnosis and was highest during the first 6
months after diagnosis.
A distinct increase in antipsychotic initiations occurs in the same time
window as Alzheimer's disease diagnosis.
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