OBJECTIVE To examine the psychological effects on clinicians of working to manage novel viral outbreaks, and successful measures to manage stress and psychological distress.
DESIGNRapid review and meta-analysis.
Clozapine is superior for treatment-refractory disorder but if there is no response by 6 months medications with lower adverse reactions should be considered.
Clozapine is the most effective antipsychotic for the 25% to 33% of people with schizophrenia who are treatment resistant, but not all people achieve response. Using data from a previously published clozapine systematic review and meta-analysis, we explored the proportion of people who achieved response and examined the absolute and percentage change in Positive and Negative Syndrome Scale (PANSS) scores. Overall, 40.1% (95% confidence interval [CI], 36.8%-43.4%) responded, with a mean reduction in PANSS of 22.0 points (95% CI, 20.9-23.1), a reduction of 25.8% (95% CI, 24.7%-26.9%) from baseline. These reductions are clinically meaningful. A 40% response rate to clozapine suggests that 12% to 20% of people with schizophrenia will be ultra-resistant.
The increased focus on the physical health of people with SMI should encompass oral health. Possible interventions could include oral health assessment conducted using standard checklists that can be completed by non-dental personnel, help with oral hygiene, management of iatrogenic dry mouth, and early dental referral.
While clozapine use has increased in most studied countries over recent years, clozapine is still underutilised in many countries, with clozapine utilisation patterns differing significantly between countries. Future research should address the implementation of interventions designed to facilitate increased clozapine utilisation.
This international guideline proposes improving clozapine package inserts
worldwide by using ancestry-based dosing and titration. Adverse drug reaction
(ADR) databases suggest that clozapine is the third most toxic drug in the
United States (US), and it produces four times higher worldwide pneumonia
mortality than that by agranulocytosis or myocarditis. For trough steady-state
clozapine serum concentrations, the therapeutic reference range is narrow, from
350 to 600 ng/mL with the potential for toxicity and ADRs as
concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female
non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer
status through phenotypic conversion is associated with co-prescription of
inhibitors (including oral contraceptives and valproate), obesity, or
inflammation with C-reactive protein (CRP) elevations. The Asian population
(Pakistan to Japan) or the Americas’ original inhabitants have lower
CYP1A2 activity and require lower clozapine doses to reach concentrations of
350 ng/mL. In the US, daily doses of
300–600 mg/day are recommended. Slow personalized
titration may prevent early ADRs (including syncope, myocarditis, and
pneumonia). This guideline defines six personalized titration schedules for
inpatients: 1) ancestry from Asia or the original people from the Americas with
lower metabolism (obesity or valproate) needing minimum therapeutic dosages of
75–150 mg/day, 2) ancestry from Asia or the original
people from the Americas with average metabolism needing
175–300 mg/day, 3) European/Western Asian
ancestry with lower metabolism (obesity or valproate) needing
100–200 mg/day, 4) European/Western Asian
ancestry with average metabolism needing 250–400 mg/day,
5) in the US with ancestries other than from Asia or the original people from
the Americas with lower clozapine metabolism (obesity or valproate) needing
150–300 mg/day, and 6) in the US with ancestries other
than from Asia or the original people from the Americas with average clozapine
metabolism needing 300–600 mg/day. Baseline and weekly
CRP monitoring for at least four weeks is required to identify any inflammation,
including inflammation secondary to clozapine rapid titration.
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