Impact of smoking behavior on clozapine blood levels – a systematic review and meta‐analysis

Objective Tobacco smoking significantly impacts clozapine blood levels and has substantial implications on individual efficacy and safety outcomes. By investigating differences in clozapine blood levels in smoking and non‐smoking patients on clozapine, we aim to provide guidance for clinicians how to adjust clozapine levels for patients on clozapine who change their smoking habits. Methods We conducted a meta‐analysis on clozapine blood levels, norclozapine levels, norclozapine/clozapine ratios and concentration to dose (C/D) ratios in smokers and non‐smokers on clozapine. Data were meta‐analysed using a random‐effects model with sensitivity analyses on dose, ethnic origin and study quality. Results Data from 23 studies were included in this meta‐analysis with 21 investigating differences between clozapine blood levels of smokers and non‐smokers. In total, data from 7125 samples were included for the primary outcome (clozapine blood levels in ng/ml) in this meta‐analysis. A meta‐analysis of all between‐subject studies (N=16) found that clozapine blood levels were significantly lower in smokers compared to non‐smokers (Standard Mean Difference (SMD) ‐0.39, 95% confidence interval (CI) ‐0.55 to ‐0.22,

System-level intersectoral linkages between the mental health and non-clinical support sectors: a qualitative systematic review

Objectives: Concerns about fragmented mental health service delivery persist, particularly for people with severe and persistent mental illness. The objective was to review evidence regarding outcomes attributed to system-level intersectoral linkages involving mental health services and non-clinical support services, and to identify barriers and facilitators to the intersectoral linkage process

The prevalence of depression and anxiety disorders in indigenous people of the Americas: a systematic review and meta-analysis

Indigenous populations are considered at higher risk of psychiatric disorder but many studies do not include direct comparisons with similar non-Indigenous controls. We undertook a meta-analysis of studies that compared the prevalence of depression and anxiety disorders in Indigenous populations in the Americas with those of non-Indigenous groups with similar socio-demographic features (Registration number: CRD42015025854). A systematic search of PubMed, Medline, PsycInfo, PsycArticles, ScienceDirect, EMBASE, and article bibliographies was performed. We included comparisons of lifetime rates and prevalence of up to 12 months. We found 19 studies (n\ua0=\ua0250, 959) from Latin America, Canada and the US. There were no differences between Indigenous and similar non-Indigenous groups in the 12-month prevalence of depressive, generalised anxiety and panic disorders. However, Indigenous people were at greater risk of PTSD. For lifetime prevalence, rates of generalised anxiety, panic and all the depressive disorders were significantly lower in Indigenous participants, whilst PTSD (on adjusted analyses) and social phobia were significantly higher. Results were similar for sub-analyses of Latin America, Canada and the US, and sensitivity analyses by study quality or setting (e.g. health, community etc.). Risk factors for psychiatric illness may therefore be a complex interaction of biological, educational, economic and socio-cultural factors that may vary between disorders. Accordingly, interventions should reflect that the association between disadvantage and psychiatric illness is rarely due to one factor. However, it is also possible that assessment tools don't accurately measure psychiatric symptoms in Indigenous populations and that further cross-cultural validation of diagnostic instruments may be needed too

Dry mouth effects from drugs used for depression, anxiety, schizophrenia and bipolar mood disorder in adults: systematic review

Background Poor oral health is increasingly recognised as an important comorbidity in people with psychiatric illness. One risk factor is psychotropic-induced dry mouth. Aims To perform a systematic review of the severity of dry mouth due to psychotropic drugs in adults (CRD42021239725). Study quality was assessed using the Cochrane risk of bias tool. Method We searched the following databases: PubMed, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL and Web of Science. We included randomised controlled trials (RCTs) measuring the severity of drug-induced hyposalivation and xerostomia. Results Eighteen RCTs with 605 participants were included. Severity of drug-induced dry mouth was compared among eight drug classes and/or against placebo. All studies were published 20 to 40 years ago and included tricyclic antidepressants (TCAs), serotonin specific reuptake inhibitors (SSRIs) and other drug classes. Meta-analysis was not feasible owing to design heterogeneity. TCAs caused more severe dry mouth, both objectively and subjectively, than placebo or other drug classes. SSRIs were generally associated with less severe symptoms. However, there was no information on antipsychotics or more recently available antidepressants, and there was minimal information on mood stabilisers. Most studies were on healthy subjects, limiting the generalisability of findings. Only one study measured both objective and subjective dry mouth, which have different clinical implications. Conclusions Psychotropic-induced dry mouth is a poorly researched area, and well-designed RCTs of newer psychotropic drugs using standardised objective and subjective measures are indicated. Given the ongoing use of TCAs for treatment-resistant depression, prescribers need to remain vigilant for xerostomia

N-acetylcysteine (NAC) in schizophrenia resistant to clozapine: a double blind randomised placebo controlled trial targeting negative symptoms

BACKGROUND: Clozapine is an effective treatment for a proportion of people with schizophrenia (SZ) who are resistant to the beneficial effects of other antipsychotic drugs. However, anything from 40-60&nbsp;% of people on clozapine experience residual symptoms even on adequate doses of the medication, and thus could be considered \u27clozapine resistant\u27. Agents that could work alongside clozapine to improve efficacy whilst not increasing the adverse effect burden are both desired and necessary to improve the lives of individuals with clozapine-resistant SZ. N-Acetylcysteine (NAC) is one such possible agent. Previous research from our research group provided promising pilot data suggesting the efficacy of NAC in this patient population. The aim of the study reported here is to expand this work by conducting a large scale clinical trial of NAC in the treatment of clozapine-resistant SZ. METHODS: This study is an investigator initiated, multi-site, randomised, placebo-controlled trial. It aims to include 168 patients with clozapine-resistant SZ, divided into an intervention group (NAC) and a control group (placebo). Participants in the intervention group will receive 2&nbsp;g daily of NAC. The primary outcome measures will be the negative symptom scores of the Positive and Negative Syndrome Scale (PANSS). Secondary outcome measures will include: changes in quality of life (QoL) as measured by the Lancashire Quality of Life Profile (LQoLP) and cognitive functioning as measured by the total score on the MATRICS. Additionally we will examine peripheral and cortical glutathione (GSH) concentrations as process outcomes. DISCUSSION: This large scale clinical trial will investigate the efficacy of NAC as an adjunctive medication to clozapine. This trial, if successful, will establish a cheap, safe and easy-to-use agent (NAC) as a \u27go to\u27 adjunct in patients that are only partly responsive to clozapine.<br /

The effectiveness of problem solving therapy in deprived South African communities: results from a pilot study

<p>Abstract</p> <p>Background</p> <p>The majority of South Africans with a DSM-IV diagnosis receive no treatment for their mental health problems. There is a move to simplify treatment for common mental disorders (CMDs) in order to ease access. Brief problem solving therapy (PST) might fill the treatment gap for CMD's in deprived communities in South Africa. This pilot study evaluates the feasibility, acceptability and effectiveness of this PST program for CMD's in deprived communities around Cape Town.</p> <p>Methods</p> <p>A Dutch problem solving program was adapted and translated into English, Xhosa and Afrikaans and thereafter implemented in townships around Cape Town. An initial attempt to recruit participants for online PST proved difficult, and so the program was adapted to a booklet format. Volunteers experiencing psychological distress were invited to participate in the either individually or group delivered 5-week during self-help program. To evaluate the effectiveness, psychological distress was administered through self-report questionnaires. After completion of the intervention participants also rated the program on various acceptability aspects.</p> <p>Results</p> <p>Of 103 participants, 73 completed 5 weeks of brief PST in a booklet/workshop format. There were significantly more dropouts in those who used the booklet individually than in the group. Psychological distress measured on the K-10 and SRQ fell significantly and the program was evaluated positively.</p> <p>Conclusions</p> <p>The results suggest that brief problem solving in a booklet/workshop format may be an effective, feasible and acceptable short-term treatment for people with CMD's in deprived communities. In this setting, group delivery of PST had lower drop-out rates than individual delivery, and was more feasible and acceptable. Randomized controlled trials are needed to evaluate the effect of brief self-help PST more rigorously.</p

Comprehensive dissection of prevalence rates, sex differences, and blood level-dependencies of clozapine-associated adverse drug reactions

Clozapine is often underused due to concerns about adverse drug reactions (ADRs) but studies into their prevalences are inconclusive. We therefore comprehensively examined prevalences of clozapineassociated ADRs in individuals with schizophrenia and demographic and clinical factors associated with their occurrence. Data from a multi-center study (n=698 participants) were collected. The mean number of ADRs during clozapine treatment was 4.8, with 2.4% of participants reporting no ADRs. The most common ADRs were hypersalivation (74.6%), weight gain (69.3%), and increased sleep necessity (65.9%), all of which were more common in younger participants. Participants with lower BMI prior to treatment were more likely to experience significant weight gain (>10%). Constipation occurred more frequently with higher clozapine blood levels and doses. There were no differences in ADR prevalence rates between participants receiving clozapine monotherapy and polytherapy. These findings emphasize the high prevalence of clozapine-associated ADRs and highlight several demographic and clinical factors contributing to their occurrence. By understanding these factors, clinicians can better anticipate and manage clozapine-associated ADRs, leading to improved treatment outcomes and patient well-being