Long-Term Real-World Effectiveness of Pharmacotherapies for Schizoaffective Disorder

ObjectiveTo investigate the long-term real-world effectiveness of antipsychotics and other psychopharmacotherapies in the treatment of schizoaffective disorder (SCHAFF). MethodTwo nationwide cohorts of SCHAFF patients were identified from Finnish and Swedish registers. Within-individual design was used with stratified Cox regression. The main exposure was use of antipsychotics. Adjunctive pharmacotherapies included mood stabilizers, antidepressants, and benzodiazepines and benzodiazepine-related drugs. The main outcome was hospitalization due to psychosis. ResultsThe Finnish cohort included 7655 and the Swedish cohort 7525 patients. Median follow-up time was 11.2 years (IQR 5.6–11.5) in the Finnish and 7.6 years (IQR 3.8–10.3) in the Swedish cohort. Clozapine and long-acting injectable (LAI) antipsychotics were consistently associated with a decreased risk of psychosis hospitalization and treatment failure (psychiatric hospitalization, any change in medication, death) in both cohorts. Quetiapine was not associated with a decreased risk of psychosis hospitalization. Mood stabilizers used in combination with antipsychotics were associated with a decreased risk of psychosis hospitalization (Finnish cohort HR 0.76, 95% CI 0.71–0.81; Swedish cohort HR 0.84, 0.78–0.90) when compared with antipsychotic monotherapy. Combination of antidepressants and antipsychotics was associated with a decreased risk of psychosis hospitalization in the Swedish cohort (HR 0.90, 0.83–0.97) but not in the Finnish cohort (1.00, 0.94–1.07), and benzodiazepine use was associated with an increased risk (Finnish cohort HR 1.07, 1.01–1.14; Swedish cohort 1.21, 1.13–1.30). ConclusionsClozapine, LAIs, and combination therapy with mood stabilizers were associated with the best outcome and use of quetiapine and benzodiazepines with the worst outcome in the treatment of SCHAFF.     

Effect of smoking habits and concomitant valproic acid use on relapse in patients with treatment-resistant schizophrenia receiving clozapine: A 1-year retrospective cohort study

Introduction

No study has investigated the impact of smoking habits and concomitant valproic acid (VPA) use on clinical outcomes in maintenance treatment with clozapine. Thus, we aimed to examine the effect of smoking habits and concomitant VPA use on relapse during the first year after discharge in patients with treatment-resistant schizophrenia (TRS) receiving clozapine.

Methods

This retrospective cohort study included patients with TRS who were initiated on clozapine during hospitalization and discharged between April 2012 and January 2021 in two tertiary psychiatric hospitals in Japan. Relapse was defined as rehospitalization due to psychiatric exacerbation during the first year after discharge. A multivariable Cox proportional hazards regression analysis was performed to analyze the effect of smoking habits and concomitant VPA use on relapse. Subgroup analyses were also conducted to examine potential interactions between smoking habits and concomitant VPA use.

Results

Among the included 192 patients, 69 (35.9%) met the criteria of relapse. While smoking habits (adjusted hazard ratio [aHR], 2.27; 95% confidence interval [CI], 1.28–4.01; p < 0.01) independently increased the risk of relapse, a significant interaction for relapse risk was found between smoking habits and concomitant VPA use (p-interaction = 0.015). Concomitant VPA use may be an effective modifier of the increased relapse risk associated with smoking habits. Among patients who smoked, those using VPA concomitantly exhibited a higher risk of relapse (aHR, 5.32; 95% CI, 1.68–16.9; p < 0.01) than those not using VPA (aHR, 1.41; 95% CI, 0.73–2.70; p = 0.30).

Conclusion

The findings suggest that the combination of smoking habits and concomitant VPA use may increase the risk of relapse after discharge. Future studies are required to elucidate the mechanisms underlying these findings, such as a decrease in clozapine blood levels.     

Predictors of death from natural causes in schizophrenia: 10-year follow-up of a community cohort

Purpose

People with schizophrenia have increased natural mortality. There is much speculation but little evidence about the reasons behind this. This paper describes a study designed to measure the impact of pre-selected clinical, demographic and lifestyle variables on the natural mortality of a cohort with schizophrenia.

Methods

Ten-year Cox proportional hazards regression analysis of a community cohort of 95 people with schizophrenia.

Results

Death from natural causes was significantly associated with psychosis (HR 2.62, 95% CI 1.13–6.07), age (HR 1.08, 95% CI 1.02–1.13) and cigarette smoking (HR 2.53, 95% CI 1.01–6.34) at outset. There was a trend to association with low dietary unsaturated fat (P?=?0.06).

Conclusions

Active psychosis appears to predict natural mortality in people with schizophrenia. Mental health services should prioritise the effective treatment of psychosis. Further research is needed to clarify other risk factors and evaluate health promotion interventions.     

Outpatient psychiatric service use is associated with a reduced risk of 1-year readmission and mortality following alcohol-related hospitalizations: A historical cohort study

Introduction

Alcohol-related hospitalizations are common and associated with high rates of short-term readmission and mortality. Providing rapid access to physician-based mental health and addiction (MHA) services post-discharge may help to reduce the risk of adverse outcomes in this population. This study used population-based data to evaluate the prevalence of outpatient MHA service use following alcohol-related hospitalizations and its association with downstream harms.

Methods

This was a population-based historical cohort study of individuals who experienced an alcohol-related hospitalization between 2016 and 2018 in Ontario, Canada. The primary exposure was whether an individual received follow-up outpatient MHA services from either a psychiatrist or primary care physician within 30 days of discharge from the index hospitalization. The outcomes of interest were alcohol-related hospital readmission and all-cause mortality in the year following discharge from the index alcohol-related hospitalization. Information on health service use and mortality was captured using comprehensive health administrative databases. The associations between receiving outpatient MHA services and the time to each outcome were assessed using multivariable time-to-event regression.

Results

A total of 43,343 individuals were included. 19.8% of the cohort received outpatient MHA services within 30 days of discharge. Overall, 19.1% of the cohort was readmitted to hospital and 11.5% of the cohort died in the year following discharge. Receiving outpatient MHA services was associated with a reduced hazard of alcohol-related hospital readmission (adjusted hazard ratio [aHR] 0.94, 95% confidence interval [CI]: 0.88–0.99) and all-cause mortality (aHR: 0.74, 95% CI: 0.66–0.83) after adjusting for demographic and clinical covariates.

Conclusions

Short-term outcomes following alcohol-related hospitalizations are poor. Facilitating rapid access to follow-up MHA services may help to reduce the risk of recurrent harm and death in this population.     

Time trends in first admission rates for schizophrenia and other psychotic disorders in Taiwan, 1998–2007: a 10-year population-based cohort study

Purpose

To examine the trend in annual first admission rates for psychotic disorders as a whole as well as individual psychotic disorders in Taiwan from 1998 to 2007, and influences of age, sex, and geographic region on the trend.

Method

Using the inpatient claims records in the National Health Insurance Research Database, we estimated the yearly first admission rates for schizophrenia and other psychotic disorders, including voluntary (1998–2007) and involuntary (2004–2007) admissions. Both narrow and broad definitions of psychotic disorders were examined.

Results

While involuntary first admission rates were stable, a crescendo–decrescendo change in voluntary first admission rates for psychotic disorders was observed, peaking in 2001. The increase from 1998 to 2001 was closely associated with health insurance expansion. Before 2001, the voluntary first admission rates in males aged 15–24 were underestimated as military personnel records were not included in the database. From 2001 to 2007, voluntary first admissions for psychotic disorders decreased 38%; the decrease could not be accounted for by the mild diagnostic shifts away from schizophrenia to affective psychosis or substance-induced psychosis. During the entire observation period, first admission rates for schizophrenia decreased 48%, while affective psychosis increased 84%. Gender disparities in the first admission rates gradually diminished, but geographic disparities persisted.

Conclusions

First admission rates for psychosis significantly reduced in Taiwan between 1998 and 2007, mainly driven by the reduced hospitalization risk for schizophrenia. Special attention should be paid to the increased hospitalization for other types of psychotic disorders (especially affective psychosis) and the unresolved geographic disparities.

     

Association of pharmacological treatments and real-world outcomes in borderline personality disorder

Objective

Most patients with borderline personality disorder (BPD) receive psychopharmacological treatment, but clinical guidelines on BPD lack consensus on the role of pharmacotherapy. We investigated the comparative effectiveness of pharmacological treatments for BPD.

Methods

We identified patients with BPD with treatment contact during 2006–2018 using Swedish nationwide register databases. By leveraging within-individual design, in which each individual was used as their own control to eliminate selection bias, we assessed the comparative effectiveness of pharmacotherapies. For each medication, we calculated the hazard ratios (HRs) for the following outcomes: (1) psychiatric hospitalization and (2) hospitalization owing to any cause or death.

Results

We identified 17,532 patients with BPD (2649 men; mean [SD] age = 29.8 [9.9]). Treatment with benzodiazepines (HR = 1.38, 95% CI = 1.32–1.43), antipsychotics (HR = 1.19, 95% CI = 1.14–124), and antidepressants (HR = 1.18, 95% CI = 1.13–1.23) associated with increased risk of psychiatric rehospitalization. Similarly, treatment with benzodiazepines (HR = 1.37, 95% CI = 1.33–1.42), antipsychotics (HR = 1.21, 95% CI = 1.17–1.26), and antidepressants (HR = 1.17, 95% CI = 1.14–1.21) was associated with a higher risk of all-cause hospitalization or death. Treatment with mood stabilizers did not have statistically significant associations with the outcomes. Treatment with ADHD medication was associated with decreased risk of psychiatric hospitalization (HR = 0.88, 95% CI = 0.83–0.94) and decreased risk of all-cause hospitalization or death (HR = 0.86, 95% CI = 0.82–0.91). Of the specific pharmacotherapies, clozapine (HR = 0.54, 95% CI = 0.32–0.91), lisdexamphetamine (HR = 0.79, 95% CI = 0.69–0.91), bupropion (HR = 0.84, 95% CI = 0.74–0.96), and methylphenidate (HR = 0.90, 95% CI = 0.84–0.96) associated with decreased risk of psychiatric rehospitalization.

Conclusions

ADHD medications were associated with a reduced risk of psychiatric rehospitalization or hospitalization owing to any cause or death among individuals with BPD. No such associations were found for benzodiazepines, antidepressants, antipsychotics, or mood stabilizers.     

Khat use among Somali mental health service users in South London

Purpose

Khat use has been suggested to be associated with psychosis, but its prevalence and associations among mental health service users have not been described in either traditional use countries or countries with immigrant populations from traditional use countries. We aimed to investigate the clinical and demographic associations of khat use in a sample of Somali users of mental health service users in South London.

Methods

We used an electronic case register of 150,000 mental health patients to investigate the associations of khat use among all 240 Somali patients in the database. We used logistic regression to generate adjusted estimates for a range of exposure variables and used multiple imputation as a principled approach to missing data.

Results

Khat use or non-use was recorded for 172 patients (72% of the total), of whom 80 (47%) were current users. Khat use was very strongly associated with ICD-10 primary diagnosis of schizophrenia, psychosis or drug and alcohol disorder (compared to ICD-10 F43 stress-related disorders and other non-psychotic disorders), male gender, harmful or dependent use of alcohol, and detention under the Mental Health Act.

Conclusions

Recording and monitoring of khat use need to be more consistent in clinical settings, and further studies are required to investigate the much higher rates of use among those with psychotic disorders compared to non-psychotic disorders.     

Diagnostic and prognostic significance of Schneiderian first-rank symptoms: a 20-year longitudinal study of schizophrenia and bipolar disorder

Objective

This research addresses the following questions: what is the prevalence and severity of first-rank symptoms (FRS) during an extended period of time in patients with schizophrenia and bipolar disorder with psychosis? Are the specific FRS listed in Diagnostic and Statistical Manual of Mental Disorders DSM, Third Edition, Revised/Fourth Edition Criterion A for schizophrenia diagnosis (a voice keeping a running commentary or voices conversing) more prevalent and severe in patients with schizophrenia than bipolar disorder with psychosis? Lastly, do FRS at index hospitalization in patients with schizophrenia predict the absence of later recovery?

Methods

This research follows a sample of patients with psychotic disorders who were evaluated at index hospitalization and then prospectively followed-up at 6 evaluations during next 20 years (n = 86). All patients were evaluated as part of a prospective research study designed to measure multiple factors of phenomenology, severity of illness, course of illness, prognosis, and global outcome.

Results

First-rank symptoms are not exclusive to schizophrenia; they also occur in some bipolar patients. However, they are more frequent and more severe in patients with schizophrenia than bipolar disorder. Schizophrenia patients with FRS during the acute phase are more likely to have poorer long-term outcome than schizophrenia patients who do not have FRS during the acute phase.

Conclusions

Our results indicate FRS at the acute phase are not a clinicopathologic correlate specific to schizophrenia. However, the presence and severity of any FRS and specifically of the 2 FRS associated with Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised/Fourth Edition Criterion A are more prevalent and more severe in patients with schizophrenia than patients with bipolar disorder.     

Health care use,drug treatment and comorbidity in patients with schizophrenia or non-affective psychosis in Sweden: a cross-sectional study

Background

This study investigated the prevalence of schizophrenia (ICD-10 F 20) and of other non-affective psychosis (NAP, ICD-10 F 21 - F 29) in Sweden. It further assessed health care use, comorbidity and medication for these patient groups.Most studies either have a study population of patients with strictly defined schizophrenia or a psychosis population of which strict schizophrenia cases form a smaller set. The present study permits comparison of the two mutually exclusive patient groups using data at the individual level in the diagnosis of non-affective psychosis, use of health care, medical treatment and comorbidity by diagnosis or medical treatment.

Methods

In 2012, data were extracted from a regional registry containing patient-level data on consultations, hospitalisations, diagnoses and dispensed drugs for the total population in the region of Stockholm (2.1 million inhabitants). The size of the total psychosis population was 18,769, of which 7284 had a diagnosis of schizophrenia. Crude prevalence rates and risk rates with 95% confidence intervals were calculated.

Results

In 2012, the prevalence of schizophrenia and NAP was 3.5/1000 and 5.5/1000, respectively. Schizophrenia was most common among patients aged 50–59 years and NAP most common among patients aged 40–49 years.Schizophrenia patients used psychiatric health care more often than the NAP patients but less overall inpatient care (78.6 vs. 60.0%).The most prevalent comorbidities were substance abuse/dependence (7.9% in the schizophrenia group vs. 11.7% in the NAP group), hypertension (7.9 vs. 9.7%) and diabetes (6.9 vs. 4.8%).The parenteral form of long-acting injectable antipsychotics was more often dispensed to patients with schizophrenia (10 vs. 2%).

Conclusions

This study, analysing all diagnoses recorded in a large health region, confirmed prevalence rates found in previous studies. Schizophrenia patients use more psychiatric and less overall inpatient health care than NAP patients. Differences between the two patient groups in comorbidity and drug treatment were found. The registered rates of a substance abuse/dependence diagnosis were the most common comorbidity observed among the patients investigated. The observed differences between the schizophrenia and the NAP patients in health care consumption, comorbidity and drug treatment are relevant and warrant further studies.

     

A longitudinal study of the association between pro-inflammatory cytokines and mood symptoms in bipolar disorder

Background

Obstetric complications (OCs) are key contributors to psychosis risk. However, it is unclear whether they increase psychosis vulnerability independently of genetic risk, in interaction with it, or are a manifestation of psychosis proneness. We examined the role of distinct types of OCs in terms of psychosis risk and tested whether they interact differently with genetic vulnerability, whilst accounting for other known environmental risk factors.

Study Design

405 participants (219 first episode psychosis patients and 186 healthy volunteers) underwent a comprehensive assessment of OCs, measured using the Lewis-Murray scale and divided into complications of pregnancy, abnormalities of foetal growth and development, and complications of delivery. Participants were compared in terms of history of OCs, polygenic risk score for schizophrenia (PRS-SZ) and interactions between these.

Results

Both complications of pregnancy and abnormalities of foetal growth were significantly associated with case–control status (p = 0.02 and 0.03, respectively), whereas complications of delivery were not. PRS-SZ showed a significant association with psychosis (p = 0.04), but there were no significant interactions between genetic risk for schizophrenia and OCs, either when these were considered globally or separated based on their timeframe.

Conclusions

We observed no significant interaction between genetic and obstetric vulnerability, yet distinct types of OCs may have a different impact on psychosis risk, based on their nature and timeframe. Examining their differential role might clarify their relative contributions to this risk.     

Patterns of psychiatric hospitalizations in schizophrenic psychoses within the Northern Finland 1966 Birth Cohort

We report patterns of hospitalization in schizophrenic psychoses by age 34 in a longitudinal population-based cohort. We test the predictive ability of various demographic and illness-related variables on patterns of hospitalization, with a special focus on the length of the first psychiatric hospitalization. All living subjects of the Northern Finland 1966 Birth Cohort with DSM-III-R schizophrenia (n=88) and other schizophrenia spectrum cases (n=27) by the year 1997 in the Finnish Hospital Discharge Register were followed for an average of 10.5 years. Measures of psychiatric hospitalization included time to re-hospitalization (as continuous and as re-hospitalization within 2 years) and the number of hospital episodes. Length of the first hospitalization, other illness-related and various socio-demographic predictors were used to predict hospitalization patterns. After adjusting for gender, age at first admission and number of hospital days a short (1–14 days) first hospitalization (reference >30 days; adjusted odds ratio 6.39; 95% CI 2.00–20.41) and familial risk of psychosis (OR 3.36; 1.09–10.39) predicted re-hospitalization within 2 years. A short first hospitalization also predicted frequent psychiatric admissions defined as the first three admissions within 3 years (OR 13.77; 3.92–48.36). A short first hospitalization was linked to increased risk of re-hospitalizations. Although short hospitalization is recommended by several guidelines, there may be a group of patients with schizophrenic psychoses in which too short a hospitalization may lead to inadequate treatment response.     

Incidence and prevalence of mental disorders among immigrants and native Finns: a register-based study

Purpose

Migrants appear to have a higher risk of mental disorders, but findings vary across country settings and migrant groups. We aimed to assess incidence and prevalence of mental disorders among immigrants and Finnish-born controls in a register-based cohort study.

Methods

A register-based cohort study of 184.806 immigrants and 185.184 Finnish-born controls (1.412.117 person-years) was conducted. Information on mental disorders according to ICD-10 was retrieved from the Hospital Discharge Register, which covers all public health care use.

Results

The incidence of any mental disorder was lower among male (adjusted HR 0.82, 95% CI 0.77–0.87) and female (aHR 0.76, 95% CI 0.72–0.81) immigrants, being lowest among Asian and highest among North African and Middle Eastern immigrants. The incidence of bipolar, depressive and alcohol use disorders was lower among immigrants. Incidence of psychotic disorders was lower among female and not higher among male immigrants, compared with native Finns. Incidence of PTSD was higher among male immigrants (aHR 4.88, 95% CI 3.38–7.05).

Conclusions

The risk of mental disorders varies significantly across migrant groups and disorders and is generally lower among immigrants than native Finns.

     

Influence of cannabis use on incidence of psychosis in people at clinical high risk

Aims

Evidence for case–control studies suggests that cannabis use is a risk factor for the development of psychosis. However, there have been limited prospective studies and the direction of this association remains controversial. The primary aim of the present study was to examine the association between cannabis use and the incidence of psychotic disorders in people at clinical high risk of psychosis. Secondary aims were to assess associations between cannabis use and the persistence of psychotic symptoms, and with functional outcome.

Methods

Current and previous cannabis use were assessed in individuals at clinical high risk of psychosis (n = 334) and healthy controls (n = 67), using a modified version of the Cannabis Experience Questionnaire. Participants were assessed at baseline and followed up for 2 years. Transition to psychosis and persistence of psychotic symptoms were assessed using the Comprehensive Assessment of At-Risk Mental States criteria. Level of functioning at follow up was assessed using the Global Assessment of Functioning disability scale.

Results

During follow up, 16.2% of the clinical high-risk sample developed psychosis. Of those who did not become psychotic, 51.4% had persistent symptoms and 48.6% were in remission. There was no significant association between any measure of cannabis use at baseline and either transition to psychosis, the persistence of symptoms, or functional outcome.

Conclusions

These findings contrast with epidemiological data that suggest that cannabis use increases the risk of psychotic disorder.     

Examining the impact of migrant status on ethnic differences in mental health service use preceding a first diagnosis of schizophrenia

Purpose

Some ethnic groups have more negative contacts with health services for first-episode psychosis, likely arising from a complex interaction between ethnicity, socio-economic factors, and immigration status. Using population-based health administrative data, we sought to examine the effects of ethnic group and migrant status on patterns of health service use preceding a first diagnosis of schizophrenia or schizoaffective disorder among people aged 14–35 over a 10-year period.

Methods

We compared access to care and intensity of service use for first-generation ethnic minority groups to the general population of Ontario. To control for migrant status, we restricted the sample to first-generation migrants and compared service use indicators for ethnic minority groups to the European migrant group.

Results

Our cohort included 18,080 people with a first diagnosis of schizophrenia or schizoaffective disorder, of whom 14.4% (n = 2607) were the first-generation migrants. Our findings suggest that the magnitude of ethnic differences in health service use is reduced and no longer statistically significant when the sample is restricted to first-generation migrants. Of exception, nearly, all migrant groups have lower intensity of primary care use, and Caribbean migrants are consistently less likely to use psychiatric services.

Conclusions

We observed fewer ethnic differences in health service use preceding the first diagnosis of psychosis when patterns are compared among first-generation migrants, rather than to the general population, suggesting that the choice of reference group influences ethnic patterning of health service use. We need a comprehensive understanding of the mechanisms behind observed differences for minority groups to adequately address disparities in access to care.

     

The contextual fear conditioning deficit presented by spontaneously hypertensive rats (SHR) is not improved by mood stabilizers

Objectives

We have recently reported that spontaneously hypertensive rats (SHR) present a contextual fear conditioning (CFC) deficit. This deficit is improved by antipsychotic drugs, potentiated by proschizophrenia manipulations and not altered by acute administration of carbamazepine, lamotrigine and valproic acid. Nevertheless, the effects of lithium—a classical mood stabilizer—or repeated treatment with these drugs were not evaluated. The main aim of the present study was to extend our previous work by investigating a possible beneficial effect of acute and/or chronic treatments with lithium or lamotrigine on the acquisition deficit of CFC presented by SHR.

Methods

Rats were submitted to CFC task after an acute treatment with lithium and/or a repeated treatment with lithium and lamotrigine.

Results

Our data revealed that the CFC deficit presented by SHR is not improved by acute or repeated treatment with lithium. Repeated lamotrigine treatment potentiated the deficit presented by SHR and impaired CFC in control animals (Wistar Rats).

Conclusions

These data reinforce the absence of beneficial effects of mood stabilizers on the emotional context processing impairment modeled by SHR.