First episode psychosis: register-based study of comorbid psychiatric disorders and medications before and after.

Comorbid psychiatric disorders are common in first episode psychosis. We investigated comorbid disorders before, at, and after a first hospital-treated psychosis in a naturalistic nation-wide cohort (n = 2091) with a first psychosis hospitalization between 2007 and 2011, and at ages between 16 and 25. Swedish population registers were used to identify the cohort and to collect data on diagnoses at hospitalizations and medications. The proportions of cases with hospitalizations or medications increased year by year before and decreased in the years after the first psychosis hospitalization. In the 2 years before, 30% had hospitalizations with other psychiatric diagnoses and 60% had psychiatric medications. At the first psychosis hospitalization, 46% had other comorbid psychiatric diagnoses or self-harm. In the 2 years before or at the first psychosis hospitalization, 17% had anxiety or stress disorders at hospitalizations, 12% depressive disorders, 5.4% manic or bipolar disorders, 8.6% personality disorders, 26% substance use disorders, and 15% neurodevelopmental disorders. 8.2% had hospitalizations for self-harm. At most, around 30% of the cases were estimated not to have had any comorbid psychiatric disorders before or at the first psychosis presentation. Early comorbid affective, anxiety or personality disorders or self-harm were associated with a worse outcome, as measured by new psychiatric hospitalizations. The outcome was worst for personality disorders with 73% re-hospitalizations within 1 year and for patients with self-harm with 70% re-hospitalizations. In conclusion, most cases with a first psychosis hospitalization had clinical presentations indicating comorbid psychiatric disorders. Cases with comorbidity had a higher risk for re-hospitalizations.

Early predictors for late hospitalizations up to 14 years after first episode psychosis.

PURPOSE: New hospitalizations after first episode psychosis (FEP) may be viewed as an indicator of instability in a psychotic disorder. In the current study we wanted to analyse long term risk for psychosis hospitalizations after FEP. We also wanted to analyse predictors for late hospitalizations, with focus on early antipsychotic medication. METHODS: First episode psychosis cases were recruited to the Swedish Parachute project in 1996-1997. The program offered highly available and continuous psychosocial support and a cautious use of antipsychotic medication for 5 years from inclusion. Longitudinal data from population registers on psychiatric hospitalizations up to 14 years after inclusion were analysed. One hundred and sixty-one cases were included of the original 175 in the project. Associations with possible early predictive factors from the original project data were analysed with COX regression. RESULTS: A majority of the cases (67%) had hospitalizations in the first year after inclusion in the study. The cohort then diverged into a group (46%) with new hospitalizations for psychosis after the first year, most of them multiple times, and another group (54%) without new hospitalizations for psychosis, many without any late antipsychotic medication. Forty-two percentage of the cases had antipsychotic medication by month 12, and it was significantly associated with later psychosis hospitalizations (HR = 2.5, p value < 0.001). CONCLUSIONS: The study demonstrates that a large part of FEP cases have a good outcome as measured by absence of new hospitalizations for psychosis, and that many cases may terminate antipsychotic medication within a year of FEP onset without later relapses needing hospitalizations.

Substance use disorders before, at and after first episode psychosis hospitalizations in a young national Swedish cohort.

BACKGROUND: Comorbidity between Substance use disorders (SUD) and psychotic disorders is common but the temporal relation of the first episodes of SUD and psychosis and how it affects the disorders has not been extensively investigated. METHODS: A nation-wide cohort (n = 2494) with a first hospitalization for psychosis at ages between 16 and 25 was identified. Psychiatric hospitalizations were followed from birth until up to 5 years after the first psychosis hospitalization. Risk factors for new SUD or psychosis hospitalization after the index hospitalization were analyzed by Cox regression. RESULTS: 30 % of the cases had SUD hospitalizations in the 5 years before or as a comorbid diagnosis at the first psychosis hospitalization. An additional 9% had a first SUD hospitalization in the five years after. The incidence of SUD hospitalizations increased year by year before and decrease year by year after the index hospitalization. The hazard ratio for a new SUD hospitalizations after the index hospitalization was significantly higher (hazard ratio 6.7, p-value<0.001) in cases with SUD before or at the index hospitalization compared to in cases without previous SUD. In cases with previous SUD, there was a strong association (p < 0.001) between a new psychosis hospitalization and a new SUD hospitalization the year after the index hospitalization, indicating that SUD may continue to aggravate the psychotic disorder in this group. CONCLUSIONS: SUD is very common before a first hospital treated psychosis. The SUD likely aggravates early psychotic disorders in many cases.

Medication, hospitalizations and mortality in 5 years after first-episode psychosis in a Swedish nation-wide cohort.

AIM: To investigate medication, rehospitalizations and mortality after first-episode hospital-treated psychosis. METHODS: A population-based nation-wide cohort (n = 2488) with a first hospitalization for psychosis at ages between 16 and 25 was identified. Cases were followed for up to 5 years after the first psychosis hospitalization with regard to mortality, hospitalizations and dispensations of antipsychotics and benzodiazepines. RESULTS: The proportion of patients dispensing antipsychotics decreased from 80% year 1 after first discharge to 55% year 5. The proportion of patients having episodes of inpatient care also decreased year by year from 46% year 1 to 27% year 5. Of 863 cases with 5 years of observation time 41% had dispensations of antipsychotics every year; 21% had no dispensation of antipsychotics or hospitalization after the first year. The cumulative 5-year mortality was 3.9%. Cumulative suicide mortality was 2.4%. Incidence of suicide was highest in the first year. Male gender, benzodiazepines, recent hospital-discharge and self-harm were identified as risk factors for suicide. CONCLUSIONS: The proportion of cases dispensing antipsychotics decreases year by year after first discharge. Mortality and rates of rehospitalization also decrease year by year from high levels the first year.

Early recovery and employment outcome 13 years after first episode psychosis.

175 cases of first episode psychosis were recruited to the Parachute project in 1996-97. The program offered highly available and continuous psychosocial support and a cautious use of antipsychotic medication for 5 years from inclusion. Outcome-data for year 13 after inclusion, were retrieved from Swedish population registries on 161 of the original cases. During the first year after inclusion the cohort improved in the scores of the Brief Psychiatric Rating Scale (BPRS) and Global Assessment of Function (GAF) to median levels that later remained rather stable. By month 12 the median GAF score was 65. 68% of the cases were in remission from psychotic symptoms as assessed with BPRS. 38% of the cases in remission and 60% not in remission had prescriptions of antipsychotic medication by month 12. By year 13 after inclusion, 42% were in employment and 55% had any dispensation of antipsychotic medication. 70% of the cases with employment had no dispensations of antipsychotic medication. In conclusion, Many first episode psychosis cases that were offered extensive psychosocial support and cautious use of antipsychotic medication had good early recovery and good late employment outcome.

First episode psychosis and comorbid ADHD, autism and intellectual disability.

BACKGROUND: Comorbidity between neurodevelopmental disorders and psychotic disorders is common, but little is known about how neurodevelopmental disorders influence the presentation and outcome of first episode psychosis. METHODS: A nation-wide cohort (n = 2091) with a first hospitalization for psychosis between 2007-2011 and at ages between 16-25 at intake was identified from Swedish population registries. Comorbid diagnoses of neurodevelopmental disorders were identified at first psychosis hospitalization and for ADHD also by dispensations of psychostimulants before the first psychosis hospitalization. Data from the registers on hospitalizations and dispensations of antipsychotic and psychostimulant medications during the year before and 2 years after the first psychosis hospitalization were analysed. Self-harm and substance use disorders were identified by ICD10 codes at hospitalizations. RESULTS: 2.5% of the cohort was identified with a diagnosis of intellectual disability, 5.0% with autism and 8.1% with ADHD. A larger proportion of cases with Autism (OR = 1.8, p < 0.05) and intellectual disability (OR = 3.1, p < 0.01) were using antipsychotic medication year 2 compared to the rest of the cohort. Delusional disorder was more common in the autism group (OR = 2.3, p < 0.05) at first psychosis hospitalization. ADHD was associated with higher risks for substance use disorders and self-harm both before and after the first psychosis hospitalization. Year 2 substance use disorder had a OR = 2.6 (p < 0.001) and self-harm OR = 4.1 (p < 0.001). CONCLUSIONS: Psychosis with comorbid ADHD is associated with high risks for substance use disorders and for self-harm, while psychosis with comorbid autism and intellectual disability is associated with longer treatment and higher doses of antipsychotic medication.

[Investigation and follow-up requires collaboration]. / Utredning och uppföljning kräver arbete i samverkan.

A thorough investigation is warranted when a person presents to health care services with signs and symptoms of schizophrenia. Positive (hallucinations and delusions) as well as negative symptoms (blunted affect, avolition, and loss of speech content) should be assessed in order to confirm the diagnosis. Further, psychosocial functioning must be evaluated. Cognitive impairment is common in persons with psychotic illness, often leading to serious disability. Treatment planning should be based on shared decision-making involving both patients and their families. Suicide risk is elevated in people with schizophrenia, and acts of violence are somewhat overrepresented, especially when substance abuse is present. However, the risk of violence is overvalued, often colored by fear of mental illness. Risk assessments should be based on careful clinical evaluation. Established assessment scales may provide further information. A coherent, structured treatment plan that includes both pharmacotherapy and psychosocial interventions is of utmost importance in preventing both suicidal behavior and acts of violence. Case management in a multiprofessional ¼Assertive Community Treatment« (ACT) setting should be used as an organizational model for psychiatric teams caring for persons with first onset psychoses as well as those with long-term psychotic illness. Collaboration between psychiatric and social services is central and mandatory by law. Models for collaboration need to be examined further.

Concomitant medication of psychoses in a lifetime perspective.

OBJECTIVE: Patients treated with antipsychotic drugs often receive concomitant psychotropic compounds. Few studies address this issue from a lifetime perspective. Here, an analysis is presented of the prescription pattern of such concomitant medication from the first contact with psychiatry until the last written note in the case history documents, in patients with a diagnosis of psychotic illness. METHODS: A retrospective descriptive analysis of all case history data of 66 patients diagnosed with schizophrenia or schizophrenia-like psychotic disorders. RESULTS: Benzodiazepines and benzodiazepine-related anxiolytic drugs had been prescribed to 95% of the patients, other anxiolytics, sedatives or hypnotic drugs to 61%, anti-parkinsonism drugs to 86%, and antidepressants to 56% of the patients. However, lifetime doses were small and most of the time patients had no concomitant medication. The prescribed lifetime dose of anti-parkinsonism drugs was associated with that of prescribed first-generation but not second-generation antipsychotics. CONCLUSIONS: Most psychosis patients are sometimes treated with concomitant drugs but mainly over short periods. Lifetime concomitant add-on medication at the individual patient level is variable and complex but not extensive.

Use of antipsychotics - an analysis of lifetime treatment in 66 patients with psychoses.

Only a minority of patients treated with antipsychotics in clinical studies continue their treatments throughout a longer study period. Few studies address this issue from a lifetime perspective. In this naturalistic study, we aimed at analysing the prescription pattern of antipsychotic drugs among a sample of Swedish patients with a diagnosis of psychotic illness, from the first contact with psychiatry (typically between 1973 and 1997) until the last written note in the case history documents. A retrospective descriptive analysis was performed of all case history data of 66 patients diagnosed with schizophrenia or related psychotic disorders. Patients with schizophrenia were prescribed antipsychotic medication more than 90% of the time. Each patient generally had been prescribed several (up to 16) different antipsychotic drugs and a quarter of the patients had been prescribed two or more antipsychotics for a third of their prescription time. Patients with psychosis were exposed to a cumulatively growing number of antipsychotics. Various factors, including clinician and patient expectations, and specific strengths and limitations of available antipsychotics may account for frequent medication changes over time.

Oxidative stress, NO* and smooth muscle cell extracellular superoxide dismutase expression.

Oxygen free radicals apparently play important roles in diseases of the blood vessel wall and increased secretion of superoxide radicals occurs in many situations. The vascular wall contains large amounts of extracellular superoxide dismutase (EC-SOD). The synthesis of the enzyme by the smooth muscle cells (SMC) is modulated by cytokines, growth factors, and vasoactive factors. Here we studied the effects of oxidants (pyrogallol, xanthine oxidase, Cu and Fe), antioxidants (SOD, catalase, and ascorbate), glutathione modulation (n-acetylcysteine and buthionine sulfoximine) and nitric oxide on EC-SOD expression by human vascular SMCs. Generally, the responses in EC-SOD synthesis were small, and no changes were noted in mRNA levels. High concentrations of some of the agents caused reductions in EC-SOD synthesis, mostly concomitantly with toxic effects on the cells. Cell cultures are normally ascorbate deficient, and addition of ascorbate to approach physiological levels doubled the EC-SOD content. Iron ions up-regulated EC-SOD synthesis but also blocked the secretion of the enzyme. Only down-regulation was found by NO*-releasing compounds.In conclusion, there is limited response to oxidant stress of EC-SOD synthesis by SMCs on a cell-autonomous level. The synthesis appears mainly regulated by factors coordinating concerted tissue responses.