Schizophrenia In Denmark Research Articles

The influence of comorbid disease on premature death due to natural and unnatural causes in persons with schizophrenia.

Comorbid disease may increase mortality in persons with schizophrenia, but how specific diseases are associated with natural and unnatural death in different age groups is unclear. To investigate the association between eight major comorbid diseases and death from natural and unnatural causes in different age groups in persons with schizophrenia. Retrospective register-based cohort study in 77,794 persons with schizophrenia in Denmark, 1977-2015. Using Cox regression in matched cohorts, we estimated hazard ratios for natural and unnatural death in three age groups (<55years, 55-64years, ≥65years). Hypertensive disease, atrial fibrillation, coronary heart disease, cerebrovascular disease, heart failure, type 2 diabetes, liver disease and chronic kidney disease were all strongly associated with natural death, with the strongest associations observed in persons <55years (hazard ratio [HR] range 1.98-7.19). The strongest associations were observed for heart failure (HR 7.19, 95% confidence interval [CI] 5.57-9.28; HR 4.56, CI 3.85-5.40; HR 2.83, CI 2.53-3.17), liver disease (HR 4.66, CI 3.59-6.05; HR 4.70, CI 3.55-6.22; HR 2.57, CI 1.98-3.34) and chronic kidney disease (HR 6.59, CI 1.66-26.1; HR 7.37, CI 3.03-17.9; HR 2.86, CI 1.84-4.46) for persons <55years, 55-64years and ≥65years, respectively. Liver disease was strongly associated with unnatural death in persons <55years (HR 5.42, CI 3.01-9.75); associations with the remaining comorbidities were weaker. Comorbid disease was strongly associated with natural death, with the strength of the associations decreasing with age. Comorbid disease was also modestly associated with unnatural death, regardless of age.

Development over time of the population-attributable risk fraction for cannabis use disorder in schizophrenia in Denmark

Development over time of the population-attributable risk fraction for cannabis use disorder in schizophrenia in Denmark

Free-of-charge dispensing of antipsychotics for schizophrenia in Denmark: Impact on the nationwide prescription registry and redemption of somatic medications.

ObjectiveFree‐of‐charge dispensing of antipsychotics for schizophrenia was introduced in Denmark around 2008. However, free‐of‐charge dispensing is not recorded in the Danish National Prescription Register (DNPR), potentially introducing bias and misclassification.MethodsWe identified all 30 275 individuals with a first‐episode schizophrenia diagnosis in Denmark between 1 January 1999 and 1 March 2017 including all redeemed prescriptions registered in the DNPR during the 2 years after the schizophrenia diagnosis. For each calendar year, we calculated the proportion of individuals who had filled ≥1 prescription for psychotropic and/or somatic medications within the first 2 years after the schizophrenia diagnosis.ResultsFrom 2007 to 2017, the proportion of individuals with prescription‐records for any psychotropic medication during the 2 years after the schizophrenia diagnosis decreased from 88% to 74%, particularly antipsychotics (from 83% to 61%) and antidepressants (from 49% to 35%). This was particularly observed among those aged 18–30 years at the schizophrenia diagnosis. A similar decrease was not observed for prescription‐records of somatic medications.ConclusionThe introduction of free‐of‐charge antipsychotics has affected the redemption of specific psychotropic drugs in the DNPR in first‐episode schizophrenia. This limitation needs to be considered in register‐based studies and emphasizes the need to identify solutions.

Development Over Time of the Population-Attributable Risk Fraction for Cannabis Use Disorder in Schizophrenia in Denmark

Cannabis use and potency of cannabis have increased during the past 2 decades. If the association between cannabis use and schizophrenia is causal, this should be reflected in an increase in the proportion of cases of schizophrenia being attributable to cannabis, the population-attributable risk fraction (PARF). To determine whether the PARF for cannabis use disorder in schizophrenia has increased over time. This nationwide, register-based historical prospective cohort study included all people in Denmark born before December 31, 2000, who were alive and 16 years or older at some point from January 1, 1972, to December 31, 2016. Data analysis was performed from August 2020 to April 2021. Diagnosis of cannabis use disorder. Diagnosis of schizophrenia, with estimated PARF of cannabis use disorder in schizophrenia from 1972 to 2016. A total of 7 186 834 individuals were included in the analysis, including 3 595 910 women (50.0%) and 3 590 924 men (50.0%). The adjusted hazard ratio for schizophrenia fluctuated at approximately 4 (with 95% CIs ranging from approximately 3 to 6) throughout most of the study period when people diagnosed with cannabis use disorder were compared with those without cannabis use disorder. The PARF of cannabis use disorder in schizophrenia also fluctuated, but with clear evidence of an increase from 1995 (when the PARF was relatively stable around 2.0%, with a 95% CI of approximately 0.3% to either side) until reaching some stability around 6.0% to 8.0% (with a 95% CI of approximately 0.5% to either side) since 2010. The results from these longitudinal analyses show the proportion of cases of schizophrenia associated with cannabis use disorder has increased 3- to 4-fold during the past 2 decades, which is expected given previously described increases in the use and potency of cannabis. This finding has important ramifications regarding legalization and control of use of cannabis.

Long-term outcome of early-onset compared to adult-onset schizophrenia: A nationwide Danish register study

ObjectiveEarly-onset schizophrenia (EOS) may have worse outcomes than adult-onset schizophrenia (AOS), but data are scarce. We compared outcomes of EOS vs. AOS. MethodsLongitudinal, register-based study of patients diagnosed with schizophrenia in Denmark between 1996 and 2012, with follow-up until 12/2014. Co-primary outcomes were psychiatric inpatient days during the initial two years after schizophrenia diagnosis and mean number of annual inpatient days for the remaining follow-up. ResultsAltogether, 16,337 patients with schizophrenia were included (EOS = 1223, AOS = 15,114, mean follow-up = 9.5 ± 5.0 years). EOS were hospitalized longer during the first two years than AOS (180.9 ± 171.0 vs 163.4 ± 183.1 days, p < 0.005; IRR = 1.27, 95% CI = 1.19–1.35, p < 0.001), but duration and annual rates thereafter did not differ (EOS = 26.8 ± 57.1 days, AOS = 26.6 ± 56.2 days, p = 0.95; IRR = 1.07, 95% CI = 0.94–1.23, p = 0.30). Fewer EOS patients were never psychiatrically hospitalized (EOS = 17.2%, AOS = 20.1%, p < 0.001), but with no difference in re-admissions in patients diagnosed during hospitalization (EOS = 77.1% vs AOS = 78.1%, p = 0.56). More EOS patients were admitted involuntarily (41% vs. 36%, p < 0.02). AOS patients had more often comorbid substance use disorders during follow-up than EOS (EOS = 21.7%, AOS = 34.2%, p < 0.001). Substance use disorders and out-of-home placement were significantly associated with more inpatient days during both short- and long-term follow-up. ConclusionAlthough EOS was associated with more inpatient days in the first two years after diagnosis, results do not seem to support a generally poorer long-term outcome of EOS compared to AOS. Longer initial hospitalization may be driven by different treatment patterns in child and adolescent vs. adult psychiatry. These data suggest that patient characteristics other than age of onset significantly affect outcomes.

Societal Costs of Schizophrenia in Denmark: A Nationwide Matched Controlled Study of Patients and Spouses Before and After Initial Diagnosis.

Information on welfare cost of patients with schizophrenia and spouses is limited. The main aim of this study to investigate factual societal mean annual costs per individual during 5 years before and after the initial diagnosis of schizophrenia. A register-based cohort study of 12 227 patients with incident schizophrenia (International Classification of Diseases, Tenth Revision F20-F20.99) with spouses and 48 907 matched controls in Denmark during 2002-2016. The total annual costs of health care and lost productivity were Euro 43 561 higher for patients with schizophrenia and health care costs and costs of lost productivity were increased during 5 years before the initial diagnosis. The total annual direct health care and indirect costs of lost productivity were Euro 21 888 higher for spouses to patients with schizophrenia than spouses of individuals with no diagnosis of schizophrenia. Also before initial diagnosis, health care costs and lost productivity were increased among spouses of patients with schizophrenia. Patients with schizophrenia differed from the general population with respect to all included costs. The study documented a significant burden on spouses. The excess health care costs of schizophrenia are further increased by psychiatric and somatic comorbidity, and the societal costs are 4-10 times higher than chronic neurological disorders such as epilepsy and multiple sclerosis. Early onset of schizophrenia implies that patients are affected before finishing school and before entrance to labor market. Cost savings could be achieved by investments in preventive interventions reaching young people's needs; in initiatives to reduce hospital admissions caused by medication side effects, substance misuse, and lifestyle factors; and in occupational training.

The effect of implementation of an early detection team: A nationwide register-based study of characteristics and help-seeking behavior in first-episode schizophrenia in Denmark

BackgroundIn an effort to make people with signs of psychosis seek help as early as possible, Region Zealand launched in 2012 an early detection team project as the first and only in Denmark. The project consisted of a combination of easy access and an information campaign targeting the public. This nation-wide study examined characteristics and help-seeking behavior of patients with first-episode schizophrenia (FES) in the early detection region in comparison with other Danish regions. MethodData from the Danish National Schizophrenia register on all Danish patients diagnosed with first-episode schizophrenia during 2012 to 2015 were linked to demographic and health care data drawn from official national registers. Binary logistic regression analyses examined the difference between the early detection region and other regions controlling for demographic characteristics and utilization of mental health care services and contacts to general practitioner (GP). ResultsPatients in the early detection region were younger (OR = 0.51; CI: 0.42–0.62; p < 0.000) than in regions without early detection teams. Furthermore, they were more likely to be of Danish origin, and less likely to have contact with mental health services and GPs prior to FES. ConclusionThe study suggests that implementing an early detection team in combination with an information campaign contributed to detecting patients with first-episode schizophrenia earlier than in regions without the early detection team. The study gives an indication of different pathways among patients in the early detection region.

The role of genetic liability in the association of urbanicity at birth and during upbringing with schizophrenia in Denmark.

Studies have indicated that the association of urbanicity at birth and during upbringing with schizophrenia may be driven by familial factors such as genetic liability. We used a population-based nested case-control study to assess whether polygenic risk score (PRS) for schizophrenia was associated with urbanicity at birth and at age 15, and to assess whether PRS and parental history of mental disorder together explained the association between urbanicity and schizophrenia. Data were drawn from Danish population registries. Cases born since 1981 and diagnosed with schizophrenia between 1994 and 2009 were matched to controls with the same sex and birthdate (1549 pairs). Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of a separate, large meta-analysis. Those with higher PRS were more likely reside in the capital compared with rural areas at age 15 [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01-1.40], but not at birth (OR 1.09, 95% CI 0.95-1.26). Adjustment for PRS produced almost no change in relative risks of schizophrenia associated with urbanicity at birth, but slightly attenuated those for urban residence at age 15. Additional adjustment for parental history led to slight attenuation of relative risks for urbanicity at birth [incidence rate ratio (IRR) for birth in capital = 1.54, 95% CI 1.18-2.02; overall p = 0.016] and further attenuation of relative risks for urbanicity at age 15 (IRR for residence in capital = 1.32, 95% CI 0.97-1.78; overall p = 0.148). While results regarding urbanicity during upbringing were somewhat equivocal, genetic liability as measured here does not appear to explain the association between urbanicity at birth and schizophrenia.

Quality of Care and Outcomes of Heart Failure Among Patients With Schizophrenia in Denmark

Research on the association between schizophrenia and the quality of care and clinical outcomes of heart failure (HF) remains sparse. This nationwide study compared the quality of care and clinical outcomes of HF among Danish patients with and without schizophrenia. In a population-based cohort study, we identified 36,718 patients with incident HF with hospital contacts, including 108 with schizophrenia, using Danish registries between 2004 and 2013. High quality of HF care was defined as receiving ≥ 80% guideline-recommended process-performance measures of care. Potential predictors of HF care among patients with schizophrenia included patient-specific factors (age, gender, Global Assessment of Functioning [GAF] score, alcohol or drug abuse, duration of schizophrenia); provider-specific factors (quality of schizophrenia care); and system-specific factors (patient-volume defined as hospital departments and clinics yearly average patient-volume of patients with incident HF). Clinical outcomes included 4-week all-cause readmission and 1-year all-cause mortality after a first-time hospital contact with incident HF. Results showed that compared with patients with incident HF who have no schizophrenia, patients with incident HF who have schizophrenia had a lower chance of receiving high-quality HF care (relative risk 0.66, 95% confidence interval 0.48 to 0.91). A high GAF score was associated with a higher chance of receiving high-quality HF care among patients with incident HF who have schizophrenia. Patients with incident HF who have schizophrenia had a higher risk of 1-year mortality (adjusted hazard ratio 2.83, 95% confidence interval 1.59 to 5.04), but not a higher risk of readmission than patients with incident HF who have no schizophrenia. In conclusion, efforts are warranted to reduce the high mortality among patients with incident HF who have schizophrenia.

Diabetic ketoacidosis and diabetes associated with antipsychotic exposure among a previously diabetes-naive population with schizophrenia: a nationwide nested case-control study.

Diabetic ketoacidosis (DKA) is a potentially fatal metabolic emergency of both type 1 and type 2 diabetes. Although there is a reduced risk of type 1 diabetes in schizophrenia, the incidence of DKA is tenfold higher than that of the general population. Thus, we aimed to investigate associations between exposure to antipsychotic medication (within 3months prior to event) and DKA, type 1 diabetes and type 2 diabetes. We also reported related, clinically relevant outcomes. Using a nested case-control study design, we identified cases of DKA, type 1 diabetes and type 2 diabetes in a previously diabetes-naive population with schizophrenia in Denmark from 1995 to 2014. Cases were matched (by age, sex and year of schizophrenia onset) 1:5 to schizophrenic control individuals who were alive and had not emigrated prior to event. Conditional logistic regression was used to compute ORs with 95% CIs. Other outcomes included diabetes aetiology of DKA, in-hospital mortality, DKA readmissions and temporal trends of use of insulin and oral glucose-lowering agents. Of 29,955 individuals with schizophrenia, we identified 28 individuals with DKA, 90 with type 1 diabetes and 2140 with type 2 diabetes. These were matched to 137, 410 and 9861 individuals in the control group, respectively. Antipsychotic exposure was associated with DKA (OR 2.60; 95% CI 1.06, 6.38) and type 2 diabetes (OR 1.64; 95% CI 1.48, 1.83). A trend towards increased risk of type 1 diabetes was found but remained insignificant (OR 1.38; 95% CI 0.84, 2.29). Diabetes aetiology of DKA was type 1 in eight cases and type 2 in 14 cases. Of the remaining six cases of DKA, aetiology could not be determined, as four were fatal within 8days and for two, no prescriptions for insulin and oral glucose-lowering agents were redeemed. Of all DKA cases, six had more than one episode of DKA, and of all type 1 diabetes and type 2 diabetes cases, four and 11, respectively, had at least one episode. Use of insulin and oral glucose-lowering agents was higher among individuals with DKA relative to those with type 1 diabetes and type 2 diabetes. Antipsychotic exposure was associated with DKA and type 2 diabetes in a previously diabetes-naive schizophrenia population. Antipsychotic-associated DKA is relevant not only for psychiatrists but also for other physicians who may manage and admit such patients.

Frequency and correlates of anticholinergic use among patients with schizophrenia in Denmark: A Nation-wide pharmacoepidemiological study

Anticholinergic medications are used to treat extrapyramidal adverse effects induced by antipsychotics. Anticholinergics are associated with adverse effects: constipation, dry mouth and worsening of cognitive function. Anticholinergics have potential for abuse and are not recommended for long term-treatment. We aimed to investigate the use of anticholinergics in patients with schizophrenia. The national health registers in Denmark were used to examine: The prevalence of anticholinergics in 1996–2012 using a cross-sectional design; geographic variations in the prescription of anticholinergics in 2012; correlates of treatment with anticholinergics.The proportion of patients using anticholinergics decreased significantly from 11.7% in 1996 to 5.7% in 2012. The prescription pattern varied considerably between national regions in 2012, ranging from 4.0% in the Capital Region to 8.1% in the Northern Denmark Region. Long-term use of anticholinergics was predicted by older age, age at debut of schizophrenia, receiving early retirement pension, typical antipsychotic use, antipsychotic polypharmacy, typical + atypical antipsychotics, antidepressant treatment, high doses of antipsychotics measured in defined-daily-dose, physical comorbidity and psychiatrists` greater caseload.Use of anticholinergics declined during the study period, and showed substantial variation across the regions in 2012. Long-term use was linked to typical antipsychotic use and variables that are associated with greater illness severity.

Predictors of Nonhospitalization and Functional Response in Clozapine Treatment: A Nationwide, Population-Based Cohort Study.

Clozapine remains the only evidence-based treatment for treatment-resistant schizophrenia, and prediction of clozapine response is important in developing stratified treatment. We studied potential predictors of clozapine response, applying functional assessments as well as service use. We performed a nationwide cohort study among all individuals diagnosed with schizophrenia in Denmark after 1995 (age, ≥18 years) who initiated clozapine treatment between 2004 and 2011 with a Global Assessment of Functioning (GAF-F) score registered at clozapine initiation. During up to 2-year follow-up, clinical response was defined as (a) no further hospitalization with schizophrenia or (b) improvement in GAF-F score (moderate improvement: increase, ≥10; substantial improvement: increase, ≥20; and GAF-F, ≥50). We performed Cox regression analysis and report adjusted hazard rate ratios (HRRs; 95% confidence intervals [95% CIs]). Among 502 clozapine users with a registered GAF-F score, 232 (46.2%) remained out of hospital, 96 (19.1%) achieved moderate functional improvement, and 29 (5.8%) substantial functional improvement. Of all potential predictors, voluntary status at clozapine initiation showed borderline statistical significance with nonhospitalization (HRR, 1.61; 95% CI, 0.97-2.67). Regarding functional improvement, living with a partner was the strongest predictor with an almost threefold increased HRR (2.78; 95% CI, 1.07-7.23). Female sex was only nonsignificantly associated with functional improvement, whereas the chance of substantial improvement decreased by 15% (HRR, 0.85; 95% CI, 0.72-1.00) for each year delay in clozapine initiation among females. Living with a partner was the strongest predictor of functioning after clozapine initiation in this study. Although potentially indicating better premorbid functioning, this finding stresses the need and importance of social support during the course of the treatment independent of clinical factors.

ISQUA16-1522QUALITY AND PREDICTORS OF DIABETES CARE AMONG PATIENTS WITH SCHIZOPHRENIA

Data on the quality of care for diabetes among patients with schizophrenia remain sparse, in particular from universal and free of charge health care systems. This study aimed to compare the quality of care for diabetes among patients with and without schizophrenia in Denmark and to identify predictors of quality of care. In a nationwide population-based …

Concomitant NSAID use during antipsychotic treatment and risk of 2-year relapse – a population-based study of 16,253 incident patients with schizophrenia

ABSTRACTObjective: Clinical trials have indicated antipsychotic effects of non-steroidal anti-inflammatory drugs (NSAIDs) among incident patients with schizophrenia. We aimed to study, in a population-based setting, whether concomitant use of NSAIDs or paracetamol, changed 2-year relapse risk for schizophrenia.Methods: We identified all incident patients with schizophrenia in Denmark diagnosed 1996–2012 initiating antipsychotic treatment within the year after diagnosis. We calculated concomitant treatment intervals for antipsychotic and NSAID or paracetamol use. Hazard rate ratios (HRR) were estimated using Cox regression adjusted for important covariates.Main outcome measures: 2-year relapse, i.e. (re)-hospitalizations with schizophrenia.Results: Among 16,235 incident patients with schizophrenia using antipsychotics, 1480 (9.1%) used NSAIDs and 767 (4.7%) paracetamol. Concomitant use of NSAIDs was associated with an increased risk of schizophrenia relapse (HRR = 1.21; 95%-CI = 1.11-1.31), particularly associated with acetylsalicylic acid and diclofenac. Concomitant use of paracetamol was not associated with schizophrenia relapse (HRR = 0.97; 95%-CI = 0.87-1.08). Subgroup analyses showed that individuals with somatic comorbidity and NSAID use had an increased relapse-risk, except for individuals with a prior hospital diagnosis for musculoskeletal disease and NSAID use who had a decreased relapse-risk (HRR = 0.82; 95%-CI = 0.71-0.94).Conclusions: The increased relapse risk associated with concomitant NSAID use among incident patients with schizophrenia may indicate a potential impact of underlying somatic comorbidity.

Changes in the utilization of psychiatric hospital facilities in Denmark by patients diagnosed with schizophrenia from 1970 through 2012: The advent of 'revolving door' patients.

The Danish psychiatric system has gone through several structural changes in the last four decades. The deinstitutionalization of the mental healthcare system was implemented in Denmark in the late 1970s with the intention of increasing out-patient treatment. One of the aims in the reorganization was to treat the patient in the local environment rather than during long-term hospitalization. This study focuses on the changes in the utilization of hospital facilities. Using register data from secondary healthcare treatment of patients diagnosed with schizophrenia in Denmark 1970-2012, we analysed the development in the use of hospital facilities. Our major finding was a 220% increase between 1970 and 2012 in the total number of hospital admissions due to schizophrenia each year, while at the same time the number of annual schizophrenia bed days was reduced by 76%. Furthermore, the readmission rate within a year after discharge with a diagnosis of schizophrenia reached 70% in 2012 compared to 51% in 1970. Finally, the total bed occupancy continued to rise over the four decades and has exceeded 100% in several years since 1999. The findings indicate that the reorganization of the Danish mental healthcare system has created a problem of 'revolving door' schizophrenia patients' who since the 1970s have been increasingly hospitalized but for shorter periods. Possible explanations of the findings are premature discharge of patients with schizophrenia due to lack of beds or/and that community psychiatry has not been providing adequate relapse prevention.

Improving quality of care among patients hospitalised with schizophrenia: a nationwide initiative.

BackgroundThe effectiveness of systematic quality improvement initiatives in psychiatric care remains unclear.AimsTo examine whether quality of care has changed following implementation of a systematic monitoring programme of hospital performance measures.MethodIn a nationwide population-based cohort study, we identified 14 228 patients admitted to psychiatric departments between 2004 and 2011 from The Danish Schizophrenia Registry. The registry systematically monitors the adherence to guideline recommended processes of care.ResultsThe overall proportion of all relevant recommended processes of care increased from 64 to 76% between 2004 and 2011. The adherence to individual processes of care increased over time, including assessment of psychopathology using a diagnostic interview (relative risk (RR): 2.01, 95% CI: 1.51–2.68), contact with relatives (RR: 1.44, 95% CI: 1.27–1.62), psychoeducation (RR: 1.33, 95% CI: 1.19–1.48), psychiatric aftercare (RR: 1.06, 95% CI: 1.01–1.11) and suicide risk assessment (RR: 1.31, 95% CI: 1.21–1.42).ConclusionsQuality of care improved from 2004 to 2011 among patients hospitalised with schizophrenia in Denmark.Declaration of interestNone.Copyright and usage© The Royal College of Psychiatrists 2015. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Frequency and correlates of antipsychotic polypharmacy among patients with schizophrenia in Denmark: A nation-wide pharmacoepidemiological study

Although evidence for efficacy of antipsychotic polypharmacy (APP) is sparse, APP is common in schizophrenia. The national Danish health registers were accessed to examine in schizophrenia patients: (1) cross-sectional prevalences of APP (1996–2012); (2) geographic variations in APP (2012); and (3) correlates of APP (2012). APP increased from 17.2% in 1996 to 30.8% in 2006 (p<0.001), declining to 24.6% in 2012 (p<0.001) (overall trend 1996–2012: α=0.653, 95% confidence interval (CI):0.327–0.979, p<0.001). Comparing the 1996–2005 and 2006–2012 cohorts APP occurred significantly faster in the 2006 cohort after schizophrenia diagnosis (p<0.0001). The predominant APP type changed from first-generation antipsychotic combinations in 1996 (77.3%) to first+second-generation antipsychotic combinations in 2003 (70.3%) and second-generation antipsychotic combinations in 2012 (59.2%). In 2012, the prevalence of APP varied from 19.4% in Copenhagen to 29.3% in the region of Zealand. Independent correlates of APP, explaining 37.9% of the variance, included a higher number of patients per psychiatrist (OR=1.04/10 patients, CI=1.03–1.06, p<0.001),lower proportion of males (OR=0.80, CI=0.74–0.86), younger age (OR=1.00, CI=0.99–1.00), several schizophrenia subtypes (paranoid: OR=1.24, CI=1.11–1.38,hebephrenic: OR=1.30, CI=1.03–1.63, other: OR=1.95 CI=1.17–3.24, unspecified: OR=1.21 CI=1.05–1.40), living alone (OR=1.12, CI=1.01–1.24), being institutionalized (OR=1.23, CI=1.06–1.42), receiving early retirement pension (OR=1.21, CI=1.10–1.34), higher Charlson Co-morbidity Index score (OR=1.13, CI=1.07–1.19), higher antipsychotic defined daily doses (OR=3.05, CI=−2.95–3.16), treatment with clozapine (OR=3.09, 95% CI=2.78–3.44), and treatment with antidepressants (OR=1.97 (CI=1.83–2.13), long-acting injectable antipsychotics (OR=1.48, CI=1.34–1.63), and anticholinergics (OR=1.74, CI=1.51–2.01). APP remains common in schizophrenia with substantial temporal and geographical variation, being associated with indicators of illness severity and chronicity.

The Global Assessment of Functioning (GAF) as Potential Predictor for Relapse Among 5,674 Incident Schizophrenia Patients – a Nationwide Study

Introduction Integration of functional aspects in the treatment of schizophrenia is important; however, little knowledge exists whether the global assessment of functioning (GAF) predicts early clinical course. Objectives To investigate associations between GAF and relapse. Aims To identify all adults (≥18 years) for the first-time diagnosed with schizophrenia in Denmark in 2004-2012 and calculate the risk of 2-year relapse. Methods Patients were categorized according to baseline GAF-scores (at initiation of outpatient or discharge from inpatient contact, respectively): 61-100, 46-60, 31-45 and 1-30. Relapse was the first schizophrenia (re)-hospitalization. We performed Cox regression analyses (hazard rate ratios (HRR), 95%-confidence intervals (95%-CI)) adjusted for: sex, age, substance abuse, duration of untreated psychosis (DUP), length of baseline hospitalization, index-year, antipsychotic treatment and side effects. Results Among 5,674 incident patients, 5,184 (91.4%) had a valid baseline GAF-score. Lower GAF-scores were associated with longer DUP and baseline hospitalization. 2,278 (40.2%) experienced relapse, 428 (20.7%) of outpatients and 1,850 (51.3%) of inpatients. Lower GAF was associated with an increased risk for relapse in a dose-response relationship. Among inpatients, GAF≤30 (compared with GAF>60) was Associated with a 43% increased risk. Among outpatients, the relapse risk increase was HRR=1.22 (95%-CI=0.76; 1.97) with GAF=46-60; HRR=1.93 (95%-CI=1.24; 3.02) with GAF=31-45, and HRR=3.07 (95%-CI=1.84; 5.13) with GAF=1-30. Conclusions Lower baseline GAF was associated with increased 2-year relapse risk in a dose-response relationship. The clinically widely used GAF may be an important tool for prediction of early clinical course among incident adult schizophrenia patients, in particular in an outpatient setting.

Characteristics and predictors of long-term institutionalization in patients with schizophrenia

Background Patients with schizophrenia requiring long-term institutionalization represent those with the worst outcome, leading to personal costs for patients and relatives and constituting a large economical burden for society. Aim To identify characteristics and predictors of outcome of institutionalized patients with schizophrenia. Method One-year follow-up cohort study, utilizing the Danish national registers, of all institutionalized and non-institutionalized patients with schizophrenia in Denmark with an ICD-10 lifetime diagnosis of schizophrenia (F20.0–F20.9) since 1969 and alive at the index date of January 1st 2006 (total number 22,395). Results Compared with non-institutionalized patients, institutionalized patients (n = 2188; 9.8%) had earlier onset of schizophrenia and lower scholastic achievements, were more often diagnosed with a hebephrenic subtype (odds ratio (OR), 2.34; 95% confidence interval (CI), 1.95–2.80; p < 0.001), received higher dosages of antipsychotics, more antipsychotic polypharmacy and more concomitant medications, and had more substance misuse and early retirement pension. In a logistic regression model adjusted for sex and age, institutionalized patients with schizophrenia had an increased risk of type II diabetes (AOR, 1.22; CI, 1.01–1.42; p < 0.001), but the mean age of onset of type II diabetes did not differ. The mean patient age was higher in the institutionalized group (62.7 vs. 58.7 years; p = 0.027), which was mainly driven by absence of death from suicide in the institutionalized group. Multivariate predictors of institutionalization included hebephrenic subtype, a diagnosis of epilepsy, early retirement pension, male sex, a greater proportion of prior hospitalization, and substance misuse. Conclusions Institutionalized patients with schizophrenia had a more complex and worse outcome of the disorder, except for less suicide, illustrated by lower scholastic achievement, receiving higher dosages of antipsychotic medications, more concomitant medications and more prior bed-days.

Antipsychotics Associated with the Development of Type 2 Diabetes in Antipsychotic-Naïve Schizophrenia Patients

Diabetes mellitus occurs in schizophrenia patients at higher rates than in the general population. Reasons for this elevated risk are poorly understood and have not been examined prospectively in antipsychotic-naïve, first-episode patients. This study aims to determine which antipsychotics are associated with diabetes development in antipsychotic-naïve schizophrenia patients. All antipsychotic-naïve patients diagnosed with schizophrenia in Denmark between 01 January 1997 and 31 December 2004, followed until 31 December 2007, allowing for >or=3 years follow-up, unless death or diabetes onset occurred. Risk factors for the time to diabetes onset were assessed, including antipsychotics taken for at least 180 defined daily doses in the first year after first antipsychotic prescription ('initial treatment'). Risk factors for diabetes incidence were assessed, including antipsychotic use within 3 months before diabetes onset or study end ('current treatment'). Of 7139 patients, followed for 6.6 years (47,297 patient years), 307 developed diabetes (annual incidence rate: 0.65%). Time to diabetes onset was significantly shorter in patients with higher age (hazard ratio (HR): 1.03, confidence interval (CI): 1.02-1.03) and those with 'initial' treatment of olanzapine (HR: 1.41, CI: 1.09-1.83), mid-potency first-generation antipsychotics (FGAs) (HR: 1.60, CI: 1.07-2.39), antihypertensive (HR: 1.87, CI: 1.13-3.09), or lipid-lowering drugs (HR: 4.67, CI: 2.19-10.00). Significant factors associated with diabetes within 3 month of its development included treatment with low-potency FGAs (odds ratio (OR): 1.52, CI: 1.14-2.02), olanzapine (OR: 1.44, CI: 1.98-1.91), and clozapine (OR: 1.67, CI: 1.14-2.46), whereas aripiprazole was associated with lower diabetes risk (OR: 0.51, CI: 0.33-0.80). In addition to general diabetes risk factors, such as age, hypertension, and dyslipidemia, diabetes is promoted in schizophrenia patients by initial and current treatment with olanzapine and mid-potency FGAs, as well as by current treatment with or low-potency first-generation antipsychotics and clozapine, whereas current aripiprazole treatment reduced diabetes risk. Patients discontinuing olanzapine or mid-potency FGA had no increased risk of diabetes compared with patient not treated with the drugs at anytime.