Discontinuation of antipsychotics in individuals with first-episode schizophrenia and its association to functional outcomes, hospitalization and death: a register-based nationwide follow-up study.

BACKGROUND: Discontinuation of antipsychotic medication may be linked to high risk of relapse, hospitalization and mortality. This study investigated the use and discontinuation of antipsychotics in individuals with first-episode schizophrenia in relation to cohabitation, living with children, employment, hospital admission and death. METHODS: Danish registers were used to establish a nationwide cohort of individuals ⩾18 years with schizophrenia included at the time of diagnosis in1995-2013. Exposure was antipsychotic medication calculated using defined daily dose and redeemed prescriptions year 2-5. Outcomes year 5-6 were analysed using binary logistic, negative binomial and Cox proportional hazard regression. RESULTS: Among 21 351, 9.3% took antipsychotics continuously year 2-5, 38.6% took no antipsychotics, 3.4% sustained discontinuation and 48.7% discontinued and resumed treatment. At follow-up year 6, living with children or employment was significantly higher in individuals with sustained discontinuation (OR 1.98, 95% CI 1.53-2.56 and OR 2.60, 95% CI 1.91-3.54), non-sustained discontinuation (OR 1.25, 95% CI 1.05-1.48 and 2.04, 95% CI 1.64-2.53) and no antipsychotics (OR 2.00, 95% CI 1.69-2.38 and 5.64, 95% CI 4.56-6.97) compared to continuous users. Individuals with non-sustained discontinuation had more psychiatric hospital admissions (IRR 1.27, 95% CI 1.10-1.47) and longer admissions (IRR 1.68, 95% CI 1.30-2.16) year 5-6 compared to continuous users. Mortality during year 5-6 did not differ between groups. CONCLUSION: Most individuals with first-episode schizophrenia discontinued or took no antipsychotics the first years after diagnosis and had better functional outcomes. Non-sustained discontinuers had more, and longer admissions compared to continuous users. However, associations found could be either cause or effect.

Predictors of Return to Work for People with Anxiety or Depression Participating in a Randomized Trial Investigating the Effect of a Supported Employment Intervention.

Purpose Common mental disorders have a severe impact on society and individuals; rates of unemployment and disability pensions are high. Knowing which factors facilitate or hinder people's return to work is important when designing effective vocational rehabilitation interventions. Methods We conducted secondary analyses on data from 289 participants with depression or anxiety included in the Individual Placement and Support modified for people with mood and anxiety disorders (IPS-MA) trial. Associations of baseline characteristics and employment or education after 24 months were tested in univariate logistic regression analyses, variables with a p-value below 0.1 were included in multivariate analyses. Results In the univariate analyses, self-reported level of functioning (p = 0.032), higher age (p = 0.070), and higher level of readiness to change (p = 0.001) were associated with the outcome and included in the multivariate analysis. Only age (p = 0.030) and readiness to change (p = 0.003) remained significantly associated with return to work or education after 24 months in the multivariate analysis. Conclusion Higher age and lower readiness to change were associated with a lower chance of having returned to work or education. Factors modifying the effect of higher age should be identified, just as vocational rehabilitation should focus on improving factors related to people's readiness to change.

Trajectories of Vocational Recovery Among Persons with Severe Mental Illness Participating in a Randomized Three-Group Superiority Trial of Individual Placement and Support (IPS) in Denmark.

PURPOSE: To investigate longitudinal trajectories of vocational recovery (VR) among individuals with severe mental illness (SMI) who participated in the Danish Individual Placement and Support (IPS) trial, and whether the IPS intervention, socio-demographic and disease-specific characteristics predicted trajectory membership. METHODS: In an observational study design, we used previously collected data from the Danish IPS trial (N = 720). VR was defined as 'weeks in competitive employment or education in the past 6 months and was measured after 0.5, 1, 1.5, 2 and 2.5 years, using data from the Danish Register for Evaluation of Marginalization (DREAM) database. Latent growth mixture modelling in Mplus statistical software (version 7) was applied to identify trajectories of VR. Multinomial logistic regression analyses were used to estimate predictors for trajectory membership. RESULTS: Four trajectories were identified: 'Low VR' (61.3%), 'Low Increasing VR (8.2%), 'Increasing Decreasing VR' (7.2%) and 'High VR' (23.4%). Receiving the IPS intervention increased odds of membership in 'High VR' compared to 'Low VR' (OR = 2.18; 95% CI 1.37-3.48) and so did higher education (OR = 2.25; 95% CI 1.39-3.64), higher cognitive function (OR = 1.17; 95% CI 1.02-1.35), higher motivation to change (OR = 1.04; 95% CI 1.02-1.05) and previous work history (OR = 1.64; 95% CI 1.09-2.46). Higher age decreased odds of membership in the 'High VR' (OR = 0.95; 95% CI 0.93-0.98) compared to 'Low VR'. CONCLUSION: There was high heterogeneity in the identified VR trajectories, despite that all participants expressed a desire for work and education at baseline. Improvements of the IPS intervention are needed to support specific groups in achieving and retaining employment.

Incidence rates and employment trends in schizophrenia spectrum disorders, bipolar affective disorders and recurrent depression in the years 2000-2013: a Danish nationwide register-based study.

AIMS: The study aimed to investigate time trends in incidence rates in schizophrenic spectrum disorders (ICD-10: F20-F29), bipolar affective disorder (ICD-10: F30, F31), and recurrent depression (ICD-10: F33) and to investigate the rates of employment for all incident cases. METHOD: We used nationwide longitudinal data from 2000 to 2013 on all psychiatric inpatients and outpatients contacts in Denmark. Age-adjusted incidence rate ratios were calculated for the three diagnostic groups, and rates of employment, education, and disability pension were measured 1 year before and 2 years after the diagnosis for all the incident cases. RESULTS: The incidence rates increased significantly in all diagnostic groups and both sexes. Comparing the incidence rates in 2013 with 2000 yielded an incidence rate ratio of 1.67 (95% CI 1.51-1.84) for schizophrenic spectrum disorders, 3.82 (95% CI 3.23-4.52) for bipolar affective disorder, and 2.80 (95% CI 2.58-3.04) for recurrent depression. During the same observation period, the employment rates decreased, both 1 year before and 2 years after diagnosis in all three subgroups. In the year 2002, employment rates, 2 years after diagnosis, were 24.6% for schizophrenia spectrum disorder, 35.0% for bipolar affective disorder and 47.1% for recurrent depression. These rates had declined to 15.8%, 26.8%, and 34.7%, respectively, in 2013. CONCLUSION: This study of three severe mental illness subgroups shows significant increasing incidence rates and decreasing employment rates both before and after the diagnosis between 2000 and 2013, highlighting the importance of timely and correct volume of the psychiatric treatment and vocational rehabilitation programs.

Predictors of work and education among people with severe mental illness who participated in the Danish individual placement and support study: findings from a randomized clinical trial.

PURPOSE: People with severe mental illness experience disproportionately high rates of unemployment. Nonetheless, a substantial amount of research has demonstrated vocational benefits of the Individual Placement and Support (IPS) model and IPS supplemented with cognitive remediation (IPSE). The present study sought to examine demographic and clinical predictors of employment or education among people with severe mental illness and to investigate if IPS or IPSE can compensate for risk factors for unemployment. METHODS: Seven hundred twenty participants were randomly assigned to IPS, IPSE or Service as Usual. During the 18-month follow-up period participants in the two experimental groups obtained significantly more work or education. A series of univariate and multiple logistic regression analyses were conducted to assess the predictive power of demographic and clinical factors for the total population and for the three groups individually. RESULTS: The strongest predictor for vocational recovery, besides treatment allocation, was previous work history (OR = 1.78; 95% CI = 1.28-2.47). Men had a lower probability for vocational recovery compared to women (OR = 0.71; 95% CI = 0.50-0.99) and higher age was also negatively associated with work or education (OR = 0.79; 95% CI = 0.67-0.93). Moreover, vocational recovery was predicted by higher readiness for change, measured on the readiness for change scale (OR = 1.42; 95% CI = 1.19-1.70). Participation in IPS or IPSE could not compensate for negative risk factors such as low cognitive function or negative symptoms. CONCLUSIONS: In a multiple logistic regression analysis age, previous work history and motivation for change were statistically significant predictors of obtaining work or education among people with severe mental illness who participated in the Danish IPS trial.

Vocational Outcomes of the Individual Placement and Support Model in Subgroups of Diagnoses, Substance Abuse, and Forensic Conditions: A Systematic Review and Analysis of Pooled Original Data.

PURPOSE: To investigate the effect of Individual Placement and Support (IPS) according to diagnoses of schizophrenia, bipolar disorder, major depression, substance use disorders, or forensic psychiatric conditions. METHODS: A systematic search of the literature was conducted in June 2017 and repeated in December 2020. The systematic review included 13 studies. Analyses of pooled original data were based on the six studies providing data (n = 1594). No studies on forensic psychiatric conditions were eligible. Hours and weeks worked were analyzed using linear regression. Employment, and time to employment was analyzed using logistic regression, and cox-regression, respectively. RESULTS: The effects on hours and weeks in employment after 18 months were comparable for participants with schizophrenia, and bipolar disorder but only statistically significant for participants with schizophrenia compared to services as usual (SAU) (EMD 109.1 h (95% CI 60.5-157.7), 6.1 weeks (95% CI 3.9-8.4)). The effect was also significant for participants with any drug use disorder (121.2 h (95% CI 23.6-218.7), 6.8 weeks (95% CI 1.8-11.8)). Participants with schizophrenia, bipolar disorder, and any drug use disorder had higher odds of being competitively employed (OR 2.1 (95% CI 1.6-2.7); 2.4 (95% CI 1.3-4.4); 3.0 (95% CI 1.5-5.8)) and returned to work faster than SAU (HR 2.1 (95% CI 1.6-2.6); 1.8 (95% CI 1.1-3.1); 3.0 (95% CI 1.6-5.7)). No statistically significant effects were found regarding depression. CONCLUSIONS: IPS was effective regarding schizophrenia, bipolar disorder, and substance use disorder; however, the effect on hours, and weeks worked was not statistically significant regarding bipolar disorder. For people with depression the impact of IPS remains inconclusive. Non-significant results may be due to lack of power. TRIAL REGISTRATION: PROSPERO protocol nr. CRD42017060524.

Cost-effectiveness analysis of a supported employment intervention for people with mood and anxiety disorders in Denmark - the IPS-MA intervention.

OBJECTIVES: We aimed to investigate the cost-utility and cost-effectiveness of a modified Individual Placement and Support intervention for people with mood and anxiety disorders (IPS-MA). METHODS: Costs were assessed from a societal perspective. Health care costs were derived from registers and combined with data on use of IPS-MA services, municipal social care, and labour market services. EQ-5D was used to compute QALY. Missing data were imputed in a sensitivity analysis. We also computed the cost per gain in hours worked. Incremental cost-effectiveness ratios (ICER) were computed and bootstrapped to obtain confidence intervals for QALY and gain in hours worked. RESULTS: We found no difference in overall costs between groups. A significant saving was found in use of labour market services in the IPS-MA group. But the IPS-MA group had significantly lower wage earnings compared to the control group. The intervention group had a higher, though statistically in-significant, increase in QALYs than the control group. The ICER did not show statistically significant results, but there was a tendency, that IPS-MA could have a positive effect on health-related quality of life without any additional costs. However, participants in the IPS-MA group had a significantly lower gain in hours worked compared to the control group. CONCLUSIONS: Despite a significant saving in use of labour market services, IPS-MA was not cost-effective. Participants in the IPS-MA group worked significantly fewer hours and earned significantly less than participants in the control group at 1-year follow-up.

30-Month Follow-Up of Individual Placement and Support (IPS) and Cognitive Remediation for People with Severe Mental Illness: Results from a Randomized Clinical Trial.

Background: The individual placement and support (IPS) model for persons with severe mental illness has proven to be more effective than traditional vocational approaches in improving competitive work over 18 months. In this study, the longer-term effects of IPS over 30 months were investigated in a Danish setting. Method: In a randomized clinical trial, we compared the effects of IPS, IPS enhanced with cognitive remediation and work-related social skills training (IPSE), and service as usual (SAU). At three locations in Denmark, 720 patients with serious mental illnesses were randomly assigned to the three groups. Competitive employment, education, and hospital admissions were tracked for 30 months using Danish national registers. Results: The beneficial effects of IPS on competitive employment and education at the 18-month follow-up were sustained over the 30-month follow-up period. Participants receiving IPS or IPSE were more likely to obtain competitive employment or education than those who received service as usual (IPS 65%, IPSE 65%, SAU 53%, p = 0.006), and they worked on average more weeks competitively (IPS 25 weeks, IPSE 21 weeks, SAU 17 weeks; IPS vs. SAU p = 0.004 and IPSE vs. SAU p = 0.007). Moreover, participants in the two IPS groups had fewer outpatient visits during the 30-month follow-up. However, this was only statistically significant when comparing IPSE with SAU p = 0.017. Conclusion: In conclusion, IPS and IPS enhanced with cognitive remediation and work-related skills training demonstrated that the vocational effects of the interventions are retrained over 30 months in a Danish context.

Integrated mental health care and vocational rehabilitation intervention to improve return to work rates for people on sick leave due to common mental and functional disorders (IBBIS-II)-a study protocol for a randomized clinical trial.

BACKGROUND: Mental illness has an estimated financial burden on the Danish economy of 3.4% of the gross national product every year due to lost productivity, social benefits, and healthcare costs, and approximately 50% of people receiving long-term sickness benefits have a common mental illness. Furthermore, a significant treatment gap exists where less than 30% are treated for their mental illness. The primary objective of the randomized trial is to examine whether people on sick leave with a diagnosis of anxiety, depression, stress, personality disorders, or functional disorders return to work faster and have higher job retention if they receive an integrated and optimized vocational rehabilitation and mental health care intervention, compared to people who receive the standard mental health care and vocational rehabilitation service. METHODS: The trial is designed as an investigator-initiated, randomized, two-group parallel, assessor-blinded, superior trial. A total of 900 participants with a common mental illness will randomly be assigned into two groups: (1) IBBIS-II, consisting of integrated mental health care and vocational rehabilitation, or (2) service as usual (SAU), at two sites in Denmark. The primary outcome is the difference between the two groups in time to return to work (RTW) at 12 months using data from the Danish Register for Evaluation of Marginalization (DREAM) database. DISCUSSION: This study will contribute with new knowledge on vocational recovery and integrated vocational and health care interventions in a Scandinavian context. TRIAL REGISTRATION: ClinicalTrials.gov NCT04432129 . Registered on June 16, 2020.

A Systematic Review of Individual Placement and Support, Employment, and Personal and Clinical Recovery.

OBJECTIVE: The objective of this review was to assess associations between Individual Placement and Support (IPS), employment, and personal and clinical recovery among persons with severe mental illness at 18-month follow-up. METHODS: A systematic literature search identified randomized controlled trials (RCTs) comparing IPS with services as usual. Outcomes were self-esteem, empowerment, quality of life, symptoms of depression, negative or psychotic symptoms, anxiety, and level of functioning. A total of six RCTs reported data suitable for meta-analyses, and pooled original data from five studies were also analyzed. RESULTS: Meta-analyses and analyses of pooled original data indicated that receipt of the IPS intervention alone did not improve any of the recovery outcomes. Participants who worked during the study period, whether or not they were IPS participants, experienced improved negative symptoms, compared with those who did not work (standardized mean difference [SMD]=-0.41, 95% confidence interval [CI]=-0.56, -0.26). For participants who worked, whether or not they were IPS participants, improvements were also found in level of functioning and quality of life (SMD=0.59, 95% CI=0.42, 0.77 and SMD=0.34, 95% CI=0.14, 0.54, respectively). CONCLUSIONS: Employment was associated with improvements in negative symptoms, level of functioning, and quality of life.

Cost-utility and cost-effectiveness of individual placement support and cognitive remediation in people with severe mental illness: Results from a randomized clinical trial.

BACKGROUND: Administrators and policymakers are increasingly interested in individual placement and support (IPS) as a way of helping people with severe mental illness (SMI) obtain employment or education. It is thus important to investigate the cost-effectiveness to secure that resources are being used properly. METHODS: In a randomized clinical trial, 720 people diagnosed with SMI were allocated into three groups; (a) IPS, (b) IPS supplemented with cognitive remediation a social skills training (IPSE), and (c) Service as usual (SAU). Health care costs, municipal social care costs, and labor market service costs were extracted from nationwide registers and combined with data on use of IPS services. Cost-utility and cost-effectiveness analyses were conducted with two primary outcomes: quality-adjusted life years (QALY) and hours in employment. Incremental cost-effectiveness ratios (ICER) were computed for both QALY, using participant's responses to the EQ-5D questionnaire, and for hours in employment. RESULTS: Both IPS and IPSE were less costly, and more effective than SAU. Overall, there was a statistically significant cost difference of €9,543 when comparing IPS with SAU and €7,288 when comparing IPSE with SAU. ICER's did generally not render statistically significant results. However, there was a tendency toward the IPS and IPSE interventions being dominant, that is, cheaper with greater effect in health-related quality of life and hours in employment or education compared to usual care. CONCLUSION: Individual placement support with and without a supplement of cognitive remediation tends to be cost saving and more effective compared to SAU.

Effects of Individual Placement and Support Supplemented With Cognitive Remediation and Work-Focused Social Skills Training for People With Severe Mental Illness: A Randomized Clinical Trial.

Importance: Individual placement and support (IPS) seems to be an effective vocational intervention for people with severe mental illness, but its effects have not yet been shown in the Danish welfare model. Also, effects may be enhanced by adding cognitive remediation and work-focused social skills training (IPS with enhancements [IPSE]). Objectives: To investigate the effects of IPS vs IPSE vs service as usual (SAU) on a population of individuals with severe mental illness in Denmark. Design, Setting, and Participants: This was an investigator-initiated, 3-group, parallel, assessor-blinded randomized clinical trial that used early-intervention teams or community mental health services in 3 Danish cities to recruit participants with severe mental illness. Participants were randomly assigned to receive IPS, IPSE, or SAU from November 2012 to February 2016, and follow-up continued until August 2017. Interventions: Participants allocated to the IPS intervention received vocational support per the principles of the IPS model. Participants in the IPSE arm received cognitive remediation and social skills training in addition to IPS. The group receiving SAU received vocational rehabilitation at the Danish job centers. Main Outcomes and Measures: The primary outcome was the number of hours in competitive employment or education during the 18-month follow-up. Secondary outcomes included intergroup differences in employment or education at any point during follow-up; time to employment or education; and cognitive and social functioning, self-esteem, and self-efficacy. Results: Of the 720 included participants (mean [SD] age, 32.8 [9.9] years; 276 [38.3%] women), 243 received IPS, 238 received IPSE, and 239 received SAU. Most participants (551 [76.5%]) were diagnosed with a schizophrenia spectrum disorder. During the 18-month follow-up, the IPSE group worked or studied a mean (SD) of 488.1 (735.6) hours, compared with 340.8 (573.8) hours in the group receiving SAU (success-rate difference [SRD], 0.151 [95% CI, 0.01-0.295]; P = .016). The mean (SD) in the IPS group was 411 (656.9) (SRD, 0.127 [95% CI, -0.017 to 0.276]; P = .004). There was no difference between IPS and IPSE in any vocational outcomes, and the 3 groups showed no differences in any nonvocational outcomes, except that the IPS and IPSE groups were more satisfied with the services received than the group receiving SAU (IPS vs SAU: SRD, 0.310 [95% CI, 0.167-0.445]); IPSE vs SAU: SRD, 0.341 [95% CI, 0.187-0.478]). Conclusions and Relevance: Compared with SAU, IPS and IPSE seem to be viable routes to increase employment and education rates in people with severe mental illness in Denmark, but no additional effects were observed by enhancing IPS. Trial Registration: ClinicalTrials.gov identifier: NCT01722344.

Individual Placement and Support supplemented with cognitive remediation and work-related social skills training in Denmark: study protocol for a randomized controlled trial.

BACKGROUND: Individual Placement and Support (IPS) appears to be an effective vocational intervention for obtaining competitive employment for people with severe mental illness. However, no IPS studies or trials have been conducted in Denmark, a country characterized by a specialized labor market with a higher minimum wage and fewer entry-level jobs in comparison with other countries such as the US. Furthermore, long-term job retention and economic self-sufficiency have not been clearly demonstrated. Integrating methods such as cognitive remediation and work-related social skills training may be ways to address these issues. METHODS/DESIGN: The trial design is an investigator-initiated, randomized, assessor-blinded, multi-center trial. A total of 750 patients with severe mental illness will be randomly assigned into three groups: (1) IPS, (2) IPS enhanced with cognitive remediation and work-related social skills training, and (3) service as usual. The primary outcome is number of hours in competitive employment or education at 18-month follow-up. Secondary and exploratory outcomes are money earned, days to first employment, symptoms, functional level, self-esteem, and self-efficacy at 18-month follow-up. Thirty- and 60-month follow-ups will be register-based. DISCUSSION: This will be one of the largest randomized trials investigating IPS to date. The trial will be conducted with high methodological quality in order to reduce the risk of bias. If the results of this trial show that IPS, or IPS enhanced with cognitive remediation and work-related social skills training, is superior to service as usual, this will support preliminary evidence. Furthermore, it will show that the method is generalizable to a variety of labor markets and welfare systems and provide important knowledge about the effect of adding cognitive remediation and social skills training to the IPS intervention. TRIAL REGISTRATION: ClinicalTrials registration number: NCT01722344 (registered 2 Nov. 2012).