Dosage effects of psychodynamic and schema therapy in people with comorbid depression and personality disorder: four-arm pragmatic randomised controlled trial.

BACKGROUND: Higher intensity of psychotherapy might improve treatment outcome in depression, especially in those with comorbid personality disorder. AIMS: To compare the effects of 25 individual sessions (weekly) of two forms of psychotherapy - short-term psychoanalytic supportive psychotherapy (SPSP) and schema therapy - with the same treatments given for 50 sessions (twice weekly) in people with depression and personality disorder. Trial registration: NTR5941. METHOD: We conducted a pragmatic, double-randomised clinical trial and, over 37 months, recruited 246 adult out-patients with comorbid depression/dysthymia and personality disorder. A 2 × 2 factorial design randomised participants to 25 or 50 sessions of SPSP or schema therapy. The primary outcome was change in depression severity over 1 year on the Beck Depression Inventory II (BDI-II). Secondary outcomes were remission both of depression and personality disorder. RESULTS: Compared with 25 sessions, participants who received 50 sessions showed a significantly greater decrease in depressive symptoms over time (time × session dosage, P < 0.001), with a mean difference of 5.6 BDI points after 1 year (d = -0.53, 95% CI -0.18 to 0.882, P = 0.003). Remission from depression was also greater in the 50-session group (74% v. 58%, P = 0.025), as was remission of personality disorder (74% v. 56%, P = 0.010). CONCLUSIONS: Greater intensity of psychotherapy leads to better outcomes of both depression and personality status in people with comorbid depression and personality disorder.

Individual psychotherapy for cluster-C personality disorders: protocol of a pragmatic RCT comparing short-term psychodynamic supportive psychotherapy, affect phobia therapy and schema therapy (I-FORCE).

BACKGROUND: Cluster-C personality disorders (PDs) are highly prevalent in clinical practice and are associated with unfavourable outcome and chronicity of all common mental health disorders (e.g. depression and anxiety disorders). Although several forms of individual psychotherapy are commonly offered in clinical practice for this population, evidence for differential effectiveness of different forms of psychotherapy is lacking. Also, very little is known about the underlying working mechanisms of these psychotherapies. Finding evidence on the differential (cost)-effectiveness for this group of patients and the working mechanisms of change is important to improve the quality of care for this vulnerable group of patients. OBJECTIVE: In this study, we will compare the differential (cost)-effectiveness of three individual psychotherapies: short-term psychodynamic supportive psychotherapy (SPSP), affect phobia therapy (APT) and schema therapy (ST). Although these psychotherapies are commonly used in clinical practice, evidence for the Cluster-C PDs is limited. Additionally, we will investigate predictive factors, non-specific and therapy-specific mediators. METHODS: This is a mono-centre randomized clinical trial with three parallel groups: (1) SPSP, (2) APT, (3) ST. Randomization on patient level will be pre-stratified according to type of PD. The total study population to be included consists of 264 patients with Cluster-C PDs or other specified PD with mainly Cluster-C traits, aged 18-65 years, seeking treatment at NPI, a Dutch mental health care institute specialized in PDs. SPSP, APT and ST (50 sessions per treatment) are offered twice a week in sessions of 50 min for the first 4 to 5 months. After that, session frequency decreases to once a week. All treatments have a maximum duration of 1 year. Change in the severity of the PD (ADP-IV) will be the primary outcome measure. Secondary outcome measures are personality functioning, psychiatric symptoms and quality of life. Several potential mediators, predictors and moderators of outcome are also assessed. The effectiveness study is complemented with a cost-effectiveness/utility study, using both clinical effects and quality-adjusted life-years, and primarily based on a societal approach. Assessments will take place at baseline, start of treatment and at 1, 3, 6, 9, 12, 18, 24 and 36 months. DISCUSSION: This is the first study comparing psychodynamic treatment to schema therapy for Cluster-C PDs. The naturalistic design enhances the clinical validity of the outcome. A limitation is the lack of a control group for ethical reasons. TRIAL REGISTRATION: NL72823.029.20 [Registry ID: CCMO]. Registered on 31 August 2020. First participant included on 23 October 2020.

G-FORCE: the effectiveness of group psychotherapy for Cluster-C personality disorders: protocol of a pragmatic RCT comparing psychodynamic and two forms of schema group therapy.

BACKGROUND: Cluster-C personality disorders (PDs), characterized by a high level of fear and anxiety, are related to high levels of distress, societal dysfunctioning and chronicity of various mental health disorders. Evidence for the optimal treatment is extremely scarce. Nevertheless, the need to treat these patients is eminent. In clinical practice, group therapy is one of the frequently offered approaches, with two important frameworks: schema therapy and psychodynamic therapy. These two frameworks suggest different mechanisms of change, but until now, this has not yet been explored. The purpose of the present G-FORCE trial is to find evidence on the differential (cost)effectiveness of two forms of schema group therapy and psychodynamic group therapy in the routine clinical setting of an outpatient clinic and to investigate the underlying working mechanisms and predictors of outcome of these therapies. METHODS: In this mono-centre pragmatic randomized clinical trial, 290 patients with Cluster-C PDs or other specified PD with predominantly Cluster-C traits, will be randomized to one of three treatment conditions: group schema therapy for Cluster-C (GST-C, 1 year), schema-focused group therapy (SFGT, 1.5 year) or psychodynamic group therapy (PG, 2 years). Randomization will be pre-stratified on the type of PD. Change in severity of PD (APD-IV) over 24 months will be the primary outcome measure. Secondary outcome measures are personality functioning, psychiatric symptoms and quality of life. Potential predictors and mediators are selected and measured repeatedly. Also, a cost-effectiveness study will be performed, primarily based on a societal perspective, using both clinical effects and quality-adjusted life years. The time-points of assessment are at baseline, start of treatment and after 1, 3, 6, 9, 12, 18, 24 and 36 months. DISCUSSION: This study is designed to evaluate the effectiveness and cost-effectiveness of three formats of group psychotherapy for Cluster-C PDs. Additionally, predictors, procedure and process variables are analysed to investigate the working mechanisms of the therapies. This is the first large RCT on group therapy for Cluster-C PDs and will contribute improving the care of this neglected patient group. The absence of a control group can be considered as a limitation. TRIAL REGISTRATION: CCMO, NL72826.029.20 . Registered on 31 August 2020, first participant included on 18 October 2020.

Which patients benefit from adding short-term psychodynamic psychotherapy to antidepressants in the treatment of depression? A systematic review and meta-analysis of individual participant data.

BACKGROUND: Adding short-term psychodynamic psychotherapy (STPP) to antidepressants increases treatment efficacy, but it is unclear which patients benefit specifically. This study examined efficacy moderators of combined treatment (STPP + antidepressants) v. antidepressants for adults with depression. METHODS: For this systematic review and meta-analysis (PROSPERO registration number: CRD42017056029), we searched PubMed, PsycINFO, Embase.com, and the Cochrane Library from inception to 1 January 2022. We included randomized clinical trials comparing combined treatment (antidepressants + individual outpatient STPP) v. antidepressants in the acute-phase treatment of depression in adults. Individual participant data were requested and analyzed combinedly using mixed-effects models (adding Cochrane risk of bias items as covariates) and an exploratory machine learning technique. The primary outcome was post-treatment depression symptom level. RESULTS: Data were obtained for all seven trials identified (100%, n = 482, combined: n = 238, antidepressants: n = 244). Adding STPP to antidepressants was more efficacious for patients with high rather than low baseline depression levels [B = -0.49, 95% confidence interval (CI) -0.61 to -0.37, p < 0.0001] and for patients with a depressive episode duration of >2 years rather than <1 year (B = -0.68, 95% CI -1.31 to -0.05, p = 0.03) and than 1-2 years (B = -0.86, 95% CI -1.66 to -0.06, p = 0.04). Heterogeneity was low. Effects were replicated in analyses controlling for risk of bias. CONCLUSIONS: To our knowledge, this is the first study that examines moderators across trials assessing the addition of STPP to antidepressants. These findings need validation but suggest that depression severity and episode duration are factors to consider when adding STPP to antidepressants and might contribute to personalizing treatment selection for depression.

Exploring the effect of group schema therapy and comorbidity on the treatment course of personality disorders.

PURPOSE OF REVIEW: To provide an update of outcome studies of schema group therapy for personality disorders and the effect of comorbidity in order to explore whether schema group therapy might be effective for this patient group and what dosage is required. RECENT FINDINGS: Studies of short-term schema group therapy for personality disorders with or without comorbidity show moderately effective results but the majority of patients fail to achieve full remission from global psychological symptom distress. Preliminary findings revealed that those unremitted patients might benefit from 40 to 60 sessions. Patients with severe personality disorders (such as borderline personality disorders) seem to need longer and/or more intensive treatment dosage to recover. SUMMARY: We advocate short-term schema therapy in groups as a valuable first step in a stepped-care programme for patients with moderate personality disorders and comorbidity.Treatment extension or treatment intensification may be indicated in patients who do not recover. Patients with severe personality disorders seem to require long-term outpatient group treatment, with a combination of group and individual treatment being preferable. High-quality randomized controlled trials are needed in order to determine which treatment dosage is necessary for whom.

The effectiveness of intensive home treatment as a substitute for hospital admission in acute psychiatric crisis resolution in the Netherlands: a two-centre Zelen double-consent randomised controlled trial.

BACKGROUND: Although de-institutionalisation has been underway for decades, admission to hospital followed by low-intensity outpatient care remains the usual treatment for patients with an acute psychiatric crisis. Intensive home treatment has been developed for patients in a severe psychiatric crisis as an alternative to inpatient care. This study aimed to evaluate the potential of intensive home treatment to reduce bed-days and its clinical effectiveness compared with treatment as usual. METHODS: We did a two-armed, two-centre, open-label, Zelen, double-consent, pragmatic randomised controlled trial. Patients aged 18-65 years were recruited at the psychiatric emergency service and psychiatric emergency wards of the two major mental health institutions (Arkin and GGZ inGeest) in Amsterdam, the Netherlands. Patients diagnosed with at least one DSM-IV-TR or DSM-5 disorder and in a psychiatric crisis and for whom psychiatrists had indicated or completed a clinical admission could be included. Trained psychiatric emergency service and hospital professionals did the automated web-based pre-randomisation procedure upon first contact with the patient. A seeded pseudo-random number generator allocated patients (2:1) to intensive home treatment or treatment as usual. Informed consent was obtained after randomisation as soon as the patient was mentally capable within 14 days. Due to the nature of this study, patients and professionals were not masked to treatment. Intensive home treatment was tailored to the nature of the crisis and goals of patients and relatives, and developed in collaboration with them and a multidisciplinary professional team. All main analyses were intention-to-treat, and the primary outcome was the total number of admission days 12 months after randomisation. To investigate the effect of treatment conditions on the outcome measures, linear mixed modelling analyses using restricted maximum likelihood estimation were done. This trial was prospectively registered with Trialregister.nl, NL-6020 (NTR-6151). FINDINGS: Between Nov 15, 2016, and Oct 15, 2018, 246 patients were included in the study (183 patients with intensive home treatment vs 63 patients with treatment as usual). 135 women (55%) and 111 men (45%) were included, with a mean age of 41·01 years (range 18-65; SD 12·68). 114 participants (46%) were born in the Netherlands and 85 (35%) elsewhere (missing data on 47 [19%] participants). Ethnicity data were not available. After 12 months, the mean number of admission days in the intensive home treatment condition was 42·47 (SD 53·92) versus 67·02 (SD 79·03) for treatment as usual, a reduction of 24·55 days (SD 10·73) or 36·6% (p=0·033). 26 adverse events were registered, 23 (89%) of which were suicide attempts. The number of patients with a reported adverse event did not differ significantly between the groups (15 [8%] in the intensive home treatment group vs five [8%] in the treatment as usual group; p=0·950). Five patients died by suicide (three [2%] in the intensive home treatment group vs two [3%] in the treatment as usual group; p=0·610). No treatment-related deaths occurred. INTERPRETATION: Intensive home treatment is a safe and effective partial substitute for conventional psychiatric crisis care that led to a reduction in admission days, causing patients to stay longer in their social environment, with similar clinical effects, patient satisfaction and adverse events. FUNDING: De Stichting tot Steun Vereniging voor Christelijke Verzorging van Geestes-en Zenuwzieken.

Exploration of symptom dimensions and duration of untreated psychosis within a staging model of schizophrenia spectrum disorders.

AIM: Clinical staging of schizophrenia entails a new method that identifies clusters of symptoms and variation in level of remission, with the goal to create a framework for early intervention. Additionally, duration of untreated psychosis (DUP) may influence symptom severity in the first episode of psychosis (FEP) and could necessitate refining of the staging model. However, consistent evidence concerning variation in symptom severity and DUP between stages is missing. Therefore, we evaluated the clinical validity of the staging model by investigating differences in symptom severity across stages in schizophrenia spectrum disorders. Second, we assessed if a prolonged DUP is associated with higher symptom severity in FEP. METHODS: We performed a cross-sectional study of 291 acutely admitted patients with a schizophrenia spectrum disorder. Patients were assigned to clinical stages following the definition of McGorry. Symptom severity was evaluated with the new DSM-5 Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS). In FEP, we determined the DUP. RESULTS: Significantly higher severity scores of CRDPSS items hallucinations (H = 14.34, df = 4, P-value = .006), negative symptoms (H = 19.678, df = 4, P-value = .001) and impaired cognition (H = 26.294, df = 4, P-value = <.001) were found in more advanced stages of disease. Moreover, patients with FEP and a DUP longer than 1 year showed significantly more severe negative symptoms (U = 314 000, P = .015) compared to patients with a DUP shorter than 1 year. CONCLUSIONS: The present study found supporting evidence for the clinical validity of the staging model in schizophrenia spectrum disorders. In addition, we found support for refining the stage "first episode" with information concerning the DUP.

Psychological symptoms, early maladaptive schemas and schema modes: predictors of the outcome of group schema therapy in patients with personality disorders.

Objective: This naturalistic study examined the outcomes of group schema therapy for patients with personality disorders (PD) and the effect of psychological symptoms, early maladaptive schemas (EMS) and schema modes on outcome.Method: Assessments were made of 194 patients at baseline, during treatment, at treatment termination and at three-month follow-up. We used the Symptom Checklist-General Severity Index (SCL-GSI) to measure the remission-rate of global psychological distress and as a dependent variable in a multilevel model to conduct univariate and multiple variate analyses.Results: The research sample achieved medium symptom reduction (pre-post d = 0.65, 95% CI [0.39-0.91]) and the remission rate was about 30% after 60 sessions. These results remained stable at three-month follow-up (pre-follow-up d = 0.61, 95% CI [0.29-0.94]; 28.9%). Higher baseline scores on the SCL scale interpersonal sensitivity, the EMS defectiveness/shame and all the maladaptive schema modes together predicted improvements in global psychological distress after treatment.Conclusions: A long-term form of group schema therapy proved effective for a broad group of patients with PD. Internalizing symptoms seems predictive for improvement at outcome. Almost a third of the patients achieved remission. There is therefore room for improvement, possibly by increasing dose or intensity in combination with individual sessions.

An old but still burning problem: Inter-rater reliability in clinical trials with antidepressant medication.

BACKGROUND: Antidepressant trials are criticized due to potential methodological flaws. Root causes of failing methodology can be found in insufficient inter-rater reliability (IRR) and training practices, leading to higher placebo response and reduced study-power. However, it is unknown to what extent reliability estimates or training procedures are currently included in antidepressant reports. Therefore, we aimed to determine the proportion of publications concerning double-blind randomized controlled antidepressant trials that report on IRR coefficients and training procedures. METHODS: We extracted all double-blind randomized clinical trials (RCTs) from the meta-analysis of Cipriani et al. (2018) concerning the period from 2000 until January 2016. Further, we conducted a Medline-search for double-blind RCTs from January 2016 until January 2020 for additional reports. We identified IRR coefficients and training procedures in these publications. RESULTS: In total we identified 179 double-blind RCTs. Only 4.5% reported an IRR coefficient whereas 27.9% reported training procedures. LIMITATIONS: We did not contact individual authors for additional information regarding implementation of training procedures or inter-rater reliability assessment. CONCLUSIONS: There is a substantial lack of reporting IRR coefficients and training procedures in RCTs with antidepressant medication. Considering the large implications of insufficient reliability, we urge researchers to conduct and report training procedures and reliability estimations.

The efficacy of adding short-term psychodynamic psychotherapy to antidepressants in the treatment of depression: A systematic review and meta-analysis of individual participant data.

PURPOSE: We examined the efficacy of adding short-term psychodynamic psychotherapy (STPP) to antidepressants in the treatment of depression by means of a systematic review and meta-analysis of individual participant data, which is currently considered the most reliable method for evidence synthesis. RESULTS: A thorough systematic literature search resulted in 7 studies comparing combined treatment of antidepressants and STPP versus antidepressant mono-therapy (n = 3) or versus antidepressants and brief supportive psychotherapy (n = 4). Individual participant data were obtained for all these studies and totaled 482 participants. Across the total sample of studies, combined treatment of antidepressants and STPP was found significantly more efficacious in terms of depressive symptom levels at both post-treatment (Cohen's d = 0.26, SE = 0.10, p = .01) and follow-up (d = 0.50, SE = 0.10, p < .001). This effect was most apparent at follow-up and in studies examining STPP's specific treatment efficacy. Effects were still apparent in analyses that controlled for risk of bias and STPP quality in the primary studies. CONCLUSIONS: These findings support the evidence-base of adding STPP to antidepressants in the treatment of depression. However, further studies are needed, particularly assessing outcome measures other than depression and cost-effectiveness, as well as examining the relative merits of STPP versus other psychotherapies as added to antidepressants.

The influence of depressive symptoms on the effectiveness of a short-term group form of Schema Cognitive Behavioural Therapy for personality disorders: a naturalistic study.

BACKGROUND: This naturalistic study examined the outcomes of Short-Term Schema Cognitive Behavioural Therapy in groups with personality disorders, and with high and low severity of depressive symptoms. METHODS: Assessments were made at baseline, at mid-treatment (week 10), at treatment termination (week 20) and at three-month follow-up (week 32) of 225 patients with personality disorders and high severity of depressive symptoms (PD-Hi) and patients with low severity of depressive symptoms (PD-Lo). The assessments focused on symptom (Symptom Checklist-90) and schema severity (Young Schema Questionnaire) and coping styles (Utrecht Coping List). We also measured the rate of symptom remission. The data obtained were subjected to multilevel analysis. RESULTS: Psychiatric symptoms and maladaptive schemas improved in both patient groups. Effect sizes were moderate, and even small for the coping styles. Symptom remission was achieved in the minority of the total sample. Remission in psychiatric symptomatology was seen in more PD-Lo patients at treatment termination. However, the difference in levels of remission between the two patient groups was no longer apparent at follow-up. CONCLUSION: A short-term form of schema therapy in groups proved to be an effective approach for a broad group of patients with personality disorders. However, the majority of patients did not achieve symptom remission. TRIAL REGISTRATION: Not applicable.

Staging and profiling for schizophrenia spectrum disorders: Inter-rater reliability after a short training course.

OBJECTIVE: Clinical staging and profiling have been proposed as a new approach in order to refine the diagnostic assessment of schizophrenia spectrum disorders. However, only limited evidence is available for the inter-rater reliability of the clinical staging and profiling model. The aim of the present study was therefore to determine the inter-rater reliability of the clinical staging and profiling model for schizophrenia spectrum disorders, and to investigate whether a short course can improve inter-rater reliability. METHODS: Consecutively recruited inpatients with schizophrenia spectrum disorders were included between January 2015 and January 2016 (study 1), and between March 2018 and October 2018 (study 2). By contrast with the assessors in study 1, all the assessors in study 2 were trained in clinical staging and profiling. We used the clinical staging model proposed by McGorry and identified profile characteristics. Inter-rater reliability was measured using the Intraclass Correlation Coefficient (ICC). RESULTS: The ICC score for clinical staging in study 1 was moderate (0.578). It improved considerably in study 2 (0.757). In general, the ICC scores for the profile characteristics in studies 1 and 2 ranged from poor to sufficient (0.123-0.781). CONCLUSION: This study demonstrated that inter-rater reliability in clinical staging was sufficient after training. However, inter-rater reliability for clinical profile characteristics was highly variable. The general implementation of the clinical staging model for schizophrenia spectrum disorders is therefore feasible but clinical profile characteristics should be used with caution.

A demonstration of a multi-method variable selection approach for treatment selection: Recommending cognitive-behavioral versus psychodynamic therapy for mild to moderate adult depression.

Objective: We use a new variable selection procedure for treatment selection which generates treatment recommendations based on pre-treatment characteristics for adults with mild-to-moderate depression deciding between cognitive behavioral (CBT) versus psychodynamic therapy (PDT). Method: Data are drawn from a randomized comparison of CBT versus PDT for depression (N = 167, 71% female, mean-age = 39.6). The approach combines four different statistical techniques to identify patient characteristics associated consistently with differential treatment response. Variables are combined to generate predictions indicating each individual's optimal-treatment. The average outcomes for patients who received their indicated treatment versus those who did not were compared retrospectively to estimate model utility. Results: Of 49 predictors examined, depression severity, anxiety sensitivity, extraversion, and psychological treatment-needs were included in the final model. The average post-treatment Hamilton-Depression-Rating-Scale score was 1.6 points lower (95%CI = [0.5:2.8]; d = 0.21) for those who received their indicated-treatment compared to non-indicated. Among the 60% of patients with the strongest treatment recommendations, that advantage grew to 2.6 (95%CI = [1.4:3.7]; d = 0.37). Conclusions: Variable selection procedures differ in their characterization of the importance of predictive variables. Attending to consistently-indicated predictors may be sensible when constructing treatment selection models. The small N and lack of separate validation sample indicate a need for prospective tests before this model is used.

Integrated treatment for patients with comorbid depression and personality disorders.

PURPOSE OF REVIEW: To provide an update on the epidemiology and the clinical consequences of depression complicated by comorbid personality disorders, and to discuss optimal treatment options. RECENT FINDINGS: Studies have confirmed the frequent co-occurrence of depression and personality disorders. These comorbid states are consistently associated with unfavourable clinical indicators such as duration of episode, symptom severity and recurrence of depression, as well as a negative effect on treatment outcome. Nevertheless, this is a neglected theme and there are hardly any well designed treatment studies available. SUMMARY: We advocate considering depression and personality as being more closely related and argue in favour of the development of integrated treatment options tailored to understanding symptoms as being interwoven with a variety of long-standing disturbing personality patterns. Both clinically and conceptually, psychodynamic and schema-focused approaches provide good opportunities to adjust available therapies and they could optimize outcomes in this complex patient group. Given the risk of treatment resistance and chronicity, a combination of psychotherapy and medication should always be considered.

The effect of comorbid personality disorder on depression outcome after short-term psychotherapy in a randomised clinical trial.

BACKGROUND: Time-limited psychotherapy for depression is effective. However, comorbid personality disorders affect therapy outcomes negatively. Studies of follow-up effects and results relating to the influence of comorbid personality disorder and treatment modality are scarce. AIMS: To determine the influence of comorbid personality disorder and treatment modality on outcomes after cognitive-behavioural therapy (CBT) or short-term psychodynamic supportive psychotherapy (SPSP) for depression. METHOD: This study draws on data from a previously published randomised clinical trial contrasting SPSP and CBT for depression (both 16 sessions). We compared the effectiveness of these psychotherapies for patients with and without personality disorder (n = 196). The primary measure was depression outcome; the secondary measurements were interpersonal functioning and quality of life. Collected data were analysed using multilevel analysis. Trial registration: ISRCTN31263312 (http://www.controlled-trials.com). RESULTS: Although participants with and without comorbid personality disorder improved at treatment termination (d = 1.04, 95% CI 0.77-1.31 and d = 1.36, 95% CI 0.97-1.76, respectively) and at follow-up (d = 1.15, 95% CI 0.87-1.43 and d = 2.12, 95% CI 1.65-2.59 respectively), personality disorder had a negative effect on depression outcome at both measurement points (P < 0.05). A similar negative effect on interpersonal functioning was no longer apparent at follow-up. Comorbid personality disorder had no influence on social functioning or quality of life outcomes, irrespective of treatment modality. CONCLUSIONS: CBT and SPSP contribute to the improvement of depressive symptoms and interpersonal problems in depressed patients with and without comorbid personality disorder. Both treatments are an effective first step in a stepped care approach, but - given remaining levels of depression in patients with personality disorder - they are probably inadequate for large numbers of patients with this comorbidity. DECLARATION OF INTEREST: None.

Dying Too Soon: Excess Mortality in Severe Mental Illness.

Aims: We aimed to identify baseline predictors of mortality in patients with a severe mental illness (SMI) over a 6-year period and to describe mortality rates as standardised mortality ratios (SMRs). We hypothesised that cardiovascular diseases, older age, cigarette smoking, more severe psychiatric symptoms and more severe psychotropic side effects, and alcohol or drug use were independent risk factors for mortality. Method: Medical examinations were conducted at baseline in a cohort of 322 SMI patients. SMRs were estimated after 6 years and an evaluation was made of the impact of a wide range of variables on survival time. Results: Almost 11% of the SMI patients had died at the end of the study period. All-cause SMRs were 4.51 (95% CI 3.07-5.95) for all SMI patients (4.89, 95% CI 2.97-6.80 for men, and 3.94, 95% CI 1.78-6.10 for women). Natural causes accounted for 86% of excess mortality and unnatural causes for 14%. Cardiovascular disease was a major contributor to this excess mortality. Multivariate Cox regression analyses showed that premature death was associated with a longer history of tobacco use (HR: 1.03, 95% CI 1.02-1.03) and more severe symptoms of disorganisation (HR: 2.36, 95% CI 2.21-2.52). Conclusions: The high SMR and the incidence of cardiovascular disease-related death in SMI patients in our study justify concern. This study underscores the urgent need for interventions to reduce excess mortality in patients with SMI.

The association between the number of previous episodes and modifiable vulnerability factors in remitted patients with recurrent depression.

OBJECTIVE: Remitted patients with a history of several previous major depressive episodes have a higher risk of relapse/recurrence than patients with fewer previous episodes, and the probability of another episode increases progressively with each successive episode. This study examines the association between the number of previous episodes and modifiable vulnerability factors in remitted patients with recurrent depression. METHODS: Patients with recurrent depression (DSM-IV-diagnosed) who were in remission (N = 214) were recruited between September 2011 and July 2016. The association was examined between the number of previous episodes and the following factors: i.e. interpersonal functioning, daily stress, sense of mastery, coping and dysfunctional beliefs. RESULTS: A history of more previous episodes was associated with higher levels of interpersonal problems (P < .001), daily stress (P = .04) and a lower sense of mastery (P = .05). Interpersonal problems were most strongly associated with more previous episodes in a Generalized Linear Regression model. In the domain of interpersonal problems, the subscales that showed the strongest relationship were domineering/controlling, vindictive/self-centred, socially inhibited and self-sacrificing. CONCLUSIONS: Patients with a history of more depressive episodes reported higher levels of interpersonal problems, daily stress and a lower sense of mastery. Future studies should examine these factors in a longitudinal cohort and look at whether the effect of interventions to prevent relapse can be explained by targeting these psychological factors. TRIAL REGISTRATION: Netherlands Trial Register: 2599.