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.

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.

Optimizing psychotherapy dosage for comorbid depression and personality disorders (PsyDos): a pragmatic randomized factorial trial using schema therapy and short-term psychodynamic psychotherapy.

BACKGROUND: Patients with comorbid depression and personality disorders suffer from a heavy disease burden while tailored treatment options are limited, accounting for a high psychological and economic burden. Little is known about the effect of treatment dosage and type of psychotherapy for this specific co-morbid patient population, in terms of treatment-effect and cost-effectiveness. This study aims to compare treatment outcome of 25 versus 50 individual therapy sessions in a year. We expect the 50-session condition to be more effective in treating depression and maintaining the effect. Secondary objectives will be addressed in order to find therapy-specific and non-specific mechanisms of change. METHODS: In a mono-center pragmatic randomized controlled trial with a 2 × 2 factorial design, 200 patients with a depressive disorder and personality disorder(s) will be included. Patients will be recruited from a Dutch mental health care institute for personality disorders. They will be randomized over therapy dosage (25 vs 50 sessions in a year) and type of therapy (schema therapy vs short-term psychodynamic supportive psychotherapy). The primary clinical outcome measure will be depression severity and remission. Changes in personality functioning and quality of life will be investigated as secondary outcomes. A priori postulated effect moderators and mediators will be collected as well. All patients are assessed at baseline and at 1, 2, 3, 6, 9-12 months (end of therapy) and at follow up (6 and 12 months after end of treatment). Alongside the trial, an economic evaluation will be conducted. Costs will be collected from a societal perspective. DISCUSSION: This trial will be the first to compare two psychotherapy dosages in patients with both depression and personality disorders. Insight in the effect of treatment dosage for this patient group will contribute to both higher treatment effectiveness and lower costs. In addition, this study will contribute to the limited evidence base on treating patients with both depression and personality disorders. Understanding the processes that account for the therapeutic changes could help to gain insight in what works for whom. TRIAL REGISTRATION: This trial has been registered on July 20th 2016, Netherlands Trial Register, part of the Dutch Cochrane Centre ( NTR5941 ).

Victimisation in adults with severe mental illness: prevalence and risk factors.

BACKGROUND: Patients with a severe mental illness (SMI) are more likely to experience victimisation than the general population. AIMS: To examine the prevalence of victimisation in people with SMI, and the relationship between symptoms, treatment facility and indices of substance use/misuse and perpetration, in comparison with the general population. METHOD: Victimisation was assessed among both randomly selected patients with SMI (n = 216) and the general population (n = 10 865). RESULTS: Compared with the general population, a high prevalence of violent victimisation was found among the SMI group (22.7% v. 8.5%). Compared with out-patients and patients in a sheltered housing facility, in-patients were most often victimised (violent crimes: 35.3%; property crimes: 47.1%). Risk factors among the SMI group for violent victimisation included young age and disorganisation, and risk factors for property crimes included being an in-patient, disorganisation and cannabis use. The SMI group were most often assaulted by someone they knew. CONCLUSIONS: Caregivers should be aware that patients with SMI are at risk of violent victimisation. Interventions need to be developed to reduce this vulnerability.

Reducing intrusive suicidal mental images in patients with depressive symptoms through a dual-task add-on module: Results of a multicenter randomized clinical trial.

OBJECTIVE: To examine the safety and efficacy of a brief cognitive dual-task (using eye movements) add-on module to treatment as usual (TAU) in reducing the severity and frequency of intrusive suicidal mental images and suicidal ideation. METHOD: We conducted a single-blind, parallel multicenter randomized trial (No. NTR7563) among adult psychiatric outpatients (N = 91; Mage = 34.4, SD = 13.54; 68% female) with elevated depressive symptoms and experiencing distressing suicidal intrusions in the Netherlands. Primary outcome was the severity (Suicidal Intrusions Attributes Scale) and frequency (Clinical Interview for Suicidal Intrusions) of suicidal mental imagery intrusions at 1-week posttreatment and 3-month follow-up. Primary analysis was intention-to-treat. RESULTS: Between November 27, 2018 and September 13, 2021, 91 patients were included and randomly assigned to intervention group (Cognitive Dual Task Add-on + TAU) (n = 46) or TAU-only (n = 45). Cognitive Dual Task Add-on + TAU had greater reductions in severity (mean difference, -15.50, 95% CI [23.81, -7.19]; p < .001, d = 0.60), and frequency (geometric mean difference, 0.47, 95% CI [0.29, 0.79]; p = .004) of suicidal intrusions over time than TAU-alone. Cognitive Dual Task Add-on + TAU patients also showed lower suicidal ideation over time (p = .008, d = 0.42). There were no significant group differences in reductions in depressive symptoms, rumination, or hopelessness. Four serious adverse events occurred (three Cognitive Dual Task Add-on + TAU; one TAU-only); all unlikely attributable to intervention/trial. CONCLUSIONS: Findings provide support for the effectiveness of adding a cognitive dual-task module to the treatment of psychiatric outpatients with elevated depressive symptoms in reducing suicidal intrusions and ideation and can be executed safely. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

What is the best sequential treatment strategy in the treatment of depression? Adding pharmacotherapy to psychotherapy or vice versa?

BACKGROUND: Insufficient response to monotreatment for depression is a common phenomenon in clinical practice. Even so, evidence indicating how to proceed in such cases is sparse. METHODS: This study looks at the second phase of a sequential treatment algorithm, in which 103 outpatients with moderately severe depression were initially randomized to either short-term supportive psychodynamic therapy (PDT) or antidepressants. Patients who reported less than 30% symptom improvement after 8 weeks were offered combined treatment. Outcome measures were the Hamilton Depression Rating Scale (HAM-D), the Clinical Global Impression of Severity and Improvement, the SCL-90 depression subscale and the EuroQOL questionnaire. RESULTS: Despite being nonresponsive, about 40% of patients preferred to continue with monotherapy. At treatment termination, patients initially randomized to PDT had improved more than those initially receiving antidepressants, as indicated by the HAM-D and the EuroQOL, independently of whether the addition was accepted or not. CONCLUSIONS: Starting with psychotherapy may be preferable in mildly and moderately depressed outpatients. For patients who receive either PDT or antidepressants, combined therapy after early nonresponse seems to be helpful. Nevertheless, this sequential strategy is not always preferred by patients.

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.

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.

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.

The developmental profile: validation of a theory-driven instrument for personality assessment.

The Developmental Profile is an instrument for personality assessment. It covers both maladaptive and adaptive characteristics. The current study examined its internal consistency and construct validity in a Dutch sample of 763 participants from various clinical and nonclinical settings. The internal consistency reliability estimates were good for the clusters of levels (adaptive, neurotic, and primitive), although not for all separate levels. Confirmatory factor analysis showed an overall good fit, with the exception of the level of primary narcissism. Furthermore, empirical evidence was found for the interpretation of a patient's Developmental Profile according to increasing levels of aggregation, with as a highest level a single maladaptivity-adaptivity scale score. This scale significantly distinguished among different patient groups.

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.

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.

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.

Patient preference compared with random allocation in short-term psychodynamic supportive psychotherapy with indicated addition of pharmacotherapy for depression.

Depressed patients randomized to psychotherapy were compared with those who had been chosen for psychotherapy in a treatment algorithm, including addition of an antidepressant in case of early nonresponse. There were no differences between randomized and by-preference patients at baseline in adherence and outcome. About half of the early nonresponders refused the additional medication. However, no clear effect of medication addition on ultimate outcome could be demonstrated. In total, 37% of the patients achieved remission. The study suggested that randomization of patients does not induce a great influence on outcome. It might be warranted to continue an initially ineffective psychotherapy for depression, because a considerable number of patients do have a pattern of delayed response.

Predictive value of self-reported and observer-rated defense style in depression treatment.

This study explored the predictive value of observer-rated and self-reported defensive functioning on the outcome of psychotherapy for the treatment of depression. Defense styles were measured according to the Developmental Profile (DP) and the Defense Style Questionnaire (DSQ) in 81 moderately severely depressed patients. All patients were treated with Short-term Psychodynamic Supportive Psychotherapy (SPSP). At baseline, women appeared to have a more mature level of overall defensive functioning. A lower level of defensive function was found in patients with recurrent depressions. We also found a rather modest relationship between self-reported and observer-rated defense. Remitted patients had a more mature overall defensive functioning on the DP and the DSQ. In particular, patients with a symbiotic defense style (giving up, apathetic withdrawal) were at risk for poor outcome. This exploratory study provides further evidence of the relevance of defense styles for depression. It suggests a differential predictive value of separate defense levels, which may help to tailor psychotherapeutic strategies.

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.

Managing the patient with co-morbid depression and an anxiety disorder.

Depression and anxiety disorders frequently co-occur. This type of co-morbidity is associated with higher severity, suicidality, chronicity and treatment resistance. However, available treatment guidelines mainly focus on treatment for singular disorders. The current paper describes diagnostic and treatment issues relevant for adequately addressing patients with depression and an anxiety disorder, using information from both guidelines and a search of recent literature. Apart from differential diagnosis, the diagnostic evaluation should include a thorough assessment of the symptoms of both disorders, preferably by using a structured clinical interview, and an assessment of depression severity in terms of suicidality, psychotic symptoms and impairment. Treatment should first address the primary disorder in terms of severity and risk. As a rule, severe depression should be treated before the anxiety disorder, using antidepressant medication or combined treatment (plus psychotherapy). In less severe pathology, the primary focus may be determined by examining the temporal pattern and the subjective burden of each disorder as experienced by the patient. Treatment is often sequential. Treatment of the primary disorder may or may not relieve the co-morbid disorder as well. If the primary disorder is an anxiety disorder, co-morbid depression generally implies earlier use of an antidepressant. Co-morbid mild depression may also react favourably to psychotherapeutic treatment of the anxiety disorder. Recent literature on concurrent treatment of both depression and anxiety shows that modern antidepressants such as sertraline, paroxetine, fluoxetine, venlafaxine, nefazodone and bupropion have demonstrated efficacy in relieving both depressive and anxiety symptoms compared with placebo. Head-to-head comparisons, although relatively scarce, tend to show superiority over tricyclic antidepressants. Venlafaxine was found to be more effective than fluoxetine in some studies. However, these results should be interpreted with caution because studies vary considerably in terms of patient selection, assessment of anxiety and primary outcome measures. Only one randomized controlled trial compared atypical antipsychotics with placebo. Psychotherapy was generally shown to have a beneficial effect on the co-morbid conditions, and available evidence appears to favour combined treatment. The results should be interpreted with caution because the number of studies on this issue was relatively small, with considerable clinical and methodological heterogeneity.

Identifying patients at risk of complete nonresponse in the outpatient treatment of depression.

BACKGROUND: Although complete nonresponse in depression treatment is considered to be a major problem in clinical practice, research in this area is very limited. The objective of this preliminary study was to determine the frequency and predictors of complete nonresponse in different treatments for depression. METHODS: Post hoc analysis of the pooled data of 3 consecutive randomized controlled trials of outpatient depression treatment was conducted. The subjects were 313 patients with major depressive disorder and 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores between 14 and 25 who were treated for 6 months with either pharmacotherapy, short-term psychodynamic supportive psychotherapy or combined therapy. Complete nonresponse was defined as a <25% response according to the HAM-D-17. Sociodemographic factors, depression features and adherence were investigated as predictors in a multivariate stepwise logistic regression analysis. RESULTS: Overall, nonresponse occurred in 34% of the patients. In pharmacotherapy this was 46%, in psychotherapy 39% and in combined therapy 28%. The severity of somatic symptoms was associated with nonresponse in both combined therapy and psychotherapy. No predictive factors were found in the case of pharmacotherapy. In psychotherapy, nonresponse was related to age above 40 years, chronic depression and nonadherence by the patient. In the case of combined therapy, younger age, previous use of an antidepressant and having a previous depressive episode were associated with nonresponse. CONCLUSION: Easily measurable patient characteristics may help to identify patients at risk of complete nonresponse to treatment. It is suggested that predictors may differ across treatment modalities. However, head-to-head comparisons are required before it can be recommended to take this into account when selecting the most appropriate treatment for individual depressed patients.