'Personality and bipolar disorder: personality profiles of patients with remitted bipolar disorder and matched controls in a Danish sample'.

BACKGROUND: The aim of the study was to investigate whether patients with bipolar disorder (BD) in remission differ in personality traits compared with a healthy control group. METHODS: A sample of patients with BD (n = 44) was compared with an individually matched control group (n = 44) using the Danish version of the Revised NEO Personality Inventory (NEO PI-R). Paired t-tests were used to analyze differences between the two groups and multiple regression models to evaluate predictors of NEO scores in the patient group. RESULTS: Patients with BD reported significantly higher scores on both Neuroticism and Openness to Experience and lower scores on Conscientiousness. No differences were found on Extraversion and Agreeableness. The effect size for Neuroticism and its facets had a range from 0.77 to 1.45 SD.Statistically significant group differences were seen on 15 of 30 lower-level traits within all five high-order dimensions. There were large effect sizes for Trust (0.77) and Self-discipline (0.85), while the other statistically significant group differences were smaller with effect sizes in the range from 0.43 to 0.74 SD.However, patients with BD showed a profile with high-order dimensions and lower-level traits within one standard deviation from the mean score except for the lower-level trait Depression. CONCLUSIONS: Our findings suggest that patients with BD differ from healthy control persons with respect to higher levels of Neuroticism, Openness to Experience and lower scores on Agreeableness and on Conscientiousness, but prospective studies are needed to evaluate the implications of this finding.

Improving the precision of depression diagnosis in general practice: a cluster-randomized trial.

BACKGROUND: Methods to enhance the accuracy of the depression diagnosis continues to be of relevance to clinicians. The primary aim of this study was to compare the diagnostic precision of two different diagnostic strategies using the Mini International Neuropsychiatric Interview (MINI) as a reference standard. A secondary aim was to evaluate accordance between depression severity found via MINI and mean Major Depression Inventory (MDI) sum-scores presented at referral. METHODS: This study was a two-armed, cluster-randomized superiority trial embedded in the Collabri trials investigating collaborative care in Danish general practices. GPs performing case-finding were instructed always to use MDI when suspecting depression. GPs performing usual clinical assessment were instructed to detect depression as they would normally do. According to guidelines, GPs would use MDI if they had a clinical suspicion, and patients responded positively to two or three core symptoms of depression. We compared the positive predictive value (PPV) in the two groups. RESULTS: Fifty-one GP clusters were randomized. In total, 244 participants were recruited in the case-finding group from a total of 19 GP clusters, and 256 participants were recruited in the usual clinical assessment group from a total of 19 GP clusters. The PPV of the GP diagnosis, when based on case-finding, was 0.83 (95% CI 0.78-0.88) and 0.93 (95% CI 0.89-0.96) when based on usual clinical assessment. The mean MDI sum-scores for each depression severity group indicated higher scores than suggested cut-offs. CONCLUSIONS: In this trial, systematic use of MDI on clinical suspicion of depression did not improve the diagnostic precision compared with the usual clinical assessment of depression. TRIAL REGISTRATION: The trial was retrospectively registered on 07/02/2016 at ClinicalTrials.gov. No. NCT02678845 .

Collaborative care for depression and anxiety disorders: results and lessons learned from the Danish cluster-randomized Collabri trials.

BACKGROUND: Meta-analyses suggest that collaborative care (CC) improves symptoms of depression and anxiety. In CC, a care manager collaborates with a general practitioner (GP) to provide evidence-based care. Most CC research is from the US, focusing on depression. As research results may not transfer to other settings, we developed and tested a Danish CC-model (the Collabri-model) for depression, panic disorder, generalized anxiety disorder, and social anxiety disorder in general practice. METHODS: Four cluster-randomized superiority trials evaluated the effects of CC. The overall aim was to explore if CC significantly improved depression and anxiety symptoms compared to treatment-as-usual at 6-months' follow-up. The Collabri-model was founded on a multi-professional collaboration between a team of mental-health specialists (psychiatrists and care managers) and GPs. In collaboration with GPs, care managers provided treatment according to a structured plan, including regular reassessments and follow-up. Treatment modalities (cognitive behavioral therapy, psychoeducation, and medication) were offered based on stepped care algorithms. Face-to-face meetings between GPs and care managers took place regularly, and a psychiatrist provided supervision. The control group received treatment-as-usual. Primary outcomes were symptoms of depression (BDI-II) and anxiety (BAI) at 6-months' follow-up. The incremental cost-effectiveness ratio (ICER) was estimated based on 6-months' follow-up. RESULTS: Despite various attempts to improve inclusion rates, the necessary number of participants was not recruited. Seven hundred thirty-one participants were included: 325 in the depression trial and 406 in the anxiety trials. The Collabri-model was implemented, demonstrating good fidelity to core model elements. In favor of CC, we found a statistically significant difference between depression scores at 6-months' follow-up in the depression trial. The difference was not significant at 15-months' follow-up. The anxiety trials were pooled for data analysis due to inadequate sample sizes. At 6- and 15-months' follow-up, there was a difference in anxiety symptoms favoring CC. These differences were not statistically significant. The ICER was 58,280 Euro per QALY. CONCLUSIONS: At 6 months, a significant difference between groups was found in the depression trial, but not in the pooled anxiety trial. However, these results should be cautiously interpreted as there is a risk of selection bias and lacking statistical power. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02678624 and NCT02678845 . Retrospectively registered on 7 February 2016.

A confirmative clinimetric analysis of the 36-item Family Assessment Device.

BACKGROUND: The Family Assessment Device (FAD) is a 60-item questionnaire widely used to evaluate self-reported family functioning. However, the factor structure as well as the number of items has been questioned. A shorter and more user-friendly version of the original FAD-scale, the 36-item FAD, has therefore previously been proposed, based on findings in a nonclinical population of adults. AIMS: We aimed in this study to evaluate the brief 36-item version of the FAD in a clinical population. METHODS: Data from a European multinational study, examining factors associated with levels of family functioning in adult cancer patients' families, were used. Both healthy and ill parents completed the 60-item version FAD. The psychometric analyses conducted were Principal Component Analysis and Mokken-analysis. RESULTS: A total of 564 participants were included. Based on the psychometric analysis we confirmed that the 36-item version of the FAD has robust psychometric properties and can be used in clinical populations. CONCLUSIONS: The present analysis confirmed that the 36-item version of the FAD (18 items assessing 'well-being' and 18 items assessing 'dysfunctional' family function) is a brief scale where the summed total score is a valid measure of the dimensions of family functioning. This shorter version of the FAD is, in accordance with the concept of 'measurement-based care', an easy to use scale that could be considered when the aim is to evaluate self-reported family functioning.

Surrogate markers of visceral fat and response to anti-depressive treatment in patients with major depressive disorder: a prospective exploratory analysis.

BACKGROUND: Body mass index (BMI) and body weight have been shown to be associated to treatment outcome in patients with major depressive disorder, but this relationship is not clear. Visceral fat might be an underlying mechanism explaining this relationship. AIMS: The aim of this study was to prospectively investigate whether visceral fat, as measured by hip-to-waist ratio and waist circumference, affects treatment outcome in patients with major depressive disorder in patients attending a hospital psychiatric care unit in Denmark. METHODS: The study was conducted as an observational prospective study including 33 patients with major depressive disorder. Assessments were made at enrolment and after 8 weeks. Primary variables were hip-to-waist ratio and waist circumference. Outcome were remission or response of depressive symptoms measured with the Hamilton Depression Rating Scale (HAM-D17) interviews and HAM-D6 self-rating questionnaires. RESULTS: No differences were found in outcome between groups of patients with high vs low visceral fat in this population. CONCLUSIONS: The lack of association was evident for all surrogate markers of visceral fat, and suggests that visceral fat has no impact on outcomes of depressive symptoms. However, study limitations might have contributed to this lack of association, especially sample size and considerable variations on multiple parameters including treatment received during the 8 weeks of follow-up.

Usage of psychiatric emergency services by asylum seekers: Clinical implications based on a descriptive study in Denmark.

BACKGROUND: Asylum seekers are found to be at high risk of mental health problems. Little is known about the use of acute psychiatric emergency services by asylum seekers. AIM: To describe the usage of an inpatient/outpatient psychiatric emergency service in Denmark by adult asylum seekers, and discuss clinical implications. METHOD: This descriptive study is based on retrospective data collected from patient charts during a 3-month period. RESULTS: A total of 31 evaluations were made (3.3% of all evaluations), based on 23 asylum seekers. Patients originated from 16 different countries, were predominantly male and married. The group consisted primarily (61%) of failed asylum seekers. Most patients (81%) presented with relevant mental health problems. The main reasons for presenting to the acute psychiatric emergency service were suicidal ideation and/or behaviour (60%). The most frequent diagnosis given at the initial evaluation was ICD-10 F43.9 "reaction to severe stress, unspecified" (50%). Evaluations were made primarily by non-psychiatrists. No standardized screening or diagnostic instrument was used. CONCLUSION: This first description of the use of an acute psychiatric emergency service by asylum seekers in Denmark shows some of the acute mental health needs asylum seekers present with. The findings of high levels of suicidal ideation and possible diagnostic difficulties are discussed, as well as possible improvements of the referral and psychiatric evaluation processes.

Psychometric analysis of the Melancholia Scale in trials with non-pharmacological augmentation of patients with therapy-resistant depression.

OBJECTIVE: The Melancholia Scale (MES) consists of the psychic core items of the Hamilton Depression Scale (HAM-D6) (depressed mood, interests, psychic anxiety, general somatic, guilt feelings, and psychomotor retardation) and the neuropsychiatric items of the Cronholm-Ottossen Depression Scale. Patients resistant to anti-depressant medication (therapy-resistant depression) have participated in our trials with non-pharmacological augmentation. On the basis of these trials, we have evaluated to what extent the neuropsychiatric subscale of the MES (concentration difficulties, fatigability, emotional introversion, sleep problems, and decreased verbal communication) is a measure of severity of apathia when compared with the HAM-D6 subscale of the MES. METHODS: We have focused on rating sessions at baseline (week 0) and after 2 and 4 weeks of therapy in four clinical trials on therapy-resistant depression with the following augmentations: electroconvulsive therapy, bright light therapy, transcranial magnetic stimulation or pulsed electromagnetic fields, and wake therapy. The item response theory model constructed by Mokken has been used as the psychometric validation of unidimensionality. For the numerical evaluation of transferability, we have tested item ranks across the rating weeks. RESULTS: In the Mokken analysis, the coefficient of homogeneity was above 0.40 for both the HAM-D subscale and the apathia subscale at week 4. The numerical transferability across the weeks was statistically significant (p < 0.05) for both subscales. CONCLUSION: The apathia subscale is a unidimensional scale with acceptable transferability for the measurement of treatment-resistant symptoms, analogue to the psychic core subscale (HAM-D6).

Alpha-defensin DEFA1A3 gene copy number elevation in Danish Crohn's disease patients.

BACKGROUND AND PURPOSE OF STUDY: Extensive copy number variation is observed for the DEFA1A3 gene encoding alpha-defensins 1-3. The objective of this study was to determine the involvement of alpha-defensins in colonic tissue from Crohn's disease (CD) patients and the possible genetic association of DEFA1A3 with CD. METHODS: Two-hundred and forty ethnic Danish CD patients were included in the study. Reverse transcriptase PCR assays determined DEFA1A3 expression in colonic tissue from a subset of patients. Immunohistochemical analysis identified alpha-defensin peptides in colonic tissue. Copy number of DEFA1A3 and individual alleles, DEFA1 and DEFA3, were compared with those for controls, by use of combined real-time quantitative PCR and pyrosequencing, and correlated with disease location. RESULTS: Inflammatory-dependent mRNA expression of DEFA1A3 (P < 0.001), and the presence of alpha-defensin peptides, were observed in colonic tissue samples. Higher DEFA1A3 gene copy number (CD: mean copy number, 7.2 vs. controls 6.7; P < 0.001) and individual DEFA1 alleles (CD mean copy number 5.6 vs. controls 5.1; P < 0.01) were associated with CD, with strong association with colonic location (P < 0.001). CONCLUSIONS: Alpha-defensins are involved in the inflammation of CD, with local mRNA and peptide expression. In combination with the findings that a high DEFA1A3 copy number is significantly linked to CD, these results suggest that a high DEFA1A3 copy number might be important in hindering the normal inflammatory response in CD, particularly colonic CD.

[Anxiety in patients with bipolar affective disorder].

Up to half of all patients with bipolar affective disorder (BP), develop a comorbid anxiety disorder during their lifetime. The consequences of comorbid anxiety in BP compared to BP without comorbid anxiety are serious, including more frequent and severe depressions and twice the risk of substance abuse and suicide attempts. In this review we argue, that due to the poorer prognosis of these conditions, it is important to diagnose comorbid anxiety when present, and to ensure proper treatment, which should be performed by a psychiatrist preferably specialised in affective disorders.

Facial skin temperature in acute stroke patients with delirium - A pilot study.

Facial skin temperature depends strongly on blood flow in small blood vessels in the skin. These are regulated by the sympathetic part of the autonomic nervous system. Delirium may pathophysiologically be associated to changes in the sympathetic part of the autonomic nervous system. In this observational study, we evaluated the influence of various exogenous and endogenous covariables on the regional facial temperatures in acute stroke patients with and without delirium. Facial thermography (FT) was performed using an infrared digital camera. Screening for delirium was done using the Confusion Assessment Method (CAM). Sixty-four patients were enrolled. Eight patients developed delirium. Sex and body temperature were positively associated to facial skin temperature, and so was ambient temperature but to an overall lesser magnitude. Stroke severity, diabetes, infection, facial palsy, facial sensory deficit, and physical activity did not influence facial skin temperature. Overall, there was no association between facial temperature and the occurrence of delirium except in one facial region, the medial palpebral commissure.

Changes in autonomic tone during delirium in acute stroke patients assessed by pupillometry and skin conductance.

Delirium is a common complication in acute ischemic stroke, possibly caused by alterations in the regulation of the sympathetic autonomic nervous system. We investigated whether such an association could be demonstrated with two easy-to-use measurement techniques: Measurement of palmar skin conductance level (SCL) and pupillometry measuring the dilation velocity in the pupillary light reflex (PLRdil.vel.). The cohort study included 64 patients admitted with acute ischemic stroke. During the study period (median 4.1 days, interquartile range 2.1 days) patients were assessed for delirium once daily as well as with measurements of SCL and PLRdil.vel up to twice daily. SCL and PLRdil.vel. during delirium were lower than without delirium present. For SCL the unadjusted difference was -40.8% (95% CI (-55.1 to -22.0), P value <.001) and for PLRdil.vel the unadjusted difference was -0.22 mm/s (95% CI (-0.42 to -0.01), P value = .041). The results demonstrate changes in sympathetic autonomic nervous system regulation during delirium in acute stroke patients.

Early intervention in psychosis: From clinical intervention to health system implementation.

AIM: Early intervention in psychosis (EIP) is a well-established approach with the intention of early detection and treatment of psychotic disorders. Its clinical and economic benefits are well documented. This paper presents basic aspects of EIP services, discusses challenges to their implementation and presents ideas and strategies to overcome some of these obstacles. METHODS: This paper is a narrative review about the evidence supporting EIP, with examples of successful implementation of EIP and of cases where major obstacles still need to be overcome. RESULTS: Experience from successfully implemented EIP services into the mental healthcare system have generated evidence, concepts and specific strategies that might serve as guidance or inspiration in other countries or systems where EIP is less well developed or not developed at all. Previous experience has made clear that evidence of clinical benefits alone is not enough to promote implementation, as economic arguments and political and social pressure have shown to be important elements in efforts to achieve implementation. CONCLUSIONS: Users' narratives, close collaboration with community organizations and support from policy-makers and known people within the community championing early intervention (EI) services are just a few of the approaches that should be considered in campaigns for implementation of EI services. Fast progress in implementation is possible.

[Family psychoeducation for affective disorders].

The aim of this article was to examine the evidence of family psychoeducation (FPE) for affective disorders. Evidence indicates that FPE can be an effective supplement to the standard treatment of patients with affective disorders. FPE can effectively reduce the patients' risk of relapse and reduce the burden experienced by the relatives. However, current studies are very heterogeneous and therefore difficult to compare. Up to this point the evidence regarding the effect of FPE on unipolar depression is still very sparse and further research is needed.

Collaborative care for panic disorder, generalised anxiety disorder and social phobia in general practice: study protocol for three cluster-randomised, superiority trials.

BACKGROUND: People with anxiety disorders represent a significant part of a general practitioner's patient population. However, there are organisational obstacles for optimal treatment, such as a lack of coordination of illness management and limited access to evidence-based treatment such as cognitive behavioral therapy. A limited number of studies suggest that collaborative care has a positive effect on symptoms for people with anxiety disorders. However, most studies are carried out in the USA and none have reported results for social phobia or generalised anxiety disorder separately. Thus, there is a need for studies carried out in different settings for specific anxiety populations. A Danish model for collaborative care (the Collabri model) has been developed for people diagnosed with depression or anxiety disorders. The model is evaluated through four trials, of which three will be outlined in this protocol and focus on panic disorder, generalised anxiety disorder and social phobia. The aim is to investigate whether treatment according to the Collabri model has a better effect than usual treatment on symptoms when provided to people with anxiety disorders. METHODS: Three cluster-randomised, clinical superiority trials are set up to investigate treatment according to the Collabri model for collaborative care compared to treatment-as-usual for 364 patients diagnosed with panic disorder, generalised anxiety disorder and social phobia, respectively (total n = 1092). Patients are recruited from general practices located in the Capital Region of Denmark. For all trials, the primary outcome is anxiety symptoms (Beck Anxiety Inventory (BAI)) 6 months after baseline. Secondary outcomes include BAI after 15 months, depression symptoms (Beck Depression Inventory) after 6 months, level of psychosocial functioning (Global Assessment of Functioning) and general psychological symptoms (Symptom Checklist-90-R) after 6 and 15 months. DISCUSSION: Results will add to the limited pool of information about collaborative care for patients with anxiety disorders. To our knowledge, these will be the first carried out in a Danish context and the first to report results for generalised anxiety and social phobia separately. If the trials show positive results, they could contribute to the improvement of future treatment of anxiety disorders. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02678624 . Retrospectively registered 7 February 2016; last updated 15 August 2016.

Collaborative care for depression in general practice: study protocol for a randomised controlled trial.

BACKGROUND: Depression is a common illness with great human costs and a significant burden on the public economy. Previous studies have indicated that collaborative care (CC) has a positive effect on symptoms when provided to people with depression, but CC has not yet been applied in a Danish context. We therefore developed a model for CC (the Collabri model) to treat people with depression in general practice in Denmark. Since systematic identification of patients is an "active ingredient" in CC and some literature suggests case finding as the best alternative to standard detection, the two detection methods are examined as part of the study. The aim is to investigate if treatment according to the Collabri model has an effect on depression symptoms when provided to people with depression in general practice in Denmark, and to examine if case finding is a better method to detect depression in general practice than standard detection. METHODS/DESIGN: The trial is a cluster-randomised, clinical superiority trial investigating the effect of treatment according to the Collabri model for CC, compared to treatment as usual for 480 participants diagnosed with depression in general practice in the Capital Region of Denmark. The primary outcome is depression symptoms (Beck's Depression Inventory (BDI-II)) after 6 months. Secondary outcomes include depression symptoms (BDI-II) after 15 months, anxiety symptoms (Beck's Anxiety Inventory (BAI)), level of functioning (Global Assessment of Function (GAF)) and psychological stress (Symptom Checklist-90-Revised (SCL-90-R)). In addition, case finding (with the recommended screening tool Major Depression Inventory (MDI)) and standard detection of depression is examined in a cluster-randomized controlled design. Here, the primary outcome is the positive predictive value of referral diagnosis. DISCUSSION: If the Collabri model is shown to be superior to treatment as usual, the study will contribute with important knowledge on how to improve treatment of depression in general practice, with major benefit to patients and society. If case finding is shown to be superior to standard detection, it will be recommended as the detection method in future treatment according to the Collabri model. TRIAL REGISTRATION: ClinicalTrials.gov. NCT02678845 . Retrospectively registered on 7 February 2016.

Family psychoeducation for major depressive disorder - study protocol for a randomized controlled trial.

BACKGROUND: Major depressive disorder has been shown to affect many domains of family life including family functioning. Conversely, the influence of the family on the course of the depression, including the risk of relapse, is one reason for targeting the family in interventions. The few studies conducted within this area indicate that family psychoeducation as a supplement to traditional treatment can effectively reduce the risk of relapse in patients with major depression as well as being beneficial for the relatives involved. However, the evidence is currently limited. This study will investigate the effect of family psychoeducation compared to social support on the course of the illness in patients with major depressive disorder. METHOD/DESIGN: The study is designed as a dual center, two-armed, observer-blinded, randomized controlled trial. Relatives are randomized to participate in one of two conditions: either four sessions of manualized family psychoeducation or four sessions in a social support group led by a health care professional. Patients will not participate in the groups and will continue their treatment as usual. A total of 100 patients, each accompanied by one relative, will be recruited primarily from two outpatient clinics in the Capital Region of Denmark. The primary outcome is the occurrence of depressive relapse at 9-month follow-up defined as a score ≥7 on the Hamilton six-item subscale. Secondary outcomes will include time to relapse. DISCUSSION: It is hoped that the results from this study will help to clarify the mechanisms behind any beneficial changes due to family psychoeducation and provide information on the long-term effect of this intervention for both patient and relatives. If the results are positive, the family psychoeducation program may be suitable for implementation within a clinical setting. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02348827 , registered 5 January 2015.

Early intervention services in psychosis: from evidence to wide implementation.

AIM: Early intervention (EI) in psychosis is a comprehensive and evidence-based approach aimed at detection and treatment of psychotic symptoms in their early stages. This paper presents core features and noteworthy aspects of the evidence basis and limitations of EI, the importance of programme fidelity, challenges for its widespread dissemination and economic perspectives related to it. METHODS: This paper is a narrative review about the evidence supporting EI and the challenges to its widespread dissemination. RESULTS: In spite of evidence of a wide range of benefits, widespread dissemination has been slow, and even currently implemented programmes might be threatened. This reflects in part the shortcomings of mental health care in general, such as low priority for funding, stigma and structural problems. Successful examples of advocacy, mobilization and destigmatization campaigns have overcome these difficulties. CONCLUSIONS: Funding for mental health in general and for EI services appears low relative to need. One key argument for better funding for EI can be found in its favourable cost-effectiveness, but not all stakeholders beyond mental health administrators are aware of this. Positive impacts of EI programmes on excess unemployment and tax forgone suggest that social affairs and labour ministries - and not only health ministries - could be more involved in governance of mental health issues; ministries of justice and education are other sector stakeholders than can benefit. Wider dissemination of EI services will probably benefit from better integration of potential funders, promotion of joint targets and shared financial or budgetary incentives.

Development and remission of depressive symptoms and treatment with hormonal contraceptives.

We present two cases of female patients with a history of depression who developed depressive symptoms after treatment with hormonal contraceptives (HC) in the form of combined oral contraceptive pill, progestin-only pill and combined contraceptive vaginal ring. The presented two cases are based on the women's medical records complemented by personal interviews. The existing literature on the effects of HC on depression is inconclusive. Patient-based decisions with consideration of the individual history and predispositions are recommended when starting oral contraceptives. If depressive symptoms occur, decisions regarding discontinuation need to be made on an individual basis.

The Hamilton Depression Scale (HAM-D) and the Montgomery-Åsberg Depression Scale (MADRS). A psychometric re-analysis of the European genome-based therapeutic drugs for depression study using Rasch analysis.

The objective of this re-analysis of the European Genome-Based Therapeutic Drugs for Depression Study (GENDEP) was to psychometrically test the unidimensionality of the full Montgomery Åsberg Depression Rating Scale (MADRS10) and the Hamilton Depression Scale (HAM-D17) versus their respective subscales (MADRS5 and HAM-D6) containing the core symptoms of depression severity. Rasch analysis was applied using RUMM 2030 software to assess the overall fit for unidimensionality. Neither the MADRS10 nor the HAM-D17 was found to fit the Rasch model for unidimensionality. The HAM-D6 (containing the items of depressed mood, guilt, work and interests, psychomotor retardation, psychic anxiety, and somatic general) as well as the analogue MADRS5 were tested for unidimensionality by use of the RUMM 2030 programme, and only the HAM-D6 was accepted. When testing for invariance across rating weeks or centres, the RUMM 2030 had to be supplemented with the Friedman two-way analysis of variance by ranks. The HAM-D6 but not the MADRS5 was accepted. It was therefore concluded that the HAM-D6 is a psychometrically valid outcome scale to measure change in clinical trials of antidepressants.

Emerging clinical trends and perspectives on comorbid patterns of mental disorders in research.

Comorbidity is a well-established and documented phenomenon in mental disorders and medicine with heuristic value. The concept of comorbidity remains however poorly defined and lacks a comprehensive and coherent theoretical framework. There is a need to develop coherent methodological strategies in order to promote a fuller understanding of the implications of comorbidity and to exploit its potential value with regard to etiopathogenic and therapeutic issues. This position paper makes recommendations of improved methodological standards and procedures and discusses a range of options that can provide incremental information that is likely to improve therapeutic outcomes.