Prevalence of depressive disorder among patients with fibromyalgia: Systematic review and meta-analysis.

BACKGROUND: It is acknowledged that fibromyalgia (FM) as a medical (rheumatological) disorder and major depressive disorder (MDD) as a mental disorder often co-occurs, but the inconsistency is prevailing at study-level and no overall estimate of the co-occurrence exist. AIMS: This systematic review and meta-analysis aimed to estimate the overall point- and life-time prevalence of MDD among FM patients based on structured clinical interviews (SCI); and to estimate the point-prevalence of MDD among FM patients based on screening symptom scales (SSS). METHOD: The electronical databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO were searched for papers that reported on prevalence of MDD among FM patients. Eligible studies were included in a random effects meta-analysis pooling the prevalence of depression. RESULTS: The literature search identified 11 eligible studies for the meta-analysis. For SCI, the overall pooled point-prevalence (PP) was 25% (95% CI 19 to 31%), and life-time prevalence (LP) was 65% (95% CI 59 to 71%). When estimating the PP with self-administered SSS the overall pooled PP was 45% (95% CI 32 to 59%), and a single clinician-administered SSS yielded a PP of 23% (95% CI 10 to 41%). There was low inconsistency for the SCI and high inconsistency for the SSS. CONCLUSION: One fourth of all FM patients had MDD, and more than half experienced MDD during their life-time according to clinician-administered instruments. Prevalence of MDD was almost twice as high when using self-administered symptom scales and may be likely to overestimate the co-occurrence.

The validity and sensitivity of PANSS-6 in treatment-resistant schizophrenia.

OBJECTIVE: To test the validity and sensitivity of the six-item version (PANSS-6) of the 30-item Positive and Negative Syndrome Scale (PANSS-30) in treatment-resistant schizophrenia (TRS). METHOD: Using data from the clozapine phase (2E) of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, we investigated the following: (i) The scalability of PANSS-6 and PANSS-30; (ii) The correlation between PANSS-6 and PANSS-30 total scores; (iii) Whether PANSS-6 could identify cross-sectional symptom remission; and (iv) The efficacy of clozapine, olanzapine, risperidone and quetiapine in TRS using the 'speed of change' on PANSS-6 and PANSS-30 (change in total score per week) as outcome measures. RESULTS: We found that (i) only PANSS-6 and not PANSS-30 was scalable; (ii) The correlation between PANSS-6 and PANSS-30 total scores was high (Spearman coefficient: 0.85), (iii) PANSS-6 accurately identified cross-sectional symptom remission as defined by the Andreasen et al. criteria; and (iv) The only antipsychotic that caused improvement (speed of change significantly lower than 0 during the first three months of treatment) was clozapine, both when using PANSS-6 (speed of change: -0.50 points/week; 95%CI: -0.84, -0.17) and PANSS-30 (speed of change: -1.41 points/week; 95%CI: -2.80, -0.02) as outcome measures. CONCLUSION: PANSS-6 validly measures severity, remission and antipsychotic efficacy in TRS.

Conceptualizing patient-reported outcome measures for use within two Danish psychiatric clinical registries: description of an iterative co-creation process between patients and healthcare professionals.

BACKGROUND: Denmark has national clinical indicator programs for adult patients diagnosed with depression and schizophrenia, respectively. Within each program, the responsible steering group (SG) decided to add some indicators based upon patient-reported outcome measures (PROMs). AIMS: The primary aim was to describe the process of selecting PROMs and defining a national measurement concept for use in clinical practice and for indicator monitoring and the secondary aim s to collect patient recommendations for implementation. METHODS: An interdisciplinary SG of healthcare professionals and a Patient Peer Board (PPB) representing both patient groups co-created the output in an iterative process. The work included literature search, PPB workshops, SG meetings, ratings of PROM topics and items, and a pilot. The PPB discussed the following: item relevance, mode of data collection, graphical format of the online PROMs, and display of results. Finally, requirements for PROM patient information were identified. Based upon input from the PPB, the SG selected the items and specified the measurement concept. RESULTS: The PPB prioritized 20 of 53 suitable items and suggested alternative wording and answer categories. A pilot was performed and 19 items covering well-being, lack of well-being, impairment of functioning, and overall health were selected for clinical testing. The patients recommended concrete, unambiguous, easily understandable information and procedures for data collection and display of results. CONCLUSIONS: The iterative co-creation process based upon a high degree of patient involvement resulted in a set of PROMs, a national measurement concept, and patient recommendations for implementation. The cooperation between patients and professionals was successful.

Effects of transcranial pulsed electromagnetic field stimulation on quality of life in Parkinson's disease.

BACKGROUND AND PURPOSE: Pulsed electromagnetic fields induce a protective and anti-inflammatory effect in the nervous system primarily due to growth factor upregulation that possibly abates neurodegeneration in Parkinson's disease (PD). This study investigated treatment effects of transcranial pulsed electromagnetic fields (T-PEMFs) on quality of life in PD and the feasibility and safety of this treatment. METHODS: In this double-blinded clinical study, 97 participants with idiopathic PD (Hoehn & Yahr stage I-IV), on optimal medical anti-parkinsonian treatment, were block randomized (3:3) to either active (n = 49) or placebo treatment (n = 48). Treatment with T-PEMFs entailed one daily 30-min home treatment for eight consecutive weeks. The 39-item Parkinson's Disease Questionnaire (PDQ-39) was assessed at baseline and endpoint. A special questionnaire was used to profile adverse events by interviewing the participants over the full treatment period. Treatment compliance was accounted for by daily treatment registration. RESULTS: The active group improved with respect to clinical effect size for the two dimensions, i.e. mobility and activities of daily living, compared with the placebo group. No between-group differences were found for the remaining PDQ-39 dimensions. There were no between-group difference in adverse events. Treatment compliance was 97.9%. CONCLUSION: Treatment with T-PEMFs improved mobility and activities of daily living scores for clinical effect size only in the active group, indicating a positive treatment response for motor symptoms. No difference was found between the two groups for the remaining PDQ-39 dimensions. The treatment had no or only mild adverse events and was performed with high compliance.

A pharmacopsychometric overview of major depressive episodes in positive psychiatry.

ABSTRACTBackground:The use of the pharmacopsychometric triangle to enhance patient-reported well-being as the ultimate goal of treatment has most intensively been studied in patients with a major depressive episode. METHODS: The review is structured on the pharmacopsychometric triangle in which the desired clinical effect of an antidepressive medication is balanced against the undesired side effects induced by this medication in terms of restored well-being. As a biological treatment, the antidepressive medication is compared clinically with both electroconvulsive therapy and psychological treatment. RESULTS: In the process of this review, evidence from a dose-response study in patients suffering from a major depressive episode with an adequate duration and symptom severity has demonstrated that the dose-response relationship emerged when using the patient-reported well-being outcome rather than the symptomatic reduction as outcome. CONCLUSION: The pharmacopsychometric triangle is in patients with major depressive episodes providing important information within positive psychiatry.

Diagnostic conversion to bipolar disorder in unipolar depressed patients participating in trials on antidepressants.

OBJECTIVE: In unipolar depressed patients participating in trials on antidepressants, we investigated if illness characteristics at baseline could predict conversion to bipolar disorder. METHOD: A long-term register-based follow-up study of 290 unipolar depressed patients with a mean age of 50.8 years (SD=11.9) participating in three randomized trials on antidepressants conducted in the period 1985-1994. The independent effects of explanatory variables were examined by applying Cox regression analyses. RESULTS: The overall risk of conversion was 20.7%, with a mean follow-up time of 15.2 years per patient. The risk of conversion was associated with an increasing number of previous depressive episodes at baseline, [HR 1.18, 95% CI (1.10-1.26)]. No association with gender, age, age at first depressive episode, duration of baseline episode, subtype of depression or any of the investigated HAM-D subscales included was found. LIMITATIONS: The patients were followed-up through the Danish Psychiatric Central Research Register, which resulted in inherent limitations such as possible misclassification of outcome. CONCLUSION: In a sample of middle-aged hospitalized unipolar depressed patients participating in trials on antidepressants, the risk of conversion was associated with the number of previous depressive episodes. Therefore, this study emphasizes that unipolar depressed patients experiencing a relatively high number of recurrences should be followed more closely, or at least be informed about the possible increased risk of conversion.

Measuring euthymia within the Neuroticism Scale from the NEO Personality Inventory: A Mokken analysis of the Norwegian general population study for scalability.

BACKGROUND: Whereas the Eysenck Neuroticism Scale only contains items covering negative mental health to measure dysthymia, the NEO Personality Inventory (NEO-PI) contains neuroticism items covering both negative mental health and positive mental health (or euthymia). The consequence of wording items both positively and negatively within the NEO-PI has never been psychometrically investigated. The aim of this study was to perform a validation analysis of the NEO-PI neuroticism scale. METHODS: Using a Norwegian general population study we examined the structure of the negatively and positively formulated items by principal component analysis (PCA). The scalability of the identified two groups of euthymia versus dysthymia items was examined by Mokken analysis. RESULTS: With a response rate of 90%, 1082 individuals with a completed NEO-PI were available. The PCA identified the neuroticism scale as the most distinct where 14 items had acceptable loadings for the euthymia subscale, another 14 items for the dysthymia subscale. However, the Mokken analysis coefficient of homogeneity only found acceptable scalability for the euthymia subscale. LIMITATIONS: A comparison with the Eysenck Neuroticism Scale was not performed. CONCLUSION: The NEO-PI neuroticism scale contains two subscales consisting of items worded in an opposite direction where only the positive euthymia items have an acceptable scalability.

PANSS-6: a brief rating scale for the measurement of severity in schizophrenia.

OBJECTIVE: The 30-item Positive and Negative Syndrome Scale (PANSS-30) is the most widely used rating scale in schizophrenia, but too long for clinical use. Shorter PANSS versions have been proposed, including the PANSS-14 and PANSS-8. However, none of these PANSS versions has been validated using the parametric Rasch rating scale model, which evaluates 'scalability'. Scalability means that each item in a rating scale provides unique information regarding syndrome severity and is a statistical prerequisite for using the total score as a measure of overall severity. METHOD: Based on data from two randomized placebo-controlled trials in schizophrenia, we tested the scalability of PANSS-30, PANSS-14 and PANSS-8 by means of the parametric Rasch rating scale model. Furthermore, we tested whether a scalable PANSS version could separate efficacy of haloperidol and sertindole from placebo. RESULTS: Neither PANSS-30, PANSS-14 nor PANSS-8 was scalable. However, PANSS-6, consisting of the items: P1-Delusions, P2-Conceptual disorganization, P3-Hallucinations, N1-Blunted Affect, N4-Social withdrawal, N6-Lack of spontaneity and flow of conversation, was scalable. Furthermore, PANSS-6 captured superior symptom reduction and higher remission rates during treatment with haloperidol and sertindole vs. placebo. CONCLUSION: PANSS-6 is a short schizophrenia severity rating scale that adequately separates antipsychotic efficacy from that of placebo.

Relapse Prevention in Major Depressive Disorder After Successful Acute Electroconvulsive Treatment: a 6-month Double-blind Comparison of Three Fixed Dosages of Escitalopram and a Fixed Dose of Nortriptyline - Lessons from a Failed Randomised Trial of the Danish University Antidepressant Group (DUAG-7).

INTRODUCTION: Electroconvulsive treatment (ECT) is an effective treatment for severe depression but carries a risk of relapse in the following months. METHODS: Major depressive disorder patients in a current episode attaining remission from ECT (17-item Hamilton Depression Rating Scale (HAM-D17) score≤9) received randomly escitalopram 10 mg, 20 mg, 30 mg or nortriptyline 100 mg as monotherapies and were followed for 6 months in a multicentre double-blind set-up. Primary endpoint was relapse (HAM-D17≥16). RESULTS: As inclusion rate was low the study was prematurely stopped with only 47 patients randomised (20% of the planned sample size). No statistically significant between-group differences could be detected. When all patients receiving escitalopram were compared with those receiving nortriptyline, a marginal superiority of nortriptyline was found (p=0.08). One third of patients relapsed during the study period, and one third completed. DISCUSSION: Due to small sample size, no valid efficacy inferences could be made. The outcome was poor, probably due to tapering off of non-study psychotropic drugs after randomisation; this has implications for future study designs. ClinicalTrials.gov Identifier: NCT00660062.

Rating scales measuring the severity of psychotic depression.

OBJECTIVE: Unipolar psychotic depression (PD) is a severe and debilitating syndrome, which requires intensive monitoring. The objective of this study was to provide an overview of the rating scales used to assess illness severity in PD. METHOD: Selective review of publications reporting results on non-self-rated, symptom-based rating scales utilized to measure symptom severity in PD. The clinical and psychometric validity of the identified rating scales was reviewed. RESULTS: A total of 14 rating scales meeting the predefined criteria were included in the review. These scales grouped into the following categories: (i) rating scales predominantly covering depressive symptoms, (ii) rating scales predominantly covering psychotic symptoms, (iii) rating scales covering delusions, and (iv) rating scales covering PD. For the vast majority of the scales, the clinical and psychometric validity had not been tested empirically. The only exception from this general tendency was the 11-item Psychotic Depression Assessment Scale (PDAS), which was developed specifically to assess the severity of PD. CONCLUSION: In PD, the PDAS represents the only empirically derived rating scale for the measurement of overall severity of illness. The PDAS should be considered in future studies of PD and in clinical practice.

Maintained superiority of chronotherapeutics vs. exercise in a 20-week randomized follow-up trial in major depression.

OBJECTIVE: To investigate the long-term antidepressant effect of a chronotherapeutic intervention. METHOD: In this randomized controlled trial 75 patients with major depression were allocated to fixed duloxetine and either a chronotherapeutic intervention (wake group) with three initial wake therapies, daily bright light therapy, and sleep time stabilization or to a group using daily exercise. Patients were followed 29 weeks. We report the last 20 weeks, a follow-up phase, where medication could be altered. Patients were assessed every 4 weeks. Remission rates were primary outcome. RESULTS: Patients in the wake group had a statistically significant higher remission rate of 61.9% vs. 37.9% in the exercise group at week 29 (OR = 2.6, CL = 1.3-5.6, P = 0.01). This indicated continued improvement compared with the 9 weeks of treatment response (44.8% vs. 23.4%) with maintenance of the large difference between groups. HAM-D17 endpoint scores were statistically lower in the wake group with endpoint scores of 7.5 (SE = 0.9) vs. 10.1 (SE = 0.9) in the exercise group (difference 2.7, CL = 0.5-4.8, P = 0.02). CONCLUSION: In this clinical study patients continued to improve in the follow-up phase and obtained very high remission rates. This is the first study to show adjunct short-term wake therapy and long-term bright light therapy as an effective and feasible method to attain and maintain remission.

Comparison of the utility of Cocaine- and Amphetamine-Regulated Transcript (CART), chromogranin A, and chromogranin B in neuroendocrine tumor diagnosis and assessment of disease progression.

CONTEXT: Prognosis in patients with neuroendocrine tumors (NETs) is often poor, frequently reflecting delayed diagnosis. Hence, accurate and practical NET markers are needed. Cocaine- and amphetamine-regulated transcript (CART) peptide is a potential novel NET marker. DESIGN AND PARTICIPANTS: Circulating levels of CART peptide and the established NET markers chromogranin A (CgA) and chromogranin B (CgB) were measured using RIA in 353 patients with NET (normal renal function) and in controls. Clinical data were collected retrospectively. MAIN OUTCOME MEASURE(S): The comparative and combined utility of CART, CgA, and CgB for diagnosis and assessment of disease progression was measured in different NET subtypes. RESULTS: CgA and CgB in combination improved diagnostic accuracy in patients with gut NETs, nongastroenteropancreatic NETs, and NETs with an unknown primary origin compared with each biomarker alone. Measuring CART did not further improve diagnosis in these NET subtypes. For pancreatic NETs, CgB was superior to CgA and CART in detecting stable disease (P < .007), whereas CgA and CART in combination were most effective in identifying progressive disease. In phaeochromocytomas/paragangliomas (PCC/PGL), CART was the most useful biomarker for identifying stable (P < .001) and progressive (P = .001) disease. Consistent with this, plasma CART decreased following PCC/PGL tumor resection, remaining low in all patients in remission, but increasing in those with progressive disease. CONCLUSIONS: CART is a useful marker for identifying progressive pancreatic NETs. CART is superior to CgA and CgB in detecting stable and progressive PCC/PGLs, and may have a role as a surveillance marker for PCC/PGL patients.

The Diagnostic Apathia Scale predicts the ability to return to work following depression or anxiety.

OBJECTIVE: The aim of this study was to evaluate the validity of a new apathy rating scale in predicting the ability to return to work (RTW) in patients with depression or anxiety a year after discharge from a psychiatric hospital. METHODS: We evaluated 56 patients with depression or anxiety, who participated in an on-going randomised clinical trial using RTW as primary outcome. The degree of apathy was measured by the Diagnostic Apathia Scale, which contains six items covering the following neuropsychological symptoms: concentration/memory problems, difficulties in decision making, lassitude, tiredness/fatigue, insomnia, and reduced ability to work and engage in personal interests. The scale was analysed for psychometric validity (scalability) and for its ability to predict RTW. Finally, the predictive validity of the Diagnostic Apathia Scale regarding RTW was compared with scales measuring severity of depression/anxiety symptoms, disability, and psychological well-being. RESULTS: The Diagnostic Apathia Scale displayed sufficient scalability, that is, the total score was a psychometrically valid measure of apathy. Only the Diagnostic Apathia Scale, and not the scales measuring severity of symptoms, disability, or psychological well-being, had predictive validity regarding RTW. Thus, 76% with 'clinically significant apathy' at baseline were unable to RTW versus 50% of the patients without apathy (p<0.05). CONCLUSION: The Diagnostic Apathia Scale was found to have an acceptable predictive validity in terms of patients' ability to RTW 1 year after discharge from hospitalisation for depression or anxiety.

Psychometric validation of the Hopkins Symptom Checklist (SCL-90) subscales for depression, anxiety, and interpersonal sensitivity.

BACKGROUND: The psychometric validity of many subscales of the 90-item Hopkins Symptom Checklist (SCL-90) remains largely unknown. Therefore, the aim of the present study was to evaluate the psychometric properties of the "Hamilton-subscales" for depression (SCL-D16), anxiety (SCL-A14), their 6-item core-measures (SCL-D6 and SCL-A6), the anxiety symptom scale (SCL-ASS8) and the interpersonal sensitivity scale (IPS5). METHODS: The psychometric properties of the SCL-D16, SCL-A14, SCL-D6, SCL-A6, SCL-ASS8, and the IPS5 were evaluated based on SCL-90 ratings from 850 day patients from a Danish psychiatric day hospital. The factor structure of the SCL-D16 and the SCL-A14 was investigated by means of principal component analysis (PCA) and the unidimensionality of all scales was estimated by Mokken analysis. Finally, the discriminant validity of the scales, i.e. their ability to distinguish between patients with various diagnoses, was tested. RESULTS: The PCA of the SCL-D16 and the SCL-A14 separated the core depression items from the arousal items on the SCL-D16 and the psychic anxiety items from the somatic anxiety items on the SCL-A14. According to the Mokken analyses, only the SCL-D6, the SCL-ASS8 and the IPS5 were unidimensional. Interestingly, the same three scales displayed discriminant validity for depression, anxiety disorders and personality disorders, respectively. LIMITATIONS: The study is based on data from Denmark. This may limit the validity of the results. CONCLUSIONS: Three unidimensional SCL-90 subscales were identified. Using these scales it is possible to perform a psychometrically valid evaluation of psychiatric patients regarding the severity of depression (HAM-D6), specific anxiety (SCL-ASS8) and interpersonal sensitivity (IPS5).

Measuring psychotic depression.

OBJECTIVE: Psychotic depression (PD) is a highly debilitating condition, which needs intensive monitoring. However, there is no established rating scale for evaluating the severity of PD. The aim of this analysis was to assess the psychometric properties of established depression rating scales and a number of new composite rating scales, covering both depressive and psychotic symptoms, in relation to PD. METHOD: The psychometric properties of the rating scales were evaluated based on data from the Study of Pharmacotherapy of Psychotic Depression. RESULTS: A rating scale consisting of the 6-item Hamilton melancholia subscale (HAM-D6 ) plus five items from the Brief Psychiatric Rating Scale (BPRS), named the HAMD-BPRS11 , displayed clinical validity (Spearman's correlation coefficient between HAMD-BPRS11 and Clinical Global Impression - Severity (CGI-S) scores = 0.79-0.84), responsiveness (Spearman's correlation coefficient between change in HAMD-BPRS11 and Clinical Global Impression - Improvement (CGI-I) scores = -0.74--0.78) and unidimensionality (Loevinger's coefficient of homogeneity = 0.41) in the evaluation of PD. The HAM-D6 fulfilled the same criteria, whereas the full 17-item Hamilton Depression Scale failed to meet criteria for unidimensionality. CONCLUSION: Our results suggest that the HAMD-BPRS11 is a more valid measure than pure depression scales for evaluating the severity of PD.

The biochemical utility of chromogranin A, chromogranin B and cocaine- and amphetamine-regulated transcript for neuroendocrine neoplasia.

Neuroendocrine neoplasia (NEN) is a heterogeneous group of tumours and often represents a therapeutic challenge to clinicians. The peptides chromogranin A (CgA), chromogranin B (CgB) and cocaine- and amphetamine-regulated transcript (CART) are widely distributed throughout the neuroendocrine system. CgA and CgB have been used as general NEN biomarkers for many years, while CART has only recently been identified. Of these biomarkers, CgA is the most commonly used. However, circulating CgA concentrations exhibit considerable intra-individual biological variation, are altered by proton pump inhibitors (PPIs) and somatostatin analogues and are elevated in non-NEN malignancies. Therefore, interpretation of CgA results must be in the context of these confounding factors. The effects of treatment and non-NEN conditions on circulating CgB and CART concentrations are less well understood. CgB is less affected by impaired renal function and PPIs than CgA; while, circulating CART concentrations lack a diurnal variation in humans and are more reliable markers of pancreatic NEN malignancy than CgA. The utility of circulating CgA measurements in NEN prognosis, surveillance and disease recurrence has been widely investigated. However, the utility of CgB and CART in NEN management is yet to be elucidated. Further studies are needed to establish whether CgB and CART are useful alternatives to CgA.