At the Core of Depression: A Diagnostic Interview of the Core Features of Depression.

INTRODUCTION: Valid and reliable methods for diagnosing depression are essential. The present study aimed to test the performance of a new diagnostic interview for depression focusing on the core symptoms of depression. METHOD: We developed a diagnostic interview for depression: the CORE Diagnostic Interview, CORE-DI, which assesses each of the core features of depression on the four dimensions: quality, reactivity, globality, and fluctuations over time. The diagnostic performance of this interview was tested in a clinical study including 83 individuals presenting with various depressive symptoms, who were interviewed independently (1) by means of the CORE-DI and the Mini-International Neuropsychiatric Interview (M.I.N.I.), and (2) by highly skilled specialists in depression representing gold standard diagnoses. RESULTS: We compared the outcome of the CORE-DI, the M.I.N.I., and the diagnosis made by clinicians, respectively, versus the gold standard diagnosis, using diagnostic efficiency statistics. The CORE-DI diagnosed depression with a high specificity (0.91, 95% CI: 0.85-0.97, for International Classification of Diseases [ICD]-10 criteria and 0.88, 95% CI: 0.81-0.95, for Diagnostic and Statistical Manual of Mental Disorders [DSM-5] criteria) compared to both M.I.N.I (specificity 0.44, 95% CI: 0.33-0.55) and clinical diagnoses (specificity 0.76, 95% CI: 0.67-0.85). The sensitivity of the CORE-DI was 0.61 (95% CI: 0.55-0.72) for ICD-10 criteria and 0.67 (95% CI: 0.57-0.77) for DSM-5 criteria. DISCUSSION/CONCLUSION: The CORE-DI increased the specificity of the depression diagnosis substantially compared to clinical diagnoses and the diagnoses obtained by M.I.N.I. The results point to the usefulness of an elaborated and systematic assessment of the core symptoms in the examination of patients with depressive symptoms and thereby indicate a way for further development of specific diagnostic tools for depression in both clinical and research settings. However, it should be noted that the sensitivity of the CORE-DI was modest, and the psychometric properties of the CORE-DI might be different in other settings with higher or lower prevalence or severity of depressive symptoms.

Treatment History Characteristics Associated With Use of Isocarboxazid: A Nationwide Register-Based Study.

PURPOSE/BACKGROUND: The monoamine oxidase inhibitor isocarboxazid (Marplan) is occasionally used in the treatment of depression, but there is only little knowledge on the nature of the use of isocarboxazid in clinical practice. We aimed to identify treatment history characteristics associated with this use. METHODS/PROCEDURES: Via the nationwide Danish registers, we identified all adult incident users of isocarboxazid in the period from 2001 to 2018, as well as up to 5 matched controls using another antidepressant (matched on date of redeemed prescription, age, sex, and region of residence). The 5-year treatment history of the isocarboxazid users and the controls was assessed via the Danish registers. The association between treatment history characteristics and isocarboxazid use was examined by multivariate conditional logistic regression. FINDINGS/RESULTS: We identified 1455 isocarboxazid users and 7045 controls using another antidepressant. The following characteristics were associated with statistically significant increased likelihood of receiving isocarboxazid treatment: Prior treatment with a selective serotonin reuptake inhibitor (odds ratio [OR], 1.80 with 95% confidence interval [CI], 1.46-2.23), a serotonin-norepinephrine reuptake inhibitor (OR, 4.90; 95% CI, 4.08-5.89), a noradrenergic and specific serotonergic antidepressant (OR, 1.56; 95% CI, 1.30-1.88), a tricyclic antidepressant (OR, 5.05; 95% CI, 4.19-6.08), other antidepressants (OR, 4.74; 95% CI, 3.74-6.01), lithium (OR, 6.70; 95% CI, 5.08-8.83), an antipsychotic (OR, 1.43; 95% CI, 1.19-1.73), and each diagnosis of depression received in relation to psychiatric hospital treatment (OR, 1.31; 95% CI, 1.23-1.39). Forty percent of those initiating isocarboxazid had received treatment with drugs from 5 or more different psychopharmacological classes in the 5 preceding years. IMPLICATIONS/CONCLUSIONS: These findings suggest that isocarboxazid is typically used for treatment-resistant depression, consistent with guideline recommendations.

Early LSD treatment in Denmark from 1960 to 1974: An analysis of possible and long-lasting changes in the adult personality following psychedelic treatment. A historical retrospective cohort study.

ABSTRACT: In view of the renewed interest in psychedelics in psychiatry it is timely to analyze psychedelic treatment in historical cohorts. Recently the therapeutic efficacy of psychedelics has been linked to the so-called phenomenon of "connectedness." The aim of the present study was to explore whether long-lasting personality changes were observed in any of the 151 Danish psychiatric patients who were treated with Lysergic acid diethylamide (LSD) from 1960 to 1974.The exploration included a reanalysis of a subgroup as well from a 1964 Danish historical cohort. Medical records and other case materials of the above mentioned 151 patients are kept in the Danish State Archives. The present author was granted access to the LSD case materials in the Danish State Archives, and respected confidentiality per the Archives Law. According to the LSD Damages Law from 1986, they all received financial compensation for LSD-inflicted harm.Analysis did not reveal any personality changes such as "connectedness;" however, other lasting personality changes were observed in 2 to 4 patients and in quite a few patients unwanted effects persisted for weeks or months following acute treatment. In the present analysis of the 1964 cohort, the same percentage of patients improved with LSD treatment as in the historical analysis. In the latter, however, little attention was given to side effects, such as suicide attempts, suicides, and one homicide.Future psychedelic research with psychiatric patients should respect the potential toxicity of LSD and other psychedelics and meticulously monitor possible side effects.

LSD treatment in Scandinavia: emphasizing indications and short-term treatment outcomes of 151 patients in Denmark.

BACKGROUND: New research has suggested the clinical use of lysergic acid diethylamide (LSD) and psilocybin in selected patient populations. However, concerns about the clinical use of LSD were advanced in a large Danish follow-up study that assessed 151 LSD-treated psychiatric patients approximately 25 years after their treatment in the 1960s. AIMS: The purpose of the present study was to give a retrospective account of the short-term outcome of LSD treatment in these 151 Danish psychiatric patients. METHODS: The LSD case material in the Danish State Archives consists of medical case records of 151 LSD-treated patients, who complained and received economic compensation with the LSD Damages Law. The author carefully read and reviewed the LSD case material. RESULTS: LSD was used to treat a wide spectrum of mental disorders. Independent of diagnoses, 52 patients improved, and 48 patients worsened acutely with the LSD treatment. In a subgroup of 82 neurotic patients, the LSD dose-index (number of treatments multiplied by the maximal LSD dose) indicated the risk of acute worsening. In another subgroup of 19 patients with obsessive-compulsive neurosis, five patients later underwent psychosurgery. A small subgroup of 12 patients was treated with psilocybin. The long-term outcome was poor in most of the patients. CONCLUSIONS: Despite the significant limitations to a retrospective design, this database warrants caution in mental health patients. The use of LSD and psilocybin in mental health patients may be associated with serious short- and long-term side effects. Until further trials with rigorous designs have cleared these drugs of their potential harms, their clinical utility in these groups of patients has not been fully clarified.

Danish translation and validation of Kessler's 10-item psychological distress scale - K10.

BACKGROUND: Psychological distress is a trans-diagnostic feature of mental suffering closely associated with mental disorders. Kessler's 10-item Psychological Distress Scale (K10), a scale with sound psychometric properties, is widely used in epidemiological studies. AIM: To translate and investigate whether K10 is a reliable and valid rating scale for the measurement of psychological distress in a Danish population. METHODS: The translation was carried out according to official WHO translation guidelines. A sample of 100 subjects was included, 54 patients from the regional Mental Health Service (MHS) and 46 subjects with no psychiatric history. All participants were assessed with a psychiatric diagnostic interview (MINI) and handed out K10. Concurrent validity was assessed by WHO Well-being Index (WHO-5). Correlation matrix analysis was conducted for the full sample and receiver operating characteristic (ROC) curves for discriminating mental health service affiliation. RESULTS: Mean K10 scores differed, with decreasing levels, between inpatients and outpatient in MHS and the subjects with no psychiatric history. Factor analysis confirmed a unidimensional structure, and Cronbach's alpha and Omega showed excellent internal reliability. AUC for the K10 ROC curves showed excellent sensitivity (0.947 [0.900-0.995]), accurately differentiating mental health from non-mental health patients. CONCLUSION: The Danish K10 has the same strong internal reliability as the original English version, and scores differ between psychiatric patients in outpatient and emergency ward settings. CLINICAL IMPLICATIONS: The Danish K10 translation is authorized and freely available for download at https://www.hcp.med.harvard.edu/ncs/k6_scales.php . The utility as an instrument for clinical screening in a mental healthcare setting is supported.

Neurotoxicity and LSD treatment: a follow-up study of 151 patients in Denmark.

LSD was introduced in psychiatry in the 1950s. Between 1960 and 1973, nearly 400 patients were treated with LSD in Denmark. By 1964, one homicide, two suicides and four suicide attempts had been reported. In 1986 the Danish LSD Damages Law was passed after complaints by only one patient. According to the Law, all 154 applicants received financial compensation for LSD-inflicted harm. The Danish State Archives has preserved the case material of 151 of the 154 applicants. Most of the patients suffered from severe side effects of the LSD treatment many years afterwards. In particular, two-thirds of the patients had flashbacks. With the recent interest in LSD therapy, we should consider the neurotoxic potential of LSD.

[The use of the monoamine oxidase inhibitor isocarboxazide in treatment-resistant depression]. / Anvendelse af monoaminooksidasehæmmeren isocarboxazid ved behandlingsresistent depression

The antidepressant efficacy of isocarboxazide is well established; however, the clinical use early became restricted and today the use of isocarboxazide in Denmark is very limited. Isocarboxazide is safe when keeping a low tyramine-containing diet and avoiding concomitant treatment with certain drugs. The risk of developing oedema can be reduced by vitamin B6 treatment. Normal dosage isocarboxazide may be prescribed for all patients because isocarboxazide is not metabolized through the CYP2D6 enzyme complex like most other antidepressants. It is recommended to include isocarboxazide in the official treatment algorithms for patients who are resistant to conventional antidepressant therapy and electroconvulsive therapy.

Clinical and psychometric validation of the psychotic depression assessment scale.

BACKGROUND: Recent studies have indicated that the 11-item Psychotic Depression Assessment Scale (PDAS), consisting of the 6-item melancholia subscale (HAM-D6) of the Hamilton Depression Rating Scale and 5 psychosis items from the Brief Psychiatric Rating Scale (BPRS), is a valid measure for the severity of psychotic depression. The aim of this study was to subject the PDAS, and its depression (HAM-D6) and psychosis (BPRS5) subscales to further validation. METHODS: Patients diagnosed with psychotic depression at Danish psychiatric hospitals participated in semi-structured interviews. Video recordings of these interviews were assessed by two experienced psychiatrists (global severity rating of psychotic depression, depressive symptoms and psychotic symptoms) and by two young physicians (rating on 27 symptom items, including the 11 PDAS items). The clinical validity and responsiveness of the PDAS and its subscales was investigated by Spearman correlation analysis of the global severity ratings and the PDAS, HAM-D6, and BPRS5 total scores. The unidimensionality of the scales was tested by item response theory analysis (Mokken). RESULTS: Ratings from 39 participants with unipolar psychotic depression and nine participants with bipolar psychotic depression were included in the analysis. The Spearman correlation analysis indicated that the PDAS, HAM-D6 and BPRS5 were clinically valid (correlation coefficients from 0.78 to 0.85, p<0.001) and responsive (correlation coefficients from 0.72 to 0.86, p<0.001) measures of psychotic depression. According to the Mokken analysis, all three scales were unidimensional. CONCLUSIONS: The clinical validity, responsiveness and unidimensionality of the PDAS and its subscales were confirmed in an independent sample of patients with psychotic depression.

Fewer re-admissions and bed days following an intensive transitional post-discharge aftercare programme for a mixed diagnostic group of patients.

BACKGROUND: The organization of aftercare is important for a successful outcome; still the optimal organization has not been fully explored. An intensive transitional post-discharge aftercare (TA) programme, for a mixed group of non-psychotic patients, was recently developed. Patients with non-psychotic diagnoses are often discharged with low well-being while still symptomatic, placing high demands on aftercare. AIMS: To evaluate retrospectively the short and long-term mental healthcare service use during and after the TA programme compared with the service use of a retrospective comparison group (RC), receiving less intensive outpatient aftercare. METHODS: Number of re-admissions, bed days and emergency visits after 10 weeks, 6 months and 1 year was retrospectively collected from electronic patient registers. Descriptive statistics, independent samples T-tests and repeated-measures analysis of variance was used to compare the groups. RESULTS: The majority of patients in both groups suffered from affective disorders, followed by personality disorders and a small number of other psychiatric diagnoses. Service use in the TA group was lower than in the RC group with fewer bed days after 10 weeks (P = 0.01) and after 6 months (P = 0.003), and fewer re-admissions after 6-12 months (P = 0.04). Emergency contacts did not differ significantly between the two groups at any point. CONCLUSIONS: The present study indicates beneficial effects of intensive TA, for a mixed group of non-psychotic patients. The lower service use in the TA programme group is in line with day treatment programme research for patients with affective disorders.

Beneficial effect of brief intensive cognitive behavioural therapy-based psychiatric aftercare for early discharged non-psychotic patients.

INTRODUCTION: In Denmark, following psychiatric emergency admission, patients with depression, anxiety or personality disorders are discharged as early as possible due to pressure on psychiatric beds. However, the receiving out-patient units frequently have waiting time. The design of a brief, cognitive-based psychiatric aftercare service and the early treatment results are presented. MATERIAL AND METHODS: This was a descriptive study of symptom levels before and after the individual therapy part of a new aftercare programme. The initial new intensive aftercare consisted of psychiatric consultations, telephone outreach and individual cognitive behavioural therapy-based therapy twice a week, in total five times. Focus was on collaborative goal setting and next-of-kin participation. Self-ratings (WHO-5 Well-Being Scale (WHO-5); Becks Depression Inventory-II (BDI)) were obtained at the first day and at end of individual therapy. RESULTS: The self-ratings at discharge showed a high BDI rating in the patient sample (mean = 32.0 (standard deviation (SD) = 11.9; n = 105)), and much lower well-being at discharge than previously seen in a comparable Danish setting (mean WHO-5 at onset = 5.6 (SD = 4.8; n = 102)). Ratings improved by the end of the individual therapy (i.e. WHO-5 = 8.3 (SD = 5.6; n = 102); BDI = 26.1 (SD = 12.3; n = 105)). CONCLUSION: Symptom reduction was evident in the first period after discharge, and the patients were satisfied with the contents and format of the service. However, the results are preliminary as we lack data from a comparable patient group receiving no treatment or treatment as usual. FUNDING: not relevant. TRIAL REGISTRATION: Danish Data Protection Agency, The Capital Region 2007-58-0015.

Mania in the Nordic countries: patients and treatment in the acute phase of the EMBLEM study.

In bipolar disorder, mood stabilizers and second-generation antipsychotics have a central role in pharmacotherapy. There are, however, substantial differences in how the treatment is realized in different countries. The aim of this paper was to compare the treatment of acute mania in the Nordic countries with other European countries during the first 12 weeks of the EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) study. Adult patients with bipolar disorder were enrolled within standard course of care as in/outpatients if they initiated/changed oral medication with antipsychotics, anticonvulsants or lithium for treatment of acute mania. Five hundred and thirty European psychiatrists including 23 Nordic psychiatrists enrolled 3459 patients including 79 Nordic patients eligible for analysis using the same study methods assessing demographics, psychiatric history, clinical status, functional status and pharmacological treatment. Psychiatric status at inclusion measured by the Young Mania Rating Scale (YMRS) and the Clinical Global Impression-Bipolar Disorder (CGI-BP) were similar in the Nordic and European patient groups, which is surprising as 73% of the Nordic patients compared with 38% of the European patients were inpatients. In the Nordic group of patients, more patients were living independently. Before inclusion in the study more patients in the Nordic group had combination therapy, but after inclusion in the study the prescription pattern of psychopharmacy was similar in the Nordic and the European patient groups. This study indicated differences in admission patterns, patient social functioning and medical treatment in the Nordic patients compared with the European patients.

Climatic factors and bipolar affective disorder.

In bipolar disorder, the factors provoking a new episode are unknown. As a seasonal variation has been noticed, it has been suggested that weather conditions may play a role. The aim of the study was to elucidate whether meteorological parameters influence the development of new bipolar phases. A group of patients with at least three previous hospitalizations for bipolar disorder was examined every 3 months for up to 3 years. At each examination an evaluation of the affective phase was made according to the Hamilton Depression Scale (HAM-D(17)), and the Bech-Rafaelsen Mania Rating Scale (MAS). In the same period, daily recordings from the Danish Meteorological Institute were received. We found no correlations between onset of bipolar episodes [defined as MAS score of 11 or more (mania) and as HAM-D(17) score of 12 or more (depression)] and any meteorological parameters. We found a statistical significant correlation between mean HAM-D(17) scores and change in mean and maximum temperature, and non-statistical significant correlations between mean MAS scores and rainfall plus atmospheric pressure, and non-statistical significant correlations between mean HAM-D(17) scores and hours of sunshine and cloudiness. Though meteorological factors may have an impact on triggering new episodes in bipolar patients, they do not constitute a dominant cause.

[Affective disorders--depression diagnosis and prognosis]. / Om affektive lidelser--saerligt med henblik på depressionsdiagnostik og prognose.

Affective disorders have been described since ancient Greece. The ICD-10 classification of mania and depression mixes typology with severity. A hierarchical model for depression separating psychotic, melancholic and non-melancholic depression is outlined. Psychometric measurements of mania and depression, including scales for use in clinical practice are presented. The course of affective disorders underlines the severity of the disorders with many recurrent episodes and long duration, especially in the depressive state.

Life events and onset of a new phase in bipolar affective disorder.

BACKGROUND: There is an increasing focus on the impact of psychosocial factors and stressors on the course of bipolar affective disorder. The life event research has revealed many biases and the results are conflicting. In a prospective study we examined the relationship between life events and affective phases in a group of bipolar patients with a long duration of the disease. METHODS: A group of patients with at least three admissions to hospital for bipolar disorder was followed every 3 months for up to 3 years. At each examination an evaluation of affective phase was made according to the Hamilton Depression Scale, the Newcastle Depression Rating Scale and the Bech-Rafaelsen Mania Rating Scale. Moreover, the patients were rated according to the Paykel Life Events Scale. Their current medical treatment was noted. RESULTS: Fifty-six patients (19 men and 37 women) were included in the study. Women experienced a significantly higher number of life events than men. In 21% of the 353 examinations of women, a new phase was preceded by life events whereas this was the case only in 8% of the 152 examinations of men. In 13% of the male examinations the patients were in a manic phase and in 5% in a depressive phase. In 5% of the female examinations the patients were in a manic phase and in 15% in a depressive phase. Half of the women's depressive phases were preceded by life events, but none of the depressive phases of men. The categories of life events preceding the depressive phases presented a significant overweight of somatic ill health and conflicts in the family. CONCLUSION: We found a gender difference in the course of bipolar affective disorder, as women had a significantly higher number of depressive episodes than men and men had a higher number of manic episodes than women. In bipolar patients with long duration of disease a significant number of depressive episodes in women were preceded by negative life events. Somatic health problems and conflicts in the family were significant factors preceding new depressive phases.

The stability of the Seasonal Pattern Assessment Questionnaire score index over time and the validity compared to classification according to DSM-III-R.

BACKGROUND: In 1984, Rosenthal et al. described a group of patients characterised by repeated winter depression with atypical symptoms eventually followed by summer mania or hypomania (seasonal affective disorder, SAD). The relationship between SAD and the classical manic-depressive disorder is uncertain. The aim of this study was to validate the Seasonal Pattern Assessment Questionnaire (SPAQ) classification in relation to the DSM-III-R criteria of seasonal patterns in a group of patients with bipolar affective disorder and to evaluate the stability of the SPAQ score index over time. METHODS: A group of bipolar patients were followed for 3 years with examinations every third month and at hospitalisation. At inclusion and at each following examination the patients were rated with the Hamilton Depression Rating Scale, the Newcastle Depression Rating Scale, and the Bech-Rafaelsen Mania Rating Scale. At inclusion and once a year the patients completed the SPAQ. RESULTS: Fifty-six patients agreed to participate and 46 patients completed 1 year or more. Eight patients, all women, had at least one SPAQ score index (SSI) of 11 or more. Women scored significantly higher than men on SPAQ. The test/re-test reliability of SSI between two consecutive years was good, but decreased as the time difference between tests increased. Moreover, we found no relation between seasonal variations of affective episodes according to SSI and DSM-III-R. LIMITATIONS: The group of patients with seasonality according to DSM-III-R or SSI was small. CONCLUSION: The validity of SSI between two consecutive years is good, but decreases as the time difference between tests increases. There is no relationship between seasonality defined by DSM-III-R and SSI. Female bipolar patients show, as the general population, seasonal variations in mood, energy, sociality, appetite, and sleep independently of their affective episodes. SSI cannot be used for the prediction of seasonal variation in a group of bipolar patients.

[Diagnosis and treatment of depression in general practice. A questionnaire study]. / Diagnostik og behandling af depression i almen praksis. En spørgeskemaundersøgelse.

INTRODUCTION: The purpose of this questionnaire study was to assess the knowledge and attitude of general practitioners (GPs) towards the use of diagnostic criteria in clinical practice, and the extent to which diagnostic tools are used as a prerequisite for the treatment of depressive patients in general practice. MATERIAL AND METHODS: A total of 758 out of 1,700 randomly selected GPs responded to the questionnaire. The GPs' demographic data (age, sex, number of years in practice, supplementary education), diagnostic practice (knowledge of depressive core symptoms and diagnostic tools and scales), and clinical practice (assessment of the effectiveness of treatment, duration of treatment, aim of treatment, and use of psychotherapy) were registered. RESULTS: The study showed that GPs, who had taken part in supplementary training in psychiatric issues within the preceding year, to a higher extent than the rest of the GPs used diagnostic tools for all or most patients. This group of GPs also had a significantly greater knowledge of the depressive core symptoms as described in the ICD-10. When compared with the other group of GPs, they also felt themselves more confident of the diagnosis of depression before prescribing antidepressive medication. The vast majority of both groups felt that many depressive patients remained undiagnosed, because they simply do not consult their GPs. They also found that it was often questionable whether the symptoms were caused by life crisis or depression--and whether or not the depressive symptoms of these patients required drug treatment. DISCUSSION: The questionnaire study shows that the GPs' level of knowledge of diagnostics of depression is insufficient. There is an obvious need for supplementary training in general practice, thereby increasing the knowledge and the use of diagnostic criteria in order to make diagnoses of depression more correct and to improve treatment.