Wake and light therapy for moderate-to-severe depression - a randomized controlled trial.

OBJECTIVE: To examine the efficacy of using wake and light therapy as a supplement to standard treatment of hospitalized patients with depression. METHOD: In this randomized, controlled study, 64 patients with moderate-to-severe depression were allocated to standard treatment or to the intervention, which additionally consisted of three wake therapy sessions in one week, 30-min daily light treatment and sleep time stabilization over the entire nine-week study period. RESULTS: Patients in the wake therapy group had a significant decrease in depressive symptoms in week one as measured by HAM-D17 , 17.39 (CI 15.6-19.2) vs. 20.19 (CI 18.3-22.09) (P = 0.04), whereas no statistically significant differences were found between the groups in weeks two to nine. At week nine, the wake therapy group had a significantly larger increase in general self-efficacy (P = 0.001), and waking up during nights was a significantly less frequent problem (1.9 times vs. 3.2) (P = 0.0008). In most weeks, significantly fewer patients in the wake therapy group slept during the daytime, and if they slept, their naps were shorter (week three: 66 min vs. 117 min P = 0.02). CONCLUSION: The antidepressant effect initially achieved could not be maintained during the nine-week study period. However, sleep and general self-efficacy improved.

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.

Psychometric evaluation of the Major Depression Inventory (MDI) as depression severity scale using the LEAD (Longitudinal Expert Assessment of All Data) as index of validity.

BACKGROUND: The Major Depression Inventory (MDI) was developed to cover the universe of depressive symptoms in DSM-IV major depression as well as in ICD-10 mild, moderate, and severe depression. The objective of this study was to evaluate the standardization of the MDI as a depression severity scale using the Visual Analogue Scale (VAS) as index of external validity in accordance with the LEAD approach (Longitudinal Expert Assessment of All Data). METHODS: We used data from two previously published studies in which the patients had a MINI Neuropsychiatric Interview verified diagnosis of DSM-IV major depression. The conventional VAS scores for no, mild, moderate, and severe depression were used for the standardization of the MDI. RESULTS: The inter-correlation for the MDI with the clinician ratings (VAS, MES, HAM-D17 and HAM-D6) increased over the rating weeks in terms of Pearson coefficients. After nine weeks of therapy the coefficient ranged from 0.74 to 0.83. Using the clinician-rated VAS depression severity scale, the conventional MDI cut-off scores for no or doubtful depression, and for mild, moderate and severe depression were confirmed. CONCLUSIONS: Using the VAS as index of external, clinical validity, the standardization of the MDI as a measure of depression severity was accepted, with an MDI cut-off score of 21 for mild depression, 26 for moderate depression severity, and 31 for severe depression. TRIAL REGISTRATION: Martiny et al. Acta Psychiatr Scand 112:117-25, 2005: None - due to trial commencement date. Straaso et al. Acta Neuropsychiatr 26:272-9; 2014: ClinicalTrials.gov ID NCT01353092 .

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.

The Pharmacopsychometric Triangle to Illustrate the Effectiveness of T-PEMF Concomitant with Antidepressants in Treatment Resistant Patients: A Double-Blind, Randomised, Sham-Controlled Trial Revisited with Focus on the Patient-Reported Outcomes.

Background. Our T-PEMF trial has been revisited with focus on the pharmacopsychometric triangle in which effect size is used when comparing wanted versus unwanted clinical effects and quality of life as outcomes. In this analysis, we have especially focused on the self-reported HAM-D(6). Methods. The antidepressive medication which the patients were resistant to was kept unchanged during the five weeks of active versus sham T-PEMF. Results. In total 21, patients received active T-PEMF, and 19 patients received sham T-PEMF. The effect size was 1.02 and 0.90, respectively, on HAM-D(6) and HAM-D(6)-S. Concerning side effects, the active T-PEMF reduced the baseline score on concentration problems with an effect size of 0.44 while inducing more autonomic symptoms than sham T-PEMF with an effect size of -0.41. The advantage of active over sham T-PEMF obtained an effect size of 0.48. Conclusion. Active T-PEMF was found superior to sham T-PEMF within the pharmacopsychometric triangle with a clinically significant effect size level above 0.40.

Identifying patients with therapy-resistant depression by using factor analysis.

INTRODUCTION: Attempts to identify the factor structure in patients with treatment-resistant depression have been very limited. METHODS: Principal component analysis was performed using the baseline datasets from 3 add-on studies [2 with repetitive transcranial magnetic stimulation and one with transcranial pulsed electromagnetic fields (T-PEMF)], in which the relative effect as percentage of improvement during the treatment period was analysed. RESULTS: We identified 2 major factors, the first of which was a general factor. The second was a dual factor consisting of a depression subscale comprising the negatively loaded items (covering the pure depression items) and a treatment resistant subscale comprising the positively loaded items (covering lassitude, concentration difficulties and sleep problems). These 2 dual subscales were used as outcome measures. Improvement on the treatment resistant subscale was 40% in the active treatment group compared to 17-30% improvement in the sham treatments. DISCUSSION: It is possible to describe patients with therapy-resistant depression by a factor structure. Both rTMS and T-PEMF had a clinical effect on the factor-derived scales when compared to sham treatment.

High cortisol awakening response is associated with an impairment of the effect of bright light therapy.

OBJECTIVE: We investigated the predictive validity of the cortisol awakening response (CAR) in patients with non-seasonal major depression. METHOD: Patients were treated with sertraline in combination with bright or dim light therapy for a 5-week period. Saliva cortisol levels were measured in 63 patients, as an awakening profile, before medication and light therapy started. The CAR was calculated by using three time-points: awakening and 20 and 60 min after awakening. RESULTS: Patients with low CAR had a very substantial effect of bright light therapy compared with dim light therapy, whereas patients with a high CAR had no effect of bright light therapy compared with dim light therapy. CONCLUSION: High CAR was associated with an impairment of the effect of bright light therapy. This result raises the question of whether bright light acts through a mechanism different from that of antidepressants.

Do we agree about when patients are psychotic?

OBJECTIVE: To investigate into the use of the term 'psychotic' as defined by ICD-10 or by the concept of impaired reality testing, among psychiatric staff members. METHOD: Questionnaire investigation using 11 short case vignettes. RESULTS: Responses were received from 266 psychiatric staff members: psychiatrists, nursing staff and psychologists. When using ICD-10, patients were identified as psychotic with a sensitivity ranging from 90% to 55%. Specificity ranged from 60% to 75%. According to the concept of impaired reality testing, all three groups showed a sensitivity of about 60%, whereas specificity ranged from 65% to 50%. The combined use of the terms correlated significantly with responses regarding indication for legal detention for psychiatrists and nursing staff. CONCLUSION: In identifying a patient as 'psychotic' a broad concept of impaired reality testing was widely used particularly in cases with legal issues. Psychotic symptoms, however, were identified with high sensitivity and specificity.

Dose response to adjunctive light therapy in citalopram-treated patients with post-stroke depression. A randomised, double-blind pilot study.

BACKGROUND: Post-stroke depression affects the outcome of stroke rehabilitation and is observed in approximately 30% of all stroke patients. We investigated whether the addition of light treatment to medical antidepressants influences the course of depression as measured by the Hamilton Depression Scale. METHODS: The effect of a combination of light therapy and citalopram in stroke victims receiving citalopram was examined by use of two different doses of light therapy under double-blind conditions. Altogether, 63 patients were included in the study. The mean age was 74.9 years. RESULTS: After 4 weeks of therapy, the 6-item subscale of the Hamilton Depression Scale showed a statistically significantly larger improvement in patients receiving high-intensity light treatment compared to those treated with medium-intensity light (p < 0.05). CONCLUSION: This pilot study demonstrates a dose response effect of light used as an adjunct therapy to antidepressants in post-stroke patients with major depression.

Adjunctive bright light in non-seasonal major depression: results from clinician-rated depression scales.

OBJECTIVE: To investigate the use of bright light therapy as an adjunct treatment to sertraline in non-seasonal major depression. METHOD: In a randomised double-blind trial, 102 patients were treated for 5 weeks with either white bright light (10 000 lux, 1 h daily) or red dim light (50 lux, 30 min daily). All patients were treated with sertraline in a fixed dose of 50 mg daily. The clinician-rated depression scales used were the Hamilton Depression Rating Scale (HAM-D17), Hamilton six-item subscale (HAM-D6), Melancholia Scale (MES) and the seven 'atypical' items from the SIGH-SAD. RESULTS: One-hundred and two patients were included in the study. Analyses showed that the reduction in depression scores in the bright light group was statistically significantly larger than in the dim light group on all scales. The scale most sensitive at endpoint was the HAM-D(6), which includes the core symptoms of depression. CONCLUSION: The study results support the use of bright light as an adjunct treatment to antidepressants in non-seasonal depression.

Adjunctive bright light in non-seasonal major depression: results from patient-reported symptom and well-being scales.

OBJECTIVE: In this study, we tested the efficacy of bright light therapy as an adjunct to antidepressant treatment (sertraline) in patients with non-seasonal major depression. METHOD: In a randomized double-blind controlled trial, 102 patients were treated for 5 weeks with either white bright light (10.000 lx, 1 h/day) or red dim light (50 lx, 30 min/day). All patients received sertraline in a dosage of 50 mg daily. The self-assessment scales used were the Major Depression Inventory (MDI), the Psychological General Well-Being Scale (PGWB) and the Symptom Check List (SCL-90R). RESULTS: On all three questionnaires the score differences between baseline and endpoint were greatest in the bright light group. On the SCL-90R, the difference reached statistical significance. Results and effect sizes are compared with results from Danish national population studies applying PGWB and SCL-90R. CONCLUSION: The results advocate the use of bright light as an adjunct treatment of non-seasonal depression.

Adjunctive bright light in non-seasonal major depression.

OBJECTIVE: Bright light treatment is an established treatment for Seasonal Affective Disorder, but in non-seasonal depression research results have been contrasting. METHOD: This study was designed as a 5-week controlled, double-blind, parallel trial in out-patients with a diagnosis (DSM-IV) of non-seasonal major depression, randomized to either active treatment (white light, 10 000 lux, 1 h daily) or placebo treatment (red light, 50 lux, 30 min daily) and concomitant treatment with sertraline in both groups. RESULTS: One hundred and two patients were included in the study. Analyses showed that on all used scales the reduction in depression scores was larger in the bright light group than in the dim light group, and this reached statistical significance on all observer rating scales and on the SCL-90R self-assessment scale. The HAM-D6 was the most sensitive scale to measure improvement at endpoint. CONCLUSION: The study results support the use of bright light as an adjunct treatment to antidepressants in non-seasonal depression.

Relapse prevention by citalopram in SAD patients responding to 1 week of light therapy. A placebo-controlled study.

OBJECTIVE: We have tested the relapse-preventive effect of citalopram when compared with placebo in 282 patients with Seasonal Affective Disorder (SAD) responding to 1 week of light therapy. METHOD: The response rate to 1-week light therapy and relapse during the continuation phase of 15 weeks were assessed by use of the Hamilton Depression Rating Scale (HAM-D17), the six-item subscale (HAM-D6), the Melancholia Scale (MES), and the combined HAM-D/SIGH-SAD. RESULTS: The response rate to light therapy was 62.5% on the HAM-D17 and the HAM-D6, 56.1% on the HAM-D/SIGH-SAD, 52.8% on the MES. In the continuation phase, citalopram was found superior to placebo on all scales, but the difference was only of statistical significance on the HAM-D6 and the MES. Mean citalopram dose was 26.3 mg. CONCLUSION: Light therapy was found to have and early onset of action. On the HAM-D6 and the MES citalopram significantly reduced the relapse rate in the continuation phase.

The internal and external validity of the Major Depression Inventory in measuring severity of depressive states.

BACKGROUND: We have developed the Major Depression Inventory (MDI), consisting of 10 items, covering the DSM-IV as well as the ICD-10 symptoms of depressive illness. We aimed to evaluate this as a scale measuring severity of depressive states with reference to both internal and external validity. METHOD: Patients representing the score range from no depression to marked depression on the Hamilton Depression Scale (HAM-D) completed the MDI. Both classical and modern psychometric methods were applied for the evaluation of validity, including the Rasch analysis. RESULTS: In total, 91 patients were included. The results showed that the MDI had an adequate internal validity in being a unidimensional scale (the total score an appropriate or sufficient statistic). The external validity of the MDI was also confirmed as the total score of the MDI correlated significantly with the HAM-D (Pearson's coefficient 0.86, P < or = 0.01, Spearman 0.80, P < or = 0.01). CONCLUSION: When used in a sample of patients with different states of depression the MDI has an adequate internal and external validity.

Provision of services for people with schizophrenia in five European regions.

BACKGROUND: An increasing diversity of public, voluntary sector and private providers offer services for the mentally ill in the ongoing process of psychiatric reform. Good service description is one important prerequisite for mental health service research. Aims 1) To describe service provision for the mentally ill in five European centres using the European Service Mapping Schedule (ESMS); and 2) to discuss the use of the instrument in describing service provision. METHODS: All services providing care for people with severe mental illness in five European catchment areas (in Amsterdam, the Netherlands; Copenhagen, Denmark; London, UK; Santander, Spain; Verona, Italy) were identified through various sources. The identified services were classified, and service provision was quantified in accordance with the ESMS manual. Descriptive information was obtained. RESULTS: We identified from 10 to 45 different services for catchment areas of between 50,000 (Copenhagen) and 560,000 (Santander) population run by three to 16 providers. They varied in aims, staffing and functioning. Hospital and non-hospital residential services, community-based services, and social support agencies were available in all sites. There was substantial variation across centres in the range, number and activities of services. Collecting comparable data sets on all service types, particularly for day and structured activity services and outpatient and community services required substantial effort. CONCLUSION: Operationalised description of mental health services across Europe is possible but requires further refinement.

[Dementia paralytica is still seen in Denmark]. / Dementia paralytica forekommer stadig i Danmark.

Two cases of neurosyphilis are presented. Both patients had developed a paranoid psychosis and needed admission to a psychiatric department. In both cases relevant treatment resulted in improvement of both the dementia and the psychotic condition, though the patients were left with some degree of dementia at follow up. Both patients had a symptom-free interval lasting several years. It still remains important to take WR, when investigating the cause of dementia, and when dealing with patients admitted to neurological and psychiatric departments with an uncertain diagnosis.