Lone Lindberg

Repetitive transcranial magnetic stimulation (rTMS) in combination with escitalopram in patients with treatment-resistant major depression: a double-blind, randomised, sham-controlled trial.

BACKGROUND The role of high-frequency rTMS over the left cortex as an add-on strategy in the treatment of major depression is still uncertain even in patients resistant to pharmacotherapy. We had planned a large sham TMS controlled study in the acute phase with a placebo-controlled relapse-prevention phase with escitalopram. However, because a recent meta-analysis showed only a small effect size of rTMS over sham TMS in the acute treatment phase of depressed patients, we decided to make an interim analysis. METHOD In patients with medication-resistant major depression we administered in a randomised trial 15 sessions of sham-controlled rTMS over three weeks in combination with 20 mg escitalopram daily. After the last rTMS, the patients were followed for another 9 weeks on 20 mg escitalopram daily. The antidepressant effect was measured by the HAM-D(6) as primary outcome scale. RESULTS A total of 45 patients with complete data were randomised so that 23 patients received sham TMS and 22 patients received active, high-frequency rTMS over the left cortex. Over the 3 weeks, the active rTMS treatment was superior to sham TMS with effect sizes on the HAM-D(6) above 0.70, which indicates not only a statistically but also a clinically significant effect. The patients had typically been through two failed antidepressant treatment attempts with non-tricyclics before inclusion in the study. Both the rTMS and escitalopram were well-tolerated. CONCLUSION High-frequency rTMS over the left cortex is an add-on strategy of clinical significance in combination with escitalopram in patients with major depression resistant to non-tricyclic antidepressants.

The Day-to-Day Acute Effect of Wake Therapy in Patients with Major Depression Using the HAM-D6 as Primary Outcome Measure: Results from a Randomised Controlled Trial

Background This paper reports day-to-day data for from a one-week intervention phase, part of a 9-weeks randomised parallel study with patient having major depression (data from weekly visits have been reported). Wake therapy (sleep deprivation) has an established antidepressant effect with onset of action within hours. Deterioration on the following night’s sleep is, however, common, and we used daily light therapy and sleep time stabilisation as a preventive measure. In particular, we evaluated the day-to-day acute effect of and tolerance to sleep deprivation and examined predictors of response. Methods Patients were assessed at psychiatric inpatient wards. In the wake group (n = 36), patients did three wake therapies in combination with light therapy each morning together with sleep time stabilisation. In the exercise group (n = 38), patients did daily exercise. Hamilton subscale scores were primary outcome (not blinded), secondary outcome was self-assessment data from the Preskorn scale and sleep. Results Patients in the wake therapy group had an immediate, large, stable, and statistically significant better antidepressant effect than patients in the exercise group with response rates at day5 of 75.0%/25.1% and remission rates of 58.6%/6.0%, respectively. The response and remission rates were diminished at day8 with response rates of 41.9%/10.1% and remission rates of 19.4%/4.7%, respectively. Patients and ward personnel found the method applicable with few side effects. Positive diurnal variation (mood better in the evening) predicted a larger response to wake therapy. In the wake group napping on days after intervention predicted greater deterioration on day8. Conclusions The intervention induced an acute antidepressant response without relapse between wake nights but with a diminishing effect after intervention. Development is still needed to secure maintenance of response. Avoiding napping in the days after wake therapy is important. Trial Registration Clinical trials.gov NCT00149110

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

To investigate the long‐term antidepressant effect of a chronotherapeutic intervention.

Psychiatric outcome studies (POS): does treatment help the patients? A Popperian approach to research in clinical psychiatry.

This book, assuming that thoughts and feelings exist and are vehicles of knowledge, thereupon contends that psychology when she has ascertained the empirical correlation of the various sorts of thought and feeling with definite conditions of the brain, can go no farther*can go no farther, that is, as a natural science. If she goes farther she becomes metaphysical. W. James (1890) Principles of psychology

Dose-remission of pulsating electromagnetic fields as augmentation in therapy-resistant depression: a randomized, double-blind controlled study.

Objective To evaluate to what extent a twice daily dose of Transcranial Pulsating ElectroMagnetic Fields (T-PEMF) was superior to once daily in patients with treatment-resistant depression as to obtaining symptom remission after 8 weeks of augmentation therapy. Methods A self-treatment set-up of the T-PEMF device was used allowing self-administration by patients in own homes. All patients were treated for 30 min per T-PEMF session. The antidepressant medication the patients were receiving at baseline remained unchanged during the trial. The patients were randomised to either one T-PEMF dose (active dose in the morning and sham in the afternoon) or two T-PEMF doses (active dose both morning and afternoon) in a double-blind procedure. A score of 7 or less on the Hamilton Depression Scale (HAM-D17) was the criterion of remission. Results In total 34 patients received active T-PEMF once a day and 31 patients twice daily. After 5 weeks of therapy remission was obtained in 26.5% and 32.3% on one dose and two doses of T-PEMF, respectively. After 8 weeks the rate of remission was 73.5% and 67.7%, respectively. The side effects as measured by the Udvalget for Kliniske Undersøgelser scale showed a better toleration of the antidepresssive medication in both treatment groups, which was reflected by the WHO-5 well-being scale with increased scores in both groups of patients. Conclusion The high remission rate obtained by the T-PEMF augmentation was not a dose effect (one versus two daily T-PEMF sessions) but was explained by the extension of the treatment period from 5 to 8 weeks.

The Diagnostic Apathia Scale predicts a dose–remission relationship of T-PEMF in treatment-resistant depression

Objective The aim of this study was to evaluate the predictive validity of the apathy subsyndrome in patients with therapy-resistant depression in the dose–remission study with transcranial pulsating electromagnetic fields (T-PEMF). Methods The apathy subsyndrome consists of the symptoms of fatigue, concentration and memory problems, lack of interests, difficulties in making decisions, and sleep problems. We evaluated 65 patients with therapy-resistant depression. In total, 34 of these patients received placebo T-PEMF in the afternoon and active T-PEMF in the morning, that is, one daily dose. The remaining 31 patients received active T-PEMF twice daily. Duration of treatment was 8 weeks in both groups. The Hamilton Depression Scale (HAM-D17) and the Bech-Rafaelsen Melancholia Scale (MES) were used to measure remission. We also focused on the Diagnostic Apathia Scale, which is based on a mixture of items from the MINI and the HAM-D17/MES. Results In patients without apathy, the remission rate after T-PEMF was 83.9% versus 58.8% in patients with apathy (p≤0.05). In patients without apathy receiving one active dose daily 94.4% remitted versus 50% for patients with apathy (p≤0.05). In patients without apathy who received two active doses 69.9% remitted versus 66.7% for patients with apathy (p≤0.05). Conclusion Taking the baseline diagnosis of the apathy syndrome into consideration, we found that in patients without apathy one daily dose of T-PEMF is sufficient, but in patients with apathy two daily doses are necessary. Including the apathy syndrome as predictor in future studies would seem to be clinically relevant.

A 2-year follow-up study of patients participating in our transcranial pulsating electromagnetic fields augmentation in treatment-resistant depression.

Objective We have made a 2-year follow-up study to evaluate the effect of repeated transcranial pulsating electromagnetic fields (T-PEMF) augmentation in patients who had achieved remission but later on relapsed, as well as to identify factors contributing to treatment-resistant depression in patients who did not respond to T-PEMF. Methods Using the Longitudinal Expert Assessment of All Data approach the patients were classified in four groups: A: patients who achieved remission; B: patients with doubtful effect; C: patients with no effect; and D: patients who were hard-to-assess. Results In group A, comprising 27 patients, 13 had relapsed; they obtained a clear remission after a repeated course of T-PEMF augmentation. In group D, comprising 16 patients, we identified misdiagnostic factors both concerning the event of remission after the previous T-PEMF augmentation and concerning the aetiology (psychosocial stressors and co-morbid conditions). Compared with the other groups, the group D patients had a smaller number of previous episodes (p=0.09) and a longer duration of the current episode (p=0.01). Conclusion T-PEMF has an effect among patients who relapsed after remission with the first series of T-PEMF. Treatment-resistant depression is a condition that has a high degree of multivariate problems. Misuse of alcohol or drugs, severe somatic disorders and other psychosocial problems may need other kinds of treatment before T-PEMF augmentation.

The Clinimetric Approach to Psychological Assessment: A Tribute to Per Bech, MD (1942–2018)

a Department of Psychology, University of Bologna, Bologna, Italy; b Department of Psychiatry, State University of New York at Buffalo, Buffalo, NY, USA; c Department of Psychological, Health, and Territorial Sciences, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy; d Psychiatric Research Unit, Psychiatric Centre North Zealand, Copenhagen University Hospital, Hillerød, Denmark Received: August 10, 2018 Accepted after revision: September 13, 2018 Published online: September 28, 2018

The Reliable Change Index (RCI) of the WHO-5 in primary prevention of mental disorders. A measurement-based pilot study in positive psychiatry

Abstract Introduction: Primary prevention of mental disorders is a major issue in positive psychiatry. Adjustment disorder is one of the very few discrete mental disorders linked to an etiological factor, namely psychosocial stressors given rise to a maladaptive reaction with a course of symptoms vanishing with the removal of the stressor. We have focused on a measurement-based method to prevent the development of an adjustment disorder. Aim: The aim of this study has been to analyze from an ongoing Worklife Barometer Survey in which the World Health Organization Well-Being Scale (WHO-5) has been applied to prevent distress leading to an adjustment disorder. Methods: Persons identified with a decrease of 15 points in their repeatedly WHO-5 ratings over three months were through a brief psychological intervention by experienced psychologists. The Reliable Change Index (RCI) was used to determine the clinically meaningful change in the WHO-5 ratings. Results: Within the group who received the psychological intervention (N = 1338), 35% of the persons were identified by the RCI analysis to have developed a clinically reliable change in the WHO-5 at the time of the intervention. The remaining 65% of the persons obtained changes in the WHO-5 which might be considered as spontaneous fluctuations. In the month after the intervention, the persons with a clinically reliable change in the WHO-5 were restored. Conclusion: In this measurement-based pilot study, the repeatedly WHO-5 ratings identified a group of persons with a clinically reliable change in WHO-5 and a clinically significant improvement after a brief psychological intervention.

It is never too late to treat anxiety neurosis or panic disorder with a serotonin-reuptake inhibitor

In a register study on patients hospitalized in the 1950s for anxiety neurosis, going until 1994 for diagnostic behaviour and until 2004 for suicidal behaviour, we found a co-existence with depression. However, the study has no information about therapy. Just after the finalization of this study, one of the patients was hospitalized in our department for depression. At that time the patient was 70 years old; at his index hospitalization in 1954 he was 30 years of age. Throughout his 40 years of illness he had received no psychiatric treatment. The spontaneous course went from panic attacks through stages of phobia and avoidance behaviour until the final stage of depression. At 70 years of age, for the first time in his life, he received antidepressant medication in the form of a specific serotonin re-uptake inhibitor. After 6 weeks of therapy not only the depression but also the anxiety disorder remitted.