M. Lunde

Relapse prevention by means of paroxetine in ECT-treated patients with major depression: a comparison with imipramine and placebo in medium-term continuation therapy

In‐patients with severe major depression were treated in the acute phase with electroconvulsive therapy (ECT) in combination with antidepressants. The drug treatment consisted of two randomized trials which were both extended into the post‐ECT continuation phase. Patients with electrocardiological impairment were randomized to either 30 mg paroxetine daily or placebo under blind conditions. Patients without electrocardiological impairment were randomized to either 30 mg paroxetine daily or 150 mg imipramine daily. There was a high level of agreement between the Hamilton Depression Scale and the Melancholia Scale, demonstrating that the patients treated with ECT plus imipramine in the acute phase showed greater symptom reduction than those treated with ECT plus paroxetine. However, in the post‐ECT phase paroxetine was superior to both imipramine and placebo in preventing relapse. Thus in the post‐ECT phase 65% of the placebo‐treated patients relapsed, compared to 30% of the imipramine‐treated patients and 10% of the paroxetine‐treated patients. The psychometric analysis of the Melancholia Scale in the continuation or post‐ECT phase showed that relapsing patients displayed a pattern with lack of interests, impaired concentration, depressed mood and anxiety among the less severe symptoms (first‐compartment symptoms). In other words, these symptoms represent the gate to full‐blown depression (second‐compartment symptoms). Serotonin‐selective antidepressants such as paroxetine appear I to be more effective in controlling the first‐compartment symptoms.

Post-stroke depression : combined treatment with imipramine or desipramine and mianserin : a controlled clinical study

In a 6-week study the efficacy of combined treatment of imipramine plus mianserin was compared to combined treatment of desipramine plus mianserin in patients with post-stroke depression. Patients were required to have a minimum baseline total score of 15 on the 17-item Hamilton Depression Scale (HAMD). The Melancholia Scale (MES) was also used to measure severity of depressive states to show that somatic symptoms had little influence on the evaluation of depression. Out of 120 stroke patients screened, 20 patients fulfilled the inclusion criteria. The doses of the drugs were flexible, using side-effects as a guide during treatment. Both intention to treat analysis and efficacy data (excluding patients who had dropped out during the first 2 weeks of treatment) showed that imipramine (mean dose 75 mg daily) plus mianserin (mean dose 25 mg daily) was superior to desipramine (mean dose 66 mg daily) plus mianserin (27 mg daily). The MES was found to be more sensitive than the HAMD for measuring change in depressive states during treatment. The assessment of side-effects using the UKU scale showed good tolerance in general. The only difference between the two treatment groups was seen in micturition disturbances, where the imipramine treated patients had most complaints after 14 days of treatment, but the symptoms disappeared despite continuous treatment.

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.

Transcranial Low Voltage Pulsed Electromagnetic Fields in Patients with Treatment-Resistant Depression

BACKGROUND Approximately 30% of patients with depression are resistant to antidepressant drugs. Repetitive transcranial magnetic stimulation (rTMS) has been found effective in combination with antidepressants in this patient group. The aim of this study was to evaluate the antidepressant effect of a new principle using low-intensity transcranially applied pulsed electromagnetic fields (T-PEMF) in combination with antidepressants in patients with treatment-resistant depression. METHODS This was a sham-controlled double-blind study comparing 5 weeks of active or sham T-PEMF in patients with treatment-resistant major depression. The antidepressant treatment, to which patients had been resistant, was unchanged 4 weeks before and during the study period. Weekly assessments were performed using both clinician-rated and patient-rated scales. The T-PEMF equipment was designed as a helmet containing seven separate coils located over the skull that generated an electrical field in tissue with orders of magnitude weaker than those generated by rTMS equipment. RESULTS Patients on active T-PEMF showed a clinically and statistically significant better outcome than patients treated with sham T-PEMF, with an onset of action within the first weeks of therapy. Effect size on the Hamilton 17-item Depression Rating Scale was .62 (95% confidence interval .21-1.02). Treatment-emergent side effects were few and mild. CONCLUSION The T-PEMF treatment was superior to sham treatment in patients with treatment-resistant depression. Few side effects were observed. Mechanism of the antidepressant action, in light of the known effects of PEMF stimulation to the brain, is discussed.

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.

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.

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.

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

BackgroundThe 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).MethodsWe 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.ResultsThe 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.ConclusionsUsing 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 registrationMartiny 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.

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

Social Adaptation Self-evaluation Scale (SASS): Psychometric analysis as outcome measure in the treatment of patients with major depression in the remission phase

INTRODUCTION: To carry out a psychometric analysis of the Social Adaptation Self-evaluation Scale (SASS), which has been found very promising during first experiences with it in the treatment of depression. METHOD: Patients in the remission phase during treatment for a major depressive episode completed the SASS over a period of 12 weeks, with monthly assessments. For comparison, the Hamilton Depression Scale with the Melancholia Scale (HAM-D/MES) was used as well as a self-reporting questionnaire, the Major Depression Inventory (MDI). In the psychometric analysis both classical tests (e.g. principal component analysis) and modern tests (Mokken analysis with the Loevinger coefficient of homogeneity) were applied. RESULTS: The SASS scale with its 21 items was found to contain at least three factors, of which the first was a general factor; this however explained less than 50% of the variance. A subscale containing the six items with the highest factor loadings was found to be a unidimensional scale. This subscale showed a much higher responsiveness than the total SASS. However, both SASS scales were found to have a lower responsiveness than the Major Depression Inventory (MDI) during the first weeks of treatment. CONCLUSION: The SASS was found to be a multidimensional scale. However, a six-items subscale (covering items with the highest loadings on the first use) was shown to be a unidimensional scale and to have a greater responsiveness than the total SASS, but still lower than the MDI. (Int J Psych Clin Pract 2002; 6: 141-146)