L. Lauritzen

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.

Post-stroke patients in rehabilitation. The relationship between biological impairment (CT scanning), physical disability and clinical depression

A study of 128 consecutive patients with thromboembolic stroke in a rehabilitation hospital from July 1988 to September 1990 found a prevalence of major depression of 17%. The patient population was described according to the principles of the World Health Organizations (WHO) International Classification of Impairments, Disabilities and Handicaps (ICIDH) according to biological impairment, measured by computerized tomography (CT) scanning of the brain and side of hemiparesis and physical disability, measured by functional movement and activities of daily living. Handicap, referring to the interaction between disability and the environmental situation, often defined as the subjective disadvantage of being ill, was not measured in this study. A stroke index with four items was generated from the parameters describing biological impairment and physical disability. The psychiatric rating scales (the 17-item Hamilton Scale for Depression (HAM-D), the Melancholia Scale [MES]and the Newcastle Diagnostic Depression Scale), and the new stroke-index showed adequate coefficients of Cronbachs alpha and Loevinger, suggesting that these scales have both adequate item correlation and homogeneity (adequate hierarchical structure). The impairment disability index of stroke thus seems to be a meaningful measurement of the specific factors of this disease. There was no correlation between the stroke-index and the psychiatric rating scales measuring the emotional dimension of disability caused by the disease expressed as depression. The results suggest that the depression found among stroke patients is not a simple reaction to the physical disability of the stroke.

Screening and treating depressed patients. A comparison of two controlled citalopram trials across treatment settings : hospitalized patients vs. patients treated by their family doctors

This study is a comparison across treatment settings of two previously published trials, namely the Danish University Antidepressant Group (DUAG) study on citalopram vs. clomipramine in hospitalized patients with major depression, and the Nordic citalopram vs. imipramine study of depressed patients treated by their family doctors. The Hamilton Depression Scale (HAM‐D) had the same level of inter‐rater reliability and construct validity in the two settings. Using a HAM‐D score of 7 or less as the criterion for full remission, clomipramine was superior to imipramine and citalopram. Using a reduction of the baseline HAM‐D score by 50% or more as a response criterion, there were no differences between the three antidepressants after 5 or 6 weeks of treatment. Citalopram showed superior tolerability to the tricyclic antidepressants.

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 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-D6. 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-D6 and HAM-D6-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.

Platelet 3H-Imipramine and 3H-Paroxetine Binding during Treatment with Psychoactive Drugs

Many, but not all, studies of 3H-imipramine binding in plate!ets from depressed patients have found decreased amounts of binding sites compared with platelets from control subjects (Mellerup and Plenge 1988). Decreased binding may .he caused by drug residues in the membranes, which interfere with the binding assay. Previous studies have shown that chlorimipramine and fluoxetine decreased platelet 3H-imipramine binding (Poirier et al 1984; Marshall et al 1985). This problem may be avoided by the use of a ligand with a higher affinity for the serotonin transporter than imipramine in the binding analysis, for example, 3H-paroxetine. In the present study the binding of 3H-imipramine and 3H-paroxetine is compared in platelets from patients or volunteers treated with various psychoactive drugs.

Platelet paroxetine binding in depressed and nondepressed chronic pain patients

Analysis of 3H‐paroxetine binding was used to determine the number of serotonin transporters in platelet membranes of chronic pain patients and controls. The pain patients who also suffered from depression in addition to the pain had significantly more serotonin transporters than the controls.

Psychometric analysis of the Melancholia Scale in trials with non-pharmacological augmentation of patients with therapy-resistant depression.

Objective The Melancholia Scale (MES) consists of the psychic core items of the Hamilton Depression Scale (HAM-D6) (depressed mood, interests, psychic anxiety, general somatic, guilt feelings, and psychomotor retardation) and the neuropsychiatric items of the Cronholm–Ottossen Depression Scale. Patients resistant to anti-depressant medication (therapy-resistant depression) have participated in our trials with non-pharmacological augmentation. On the basis of these trials, we have evaluated to what extent the neuropsychiatric subscale of the MES (concentration difficulties, fatigability, emotional introversion, sleep problems, and decreased verbal communication) is a measure of severity of apathia when compared with the HAM-D6 subscale of the MES. Methods We have focused on rating sessions at baseline (week 0) and after 2 and 4 weeks of therapy in four clinical trials on therapy-resistant depression with the following augmentations: electroconvulsive therapy, bright light therapy, transcranial magnetic stimulation or pulsed electromagnetic fields, and wake therapy. The item response theory model constructed by Mokken has been used as the psychometric validation of unidimensionality. For the numerical evaluation of transferability, we have tested item ranks across the rating weeks. Results In the Mokken analysis, the coefficient of homogeneity was above 0.40 for both the HAM-D subscale and the apathia subscale at week 4. The numerical transferability across the weeks was statistically significant (p < 0.05) for both subscales. Conclusion The apathia subscale is a unidimensional scale with acceptable transferability for the measurement of treatment-resistant symptoms, analogue to the psychic core subscale (HAM-D6).

A psychometric evaluation of dementia rating scales

The paper discusses the relevance of sufficient psychometric standards for dementia rating scales. The concurrent, convergent and construct validity of the Mini Mental State Examination (MMSE), the Alzheimers Disease Assessment Scale (ADAS) and the CAMCOG are assessed. The Clinical Global Impressions and the Global Deterioration Scale are used as global scales. The concurrent and convergent validity are satisfactory. The construct validity expressed by the Cronbach and Loevinger coefficient are very good for all scales and subscales. The Mokkens single item coefficients show that the MMSE has the best individual hierarchical fit, the item reading can be left out. The ADAS is less uni-dimensional, eight items can be left out. The CAMCOG consists of too many items to apply the Mokkens single item coefficients or the Loevinger coefficient. Instead, the CAMCOG subscales are analyzed. This results in a possible reduction of the CAMCOG by 30 items to a total of 35 items. The factor analysis reveals two factors in both the MMSE and the ADAS while the number of observations does not allow a factor analysis of the CAMCOG to be performed.