Michel Dierick

Sex Steroid Level, Androgen Receptor Polymorphism, and Depressive Symptoms in Healthy Elderly Men

Objectives: To determine the prevalence of depression in a cohort of elderly men as assessed using a 30‐item Geriatric Depression Scale (GDS) score and to describe the association between this score and sex steroids, androgen receptor (AR) polymorphism, and general health status.

Controlled comparison of nefazodone and amitriptyline in major depressive inpatients.

Nefazodone, a phenylpiperazine antidepressant, exhibits novel dual activity on serotonin (5-HT) neurons; it binds to 5-HT2 receptors and inhibits 5-HT reuptake. Flexible doses of nefazodone (100–400 mg/day) and amitriptyline (50–200 mg/day) were compared in 106 major depressive inpatients in a 6-week double-blind study. Results showed significant superiority of amitriptyline over nefazodone on all rating instruments: Montgomery and Asberg depression rating scale (P<0.0001), Hamilton depression scale (P<0.0006), Clinical Global Impressions (P<0.0001) and Patient Global Assessment (P<0.01). A total of 65% of patients under amitriptyline and 56% of patients under nefazodone reported adverse events during the study, with significantly more dry mouth in the amitriptyline group (39% versus 11%,P=0.001). Modal daily doses within the last treatment week reached 242 mg with nefazodone and 124 mg with amitriptyline. The lower efficacy of nefazodone, which contradicts comparative trials with imipramine in US patients, is discussed with regard to the dose of nefazodone, probably below the optimal therapeutic range for melancholic patients, and to the clinical differences between the patient samples.

Effect of repetitive transcranial magnetic stimulation on saccades in depression: a pilot study.

Therapeutic repetitive transcranial magnetic stimulation (rTMS) in depression is applied over the prefrontal cortex. This brain region is known to play an important role in the control of saccades. We wanted to investigate whether the fast rTMS procedure affected saccadic activity in depression. Reflexive saccades (RS) and voluntary saccades were studied in 11 patients before and after therapeutic rTMS for depression. Two types of voluntary saccade tasks were used: a voluntary prosaccade (VpS) task and an antisaccade (AS) task. Eye movements were registered by infrared oculography. Latency and directional error rate were analyzed. rTMS was applied over the left dorsolateral prefrontal cortex (DLPFC). RS and VpS parameters were unchanged after 10 sessions of rTMS. However, the latency of antisaccades (AS) was significantly shorter after rTMS than before rTMS. It can be concluded that rTMS over the left DLPFC cortex in depression seems to have no important effect on reflexive saccades, while antisaccade activity is clearly favored by shortening of latency. As voluntary prosaccades were not significantly influenced, our findings may indicate that not merely the voluntary triggering of saccades but the inhibition of unwanted reflexive saccades is influenced by fast rTMS delivered over the DLPFC. These results suggest the intriguing possibility that rTMS might differentially affect specific aspects of saccade behavior.

Noradrenaline (norepinephrine) and depression : Role in aetiology and therapeutic implications

In the pharmacological treatment of depression the focus has recently shifted from serotonin (5-hydroxytryptamine; 5-HT) to noradrenaline (norepinephrine), with the advent of new antidepressants such as noradrenaline reuptake inhibitors, noradrenergic and selective serotonergic antidepressants, and serotonin/noradrenaline reuptake inhibitors. It has been suggested that noradrenergic compounds may prove to have beneficial activity in those depressions that are characterised by a ‘noradrenergic deficiency syndrome’, which is clinically manifested through emotional withdrawal, psychomotor retardation, as well as concentration and memory deficits.The role of noradrenergic mechanisms in the aetiology of depression has been assumed since the catecholamine hypothesis, based on the inhibitory action of tricyclic antidepressants and monoamine oxidase inhibitors on noradrenaline uptake, was formulated. In this article, the aetiological significance of noradrenaline in depression is discussed with regard to the anatomical basis of the noradrenergic system (the locus caeruleus), noradrenaline metabolites, noradrenergic receptors, some aspects of thyroid function and the hypothalamic-pituitary-adrenal axis.The efficacy and tolerability profiles of new antidepressant compounds reboxetine, milnacipran, mirtazapine and venlafaxine are discussed in view of their noradrenergic activity.

An eight-week, open-label, uncontrolled, multicenter, phase IV study of remission rates in outpatients and inpatients with major depression treated with venlafaxine

Background: Venlafaxine is a structurally novel antidepressant that is believed to potentiate monoamine activity in the central nervous system. In preclinical studies, venlafaxine was shown to inhibit the neuronal uptake of serotonin and norepinephrine and, to a lesser degree, dopamine reuptake, but was without effect on monoamine oxidase (MAO) activity. Clinical trial results from similar to3000 patients suggest that venlafaxine is a safe and effective antidepressant with the potential to invoke an early onset of clinical activity. Objective: The purpose of this 8-week, open-label, uncontrolled, multi-center, Phase IV study was to examine the extent of remission and symptom relief in outpatients and inpatients with major depressive disorder treated with venlafaxine. Methods: This study was conducted at 12 centers across Belgium and Luxembourg. Consecutive, severely depressed inpatients and moderately depressed outpatients aged 18 to 70 years were eligible. Patients were administered open-label venlafaxine for 8 weeks. Dosing was initiated at venlafaxine 75 mg/d (37.5 mg BID), with dose adjustments made throughout the study, to a maximum daily dose of 375 mg for inpatients and 225 mg for outpatients. Results were measured using the Hamilton Depression (HAM-D) scale, the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impression (CGI) scale. Results: A total of 149 consecutive patients (84 females, 65 males; mean age, 46.5 years; 88 outpatients, 61 inpatients) were enrolled; the intent-to-treat (ITT) population comprised 144 patients (84 outpatients, 60 inpatients); 111 patients (64 outpatients, 47 inpatients) completed the study. At the week 8 visit, 71.3% of patients (77/108) were considered to be responders according to the HAM-D scale; 73.8% (79/107) according to the MADRS; and 78.7% (85/108) according to the CGI scale. A sustained response was achieved in 33.3% of the ITT population (48/144), and at week 8, 50.8% of outpatients (32/63) and 37.8% of inpatients (17/45) were in remission according to the HAM-D scale. Venlafaxine was well tolerated at all doses, with the most frequently experienced adverse events (AEs) being nausea, sweating, and headache. Fewer inpatients than outpatients reported greater than or equal to 1 AE (57.4% [35/61] and 73.9% [65/88], respectively), despite receiving a higher maximum daily dose of venlafaxine. Conclusion: The results of this study indicate that venlafaxine was a tolerable and effective antidepressant in both outpatients and inpatients, with a significant proportion of patients achieving remission.