Gérard Charles

Controlled comparison of milnacipran and fluoxetine in major depression.

The efficacy and the tolerance of milnacipran (100 mg/day), a second generation antidepressant which equipotently inhibits both noradrenaline and serotonin reuptake, was compared to fluoxetine (20 mg/day), a selective serotonin reuptake inhibitor, in two parallel groups of, respectively, 97 and 93 major depressive outpatients. The duration of the study was 6 weeks, with assessments every 2 weeks by means of the Montgomery and Asberg depression scale (MADRS), the Hamilton depression scale, the clinical global impressions (CGI), and a checklist of symptoms and side-effects. Results showed significant superiority of fluoxetine over milnacipran on most rating instruments: MADRS (P=0.01) including five individual items, Hamilton depression scale (P=0.002) including ten individual items, CGI of severity (P=0.01) and therapeutical index (P=0.002). On visual analogue scales assessing the clinical profile of the compounds, fluoxetine was rated as exhibiting more psychostimulating activity than milnacipran (P=0.0008). The tolerance of the two antidepressants was very similar, with the exception of symptoms of dizziness which were more frequently reported with milnacipran (P=0.01). These differences in efficacy favoring fluoxetine could result from the selection of a dose of milnacipran below the optimal therapeutic dose for this type of psychiatric patients or to the administration of the compounds in single daily intakes, whereas milnacipran possesses a plasma elimination half-life of only 7 h.

Growth hormone response to clonidine in panic disorder patients

The growth hormone (GH) response to clonidine administration (2 micrograms/kg) was compared in three groups of subjects: seven panic disorder patients, seven depressed patients matched for age and sex, and seven normal controls. As previously reported, patients with affective disorders show a blunted GH response to clonidine. Only one panic disorder patient had a blunted GH response to clonidine, and this patient had recently received a tricyclic antidepressant.

Plasma and urinary cortisol levels after dexamethasone in affective disorders

The validity of the dexamethasone suppression test was evaluated for the differential diagnosis of primary and secondary depressions. Forty hospitalized psychiatric patients (14 primary depressed, 15 secondary depressed and 11 non-depressed controls) were studied. The Research Diagnostic Criteria of Spitzer et al. (1978) were used to classify these patients. Eight out of the 14 primary depressed patients had an abnormally high plasma cortisol at 4 p.m. after dexamethasone. Only 2 out of the 15 secondary depressed patients and none of the 11 controls had an abnormal response to dexamethasone. Based on these results, the dexamethasone suppression test has a sensitivity of 57%, a specificity of 87% and a predictive value of 80%. The determination of urinary free cortisol excretion does not improve the performance of the test.

Persistent cortisol non-suppression after clinical recovery predicts symptomatic relapse in unipolar depression

We assessed the length and the quality of remission of 13 unipolar endogenous depressed patients, DST non-suppressors before treatment, in a 2-year prospective study. During this period, we recorded stressful life events. Persistent dexamethasone non-suppression, after treatment and complete clinical recovery, correlated highly with early clinical relapse. All six non-normalizers but only one normalizer were rehospitalized within the following 2 years for a major depressive relapse. Persistent DST non-suppression was unrelated to any impact of drug discontinuation, the occurrence of stressful life events or the length of illness-free intervals in the patients prior course of illness. Persistent DST non-suppression appears to have significant prognostic value.

Age and gender effects on the diagnostic power of the DST

Among 365 major and 158 minor depressive inpatients, the dexamethasone suppression test (DST) yielded an overall diagnostic sensitivity of 50%, a specificity of 85%, and a confidence level of 88%. Age was significantly correlated with the post-dexamethasone cortisol levels in the whole sample (r = 0.11; P less than 0.01); however, this low relationship disappeared when all subgroups defined by gender or diagnostic were considered. Gender did not appear to influence DST results; however, among the patients between 30 and 39 years, the diagnostic performance of the DST was significantly lower among female as compared to male patients, suggesting possible interferences with endocrine variables.

Growth hormone release after desipramine in depressive illness

SummaryThe effect of i.m. administration of 75 mg of desipramine on growth hormone (GH) secretion was investigated in a sample of 87 patients with major depressive disorders and in 31 normal controls. The GH response was lower in depressed females compared to depressed males, but no such difference was present in controls. In the premenopausal female group, GH response was significantly lower in depressed patients than in controls. No significant difference was found between normal males and male depressed patients. In the premenopausal group, no difference emerged between endogenous and nonendogenous depressed women.

Lymphocyte subsets in major depressive patients. Influence of anxiety and corticoadrenal overdrive.

We studied 26 inpatients (17 females; mean age +/- SD: 41.2 +/- 14.3 years) who met the DSM III criteria for a major depressive episode and had a mean (+/- SD) Hamilton Depression Score of 19.3 +/- 8.0. All patients were drug free and medically healthy at the time of experimentation. We found a significant correlation between the CD4/CD8 ratio and the Hamilton Anxiety Score (r = 0.57, p less than 0.005). When splitting our sample in dexamethasone suppression test suppressors (DST-S) and nonsuppressors (DST-NS), this relationship appeared only in DST-NS (DST-NS: r = 0.81, p less than 0.005; DST-S: r = 0.20, p = NS). These results are discussed in terms of heterogeneity among major depressive disorders and possible relationships between catecholaminergic activity and the immune system.

Suppression of cortisol following dexamethasone in demented patients

Sixty-four nondepressed, carefully selected senile demented inpatients underwent two 1-mg overnight dexamethasone suppression tests (DSTs) separated by 7 days. These patients were in a clinically stable and drug-free state for at least 6 months before testing. The Modified Ischemic Score and ICD-9 criteria for Alzheimers disease were used to dichotomize subjects into Alzheimers and multi-infarct types of dementia. Patients with vascular dementias were significantly more likely to evidence DST nonsuppression. Furthermore, DSTs in this group were less reproducible from week to week than DSTs in Alzheimers patients.

Growth hormone response to clonidine in untreated depressed patients

Growth hormone (GH) responses to i.v. clonidine administration (150 micrograms) were compared in untreated depressed patients and controls. There were 8 controls (6 males, 2 females), 16 patients with a major depressive episode (8 males, 8 females), and 16 matched patients with a minor depressive episode according to Research Diagnostic Criteria. Differences in the GH response to clonidine only occurred between male patients and controls. These results suggest that endocrinological variables are important in the interpretation of this neuroendocrine test. Findings in the subgroup of unmedicated male patients with a nonendogenous major depressive episode support the hypothesis of decreased noradrenergic receptor sensitivity.

Growth hormone response to clonidine in male patients with panic disorder untreated by antidepressants

We report a non-significantly higher growth hormone (GH) response to intravenous clonidine administration (150 micrograms) in 10 male patients with panic disorder who had never received antidepressant therapy than in 10 matched controls. These results are consistent with data suggesting a normal or increased adrenergic receptor sensitivity in panic disorder patients.