Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial.

OBJECTIVE: In a double-blind, randomized, placebo-controlled trial with 375 patients the authors investigated the antidepressant efficacy and safety of 300 mg t.i.d. of hydroalcoholic Hypericum perforatum extract WS 5570. METHOD: The study participants were male and female adult outpatients with mild to moderate major depression (single or recurrent episode, DSM-IV criteria). After a single-blind placebo run-in phase, the patients were randomly assigned, 186 to WS 5570 and 189 to placebo, after which they received double-blind treatment for 6 weeks. Follow-up visits were held after 1, 2, 4, and 6 weeks. The primary outcome measure was the change from baseline in the total score on the 17-item Hamilton Depression Rating Scale. In addition, analyses of responders (patients with at least a 50% reduction in Hamilton total score) and patients with remissions (patients with a total score of 6 or less on the Hamilton scale at treatment end) were carried out, and subscale/subgroup analyses were conducted. The design included an adaptive interim analysis performed after random assignment of 169 patients with options for group size adjustment or early termination. RESULTS: Compared to placebo, WS 5570 produced a significantly greater reduction in total score on the Hamilton depression scale and significantly more patients with treatment response or remission. It was more effective in patients with higher baseline Hamilton scores and led to global reduction of depression-related core symptoms, assessed with the melancholia subscale of the Hamilton scale. The placebo and WS 5570 groups had comparable adverse events. CONCLUSIONS: H. perforatum extract WS 5570 was found to be safe and more effective than placebo for the treatment of mild to moderate depression.

Antidepressant efficacy and tolerability of milnacipran, a dual serotonin and noradrenaline reuptake inhibitor: a comparison with fluvoxamine.

The antidepressant efficacy and tolerability of milnacipran, a dual action serotonin-noradrenaline reuptake inhibitor, were compared with those of the selective serotonin reuptake inhibitor, fluvoxamine, in 113 patients with moderate to severe major depression. Treatment with milnacipran, 50 mg b.d. for 6 weeks, produced a significantly greater reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores than fluvoxamine, 100 mg b.d. (P = 0.007; 65.4% versus 49.9%, respectively); significantly greater decreases were also seen on days 7 (P = 0.04) and 28 (P = 0.03). The response rate (the proportion of patients showing a decrease in MADRS scores of at least 50%) was 78.9% in patients receiving milnacipran, compared with 60.7% in fluvoxamine-treated patients (P = 0.04). Milnacipran also produced greater improvements in 24-item Hamilton Depression Rating Scale scores (P = 0.05). On the Clinical Global Impression Improvement scale, 77.2% of milnacipran-treated patients were rated as considerably or markedly improved, compared with 60.7% of patients receiving fluvoxamine (P = 0.06 chi-squared). Both treatments were well tolerated; the only significant difference between the two groups was a higher incidence of tremor and drowsiness in patients treated with fluvoxamine. It is concluded that milnacipran may offer some advantages over selective serotonin reuptake inhibitors, such as fluvoxamine, in the treatment of moderate to severe major depression.

Citalopram versus fluoxetine: a double-blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice.

Two selective serotonin reuptake inhibitors (SSRIs), citalopram and fluoxetine, both at a daily dose of 20 mg, were compared in patients with unipolar major depression treated in general practice. This was a multicentre, double-blind, randomized trial carried out in France. The duration of treatment was 8 weeks. Patients were assessed by means of the Montgomery-Asberg Depression Rating Scale (MADRS), the 17 items Hamilton Depression Rating Scale (HAMD) and the investigator's Clinical Global Impressions (CGI), Observed and spontaneously reported adverse events were also recorded. A total of 357 patients of both sexes, aged between 21 and 73 years, entered the double-blind phase of the trial. A clear reduction of both the MADRS and the HAMD mean total scores was observed in both treatment groups with no statistically significant differences between treatments. Apart from back pain recorded more frequently in the citalopram group, no significant difference was found between the two treatment groups with regard to adverse events, and both citalopram and fluoxetine were considered to be well tolerated. It was concluded that citalopram was as effective as fluoxetine in the treatment of unipolar major depression. Citalopram showed an earlier onset of recovery than fluoxetine.

Cholesterol content of circulating immune complexes in patients with coronary stenosis and subjects without evidence of atherosclerosis.

The biological variation factors for cholesterol in circulating immune complexes (CIC-cholesterol) were studied in 941 unselected supposedly healthy volunteers, ages 4 to 78 years. We found a complex effect of age, including the existence of two peaks of CIC-cholesterol, one in males between 11 and 14 years and in females between 11 and 30 years, and in both sexes another peak between 41 and 60 years, and in both sexes a decrease between 31 and 40 years. By use of multiple regression analysis and after adjustment for age, CIC-cholesterol was positively related to plasma cholesterol concentration and leukocyte count, values being lower in females than in males and among subjects taking anti-inflammatory drugs. In addition, CIC-cholesterol was measured in 76 coronary angiography patients and in 100 supposedly healthy controls, ages 30 to 77 years. We noticed a significant increase (P < or = 0.05) of CIC-cholesterol when patients were affected by coronary stenosis between 20% and 50% (71.8 +/- 52.5 mumol/L vs 46.2 +/- 45.9 mumol/L in controls), but this was less pronounced in those with > 50% of obstruction (58.9 +/- 54.3 mumol/L); however, serum total cholesterol was not modified or even surprisingly slightly decreased in the coronary angiography individuals. Nevertheless, an important overlap of values in controls and patients makes questionable the usefulness of this variable in clinical practice.

A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. The Venlafaxine French Inpatient Study Group.

The antidepressant efficacy and short-term safety of venlafaxine and fluoxetine were compared in 68 patients hospitalized with major depression and melancholia. Venlafaxine was superior in efficacy to fluoxetine; total scores for both the MADRS and the HAM-D were significantly (p < or = 0.05) lower in the venlafaxine group than in the fluoxetine group at Weeks 4 and 6. Overall tolerance was similar for the two treatments.

Atherosclerosis as an immune disease?

Immunology has many effects on atherogenesis. In addition to their usual action risk factors for atherosclerosis have an immunomodulating effect and immunomodulation may be a new treatment of atherosclerosis.

Comparative study of azithromycin and amoxicillin/clavulanic acid in the treatment of lower respiratory tract infections.

Forty-eight patients with acute bronchitis and four with pneumonia were randomly assigned to receive five doses (500 mg on day 1, plus 250 mg/day on days 2-5) of azithromycin; 54 patients with acute bronchitis and four with pneumonia were assigned 30 doses (625 mg every eight hours for ten days) of amoxicillin/clavulanic acid (CA). The two regimens were equally effective, with clinical improvement or cure in 92% and 87% of patients respectively, bacteriological cure in 89% and 86%, with 91% and 89% of pathogens eliminated. Minor side effects occurred in 6% and 12% of patients in the two groups, respectively. No major abnormalities in laboratory safety parameters were seen in either group.

[Difficulties in the echocardiographic diagnosis of false aneurysm of the left ventricle. Apropos of 2 cases]. / Difficultés du diagnostic échocardiographique des faux anévrysmes ventriculaires gauches. A propos de deux cas.

The echocardiographic diagnostic criteria of left ventricular pseudo-aneurysm are well established: the demonstration of a narrow-necked communication between the left ventricular cavity and the aneurysm and endocardial discontinuity at the site of myocardial rupture. The authors report two cases in which these criteria were fulfilled, leading to an echocardiographic diagnosis of pseudo-aneurysm which was erroneous as the operative findings were those of true left ventricular aneurysms.

Ecology and arteriosclerosis.

An ecological theory of arteriosclerosis invokes antirisk factors dependent on infections and parasitic infestations through the medium of immunoglobulins. Dysglobulinemia modifies blood cholesterol, platelet function, hemostasis, and biophysics of the blood in the vessels. This could explain the differences in epidemiology of arteriosclerosis between northern developed countries and tropical countries, and the present frequency of coronary heart disease in developed countries. Arteriosclerosis is conditioned by environmental factors other than diet.

[M monoclonal macroglobulinemia induced in BALB/C mice. Effect on blood cholesterol and its significance]. / Macroglobulinémie M monoclonale provoquée chez la souris BALB/C. Incidence sur la cholestérolémie et intérêt.

BALB/C mice have been inoculated with a monoclonal IgM secreting hybridoma and have developed an hypocholesterolemia strongly dependent of the hypermacroglobulinemia M obtained (P less than 0.001). Cholesterolegram shows cholesterol is carried on the monoclonal IgM fraction. This result has been established in comparison with a lot of mice treated with the same no secreting hybridoma and a lot of untreated-mice, in these cases cholesterolemia is not modified. The whole aminoacids sequence of this IgM being nearly achieved, it is thinked of check the hypocholesterolemic activity of several parts of this immunoglobulin.

[Haloperidol decanoate. Results of an open-ended multicentric study in chronic psychotic states]. / Décanoate d'halopéridol. Résultats d'une étude ouverte multicentrique dans les états psychotiques chroniques.

UNLABELLED: An open multicentric study of 196 in-patients was carried out in 9 centres. After an initial stabilization (min. 15 days) with oral haloperidol, patients received haloperidol decanoate IM for at least 24 weeks (or a minimum of 9 injections). RESULTS: - esterification of haloperidol increased the duration of its efficacy (interval between 2 injections: average 4 weeks) without interfering with its therapeutic activity (global appreciation scale, BPRS at each injection and at the end of the treatment); - equivalent quantities of haloperidol injected at a time were 15 to 20 times those administered daily during the initial stabilisation period; - side-effects were not different with haloperidol decanoate as compared to those of the previous period (haloperidol).