Meta-analyses of 417 patients diagnosed either prospectively (316 US patients) or retrospectively (101 European patients) as suffering from melancholia according to DSM III criteria have shown that paroxetine was significantly better than placebo with respect to all outcome measures. There was no significant difference between active control and placebo in these analyses. In a group of 216 severely depressed hospitalised patients with a HAMD score of 25 or more, paroxetine was as effective as active control.

The effects of the novel antidepressant tianeptine, after acute or chronic administration, were compared in normal and restraint-stressed (30 min or 2 h) Wistar rats. Tianeptine, at the dose of 10 mg/kg, did not exert any effect in non-stressed rats. However, in animals restrained for 30 min, tianeptine reduced the increase of circulating ACTH and β-endorphin levels without modification of corticosterone. Moreover, it antagonized the deficit of vertical exploratory activity in an open field. In rats restrained for 2 hours, a single injection of tianeptine suppressed the stress-induced increase of TAT hepatic activity and moderately attenuated the deficit of activity in the open field. This effect was less marked and not statistically significant after chronic treatment.

The effect of paroxetine on symptoms of anxiety associated with depression were assessed by meta-analysis of data on the use of paroxetine (n = 2963), active control (n = 1151), and placebo (n = 554) in six-week clinical trials. Paroxetine significantly reduced psychic anxiety by comparison with placebo from week 1 and was more effective than active control from week 2. Paroxetine improved somatic anxiety from week 4 of treatment. There was no association between antidepressant therapy and the emergence of anxiety symptoms in patients with little or no baseline anxiety. Paroxetine resolved baseline symptoms of agitation from week 1 of treatment, and both paroxetine and active control prevented the emergence of agitation. There was no difference between placebo and antidepressant therapy in the frequency of adverse events indicative of increased arousal. The results indicate the utility of paroxetine in depressed patients presenting with associated anxiety symptoms.

Stress-induced stimulation of corticotropic function involves the activation of hypothalamic corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), which can be measured by improved methods of neuroendocrine investigation. The antiserotoninergic tricyclic antidepressant, tianeptine, reduces the corticotropic response to stress, as shown by a reduction in hypothalamo-hypophyseal portal CRH and AVP levels.

The effect of the antidepressant agent, tianeptine, on the hypothalamo-pituitary-adrenal (HPA) axis was studied in adult male rats under basal and stressed conditions. Chronic treatment with tianeptine (10 mg/kg; 2 weeks; twice a day) induced a significant decrease of hypothalamic CRF (–12%) and pituitary ACTH concentrations (–21%), suggesting that tianeptine reduces the activity of hypothalamic CRF neurons and pituitary corticotrophs. The possible effect of tianeptine in the neuroendocrine response to stress was thus investigated. Rats were submitted to restraint stress for 30 min; under these conditions ACTH and corticosterone levels were considerably increased. A single injection of tianeptine was found to significantly reduce stress-evoked elevations of plasma ACTH and corticosterone. Time-course experiments, consisting of administering tianeptine 1–3 h before immobilization stress, revealed that the maximum inhibitory effect of tianeptine occurs about 2 h after injection of the antidepressant. Administration of various doses of tianeptine (from 2.5 to 20 mg/kg) showed that the effect of the drug was dose-dependent; the maximum effective dose being 10 mg/kg. Taken together, these data indicate that tianeptine may exert original ‘anti-stress’ activity.