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.

A double-blind comparative clinical trial of citalopram vs maprotiline in hospitalized depressed patients.

In a double-blind clinical trial comprising 29 depressed patients citalopram, a highly selective 5-HT re-uptake inhibitor and maprotiline, a specific NA re-uptake inhibitor, were compared. Allowing for the small sample and taking into consideration that both groups consisted of severely ill, hospitalized patients, it is notable that half of them appeared to respond to treatment. Comparison of the clinical efficacy of the two drugs showed no significant difference, but the profiles of the side-effects appeared to be different. The patients treated with citalopram showed increased sweating, drowsiness, restlessness and headache. These side-effects were almost entirely reported by the non-responders. The maprotiline patients had anticholinergic symptoms, such as dryness of mouth and constipation, side-effects which were also reported by the responders. No correlation was found between plasma steady-state levels of either drug and clinical outcome. The Dexamethasone Suppression Test (DST) appeared to show some predictive value as regards treatment response. There was a tendency towards better overall treatment results in the non-suppressor group. Determination of post-probenecid 5-HIAA, HVA and MHPG concentrations in lumbar-CSF was made in 22 patients. There was a significant negative correlation between HVA and the severity of depression, as well as a significant negative correlation of MHPG with the Newcastle score. The 5-HIAA concentration was found to be correlated with HVA, but not with MHPG. Rather surprisingly significant negative correlation between 5-HIAA and treatment results with maprotiline was found, but no correlation with MHPG. The lumbar-CSF MHPG and HVA values did not appear to have any predictive value as regards treatment response to citalopram or maprotiline. As expected the serotonin (5-HT) concentration in blood and thrombocytes in patients treated with citalopram showed a highly significant reduction after 2 and 4 weeks of treatment.

Citalopram--a highly selective 5-HT uptake inhibitor--in the treatment of depressed patients.

In an open, clinical trial comprising a total of 21 depressed in-patients (6 men and 15 women) citalopram was administered in doses of 20-60 mg once daily for a period of at least 3 weeks. Fourteen of the patients were treated for 4 weeks, and 6 of these patients were treated for another 2 weeks. The CPRS subscale for depression (MADRS) and a global evaluation were used for assessment of the therapeutic effect. Twelve patients showed complete or partial response to treatment, and generally onset of therapeutic effect was seen within the first 2 weeks of treatment. Side-effects were generally few and mild, anxiety being the most frequent one. No pathological laboratory values were recorded, and apart from one case of slight and transient bradycardia no changes were observed in the cardiovascular parameters. Determination of plasma levels in 16 of the patients under presumed steady-state conditions showed an inter-individual variation between 28 and 616 nM/l for citalopram and between 32 and 338 nM/l for its monodemethylated metabolite for daily citalopram doses of 30-60 mg. The average ratio citalopram-desmethyl citalopram was 1.70. No correlation was found between clinical response and the plasma levels.