En dubbel-blind jämförelse mellan Amoxapin och Clomipramin

Abstract

Amoxapine (Amx), a new dibensoxazepine - tricyclic, is structurally very similar to the neuroleptic loxapine but has antidepressive properties. Amx has been shown to have a more rapid onset of action than imipramine and amitriptyline and less pronounced anticholinergic and cardiovascular side effects. In a pilot study performed at this clinic several cases showed a remarkable increase of engagement in tasks at hand and creativity, i.e. motivation and drive, which is considered to be an effect of the norepinephrine re-uptake. These effects of Amx were considered worthy of further investigation in a double-blind study, and clomipramine (Clo) was chosen as a reference drug, since in some studies it has also been shown to have a more rapid onset of action than amitriptyline and a less initial sedating effect.Forty-two adult outpatients with moderate to severe endogenous depression were treated, of whom 20 received Amx and 22 Clo. The study continued for 12 weeks, and 30 patients completed the program.Amx was as effective as Clo. All the patients on Amx showed a clinical response to the treatment. A therapeutic response of a total score reduction in Hamilton Depression Scale (HDS) of at least 50 % was obtained in 90 % of the patients after four weeks treatment. Measured as total score, factors and single items of the scales, the effect was equally rapid for both drugs. However, there seemed to be a tendency to a more rapid response with Amx when 50 % reduction in total score in HDS was used as a measure of therapeutic effect. A support for the observation of a stronger effect on motivation was observed for rapid responders, i.e. those with a 50 % reduction in total score in HDS within two weeks. In those patients there was a significant difference in favour of Amx in the self-rating scale «Engagement in the task» at week 1. In a questionnaire for measuring creativity there was an increase of total score in some patients. Of these there were significantly more Amx patients responding within 2-4 days than in the Clo group. The latter group responded mainly after two weeks.Measurements of skin resistance showed a tendency of better balance for Amx in the autonomic nervous system.The side effects of Amx were milder, with less pronounced anticholinergic effects and cardiovascular influences. In ECG no Amx patients showed changes, compared to three patients treated with Clo. The decrease in the systolic blood pressure in the orthostatic test was statistically significantly less with Amx. In the Amx group only constipation was reported in a significantly higher frequency. Four cases of dystonia-akatisia (Amx 3 and Clo 1) and two allergic reactions (Amx) were also reported.This study has shown that Amx is a safe and effective antidepressive agent, with a relatively rapid onset of action. The drug seems to have a notable action on motivation and drive, but this finding needs further analysis in order to be confirmed. In most cases the side effects were mild and well tolerated by the patients. □ Amoxapin, Clomipramin, Tricyclic antidepressants.