Double-blind trial with oral versus intravenous clomipramine in primary depression.

Intravenous clomipramine and oral clomipramine at a daily dose of 2 mg/kg body weight were compared in a double-blind study of 40 inpatients with primary depressive illness. No significant differences between the two routes of clomipramine administration were found, either in response or in side effects. Steady state was not attained at the 4th week of treatment in 30% of patients. However, combined plasma levels of clomipramine (CI) plus desmethylclomipramine (DMCI) were similar in the two groups at all stages of treatment. The only significant pharmacokinetic difference that was found was in the ratio of DMCI to CI, which was higher among the patients who received the drug orally, but this did not correlate with clinical response. Conversely, Day 28 plasma concentrations of CI, DMCI, and the sum CI + DMCI were significantly related to clinical outcome in the patients treated orally. Among the patients who received the drug intravenously only CI was significantly associated with the percentage reduction of symptoms. By pooling the two groups, CI, DMCI, and their sum all bore relationships to clinical response significant at the 0.01 level.

Depressive relapses and incomplete recovery from index episode.

Of 101 patients suffering from primary unipolar depression who were followed up for at least 1 year after recovery from the index episode, 51 relapsed into a new depressive episode within the year of recovery. Only those variables related to the period immediately after discharge distinguished nonrelapsers from relapsers; relapsers showed higher levels of residual symptoms, inferior social adaptation, a more pathological mean personality profile, and lower tricyclic plasma levels, despite similar dosage. The data are consistent with the hypothesis of an incomplete recovery from the index episode as a risk factor for relapse within 1 year.

Prevalence of traumatic early life events in 31 agoraphobic patients with panic attacks.

The rate of traumatic early life events in 31 agoraphobic subjects with panic attacks was significantly higher than that in matched control subjects. Experience of maternal separation, parental divorce, and events occurring after the age of 4 years was significantly more common.

Plasma levels and clinical response during treatment with clomipramine.

The plasma levels of clomipramine (CI) and its major metabolite desmethylclomipramine (DMCI) may be related to clinical response during treatment of depression. Not all workers have been able to demonstrate such a relationship. The many factors which may affect clinical response include sample selection, assessment and its quantification and kinetic factors. A further investigation into the relationship between plasma levels and response was, therefore, carried out taking these into account and attempting to control them. Sixty-two patients with depressive illness were included. The plasma levels of CI + DMCI as measured on the 28th day of treatment were correlated against clinical response at the time. Patients with the highest combined plasma levels showed the best response. Patients with intermediate plasma levels showed more modest response, whilst lowest plasma levels tended to be shown by patients who exhibited an inadequate response or who relapsed during subsequent outpatient follow-up. The threshold value for satisfactory antidepressant effect appeared to be a combined CI + DMCI plasma level of 160-200 mg/ml.

Early life events and affective disorder revisited.

The incidence of traumatic events during the first ten years of life was investigated in two groups of patients suffering from major affective disorder, as well as in mixed psychiatric patients and in healthy subjects. While there were no significant differences between the two groups of affective patients or between the two control groups, the incidence of subjects who underwent such trauma was significantly higher in depressives, compared with controls. These differences are small and are further reduced if events secondary to psychiatric disturbances of family members are excluded.