1 High speed surface electrocardiograms were recorded in 35 patients during the baseline and after four weeks' treatment in a placebo‐ controlled trial of mianserin and maprotiline in primary depressive illness. 2 Measurements of the RR, PR and QT intervals, QRS width and T wave height were made blind to patient, drug and treatment interval and compared with plasma drug concentrations. The presence or absence of cardiac arrhythmias was recorded. 3 The only significant findings were an increased heart rate and PR interval and decreased QTc interval in the maprotiline group. Only one patient receiving maprotiline had a cardiac arrhythmia. There was no significant correlation between measurements of ECG parameters and plasma drug levels. 4 The results confirm the lack of cardiac effects of mianserin and show both anticholinergic activity and effects of an intracardiac conduction in the case of maprotiline. The mechanisms of these effects are discussed.

No abstract

1. A double-blind, multicentre study comparing the efficacy and safety of minaprine and amitriptyline in patients with major depression was carried out. Five hundred and thirty-one patients were randomly assigned to treatment with either minaprine 100 mg, 200 mg or 300 mg day-1 or with amitriptyline 150 mg day-1 (75 mg during the first week). The medication was administered for 6 weeks. 2. Efficacy was assessed using the Hamilton rating scale for depression (HDRS), the Montgomery-Asberg depression rating scale (MADRS) and visual analogue assessments of depression carried out by both the investigators and patients. Unwanted effects were assessed by a questionnaire and spontaneous reporting. In a subgroup of patients cardiovascular effects were investigated by high speed ECG and systolic time intervals. 3. Patients in each treatment group showed a significant clinical improvement (P < 0.01) from baseline. The mean HDRS and MADRS scores adjusted for baseline differences, showed significantly less improvement in the minaprine 100 mg once daily (P < 0.01) and the minaprine 300 mg daily (P < 0.01) groups than in the amitriptyline group at both week 4 and week 6. The MADRS score at week 4 suggested that 200 mg day-1 minaprine was less effective than amitriptyline (P < 0.05), but there was no difference between the two groups at week 6 on either the HDRS or the MADRS. 4. Both drugs were well tolerated and there were no significant differences between treatment groups in any of the safety and tolerance assessments. In the ECG, amitriptyline produced a significant increase in the heart rate and PR interval while minaprine had no effect on electrocardiographic measurements. Neither drug produced changes in the systolic time intervals.

Four cases of convulsive seizures occurring during treatment with nomifensine have been notified to the Committee on the Safety of Medicines of the United Kingdom, and 22 cases have been reported from other countries. The occurrence of convulsions is not in keeping with the results of animal experiments, studies of epileptic patients treated with nomifensine or observations made following overdoses of this drug. Nomifensine may thus not be entirely free from epileptogenic properties as previously presumed.

1 Preliminary results of a double‐blind placebo‐controlled trial of mianserin and maprotiline carried out in 58 outpatients with primary depressive illness are reported. 2 Patients received six weeks' treatment with 30 to 90 mg mianserin, 75 to 225 mg maprotiline or one to three capsules of placebo, all medication being taken at night. 3 There were statistically significant improvements in each treatment group and a better response to mianserin than to placebo or maprotiline on the Hamilton Rating Scale for Depression, after one week's treatment. 4 Neither mianserin nor maprotiline was superior to placebo after two or four weeks' treatment and relatively few patients completed six weeks' treatment because of a generally unsatisfactory response. 5 Unwanted effects were not particularly troublesome, though mianserin and maprotiline caused more drowsiness and blurred vision than did placebo, while maptrotiline produced more constipation than either of the other two treatments. 6 The importance of placebo‐ controlled trials of antidepressants is emphasized and the precautions that should be taken when they are carried out in outpatients are described.