A double-blind, comparative study of dothiepin and clomipramine in the treatment of major depressive illness.

Dothiepin, a well-established antidepressant, has been compared with clomipramine in a single-blind study which demonstrated that dothiepin was better tolerated but there was no difference in efficacy. The present study was performed to recent European guidelines on good clinical practice using a randomised, double-blind, parallel-group methodology. One hundred and one patients suffering from major depressive disorder as defined by DSM-III-R were randomised to receive either clomipramine (25-150 mg daily) or dothiepin (75-150 mg daily) for up to six weeks. The clomipramine group comprised 51 patients, the dothiepin group 50 patients. At baseline, both groups had a mean age of 41-43 years and gave similar mean scores on the Hamilton Depression Rating Scale (23.5 for clomipramine, 23.6 for dothiepin). At endpoint it was reduced in both groups but there were no significant differences between the groups (mean change from baseline for the clomipramine and dothiepin groups was -14.6 and -14.1 respectively). Thirty-one clomipramine patients and 41 dothiepin patients completed six weeks' treatment. Withdrawal from treatment (20 patients for clomipramine, nine for dothiepin) was significantly different (p = 0.0105). When reasons for withdrawal were analysed, 13 clomipramine patients and two dothiepin patients withdrew because of adverse events, this difference being significant (p = 0.002). Thus both treatments were effective in treating patients suffering from major depressive disorder, but patients receiving dothiepin suffered fewer adverse events and were more likely to complete their treatment.

Proportion of patients with isolated systolic hypertension who have burned-out diastolic hypertension.

In a community survey of 3242 subjects, 1663 did not initially have isolated systolic hypertension (ISH) and were re-screened an average of 8 years later. ISH developed in 53 (22%) of untreated patients with previous diastolic hypertension. Similarly, 8% of subjects with transient hypertension and 8% of normotensive controls developed ISH. Of all cases of ISH, 16% had previous diastolic hypertension. These subjects were more likely to have continued to smoke (P = 0.01) and lost more weight (P = 0.001) than patients with ISH who did not have burned-out diastolic hypertension.

Survival of hypertensive subjects identified on screening: results for sustained and unsustained diastolic hypertension.

Casual readings of blood pressure predict mortality and may reflect either the risk of sustained hypertension, additional components of 'white coat' hypertension or variable blood pressure. This study investigated mortality in 442 men and 360 women with a diastolic pressure (Phase IV) of 90 mmHg and over, unsustained on two subsequent monthly visits, followed for an average of 11 years and compared with a matched control cohort with an initial diastolic pressure (DBP) of less than 90 mmHg. Subjects were identified between 1975 and 1979 by screening 28,257 subjects aged 18-65 years on the lists of general practitioners in seven practices in the United Kingdom. Additionally, 912 men and 844 women with sustained hypertension (DBP > 90 mmHg on at least two out of three occasions) were identified and matched with normotensive controls. In men with sustained hypertension the relative risk (RR) for death from circulatory disease was 1.76, P < 0.01, 95% confidence interval 1.21, 2.58 and in women 1.85, P < 0.05, 95% confidence interval 1.06, 3.24 respectively, while in men with unsustained hypertension the RR = 1.52, P = 0.2, 95% confidence interval 0.81, 2.84. Few circulatory deaths occurred in women with transient hypertension or their controls (five and seven respectively). Despite the screening programme and further treatment, newly discovered subjects with sustained hypertension, both men and women, remain at high risk of cardiovascular mortality. The 95% confidence interval for men with transient hypertension does not exclude a similar adverse effect.

A patient-powered treadmill--a simple alternative means of assessing heart failure and treatment in family practice.

A patient-powered treadmill was compared with the covered corridor walking test as assessments of exercise capacity in heart failure patients, and used to investigate their sensitivity in discriminating between the effects of xamoterol and placebo. The two methods were comparable, and sufficiently sensitive to demonstrate improvements in exercise capacity on xamoterol. The treadmill was more sensitive and could be useful as an assessment of treatment of heart failure in family practice.

A randomised comparative trial of nicardipine versus amiloride and hydrochlorothiazide in mild to moderate hypertension. A report from the General Practitioner Hypertension Study Group.

In 1984 the General Practitioner Hypertension Study Group undertook a rescreening of their patient population, looking for patients who still had untreated mild to moderate essential hypertension. Suitable patients were entered into a clinical trial comparing the safety and efficacy of nicardipine (a calcium antagonist) and amiloride + hydrochlorothiazide (HCTZ) (moduretic). The study included one year of long-term follow-up. Both drugs significantly lowered BP in both the short and long term. Numbers and percentages of patients from each group reporting adverse experiences were similar in the short term, but in the long term the frequency of adverse event reporting was much lower with nicardipine treatment than with amiloride + HCTZ treatment (2/10 versus 9/17). Treatment with amiloride + HCTZ led to elevations in serum levels of cholesterol, uric acid and urea, which were maintained at one year, whilst no abnormalities in blood biochemistry were seen in patients treated with nicardipine. In conclusion we have found that nicardipine compares very favourably with amiloride + HCTZ in the treatment of mild to moderate hypertensive patients.

A dose-response study of atenolol in mild to moderate hypertension in general practice.

A double-blind, crossover, multicentre study of 98 previously untreated patients with mild to moderate essential hypertension was carried out in general practice to assess the effect of 50 mg, 100 mg, and 200 mg atenolol, given once daily, compared with that of placebo over a period of 4 weeks each. At the end of the double-blind phase, all patients took 100 mg atenolol daily for a further 8 weeks. All three doses of atenolol produced statistically significant falls in systolic and diastolic pressure and pulse rate (p less than 0.001). The lowest pressures were achieved with 100 mg daily; a difference of 22/15 mmHg at the end of the double-bling phase, and a difference of 25/16 mmHg at the final observation. Body weight, blood urea, blood uric acid, and serum electrolytes remained within normal limits throughout the study. The incidence of side-effects with 50 mg and 100 mg atenolol was not significantly different from that caused by placebo, but the incidence of tiredness at the 200 mg dose level was greater than that caused by placebo and by the lower doses. The incidence of possible side-effects elicited by a questionnaire was low, the greatest number being volunteered by patients taking placebo. It is concluded that the optimal dose of atenolol for treating patients with mild to moderate hypertension in general practice is 100 mg daily.

A comparison of various clomipramine (Anafranil) dosage regimes.

This study was a multicentre general practitioner trial comparing four dosage regimes of clomipramine (Anafranil, Geigy Pharmaceuticals): 10 mg t.d.s., 30 mg o.n., 25 mg t.d.s. and 75 mg o.n. This paper concerns the clinical results obtained using a series of twelve visual analogue scales completed independently by doctor and patient. Also side-effects, recorded on a standard list of unwanted effects of tricyclic antidepressants, were studied. Very few statistical differences were found between the dosage regimes, and they were difficult to interpret clinically. It was concluded that although 25 mg t.d.s. was most effective, 30 mg o.n. was probably the best compromise in terms of efficacy and tolerability.