The safety and efficacy of zotepine in the treatment of schizophrenia: Results of a one-year naturalistic clinical trial.

INTRODUCTION AND METHOD: The safety and efficacy of zotepine,75 - 450 mg/day, were evaluated in an open multicentre one-year study in patients suffering from acute exacerbation of schizophrenia; total exposure amounted to 152.78 years. RESULTS: Mean BPRS total score was reduced from 51.7 at baseline to 40.8 at end-point (P<0.05). Similar significant reductions at all study time-points were recorded for BPRS total and subscores, CGI severity and improvement, BAS total scores and SANS total and global scores. Significant improvements in EPMS and AIMS were recorded from week 12 to end-point. Clinically significant improvements in acute symptoms, detected early in the study, were maintained to end-point. CONCLUSION: Zotepine was well tolerated: weight gain, reduced serum uric acid, raised liver enzymes and increased heart rate were associated with chronic zotepine treatment. Seven patients experienced seizures during the study, although concomitant medications and a known historical predisposition to seizure are factors likely to have contributed to these events. The improvements in negative symptoms and low propensity to cause further extrapyramidal side-effects support the importance of zotepine in maintenance treatment.

The efficacy of zotepine in treating acute negative symptoms of schizophrenia: The results of a meta-analysis.

INTRODUCTION: Zotepine is a unique antipsychotic drug, having effects which are both antiserotonergic and antidopaminergic that may make it more effective in the treatment of negative symptoms of schizophrenia than more conventional agents. METHOD: A meta-analysis was performed on the effect of zotepine on the negative symptoms in seven double-blind studies, as measured by the SANS scale. RESULTS: Of the trials selected for this meta-analysis, one showed significant improvement in acute negative symptoms in favour of zotepine. Negative symptoms measured in the other trials showed trends in favour of zotepine, except for one study where the trend was in favour of perazine. The meta-analysis showed zotepine to be significantly better then either placebo or conventional antipsychotic comparators using the standardized treatment difference methodology, and it confirmed the results from a previous study using patients with predominantly negative symptoms. CONCLUSION: Zotepine may have a place in the treatment of this group of patients where conventional antipsychotic drugs have had little effect. ( Int J Psych Clin Pract 2000; 4: 209 - 214).

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.

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 comparative study of atenolol/nifedipine and atenolol/diuretic in hypertension.

A prospective, randomized, double-blind between-patient study was carried out to compare the efficacy and tolerance of atenolol with nifedipine and atenolol with diuretic. Ninety-eight hypertensive patients inadequately controlled after 1-month's treatment with 100 mg atenolol alone once daily received, in addition, either 20 mg nifedipine twice daily or 5 mg amiloride plus 50 mg hydrochlorothiazide once daily for a further 8 weeks. The results of blood pressure measurements in the lying and standing positions showed that the mean reduction in standing blood pressure from atenolol baseline was 28/12 mmHg for atenolol/diuretic and 18/13 mmHg for atenolol/nifedipine. The only significant difference between treatments in blood pressure control was in lying systolic blood pressure favouring atenolol/diuretic and a trend in favour of this combination for standing systolic blood pressure. Both regimens were reasonably well tolerated, although 19 patients withdrew during the course of the trial because of side-effects (2 on atenolol alone, 10 on atenolol/diuretic and 7 on atenolol/nifedipine).

Randomized comparison of atenolol and placebo in the treatment of anxiety: a double-blind study.

In a randomized double-blind prospective between-patients trial in patients presenting with primary anxiety, atenolol significantly improved mean values on the Hamilton rating scale at two and four weeks when compared with placebo. There was also a significant improvement in affective symptoms at 28 days for atenolol when compared with placebo.

Atenolol and chlorthalidone in combination in the management of older hypertensive patients: a randomized clinical trial.

In a double-blind, crossover study in 100 elderly hypertensive patients, the hypotensive effect of a fixed combination of atenolol (50 mg) with chlorthalidone (12.5 mg) was compared with that of each of its component drugs given alone. Patients were allocated at random into two groups: one group received treatment for 4 weeks with either the combination or atenolol alone before being crossed over to the alternative medication for a further 4 weeks; the other group received either the combination or chlorthalidone alone and followed the same treatment pattern. Dosage was a single tablet per day given in the morning. Blood pressure and pulse rate were measured approximately 24 hours after dosing at the end of each treatment period. The results showed that significantly lower blood pressures were achieved, both in the standing and lying positions, with the combination than with either atenolol or chlorthalidone used alone. Combination treatment was well tolerated, few side-effects being reported and there was no significant disturbance of plasma electrolytes.

Multicentre general practitioner assessment of 'Tenormin' and methyldopa.

A large scale study in general practice was set up to investigate the effects of transferring hypertensive patients from treatment with usually less than 1 g daily of methyldopa to atenolol ('Tenormin') 100 mg daily. The results demonstrate an improvement in blood pressure control with atenolol treatment and a reduction in the incidence of side-effects. The simple dosage regime, combined with proven effectiveness and a relative lack of side-effects makes atenolol a useful treatment for the hypertensive patient.

A study of once daily tenormin (atenolol) in hypertension: some implications in patient compliance.

A clinical study is described in which hypertensive patients on no drug therapy were given atenolol in increasing doses from 50 mg twice daily to 200 mg twice daily until the diastolic blood pressure was 90 mm Hg or below. At this stage the drug was withdrawn until blood pressure readings had risen to pre-treatment levels. The same dose of atenolol was then re-introduced but now given once-a-day (in the morning) and was continued for four weeks. Of the elevel patients entering the study, one withdrew as his blood pressure was not controlled on a dose of 200 mg of atenolol twice daily, and another because on withdrawal of atenolol his blood pressure did not rise to pre-treatment levels. The remaining nine patients completed the study. There was a statistically significant fall in blood pressure on both atenolol regimes and there was no significant difference between the blood pressure control achieved on twice-a-day and once-a-day administration. Only one patient developed side-effects; this being an asthmatic who developed mild dyspnoea on atenolol which did not necessitate withdrawal of the drug. It is concluded that once-a-day administration of a given dose of atenolol is therapeutically equivalent to twice-a-day administration. The implications of this in terms of better patient compliance, and thus better prognosis, are discussed.