A randomized, double-blind, multi-centre, parallel-group study comparing the tolerability and efficacy of moclobemide and dothiepin hydrochloride in depressed patients in general practice.

A randomized, double-blind, multi-centre, parallel-group study compared the tolerability and efficacy of 450 mg of moclobemide and 75-150 mg of dothiepin in the management of depressed patients in general practice. Patients who fulfilled the DSM-III-R criteria for major depressive disorder and who scored 13 or more on the Hamilton Depression Rating Scale were admitted. The trial lasted six weeks. The dose of moclobemide was 150 mg three times daily and that of dothiepin was 75 mg daily for the first two weeks and 150 mg thereafter. Assessments were made at baseline and after one, three and six weeks using the HDRS, the Zung SRS and the CGI. Adverse events and vital signs were monitored at each visit, and laboratory screening tests performed at the beginning and end of the study. Sixty-four general practitioners from four centres recruited 345 patients: 175 received dothiepin and 170 moclobemide; 265 completed six weeks of treatment. Thirty-eight dothiepin-treated patients (22%) and 42 who received moclobemide (25%) dropped out, most commonly because they experienced adverse events. More patients on dothiepin (24) than on moclobemide (16) dropped out for this reason; the incidence of adverse events was 10% higher in the dothiepin-treated group and of "side effects" more than 10% higher, the latter difference being statistically significant. Both treatments resulted in significant improvement; this was greater in the dothiepin-treated group and the difference was statistically significant, although clinically small.

A comparison of the hypnotic activity of loprazolam, temazepam and placebo in general practice.

One hundred and ninety-seven patients exhibiting a disturbed sleep pattern were recruited by thirty-five general practitioners into this single-blind randomized parallel group multicentre study. There were twelve patient withdrawals or drop-outs leaving sixty-one, sixty-three and sixty-one patients who, following 2 nights on placebo as baseline, completed 5 consecutive nights of treatment on loprazolam (1 mg), temazepam (20 mg) and placebo, respectively. Loprazolam and temazepam were found to have similar hypnotic activity with both treatments being superior to placebo. There was no statistical difference in the side-effect profile of the three treatment groups.

Trazodone and mianserin in general practice.

In a double-blind, noncrossover study, general practice patients suffering from depression were treated with either trazodone (100-200 mg, nocte ) or mianserin (60-120 mg, nocte ) for 6 weeks. For entry into the study, a minimum score of 14 on the 17-point Hamilton Depression Rating Scale ( HDRS ) was necessary. By random allocation, 125 patients (61 on trazodone and 64 on mianserin) entered the study. Altogether there were 43 withdrawals, of whom 31 (72%) had received mianserin. At least one of the reasons for 22 withdrawals from the mianserin group was an unacceptable side effect, frequently being daytime drowsiness. In contrast, only 5 of the trazodone group withdrew because of side effects. These differences in the withdrawal rates for those patients entering the study were statistically significant (p less than 0.001). A total of 82 patients completed treatment and entered the analysis for efficacy; 49 on trazodone and 33 on mianserin. Results show that both treatments were equally effective in reducing symptoms of depression and anxiety. Thus, the mean HDRS score was 21.3 and 21.5 for trazodone and mianserin, respectively, at the start of treatment which decreased to 6.2 and 5.9, respectively, at the end of 6 weeks. The mean Zung self-rating anxiety scores for trazodone and mianserin were 45.6 and 44.4 at the start of treatment and 33.6 and 31.1 at the end of the study. The results suggest that, on the basis of fewer significant side effects, trazodone is more acceptable to mianserin in treating depression, with or without anxiety, in general practice patients.

Validation of the General Practitioner Clinical Research Group 11-item depression scale.

In trials performed by the General Practitioner Clinical Research Group two rating scales have been employed extensively to measure depression. One includes some 17 target symptoms whilst the second is a shorter scale of 11 items. Although extensively used, neither scale has been validated against other measures of depression. An attempt was made to validate the 11-item scale, completed by the physician, against the Zung self-rating depression scale and the Wakefield Inventory, both patient-completed scales. Using thirty depressed patients the correlation between the 11-item scale and the Zung was 0.59 and between the 11-item scale and the Wakefield it was 0.5. Surprisingly, although the two scales are patient-completed and purport to measure the same thing, the correlation between the Zung and the Wakefield scales was only 0.69. All the correlations were statistically significant at the 1% level.

Clomipramine and oral contraceptives: an interaction study--clinical findings.

Forty-six depressed females were admitted to a study primarily designed to investigate the steady-state plasma levels of clomipramine and desmethyl-clomipramine in two groups of patients--one taking oral contraceptives, and one not. Twenty-one patients were taking oral contraceptives and twenty-five were not. Six 'pill'-takers dropped out of the study, two for drug-related reasons, and five non-'pill'-takers, two of whom also developed side-effects. Oral contraceptive takers were found to be significantly more depressed initially than controls, overall. Moreover, when the control group was examined in detail it was found to contain two sub-groups--one moderately depressed and one severely depressed. This latter sub-group was similar to the 'pill'-taking group. Both groups of patients improved similarly. There was no difference in the side-effects experienced. Clinically the study did not suggest that taking oral contraceptives had any influence on the effects of antidepressant medication. It did, however, suggest that either oral contraceptives cause depressed mood and loss of libido or, more likely, that when oral contraceptive takers become depressed these two factors interact to particularly influence mood and libidinous desire.

Vaccination of rubella-susceptible women during oral contraceptive care in general practice.

Over a six-month period women attending a general practice surgery for contraceptive pill prescriptions were asked whether they had had rubella and if they would give a blood sample to test for immunity. Of 459 interview, 104 (23%) did not want any more children and 69 (15%) had been vaccinated or had been shown to be immune by serotesting. Only three refused to give a blood sample, and 283 patients (62%) had their antibody concentrations checked. Two hundred and twenty-five (79-5%) could be reassured that they were immune, and the rest were offered rubella vaccination. It is thus quite feasible, and would add little to the work load, to screen the susceptible women in a practice and offer rubella vaccination to those needing it.

Experiences with some new scales for use in general practice trials.

The proper assessment of depression in general practice requires the use of adequate and sensitive measurement of target symptoms. In a pilot trial of a new 50 mg formulation of clomipramine (Anafranil) various new techniques of measurement were explored, namely, the General Health Questionnaire, a series of visual analogue scales with a centre reference point and a new physician rating scale for depression.

An uncontrolled trial of clomipramine (Anafranil) in the treatment of phobic and obsessional states in general practice.

A small, open, multicentre trial of clomipramine (Anafranil, Geigy Pharmaceuticals) in the management of phobic and obsessional states was performed in general practice. New rating devices were used. Twenty-seven patient suffering from a variety of phobias and obsessions were treated with doses of clomipramine up to a maximum of 225 ng daily for six weeks. In phobic subjects best results were obtained in social phobias, agoraphobia and diffuse phobic anxiety, situational anxiety, interference, avoidance and autonomic effects all responding. An improvement of between 33% and 47% was seen in obsessional symptoms.

A clinical trial of a 50 mg formulation of clomipramine (Anafranil) with steady-state plasma level measurements.

Twenty depressed patients seen in general practice were admitted to an open, uncontrolled pilot trial of a new 50 mg formulation of clomipramine. Treatment was administered for four weeks and clinical progress assessed by the General Health Questionnaire, a new depression rating scale and a new design of a visual analogue scale. Two patients dropped out of the study, one because of side-effects and a second because it was necessary to change the dosage. Of the 18 patients remaining 17 showed significant improvement during the four weeks treatment as assessed by the three clinical measures. Plasma levels of clomipramine and desmethylclomipramine were assayed. Steady-state appeared to be achieved between one and two weeks. Between two and four weeks levels of clomipramine varied between 14 and 136 microng/ml with a mean level of 54-6 microng/ml and of desmethylclomipramine, between 3-5 and 344-3 microng/ml with a mean level of 76-7 microng/ml The 50 mg formulation of clomipramine appeared to produced therapeutic levels in 17 of the 18 patients treated. Because so many patients recovered in spite of individually variable plasma levels no correlations between clinical effect and plasma levels were demonstrable. Side-effects were not generally troublesome and were low in incidence. Correlations between plasma level and side-effects were inexplicably negative but rarely significantly so.

A clinical trial of Tofranil in rheumatic pain in general practice.

A multicentre double-blind clinical trial was conducted in general practice in which imipramine (Tofranil) was added to existing standard analgesic anti-rheumatic therapy in patients suffering from osteo-arthritis, rheumatoidtero-arthritis, rheumatoid arthritis or ankylosing spondylitis. Twelve doctors admitted sixty-five patients to the trial. Fifty-five patients completed an eitht-week treatment period. According to clinical assessments imipramine brough about statistically significant improvements in pain, stiffness and grip strength and, according to patient self-rating, significant improvement in pain and stiffness. On the basis of a global assessment patients showed a highly significant preference for imipramine compared with placebo as adjunctive therapy.