A double blind, placebo controlled trial was carried out to examine the contribution of propranolol as an adjunct to neuroleptic medication in the treatment of chronic schizophrenic patients whose florid symptoms had not remitted with neuroleptic medication alone. Propranolol was shown to have a more beneficial effect than placebo, but the results were much less dramatic than those which have been described in previous studies. Recent work has shown that there may be a pharmacokinetic interaction between propranolol and neuroleptics, and this should be considered as one possible explanation of our findings.
A very large number of therapeutic trials of antidepressant drugs have been reported in the scientific literature. Until now, the comparison of one drug with another, or with placebo, has been performed typically by comparing the scores on depression rating scales of the two groups of patients at fixed points of time after the beginning of therapy. It was postulated in 1989 that the curves of the recovery scores followed an exponential curve of the formula y = ae-bx + c. This hypothesis was tested in a double-blind controlled trial of the antidepressant minaprine, with the use of the scores on the Hamilton Rating Scale for Depression (HAM-D). We found that the correlation coefficient, Pearson's r, between the log of the HAM-D value and the week number of the study was -0.99. This gives a coefficient of determination of 0.98, which makes it clear that the model adequately fits the data. We conclude that the use of the formula gives a method of testing the statistical significance of the difference between treatments as a valuable alternative to traditional tests. We believe that this would give a much more sensitive discrimination between treatments because all of the data points are used to calculate a single parameter--the slope of the curve.
The clinically tested reversiblc inhibitors of monoamine oxidase A (RIMAs) include brofaromine, moclobemide and toloxatone. Moclobemide has shown unequivocal antidepressant activity against serious deprcssivc illness in 4 placebo‐controlled double‐blind trials. It has been compared with amitriptyline, imipramine, clomipramine, desipramine, maprotiline, fluoxetine, fluvoxamine, tranylcypromine. toloxatone, mianserin and amineptine in the treatment of depressive disorders. Meta‐analysis showed convincing evidence of moclobemide efficacy, comparable with the most potent antidepressants available. The efficacy of moclobemide has been demonstrated in psychotic and non‐psychotic depression, in depression with and without melancholia, in endogenous depression (both unipolar and bipolar), in retarded depression and in agitated depression. The efficacy of moelobemide, allied to the unusually benign side effect profile, has led to exploration of its use in other disorders. Two small studies have given encouraging results in the treatment of attention‐deficit hyperactivity disorder. Large placebo‐controlled studies have shown the activity of moclobemide in the depression that accompanies dementia (such as senile dementia of Alzheimer type). The results also suggested that, in this patient population, cognitive ability improved in parallel. Social phobia has also been shown to improve on treatment with either moclobemide or brofaromine. Clinical trials are in progress on the effect of moclobemide in chronic fatigue syndrome. Moreover, there are encouraging results with the use of brofaromine and moclobemide in panic disorder. Other disorders in which treatment with RIMA is of interest include agoraphobia, bulimia, borderline personality disorder, post‐traumatic stress disorder, compulsive hair pulling (trichotillomania), dysmorphophobia, kleptomania as well as various anxiety syndromes.
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