Alprazolam is an Effective Treatment for Major Depression Fewer side effects and rapid onset of action improve patient compliance

Alprazolam, a triazolobenzodiazepine antidepressant, was compared with imipramine and placebo in 129 patients with Major Depressive Disorder fer 6 weeks. The dese was adjusted fer .optimum clinical effect from O.Smg to 4.Smg alprazo/am and from 25mg to 225mg imipramine giving an average final dosage of 2.7mg a/prazolam and 117.3mg imipramine.

Beth alprazolam and imipramine were more effective than placebo in treating the symptoms of depression according to all the rating scales used. Alprazolam and imipramine did not differ consistently except for differences favouring alprazolam in the somatic symptom cluster of the Hamilton Anxiety Rating Scale. Patients on alprazolam reported fewer side effects cempared with imipramine and a similar number compared with placebo. The most com men side effects with imipramine were anticholinergic, while drowsiness was noted more frequently for alprazolam than for imipramine or placebo. Fewer patients discontinued treatment with alprazolam, reflecting its more rapid onset of action and fewer side effects. Feighner, JP et al.: Acta Psychiatrica Scandinavica 68: 223 (Oct 1983)

and pessible texicity should be considered before their use is adVocated for CHD prevention, Altheugh not an aim of the trial, dietary lowering of cholesterol was seen to be beneficial.

The consistency of reductions in all forms of CHD, from angina and coronary bypass surgery to non­fatal myocardial infarction and CHD death, leave little doubt of the benefits of cholestyramine, Although conducted in middle-aged men .only, the trial's implicati.ons should be extended to ether groups. Lipid Research Clinics Program: Journal of the American Medical Association 251: 351 (20 Jan 1984)

On diet alone, tetal chelesterol fell by 3.4%, LDL-cholesterol by 3.8% and high density lipoprotein (HDl) cholesterol by 0.4%, while triglycerides rose 1% in both cholestyramine and placebo groups,

On ch.olestyramine, additional falls of 14% in total chelesterol and 21 % in LDL-chelesterol occurred during the first year. Slight falls were also seen in the placebe group, Mean total cholesterol and LDL-cholesterol levels rese slowly in actively treated patients in subsequent years and the treatment differential had reduced to 6,5% in total chelesterol and 9.6% in LDL-chelesterel by the seventh year, HDl-chelesterol levels were consistently 3% higher with cholestyramine. Triglycerides rose in both groups during the study but were always 2-4,S% higher with cholestyramine. With the exception of HDL-cholesterol there was a clear dose­respense between lipid and lipoprotein levels and the dose of cholestyramine resin reportedly taken.

In the first year, men taking 20g daily showed a 23% fall in tetal cholesterol and a 33% fall in LDL­cholesterol. In the seventh year on the same dese, falls .of 17% and 26%, respectively, were recorded, This may indicate either a reduction of drug efficacy with time or pregressive unreliability of 'packet count' as a measure of compliance.

Patients who experienced CHD were compared with others who were at risk at the same time of follow­up, Except in the first and sixth years, aU CHD cases showed substantially smaller mean decreases in LDL­cholesterol levels than those without CHD. Lack of effect in the first year can be expected and the apparent lack of effect in the sixth year may be due te the smaU number of CHD cases (12) reported,

The relationship between decreases in total cholesterol and LDL-cholesterol and reduction in CHD in those taking 'cholestyramine was significant (p < 0.001), Analysis showed that mere compliance to medi­cation had no effect on the incidence of CHD, CHD was reduced .only in response to a lowering of total and LDL-cholesterollevels. However, increases in HDL-C levels were also related to reduced'CHD incidence in the cholestyramine group, No association between lipid and lipoprotein changes and CHD incidence was seen in the placebo group.

There was a strong and consistent correlation between cholestyramine use, lowering of total cholesterol and LDL-cholesterol levels and a reduction of coronary heart disease risk. Increases in HDL-cholesterol were also associated with an additional reduction in CHD risk. Although the average risk reduction in this study may seem small it was achieved with only an 8% reduction in total cholesterol and a 12% reduction in LDL-cholesterol. If the higher response of 35% reduction In LDL-cholesterollevels (seen in those patients taking the full dose daily) could be sustained, then a 49% reduction in CHD incidence could be predicted, In a clinical setting, with dosage adjustments made en an individual basis, this rate of compliance could be maintained and the overall risk of CHD events reduced by half in hypercholesterolaemic men,

'ThuS, the benefit of effective cholesterol-lowering therapy in men with type II hyperlipoproteinaemia with regard to incidence of CHD is of great potential clinical as well as statistical significance.'

Lipid Research Clinics Program: ·Journal of the American Medical Association 251: 365 (20 Jan 1984)

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