Melatonin production decreases with advancing age, leading to insomnia and changes in circadian rhythmicity. Administration of melatonin in variable doses resulting in supraphysiological or physiological night-time blood levels of melatonin has been shown to improve sleep quality in the elderly. To study the effect of low doses of melatonin, which do not affect daytime blood melatonin concentrations, night-time milk containing 10-40 ng/l melatonin was used as a drink with meals. The effect of about 0.5 l night-time milk daily on sleep quality and circadian activity was studied in elderly institutionalized subjects in two long-term double-blind, placebo-controlled, crossover studies. Night-time milk was given for 8 weeks and normal day-time milk for 8 weeks with a 1-week washout period in between. In the first study, which was performed during spring with sleep quality evaluated subjectively by specially trained nurses, 70 demented patients showed only a seasonal effect on their sleep quality. In the second study performed around the winter solstice, 81 fairly healthy subjects living in rest-homes were divided into three groups, two for the crossover study as in the first investigation with a third group consuming only normal daytime milk as a control group to evaluate the effect of season. Caregivers graded the sleep quality and activity that was monitored separately for the morning before noon and for the evening after noon. In the second study, the effect of season was recognizable in the scores for sleep quality, which increased in all groups after the winter solstice. However, there were no changes in activity in the control group or in the group that consumed night-time milk during the first period of the crossover study, whereas both morning and evening activity increased significantly in the group that consumed night-time milk during the later period. Even ultra-low doses of melatonin may benefit the elderly by increasing their daytime activity.
The efficacy of moclobemide (300-450 mg/day) was compared with fluoxetine (20-40 mg/day) in a double-blind, multicentre study in 209 patients with new episodes of depression selected from 612 consecutive depressed patients representative of those consulting psychiatric services in Finland. Antidepressant efficacy was assessed with the Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Rating Scale and Clinical Global Impression (CGI). The Medical Outcome Study Short-form General Health Survey (SF-20) and 15D Measure of Quality of Life were used to measure effectiveness in terms of health-related quality of life. Efficacy was evident with both drug treatments, with 67% in the moclobemide group and 57% in the fluoxetine group having a reduction in HDRS of more than 50%. Similarly, 77% of the patients in the moclobemide group and 67% in the fluoxetine group were assessed on the CGI as much better or very much better after 6 weeks of treatment. The most commonly reported adverse events were nausea, other gastrointestinal symptoms, nervousness, dizziness and sleep disorders. Nausea was significantly more common in the fluoxetine group and was found especially in women. Premature terminations of treatment were 18% in the moclobemide and 21% in the fluoxetine group. A significant change for the better in quality of life was found in both treatment groups, even at week 2 but especially after 6 weeks of treatment. Improvement was not only seen in dimensions measuring depression or mental health but also in other dimensions.
Zuclopenthixol decanoate (ZPT-D) and haloperidol decanoate (HAL-D) were compared in the maintenance treatment of chronic schizophrenic patients. All patients were treated with either ZPT-D or HAL-D for at least 3 months and were then randomly allocated to treatment with either ZPT-D (100-600 mg every 4 weeks) or HAL-D (38-200 mg every 4 weeks) for 9 months. Sixty-four patients entered the study. Three patients were only assessed at baseline. Four patients in the HAL-D group were withdrawn because of deterioration. One patient in the ZPT-D group committed suicide. Fifty-six patients completed the trial. The assessment programme comprised Clinical Global Impressions by psychiatrists and nurses, the Brief Psychiatric Rating Scale (BPRS), Montgomery-Asberg Depression Rating Scale (MADRS), UKU Side Effect Scale and Simpson-Angus Scale, Ratings were made at baseline and after 12, 24 and 36 weeks of treatment. The severity of illness scores remained almost constant. The only between-group difference was recorded at month 6 in favour of ZPT-D. The BPRS total scores were reduced significantly in both groups with no between-group differences. The depression scores on the MADRS were very low. Both treatments caused few and mild side effects according to the UKU Side Effect Scale and the Simpson-Angus scale, and there were no significant differences between the groups. Both ZPT-D and HAL-D seem to be effective in the maintenance treatment of chronic schizophrenic patients and cause few side effects. The injections of ZPT-D and HAL-D can be given at 4-week intervals.
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