Leeds Sleep Evaluation Questionnaire Research Articles

A randomized double-blind placebo-controlled3-way crossover study investigating psychomotor and cognitive residual effects of a new zolpidem modified-release formulation in healthy volunteers

Aims/Background To assess the residual psychomotor and cognitive effects and safety of a new zolpidem modified-release (MR) formulation 8h after a single dose. Methods A randomized, double-blind, placebo- and reference-controlled, 3-period crossover study in 18 healthy volunteers (22 to 38 years old, 10 male) comparing zolpidem MR 12.5 mg or flurazepam 30 mg to placebo. Cognitive and psychomotor tests were performed 8h postdose: Critical Flicker Fusion (CFF), Choice Reaction Time (CRT), Compensatory Tracking Time (CTT), Immediate and Delayed Word Recall (WRi, WRd), and Digit Symbol Substitution Test (DSST). Subjective sleep quality was evaluated using the Leeds Sleep Evaluation Questionnaire. Clinical laboratory parameters, vital signs, and adverse event recording evaluated safety. Results Pairwise comparisons between zolpidem MR and placebo demonstrated no significant difference in performance in CFF, CRT, WRi, WRd and DSST, 8h postdose. A significant increase in CTT time reaction was half that observed with flurazepam. Flurazepam significantly impaired performance in all tests except DSST compared to placebo. Conclusion This study demonstrates that unlike flurazepam (positive control), zolpidem MR 12.5 mg has no residual effects on CNS integrative capacity, sensorimotor or psychomotor performance, immediate and delayed memory recall except for CTT time reaction compared to placebo. Zolpidem MR is well tolerated and exhibits a comparable safety profile to placebo. Clinical Pharmacology & Therapeutics (2005) 77, P27–P27; doi: 10.1016/j.clpt.2004.11.106

Comparison of the Effects of Mirtazapine and Fluoxetine in Severely Depressed Patients

Depression is a major global problem associated with large medical, sociological and economic burdens. Mirtazapine (Remeron, Organon NV, The Netherlands) is an antidepressant with a unique mechanism of action that has similar or superior efficacy to TCAs and SSRIs in moderate-to-severe depression. However, this agent has not yet been tested in patients with severe depression alone. To compare the antidepressant efficacy and tolerability of mirtazapine and fluoxetine and their effects on anxiety and quality of life in patients with severe depression (> or = 25 points on the first 17 items of the Hamilton Depression Rating Scale [HDRS-17]). In this double-blind study, 297 severely depressed patients were randomised to receive mirtazapine 15-60 mg/day (n = 147) or fluoxetine 20-40 mg/day (n = 152) for 8 weeks. 294 subjects were actually treated and 292 included in the intent-to-treat population. Symptom severity was measured by the HDRS-17, Montgomery-Asberg Depression Rating Scale (MADRS) and Clinical Global Impression (CGI) rating scale. Quality of life was self-assessed by patients using the Leeds Sleep Evaluation Questionnaire and the Quality of Life, Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study. No statistically significant differences were noted between the two groups in change from baseline HDRS-17 score at any time point; both treatments were associated with large (approximately 15 points) decreases by study end. However, more mirtazapine-treated patients tended to exhibit a > or = 50% decrease in HDRS score (significant at day 7; 9.0% vs 0.7%, p = 0.002). Significant differences in favour of mirtazapine were also observed at day 14 for changes in MADRS scores (-10.9 vs -8.5, p = 0.006) and the proportion of patients with > or = 50% decrease in MADRS score (21.4% vs 10.9%, p = 0.031). On the CGI, the proportion of 'much/very much improved' patients tended to be greater with mirtazapine (significant at day 7; 9.7% vs 3.4%, p = 0.032). No significant between-group differences were observed for the majority of quality-of-life measures. However, mirtazapine produced significantly better improvements on 'sleeping assessment 1' (14.9 +/- 5.2 vs 13.7 +/- 5.4, p = 0.028) and 'sleeping assessment 2' (p = 0.013) than fluoxetine. Both agents were generally well tolerated but mirtazapine-treated patients experienced a mean weight gain of 0.8 +/- 2.7 kg compared with a mean decrease in weight of 0.4 +/- 2.1 kg for fluoxetine-treated patients (p < 0.001). Mirtazapine is as effective and well tolerated as fluoxetine in the treatment of patients with severe depression.

A Systematic Review of Patient-Reported Outcome Instruments Measuring Sleep Dysfunction in Adults

Sleep dysfunction can manifest in several ways, ranging from insomnia to somnolence, and from disrupted sleep to lack of restful sleep. Measuring sleep dysfunction is an area of active research and there exist a number of patient-reported outcome instruments that measure various aspects of sleep dysfunction. However, these instruments have not been evaluated systematically. We used a conceptual model of sleep that included four physical domains of general interest to patients and investigators, and cover the breadth of this disorder: sleep initiation; sleep maintenance; sleep adequacy; and somnolence. We next considered the additional health-related quality-of-life (HR-QOL) domains of psychological and social functioning, progressing along the continuum to include health perceptions and opportunity. We then conducted a literature review to identify instruments and, using criteria developed by the Medical Outcomes Trust Scientific Advisory Committee, evaluated these instruments for their potential use in measuring sleep dysfunction. Twenty-two instruments were identified. Six instruments were found to include the four physical domains defined a priori (Basic Nordic Sleep Questionnaire, Leeds Sleep Evaluation Questionnaire, Medical Outcomes Study - Sleep Problems Measures, Pittsburgh Sleep Diary, Pittsburgh Sleep Quality Index, Self-Rated Sleep Questionnaire and the Sleep Dissatisfaction Questionnaire). Several additional instruments addressed at least some of the domains and thus may be useful for specific purposes. A few instruments addressed overall HR-QOL, but did not include all four domains of interest (Functional Outcomes of Sleep Questionnaire, Quality of Life in Insomniacs and the Sleep-Wake Activity Inventory). Two instruments had undergone extensive psychometric evaluation (Medical Outcomes Study - Sleep Problems Measures and Pittsburgh Sleep Quality Index), with only the latter reporting information about interpretability. Our review indicates that measuring sleep dysfunction in adults is an area of active research and that much work still needs to be completed, specifically the study of interpretability and the application of patient preferences or item response theory. The specific research focus should dictate instrument selection.

Comparing effects of methylphenidate, sertraline and placebo on neuropsychiatric sequelae in patients with traumatic brain injury

This study aimed to investigate the effects of methylphenidate and sertraline compared with placebo on various neuropsychiatric sequelae associated with traumatic brain injury (TBI). This was a 4 week, double-blind, parallel-group trial. Thirty patients with mild to moderate degrees of TBI were randomly allocated to one of three treatment groups (n = 10 in each group) with matching age, gender and education, i.e. methylphenidate (starting at 5 mg/day and increasing to 20 mg/day in a week), sertraline (starting at 25 mg/day and increasing to 100 mg/day in a week) or placebo. At the baseline and at the 4 week endpoint, the following assessments were administered: subjective (Beck Depression Inventory) and objective (Hamilton Depression Rating Scale) measures of depression; Rivermead Postconcussion Symptoms Questionnaire for postconcussional symptoms; SmithKline Beecham Quality of Life Scale for quality of life; seven performance tests (Critical Flicker Fusion, Choice Reaction Time, Continuous Tracking, Mental Arithmetic, Short-Term memory, Digit Symbol Substitution and Mini-Mental State Examination); subjective measures of sleep (Leeds Sleep Evaluation Questionnaire) and daytime sleepiness (Epworth Sleepiness Scale). All adverse events during the study period were recorded and their relationships to the drugs were assessed. Neuropsychiatric sequelae seemed to take a natural recovery course in patients with traumatic brain injury. Methylphenidate had significant effects on depressive symptoms compared with the placebo, without hindering the natural recovery process of cognitive function. Although sertraline also had significant effects on depressive symptoms compared with the placebo, it did not improve many tests on cognitive performances. Daytime sleepiness was reduced by methylphenidate, while it was not by sertraline. Methylphenidate and sertraline had similar effects on depressive symptoms. However, methylphenidate seemed to be more beneficial in improving cognitive function and maintaining daytime alertness. Methylphenidate also offered a better tolerability than sertraline.

Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy

Purpose Melatonin, which is produced by the pineal gland at night, is an endogenous sleep regulator. Both sleep disorders and impaired melatonin production are common among the elderly. We examined the excretion of the major melatonin metabolite 6-sulfatoxymelatonin in insomnia patients aged ≥55 years and its relation with the subsequent response to melatonin therapy. Methods We studied 517 insomnia patients, along with 29 age-matched and 30 younger healthy volunteers. Nocturnal urinary 6-sulfatoxymelatonin excretion was assessed between 10 pm and 10 am. Three hundred and ninety-six of the insomnia patients were treated for 2 weeks with placebo and for 3 weeks with 2 mg per night of controlled-release melatonin, of which 372 provided complete datasets. Clinical response, assessed with the Leeds Sleep Evaluation Questionnaire, was defined as an improvement of 10 mm or more on the visual analog scales. Results Mean (± SD) 6-sulfatoxymelatonin excretion was lower in the insomnia patients (9.0 ± 8.3 μg per night) than in volunteers of the same age (18.1 ± 12.7 μg per night, P <0.05) and in younger volunteers (24.2 ± 11.9 μg per night, P <0.05). About 30% of patients (112/372) excreted ≤3.5 μg of sulfatoxymelatonin per night, which is considered to be lower than normal for this age group. These “low excretors” had a significantly higher response to melatonin replacement therapy (58% [65/112] vs. 47% [122/260], P <0.05). Conclusion Low nocturnal melatonin production is associated with insomnia in patients aged 55 years or older, and identifies patients who are somewhat more likely to respond to melatonin replacement.

Does melatonin improve sleep in older people? A randomised crossover trial

to determine whether melatonin will improve quality of sleep in healthy older people with age-related sleep maintenance problems. a double blind randomised placebo controlled crossover trial in healthy older volunteers. a largely urban population, Auckland, New Zealand. participants were part of the larger Possible Role of Melatonin in Sleep of Elders study. People 65 years or more of age were recruited through widespread advertising. We screened 414 potential participants by mail using the Pittsburgh Sleep Quality Index, and selected 194 for clinic interview. Exclusions included depression, cognitive impairment, hypnosedative medications, sleep phase abnormalities, medical and/or environmental problems that might impair sleep. Twenty normal and 20 problem sleepers were randomly allocated for this study from a larger sample of 60 normal and 60 problem sleepers. 24-hour urine 6-sulphatoxymelatonin was measured to estimate melatonin secretion in each participant. Five milligrams of melatonin, or matching placebo were each taken at bedtime for 4 weeks, separated by a 4-week washout period. Sleep quality was measured using sleep diaries, the Leeds Sleep Evaluation Questionnaire, and actigraphy. There was a significant difference between the groups in self-reported sleep quality indicators at entry, but no difference in melatonin secretion. Melatonin did not significantly improve any sleep parameter measured in either group. 5 mg of fast release melatonin taken at bedtime does not improve the quality of sleep in older people with age-related sleep maintenance problems.

Mirtazapine and paroxetine: a drug-drug interaction study in healthy subjects.

Paroxetine inhibits cytochrome P(450) 2D6, which is involved in the metabolism of mirtazapine. The possible drug-drug interaction between two pharmacologically distinct antidepressants, mirtazapine and paroxetine, has been investigated in a randomized, three-way crossover study in 24 healthy male and female subjects. After a titration phase of 3 days, each subject received single daily doses of 30 mg mirtazapine, 40 mg paroxetine or the combination for 6 days. Assessments included serial blood sampling for pharmacokinetics at steady state, cognitive testing using the test battery of CDR Ltd, a visual analogue mood rating scale (Bond and Lader) and the Leeds Sleep Evaluation Questionnaire. Paroxetine inhibits the metabolism of mirtazapine, as shown by increases of approximately 17% and 25% of the 24 h AUC's of mirtazapine and its demethyl metabolite, respectively. Mirtazapine did not alter the pharmacokinetics of paroxetine. The combined administration of mirtazapine and paroxetine probably does not alter cognitive functioning or result in major changes on the visual analogue mood rating scale and Sleep Evaluation Questionnaire, compared with the administration of either drug alone. The incidence of adverse events was lower during combined administration of mirtazapine and paroxetine than during administration of either drug alone. Fatigue, dizziness, headache, nausea, anxiety and somnolence were the most common adverse events during combined administration. These data suggest that the combination of mirtazapine and paroxetine is unlikely to lead to clinically relevant drug-drug interactions and can be used without dose adjustment of either drug. The combination may even be better tolerated than either drug alone. Copyright 2001 John Wiley & Sons, Ltd.

Clinical observation on chinese herbal medicine in treatment of long-term insomnia

Objective: To investigate the clinical efficacy of Serenity, an Australia Government listed Chinese herbal patent medicine, in the treatment of long-term insomnia.Methods: Adopting randomized double blind placebo controlled cross-over method, 19 volunteers participated were enrolled in this study for a period of 12 weeks. Each phase of the trial lasted for six weeks. No washout period was implemented. Assessment was based on the Vital Sign Test, Sleep Parameter Questionnaire, Leeds Sleep Evaluation Questionnaire and the Side Effects Questionnaire.Results: Serenity improved significantly the Overall Sleep Evaluation in the treated group, in comparing with that in the control group, P<0.01. Therapeutic effect reached the peak at the end of the fourth week of the treatment period.Conclusion: Serenity, a Chinese herbal patent medicine, is effective for the clinical management of long-term insomnia.

The impact of antidepressants on sleep and anxiety: a comparative study of fluoxetine and dothiepin using the Leeds Sleep Evaluation Questionnaire.

Fluoxetine (20 mg) was compared to dothiepin (150 mg) in a multicentre, prospective, double blind, randomised clinical trial involving 125 patients with major depression treated for an initial phase of 6 weeks and then followed up for a further 6 months. There was no difference in the efficacy of the two drugs based on the results of established rating scales (MADRS, HAM-D, BPRS). The impact of both drugs on sleep measured using the Leeds Sleep Evaluation Questionnaire showed no significant differences between treatments, however drowsiness and disturbed sleep were reported more frequently as side effects with dothiepin. Symptoms of anxiety responded equally well to both treatments. The short term and long term tolerability of dothiepin was inferior to that of fluoxetine. The place of dothiepin in treatment should be reassessed in the light of its anticholinergic adverse event profile, particularly in the elderly. Copyright 2000 John Wiley & Sons, Ltd.

Treatment of bipolar depression with topiramate

A 10-week study is reported on the safety and efficacy of fluoxetine (32 patients, 20 mg/day) and amitriptyline (33 patients, 50–100 mg/day). The subjects were aged ≧ 60 years, meeting the criteria of the American Psychiatric Association (DSM-III-R) for major depressive disorders and scoring ≧ 16 on the 17-item Hamilton rating scale for depression. After the administration of single-blind placebo for 1 week, eligible patients were randomized to a 10-week double-blind fluoxetine or amitriptyline treatment. Efficacy and adverse reactions were assessed at weeks 1, 2, 4, 7 and 10. The scores of Hamilton depression rating scale, Montgomery-Asberg depression rating scale, the Covi anxiety scale, the clinical global impressions scales, the patient global impression, the Nottingham health profile and the Leeds sleep evaluation questionnaire significantly (p < 0.001) improved in both treatment groups by the end of treatment compared to the starting values. Significant differences (p < 0.0001) were found between the two groups in the central nervous system adverse effects profile. Amitriptyline was associated more frequently to dizziness, reduced attention and confusion, and fluoxetine to headache, somnolence and asthenia. A significant increase in body weight (p = 0.002) was also observed in the amitriptyline group. A similar linear decreasing trend of adverse reactions was found int the two groups, but patients treated with amitriptyline displayed a higher persistency of the adverse reactions.

Fluoxetine and amitriptyline in elderly depressed patients. A 10-week, double-blind study on course of neurocognitive adverse events and depressive symptoms

A 10-week study is reported on the safety and efficacy of fluoxetine (32 patients, 20 mg/day) and amitriptyline (33 patients, 50–100 mg/day). The subjects were aged ≧ 60 years, meeting the criteria of the American Psychiatric Association (DSM-III-R) for major depressive disorders and scoring ≧ 16 on the 17-item Hamilton rating scale for depression. After the administration of single-blind placebo for 1 week, eligible patients were randomized to a 10-week double-blind fluoxetine or amitriptyline treatment. Efficacy and adverse reactions were assessed at weeks 1, 2, 4, 7 and 10. The scores of Hamilton depression rating scale, Montgomery-Asberg depression rating scale, the Covi anxiety scale, the clinical global impressions scales, the patient global impression, the Nottingham health profile and the Leeds sleep evaluation questionnaire significantly (p < 0.001) improved in both treatment groups by the end of treatment compared to the starting values. Significant differences (p < 0.0001) were found between the two groups in the central nervous system adverse effects profile. Amitriptyline was associated more frequently to dizziness, reduced attention and confusion, and fluoxetine to headache, somnolence and asthenia. A significant increase in body weight (p = 0.002) was also observed in the amitriptyline group. A similar linear decreasing trend of adverse reactions was found int the two groups, but patients treated with amitriptyline displayed a higher persistency of the adverse reactions.

Effects of three doses of 3-indole pyruvic acid on subjective and objective measures of sleep and early morning performance

The effects of 3-indole pyruvic acid (IPA) on sleep and morning after performance were investigated in 10 volunteers with previous complaints of mild insomnia. Three doses of IPA (100, 200 and 300 mg) were compared to placebo to assess their effect on sleep, cognitive function and psychomotor performance. The psychometric battery consisted of tests of Critical Flicker Fusion, Choice Reaction Time, Short Term Memory and Compensatory Tracking. The Leeds Sleep Evaluation Questionnaire was also administered shortly after waking the morning following medication. Results show that IPA had no significant effects on any aspect of sleep architecture. However, sleep efficiency was significantly higher on night 1 when subjects had taken 200 or 300 mg IPA compared to those who had received either placebo or 100 mg IPA. No further effects were found on subsequent nights with any of the treatments. There were no morning after effects of IPA on cognitive function or psychomotor performance. The ‘first night’ effect of sleeping in an unfamiliar environment possibly caused transient insomnia in the subjects and while this effect was not mitigated by placebo or 100 mg IPA, 200 and 300 mg IPA seem to exert sufficient hypnotic effects to overcome the sleep disturbance. These results suggest that the two higher doses of IPA exert a mild hypnotic action, perhaps by relieving the stress experienced in situations that are liable to cause transient insomnia.

Effects of single and multiple doses of a new reversible MAO‐A inhibitor, befloxatone, on psychomotor performance and memory in healthy subjects

AbstractThe effects on memory, psychomotor performance and mood of two dosage regimens of befloxatone, a new reversible and selective MAO‐A inhibitor were assessed in a randomized, double‐blind, cross‐over, placebo‐controlled study involving 12 healthy young male volunteers. Befloxatone and a placebo were orally administered as single (5 and 10 mg) and repeated doses (10 mg once daily and 5 mg twice daily) at one week wash‐out intervals. Objective tests evaluated both memory (working memory, immediate and delayed free recall of a word list, dual coding and faces recognition) and vigilance continuous performance task (CPT), and digit symbol substitution (DSST). Subjective mood and sleep were assessed using visual analogue scales and the Leeds Sleep Evaluation Questionnaire. Statistical analysis was conducted using an ANOVA with pairwise comparisons using the Student Newman Keuls procedure.Both dosage regimens of befloxatone (10 mg once daily or 5 mg twice daily) were free of any detrimental effect on vigilance (CPT) and information processing (DSST) and did not significantly disrupt short‐ and long‐term memory (working memory, free recall of words, dual coding and faces recognition). In addition, no subjective sedation or sleep disturbances were recorded.In conclusion, this study gives no evidence to suggest that befloxatone, at a daily dose which shows potent MAO‐A inhibition, has any sedative or amnestic properties likely to interfere with the activities of everyday‐life in young subjects and therefore may be safely administered in depressed outpatients.

A comparison of the psychometric effects of remoxipride with those of haloperidol, thioridazine, and lorazepam in healthy volunteers

AbstractIn this placebo and verum (lorazepam 2 mg) controlled double‐blind crossover study the acute effects of Remoxipride 50 mg and 100 mg; Haloperidol 2·5 mg; and Thioridazine 50 mg were examined in 18 healthy volunteers. CNS function was assessed using a battery of psychometric measures, viz: Critical Flicker Fusion Threshold (CFFT); Choice Reaction Time (CRT); Tracking Accuracy (RMS) and Peripheral Reaction Time (PRT); Sternberg Memory Scanning (SMS); Word Memory (WM) as well as Line Analogue Ratings of subjective sedation (LARS) and the Leeds Sleep Evaluation Questionnaire (LSEQ). Both doses of remoxipride were associated with a reduction of CFFT: 0·9 Hz for 50 mg and 1·3 Hz for 100 mg. The 100 mg dose caused an increase (impairment) in CRT total time of 38 msec. Haloperidol reduced CFFT, while thioridazine and lorazepam impaired performance on the majority of objective measures, as expected for known sedative drugs. Thioridazine led to hypotension in three subjects, and to subjective sedation (LARS), but no treatment affected responses on the LSEQ administered the morning of the day following treatment. These results show that remoxipride has some depressant effects on CNS function, but that these are less prominent than those of sedative neuroleptics such as thioridazine.

A placebo controlled double‐blind evaluation of the pharmacodynamics of fengabine vs amitriptyline following single and multiple doses in elderly volunteers.

1. The effects of fengabine were compared with those of amitriptyline in healthy elderly volunteers. Doses were administered double-blind and assessments were made before and after ingestion. 2. Psychomotor performance and cognitive ability were measured using tests of choice reaction time, tracking, critical flicker fusion threshold, memory scanning and word recognition. Subjective feelings were assessed using the Leeds sleep evaluation questionnaire (LSEQ) and line analogue rating scales (LARS). 3. Pharmacokinetic data suggest that fengabine may induce its own metabolism following repeated dosing. 4. The findings of this study show that fengabine 200 mg and 400 mg does not produce any noticeable behavioural toxicity in elderly volunteers, in contrast to amitriptyline which had a disruptive effect throughout.

The effects of moclobemide on psychomotor performance and cognitive function

Sixteen young male volunteers received single doses of moclobemide 200 mg, moclobemide 400 mg, amitriptyline 50 mg and placebo in a double-blind crossover study. Subjects then completed a test battery which is sensitive to the effects of psychoactive drugs at 1, 2, and 4 h post-dose. The test battery included tasks of choice reaction time, tracking, critical flicker fusion threshold and memory scanning. Subjective feelings were assessed using the Leeds sleep evaluation questionnaire (LSEQ) and line analogue rating scales (LARS). The results show that the positive internal control (amitriptyline) has a sedative effect in that it increased critical flicker fusion threshold, reaction time and tracking error. Moclobemide 400 mg increased reaction time in the tracking task but neither dose of moclobemide impaired psychomotor performance or cognitive ability in any of the other tests.

Double-blind study of the efficacy and safety of sertraline versus fluoxetine in major depression

An eight-week double-blind, multicentre study was performed to evaluate the efficacy and safety of sertraline vs. fluoxetine in the treatment of major depression (DSM-III-R). There were 108 out-patients, from nine Italian centres, entered into the study, of whom 88 were evaluable (48 sertraline, 40 fluoxetine). The final mean daily dose of sertraline was 72 mg and for fluoxetine it was 28 mg. Both treatment groups showed a statistically significant improvement from baseline at one week, and this was maintained until the end of treatment for all of the following measures: Hamilton Rating Scales for Depression and Anxiety, the Montgomery Asberg Depression Rating Scale, Clinical Global Impressions Scale, Zung Self-Rating Scale for Anxiety and the Leeds Sleep Evaluation Questionnaire. Although there was a numerical advantage for sertraline on several efficacy measures, there was no statistically significant difference found between the treatment groups. The incidence of adverse events was similar for both treatments; 40.4% for sertraline and 39.3% for fluoxetine. However, adverse events were generally rated by patients as of lower severity in the sertraline group. In addition, for the fluoxetine group, there was a higher incidence of agitation, anxiety and insomnia than for sertraline. Sertraline was considered to be better tolerated than fluoxetine overall, since only 9.6% of sertraline-treated patients discontinued treatment due to therapy failure whereas in the fluoxetine-treated group this figure was 19.6%. By contrast, 13.5% of sertraline-treated patients discontinued prematurely because of clinical improvement, compared with 10.7% of fluoxetine-treated patients.

The effects of acute and repeated doses of moclobemide on psychomotor performance and cognitive function in healthy elderly volunteers

AbstractThe effects of moclobemide, a new selective and reversible MAO‐A inhibitor, on cognitive function and psychomotor performance were measured in 12 healthy elderly male volunteers (with a mean age of 72.5 years). Subjects received moclobemide 200 mg, amitriptyline (positive internal control) 25 mg or placebo twice daily and were assessed on a battery of psychometric tests on the mornings following the first (acute) day and seventh (sub‐chronic) day. The tests were: Choice Reaction Time; Tracking; Critical Flicker Fusion Threshold; Memory Scanning; Continuous Attention Task; the Leeds Sleep Evaluation Questionnaire and a Visual Line Analogue Rating Scale. The results show that amitriptyline produced impairment of cognitive and psychomotor functions. Moclobemide, however, did not disrupt sleep or cause daytime sedation, and remained neutral in the assessment of behavioural toxicity.

Sleep and Paroxetine

A total of 60 patients aged 65 years and over who were suffering from unipolar depression were entered into a double-blind 6-week comparative study of paroxetine and mianserin. Assessments of efficacy of treatment included the Hamilton Depression Rating Scale, Clinical Global Impression, and the Leeds Sleep Evaluation Questionnaire. The results showed that the two drugs had equal and acceptable clinical efficacy. There was a similar overall incidence of spontaneously reported adverse events, but with clearly different profiles and a suggestion that mianserin was associated with more anticholinergic effects. In terms of sleep, the study provided evidence of a more beneficial effect from paroxetine.

A double-blind, randomized comparison of fluvoxamine with mianserin in depressive illness

The efficacy and CNS effects of the selective 5-HT re-uptake inhibitor fluvoxamine were compared with mianserin in depressed hospital out-patients in a double-blind randomized trial. Patients had to meet DSM-III criteria for Major Depressive Episode and achieve a score of at least 30 on the Montgomery-Asberg Depression Rating Scale (MADRS) after a 1-week placebo baseline period. Active treatment was for 6 weeks with an initial dose of either 100 mg fluvoxamine or 60 mg mianserin; after 1 week the dosage could be increased to 300 mg or 180 mg, respectively. Data from 63 patients (30 received fluvoxamine) were analyzed. The treatment groups were comparable with regard to age and history and severity of depression. Efficacy assessments showed similar improvements with each drug; MADRS scores improved by 65.6% with fluvoxamine and by 60.8% with mianserin. There were no significant differences between treatments at any assessment. Sedative effects were assessed using the Leeds Sleep Evaluation Questionnaire and the Digit Symbol Substitution Test. Mianserin caused a shift towards sedation in the first week in all visual analogue scales; getting to sleep and sleep quality were improved but waking was more difficult than with fluvoxamine. Similarly, the mianserin group performed less well on the Digit Symbol Substitution Test. The study confirmed that both drugs are effective treatments for depressive illness but that mianserin gives rise to sedation during the first week.