Effects of trazodone on EEG sleep and clinical state in major depression

Journal of Sleep Research, 2011

Trazodone is prescribed widely as a sleep aid, although it is indicated for depression, not insomnia. Its daytime cognitive and psychomotor effects have not been investigated systematically in insomniacs. The primary goal of this study was to quantify, in primary insomniacs, the hypnotic efficacy of trazodone and subsequent daytime impairments. Sixteen primary insomniacs (mean age 44 years) participated, with insomnia confirmed by overnight polysomnography (sleep efficiency £ 85%). Trazodone 50 mg was administered to participants 30 min before bedtime for 7 days in a 3-week, withinsubjects, randomized, double-blind, placebo-controlled design. Subjective effects, equilibrium (anterior ⁄ posterior body sway), short-term memory, verbal learning, simulated driving and muscle endurance were assessed the morning after days 1 and 7 of drug administration. Sleep was evaluated with overnight polysomnography and modified Multiple Sleep Latency Tests (MSLT) on days 1 and 7. Trazodone produced small but significant impairments of short-term memory, verbal learning, equilibrium and arm muscle endurance across time-points. Relative to placebo across test days, trazodone was associated with fewer night-time awakenings, minutes of Stage 1 sleep and self-reports of difficulty sleeping. On day 7 only, slow wave sleep was greater and objective measures of daytime sleepiness lower with trazodone than with placebo. Although trazodone is efficacious for sleep maintenance difficulties, its associated cognitive and motor impairments may provide a modest caveat to health-care providers.

Depression and Anxiety, 2001

Anxiety 14:19-28, 2001. a MAOIs, monoamine oxidase inhibitors; SSRIs, selective serotonin reuptake inhibitors; 5-HT, serotonin; EEG, electroencephalogram; REM, rapid eye movement; SWS, slow-wave sleep; ND, no data available. b No significant effect. c ↑, increased; ↓, decreased; ↔, no change. d ++++, great effect; +++, moderate effect; ++, small effect; +, slight effect.

Neuropsychobiology, 2003

Early human pharmaco-EEG and subsequent sleep laboratory studies identified trazodone, a 5-HT2 antagonist and 5-HT reuptake inhibitor (SARI), as an antidepressant with therapeutic effects on its target symptoms depressed mood, anxiety and insomnia. On the occasion of the introduction of a controlled-release (CR) formulation (Trittico® 150 mg retard, marketed in Austria by CSC Pharmaceuticals Handels GmbH, Vienna, Austria) in Austria in July 2000, a multi-center, open, clinical post-marketing study on the therapeutic effects, safety and target symptoms of trazodone CR in depression was carried out at 80 offices of Austrian neuropsychiatrists. 549 outpatients (63% females) of all age groups suffering from five different subtypes of depression were enrolled in the study. After a 2-week fixed dose-titration regimen up to 150 mg and a 4-week adjustment period to the optimum dose, 66% of the patients remained on 150 mg, 20% increased the dose and 11% decreased it. Only 3.7% discontinued t...

Neuro Endocrinology Letters, 2009

OBJECTIVES: Cognitive behaviour therapy (CBT) of primary insomnia is frequently combined with various pharmacological treatments, including sedative antidepressants. The present study was undertaken to evaluate the clinical efficacy of CBT, singly and combined with trazodone pharmacotherapy, for primary insomnia. DESIGN AND SETTING: Randomised, comparative clinical trial, at a single academic medical centre. METHODS: Twenty outpatients (15 women, 5 men) with chronic primary insomnia were randomly assigned to CBT or CBT +100mg trazodone and treated for 8 weeks. The treatment outcome was estimated by mean changes from baseline in self-reported clinical scales, sleep continuity data and sleep architecture parameters. RESULTS: All patients perceived significant subjective sleep improvements. Sleep latency significantly shortened (p=0.03), sleep efficiency increased (p=0.004) and the total sleep time was significantly prolonged (p=0.006) after the CBT treatment in both groups. Sleep architecture showed that the combined approach (CBT + trazodone) resulted in a significant increase in slow wave sleep duration compared to treatment by CBT only (p=0.04). CONCLUSIONS: CBT, singly and combined with the sedative antidepressant trazodone, is effective for the short-term management of chronic primary insomnia. Trazodone combined with CBT significantly increases slow wave sleep duration and this influence seems to be unrelated to its antidepressant effect.

1999

Drugs, 2005

patterns of sleep stages recorded overnight with EEG and other physiological measures. These effects are greatest and most consistent on rapid eye movement (REM) sleep, and tend to be in the opposite direction to the sleep abnormalities found in major depression, but are usually of greater degree. Reductions in the amount of REM sleep and increases in REM sleep onset latency are seen after taking antidepressants, both in healthy volunteers and in depressed patients. Antidepressants that increase serotonin function by blocking reuptake or by inhibiting metabolism have the greatest effect on REM sleep. The decrease in amount of REM sleep appears to be greatest early in treatment, and gradually diminishes during long-term treatment, except after monoamine oxidase inhibitors when REM sleep is often absent for many months. Sleep initiation and maintenance are also affected by antidepressants, but the effects are much less consistent between drugs. Some antidepressants such as clomipramine and the selective serotonin receptor inhibitors (SSRIs), particularly fluoxetine, are sleepdisturbing early in treatment and some others such as amitriptyline and the newer serotonin 5-HT2-receptor antagonists are sleep promoting. However, these effects

European Neuropsychopharmacology, 1996

Background: Sleep disturbances are common in major depressive disorder. In previous open-label trials, nefazodone improved sleep continuity and increased rapid eye movement (REM) sleep, while not affecting stage 3/4 sleep or REM latency; in contrast, fluoxetine suppressed REM sleep. This study compared the objective and subjective effects of nefazodone and fluoxetine on sleep. Methods: This paper reports combined results of three identical, multisite, randomized, double-blind, 8-week, acute-phase trials comparing nefazodone (n ϭ 64) with fluoxetine (n ϭ 61) in outpatients with nonpsychotic major depressive disorder and insomnia. Sleep electroencephalographic (EEG) recordings were gathered at baseline and weeks 2, 4, and 8. Clinical ratings were obtained at weeks 1-4, 6, and 8. Results: Nefazodone and fluoxetine were equally effective in reducing depressive symptoms; however, nefazodone differentially and progressively increased (while fluoxetine reduced) sleep efficiency and reduced (while fluoxetine increased) the number of awakenings in a linear fashion over the 8-week trial. Fluoxetine, but not nefazodone, prolonged REM latency and suppressed REM sleep. Nefazodone significantly increased total REM sleep time. Clinical evaluations of sleep quality were significantly improved with nefazodone compared with fluoxetine. Conclusions: Nefazodone and fluoxetine were equally effective antidepressants. Nefazodone was associated with normal objective, and clinician-and patient-rated assessments of sleep when compared with fluoxetine. These differential sleep EEG effects are consstent with the notion that nefazodone and fluoxetine may have somewhat different modes and spectra of action. Biol Psychiatry 1998;

Clinical Biochemistry, 2016

Objective: To preliminary investigate the link between the darkness hormone melatonin (MLT) and the pro-hypnotic effectiveness of the atypical antidepressant Trazodone (TRZ) in a group of mood disorder patients suffering of insomnia. Design and Methods: The study's design comprised: i) the enrolment of insomniac outpatients, ii) baseline (t 0) psychiatric and biochemical examinations; iii) the subsequent patients' introduction into a treatment with TRZ for 3-4 weeks, followed by post-therapy re-evaluations (t 1). The MLT function was investigated by t 0 /t 1 ELISA determinations of 6-hydroxy-MLT sulfate (6-OH-MLTs) levels in early-morning urines and HPLC analysis of morning MLT serum amount. Concomitantly, TRZ and its metabolite m-chloro-phenylpiperazine (m-CPP) were measured by HPLC in serum to monitor patients' compliance/metabolism. Results: Seventeen insomniac outpatients, displaying mild symptoms of depression/anxiety resistant to antidepressants, completed TRZ therapy (dose:10-20 mg/day, bedtime). Serum TRZ levels (127± 57 ng ml-1 , mean ± SD) confirmed patients' compliance, while the anxiogenic metabolite m-CPP resulting almost undetectable. Moreover, the 6-OH-MLTs output was found increased at t 1 vs. baseline values (t 1 : 58.4 ± 45.02 ng ml-1 ; t 0 : 28.6 ± 15.8 ng ml-1 ; mean ±SD, P < .05) in 9 patients who recovered both insomnia and depression/anxiety (P < .01). Unresponsive subjects showed instead no post-therapy 6-OH-MLTs variation (t 1 : 48.53 ± 50.70 ng ml-1 ; t 0 : 49.80 ± 66.53 ng ml-1). Morning MLT in serum slightly diminished at t 1 without reaching the statistical significance, not allowing therefore to define the patients' outcome. Conclusions: This initial investigation encourages to explore MLT networks as possible correlates of TRZ pro-hypnotic responses.

Archives of General Psychiatry, 2001

Background: The beneficial effect of antidepressant interventions has been proposed to depend on suppression of rapid eye movement (REM) sleep or inhibition of electroencephalographic (EEG) slow-wave activity (SWA) in non-REM sleep. Use of the monoamine oxidase inhibitor phenelzine sulfate can eliminate REM sleep. We studied the relation between REM sleep suppression and antidepressant response and the effect of phenelzine therapy on sleep EEG power spectra. Methods: Open-labeled prescriptions of 30 to 90 mg of phenelzine were given to 11 patients with major depressive disorder (6 men and 5 women; mean age, 41.4 years); all were physically healthy. Mood, dream recall, sleep, sleep EEG, and ocular and muscular activity during sleep were studied before treatment and during the third and fifth weeks of pharmacotherapy. Results: Six patients remitted from depression, 2 responded partially, and 3 showed no antidepressant response. Independent from clinical response, REM sleep was dramatically suppressed. On average, only 4.9 minutes of REM sleep was observed in treatment week 5, and it was completely absent in 6 patients. This effect was compensated for by increased stage 2 sleep. In non-REM sleep, EEG power was higher than at baseline between 16.25 and 25 Hz. Slow-wave activity (power within 0.75-4.5 Hz) and the exponential decline of SWA during sleep were not affected. Conclusions: Antidepressant response to phenelzine treatment does not depend on elimination of REM sleep or inhibition of SWA in non-REM sleep. In depressed patients, REM sleep is regulated independently from non-REM sleep and can be manipulated without altering the dynamics of SWA.

The British Journal of …, 2002

Background Sleep effects of antidepressants are important clinically and for elucidating mechanism of action: selective serotonin reuptake inhibitors disturb sleep and 5-HT 2 receptor-blocking compounds may enhance sleep quality. ... Aims To compare the objective and subjective effects on ...