Pharmacotherapy for disordered sleep in post-traumatic stress disorder: a systematic review

Sleep disorders, such as insomnia and nightmares, are common problems in post-traumatic stress disorder (PTSD), exert a strong negative influence on the quality of life and are a great challenge for clinical psychiatry. Several studies have reported on the efficacy of drugs for the treatment of PTSD-related sleep disorders. These studies have not been systematically reviewed. This is the first review on the effectiveness of sleep medication in PTSD. We performed a Medline, EMBASE and Cochrane Library Indexed search, using the keywords: PTSD, pharmacotherapy, therapy, sleep, nightmares, insomnia and review. From this database, English-language, human subject, data driven papers published after 1980 were selected. Forty eight articles are discussed. Open-label and case studies suggest efficacy for some antidepressants, anticonvulsants and atypical antipsychotics. Only a few placebo-controlled studies have been published. They show promising results for the atypical antipsychotic olanzapine, and the alpha1-adrenoceptor antagonist prazosin. In comparison to the incidence and impact of sleep complaints in PTSD, the pharmacotherapeutic armamentarium for PTSD-related sleep complaints remains poorly investigated. Some recent studies show promising results, especially for alpha1-adrenoceptor and 5-HT2 receptor antagonists. However, randomized controlled trials with larger populations need to be conducted.     

Pharmacology for sleep disturbance in PTSD

Symptoms of sleep disturbance, particularly nightmares and insomnia, are a central feature of post‐traumatic stress disorder (PTSD). Emerging evidence suggests that specific treatment of PTSD‐related sleep disturbance improves other symptoms of the disorder, which in turn suggests that such disturbance may be fundamental to development and maintenance of the disorder. This mini‐review focuses on pharmacological treatment of sleep disturbance in adult PTSD (specifically, studies testing the efficacy of antidepressants, adrenergic inhibiting agents, antipsychotics and benzodiazepine and non‐benzodiazepine hypnotics). We conclude that only prazosin, an adrenergic inhibiting agent, has had its efficacy established by multiple randomised controlled trials. There is also high‐level evidence supporting use of eszopiclone, as well as risperidone and olanzapine as adjunct therapy. Antidepressants such as sertraline, venlafaxine and mirtazapine, benzodiazepines such as alprazolam and clonazepam and non‐benzodiazepine hypnotics such as zolpidem appear ineffective in treating PTSD‐related sleep disturbance. Most studies that report reduced frequency of nightmares and insomnia also report decreases in overall symptom severity. Such findings suggest that (i) sleep disruption is central to PTSD; (ii) treating sleep disruption may be an effective way to address other symptoms of the disorder and (iii) PTSD symptoms tend to cluster together in predictable ways. Copyright © 2016 John Wiley & Sons, Ltd.     

Treating nightmares and insomnia in posttraumatic stress disorder: a review of current evidence

Emerging evidence supports the notion of disrupted sleep as a core component of Posttraumatic Stress Disorder (PTSD). Effective treatments for nighttime PTSD symptoms are critical because sleep disruption may be mechanistically linked to development and maintenance of PTSD and is associated with significant distress, functional impairment, and poor health. This review aimed to describe the state of science with respect to the impact of the latest behavioral and pharmacological interventions on posttraumatic nightmares and insomnia. Published studies that examined evidence for therapeutic effects upon sleep were included. Some behavioral and pharmacological interventions show promise, especially for nightmares, but there is a need for controlled trials that include valid sleep measures and are designed to identify treatment mechanisms. Our ability to treat PTSD-related sleep disturbances may be improved by moving away from considering sleep symptoms in isolation and instead conducting integrative studies that examine sequential or combined behavioral and/or pharmacological treatments targeting both the daytime and nighttime aspects of PTSD. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.     

Prazosin for the treatment of posttraumatic stress disorder sleep disturbances

An estimated 70-87% of patients who suffer from posttraumatic stress disorder (PTSD) experience sleep disruption. These patients have distressing dreams or nightmares in which the traumatic event is reexperienced, and they also have difficulty in falling or staying asleep. Selective serotonin reuptake inhibitors are the treatment of choice for PTSD, but with the exception of fluvoxamine, they are often ineffective or only partially effective for sleep problems. Sedative-hypnotics may be helpful in the short term but are associated with tolerance and addiction potential. In the central nervous system, alpha(1)-adrenergic receptors are known to be important in both the startle and sleep responses. Stimulation of these receptors may contribute to PTSD-related trauma-content nightmares. Prazosin, a highly lipophilic alpha(1)-adrenergic receptor blocker that is traditionally used to treat hypertension and benign prostatic hyperplasia, has been shown to decrease the occurrence of trauma nightmares in both combat veterans and patients with non-combat-related PTSD. The available data, although mostly from open-label trials, suggest that this agent also improves sleep quality and patients' sense of wellbeing and ability to function in daily activities. The optimum dose is unknown; however, a dose-related response appears to be evident. Clinicians should monitor for orthostatic hypotension, usually seen early in therapy, when prazosin is started in patients with PTSD.     

Effects of sertraline on sleep architecture in patients with depression

Previous studies indicate that selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, fluvoxamine, citalopram and paroxetine, suppress rapid eye movement sleep, and increased nocturnal arousals. There has been no published report of the impact of sertraline on the sleep of depressed patients. This study examines such effects. Forty-seven patients with major depressive disorder, randomized to double-blind treatment with sertraline or placebo, completed sleep studies before and after 12 weeks of pharmacotherapy. Groups were compared using multivariate analyses of covariance and/or analyses of covariance to examine 4 empirically defined sets of sleep measures. Compared to the placebo-treated group, patients who received sertraline experienced an increase in delta wave sleep in the first sleep cycle and prolonged rapid eye movement (REM) sleep latency. Although, sertraline therapy decreased the average number of REM periods (from 3.86 to 2.40), the activity of both REM period 1 and REM period 2 was significantly increased. Aside from an increase in sleep latency, sertraline therapy was not associated with a worsening of measures of sleep continuity. There was also no significant difference between the groups on a measure of subjective sleepiness. These findings are both similar and different from those observed in previous studies of other SSRIs. The increase in delta sleep ratio and consolidation of REM sleep may have some other clinical implications. However, the generalizability of these findings is limited because of a number of reasons. Further studies are needed to examine the effects of SSRIs in acute treatment of depressed patients with severe insomnia, and the relationship of acute changes and relapse prevention of recurrent depression.     

Fluvoxamine. An updated review of its use in the management of adults with anxiety disorders

Fluvoxamine is a potent and selective serotonin reuptake inhibitor (SSRI) that has little or no effect on other monoamine reuptake mechanisms. Relative to other SSRIs, fluvoxamine is a weak inhibitor of cytochrome P450 (CYP) 2D6, a moderate inhibitor of CYP2C19 and CYP3A4 and a potent inhibitor of CYP1A2. In randomised, double-blind trials. fluvoxamine 100 to 300 mg/day for 6 to 10 weeks significantly reduced symptoms of obsessive-compulsive disorder (OCD) compared with placebo. Response rates of 38 to 52% have been reported with fluvoxamine, compared with response rates of 0 to 18% with placebo. In patients with OCD, fluvoxamine had similar efficacy to that of clomipramine and, in smaller trials, the SSRIs paroxetine and citalopram and was significantly more effective than desipramine. Maintenance therapy with fluvoxamine may reduce the likelihood of relapses in up to 67% of patients with OCD. Fluvoxamine < or = 300 mg/day for 6 to 8 weeks was as effective as imipramine in patients with panic disorder, and significantly more effective than placebo. In addition, treatment with fluvoxamine < or = 300 mg/day for > or = 8 weeks improved symptoms of social phobia (social anxiety disorder), post-traumatic stress disorder (PTSD), pathological gambling, compulsive buying, trichotillomania, kleptomania, body dysmorphic disorder, eating disorders and autistic disorder. Large trials comparing the efficacy of fluvoxamine and other SSRIs in patients with anxiety disorders are warranted. Fluvoxamine is generally well tolerated; in postmarketing studies, nausea was the only adverse event occurring in >10% of patients with less commonly reported events including somnolence, asthenia, headache, dry mouth and insomnia. Fluvoxamine is associated with a low risk of suicidal behaviour, sexual dysfunction and withdrawal syndrome. Fewer anticholinergic or cardiovascular events are associated with fluvoxamine than tricyclic antidepressants. Although comparative data are lacking, the tolerability profile of fluvoxamine appears to be broadly similar to those of other SSRIs. CONCLUSION: Fluvoxamine has demonstrated short term efficacy in the treatment of OCD, panic disorder, social phobia, PTSD and in a range of obsessive-compulsive spectrum disorders. The drug is as effective as clomipramine in patients with OCD but appears to have a better tolerability profile. On the basis of current treatment guidelines, fluvoxamine, like other SSRIs, is recommended as first-line treatment for a number of anxiety disorders. It appears to offer some pharmacokinetic advantages and a different drug interaction profile to the other SSRIs with a broadly similar spectrum of adverse events. However, direct comparisons are required to assess the relative efficacy and tolerability of the different agents of this drug class.     

Treatment of posttraumatic stress disorder: the impact of paroxetine

The past decade has seen remarkable advances in our ability to treat patients with posttraumatic stress disorder (PTSD). In addition, we are now much more aware of the prevalence of PTSD in civilian populations, and treatment studies now reflect the broad spectrum of patients with PTSD. Findings of studies conducted with the tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), mood stabilizers, and benzodiazepines suggest varying degrees of efficacy, with the MAOIs being particularly efficacious. However, the adverse-effect profiles of these agents, especially the TCAs and the MAOIs, limit their widespread use. The efficacy and tolerability of the selective serotonin reuptake inhibitors (SSRIs), paroxetine, sertraline, and fluoxetine, also have been demonstrated in clinical trials. Paroxetine is especially well studied in this regard, with demonstrated efficacy in men and women, in both short-term and long-term studies, and in combat veterans and civilians. Paroxetine also has been shown to improve quality of life, and to improve sleep disturbances, which can be remarkably disabling, in patients with PTSD. Emerging evidence also suggests that long-term treatment with paroxetine reverses the reductions in hippocampal volume and hypothalamic-pituitary-adrenal axis abnormalities associated with PTSD.     

Homeopathy for insomnia and sleep‐related disorders: a systematic review of randomised controlled trials

The aim of this review was the critical evaluation of evidence for the effectiveness of homeopathy for insomnia and sleep‐related disorders. A search of MEDLINE, AMED, CINAHL, EMBASE and Cochrane Central Register was conducted to find RCTs using any form of homeopathy for the treatment of insomnia or sleep‐related disorders. Data were extracted according to predefined criteria; risk of bias was assessed using Cochrane criteria. Six randomised, placebo‐controlled trials met the inclusion criteria. Two studies used individualised homeopathy, and four used standardised homeopathic treatment. All studies had significant flaws; small sample size was the most prevalent limitation. The results of one study suggested that homeopathic remedies were superior to placebo; however, five trials found no significant differences between homeopathy and placebo for any of the main outcomes. Evidence from RCTs does not show homeopathy to be an effective treatment for insomnia and sleep‐related disorders.     

Antidepressants and sleep: a qualitative review of the literature

Most antidepressants change sleep; in particular, they alter the physiological 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 sleep-disturbing early in treatment and some others such as amitriptyline and the newer serotonin 5-HT2-receptor antagonists are sleep promoting. However, these effects are fairly short-lived and there are very few significant differences between drugs after a few weeks of treatment. In general, the objectively measured sleep of depressed patients improves during 3-4 weeks of effective antidepressant treatment with most agents, as does their subjective impression of their sleep. Sleep improvement earlier in treatment may be an important clinical goal in some patients, perhaps when insomnia is particularly distressing, or to ensure compliance. In these patients, the choice of a safely used and effective antidepressant which improves sleep in short term is indicated. Patients with other sleep disorders such as restless legs syndrome and REM sleep behaviour disorder should be identified before choosing a treatment, as some antidepressants worsen these conditions. Conversely, there is evidence that some antidepressants may be useful in the treatment of sleep disorders such as night terrors.     

Disturbed sleep and its relationship to alcohol use.

STUDY OBJECTIVES: To review evidence of an association between disturbed sleep and alcohol use. DESIGN: We searched MEDLINE, PSYCHINFO, ETOH, BIBLIOSLEEP and the Rutgers Alcohol Studies databases between January 1966 and August 2002. Search terms included alcohol-related disorders or alcoholism in combination with sleep, sleep initiation and maintenance disorders, or sleep apnea syndromes. The search produced over 440 citations. We reviewed 107 relevant articles, of which 60 included quantitative measures of both alcohol use and sleep. MEASUREMENTS AND RESULTS: Behavioral studies suggest that up to 2 to 3 standard drinks before bedtime initially promotes sleep, but these effects diminish in as few as 3 days of continued use. Clinical investigations support a relationship between sleep disturbance and alcohol use, but variability in the definition and measurement of these domains and a preponderance of cross-sectional studies make uncertain the strength and direction of the association. CONCLUSIONS: The association of insomnia with alcohol use disorders suggests that the clinical evaluation of patients with sleep problems should include a careful assessment of alcohol use. Future studies of this relationship should employ prospective designs with standardized, validated measures of both sleep and alcohol use. Rigorous treatment studies for chronic insomnia in alcohol dependent patients are also needed.     

SSRIs versus non-SSRIs in post-traumatic stress disorder: an update with recommendations

Post-traumatic stress disorder (PTSD) is a highly prevalent (7.8% lifetime rate) anxiety disorder with impairment in daily functioning, frequent suicidal behaviour and high rates of co-morbidity. Fortunately, PTSD is responsive to pharmacotherapy and psychotherapy. The selective serotonin reuptake inhibitors (SSRIs) are the most studied medications for PTSD, with the largest number of double-blind, placebo-controlled trials. Of the SSRIs, sertraline, paroxetine and fluoxetine have been the most extensively studied, with sertraline and paroxetine being US FDA-approved for PTSD. These studies have demonstrated that SSRIs are effective in short-term trials (6-12 weeks). Furthermore, continuation and maintenance treatment for 6-12 months decrease relapse rates. Besides being the most studied and effective drugs for PTSD, SSRIs have a favourable adverse effect profile, making them the first-line treatment for PTSD. If SSRIs are not tolerated or are ineffective, non-SSRIs should be considered. Serotonin-potentiating non-SSRIs, such as venlafaxine, nefazodone, trazodone and mirtazapine, have been evaluated in PTSD only in open-label and case studies. Because of their promising results and relatively good safety profile, they should be considered as second-line treatment. Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs) have both been evaluated in a small number of double-blind, placebo-controlled studies. The results have been inconsistent but promising. In the limited comparative studies, MAOIs appeared superior to TCAs but patients continued to have residual symptoms. These drugs have significant adverse effects, such as cardiovascular complications, and safety issues, such as ease of overdose. Therefore, TCAs and MAOIs should be considered as third-line treatment. Anticonvulsants have been evaluated in PTSD in open-label studies and results have been positive for carbamazepine, valproic acid, topiramate and gabapentin. A small double-blind, placebo-controlled study demonstrated efficacy of lamotrigine for PTSD. Anticonvulsants should be considered where co-morbidity of bipolar disorder exists, and where impulsivity and anger predominate. Bupropion (amfebutamone), a predominantly noradrenergic reuptake inhibitor, was ineffective in PTSD in an open-label study. Benzodiazepines were ineffective in a double-blind, placebo-controlled study despite encouraging case reports. They should be avoided or used only short term because of potential depressogenic effects, and the possibility that they may promote or worsen PTSD. Buspirone, a non-benzodiazepine anxiolytic, was found to be effective in PTSD only in open-label studies. Recently, atypical antipsychotics were as effective as monotherapy and as an augmenter to SSRIs in open-label/case studies and small double-blind, placebo-controlled trials; atypical antipsychotics should be considered in PTSD where paranoia or flashbacks are prominent and in potentiating SSRIs in refractory cases.     

Pharmacological and Non-pharmacological Treatments of Sleep Disorders in Parkinson's Disease

Sleep disorders are one of the most common non-motor symptoms in Parkinson''s disease (PD). It can cause a notable decrease in quality of life and functioning in PD patients, as well as place a huge burden on both patients and caregivers. The most cited sleep disorders in PD included insomnia, restless legs syndrome (RLS), rapid eye movement (REM), sleep behavior disorders (RBD), excessive daytime sleepiness (EDS) and sleep disordered breathing (SDB), which can appear alone or several at the same time. In this review, we listed the recommended pharmacological treatments for common sleep disorders in PD, and discussed the recommended dosages, benefits and side effects of relative drugs. We also discussed non-pharmacological treatments to improve sleep quality, including sleep hygiene education, exercise, deep brain stimulation, cognitive behavior therapy and complementary therapies. We tried to find proper interventions for different types of sleep disorders in PD, while minimizing relative side effects.     

Selective serotonin reuptake inhibitors for premenstrual dysphoric disorder: the emerging gold standard?

There have been a large number of studies conducted investigating the use of selective serotonin reuptake inhibitors (SSRIs) in the treatment of patients with premenstrual dysphoric disorder (PMDD). The 12 randomised, controlled trials with continuous dose administration of SSRIs and the eight randomised, controlled trials with luteal phase dose administration (from ovulation to menses) are reviewed. All the treatment studies on fluoxetine, sertraline, paroxetine and citalopram have reported positive efficacy. Fluoxetine and sertraline have the largest literature, with a smaller number of studies endorsing paroxetine and citalopram. Mixed efficacy results have been reported with fluvoxamine. In general, adverse effects from the use of SSRIs in women with PMDD are the usual mild and transient adverse effects from SSRIs including anxiety, dizziness, insomnia, sedation, nausea and headache. Sexual dysfunction and weight gain can be problematic long-term adverse effects of SSRIs, but these effects have not been systematically evaluated with long-term SSRI use in women with PMDD. Serotonergic antidepressants have differential superiority over nonserotonergic antidepressants in the treatment of PMDD. Treatments that enhance serotonergic action improve premenstrual irritability and dysphoria with a rapid onset of action, suggesting a different mechanism of action than in the treatment of depression. It is possible that neurosteroids, such as progesterone metabolites, are involved in the rapid action of serotonergic antidepressants in PMDD. Future research needs to address less frequent dose administration regimens, such as 'symptom-onset' dose administration, and the recommended length of treatment.     

Long-term pharmacotherapy for post-traumatic stress disorder

This article reviews the literature on the long-term pharmacological treatment of post-traumatic stress disorder (PTSD). A PUBMED search was conducted; only studies on the effects of long-term (>14-weeks) pharmacological treatment for PTSD in adults or children were considered. Our search identified three randomised, double-blind, placebo-controlled studies (one each for sertraline, fluoxetine and risperidone), four open-label studies (one each for sertraline, paroxetine, nefazodone and valproate), one retrospective case series (clozapine) and one pooled analysis (sertraline). All studies involved adult populations, with the exception of the study of clozapine. The studies demonstrate that long-term treatment of PTSD with SSRIs effectively maintains the previous treatment response and improvement in quality of life, converts more patients to responder status and accounts for one-third of overall treatment gains. Greater PTSD severity predicts a longer time to response to these drugs. Discontinuation of SSRI treatment after 12 weeks results in a greater risk of relapse and symptom exacerbation compared with extended treatment. In addition to improved PTSD symptoms, extended treatment with paroxetine improves verbal declarative memory and increases hippocampal volume. Long-term treatment of PTSD with atypical antipsychotics (risperidone and clozapine), non-SSRI antidepressants (nefazodone) and antiepileptic drugs (AEDs; valproate) also appears to result in significant improvements in PTSD symptoms. In conclusion, long-term treatment of PTSD with SSRIs improves the psychiatric and clinical outcome of patients with the disorder and prevents relapse and symptom exacerbation. The effect of other agents (atypical antipsychotics, AEDs and other psychotropic medications) requires further controlled study.     

Sleep and hypnotic drugs.

In recent years the effectiveness of hypnotic drugs has had to be assessed in terms of a greatly increased knowledge of the physiology and pathology of sleep. The normal pattern of sleep and wakefulness involves a cyclic alternation between three rather than two basically dissimilar states of the brain and body - alert wakefulness, rapid-eye-movement (REM) sleep and non-rapid-eye-movement (NREM) sleep. The pattern of this alternation in individual people results from the interaction of many influences - biological (including genetic, early developmental and later degenerative influences), psychological, social and environmental factors, various physical and psychiatric disorders, and most drugs which affect the central nervous system. The quality of sleep is not related in any simple or constant manner either to its duration or to the proprotions of time spent in each stage of sleep. Among the disorders of sleep, insomnia is a far more common problem of medical management than are enuresis, narcolepsy, somnambulism or nightmares. With a few exceptions, most hypnotic drugs now in widespread use cease to be effective in treating insomnia after the first few nights. However, the ineffective treatment is often continued because insomnia will be even worse during the initial period of drug withdrawal. These factors and the toxicity of hypnotic drugs when taken in overdose make the long-term treatment of insomnia more difficult than was previously supposed. Barbiturates should no longer be prescribed. Some of the non-barbiturates, such as glutethimide and methaqualone, have no advantage over the barbiturates. The benzodiazepine hypnotics, nitrazepam and flurazepam, are less toxic in overdose and are relatively effective in treating insomnia. Chloral hydrate and its derivates are useful alternative drugs for short-term use. Measures to improve sleep without drugs deserve greater emphasis than they have had in the past.     

Cognitive and behavioral treatment options for insomnia

Insomnia is a costly disorder that affects a significant number of people. In many cases, insomnia is comorbid with other illnesses, which complicates its diagnosis and treatment. Most often it is treated with medication; however, patients are not always safe using hypnotics, and medication does not attack the source of the disorder. Cognitive behavioral therapies are better for long-term treatment because they address factors causing or perpetuating insomnia, as opposed to treatments that focus on symptoms. This article examines various nonpharmacological treatments for insomnia. In addition, because circadian rhythm disorders may exhibit symptoms similar to insomnia, there is also a brief overview of 2 common circadian rhythm disorders, delayed sleep phase syndrome and advanced sleep phase syndrome.     

Sleep changes during long-term treatment of depression with fluvoxamine – a home-based study

Rationale: The effects of antidepressants on sleep in depression have been extensively investigated, although to date there have been relatively few studies of newer drug classes such as specific serotonin reuptake inhibitors (SSRIs). All reported studies on SSRIs have been conducted in patients admitted to sleep laboratories and very few longitudinal studies have continued to measure sleep beyond 5 weeks of treatment. The growing trend towards outpatient and community care has highlighted the need for studies of sleep in depression in a more naturalistic setting, and during longer periods of treatment in line with recommended clinical practice. Objectives: To establish if the changes in sleep architecture and continuity described during early treatment with SSRIs persist after 3 months, to relate these changes to clinical state, and to establish whether home recordings would yield similar results to previous laboratory studies. Methods: We have recorded objective sleep parameters in 12 depressed patients before and during 12-week treatment with an SSRI, fluvoxamine. All the sleep recordings were performed in the patients’ own homes, using the Oxford Medilog system. Results: At 12 weeks, 7/12 patients had responded (HAM-D decreased by >50%). REM latency showed the expected increase early in treatment; this change was less obvious at weeks 3 and 12. Amount of REM sleep was decreased at day 2 and week 3, but returned to baseline by week 12. Slow wave sleep was slightly increased at day 2 and decreased at week 12. Of the sleep continuity measures, the only significant change was in sleep onset latency, which was increased at week 3; the other measures showed non- significant worsening at night 2 and week 3, but most were better than baseline by 12 weeks. Subjective sleep (the three sleep items on the HAM-D) showed a progressive improvement over time, especially in the responders. Conclusions: The effects of the SSRI fluvoxamine on objective sleep measures are in the direction predicted by its pharmacological actions and some persist for at least 12 weeks. In addition subjective appraisal of sleep is strongly affected by mood state. All patients found the home recording procedure acceptable and only minimally disruptive. Received: 5 July 1999 / Final version: 22 November 1999     

Antidepressants and their effect on sleep

Given the relationship between sleep and depression, there is inevitably going to be an effect of antidepressants on sleep. Current evidence suggests that this effect depends on the class of antidepressant used and the dosage. The extent of variation between the effects of antidepressants and sleep may relate to their mechanism of action. This systematic review examines randomised-controlled trials (RCTs) that have reported the effect that antidepressants appear to have on sleep. RCTs are not restricted to depressed populations, since several studies provide useful information about the effects on sleep in other groups. Nevertheless, the distinction is made between those studies because the participant's health may influence the baseline sleep profiles and the effect of the antidepressant. Insomnia is often seen with monoamine oxidase inhibitors (MAOIs), with all tricyclic antidepressants (TCAs) except amitriptyline, and all selective serotonin reuptake inhibitors (SSRIs) with venlafaxine and moclobemide as well. Sedation has been reported with all TCAs except desipramine, with mirtazapine and nefazodone, the TCA-related maprotiline, trazodone and mianserin, and with all MAOIs. REM sleep suppression has been observed with all TCAs except trimipramine, but especially clomipramine, with all MAOIs and SSRIs and with venlafaxine, trazodone and bupropion. However, the effect on sleep varies between compounds within antidepressant classes, differences relating to the amount of sedative or alerting (insomnia) effects, changes to baseline sleep parameters, differences relating to REM sleep, and the degree of sleep-related side effects.