Treatments of Sexual Dysfunction in Opioid Substitution Therapy Patients: A Systematic Review and Meta-Analysis.

Sexual dysfunction is a common condition in the opioid substitution therapy (OST) population. We aimed to determine the efficacy and safety of treatment for sexual dysfunction in the OST population. We searched for interventional studies from Medline, PubMed, and Scopus. Three independent authors conducted a risk-of-bias assessment (RoB 2). A total of seven studies (five randomized-controlled trials, two quasi-experimental), including 473 patients with sexual dysfunction, were identified. Among these, three bupropion (n=207), one trazodone (n=75), two rosa Damascena (n=100), and one ginseng (n=91) studies had reported significantly improve various sexual functioning domains in both genders. In a meta-analysis, bupropion significantly increased male sexual function with standardized mean difference of 0.53; 95% confidence interval of 0.19-0.88; P < 0.01; I2=0. The adverse effects were minor for all agents, and no significant difference between treatment and placebo groups in randomized-controlled trials. These agents have a promising future as therapy for sexual dysfunction in the OST population. However, given the limited sample size and number of studies, further studies should be conducted to confirm the use of these agents.

Pharmacotherapies for sleep disturbances in dementia.

BACKGROUND: Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia, and are associated with significant carer distress, increased healthcare costs, and institutionalisation. Although non-drug interventions are recommended as the first-line approach to managing these problems, drug treatment is often sought and used. However, there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this clinically vulnerable population. OBJECTIVES: To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with dementia. SEARCH METHODS: We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, on 19 February 2020, using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence, rest-activity, and sundowning. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared a drug with placebo, and that had the primary aim of improving sleep in people with dementia who had an identified sleep disturbance at baseline. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on study design, risk of bias, and results. We used the mean difference (MD) or risk ratio (RR) with 95% confidence intervals (CI) as the measures of treatment effect, and where possible, synthesised results using a fixed-effect model. Key outcomes to be included in our summary tables were chosen with the help of a panel of carers. We used GRADE methods to rate the certainty of the evidence. MAIN RESULTS: We found nine eligible RCTs investigating: melatonin (5 studies, n = 222, five studies, but only two yielded data on our primary sleep outcomes suitable for meta-analysis), the sedative antidepressant trazodone (1 study, n = 30), the melatonin-receptor agonist ramelteon (1 study, n = 74, no peer-reviewed publication), and the orexin antagonists suvorexant and lemborexant (2 studies, n = 323). Participants in the trazodone study and most participants in the melatonin studies had moderate-to-severe dementia due to Alzheimer's disease (AD); those in the ramelteon study and the orexin antagonist studies had mild-to-moderate AD. Participants had a variety of common sleep problems at baseline. Primary sleep outcomes were measured using actigraphy or polysomnography. In one study, melatonin treatment was combined with light therapy. Only four studies systematically assessed adverse effects. Overall, we considered the studies to be at low or unclear risk of bias. We found low-certainty evidence that melatonin doses up to 10 mg may have little or no effect on any major sleep outcome over eight to 10 weeks in people with AD and sleep disturbances. We could synthesise data for two of our primary sleep outcomes: total nocturnal sleep time (TNST) (MD 10.68 minutes, 95% CI -16.22 to 37.59; 2 studies, n = 184), and the ratio of day-time to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03; 2 studies; n = 184). From single studies, we found no evidence of an effect of melatonin on sleep efficiency, time awake after sleep onset, number of night-time awakenings, or mean duration of sleep bouts. There were no serious adverse effects of melatonin reported. We found low-certainty evidence that trazodone 50 mg for two weeks may improve TNST (MD 42.46 minutes, 95% CI 0.9 to 84.0; 1 study, n = 30), and sleep efficiency (MD 8.53%, 95% CI 1.9 to 15.1; 1 study, n = 30) in people with moderate-to-severe AD. The effect on time awake after sleep onset was uncertain due to very serious imprecision (MD -20.41 minutes, 95% CI -60.4 to 19.6; 1 study, n = 30). There may be little or no effect on number of night-time awakenings (MD -3.71, 95% CI -8.2 to 0.8; 1 study, n = 30) or time asleep in the day (MD 5.12 minutes, 95% CI -28.2 to 38.4). There were no serious adverse effects of trazodone reported. The small (n = 74), phase 2 trial investigating ramelteon 8 mg was reported only in summary form on the sponsor's website. We considered the certainty of the evidence to be low. There was no evidence of any important effect of ramelteon on any nocturnal sleep outcomes. There were no serious adverse effects. We found moderate-certainty evidence that an orexin antagonist taken for four weeks by people with mild-to-moderate AD probably increases TNST (MD 28.2 minutes, 95% CI 11.1 to 45.3; 1 study, n = 274) and decreases time awake after sleep onset (MD -15.7 minutes, 95% CI -28.1 to -3.3: 1 study, n = 274) but has little or no effect on number of awakenings (MD 0.0, 95% CI -0.5 to 0.5; 1 study, n = 274). It may be associated with a small increase in sleep efficiency (MD 4.26%, 95% CI 1.26 to 7.26; 2 studies, n = 312), has no clear effect on sleep latency (MD -12.1 minutes, 95% CI -25.9 to 1.7; 1 study, n = 274), and may have little or no effect on the mean duration of sleep bouts (MD -2.42 minutes, 95% CI -5.53 to 0.7; 1 study, n = 38). Adverse events were probably no more common among participants taking orexin antagonists than those taking placebo (RR 1.29, 95% CI 0.83 to 1.99; 2 studies, n = 323). AUTHORS' CONCLUSIONS: We discovered a distinct lack of evidence to guide decisions about drug treatment of sleep problems in dementia. In particular, we found no RCTs of many widely prescribed drugs, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks for these common treatments. We found no evidence for beneficial effects of melatonin (up to 10 mg) or a melatonin receptor agonist. There was evidence of some beneficial effects on sleep outcomes from trazodone and orexin antagonists and no evidence of harmful effects in these small trials, although larger trials in a broader range of participants are needed to allow more definitive conclusions to be reached. Systematic assessment of adverse effects in future trials is essential.

Interventions to reduce bruxism in children and adolescents: a systematic scoping review and critical reflection.

The aim of the present study was to perform a critical reflection about intervention options for bruxism reduction in children and adolescents. Search was conducted based on the PICO-structured question: "What are the intervention options to reduce bruxism in children/adolescents?". No language, year, or study design restrictions were imposed. Studies reporting interventions to reduce bruxism in children (< 10) and adolescents (10 to 19 years old) were included. Reviews and letters to editors were not included. From 2723 records, 17 papers were included. Included studies were primarily randomized clinical trials performed in Brazil (35.3%) and using different criteria for the diagnosis of bruxism. Reduction in self-reported bruxism and headaches associated with bruxism were observed in studies that used medications (hydroxyzine/trazodone/flurazepam), occlusal splints, orthodontic interventions, and psychological and physical therapy interventions. Reduction in Rhythmic Masticatory Muscle Activity was observed with the use of the occlusal splint and in orthodontic interventions. Alternative treatments (medicinal extracts such as Melissa officinalis-L) have shown inconclusive results.Conclusions: Several intervention options are available to inhibit or reduce bruxism activity. The respective indication, contraindications, and side effects of each treatment option must be assessed individually and carefully, taking into account that bruxism is not considered a disorder in otherwise healthy individuals.What is known• Biological and psychological factors have been strongly correlated to the development of bruxism• Bruxism prevalence ranging from 6 to 50% in childrenWhat is new• Reduction in self-reported bruxism and headaches associated with bruxism were observed in studies that used medication (Hydroxyzine/ Trazodone/ Flurazepam), occlusal splints, orthodontic interventions, psychological, and physical therapy interventions• A reduction in Rhythmic Masticatory Muscle Activity was observed with the use of the occlusal splint and orthodontic interventions. Alternative treatments (medicinal extracts such as Melissa officinalis L) show inconclusive results in respect of the reduction in bruxism.

Efficacy of trazodone for treating paroxysmal sympathetic hyperactivity presenting after thalamic hemorrhage: A case report.

Paroxysmal sympathetic hyperactivity (PSH) is a clinical condition characterized by abnormal paroxysmal surges in sympathetic nervous system activity. PSH is known to occur after severe head injury and hypoxic encephalopathy. Cases of PSH that develop after stroke have been reported worldwide; however, PSH is not commonly reported in the field of stroke research in Japan. Some studies have suggested that gabapentin may improve the symptoms of PSH. To our knowledge, this is the first case report demonstrating the efficacy of trazodone for the treatment of PSH that developed after thalamic hemorrhage. A 45-year-old woman presented to our clinic with headache and paralysis of the left side of her body after experiencing right thalamic hemorrhage; a conservative treatment was initiated at our hospital. Immediately upon hospitalization, she developed high fever, tachycardia, tachypnea, constipation, and overactive bladder and had breathing difficulties. Blood sampling revealed elevated levels of myocardial escape enzymes; however, coronary angiography did not show any significant stenosis or occlusion. The patient's symptoms improved after the administration of trazodone. She was diagnosed with catecholamine cardiomyopathy associated with PSH after intracranial hemorrhage and was subsequently transferred to a recovery and rehabilitation hospital unit where the oral administration of trazodone continued. Prolonged PSH contributes significantly to the impairment of daily activities in patients with stroke; therefore, early diagnosis and treatment are critical. Here, we report on the efficacy of trazodone as an effective treatment option for improving clinical outcomes and reducing the stay in the stroke care unit.

Pharmacotherapies for sleep disturbances in dementia.

BACKGROUND: Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering, and daytime sleepiness are common clinical problems in dementia, and are associated with significant caregiver distress, increased healthcare costs, and institutionalisation. Drug treatment is often sought to alleviate these problems, but there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this vulnerable population. OBJECTIVES: To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with dementia, through identification and analysis of all relevant randomised controlled trials (RCTs). SEARCH METHODS: We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, in March 2013 and again in March 2016, using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence, rest-activity, sundowning. SELECTION CRITERIA: We included RCTs that compared a drug with placebo, and that had the primary aim of improving sleep in people with dementia who had an identified sleep disturbance at baseline. Trials could also include non-pharmacological interventions, as long as both drug and placebo groups had the same exposure to them. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data on study design, risk of bias, and results from the included study reports. We obtained additional information from study authors where necessary. We used the mean difference as the measure of treatment effect, and where possible, synthesized results using a fixed-effect model. MAIN RESULTS: We found six RCTs eligible for inclusion for three drugs: melatonin (222 participants, four studies, but only two yielded data on our primary sleep outcomes suitable for meta-analysis), trazodone (30 participants, one study), and ramelteon (74 participants, one study, no peer-reviewed publication, limited information available).The participants in the trazodone study and almost all participants in the melatonin studies had moderate-to-severe dementia due to Alzheimer's disease (AD); those in the ramelteon study had mild-to-moderate AD. Participants had a variety of common sleep problems at baseline. All primary sleep outcomes were measured using actigraphy. In one study of melatonin, drug treatment was combined with morning bright light therapy. Only two studies made a systematic assessment of adverse effects. Overall, the evidence was at low risk of bias, although there were areas of incomplete reporting, some problems with participant attrition, related largely to poor tolerance of actigraphy and technical difficulties, and a high risk of selective reporting in one trial that contributed very few participants. The risk of bias in the ramelteon study was unclear due to incomplete reporting.We found no evidence that melatonin, at doses up to 10 mg, improved any major sleep outcome over 8 to 10 weeks in patients with AD who were identified as having a sleep disturbance. We were able to synthesize data for two of our primary sleep outcomes: total nocturnal sleep time (mean difference (MD) 10.68 minutes, 95% CI -16.22 to 37.59; N = 184; two studies), and the ratio of daytime sleep to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03; N = 184; two studies). From single studies, we found no difference between melatonin and placebo groups for sleep efficiency, time awake after sleep onset, or number of night-time awakenings. From two studies, we found no effect of melatonin on cognition or performance of activities of daily living (ADL). No serious adverse effects of melatonin were reported in the included studies. We considered this evidence to be of low quality.There was low-quality evidence that trazodone 50 mg given at night for two weeks improved total nocturnal sleep time (MD 42.46 minutes, 95% CI 0.9 to 84.0; N = 30; one study), and sleep efficiency (MD 8.53%, 95% CI 1.9 to 15.1; N = 30; one study) in patients with moderate-to-severe AD, but it did not affect the amount of time spent awake after sleep onset (MD -20.41, 95% CI -60.4 to 19.6; N = 30; one study), or the number of nocturnal awakenings (MD -3.71, 95% CI -8.2 to 0.8; N = 30; one study). No effect was seen on daytime sleep, cognition, or ADL. No serious adverse effects of trazodone were reported.Results from a phase 2 trial investigating ramelteon 8 mg administered at night were available in summary form in a sponsor's synopsis. Because the data were from a single, small study and reporting was incomplete, we considered this evidence to be of low quality in general terms. Ramelteon had no effect on total nocturnal sleep time at one week (primary outcome) or eight weeks (end of treatment) in patients with mild-to-moderate AD. The synopsis reported few significant differences from placebo for any sleep, behavioural, or cognitive outcomes; none were likely to be of clinical significance. There were no serious adverse effects from ramelteon. AUTHORS' CONCLUSIONS: We discovered a distinct lack of evidence to help guide drug treatment of sleep problems in dementia. In particular, we found no RCTs of many drugs that are widely prescribed for sleep problems in dementia, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks associated with these common treatments. From the studies we identified for this review, we found no evidence that melatonin (up to 10mg) helped sleep problems in patients with moderate to severe dementia due to AD. There was some evidence to support the use of a low dose (50 mg) of trazodone, although a larger trial is needed to allow a more definitive conclusion to be reached on the balance of risks and benefits. There was no evidence of any effect of ramelteon on sleep in patients with mild to moderate dementia due to AD. This is an area with a high need for pragmatic trials, particularly of those drugs that are in common clinical use for sleep problems in dementia. Systematic assessment of adverse effects is essential.

Diagnostic conundrum: lessons from the man who accidently set fire to his home.

A 62-year-old man presented to psychiatric services with a 3-month history of a range of symptoms which included obsessional thoughts, self-neglect, lack of mental flexibility, reduced ability to plan, organise and follow instructions, reduced capacity to empathise and disinhibition. He also accidently set fire to his house. Overall these findings are compatible with a dysexecutive syndrome. This man has a significant history of polysubstance misuse and chronic hepatitis C infection. Neuroimaging revealed an acquired traumatic brain injury which could account for his dysexecutive syndrome. The patient was managed in a holistic manner. A community psychiatric nurse was allocated, he had social services input and he was started on trazodone. He is currently housed in short-term housing and is awaiting a long-term residential placement.

Outpatient treatment of sleep disorders in Alzheimer patients / Tratamento ambulatorial dos transtornos do sono em pacientes com doença de Alzheimer

Sleep disorders are common in patients with Alzheimer dementia and affect the quality of life of patients and of their caregivers. Despite the rising number of studies in the area, almost all of them are about non-pharmacological treatment. Our objective was to review the literature concerning pharmacological and non-pharmacological approaches to treat sleep disorders of elderly patients with Alzheimer dementia in the ambulatory setting. The treatments revised consisted of sleep hygiene and/or use of intense light coupled or not with use of melatonin, cholinesterase inhibitors, antipsychotics, hypnotics or antidepressants. In addition to the non-pharmacological measures, there is evidence that the use of trazodone may aid the treatment of sleep disorders of older individuals with Alzheimer dementia. More studies are necessary to examine the non-pharmacological and pharmacological treatments revised herein.

Os transtornos do sono são comuns nos pacientes com doença de Alzheimer e interferem na qualidade de vida do paciente e de seu cuidador. Apesar da alta prevalência desses transtornos, existe pouca evidência em relação ao seu tratamento. Nosso objetivo foi revisar a literatura em relação ao tratamento não farmacológico e farmacológico dos transtornos do sono nos idosos com doença de Alzheimer em comunidade. Os tratamentos incluídos consistiram na higiene do sono e/ou no uso da luz intensa, combinados ou não com o uso da melatonina, nos inibidores de acetilcolinesterases, antipsicóticos, hipnóticos ou antidepressivos. Para além das medidas não farmacológicas, há evidência de que o uso da trazodona é efetivo no tratamento dos transtornos do sono de pacientes com doença de Alzheimer. Mais estudos sobre as estratégias farmacológicas e não farmacológicas aqui revisadas ou outras são desejáveis.

Outpatient treatment of sleep disorders in Alzheimer patients.

Sleep disorders are common in patients with Alzheimer dementia and affect the quality of life of patients and of their caregivers. Despite the rising number of studies in the area, almost all of them are about non-pharmacological treatment. Our objective was to review the literature concerning pharmacological and non-pharmacological approaches to treat sleep disorders of elderly patients with Alzheimer dementia in the ambulatory setting. The treatments revised consisted of sleep hygiene and/or use of intense light coupled or not with use of melatonin, cholinesterase inhibitors, antipsychotics, hypnotics or antidepressants. In addition to the non-pharmacological measures, there is evidence that the use of trazodone may aid the treatment of sleep disorders of older individuals with Alzheimer dementia. More studies are necessary to examine the non-pharmacological and pharmacological treatments revised herein.

Treatment of Sleep Disturbances in Post-Traumatic Stress Disorder: A Review of the Literature.

Sleep disturbances are among the most commonly endorsed symptoms of post-traumatic stress disorder (PTSD). Treatment modalities that are effective for the waking symptoms of PTSD may have limited efficacy for post-traumatic sleep problems. The aim of this review is to summarize the evidence for empirically supported and/or utilized psychotherapeutic and pharmacological treatments for post-traumatic nightmares and insomnia. While there are few controlled studies of the applicability of general sleep-focused interventions to the management of the sleep disturbances in PTSD, evidence is growing to support several psychotherapeutic and pharmacological treatments. Future investigations should include trials that combine treatments focused on sleep with treatments effective in managing the waking symptoms of PTSD.

Subjective hypnotic efficacy of Trazodone and Mirtazapine in patients with chronic insomnia: a retrospective, comparative study.

OBJECTIVE: To compare the efficacy of two sedating antidepressants, trazodone and mirtazapine, for the treatment of chronic insomnia. DESIGN: Retrospective cross-sectional study. Patients received trazodone or mirtazapine for at least three months at the dosage that was effective in the titration period. MATERIAL AND METHODS: 150 patients with chronic insomnia, referred to the Sleep Disorder Center of Bari, diagnosed as chronic insomniacs according to ICSD-3 diagnostic criteria, with or without dysthymic disorder according to DSM V diagnostic criteria, and treated with trazodone or mirtazapine were retrospectively chart-reviewed. 79 patients satisfying inclusion criteria were enrolled: 33 had been treated with trazodone (12 males and 21 females aged 36 to 77 years, mean age 63.57+10.38 years; 18 with psychophysiological insomnia and 15 with insomnia associated with dysthymic disorder) and 46 with mirtazapine (26 males and 20 females aged 25 to 86 years, mean age 60.04+16.67 years; 25 with psychophysiological insomnia and 21 with insomnia comorbid with dysthymic disorder). The patients were considered responsive to the treatment when they no longer met the criteria for insomnia at the end of the maintenance period. RESULTS: Both drugs were efficacious in more than 60% without any difference in the proportion of responders between the two medication groups (87.87% in the trazodone group versus 86.95% in the mirtazapine group; p=0.26 and regardless of sex, age and possible association of insomnia with depression). The minimum dosages used for both drugs (25 mg for trazodone and 7.5 mg for mirtazapine) corresponded to the highest percentage of responders in the groups treated successfully with either trazodone (37.93%) or mirtazapine (52.5%). For each medication group, subgroup analysis revealed higher statistically significant rates of responders in patients with lower final dosage (25 to 75 mg for trazodone and 7.5 to 15 mg for mirtazapine) than in those with higher final dosage (100 to 150 mg for trazodone and 15 to 30 mg for mirtazapine) (100% versus 42.85%; p<0.001 in the trazodone group and 100% versus 53.84%; p<0.001 in mirtazapine group) Conclusion. On a long term basis trazodone administration appeared as effective and well tolerated as mirtazapine in the treatment of chronic insomnia regardless of its association with dysthymia. Both medications resulted efficacious at very low doses and had a sustained efficacy, likely without problems of tolerance.

Pharmacotherapies for sleep disturbances in Alzheimer's disease.

BACKGROUND: Sleep disturbances, including reduced nocturnal sleep time, sleep fragmentation, nocturnal wandering and daytime sleepiness are common clinical problems in dementia due to Alzheimer's disease (AD), and are associated with significant caregiver distress, increased healthcare costs and institutionalisation. Drug treatment is often sought to alleviate these problems, but there is significant uncertainty about the efficacy and adverse effects of the various hypnotic drugs in this vulnerable population. OBJECTIVES: To assess the effects, including common adverse effects, of any drug treatment versus placebo for sleep disorders in people with Alzheimer's disease through identification and analysis of all relevant randomized controlled trials (RCTs). SEARCH METHODS: We searched ALOIS (www.medicine.ox.ac.uk/alois), the Cochrane Dementia and Cognitive Improvement Group's Specialized Register, on 31 March 2013 using the terms: sleep, insomnia, circadian, hypersomnia, parasomnia, somnolence, "rest-activity", sundowning. SELECTION CRITERIA: We included RCTs that compared a drug with placebo and that had the primary aim of improving sleep in people with Alzheimer's disease who had an identified sleep disturbance at baseline. Trials could also include non-pharmacological interventions as long as both drug and placebo groups had the same exposure to them. DATA COLLECTION AND ANALYSIS: Two authors working independently extracted data on study design, risk of bias and results from the included study reports. Additional information was obtained from study authors where necessary. We used the mean difference as the measure of treatment effect and, where possible, synthesized results using a fixed-effect model. MAIN RESULTS: We found RCTs eligible for inclusion for three drugs: melatonin (209 participants, three studies, but only two yielded data suitable for meta-analysis), trazodone (30 participants, one study) and ramelteon (74 participants, one study, no peer-reviewed publication, very limited information available).The melatonin and trazodone studies were of people with moderate-to-severe AD; the ramelteon study was of people with mild-to-moderate AD. In all studies participants had a variety of common sleep problems. All primary sleep outcomes were measured using actigraphy. In one study of melatonin, drug treatment was combined with morning bright light therapy. Only two studies made a systematic assessment of adverse effects. Overall, the published studies were at low risk of bias, although there were areas of incomplete reporting and some problems with participant attrition, related largely to poor tolerance of actigraphy and technical difficulties. The risk of bias in the ramelteon study was unclear due to incomplete reporting.We found no evidence that melatonin, either immediate- or slow-release, improved any major sleep outcome in patients with AD. We were able to synthesize data for two sleep outcomes: total nocturnal sleep time (MD 10.68 minutes, 95% CI -16.22 to 37.59, two studies), and the ratio of daytime sleep to night-time sleep (MD -0.13, 95% CI -0.29 to 0.03, two studies). Other outcomes were reported in single studies. We found no difference between intervention and control groups for sleep efficiency, time awake after sleep onset or number of night-time awakenings, nor in cognition or performance of activities of daily living (ADLs). No serious adverse effects of melatonin were reported in the included studies.Trazodone 50 mg administered at night for two weeks significantly improved total nocturnal sleep time (MD 42.46 minutes, 95% CI 0.9 to 84.0, one study) and sleep efficiency (MD 8.53, 95% CI 1.9 to 15.1, one study), but there was no clear evidence of any effect on the amount of time spent awake after sleep onset (MD -20.41, 95% CI -60.4 to 19.6, one study) or the number of nocturnal awakenings (MD -3.71, 95% CI -8.2 to 0.8, one study). No effect was seen on daytime sleep, nor on cognition or ADLs. No serious adverse effects were reported.Results from a phase 2 trial investigating ramelteon 8 mg administered at night were available in summary form in a sponsor's synopsis. Ramelteon had no effect on total nocturnal sleep time at one week (primary outcome) or eight weeks (end of treatment). The synopsis reported few significant differences from placebo for any sleep, behavioural or cognitive outcomes; none were likely to be of clinical significance. There were no serious adverse effects of ramelteon. AUTHORS' CONCLUSIONS: We discovered a distinct lack of evidence to help guide drug treatment of sleep problems in AD. In particular, we found no RCTs of many drugs that are widely prescribed for sleep problems in AD, including the benzodiazepine and non-benzodiazepine hypnotics, although there is considerable uncertainty about the balance of benefits and risks associated with these common treatments. From the studies we identified for this review, we found no evidence that melatonin is beneficial to AD patients with moderate to severe dementia and sleep problems. There is some evidence to support the use of a low dose (50 mg) of trazodone, although a larger trial is needed to allow a more definitive conclusion to be reached on the balance of risks and benefits. There was no evidence of any effect of ramelteon on sleep in patients with mild to moderate dementia due to AD. This is an area with a high need for pragmatic trials, particularly of those drugs that are in common clinical use for sleep problems in AD. Systematic assessment of adverse effects is essential.

[Yimusake alone or combined with trazodone hydrochloride for primary premature ejaculation].

OBJECTIVE: To study the clinical effects of the Chinese drug Yimusake, used alone or in combination with trazodone hydrochloride, on primary premature ejaculation (PE). METHODS: Sixty-eight primary PE patients were randomized to a control (n=32) and an experimental group (n=36), the former treated with Yimusake 1 tablet (50 mg) pre day, and the latter with 1 tablet of trazodone hydrochloride (50 mg) pre day in addition, both given orally after supper and for 4 weeks, followed by observation of the therapeutic effects. RESULTS: Eighteen cases (56.25%) responded in the control and 25 (69.44% ) in the experimental group, with statistically significant difference between the two groups (P<0.05). CONCLUSION: Yimusake combined with trazodone hydrochloride is highly efficacious for primary PE.

[Effect of acupuncture treatment of relieving depression and regulating mind on insomnia accompanied with depressive disorders].

OBJECTIVE: To compare the therapeutic effects of insomnia accompanied with depressive disorders treated by acupuncture of relieving depression and regulating mind and oral administration of Trazodone. METHODS: Sixty-five cases were randomly divided into a acupuncture group (33 cases) and western medication group (32 cases). In acupuncture group, Shenmen (HT 7), Baihui (CV 20), Hegu (LI 4) and Taichong (LR 3) were selected. In western medication group, Trazodone was applied with oral administration for 4 weeks. The curative effect comparison was carried on by Pittsburgh Sleep Quality Index (PSQI), Self-Rating Depression Scale (SDS), and Side Effect Rating Scale (SERS) of Asberg. RESULTS: The cured and markedly effective rate of 72.7% (24/33)in acupuncture group was superior to that of 46.8% (15/32) in western medication group; after treatment, the scores of all items and the total cumulative scores of PSQI and SDS of both groups were reduced (P < 0.01, P < 0.05), of which, the sleep quality and daytime function evaluation in acupuncture group reduced more obviously than those in western medication group (both P < 0.05); the SERS scores of Asberg in western medication group were higher than those in acupuncture group. CONCLUSION: Acupuncture treatment of relieving depression and regulating mind is superior to Trazodone with oral administration for sleep quality and daytime function, with milder adverse reactions.

Síndrome de ardor bucal: actualización diagnóstica y terapéutica / Burning mouth syndrome: diagnostic and therapeutic actualisation

El síndrome de boca ardiente (SBA) es una entidad patológica caracterizada por la presencia de síntomas crónicos de ardor o dolor en la mucosa bucal clínicamente normal. El SBA afecta principalmente a mujeres peri y posmenopáusicas. Su causa es desconocida, pero su relación con una compleja asociación de factores biológicos y psicológicos hace suponer una etiología multifactorial. Aunque se han encontrado tratamientos eficaces en casos particulares, se sigue buscando un tratamiento que resulte eficaz en la mayoría de los casos. Esta revisión hace especial referencia a los factores etiológicos y al tratamiento del síndrome (AU)

The burning mouth syndrome (BMS) is characterized by the presence of chronic symptoms of burning or paining clinically normal oral mucosa. This syndrome primarily affects peri and postmenopausal women. The cause is unknown, but the relationship between the BMS and a complex association of biological and psychological factors suggest a multifactorial etiology. Although some treatments have been found effective in particular cases, the clinical searchers are still looking for a treatment that can be effective in most cases. This review makes particular reference to the etiological factors and the treatment of the síndrome (AU)

Extremely prolonged INR associated with warfarin in combination with both trazodone and omega-3 fatty acids.

We report the case of a 65-year-old Caucasian male who had been taking warfarin for 6 months after an episode of postoperative pulmonary thromboembolism (PTE). His medical history was otherwise insignificant. He received a prescription of trazodone and fish oil for not-very-well defined complaints. Two weeks after taking these medications, when he routinely checked his international normalized ratio (INR), he arrived at the Emergency Department (ED) with a test result showing an INR of 8.06. He was admitted for observation and all medications were discontinued. His INR returned to normal within 2 days. He was then restarted on his previous warfarin dose, while other drugs were not restarted. Two weeks later, his coagulation profile was within the desired therapeutic range. Coadministration of warfarin with omega-3 fatty acids can lead to additional anticoagulation. This can result from changes either in platelet aggregation or vitamin K-dependent coagulation factors. Trazodone also has interactions with warfarin through not well-understood mechanisms. Although drug interaction reference texts classify warfarin-trazodone interaction as late-onset and clinically insignificant, this has been questioned in other studies. This particular case illustrates a possible interaction between warfarin and these two medications.

Therapeutic options for sleep-maintenance and sleep-onset insomnia.

Insomnia, defined as difficulty falling asleep, staying asleep, and/or experiencing restorative sleep with associated impairment or significant distress, is a common condition resulting in significant clinical and economic consequences. Many options are available to treat insomnia, to assist with either falling asleep (sleep onset) or maintaining sleep. We searched MEDLINE for articles published between January 1996 and January 2006, evaluated abstracts from recent professional meetings, and contacted the manufacturer of the most recent addition to the pharmacologic armamentarium for insomnia treatment (ramelteon) to gather information. Nonpharmacologic options include stimulus control, sleep hygiene education, sleep restriction, paradoxical intention, relaxation therapy, biofeedback, and cognitive behavioral therapy. Prescription and over-the-counter drug therapies include benzodiazepine and nonbenzodiazepine sedative-hypnotic agents; ramelteon, a melatonin receptor agonist; trazodone; and sedating antihistamines. Herbal and alternative preparations include melatonin and valerian. Before recommending any treatment, clinicians should consider patient-specific criteria such as age, medical history, and other drug use, as well as the underlying cause of the sleep disturbance. All pharmacotherapy should be used with appropriate caution, at minimum effective doses, and for minimum duration of time.

Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials.

The objective of this review was to determine the effectiveness, adverse effects and acceptability of folate in the treatment of depression. Electronic databases (Cochrane Controlled Trials Register and the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register) and reference lists were searched, and authors, experts and pharmaceutical companies contacted to identify randomized controlled trials that compared treatment with folic acid or 5'-methyltetrahydrofolic acid to an alternative treatment, for patients with a diagnosis of depressive disorder. Three randomized trials (247 participants) were included. Two studies assessed the use of folate in addition to other treatment, and found that adding folate reduced Hamilton Depression Rating Scale (HDRS) scores on average by a further 2.65 points [95% confidence interval (CI) 0.38-4.93]. Fewer patients treated with folate experienced a reduction in their HDRS score of less than 50% at 10 weeks (relative risk 0.47, 95% CI 0.24-0.92). The remaining study found no statistically significant difference when folate alone was compared with trazodone. The identified trials did not find evidence of any problems with the acceptability or safety of folate. The limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.

Evaluation of the anti-inflammatory and anti-nociceptive effects of different antidepressants in the rat.

The present study was designed to compare the anti-inflammatory and anti-nociceptive effects of different classes of antidepressant drugs on the carrageenan paw oedema and tail-electric stimulation assays in the rat. Drugs were intraperitoneally administered 30 min prior to carrageenan or nociceptive testing. The non-selective noradrenaline (NA) and serotonin (5-HT) reuptake inhibitors imipramine, amitriptyline and clomipramine displayed anti-inflammatory activity in the carrageenan model of paw inflammation. The maximal degree of oedema inhibitions seen with these agents were 28.8, 41.5 and 46.8% for 5, 10 and 20 mg kg(-1) amitriptyline, 26.2, 38.2 and 51.4% for 3.75, 7.5 and 15 mg kg(-1) imipramine and 51.2 and 54.1% for 16 and 32 mg kg(-1) clomipramine, respectively. The heterocyclic agent trazodone significantly inhibited paw oedema by 46 and 41% at 1 and 2h after dosing at the highest dose (40 mg kg(-1)) examined. Fluoxetine, a selective 5-HT reuptake inhibitor (SSRI) caused dose-related reduction of paw oedema, with 20.7% inhibition at the dose of 10 mg kg(-1). In contrast, sertraline, another SSRI caused dose-dependent enhancement of paw oedema. All antidepressant drugs in the study showed anti-nociceptive properties in the tail-electric stimulation assay with amitriptyline and trazodone being the most effective in this respect. Taken together, data in the present study confirm anti-inflammatory and anti-nociceptive effect for some antidepressant drugs and indicate that SSRIs differently affects inflammation.

Noncardiac chest pain.

GOALS: Review of research directions in the etiology, evaluation, and treatment of patients with noncardiac chest pain. The author proposes a combined practical approach to noncardiac chest pain that incorporates these findings, which is useful in a clinical practice setting. BACKGROUND: Several major schools of thought have emerged in the etiology of noncardiac chest pain: acid reflux, motor disorder, altered pain threshold/hypersensitivity, and association with psychiatric dysfunction. There is significant overlap among these. Occult gastroesophageal reflux disease (GERD) is more common than motor disorders and is found in 30% to 40% of these patients; a subset has hypersensitivity, with a normal pH profile. Esophageal motility testing and endoscopy have a more limited role than 24-hour pH testing. Impedance planimetry and balloon sensory provocative testing remain research tools. Provocative testing with hydrochloric acid or edrophonium is less helpful than pH monitoring. Gastroesophageal reflux disease-induced chest pain requires high-dose long-term proton pump inhibitors (PPIs): at least 4 to 8 weeks. Psychotropics are superior to placebo, both in patients with and without psychiatric dysfunction. RESULTS: The author found combined PPIs and psychotropics helpful in patients with esophageal hypersensitivity and GERD, although supporting data is scant. CONCLUSIONS: A brief 1-week high-dose PPI challenge, i.e., omeprazole test, may be cost-effective in a primary care setting. However, this approach may not be useful in a referral setting, where pH data and diary assessment of associated symptoms provide useful management help. A behavioral model approach, with early emphasis on patient education, integrated with physiologic data helps the most.