Efficacy Of Trazodone Research Articles

Pharmacokinetics of Trazodone in Hispaniolan Parrots (Amazona ventralis).

The objective of this study was to establish the pharmacokinetics of a single oral dose of trazodone in the Hispaniolan Amazon parrot (Amazona ventralis). Trazodone is a selective serotonin antagonist and reuptake inhibitor used commonly in both human and veterinary medicine as an antidepressant behavioral modification medicine. A single oral dose of compounded trazodone hydrochloride solution (20 mg/mL) at 50 mg/kg was administered to a total of 7 healthy adult Hispaniolan Amazon parrots. The 7 healthy adult parrots ranged in age from 10 to 15 years and weighed 228 to 323g. Blood was collected at baseline (2 weeks before study) and at 1, 2, 4, 6, 10, and 14 hours post-drug administration. Plasma concentrations of both trazodone and its active metabolite m-chlorophenylpiperazine (mCPP) were measured via liquid chromatography tandem mass spectrometry. Noncompartmental pharmacokinetic analysis was completed. The half-life (t1/2) ± SD of trazodone for the Hispaniolan parrots was 1.89 ± 0.49 hours, and the t1/2 ± SD of mCPP metabolite was 1.9 ± 0.55 hours. Maximum serum drug concentrations, or Cmax (ng/mL), were 738.3 ± 285.3 for trazodone. Times to achieve Cmax (hours) for trazadone and the mCPP metabolite were 1 hour and 2 hours postdosing, respectively. While this study did not establish the behavioral effects of trazodone, no adverse side effects were observed throughout the 48-hour period following drug administration and blood collection. Our results indicate that the oral administration of a 50-mg/kg single dose of trazodone to Hispaniolan parrots may be considered a safe dose. Plasma concentrations are comparable to previously published values in humans, dogs, horses, and pigeons (Columba livia domestica) for up to 14 hours following dosing. This study indicates that further studies are needed to establish the pharmacodynamics and the efficacy of trazodone in the medical management of behavioral problems in psittacine species.

The efficacy of trazodone in reducing stress related behaviours in hospitalised dogs or dogs confined postsurgery

Clinical bottom line Category of research Treatment. Number and type of study designs reviewed Three papers were critically reviewed. One was a prospective, randomised, blinded observational study, another was a randomised, placebo-controlled clinical trial, and the last was a non-randomised prospective, open-label clinical trial. Strength of evidence Weak. Outcomes reported The administration of trazodone to hospitalised dogs reduced several observed stress related behaviours compared to a control group that was environmentally matched to the treatment group (Gilbert-Gregory et al., 2016). In dogs subjected to postsurgical confinement at home, trazodone administration was not more effective at reducing stress related behaviours compared with a placebo in one study (Gruen et al., 2017); however, it was effective when observed in a non-placebo controlled clinical trial (Gruen et al., 2014). Further investigation with a larger sample size would assist in strengthening the evidence of an association between trazodone administration and a reduction in the behavioural signs of stress in dogs. Conclusion The available evidence weakly supports the hypothesis that administration of trazodone is an effective treatment in reducing stress related behaviours in hospitalised dogs and dogs confined post-surgery, and further studies are required to confirm its efficacy. The quality of the evidence when hospitalised dogs was studied was moderate (Gilbert-Gregory et al., 2016), however in dogs studied that were confined postsurgery, the evidence is weaker (Gruen et al., 2014; Gruen et al., 2017). Different trazodone doses were evaluated in the studies and so further studies focusing on dose effects are required to determine appropriate dose rates. Further studies also need to be conducted to evaluate the appropriate length of time that trazodone should be given prior to a stressful event, as well as whether trazodone needs to be used in conjunction with other anxiolytic drugs to optimise efficacy. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

TED-Trazodone Efficacy in Depression: A Naturalistic Study on the Efficacy of Trazodone in an Extended-Release Formulation Compared to SSRIs in Patients with a Depressive Episode-Preliminary Report.

These are the preliminary results of a 12-week non-randomized, open-label, non-inferiority study comparing the effectiveness of trazodone in an extended-release formulation (XR) versus SSRIs in the treatment of major depressive disorder (MDD). Participants (n = 76) were recruited, and 42 were assigned to the trazodone XR group and 34 to the SSRIs group. The choice of drug was based on clinical presentation and relied upon the attending physician. Assessments were made at five observation time points, at the following weeks: 0, and after 2, 4, 8, and 12 weeks. The evaluations included: symptoms of depression (MADRS, QIDS-clinician, and self-rated versions-primary study endpoints), anhedonia (SHAPS), anxiety (HAM-A), insomnia (AIS), psychosocial functioning (SDS), and therapeutic efficacy (CGI). At baseline, the trazodone group had significantly more severe depressive, anxiety, and insomnia symptoms and worse psychosocial functioning compared to the SSRIs group. After 12 weeks, trazodone XR was more effective than SSRIs in reducing the severity of insomnia and depression. There were no differences between the groups in the frequencies of therapeutic response and remission, which indicated the non-inferiority of the trazodone XR treatment. In conclusion, our results showed that in a "real world" setting, trazodone XR is effective in the treatment of patients with MDD.

Safety and efficacy of melatonin, clonazepam, and trazodone in patients with Parkinson's disease and sleep disorders: a randomized, double-blind trial.

Sleep disturbances are common non-motor symptoms of Parkinson's disease (PD). We aimed to compare the safety and efficacy of trazodone with melatonin and clonazepam in patients with PD and sleep complaints. This single-center, double-blind, randomized clinical trial was conducted on PD patients with subjective sleep complaints. Eligible patients were randomized 1:1:1 to receive melatonin 3mg/day, clonazepam 1mg/day, or trazodone 50mg/day for 4weeks. The primary outcome measure was the changes in Pittsburgh Sleep Quality Index (PSQI) scores. The mean change in Epworth Sleepiness Scale (ESS) and RBD screening questionnaire (RBDSQ) was considered as the secondary outcome measures. A total of 112 eligible patients were randomized and 93 participants, melatonin (n = 31), trazodone (n = 31), and clonazepam (n = 31), completed the study. There was a significant decrease in PSQI scores after 4weeks of treatment in all groups. The mean changes of PSQI from baseline were similar among the treatment arms (P = 0.325). Mean changes of RBDSQ and ESS from baseline were significantly different between study arms (P < 0.05). Melatonin intake was associated with a higher decrease in RBDSQ score compared to trazodone (P = 0.011) and clonazepam (P = 0.004). Trazodone intake was associated with a higher decrease in ESS score compared to clonazepam (P = 0.010). Mild adverse events were reported in three patients in the clonazepam, two patients in the trazodone group, and none in the melatonin group. Trazodone 50mg/day, clonazepam 1mg/day, and melatonin 3mg/day were all tolerable and effective in improving sleep quality in patients with PD. Iranian Registry of Clinical Trials (registration number; IRCT20170821035819N2).

Pharmacokinetics and efficacy of trazodone following rectal administration of a single dose to healthy dogs.

To determine the pharmacokinetics and efficacy of trazodone following rectal administration of a single dose to healthy dogs. 6 healthy adult dogs. Each dog received a single dose of trazodone (approx 8 mg/kg) per rectum. Trazodone tablets were crushed into a powder, mixed with 5 mL of tap water, and injected into the rectum via a red rubber catheter. Sedation scores were assigned, and blood samples were collected for determination of plasma trazodone concentration at predetermined times before and after drug administration. Pharmacokinetic parameters were estimated by noncompartmental analysis. Plasma trazodone concentration remained below the detection limit for 1 dog even though it became moderately sedate. Median (interquartile [25th to 75th percentile] range [IQR]) maximum plasma trazodone concentration and volume of distribution and clearance corrected for bioavailability were 1.00 μg/mL (0.66 to 1.40 μg/mL), 10.3 L/kg (7.37 to 14.4 L/kg), and 639 mL/kg/h (594 to 719 mL/kg/h), respectively. Median time to maximum plasma trazodone concentration and elimination half-life were 15 minutes (range, 15 to 30 minutes) and 12 hours (IQR, 7.99 to 12.7 hours), respectively. All dogs became mildly or moderately sedate, and the extent of sedation was maximal at a median of 30 minutes (IQR, 30 to 60 minutes) after trazodone administration. No adverse effects were observed. Rectal administration of trazodone may be a viable option for sedation and treatment of anxiety in dogs for which administration of sedatives and anxiolytics by other routes is contraindicated. Further research is necessary to better elucidate the pharmacokinetics and efficacy of trazodone following rectal administration and determine optimal dosing.

P.290 Early efficacy of trazodone for the treatment of depressive episodes with mixed features in patients with major depressive disorder

P.290 Early efficacy of trazodone for the treatment of depressive episodes with mixed features in patients with major depressive disorder

The use of trazodone to facilitate calm behavior after elective orthopedic surgery in dogs: Results and lessons learned from a clinical trial

Abstract Trazodone hydrochloride is an atypical antidepressant that has entered clinical use for dogs and cats for a variety of indications. These include management of anxiety disorders, facilitation of travel and veterinary examinations, and facilitation of calm behavior in hospitalized and postoperative patients. Despite the increasingly common use of trazodone in dogs, very little literature exists evaluating trazodone's efficacy against a placebo control. The aim of the study reported here was to evaluate trazodone in a randomized placebo-controlled clinical trial for use in facilitating calmness and ease of confinement in postoperative dogs. The study enrolled 29 dogs (14 in the trazodone group and 15 in the placebo group) and followed them during 4 postoperative weeks. Trazodone was well tolerated by dogs in the trazodone group. Although dogs in both groups were rated as improved on some behavioral measures, no difference was found between the trazodone and placebo groups in efficacy, with more than 70% of owners in both groups rating the test article (trazodone or placebo) as moderately or extremely helpful for facilitating both calming and crating of their dog. This observed lack of efficacy, over placebo, may be attributed to one or more of several factors that include features about the trial itself and the trial population, a caregiver or placebo-by-proxy effect, a lack of sensitive outcome measures for assessment, or a lack of true efficacy for the medication. It is concluded that future work will be needed to address these factors, and this report aims to provide not only results but lessons learned from the conduct of the described trial.

Mirtazapine and trazodone efficacy on major depressive disorder (MDD) is moderated by patients’ age and sex: A randomized, controlled trial

IntroductionNaSSA antidepressant mirtazapine and SARI trazodone has proven efficacy on MDD.AimTo compare differences in mirtazapine and trazodone efficacy on MDD in different age and sex groups.MethodsA consecutive sample of 60 MDD outpatients were randomized to mirtazapine 30 mg/day or trazodone 150 mg/day for a 3 months stable dosing period at the department of biological psychiatry and psychogeriatrics of the university psychiatric hospital Vrapče, Croatia. Outcome was relative lowering of HAMD-17 scale result. The study was single blind: rater was blinded, while patients informed regarding prescribed medication.ResultsOverall efficacy of mirtazapine and trazodone was comparable (84% lowering of HAMD–17 in both cases; difference P = 0.754). After adjustment for MDD baseline severity (CGI–S), education, marital and working status, interaction of age and sex significantly moderated two drugs’ efficacies. In patients older than 47 years, in male patients trazodone was significantly more effective, and in female patients significantly less effective than mirtazapine. This effect was increasing by aging.ConclusionMirtazapine and trazodone efficacy on MDD is moderated by patients’ age and sex.

Trazodone Improves Sleep Parameters in Alzheimer Disease Patients: A Randomized, Double-Blind, and Placebo-Controlled Study

There are no randomized clinical trials regarding efficacy of trazodone in the treatment of sleep disturbances (SD) in patients with Alzheimer disease (AD). We tested the efficacy and safety of trazodone to treat SD in patients with AD. We conducted a double-blind, randomized and controlled trial during periods of 7-9 days at baseline and 2 weeks of treatment. Geriatric medical center of the university's general hospital. Individuals with probable AD and SD. The complete analysis comprised 30 patients assigned to either the active treatment group (N= 15) or the placebo group (N= 15). Patients received 50 mg of trazodone once daily at 10:00 P.M. or placebo in a 1:1 ratio for 2 weeks. Patients were evaluated using actigraphy and structured scales before and after intervention. Compared with the placebo group, trazodone users slept 42.5 more minutes per night and had their nighttime percent sleep increased 8.5 percentage points according to actigraphic data post-treatment. Neither trazodone nor placebo induced significant daytime sleepiness or naps. The treatments with trazodone or placebo did not show any effects either on cognition (Mini-Mental State Examination, forward/backward digit span task, letter-number sequencing, arithmetic, digit symbol-coding, and symbol search) or functionality (Katz index). There were no differences in frequency or severity rating of adverse events between the groups. This study shows significant therapeutic effects of trazodone 50 mg in community-dwelling AD patients with SD.

Evaluation of trazodone and quetiapine for insomnia: an observational study in psychiatric inpatients.

Insomnia is symptomatic of most psychiatric disorders. Non-habit-forming agents such as trazodone and quetiapine are commonly used off-label to treat patients with insomnia. The safety and efficacy of trazodone and quetiapine as medications for treatment of insomnia have never been directly contrasted. The objective of this study was to compare the effectiveness of trazodone to quetiapine among inpatient psychiatric patients by measuring the traditional sleep parameters of total sleep time, number of nighttime awakenings, sleep efficiency, sleep latency, length of hospitalization, and patient-reported side effects. Participants were recruited from St Helena Hospital Center for Behavioral Health, Vallejo, California. Patient inclusion criteria were age 18 to 65 years, admitted between September 2011 and February 2012, and a physician order for trazodone or quetiapine for insomnia. Exclusion criteria included primary insomnia, pregnancy, concomitant order of trazodone and quetiapine, receiving trazodone or quetiapine up to 2 weeks prior to the study, and inability to coherently communicate. Subjective patient interviews and objective nursing sleep log reviews composed the data set. On average, mean total sleep time hours were longer among patients receiving trazodone versus those receiving quetiapine according to patients' subjective reports (7.80 vs 6.75, respectively, P < .01) and the nursing sleep logs (9.13 vs 8.68, respectively, P = .04). Patients receiving trazodone experienced fewer mean nighttime awakenings versus those receiving quetiapine (0.52 vs 0.75, respectively, P = .04) according to the nursing sleep log report. Patients receiving trazodone reported more side effects of constipation, nausea, and diarrhea than patients receiving quetiapine. With respect to total sleep time and nighttime awakenings, trazodone was a more effective alternative than quetiapine. However, patients receiving trazodone experienced more gastrointestinal patient-reported side effects.

Trazodone: properties and utility in multiple disorders

Trazodone is an established antidepressant that is prescribed frequently as an off-label hypnotic with wide acceptance among psychiatrists. Owing to its atypical mixed serotonergic and adrenolytic pharmacology, trazodone has been investigated in a number of disorders besides depression and insomnia, including anxiety disorders, chronic pain, frontal cognitive dysfunctions, erectile dysfunction and others. Clinical studies using subjective and objective measures generally tend to support its efficacy as a hypnotic in depressed subjects. Various other attributes of trazodone, including interaction with adrenergic receptors, formation of an active metabolite with potent serotonergic activity, low abuse potential and putative utility in various disorders, warrant further exploration. The adverse effects of trazodone generally mirror its serotonergic activity and include sedation, headache, sweating, weight changes and gastrointestinal effects such as nausea and vomiting. Clinicians and patients should be cognizant of the risk for potential, but rare, cardiovascular adverse effects of trazodone. The safety and toxicology of trazodone should be examined under current standards of drug development before exposure to new patient populations. This article provides an overview of trazodone with a focus on its clinical pharmacology and opportunities, gaps and scientific strategies in developing it for new indications such as insomnia, anxiety disorders, chronic pain and frontal cognitive dysfunction. Modified release formulations, alternate forms of drug delivery and combination products are discussed as strategies to optimize the efficacy of trazodone and improve its safety profile.

The use of trazodone as a hypnotic: a critical review.

The last few years have seen a remarkable rise in the off-label use of trazodone for inducing sleep in nondepressed patients, to a degree that it is prescribed for this purpose as commonly as the leading hypnotic. In view of this widespread popularity, it seems prudent to review what is known of the safety and efficacy of trazodone when used in this context. A MEDLINE search of the literature published in English between 1975 and 2003 that included the keywords sleep, trazodone, Desyrel, depression, sleeping pill, and sedative-hypnotics was conducted. From this review, it is concluded that there are very few data to suggest that trazodone improves sleep in patients without mood disorder, though it does increase total sleep in patients with major depressive disorder. There are virtually no dose-response data for trazodone vis-à-vis sleep and, similarly, no available data on tolerance to its possible hypnotic effects. Areas of concern with its use include reports of significant dropout rates and induction of arrhythmias, primarily in patients with histories of cardiac disease, as well as the development of priapism. In summary, there are few data to support the use of trazodone in nondepressed subjects. When the risk-benefit ratio of trazodone is assessed, its side effect profile, which is much more significant than that of conventional hypnotics, should be considered.

Trazodone for erectile dysfunction: a systematic review and meta-analysis.

To determine the efficacy and safety of trazodone in the treatment of erectile dysfunction (ED) in a meta-analysis. The data sources used were Medline and the Cochrane Library databases (January 1966 to May 2002), bibliographies of retrieved articles and review articles, and conference proceedings and abstracts. Trials were eligible for inclusion in the review if they included men with ED, compared trazodone with a control, were randomized, of > or = 7 days' duration and assessed clinically relevant outcomes. Two reviewers independently evaluated study quality and extracted data in a standardized fashion. Six trials (comprising 396 men) met the inclusion criteria; they consisted of heterogeneous populations, were small, brief and in some cases methodologically weak. Three of the six trials showed an apparently clinically meaningful benefit of trazodone for ED compared with placebo, the differences being statistically significant in two. In pooled results, trazodone monotherapy appeared more likely than placebo to lead to a 'positive treatment response', although this difference was not statistically significant (37% vs 20%; relative benefit increase, 1.6; 95% confidence interval, CI, 0.8-3.3). Subgroup analyses suggested that men with psychogenic ED might be more likely to benefit from trazodone than those with mixed or physiological ED. The efficacy of trazodone also appeared greater at higher doses (150-200 vs 50 mg/day). Men randomized to trazodone were not significantly more likely than those receiving placebo to withdraw for any reason or for an adverse event, or to have specific adverse events, but wide CIs could not exclude a greater risk of these adverse outcomes with trazodone. Specific adverse events with trazodone included dry mouth (19%), sedation (16%), dizziness (16%) and fatigue (15%). Trazodone may be helpful in men with ED, possibly more so at higher doses, and in men with psychogenic ED. Future high-quality trials should compare trazodone with placebo and other therapies in men with depression and psychogenic ED.

Efficacy of trazodone as an anti-obsessional agent.

Eight patients with chronic obsessive-compulsive neurosis were subjected to trazodone, an antidepressant acting on the serotonergic system. After 4 weeks of treatment, 6 showed significant reduction in the obsessional symptoms which was sustained after a 6-week follow-up. The 2 patients who did not show improvement had a significantly higher trait score than the others on psychometric ratings.

Efficacy of trazodone as an anti obsessional agent

Eight patients with chronic Obsessive-Compulsive Neurosis were subjected to Trazodone, an antidepressant acting on the serotinergic system. After 4 weeks of treatment, 6 showed significant reduction in the obsessional symptoms which was sustained after a 6-week follow-up. The 2 patients who did not show improvement had a significantly higher trait score than the others on psychometric ratings.

Efficacy of Trazodone: Data from European and United States Studies

Combined results of approximately two dozen studies of the efficacy of trazodone, conducted in the United States and Europe, indicate that trazodone is superior to placebo in alleviating depression. Moreover, trazodone is at least as effective as standard tricyclic antidepressants. Possible biases introduced by combining results obtained with different methodologies are minimized by including, with one exception, only double-blind, random assignment, controlled studies.