Effects Of Trazodone Research Articles

A Randomized-Controlled Trial Targeting Cognition in Early Alzheimer's Disease by Improving Sleep with Trazodone (REST).

Alzheimer's disease (AD) is a leading cause of mortality and morbidity among aging populations worldwide. Despite arduous research efforts, treatment options for this devastating neurodegenerative disease are limited. Sleep disturbances, through their link to changes in neural excitability and impaired clearance of interstitial abnormal protein aggregates, are a key risk factor for the development of AD. Research also suggests that the neuroprotective effects of sleep are particularly active during slow wave sleep. Given the strong link between sleep disturbance and AD, targeting sleep in the prodromal stages of AD, such as in mild cognitive impairment (MCI), represents a promising avenue for slowing the onset of AD-related cognitive decline. In efforts to improve sleep in older individuals, several pharmacologic approaches have been employed, but many pose safety risks, concern for worsening cognitive function, and fail to effectively target slow wave sleep. Trazodone, a safe and widely used drug in the older adult population, has shown promise in inducing slow wave sleep in older adults, but requires more rigorous research to understand its effects on sleep and cognition in the prodromal stages of AD. In this review, we present the rationale and study design for our randomized, double-bind, placebo-controlled, crossover trial (NCT05282550) investigating the effects of trazodone on sleep and cognition in 100 older adults with amnestic MCI and sleep complaints.

Evaluation of the sedative properties of oral trazodone, gabapentin or their combination in healthy cats.

Sedation before veterinary visits is advocated to help reduce fear and anxiety in cats and facilitate safe handling. The aim of this study was to evaluate the effectiveness of trazodone, gabapentin and a trazodone/gabapentin combination for oral sedation in healthy feline patients before blood donation. A total of 21 cats were included in the study. Baseline sedation scores were obtained, and cats were randomly assigned to receive oral trazodone at 5 mg/kg (T), oral gabapentin at 10 mg/kg (G), their combination (TG) or placebo (control group). A sedation score was obtained 1 h after drug administration. A blood sample was obtained at the time of blood collection for quantification of drug plasma concentrations. Agreement between observers was tested with a Cohen's Kappa test. Sign tests to compare change within treatment and a Skilling-Mack rank ANOVA to test for differences between groups were performed to compare pre- and post-sedation scores as well as a magnitude of differences over time between the groups. A Spearman's rank correlation coefficient test was used to correlate sedation scores with drug plasma concentrations. Post-sedation final scores were significantly higher only in the T (P = 0.022) and TG groups (P <0.001). The magnitude of change between pre- and post-sedation scores was larger in the TG (P <0.0032) and T groups (P <0.038) compared with the control group. There were no other significant differences between the groups. There was no correlation between drug plasma concentrations and sedation scores in any of the groups. Administration of oral trazodone alone at 5 mg/kg or in combination with gabapentin at 10 mg/kg resulted in significant sedation in healthy cats with no evident side effects. The degree of sedation was more profound when both drugs were combined, but a gabapentin dose of 10 mg/kg alone failed to provide significant sedation in this population.

Trazodone counteracts the response of microglial cells to inflammatory stimuli.

Microglia are resident brain cells that regulate neuronal development and innate immunity. Microglia activation participates in the cellular response to neuroinflammation, thus representing a possible target for pharmacological strategies aimed to counteract the onset and progression of brain disorders, including depression. Antidepressant drugs have been reported to reduce neuroinflammation by acting also on glial cells. Herein, the potential anti-inflammatory and neuroprotective effects of trazodone (TRZ) on the microglial human microglial clone 3 (HMC3) cell line were investigated. HMC3 cells were activated by a double inflammatory stimulus (lipopolysaccharide [LPS] and tumour necrosis factor-alpha [TNF-α], 24 h each), and the induction of inflammation was demonstrated by (i) the increased expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and ionized calcium-binding adapter molecule 1 (IBA-1), and (ii) the increased release of interleukin 6 (IL-6) and transforming growth factor-beta (TGF-β). TRZ effects were evaluated by treating HMC3 cells for 24 h before (pre-treatment) and after (post-treatment) the double inflammatory stimulus. Notably, TRZ treatments significantly decreased the expression of NF-kB and IBA-1 and the release of the cytokines IL-6 and TGF-β. Moreover, TRZ prevented and reduced the release of quinolinic acid (QUIN), a known neurotoxic kynurenine metabolite. Finally, cellular supernatants collected from microglial cells pre-treated LPS-TNF-α with TRZ were able to improve neuronal-like cell viability, demonstrating a potential neuroprotective effect. Overall, this study suggests the anti-inflammatory effects of TRZ on human microglia and strives for its neuroprotective properties.

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.

Impact of trazodone once-a-day on quality of life and functional recovery in adults with major depressive disorder: A prospective, observational study.

Health-related quality of life (HRQL) is an important goal for patients with major depressive disorder (MDD), but whether antidepressants improve HRQL in these patients is unclear. Here, we describe the real-world effects of trazodone once-a-day (TzOAD) and selective serotonin reuptake inhibitor (SSRI) treatments on HRQL and functioning in adults with MDD. This 8-week prospective, observational, open-label, multicenter study was conducted in adults with moderate or severe MDD for whom TzOAD or SSRI were prescribed as monotherapy. The primary outcome was life enjoyment and satisfaction assessed via the patient-reported Quality-of-Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF) from baseline to week 8. Secondary outcomes included change in Q-LES-Q-SF from baseline to weeks 1 and 2; severity of depressive symptoms using the Montgomery Åsberg Depression Rating Scale (MADRS) and sleep disturbance via the PROMIS SF-SD 8b questionnaire at weeks 1, 2, and 8; and overall functioning via the Sheehan Disability Scale (SDS), hedonic capacity using the Snaith-Hamilton Pleasure Scale (SHAPS), and cognitive dysfunction using the Perceived Deficits Questionnaire (PDQ-5) at baseline and week 8. The study included 208 adults with MDD (mean [SD] age=50.2 [14.3] years; 68.6% female; 98.4% White). Life enjoyment and satisfaction improved from baseline to week 8 for both treatment groups: Q-LES-Q-SF mean (SD) scores were 27.5 (20.4) for the SSRI group and 39.0 (22.1) for the TzOAD group. Depressive symptoms and sleep disturbances also reduced from baseline to week 8: MADRS (SSRI, -15.7 [8.3]; TzOAD, -21.0 [9.8]); PROMIS SF-SD 8b (SSRI, -9.9 [12.6]; TzOAD, -22.0 [12.6]). Mean change scores in Q-LES-Q-SF, MADRS, and PROMIS SF-SD 8b improved as early as week 1 in both groups. Mean scores also improved from baseline to week 8 on SDS (SSRI, -9.2 [7.4]; TzOAD, -14.3 [7.5]), SHAPS (SSRI, -6.6 [4.3]; TzOAD, -8.3 [4.4]), and PDQ-5 (SSRI, -5.8 [4.5]; TzOAD, -7.7 [5.0]). In adults with MDD who received TzOAD or SSRIs, overall and individual HQRL domains improved rapidly and in parallel with improvements in depressive symptoms, with a slightly greater improvement observed in the TzOAD group.

BLOOD PRESSURE EFFECTS OF TRAZODONE IN HYPERTENSIVE OLDER ADULTS

Objective: Trazodone is commonly prescribed in older adults and may have hypotensive effects due to the inhibition of alpha-adrenergic receptors. The present study aimed to investigate the effects of trazodone on blood pressure (BP) and its related risk of syncope and falls in hypertensive older adults. Design and method: A longitudinal observational study involving patients aged 75 or older was conducted at the Hypertension Clinic and Memory Clinic of the Division of Geriatric and Intensive Care Medicine, Careggi Hospital, Florence. Participants underwent multidimensional geriatric assessment including office BP measurement, 3-minute active stand test (BP measurement immediately after standing [T0] and at 1 [T1] and 3 minutes [T3]), home and ambulatory BP monitoring. The composite outcome of syncope and falls was assessed at 12 months and its association with trazodone was analysed using multivariate Cox regression analysis. Results: Among 123 participants (mean age 81 years, 59% female), 12 (10%) reported regular trazodone use. Participants receiving trazodone showed lower office diastolic BP (71.8 mmHg vs. 80.1 mmHg, p=0.042) and a greater systolic and diastolic BP reduction immediately after standing (δsystolicT0 16.2 mmHg vs. 9.7 mmHg, p=0.038; δdiastolicT0 11 mmHg vs. 1.7 mmHg, p=0.003). No differences were reported as regards home and ambulatory BP. Incidence of syncope and falls at 12 months was 25%, with a significantly higher rate in patients receiving trazodone (58.3% vs. 21.2%, p=0.005). Trazodone was associated with an increased risk of syncope or falls independently of physical performance (HR 2.654, 95% CI 1.104 - 6.378). This association was not confirmed when multivariate Cox analysis was adjusted for dementia diagnosis (HR for trazodone 1.874, 95% CI 0.736 – 4.773; HR for dementia 2.556, 95% CI 1.018 – 6.419). Conclusions: In older adults with hypertension, trazodone is associated with a greater orthostatic BP drop and might increase the risk of syncope and falls.

The effects of selected sedatives on basal and stimulated serum cortisol concentrations in healthy dogs.

Hormone assessment is typically recommended for awake, unsedated dogs. However, one of the most commonly asked questions from veterinary practitioners to the endocrinology laboratory is how sedation impacts cortisol concentrations and the adrenocorticotropic hormone (ACTH) stimulation test. Butorphanol, dexmedetomidine, and trazodone are common sedatives for dogs, but their impact on the hypothalamic-pituitary-adrenal axis (HPA) is unknown. The objective of this study was to evaluate the effects of butorphanol, dexmedetomidine, and trazodone on serum cortisol concentrations. Twelve healthy beagles were included in a prospective, randomized, four-period crossover design study with a 7-day washout. ACTH stimulation test results were determined after saline (0.5 mL IV), butorphanol (0.3 mg/kg IV), dexmedetomidine (4 µg/kg IV), and trazodone (3-5 mg/kg PO) administration. Compared to saline, butorphanol increased basal (median 11.75 µg/dL (range 2.50-23.00) (324.13 nmol/L; range 68.97-634.48) vs 1.27 µg/dL (0.74-2.10) (35.03 nmol/L; 20.41-57.93); P < 0.0001) and post-ACTH cortisol concentrations (17.05 µg/dL (12.40-26.00) (470.34 nmol/L; 342.07-717.24) vs 13.75 µg/dL (10.00-18.90) (379.31 nmol/L; 275.96-521.38); P ≤ 0.0001). Dexmedetomidine and trazodone did not significantly affect basal (1.55 µg/dL (range 0.75-1.55) (42.76 nmol/L; 20.69-42.76); P = 0.33 and 0.79 µg/dL (range 0.69-1.89) (21.79 nmol/L; 19.03-52.14); P = 0.13, respectively, vs saline 1.27 (0.74-2.10) (35.03 nmol/L; 20.41-57.93)) or post-ACTH cortisol concentrations (14.35 µg/dL (range 10.70-18.00) (395.86 nmol/L; 295.17-496.55); (P = 0.98 and 12.90 µg/dL (range 8.94-17.40) (355.86 nmol/L; 246.62-480); P = 0.65), respectively, vs saline 13.75 µg/dL (10.00-18.60) (379.31 nmol/L; 275.86-513.10). Butorphanol administration should be avoided prior to ACTH stimulation testing in dogs. Further evaluation of dexmedetomidine and trazodone's effects on adrenocortical hormone testing in dogs suspected of HPA derangements is warranted to confirm they do not impact clinical diagnosis.

Effects of trazodone on viability in healthy and malignant ovarian cells

OBJECTIVE: Trazodone is a triazole pyridine derivative antidepressant, the design of which dates back to the 1980s. It is mainly used in the treatment of major depression, as well as in psychological disorders such as anxiety, insomnia, and schizophrenia. Considering how widespread the use of antidepressants is, it sensible to evaluate the effects of this group of drugs in different pathologies other than the disease group they target. Cancer is the most common cause of death in the world after cardiovascular diseases. The use of trazodone in cancer patients and the relationship between the use of trazodone and the development of cancer have been reported in various studies. However, these studies are mostly observational and population-based and the molecular effects of trazodone in the cancer model are not clearly known. MATERIALS AND METHODS: Trazodone was applied to healthy ovarian cells and OVCAR-3 and A2780 ovarian cancer cell lines at a certain dose range (0.1-20 μM). Viability in cells treated and untreated with trazodone was analyzed by MTT assay. RESULTS: The results revealed that trazodone treatment (0.1-20 μM) did not have a significant effect on healthy and cancerous ovarian cell viability. CONCLUSION: Trazadone (0.1-20 μM) does not significantly affect the viability of both healthy and cancer cells.

Trazodone in the Management of Major Depression Among Elderly Patients with Dementia: A Narrative Review and Clinical Insights.

Major depressive disorder (MDD) often co-occurs with dementia and other neurological disorders, and treatment with antidepressants can improve symptoms, quality of life, and survival in these patients. This narrative review provides an expert opinion about the role and effectiveness of trazodone in the treatment of older adults with MDD and cognitive impairment due to physical illnesses, such as dementia. Because of its mechanism of action, trazodone can treat several depression symptoms often seen in people with dementia, including insomnia, agitation, anxiety, cognitive impairment, and irritability. Trazodone may be beneficial for patients with dementia or other neurological disorders comorbid with MDD, especially when the clinical picture of depression includes or is comorbid to symptoms of insomnia, irritability, inner tension, anxiety, or psychomotor agitation.

The effect of trazodone on alfaxalone induction dose in rabbits

The effect of trazodone on alfaxalone induction dose in rabbits

Adverse effects of trazodone in dogs on primary hemostasis and electrocardiogram: A single-blinded placebo-controlled crossover study.

Trazodone is a serotonin antagonist/reuptake inhibitor medication commonly used for anxiety in dogs. Therapy with selective serotonin reuptake inhibitors in humans is associated with bleeding disorders and increased arrhythmogenesis. To evaluate markers of primary hemostasis and corrected QT (cQT) interval in dogs before and after oral administration of standard dosages of trazodone or placebo. Fifteen apparently healthy, client-owned dogs. A single-blinded, randomized placebo-controlled crossover study was performed. Dogs were administered trazodone (5 to 7.5 mg/kg PO Q12h) or placebo. [Correction added after first online publication on 14 October 2023. In the abstract (methods) section (57.5 mg/kg PO Q12h) changed as (5 to 7.5 mg/kg PO Q12h).] Buccal mucosal bleeding time (BMBT), platelet count, platelet aggregation via Plateletworks, PFA-100 closure time and cQT interval were measured. A Shapiro-Wilk test was performed followed by either a paired t test or a Wilcoxon signed-rank test. No significant difference was detected in the BMBT, PFA-100 closure times, platelet counts, and cQT interval between trazodone or placebo. However, using Plateletworks, there was a significant decrease in platelet aggregation after administration of trazodone (95%; 81-97 vs 62%; 39-89, P = .002) and not placebo (95%; 81-97 vs 91%; 81-96, P = .21). It is unknown if this represents a clinically relevant change or if dogs with preexisting impairment in primary hemostasis or receiving higher dosages or longer durations of trazodone could have a more substantial change in hemostatic variables.

Effects of trazodone and dexmedetomidine on fentanyl-mediated reduction of isoflurane minimum alveolar concentration in cats

ObjectiveTo screen modulators of biogenic amine (BA) neurotransmission for the ability to cause fentanyl to decrease isoflurane minimum alveolar concentration (MAC) in cats, and to test whether fentanyl plus a combination of modulators decreases isoflurane MAC more than fentanyl alone. Study designProspective, experimental study. AnimalsA total of six adult male Domestic Short Hair cats. MethodsEach cat was anesthetized in three phases with a 1 week washout between studies. In phase 1, anesthesia was induced and maintained with isoflurane, and MAC was measured in duplicate using a tail clamp stimulus and standard bracketing technique. A 21 ng mL–1 fentanyl target-controlled infusion was then administered and MAC measured again. In phase 2, a single cat was administered a single BA modulator (buspirone, haloperidol, dexmedetomidine, pregabalin, ramelteon or trazodone) in a pilot drug screen, and isoflurane MAC was measured before and after fentanyl administration. In phase 3, isoflurane MAC was measured before and after fentanyl administration in cats co-administered trazodone and dexmedetomidine, the two BA modulator drugs associated with fentanyl MAC-sparing in the screen. Isoflurane MAC-sparing by fentanyl alone, trazodone–dexmedetomidine and trazodone–dexmedetomidine–fentanyl was evaluated using paired t tests with p < 0.05 denoting significant effects. ResultsThe MAC of isoflurane was 1.87% ± 0.09 and was not significantly affected by fentanyl administration (p = 0.09). In the BA screen, cats administered trazodone or dexmedetomidine exhibited 26% and 22% fentanyl MAC-sparing, respectively. Trazodone–dexmedetomidine co-administration decreased isoflurane MAC to 1.50% ± 0.14 (p < 0.001), and the addition of fentanyl further decreased MAC to 0.95% ± 0.16 (p < 0.001). Conclusions and clinical relevanceFentanyl alone does not affect isoflurane MAC in cats, but co-administration of trazodone and dexmedetomidine causes fentanyl to significantly decrease isoflurane requirement.

PK/PD analysis of trazodone and gabapentin in neuropathic pain rodent models: Translational PK-PD modeling from nonclinical to clinical development.

A pharmacokinetic/pharmacodynamic (PK/PD) model was developed to describe the time course of writhings after intraperitoneal injection of acetic acid in mice. The model was applied to investigate the antinociceptive effect of trazodone and gabapentin alone and in combination. Writhings time course was described by a transit compartment model with the delay due to the transit of the acetic acid being represented by a chain of intermediate compartments. In the drug-treated animals, the number of writhings decreases according to a k2 factor linking drug concentration and antinociceptive effect. Compounds' potency parameters were 10.9 and 0.0459 L/μmoles/min for trazodone and gabapentin, respectively, indicating a much higher in vivo potency of trazodone in the PD writhing test. The PK/PD parameters were used to simulate the expected writhing counts in mice at combined doses without efficacy alone, assuming pharmacological additivity. Simulation results indicated that, at low dose combinations, experimental data were mostly below the simulated writhings median, suggesting possible synergic effect. Such hypothesis was tested by adding the γ parameter in the PK/PD model to represent the deviation from the assumption of no-interaction, leading to a reduction of the objective function compared to the additive model. On this basis, several simulations were performed to identify possible starting dose combinations of trazodone and gabapentin in humans, by selecting doses yielding systemic exposures close to those being synergic in the mouse. Simulations indicated that doses of 50-100 mg trazodone could enhance gabapentin antinociceptive effect in humans, supporting the development of a low dose combination for optimal analgesia treatment.

Investigating the Neuroprotective and Neuroregenerative Effect of Trazodone Regarding Behavioral Recovery in a BL6C57 Mice Stroke Model.

Stroke is a major cause of death and disability worldwide. Between 1990 and 2010, its global burden increased notably with reference to the absolute number of incident events, number of deaths, and disability-adjusted life-years lost. Trazodone is a triazolopyridine derivative that was approved for more than 40 years as monotherapy or in combination with other antidepressant drugs for the treatment of major depressive disorder in adult patients. The aim was investigated if trazodone can improve behavioural outcome after stroke in a mice model of middle cerebral artery occlusion (MCAo) due to the potential neuroprotective and neurodegenerative effects by using three behavioural tests: adhesive tape test, beam test and hole board test. Trazodone administration show modest improvements regarding the motor-sensorial function after stroke especially in the acute post-stroke phase in aged and young animals. The antidepressant effect of the drug was observed in the post-stroke period in aged animals and to a lesser extent in young animals. Future research is needed to evaluate the effects of trazodone at the cellular level to be sure that it has no benefit in stroke patients who do not suffer from depression.

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.

Exploring neuroprotective effect of trazodone in a microglia cell culture model of neuroinflammation

Exploring neuroprotective effect of trazodone in a microglia cell culture model of neuroinflammation

The Synergistic Effect of Trazodone on the Development of Priapism in the Background of Chronic Myeloid Leukemia

The Synergistic Effect of Trazodone on the Development of Priapism in the Background of Chronic Myeloid Leukemia

Trazodone and Mianserin for Delirium: A Retrospective Chart Review.

Although antipsychotics are commonly used for delirium, their adverse effects are a serious concern in light of extrapyramidal symptoms and cardiovascular disturbances. In clinical practice, sedative antidepressants are frequently used as an alternative treatment for delirium; however, there is scarce evidence. Thus, we conducted a retrospective chart review to examine the use and effectiveness of trazodone and mianserin for delirium. Patients who were admitted to a university hospital during 4 years and received either trazodone or mianserin on a regular schedule as monotherapy for the treatment of delirium were included. The rates of and times to the improvement of delirium were compared. Among 3971 patients who developed delirium, 379 (9.5%) and 341 (8.6%) patients received trazodone and mianserin on a regular schedule; 52 and 46 patients met the eligibility criteria (ie, monotherapy) for trazodone and mianserin, respectively. The percentages of patients 65 years or older were 86.5% (n = 45) for trazodone and 89.1% (n = 41) for mianserin. The rates of the improvement of delirium were 63.5% for trazodone and 50.0% for mianserin. Times to the improvement of delirium were 5.3 days (95% confidence interval, 3.2-7.4 days) for trazodone and 9.3 days (95% confidence interval, 5.3-13.3 days) for mianserin. There were no significant differences in the primary outcomes between the 2 groups ( P = 0.17 and P = 0.13, respectively). Considering potentially serious, sometimes lethal, adverse effects of antipsychotics, sedative antidepressants such as trazodone and mianserin may be a treatment option for delirium, especially in the elderly.

Trazodone changed the polysomnographic sleep architecture in insomnia disorder: a systematic review and meta-analysis

Trazodone has been widely prescribed for off-label use as a sleep aid. Identifying how trazodone impacts the performance of polysomnographic sleep architecture in insomnia disorder will provide additional data that can be used to guide clinical application. To assess the efficacy of trazodone in altering the polysomnographic sleep architecture in insomnia disorder so that sleep can be facilitated. PubMed, EMBASE, Web of Science, PsycINFO, Cochrane Library, Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure, Wanfang Database, and the China Science and Technology Journal Database were searched for articles published between inception and June 2022. RCTs in patients with insomnia disorder applying trazodone in one arm of interventions at least 1 week, and reporting PSG parameters in the outcomes were eligible. RoB 2 was used to evaluate the risk of bias. The results of quality of evidence assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. When I2 < 50%, the fixed effects model was used. When I2 ≥ 50%, the random effects model was used. The mean differences (MD) or standardized mean differences (SMD) and odds ratios (OR) with 95% confidence intervals (CIs) were estimated. Eleven randomized controlled trials were selected and participants were 466. Risk of bias was low in 5 trials (45.5%), and was moderate in 6 (54.5%). Compared with the control group, trazodone significantly increased total sleep time (TST, min) (MD = 39.88, 95% CI 14.44–65.32, P = 0.002) and non-rapid eye movement stage 3 (N3, mixed min and %) (SMD = 1.61, 95% CI 0.69–2.53, P = 0.0006); trazodone significantly decreased latency to onset of persistent sleep (LPS, min) (MD = − 19.30, 95% CI − 37.28 to − 1.32, P = 0.04), non-rapid eye movement stage 1 (N1, mixed min and %) (SMD = − 0.62, 95% CI − 1.13 to − 0.12, P = 0.02), the number of awakenings (NAs, including both arousal times and arousal index) (SMD = − 0.67, 95% CI − 0.91 to − 0.42, P < 0.00001), and waking time after persistent sleep onset (WASO, mixed min and %) (SMD = − 0.42, 95% CI − 0.81, − 0.03, P = 0.04), with no obvious effect on non-rapid eye movement stage 2 (N2, mixed min and %) (SMD = − 0.15, 95% CI − 0.41 to 0.11, P = 0.25), rapid eye movement (REM, mixed min and %) (SMD = 0.22, 95% CI − 0.26 to 0.70, P = 0.37), rapid eye movement latency (REML, min) (MD = 2.33, 95% CI − 27.56 to 32.22, P = 0.88), or apnea–hypopnea index (AHI) (MD = − 4.21, 95% CI − 14.02 to 5.59, P = 0.40). Daytime drowsiness (OR = 2.53, 95% CI 1.14–5.64, P = 0.02) and decreased appetite (OR = 2.81, 95% CI 1.14–6.92, P = 0.02) occurred with greater frequency in the trazodone group as compared to the control group, and the differences were significant. The results of quality of evidence were very low in TST, N3 and AHI, were low in LPS, WASO and REM, and were moderate in N1 and NAs. The sources of heterogeneity in TST and N3 were not found out from sensitive and subgroup analysis and there was no high quality of evidence in outcomes by GRADE Assessment. Trials with combination of other therapy could be a problem in this meta-analysis as the possibility of interactions were found from sungroup analysis. Trazodone could improve sleep by changing the sleep architecture in insomnia disorder, but it should be used with caution due to the adverse events that may occur.PROSPERO registration register name: The effect of trazodone on polysomnography sleep architecture in patients with insomnia: a systematic review and meta-analysis protocol; Registration Number CRD42020215332.

Trazodone and patient outcomes in dementia-Limitations of naturalistic cohort data.

The unfolded protein response has been increasingly implicated as an important pathological pathway and target for therapeutic intervention in neurodegeneration. The licensed antidepressant trazodone is one drug which has been proposed to act on this pathway and may therefore be a potential therapy. Previous examination of existing data for patients with dementia prescribed trazodone did not find a signal suggesting a disease modifying effect. Here we add to that literature by examining the electronic patient record of patients with dementia in Cambridgeshire UK. We found that trazodone is rarely prescribed and where it is used it is at a dose less than half that predicted to be disease modifying. We also found that patients prescribed trazodone had higher levels of neuropsychiatric symptoms and were relatively late in the disease course, likely beyond the optimal point for therapeutic intervention. We suggest it is therefore premature to discard potential therapies based on observational data alone, particularly when experimental medicine approaches to examine the effects of trazodone are feasible.