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To determine whether the administration of trazodone to dogs 2 hours prior to radiotherapy treatment reduced the dose of propofol required to induce anaesthesia.Retrospective, crossover, case-matched study.Records of 30 client-owned dogs.Anaesthetic records from all dogs undergoing weekly radiotherapy treatment between January 2020 and December 2020 were retrospectively assessed. All dogs were premedicated with 10 μg kgIn part 1, 15 study dogs that were administered trazodone prior to at least one anaesthetic were identified. A significant difference in propofol induction dose between groups NT and T was identified [3.3 (2.1-7.4) and 2.0 (1.5-5.0) mg kgPreanaesthetic trazodone administration reduced the induction dose of propofol compared to when it was not administered to dogs following premedication with IV atropine and alfentanil.

Objectives To review medical malpractice trends and to identify the most common claims filed against medical providers for the management of patients with priapism. Methods Using the Westlaw legal database, a search was done for the keyword “priapism” between July 1, 1980 and July 1, 2020. Cases were evaluated for plaintiff demographics, reasons for filing claims, management outcomes, legal verdicts and awards and further categorized based upon the timing of the alleged malpractice. Results Alleged negligence during the pre-management period was cited in 30 cases. Administration of psychotropic medications was the most common reasons for filing pre-management claims 22/56 (39.3%). Delay in care accounted for 18/56 (32.1%) and complications of surgery were 5/56 (8.9%) of claims. The majority of the completed cases were in favor of the defendants (39/47; 83.0%). There was no association between type of health care provider or timing of alleged malpractice and ultimate verdict. Conclusions Prescribing psychoactive medications without warning of the adverse effect profile is the most common reason for claims filed against providers with trazodone as the leading medication. Medical providers should ensure that patients are well informed of this adverse effect prior to prescription. Regardless, the majority of medical malpractice cases carry a verdict in favor of the defendant.

Companion dogs housed in animal shelters are subject to a great number of uncontrollable and unalterable stressors. To combat these stressors and the associated immunosuppression that can result in high rates of contagious disease in sheltered dogs, a large open admission municipal animal shelter in New York City introduced trazodone hydrochloride, a serotonin receptor antagonist and reuptake inhibitor, to help reduce their transitional stress. Dogs were given low doses of trazodone at intake (5 mg/kg), one to two doses within 48 hours of arrival. Prevalence of illness was calculated for two time periods at the Brooklyn and Manhattan Care Center locations (N = 1,766): November and December 2018, when trazodone was administered to the population, and a historical control in November and December 2017 and 2016, when no trazodone was administered. A statistically significant difference in the percentage of sick dogs was found when comparing the No Trazodone group (2016/2017) and Trazodone treatment group in 2018 (Chi2 [1, N = 1766] = 19.4, P

Trazodone is used as an antidepressant in doses between 150 and 600 mg. At lower doses, it is commonly used to treat insomnia. There are few case reports about confusional symptoms as an undesirable side effect of this drug. We report a case of a patient who presented with delirium after prescription of trazodone 100 mg. She required hospitalisation but, shortly after discontinuation of trazodone, the symptoms disappeared without antipsychotic medication. Seven months after the episode, the patient remains asymptomatic.

Introduction The Center for Medicare and Medicaid Services (CMS) has called for a reduction in antipsychotic use in the geriatric population, in large part due to the association of these medications with increased mortality. Antipsychotics have significant side effect profiles, including QTc prolongation, weight gain, diabetes mellitus, hypercholesterolemia, and sedation, and may contribute to overall mortality in ways that are not completely understood. As long term care facilities work to decrease their antipsychotic prescribing rates in line with CMS recommendations, they must contend with the challenge of finding alternative treatments for episodes of acute agitation. This observational study aimed to describe the response to this challenge in a geriatric subacute care facility by examining the Medication Administration Record (MAR) to determine if prescribing rates of other medications commonly used to treat agitation increased when antipsychotics were no longer used for this purpose. Methods The study site was a university-affiliated geriatric care facility, which contains long term chronic hospital units, memory support units, and subacute rehabilitation units. Medications were prescribed by geriatric medicine attendings, nurse practitioners, and physician assistants on each unit, with input at times from consulting psychiatrists. Prescribers were employed as members of the facility's closed medical staff. Nursing and administrative staff were generally stable over the time period study. The total census at both sites ranged from 668-725 patients. Over the course of our study, we examined two long term care units at the facility The study units discontinued the use of prescribing antipsychotics on an as needed (PRN) basis and began an initiative modeled after “Appropriate Use of Antipsychotics,” based on the Canadian Foundation for Healthcare Improvement and Appropriate Use of Antipsychotics collaborative. This initiative included a series of interventions to reduce antipsychotic use overall, including staff education and training in specific behavioral interventions. We collected data on the rates of prescribing medications, including antipsychotics, benzodiazepines and trazodone at four time periods: at baseline, some months prior to the start of the initiative (Jan – March 2017), after PRN antipsychotics were discontinued immediately prior to the start of the initiative (July – Sept 2017), during the initiative (January – March 2018) and later after the start of the initiative in follow-up (July – Sept 2018). Six days during each time period (the 15th and last day of the month for each of the 3 months in the period) were selected during which data were collected from the MAR examining the number of medication administrations of each medication. Further analysis was performed looking specifically at the rates of benzodiazepine and trazodone administrations, since these were found to be commonly prescribed medications. Results Administrations of antipsychotics decreased (from 22.0% of the total number of patients at the facility receiving an antipsychotic at time 1 to 19.0% in time 3; to 16.7% at time 4). Concurrently, rates of trazodone prescription rose significantly both by average number of doses per day prescribed (see figure 1; ANOVA for differences between the four time periods F(3,20)=95.43, P Conclusions As rates of antipsychotic prescribing on the units decreased, we observed a phenomenon of substitute prescribing in the form of a significant increase in the amount of trazodone prescribed. At the same time, there was a slight decrease in the amount of benzodiazepines prescribed. Our findings suggest that trazodone was felt by prescribers to be a safer alternative to antipsychotics. The absence of a similar increase in benzodiazepine prescribing suggests that prescribers remained wary of this class of medication because of its longstanding association with adverse effects such as falls. These data also suggest that an ongoing focus on behavioral interventions for agitation in dementia is still needed in order to minimize the phenomenon of substituting one medication with side effects for another with a different set of side effects. Side effects of trazodone include oversedation (which leads to risks of falls), hypotension, QT prolongation, and cognitive effects. A strength of this study is our access to accurate, detailed prescribing data. An additional strength is that the study took place at a facility with stable nursing and medical staffs, thereby decreasing the possibility that staff changes acted as confounders. Limitations of our study include that our data was observational, did not differentiate between PRN doses of a medication and standing doses, did not investigate the symptoms for which each medication was prescribed, and did not compare the effectiveness or adverse effects of these prescriptions. Future research is needed to describe the clinical impact of the phenomenon of medication substitution as antipsychotic prescribing continues to be reduced. This research was funded by: This study took place at Hebrew Rehabilitation Center/Hebrew SeniorLife and was supported by the Canadian Foundation for Healthcare Improvement, a not-for-profit organization funded by Health Canada.

The objectives of this retrospective descriptive study were to compare the efficacy of fluoxetine in conjunction with a behavior modification plan for the treatment of common canine behavioral disorders, and to compare the effects of other factors, including patient sex, fluoxetine dosage, and concurrent drug administration. Owners of all dogs prescribed fluoxetine through the Animal Behavior Clinic at the Cornell University Hospital for Animals in Ithaca, NY, between June 15th, 2012, and December 31st, 2016, were queried regarding their dogs’ behavior after prescription of fluoxetine. Behavioral diagnosis, fluoxetine dosage, concurrently administered psychoactive medications, sex, and response to fluoxetine for each dog were recorded. Of the 134 owners contacted, 93 responded. Eighty-eight dogs met inclusion criteria and were included in the study. Overall, 59% of owners reported that their dogs showed improvement, 32% reported no appreciable response, and 9% reported negative responses. Behavioral diagnoses were grouped into three categories: “Anxiety”, “Aggression”, and “Other” (which included compulsive/obsessive-compulsive behavior and self-mutilation). Most dogs in each category of diagnosis responded positively to treatment: 69% of dogs diagnosed with “Anxiety”, 55% of dogs diagnosed with “Aggression”, and 50% of dogs with a diagnosis of “Other”. A negative response to treatment was reported in 0% of dogs with a diagnosis of “Anxiety”, 13% of dogs diagnosed with “Aggression”, and 0% of dogs with a diagnosis of “Other”. More dogs prescribed fluoxetine at a daily dose of 0.5–0.99 mg/kg and 1.0–1.49 mg/kg responded positively to treatment (63% and 64%, respectively) than did dogs prescribed fluoxetine at 1.5–1.99 mg/kg daily (31%). Sixty-seven percent (N = 14/21) of dogs prescribed only trazodone in addition to fluoxetine and 63% (N = 5/8) of dogs prescribed only clonidine concurrently with fluoxetine responded positively to treatment, as compared with 59% (N = 23/39) of dogs prescribed fluoxetine as the sole agent. However, this difference was not significant. There was no significant effect of sex on treatment efficacy (Pearson chi square; [χ2 = 0.000; P = 0.999]). Sixty-eight percent (N = 19/28) of spayed females responded positively to treatment and 14% (N = 4/28) responded negatively, whereas 55% (N = 31/56) of castrated males responded positively and 9% (N = 5/56) responded negatively, a nonsignificant difference (Pearson chi square; (χ2 = 2.990; P = 0.224). Limitations of this study included its retrospective nature, number of owners who responded (N = 93; 66%) owner recall bias, and lack of control group (i.e., dogs with the same behavioral disorders that were not prescribed fluoxetine).

Introduction: REM sleep behaviour disorder (RBD) is characterised by violent behaviours (screaming, kicking, vivid dreams) during REM sleep. It has a prevalence of 1% to 2% of the general population and is especially frequent in men and the population older than 60. In the last decade, RBD has been suggested to be a prodrome of neurodegenerative disease. We analysed associated neurological diseases and responses to drug treatment in 33 patients with RBD treated in the multidisciplinary sleep disorders unit at Hospital Infanta Sofía. Patients and methods: We conducted an observational descriptive retrospective analysis of patients diagnosed with RBD and treated in our multidisciplinary sleep disorders unit between October 2012 and December 2015. We recorded age, sex, associated diseases, and treatments administered to these patients. Results: A total of 365 patients were attended at our unit, including 33 with RBD: 13 women (40%) and 20 men (60%). Mean age was 62.72 years. An associated disorder was identified in 48%, with the most common being mild cognitive impairment (69%). The percentage of patients with RBD and an associated disorder among patients older than 60 was 68%. Eighty-two percent of the patients required treatment. The most commonly used drug was clonazepam (76%), followed by melatonin (9%), gabapentin (6%), and trazodone (3%). Discussion: In our series, 48% of the patients had an associated disorder. The likelihood of detecting an associated disorder increases with patients’ age. The vast majority of patients required drug treatment due to symptom severity; the most frequently administered drug was clonazepam (76%). Resumen: Introducción: El trastorno de conducta de sueño REM (TCSR) se caracteriza por conductas violentas (gritos, patadas, sueños vívidos) durante la fase REM del sueño. Tiene una prevalencia del 1-2% de la población general, especialmente en varones y en mayores de 60 años. En la última década se ha asociado como pródromo a una enfermedad neurodegenerativa. Nos proponemos analizar las patologías asociadas a los 33 pacientes con TCSR atendidos en la Unidad Multidisciplinar de Trastornos del Sueño del Hospital Infanta Sofía, y su respuesta al tratamiento farmacológico. Pacientes y métodos: Análisis descriptivo, retrospectivo, observacional, de los pacientes con diagnóstico de TCSR, atendidos en la consulta monográfica de Neurología, desde octubre de 2012 hasta diciembre de 2015. Se valoran la edad, el sexo, las enfermedades asociadas, y los tratamientos empleados. Resultados: De los 365 pacientes valorados en la consulta, 33 presentan TCSR: 13 mujeres (40%) y 20 hombres (60%), con una edad media de 62,72 años. En el 48% se identifica una patología asociada: la más frecuente es el deterioro cognitivo leve (69%). El porcentaje de TCSR con patología asociada en mayores de 60 años se eleva al 68%. El 82% de los casos han requerido tratamiento. El fármaco más utilizado ha sido el clonazepam (76%), seguido de melatonina (9%), gabapentina (6%) y trazodona (3%). Discusión: En nuestra serie el 48% de los pacientes presentan una patología asociada. La mayor edad influye directamente en la posibilidad de encontrar una patología asociada. La gran mayoría han precisado tratamiento farmacológico por la severidad de los síntomas, siendo el clonazepam (76%) el fármaco más utilizado. Keywords: REM sleep behaviour disorder, Parkinson's disease, Dementia, Sleep disorders, Multidisciplinary sleep disorders unit, Prodrome, Palabras clave: Trastorno de conducta del sueño REM, Enfermedad de Parkinson, Demencia, Trastornos del sueño, Unidad Multidisciplinar de trastornos del sueño, Pródromo

When a patient suffering from bipolar II disorder is misdiagnosed as experiencing unipolar depression, the recommended treatment of the latter may precipitate a hypomanic or manic episode. Unchecked hypomanic symptoms may include risky behaviors, through which a patient could sustain irreparable damage to relationships, careers, and finances. Sometimes, patients are familiar enough with bipolar illness that they may anticipate or interpret inquiry regarding hypomanic symptomology (Goodwin & Jamison, 1990). Applying their own stigmas to bipolar illness, such patients may only admit to depressive symptoms to avoid a bipolar diagnosis (Goodwin & Jamison, 1990). Also, hypomanic symptoms can be nuanced and difficult to detect in patients who may misinterpret the elevated mood state as a return to good mental health rather than the pathologic condition it is. These and other factors, such as poor memory, substance use, physical problems, and co-morbid mental illnesses, contribute to the misdiagnosis and delayed diagnosis of bipolar II disorder for many patients (APA, 2013; Goodwin & Jamison, 1990). The astute clinician, however, can bypass the cascade of events leading up to the poor outcomes associated with unrecognized and mistreated hypomanic symptoms by committing to due diligence when assessing mood symptoms, depressed and elevated.

Objective Mild cognitive impairment (MCI) is associated with increased memory problems although the ability to complete daily life activities remains relatively intact. This study examined: (1) if sleep disturbance increased the hazard of MCI; (2) if APOE e4 carriers with sleep disturbance experience an increased risk of MCI; and, (3) if prescription sleep medications provide a protective effect against MCI. We hypothesized that sleep disturbance increases the hazard of MCI, this relationship is stronger among APOE e4 carriers reporting a sleep disturbance. Furthermore, we hypothesized that sleep medications decrease the hazard of MCI. Methods To determine whether sleep medication mediates the risk of developing MCI for individuals with sleep disturbance and/or APOE e4, we analyzed the National Alzheimer's Coordinating Center Uniform Data Set. We selected participants with normal cognition at baseline (n = 6798), and conduced survival analyses. Results Our main findings indicated that the hazard of MCI was significantly associated with sleep disturbance. The hazard remained among those who did not use sleep medication. Trazodone and zolpidem users did not have a significant hazard of MCI, but the significant hazard remained for those who did not use these medications. APOE e4 carriers had a significantly higher hazard of MCI. Among e4 carriers who used trazodone or zolpidem, there was not a statistically significant risk of MCI. Conclusion This study demonstrated the potential utilization of trazodone and zolpidem in the treatment of sleep disturbance while potentially mitigating the risk of MCI. While trazodone and zolpidem have been shown to positively impact sleep disturbance in individuals with normal cognition, further research should explore these findings given that these medications are potentially inappropriate for older adults.

Trazadone is an antidepressant and may affect reproductive hormones and spermatogenesis. l-carnitine is an amino acid that exhibits antioxidant actions. This study was designed to investigate the potential protective effects of l-carnitine against trazadone-induced testicular toxicity in male rats and the possible underlying mechanisms such as oxidative stress, inflammation and autophagy.thirty-two male Wistar rats were divided randomly into four equal groups (n = 8). Testicular damage was induced by oral administration of Trazadone (TRZ, 20 mg/kg/day, p.o.) for four weeks (TRZ group). l-carnitine (LC, 200 mg/kg/day, p.o.) was applied for four weeks (LC group). LC + TRZ group administered the same doses of LC and TRZ concomitantly. The control group received distilled water (as vehicle).the protective treatment with LC attenuated the decline of sperm count and motility resulted from trazadone administration. Moreover, LC ameliorated trazadone increased lipid peroxidation (MDA) and reduction of total thiol and catalase activity. LC modulated the elevation in tumor necrosis factor- α (TNF-α), and increased the expression of autophagy related genes Becline-1, ATG 5 and ATG-12 in rat testes. Serum level of FSH, LH and total testosterone were increased significantly (p 0.001) in LC + TRZ group. Histopathological findings further supported the protective effects of LC against trazadone -induced testicular injury by increasing free sperms within the lumen of spermatogenic cells and improving testicular degeneration.These findings supported the protective effects of l-carnitine on rat testes due to suppression of oxidative stress, inflammation and enhancing autophagy. l-carnitine may be recommended as adjuvant therapy to trazadone treatment.

In this study, the adsorption of a multicomponent mixture of active pharmaceutical compounds, such as Venlafaxine (VLX), Trazodone (TRZ) and Fluoxetine (FLX), was studied in a biochar fixed-bed column. The selection of appropriate biochar (eucalyptus, grapevine cane and holm tree biochar) as an adsorbent was carried out through batch assays. An insight into the adsorption mechanism and its correlation with the chosen biochars was performed, showing that electron donor/acceptor interaction is the main mechanism involved. Equilibrium and kinetic batch adsorption experiments were performed and the results demonstrated that eucalyptus biochar was the most viable option for the removal of the pollutants, individually and combined. Column adsorption experiments were performed and Thomas, Yoon-Nelson and Yan models were adjusted to the breakthrough curves. This multicomponent system exhibited a synergetic behavior for TRZ and an antagonist for VLX and FLX, when compared to the single and multicomponent systems previously evaluated in batch assays. The treatment of real wastewaters, spiked with pollutants, has demonstrated the removal efficiency of multicomponent mixtures. Finally, the adsorbent regeneration by elution in different solutions was also investigated and methanol proved to be the most effective eluent for the column regeneration, This work has been finantially supported by the project CTM2017-87326-R funded by MCIN/ AEI/10.13039/501100011033/ FEDER "Una manera de hacer Europa", project ED431C 2021/43 funded by Xunta de Galicia and ERDF, and ERA-NET Cofund WaterWorks2015 Call funded by the EU and FCT/UEFISCDE/FORMAS through the REWATER International Research project. This work was also supported by UIDB/50006/2020 and UIDP/50006/2020 by the Fundação para a Ciência e a Tecnologia (FCT Portugal)/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES Portugal) through national funds. Manuela M. Moreira (project CEECIND/02702/2017) also acknowledge for her financial support financed by national funds through FCT and to REQUIMTE/LAQV. Funding for open access charge: Universidade de Vigo/CISUG

Introduction Trazodone was authorized for the treatment of depression in the 1970s. Several additional therapeutic uses have been proposed due to its heterogeneous mechanism. This study aims to determine the use of trazodone in the elderly in Spain. Methods A nationwide, longitudinal and descriptive analysis was conducted using data from patients aged >65 years with a first prescription of trazodone during the period 2002–2011. Information on dose, comorbidities and relevant co-medication was gathered from the Spanish Primary Care database BIFAP. Incidence rates of trazodone use per 10,000 person-years were calculated by sex and age. Results A total of 11,766 patients receiving a first prescription of trazodone were included. The incidence rate of trazodone use was 47.2 (95% CI: 46.33–48.04) per 10,000 person-years. An increasing trend in the use of trazodone was observed (5-fold increase in 2011 as compared to 2002). The most common therapeutic indications were: depression (21.41%), Alzheimer/dementia (20.36%), sleep disorders (16.22%), and anxiety disorder (8.91%). The median dose was 100 mg/day. The use of trazodone concomitantly with interacting medicines was frequent: anti-hypertensives (53.60%), and CNS depressors (59.32%). Conclusions Trazodone use is increasing in elderly patients, and a high proportion of use in non-approved indications was observed. Trazodone is not being used at high doses, but interacting medicines were frequent, and it may pose additional risks for elderly patients.

The piperazine derivatives correspond to an extensive chemical class of compounds with numerous neuropharmacological activities, including antidepressant (e.g., nefazodone, trazodone) and anxiolytic (e.g., buspirone) properties. Therefore, aiming to identify a new antidepressant and antianxiety lead-compound, our group designed, synthesized, and investigated the effects of a new piperazine compound, namely, LQFM104, on the behavior of mice. Male albino Swiss mice were treated with LQFM104 prior to predictive behavioral tests as open field (OFT), elevated plus maze (EPM), forced swimming (FST), and tail suspension tests (TST). The participation of the serotonergic system was evaluated by pretreatment with a 5-HT1A antagonist receptor (WAY100635) and serotonin (5-HT) synthesis inhibitor (p-chlorphenylalanine, pCPA) before oral administration of LQFM104 and behavioral tests. The treatment with LQFM104 did not interfere with locomotor activity but revealed suggestive data of anxiolytic-like effects by the increase in the time spent in the center of the OFT. This activity was confirmed by the results obtained in the EPM, and it was abolished after pretreatment with WAY100635 and pCPA. The immobility time decreased in both the FST and TST. The antidepressant-like activity was completely abolished after WAY100635 pretreatment. Altogether, these data revealed that LQFM104 possesses anxiolytic and antidepressant-like properties in behavioral tests on mice, and these activities are possibly mediated, directly and/or indirectly, by serotonergic pathways.

Restless legs syndrome is commonly co-morbid with medical conditions that are treated with antidepressant medications, such as depression, anxiety, fibromyalgia, and chronic insomnia disorder. Evidence from case reports and cross-sectional studies suggests that antidepressants may induce or worsen restless legs syndrome and increase periodic limb movements. We undertook a systematic review of the literature to identify and collate all prospective studies that measured restless legs syndrome symptoms and/or periodic limb movements following the introduction of an antidepressant. Eighteen studies were eligible for inclusion. Current data indicate that onset or exacerbation of restless legs syndrome and rise in frequency of periodic limb movements are uncommon following the initiation of an antidepressant. Among the various antidepressants, mirtazapine may be associated with higher rates of restless legs syndrome and periodic limb movements. One small study of normal volunteers suggested that venlafaxine may be associated with an increase in restless legs syndrome symptoms and periodic limb movements. Sertraline, fluoxetine, and amitriptyline appear to increase periodic limb movements that do not disrupt sleep and are thus unlikely to be clinically significant. On the other hand, bupropion may reduce restless legs syndrome symptoms, at least in the short term. Sedating antidepressants such as trazodone, nefazodone, and doxepin do not seem to aggravate periodic limb movements. The current evidence is limited by poor study design, inadequate use of standardized questionnaires, and heterogeneous populations studied for variable lengths of time. Future research should attempt to remedy these shortcomings.

There are currently no approved medications to effectively counteract the effects of methamphetamine (METH), reduce its abuse and prolong abstinence from it. Data accumulated in recent years have shown that a range of N-substituted benztropine (BZT) analogues possesses psychopharmacological features consistent with those of a potential replacement or "substitute" treatment for stimulant addiction. On the other hand, the evidence that antidepressant therapy may effectively prevent relapse to stimulant seeking is controversial. Here, we compared in rats the ability of the BZT analogue and high affinity dopamine (DA) reuptake inhibitor, JHW-007, and the antidepressant, trazodone, administered during extinction sessions after chronic METH self-administration, to alter METH-primed reinstatement of drug seeking. The data showed that trazodone produced paradoxical effects on lever pressing during extinction of METH self-administration, decreasing active, but increasing inactive, lever pressing. JHW-007 did not have any observable effects on extinction training. Importantly, JHW-007 significantly attenuated METH-primed reinstatement, whereas trazodone enhanced it. These findings lend support to the candidacy of selective DA uptake blockers, such as JHW-007, as potential treatments for METH addiction, but not to the use of antidepressant medication as a single therapeutic approach for relapse prevention.

Aim We examined the first- and second-line pharmacological treatment for delirium to determine which drugs were chosen, how and when second-line drugs were started, and the effectiveness and tolerability of those treatments. Methods A retrospective medical chart review was performed for delirium inpatients referred to the Department of Psychiatry, Hiroshima Citizens Hospital, from October 2011 to September 2012. Clinical diagnoses were based on ICD-10. We compared the baseline severity of delirium, duration needed for improvement, and rescue with antipsychotics between subjects given only first-line drugs and those switched to second-line drugs. Results We studied 194 consecutive patients including 127 men and 67 women whose average age was 76.5 ± 9.8 years. For first-line drugs, trazodone was most frequently prescribed (n = 100, 51.5%), followed by quetiapine (n = 57, 29.4%). Among patients treated with trazodone or quetiapine as first line treatment, 59 of 100 (59%) continued trazodone and 52 of 57 (91.2%) continued quetiapine. Duration needed for improvement did not differ significantly between patients treated with trazodone as a first line drug and those with quetiapine as same. Conclusion Trazodone can be a candidate drug as one of the first line drugs for delirium.

Although an inhibition of action potential conduction in nerve fibers possibly contributes to at least a part of antinociception produced by analgesics and the adjuvants, it has not been fully examined yet how the conduction inhibition differs in extent among their drugs. We investigated the effects of various antidepressants used as analgesic adjuvants on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. The results were compared with those of the other adjuvants that were reported previously. Antidepressants, duloxetine (serotonin and noradrenaline reuptake inhibitor, SNRI), fluoxetine (selective serotonin reuptake inhibitor, SSRI), amitriptyline (tricyclic tertiary amine), desipramine (tricyclic secondary amine) and maprotiline (tetracyclic secondary amine), reduced the peak amplitude of the CAP with half-maximal inhibitory concentration (IC50) values of 0.23, 1.5, 0.26, 1.6 and 0.95mM, respectively. Trazodone (non-SNRI, -SSRI, -tricyclic and -tetracyclic antidepressant) at 1.0mM reduced CAP amplitude by about 50%. The duloxetine and amitriptyline values were comparable to those of lamotrigine and carbamazepine (antiepileptics), dexmedetomidine (α2-adrenoceptor agonist) and ropivacaine, levobupivacaine and pramoxine (local anesthetics). The fluoxetine, desipramine, maprotiline and trazodone values were similar to those of oxymetazoline (α2-adrenoceptor agonist) and lidocaine, cocaine, procaine and prilocaine (local anesthetics). The antidepressants' IC50 values were much larger than that of tetracaine (local anesthetic). In conclusion, the six antidepressants inhibited CAPs with efficacies comparable to some antiepileptics, α2-adrenoceptor agonists and local anesthetics. It was suggested that antidepressants inhibit nerve conduction with efficacies comparable to those of the other adjuvants.

Objectives Antidepressants are associated with an increased risk of falls although little is known of the comparative risks of different types of antidepressants or individuals who are at greatest risk for falls. We examined the association between new use of antidepressants and fall-related injuries among older adults in long-term care (LTC). Design, Setting, Participants This was a matched, retrospective cohort study involving LTC residents in Ontario, Canada, from 2008 to 2014. New users of antidepressants were matched to non-users of antidepressants. Measurements The primary outcome was any fall resulting in an emergency department (ED) visit or hospitalization within 90 days after exposure. Secondary outcomes included hip fractures, wrist fractures, and falls reported in LTC. Multivariate logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval associated with antidepressants and outcomes. Results New users of any antidepressant had an increased risk of ED visits or hospitalization for falls within 90 days when compared with individuals not receiving antidepressants (5.2% versus 2.8%; adjusted OR: 1.9, 95% CI: 1.7–2.2). Antidepressants were also associated with an increased risk of all secondary outcomes. The increased risk of fall-related injuries was evident among selective-serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, trazodone, and across multiple patient subgroups. Conclusions New use of antidepressants is associated with significantly increased risk of falls and fall-related injuries among LTC residents across different patient subgroups and antidepressant classes. The potential risk of fall-related outcomes should be carefully considered when initiating antidepressants among older adults in LTC.

Background Several studies have investigated the prevalence and risk factors of excessive daytime sleepiness in the general population. However, few studies have investigated these in the particular subpopulation of insomnia sufferers. Thus, the aim of this study was to examine the prevalence and risk factors of excessive daytime sleepiness in a large sample of insomnia sufferers. Methods Data from 1311 insomnia sufferers with age ≥ 18 years and recruited from the research database of the sleep laboratory of the Erasme Hospital were analysed. A score > 10 on the Epworth scale was used as the cut-off score for excessive daytime sleepiness. Logistic regression analyses were conducted to examine clinical and demographic risk factors of excessive daytime sleepiness in insomnia sufferers. Results The prevalence of excessive daytime sleepiness in our sample was 45.61%. Multivariate logistic regression analysis revealed that non-use of Z-drugs, non-use of Trazodone alone or in combination, body mass index ≥ 25 & Conclusion Excessive daytime sleepiness is a common complaint for individuals with insomnia. In this subpopulation, most of the risk factors for excessive daytime sleepiness are reversible, which justifies better management of this complaint to avoid its negative consequences.

There are currently no validated pharmacotherapies for posttraumatic stress disorder (PTSD)-related insomnia. The purpose of the National Adaptive Trial for PTSD-Related Insomnia (NAP Study) is to efficiently compare to placebo the effects of three insomnia medications with different mechanisms of action that are already prescribed widely to veterans diagnosed with PTSD within U.S. Department of Veterans Affairs (VA) Medical Centers. This study plans to enroll 1224 patients from 34 VA Medical Centers into a 12- week prospective, randomized placebo-controlled clinical trial comparing trazodone, eszopiclone, and gabapentin. The primary outcome measure is insomnia, assessed with the Insomnia Severity Index. A novel aspect of this study is its adaptive design. At the recruitment midpoint, an interim analysis will be conducted to inform a decision to close recruitment to any "futile" arms (i.e. arms where further recruitment is very unlikely to yield a significant result) while maintaining the overall study recruitment target. This step could result in the enrichment of the remaining study arms, enhancing statistical power for the remaining comparisons to placebo. This study will also explore clinical, actigraphic, and biochemical predictors of treatment response that may guide future biomarker development. Lastly, due to the COVID-19 pandemic, this study will allow the consenting process and follow-up visits to be conducted via video or phone contact if in-person meetings are not possible. Overall, this study aims to identify at least one effective pharmacotherapy for PTSD-related insomnia, and, perhaps, to generate definitive negative data to reduce the use of ineffective insomnia medications. NATIONAL CLINICAL TRIAL (NCT) IDENTIFIED NUMBER: NCT03668041.

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.

Smith-Lemli-Opitz syndrome is a recessive disorder caused by mutations in 7-dehydrocholesterol reductase (DHCR)7 with a heterozygous (HET) carrier frequency of 1–3%. A defective DHCR7 causes accumulation of 7-dehydrocholesterol (DHC), which is a highly oxidizable and toxic compound. Recent studies suggest that several antipsychotics, including the highly prescribed pharmaceuticals, aripiprazole (ARI) and trazodone (TRZ), increase 7-DHC levels in vitro and in humans. Our investigation was designed to compare the effects of ARI and TRZ on cholesterol (Chol) synthesis in fibroblasts from DHCR7+/− human carriers and controls (CTRs). Six matched pairs of fibroblasts were treated and their sterol profile analyzed by LC-MS. Significantly, upon treatment with ARI and TRZ, the total accumulation of 7-DHC was higher in DHCR7-HET cells than in CTR fibroblasts. The same set of experiments was repeated in the presence of 13C-lanosterol to determine residual Chol synthesis, revealing that ARI and TRZ strongly inhibit de novo Chol biosynthesis. The results suggest that DHCR7 carriers have increased vulnerability to both ARI and TRZ exposure compared with CTRs. Thus, the 1–3% of the population who are DHCR7 carriers may be more likely to sustain deleterious health consequences on exposure to compounds like ARI and TRZ that increase levels of 7-DHC, especially during brain development.

Objectives The preparation of 131I-trazodone hydrochloride and its biological evaluation as a promising brain imaging radiopharmaceutical using two routes of administration. Material and methods Trazodone (TZ) was radiolabelled with 131I using direct electrophilic substitution, and different factors affecting labelling yield were studied. Quality control of 131I-TZ was carried out using ascending paper chromatography, paper electrophoresis, and high pressure liquid chromatography (HPLC). In vivo biodistribution of 131I-TZ was evaluated in Swiss albino mice using 3 methods: intravenous 131I-TZ solution (IVS), intranasal 131I-TZ solution (INS), and intranasal 131I-TZ microemulsion (INME). Results Optimum labelling yield of 91.23 ± 2.12% was obtained with in vitro stability of 131I-TZ up to 6 h at room temperature. The biodistribution results showed a notably higher and sustained brain uptake for INME compared to IVS and INS at all time intervals. In addition, heart and blood uptake levels for INME were lower than those for IV solution which, in turn, could decrease the systemic side effects of trazodone. Also, the 131I-trazodone INME brain uptake of 6.7 ± 0.5%ID/g was higher than that of 99mTc-ECD and 99mTc-HMPAO (radiopharmaceuticals currently used for brain imaging). Conclusion 131/123I-trazodone formulated as INME could be used as a promising radiopharmaceutical for brain imaging.

Objective To determine the risk of recurrent falls associated with antidepressants other than tricyclics (TCAs) and selective serotonin reuptake inhibitors (SSRIs) among frail older women. Methods This is a secondary analysis of the Zoledronic acid in frail Elders to STrengthen bone, or ZEST, trial data treated as a longitudinal cohort in 181 frail, osteoporotic women aged ≥65 years in long-term care. The primary exposure was individual non-TCA/non-SSRI antidepressants (i.e., serotonin norepinephrine reuptake inhibitors, mirtazapine, trazodone, and bupropion) at baseline and 6 months. The main outcome was recurrent (at least two) falls within 6 months after antidepressant exposure. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were derived using a generalized estimating equations model. Results At least 15% of women experienced recurrent falls between 0–6 and 6–12 months. At baseline and 6 months, 18.2% and 6.9% had a non-TCA/non-SSRI antidepressant, respectively. Adjusting for demographics, health status, and other drugs that increase risk of falls, non-TCA/non-SSRI antidepressant exposure significantly increased the risk of recurrent falls (AOR: 2.14; 95% CI: 1.01–4.54). Fall risk further increased after removing bupropion from the non-TCA/non-SSRI antidepressant group in sensitivity analyses (AOR: 2.73; 95% CI: 1.24–6.01). Conclusions Other antidepressant classes may not be safer than TCAs/SSRIs with respect to recurrent falls in frail older women.

Antidepressants are widely used nowadays. Due to the potential detrimental consequences and involvement in forensic cases, therapeutic drug monitoring of antidepressants is desired. Herein we report a method for sensitive determination of 13 commonly used antidepressants in blood. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method with supported liquid extraction (SLE) was developed for analysis of imipramine, desipramine, fluoxetine, norfluoxetine, paroxetine, maprotiline, sertraline, citalopram, clomipramine, trazodone, doxepin, clozapine and amitriptyline in this study. The limits of detection (LODs) are in the range of 0.0003–0.003 ng/mL, which are lower than other reported methods by several orders of magnitude. The linear ranges are 0.01–200 ng/mL for norfluoxetine, paroxetine and doxepin, while the linear ranges are 0.001–200 ng/mL for the rest antidepressants. The correlation coefficients are over 0.99. Extraction recoveries (ER) ranging in 82.4–101.5% were obtained for the target analytes. The intra-day relative standard deviations (RSDs) range in 4.5–10.3% and inter-day RSDs range in 5.1–12.7%. Reasonable values of matrix effect (ME) ranging in 82.5–110.4% were obtained for quality control samples. The present methodology was used for the analysis of antidepressants in real cases and is expected to have a wide usage for analysis of antidepressants in biomedical area and forensic practice.

Depressed patients are at increased risk of cardiovascular (CV) disease (CVD) and those with concomitant depression and CVD are at increased risk of death. The safety and efficacy of antidepressants in patients with CVD varies greatly between the agent used and type of disease. This review will summarize the CV adverse effect and drug interaction profile of antidepressants and discuss the use of antidepressants in CVD patients. We searched MEDLINE, PubMed, CINAHL, Web of Science, PsycINFO, and The Cochrane Library from inception to June 2014 to identify studies relevant to antidepressant use in patients with CVD. Primary references from the identified articles were also evaluated for inclusion. Descriptive analysis was performed for the included studies in this review. Orthostatic hypotension was more common with tricyclic antidepressants (TCAs), trazodone and monoamine oxidase inhibitors (MAOIs). Hypertension can be significant with serotonin norepinephrine reuptake inhibitors (SNRIs) and MAOIs. The potential for QT prolongation is present with TCAs, certain selective serotonin reuptake inhibitors (SSRIs), certain SNRIs and mirtazapine. Due to its low risk of drug-drug interactions, adverse effect profile and potential for beneficial antiplatelet activity, sertraline could be considered the choice antidepressant for patients with ischemic heart disease. SSRIs and potentially SNRIs are relatively safe and effective options for patients with heart failure. In patients at high risk for ventricular arrhythmias, bupropion has the overall lowest risk for QT prolongation. TCAs and MAOIs should be avoided in patients with concomitant CVD. In conclusion, due to the increased morbidity and mortality associated with comorbid CVD and depression, practitioners should readily assess and initiate management of depression in such patients. The choice of antidepressant should take into account the potential CV impact of the various agents balancing safety and efficacy.

A series of triazolopyridinone derivatives originating from the antidepressant trazodone was designed and pharmacologically evaluated. Most of the compounds with a multireceptor functional profile exhibited high potency at the D2, 5-HT1A, and 5-HT2A receptors. Compounds S1, S3, S9 and S12 were selected for further evaluation of druggable potential. Among these compounds, S1, as a D2 receptor partial agonist, demonstrated very potent inhibition of quipazine-induced head-twitch response, which validated its 5-HT2A receptor antagonistic efficacy in vivo. S1 also demonstrated a dose-dependent effect on PCP-induced hyperactivity when administered orally. Thus, S1 endowed with a triazolopyridinone scaffold represents a valuable lead for the development of novel atypical antipsychotics.

Aim Psychiatric disorders, especially depression and anxiety, are among the most disabling comorbidities in patients with epilepsy, and they are difficult to treat because many antidepressants cause proconvulsive effects. Thus, it is important to identify the seizure risks associated with antidepressants. Trazodone is one of the most frequently prescribed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs for the treatment of depression and anxiety. The aim of the present study was to evaluate the effects of trazodone on epileptiform activity in a penicillin-evoked focal seizure model in Wistar rats and in a genetic absence epilepsy model in Wistar Albino Glaxo/Rijswijk strain (WAG/Rij) rats. Methods Trazodone at 5-, 10-, and 30-mg/kg doses was injected intraperitoneally in Wistar rats 30 min after penicillin injection, and spike frequency and amplitude of penicillin-induced epileptiform activity were evaluated. In a separate experimental model, the same trazodone doses were injected in WAG/Rij rats to elucidate their effects on number, duration, and amplitude of spike-and-wave discharges (SWDs) and on depression–anxiety like behavior. In both experimental groups, after trazodone injections recordings were made for 3 h. Depression–anxiety like behaviors in WAG/Rij rats were examined using forced swim test and open-field test. Results Trazodone at 10- and 30-mg/kg doses significantly reduced the frequency of penicillin-induced epileptiform activity without changing the amplitude. Trazodone at a 5-mg/kg dose had no effect on either frequency or amplitude of epileptiform activity. Trazodone at all doses significantly increased number and duration of SWDs without changing the amplitude. In addition, all doses of trazodone decreased the number of squares crossed and duration of grooming in open-field test, and reduced swimming time activity and increased immobility time in forced swim test. Conclusion Our results suggest that depending on the dose used, trazodone had an anticonvulsant effect or no effect on penicillin-evoked focal seizure model, but all trazodone doses resulted in proconvulsant and depression–anxiety like behavior in WAG/Rij rats, which represent a genetic absence model of epilepsy.

Objective To evaluate the incidence, characteristics, and correlates of antidepressant drug therapy initiation among community-dwelling older adults following hip fracture. Design Retrospective cohort study using linked, population-based administrative data. Setting Province of Ontario, Canada. Participants Older adults, aged 65 years or older, with a hip fracture and hip fracture surgery between April 1, 2003, and February 28, 2011. The study sample was restricted to individuals who returned home following surgery and who had not been dispensed an antidepressant in the year prior to their fracture (N = 25,436). Measurements We determined the incidence of new antidepressant use defined by the dispensing of antidepressant drug therapy within 90 days of discharge home. We identified independent correlates of antidepressant initiation using multivariate regression. Results Overall, antidepressants were newly initiated in 8.8% of older adults with hip fracture in the 90 days following hospital discharge. There was a statistically significant, 1.3-fold increase in incidence of antidepressant prescribing from 2003 to 2010. Trazodone, frequently prescribed at a low dose, accounted for 39.0% of newly dispensed antidepressants, followed by selective serotonin reuptake inhibitors (36.9%). Rehabilitation admission, psychiatric evaluation, a diagnosis of dementia, and baseline benzodiazepine use were the strongest independent correlates of antidepressant initiation. Conclusion The period after a hip fracture is associated with a high rate of initiation of antidepressant therapy. The data raise the possibility that antidepressants are frequently prescribed off-label in these patients. Further research is needed to investigate the safety and efficacy of antidepressant use in this vulnerable population.

Objective To observe the influence of Kaixin Powder on ethology, content of 5-HT in the hippocampus, expression of mRNA, and protein in 5-HT1A and 5-HT2A receptors in the hippocampus of depressed rats induced by chronic unpredictable mild stress (CUMS). Methods Twenty-four male Wistar rats were randomly divided into blank, model, Trazodone, and Kaixin Powder groups, six rats in each group. In addition to the blank control group, other groups were established the depression model induced by CUMS combined with isolated feeding. At the same time, Trazodone group and Kaixin Powder group were treated with corresponding drugs for 3 weeks. After 3 weeks of administration, the rats were sacrificed, and a series of indexes were measured such as the contents of 5-HT, mRNA expression levels of 5-HT1A and 5-HT2A receptors, protein expression levels of 5-HT1A and 5-HT2A receptors, and so on. Results A series of indexes in the model group were decreased significantly such as the body weight growth, the sugar water intake, the score of Open Field Test, the content of 5-HT in the hippocampus, expression of mRNA, and protein in 5-HT1A receptor, while the expression of mRNA and protein in 5-HT2A receptor were increased significantly. Compared with the model group, the indexes were ameliorated in Trazodone and Kaixin Powder groups. Kaixin Powder is better than Trazodone in decreasing the level of protein in 5-HT2A receptor. Conclusion The result indicated that the depression performance of depressed rats induced by CUMS can be ameliorated by Kaixin Powder, and the mechanism maybe concerned with increasing the contents of 5-HT, exciting 5-HT1A receptor, and antagonising 5-HT2A receptor.

Background Selective serotonin reuptake inhibitors (SSRIs) are common treatments for patients with major depressive disorder (MDD). However, adverse effects of SSRIs on sexual function are common in the treatment of patients with MDD. There is a discrepancy in the reported frequency of SSRI-induced sexual dysfunction. On the other hand, there is also less evidence about sexual dysfunction with serotonin receptor antagonists and reuptake inhibitors (SARIs). Therefore, we aimed to assess sexual dysfunction in MDD patients who received fluoxetine, sertraline and trazodone. Method In a single-blind, randomized, controlled trial in Kermanshah, Iran, during 2009–2010, 195 patients who met the DSMIV-IR criteria for MDD were enrolled. The patients completed the Hamilton Depression Rating Scale (HAM-D) and the sexual function questionnaire (SFQ). Eligible patients were allocated in three treatment groups (receiving fluoxetine, sertraline or trazodone) for 14 weeks randomly. Measurement of HAMD was repeated in 4-week interval. Analysis for comparing sexual dysfunction among three groups and men and women was performed. Results There were 102 men and 93 women in the three groups receiving fluoxetine ( n =64), sertraline ( n =67) and trazodone ( n =64). There was no significant difference in the sexual dysfunction of the patients in the three groups at baseline ( P >.05). After treatment, both men and women who had received fluoxetine had the most impairment in desire/drive items (43%–51% and 44%–50%, respectively), while patients receiving trazodone had the least impairment in these items (12%–18% and 23%–24%, respectively). Trazodone was also induced with a lower rate of impairment in arousal/orgasm items in men (9%–15%) compared with the other two drugs. Compared with fluoxetine and trazodone, sertraline was associated with intermediate impairment in sexual function (39%–42% in desire/drive items and 32%–39% in arousal/orgasm items) that was lower than that with fluoxetine and more than that with trazodone. Conclusion There were different rates of sexual dysfunction with different antidepressants drugs in under treated patients. Compared with fluoxetine, and sertraline, trazodone was associated with the fewest sexual dysfunction. Fluoxetine was also associated with more sexual dysfunction than sertraline. Further research to better identify the differences among antidepressant drugs is recommended.

Objectives 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. Design We conducted a double-blind, randomized and controlled trial during periods of 7–9 days at baseline and 2 weeks of treatment. Setting Geriatric medical center of the university's general hospital. Participants 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). Intervention Patients received 50 mg of trazodone once daily at 10:00 P.M. or placebo in a 1:1 ratio for 2 weeks. Measurements Patients were evaluated using actigraphy and structured scales before and after intervention. Results 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. Conclusions This study shows significant therapeutic effects of trazodone 50 mg in community-dwelling AD patients with SD.

The interaction of antidepressant drug trazodone hydrochloride (TRZ) with dipalmitoyl phosphatidylcholine (DPPC) multilamellar liposomes (MLVs) in the presence and absence of cholesterol (CHO) was investigated as a function of temperature by using Electron Paramagnetic Resonance (EPR) spin labeling, Fourier Transform Infrared (FTIR) Spectroscopy and Differential Scanning Calorimetry (DSC) techniques. These interactions were also examined for dimyristoyl phosphatidylcholine (DMPC) multilamellar liposomes by using Electron Paramagnetic Resonance (EPR) spin labeling technique. In the EPR spin labeling studies, 5- and 16-doxyl stearic acid (5-DS and 16-DS) spin labels were used to monitor the head group and alkyl chain region of phospholipids respectively. The results indicated that TRZ incorporation causes changes in the physical properties of PC liposomes by decreasing the main phase transition temperature, abolishing the pre-transition, broadening the phase transition profile, and disordering the system around the head group region. The interaction of TRZ with unilamellar (LUV) DPPC liposomes was also examined. The most pronounced effect of TRZ on DPPC LUVs was observed as the further decrease of main phase transition temperature in comparison with DPPC MLVs. The mentioned changes in lipid structure and dynamics caused by TRZ may modulate the biophysical activity of membrane associated receptors and in turn the pharmacological action of TRZ. (C) 2014 Elsevier B.V. All rights reserved.

Antidepressants, even at low concentrations, can reveal some adverse effects on aquatic life due to disturbing homeostasis throughout the central and peripheral nervous system both in vertebrates and invertebrates. To date there have not been any reports regarding the presence of these pharmaceuticals in surface and tap waters in Eastern Europe. Therefore the aim of this study was to determine the presence of 21 antidepressant pharmaceuticals at specific points of the main Polish river - the Vistula, a smaller river of the Warsaw region - the Utrata, as well as in tap water samples of Warsaw. Samples were collected twice at one month intervals and analysed using solid-phase extraction (SPE) technique coupled with the liquid chromatography-electrospray ionisation-tandem mass spectrometer (LC-MS/MS) method operated under the multiple reaction monitoring mode (MRM). This is the first study where active compounds such as moclobemid or trazodone in the environment have been investigated. Environmental risk assessment of antidepressants in Poland was estimated on the basis of annuals sale data extracted from the NFZ (Narodowy Fundusz Zdrowia-National Health Service) base of reimbursed pharmaceuticals(1). Predicted environmental concentration (PEC) of target pharmaceuticals were compared with their measured concentration (MEC). Moreover, the application of the EMEA/CHMP guideline for environmental risk assessment of the antidepressants was discussed. The highest concentration of antidepressants was observed in the small river Utrata. In tap water only trace amounts of antidepressants including citalopram (up to 1.5ng/l), mianserin (up to 0.9ng/l), sertraline (

Because of their known serotonergic activity, antidepressants are well recognized in the precipitation of serotonin syndrome (SS). Serotonergic effects of the analgesic tramadol, however, are not as well understood. Several reports detail cases of SS caused by tramadol overdose. To our knowledge, only one case report has ever raised the possibility of SS in a patient on a therapeutic dose of tramadol alone. Other reports demonstrate the development of SS on nonexcessive doses of tramadol due to interactions with other drugs, usually serotonin-specific reuptake inhibitors. Here, we describe a case of SS in a patient on a routine dose of tramadol, combined with several nonserotonin-specific reuptake inhibitor medications: bupropion, trazodone, and oxycodone.

Purpose Serotonergic antidepressants (SA) are commonly used for a variety of indications in patients supported with durable left ventricular assist devices (LVAD). Reduced serotonin reuptake with SAs leads to platelet dysfunction and is associated with an increased risk of bleeding across diverse populations. There is limited data on the bleeding risk with SAs in the LVAD population prone to hemorrhagic complications due to other mechanisms. Methods We performed a retrospective analysis of LVAD patients (pts) managed at our institution from January 2016 to August 2018. Pertinent demographics and clinical variables related to bleeding were collected at the time of discharge from LVAD implantation and on admission for a bleeding event. Pts were divided into those prescribed an SA at discharge from LVAD implantation or admitted for a bleeding event with documented SA use prior to admission (Group 1) and those without SA exposure after implant (Group 2). Primary and secondary endpoints included incidence of bleeding requiring hospitalization, time from implant to first hospitalization for a bleeding event, and incidence rate of hospitalizations for bleeding per patient years. Results A preliminary analysis of 20 randomly selected pts out of 95 total implants performed. Ten pts were prescribed an SA (Group 1) and 10 were not (Group 2). Baseline demographics and bleeding risk factors were similar between the (two) 2 groups. Trazodone and sertraline were the most commonly prescribed SAs (35% each) and multiple SA use was common (50%). Acid suppressive therapy was used in all pts at discharge. In Group 1, 50% of the pts were hospitalized for a bleeding event compared to 10% of pts in Group 2 (p=0.1). At 1 year, 60% of pts remained free from hospitalization for a bleeding event in Group 1 compared to 100% in Group 2 (p=0.16). The number of bleeds per patient-year in Group 1 vs. those in Group 2 was 0.79 vs 0.4, respectively (p=0.26). Gastrointestinal (6 vs. 3 events) and intracranial (2 vs. 0 events) bleeding was more common in Group 1. Conclusion A preliminary analysis of patients with an LVAD treated with SA therapy demonstrated a trend towards an increased rate of hospitalization due to bleeding and a shorter time to first hospitalization compared to those who were not treated with an SA. Our final analysis will expand to all 95 patients to determine the significance of these findings.

Mental health is an important medical issue in perinatal care, and there is increasing evidence that insomnia during pregnancy is associated with postpartum depression (PPD). Therefore, the present study evaluated the effect of insomnia treatment during the third trimester of pregnancy on PPD symptoms. Fifty-four pregnant women with insomnia were randomly assigned to trazodone, diphenhydramine, or placebo treatment. Sleep quality was measured by actigraphy at baseline, and after 2 and 6 weeks of treatment. In addition, depression was assessed 2 and 6 weeks after delivery. Trazodone and diphenhydramine improved sleep profile compared to placebo after 6 weeks of treatment. Further, depressive symptoms were reduced 2 and 6 weeks after delivery in trazodone and diphenhydramine groups compared to placebo. No differences in depressive symptoms were observed between the trazodone and diphenhydramine groups. These findings indicate that insomnia treatment with trazodone or diphenhydramine during the third trimester of pregnancy may prevent PPD.

Background A secondary analysis was conducted to compare treatment outcomes for anxious depression and nonanxious depression in previous published OPERATION trials of a variety of antidepressants and augmentation strategies for patients with treatment-resistant depression (TRD). Methods A total of 375 patients that met DSM-IV criteria for major depressive disorder (MDD) and the stage 2 TRD criteria (described by Thase & Rush) were enrolled. Anxious depression was defined as MDD with a HRSD-17 anxiety/somatization factor score ≥7. Data were derived from an earlier study, designed to compare efficacy and tolerability of fixed dosage of extended-release venlafaxine, mitazapine, paroxetine, and risperidone, sodium valproate, buspirone, trazodone or thyroid hormone augmenting to paroxetine in those patients. Treatment outcomes were compared between patients with anxious and nonanxious TRD. Results Nearly 70% of participants had anxious depression. Remission rates were significantly lower and ratings of adverse event frequency were significantly greater in patients with anxious TRD than in those with nonanxious TRD. Presence of anxious depression predicted worse outcomes. Limitations Lack of a placebo control arm prevents us from ruling out placebo effects. The two groups were non-randomly allocated to medications. Only patients with stage 2 TRD were enrolled, which may limit generalizablity to patients without a history of resistance. Comorbid anxiety disorders that might confound the specific treatment effects were not addressed. Conclusions The findings support and extend the hypothesis that anxious depression is associated with poorer outcomes. It suggests a dimensional assessment of co-occurring anxious features of MDD patients may be clinically feasible for countries like China where difficulties in making comorbidity diagnosis exist.

The presence of distinct class of 5-HT receptors in the melanophores of tilapia (Oreochromis mossambicus) is reported. The cellular responses to 5-HT (5-hydroxytryptamine), 5-HT(1), and 5-HT(2), agonists on isolated scale melanophores were observed with regard to pigment translocation within the cells. It was found that 5-HT exerted rapid and strong concentration dependent pigment granule dispersion within the melanophores. The threshold pharmacological dose of 5-HT that could elicit a measurable response was as low as 4.7×10(-12) M/L. Selective 5-HT(1) and 5-HT(2) agonists, sumatriptan and myristicin were investigated and resulted in dose-dependent pigment dispersion. The dispersing effects were effectively antagonized by receptor specific antagonists. It is suggested that 5-HT-induced physiological effects are mediated via distinct classes of receptors that possibly participate in modulation of pigmentary responses of the fish.

Objectives To evaluate the literature regarding the use of histamine-1 (H 1 ) receptor antagonists and to describe their role in the treatment of insomnia in adult patients, including the elderly. Data sources Literature was identified via PubMed and Medline through April 1, 2012, using the search terms insomnia and sleep , each individually combined with histamine antagonist, tricyclic antidepressant, trazodone, mirtazapine, doxepin, amitriptyline, nortriptyline, trimipramine, doxylamine, diphenhydramine , and antihistamine . Study selection and data extraction Data included randomized double-blind trials that statistically evaluated H 1 receptor antagonist treatment in patients with insomnia compared with a placebo control or Food and Drug Administration–approved insomnia treatment. Trials selected evaluated sleep latency, wake after sleep onset, total sleep time, number of awakenings, and/or sleep efficiency in a subjective or objective manner. A total of 65 trials were evaluated, and 16 met inclusion criteria. Data synthesis With the exception of low-dose doxepin (Silenor—Somaxon), trials evaluating the clinical effectiveness of H 1 receptor antagonists show mixed results and are limited by sample size and generalizability. Large, randomized, appropriately controlled trials are lacking, making it difficult to define the safety and efficacy of these agents. In contrast, low-dose doxepin has been shown to provide consistent sleep benefit compared with placebo. Conclusion Over-the-counter antihistamines may have a role for short-term insomnia treatment in younger adults, but tolerance develops rapidly. Mirtazapine should not be used solely for the treatment of insomnia. Sedating antidepressants can be considered after failure of first-line insomnia treatments. Patients taking these agents chronically should be evaluated for continued efficacy and potential harm. Low-dose doxepin may have a unique role in the treatment of insomnia in elderly patients given its tolerability, documented efficacy, and lack of important adverse effects.