We studied the effects of trazodone on arterial blood pressure in anesthesized guinea pigs, and on vascular responses in isolated thoracic aorta. Trazodone produced a concentration-dependent relaxation in phenylephrine-precontracted endothelium intact (+E) rings, but not in a KCl-precontracted aortic rings. These relaxant effects of trazodone on +E rings were significantly greater than those on denuded (-E) rings. The trazodone-induced relaxation was suppressed by glibenclamide and tetrabutylammonium, but not by N(G)-nitro-L-arginine (L-NNA), N(omega)-nitro-L-arginine methyl ester (L-NAME), methylene blue (MB), nifedipine, indomethacin, 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC) and clotrimazole. In vivo, infusion of trazodone elicited a significant decrease in arterial blood pressure. Trazodone-induced blood pressure lowering was markedly inhibited by intravenous pretreatment of prazosin but not by pretreatment of saponin, L-NNA, L-NAME, MB, nifedipine, glibenclamide, clotrimazole and NCDC. In addition, trazodone produced an increase in twitch force of isolated papillary muscle and left ventricular pressure of perfused heart. These findings suggest that the endothelium-independent vasorelaxant effect of trazodone may be explained by activation of $Ca^{2+}$-activated and ATP-sensitive $K^+$ channels, and the hypotensive effect of trazodone is not associated with cardiac contraction.
The aim of this study was to investigate trazodone's effect on vasorelaxation and blood pressure lowering and to examine its underlying mechanism of action in isolated thoracic aorta and anesthesized rats. Precontracted aortic rings with high KCl were relaxed with trazodone, at concentrations of $50{\mu}M$ or greater. However, precontracted rings with phenylephrine (PE) were relaxed with trazodone, at concentrations of $0.03{\mu}M$ or greater, in a concentration-dependent manner. These relaxant effects of trazodone on endothelium intact rat aortic rings were significantly greater than those on denuded rings. The trazodone-induced relaxations were suppressed by nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA) and N(omega)-nitro-L-arginine methyl ester (L-NAME), guanylate cyclase inhibitors, methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a $Ca^{2+}$-activated $K^+$ channel blocker, tetrabutylammonium (TBA), a $Ca^{2+}$ channel blocker, nifedipine, $Na^+$ channel blockers, lidocaine and procaine, and removal of extracellular $Na^+$, but not by aminoguanidine, 2-nitro-4-carboxyphenyl-n, n-diphenylcarbamate (NCDC), indomethacin, glibenclamide and clotrimazole. In vivo, infusion of trazodone elicited significant decrease in arterial blood pressure. Trazodone-induced decrease in blood pressure was markedly inhibited by pretreatment of intravenous injection of saponin, L-NNA, methylene blue, TBA, lidocaine or nifedipine. These findings suggest that the endothelium-dependent relaxation and decrease in blood pressure induced by trazodone is mediated by release of NO from the endothelium, activation of TBA-sensitive $Ca^{2+}$-activated $K^+$ channels or inhibition of $Ca^{2+}$ entry through voltage-gated channel.
A study was designed to investigate the effectiveness of Korean Red Ginseng (ERG) as an oral agent for erectile dysfunction (EF), which was compared to that of placebo and trazodone. Patients who were believed to have EF of mild or non-organic etiologies, randomized into 3 groups to receive 600 mg KRG 3 times daily (group A), placebo (group B) and 25mg trazodone once a day after evening (group C). All agents were given orally. Ninety patients, composed of 30 in each group, were included and analyzed only when clinical follow-up could be achieved at the end of the study for at least 3 months. There were no significant differences(p>0.05) between each group in mean age (43.7 years), duration of EF (5.8 years), the state of marriage (married : 80 patients) and duration of marriage (18.2 years). In group A, the parameters such as rigidity and tumescence on erection, early detumescence, libido and patient's satisfaction were significantly more effective than that of other group (p<0.05). But there were no significant differences in the parameters such as the frequency of coitus, premature ejaculation and morning erection between 3 groups (p>0.05). The efficacy achieved with KGR (60%) was significantly higher (p<0.05) than that of placebo (30%) and trazodone (30%). There were no significant changes on level of serum testosterone and type of AVS-penogram in group A. No side effect was demonstrated in all patients.
The antidepressant drug trazodone (TRZ) is commonly used for treating depression, anxiety, and insomnia, however, it causes cardiotoxicity, which is one of its limitations. The objective of this work was to investigate the impact of sage (Salvia officinalis) in rats against cardiotoxicity induced by TRZ and to investigate the mechanisms involved in its cardio-protective properties through autophagy and oxidative stress. Fifty male albino rats were split randomly into five experimental groups: control group, sage oil group (100 mg/kg), TRZ group (20 mg/kg), protective group, and curative group. Cardiac function biomarkers (aspartate aminotransferase [AST], creatine kinase-MB [CK-MB], and cardiac troponin T [cTnI]) were assessed in serum. Oxidative stress and inflammatory biomarkers in cardiac tissue (total antioxidant capacity, malondialdehyde, and tumor necrosis factor-α) were evaluated. Heart tissues were subjected to histological, immunohistochemical, and ultrastructural evaluations. DNA damage also evaluated. Significant rise in the levels of AST, CK-MB, and cTnI were observed with enhanced autophagy along with marked histopathological changes in the form of interrupted muscle fibers with wide interstitial spaces with areas of hemorrhage and extravasated blood and interstitial mononuclear cellular infiltration in TRZ group. DNA damage was also significantly increased in TRZ group. However, administration of sage in both protective and curative groups show marked improvement of the cardiac alterations. In conclusion, sage ameliorated the alterations in the heart induced by trazadone through modulation of autophagy and oxidative stress.
The clinical efficacy of serotonin reuptake inhibitors such as clomipramine in the treatment of obsessive compulsive disorder(OCD) has fueled interest in the neurobiological basis of this illness. OCD is responsive exclucively to potent serotonin reuptake inhibitors clomipramine, fluoxetine, fluvoxamine, sertraline, and paroxetine and this point forms the important evidence supporting a cental role for serotonin in the pathogenesis of the disorder. Other serotonergic medications such as lithium, buspirone, trazodone, or fenfluramine may be useful as adjuvant treatments in treatmentrefractory OCD and adjuvant antipsychotics are useful in tic disorders, personality disorders, and psychotic disorders. This paper reviews results of treatment studies, investigations of biological markers, and neuroendocrine challenges and implications for the role of serotonin in pathophysiology and treatment of OCD.
Compulsive behavior is a sequence of movements usually derived from normal maintenance behaviors that are performed out of context in a repetitive, exaggerated, ritualistic, and sustained manner. In general, the treatment plan includes environmental management, behavior modifications, and psychotropic medications, however, the prognosis is varied. In this case report, a 9-year-old neutered male miniature poodle presented with a lifelong history of tail chasing and mutilation. Based on the behavioral history, observations, and physical examination, compulsive disorder was diagnosed. The dog's compulsive tail chasing behavior improved only with a combination of psychotropic medications, including fluoxetine, trazodone, and gabapentin.
Background: Depression is the leading cause of lowering the quality of life of cancer patients and lung cancer is the most likely to cause depression. It is necessary to find out depression-related factors in lung cancer patients. Methods: The study was a retrospective cohort study using medical records, and was a non-equivalent comparison group design. It involved patients diagnosed of lung cancer at the Konkuk University Medical Center from January to December 2012. Between antidepressants prescription group and non prescription group, socio-demographic factors, clinical factors, treatment-related factors and other factors were analyzed statistically. Results: Antidepressant prescription group consisted of 23 people and non-prescription group of 206 people. Prescription rate of quetiapine was the highest 47.8% (11/23), followed by escitalopram (43.5%, 10/23), amitryptyline and trazodone (30.4%, 7/23). The prescription group was prescribed with an average of 1.9 antidepressants. Antidepressants were prescribed after average of 248 days from lung cancer diagnosis and prescription period per patient was average 177.5 days. According to the result of univariate logistic regression analysis between 2 groups, factors such as number of outpatient visit, number of admission, days of hospitalization, sleep disorder, and comorbidity were found to be statistically significant (p < 0.05). However, According multivariate logistic regression analysis showed that number of admission, days of hospitalization and sleep disorder were statistically significant (p < 0.05) excluding comorbidity. Conclusion: About 10% of lung cancer patients had received a prescription for antidepressants after lung cancer diagnosis. A sleep disorder, number of hospitalization and length of stay were identified as factors influencing the prescribing antidepressants.
A total of 2,080 forensic autopsies in Seoul, Incheon and Gyeonggi province were performed by the National Forensic Service (NFS) in 2010. After analysing blood samples collected at autopsies by GC-MS and LC-MS/MS, the types and prevalence of drugs and poisons in blood were investigated using our laboratory information management system. Among 2,080 cases, 1,061 cases (51%) were positive for drugs and poisons. Surprisingly, antidepressants were identified in 137 cases which comprised 13% of the positive cases. Twelve different kinds of antidepressants were determined: Amitriptyline, fluoxetine, nortriptyline, trazodone, imipramine, mirtazapine, citalopram, venlafaxin, clomipramine, paroxetine, sertraline and bupropion. Amitriptyline was the most frequently detected antidepressant and was identified in 39 cases. Moreover, amitriptyline, fluoxetine, and nortriptyline were included in the list of the 20 most commonly encountered drugs or poisons in the analysis of blood collected at autopsies from 2007 to 2009, indicating the prevalence of their use. In this study, the 137 antidepressant-related deaths were classified by the mode of death to predict the prevalence of these drugs. As a result, those deaths were divided into four groups based on the cause and mode of death: 56 cases of suicide with fatal concentrations of antidepressant drugs in blood, 6 homicidal cases directly or indirectly related to antidepressants, 59 natural deaths with antidepressants detected in blood and 16 deaths caused by fire or other accidents with antidepressants detected in blood. Because incidents involving antidepressants have been increasing, especially in suicides or homicides, it is necessary for the health authorities and law enforcement administrations to cooperate and share the statistical data for curbing the abuse of antidepressants. This report is expected to provide the reference data related with antidepressants for the investigation of the deaths.
Purpose: The aim of this study was to investigate the current state of antidepressant prescriptions in breast cancer patients and factors affecting the prescription of antidepressants. Methods: This study targeted female breast cancer patients who were prescribed antidepressants by a psychiatrist at least once between August 2010 and July 2011 at the Asan Medical Center in Seoul. The prescription history of each study subject was investigated to analyze the current state of antidepressant prescriptions in breast cancer patients. Results: The analysis of the prescription histories of 136 subjects in the antidepressant group determined that escitalopram, mirtazapine, and trazodone were the three most commonly prescribed medications with an average of 1.54 antidepressants prescribed per patient. A logistic regression analysis showed a statistically significant increase in antidepressant prescriptions in patients who were divorced or widowed, had sleep disturbances, or had undergone oncologic surgery for the breast cancer (p<0.050). In contrast, the prescription rate was lower for patients with tumour sizes greater than 50 mm (p<0.050). Conclusion: The sociodemographic factor of marital status, clinical factors of sleep disorders and tumour size, and a treatment-specific factor of the use of surgical therapy were identified as affecting the prescription of antidepressants in female breast cancer patients.
Recently a non-electronic, disposable and portable infusor(Baxter infusor with patient control module, Baxter health care Co., Deerfield IL 60015 USA: BI $\bar{c}$ PCM) has been developed that will deliver both a continuous drug infusion as well as allow the patient to deliver extra doses of medication on a demand basis under predetermined limitation of analgesics. Patients may also not require as high analgesic dose rate to control pain when the acceptable and tolerable level of pain relief can be maintained by this device. From April l99l, we have used a total l93 units of BI $\bar{c}$ PCM. These units consisting of two components which one made by a balloon reservoir(capacity 65 ml, flow rate 0.5 ml/hr) to store medication and to regulate the pump power(490 torr), and another two PCMs to regulate additional analgesic administration by patients demand at intervals of 1S minutes and 60 minutes. The dose administered to the patient can be varied by changing the concentration of the infusate within the balloon reservoir. These devices were utilized for the pain control of 44 patients. These patients were divided into two groups. Twenty seven cases had cancer pain and 17 cases had non-cancer pain. The Touhy needle(No. l8 G.) tip was inserted into the epidural space and was used to guide the catheter to the spinal nerve level corresponding to the most painful area. The device was connected to the opposite site of the catheter tip and was filled with 60 ml of mixture solution such as 0.5% bupivacaine 15 ml, morphine HCl 10 mg, trazodone 10 ml, Tridol 3 ml and normal saline 31 ml were administed as the initial dose. When the initial dose was less effective, the next dose could be varied by increasing the concentration of bupivacaine, by adding more morphine (5~10 mg), and by reducing the volume of normal saline. Using these modules of drug self administration, we experienced the following: 1) Improvement of patient's self titration of analgesic requirement was provided. 2) The patients anxiety with pain recurrence resulting from delays in administering pain control medication was decreased significantly. 3) The working load accompanying with the single bolus injection as the usual method was reduced remarkably. 4) There was urinary retention in 5 cases and pruritus in 4 eases which developed as side effects but respiratory depression and vomiting was not encountered in a single case.
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