Trazodone Loaded Lipid Core Poly (ε-caprolactone) Nanocapsules: Development, Characterization and in Vivo Antidepressant Effect Evaluation.

Trazodone hydrochloride (TRH) is a lipophilic drug which is used effectively as an antidepressant. Its poor solubility and short half-life represent an obstacle for its successful use. Nanocapsules with biodegradable polymeric shell are successful drug delivery systems for controlling the release of drugs. To enhance the entrapment of lipophilic drugs, oils can be added forming a lipophilic core in which the drug is more soluble. The aim of this study was to enhance the efficacy of TRH and prolong its action by formulating it into lipid core polymeric shell nanocapsules. Nanocapules were prepared using nanoprecipitation technique. All prepared formulations were in nano size range and negatively charged. The TRH entrapment efficiency (EE%) in lipid core nanocapsules was up to 74.8 ± 0.5% when using Labrafac lipophile as a lipid core compared to only 55.7 ± 0.9% in lipid free polymeric nanospheres. Controlled TRH release was achieved for all prepared formulations. Forced swim test results indicated the significant enhancement of antidepressant effect of the selected TRH loaded Labrafac lipophile core nanocapsules formulation compared to control and TRH dispersion in phosphate buffer. It is concluded that lipid core nanocapsules is a promising carrier for the enhancement of TRH efficacy.

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

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

Serotonergic medications, herbal supplements, and perioperative serotonin syndrome.

PURPOSE: Perioperative use of serotonergic agents increases the risk of serotonin syndrome. We describe the occurrence of serotonin syndrome after fentanyl use in two patients taking multiple serotonergic agents. CLINICAL FEATURES: Two patients who had been taking multiple serotonergic medications or herbal supplements (one patient taking fluoxetine, turmeric supplement, and acyclovir; the other taking fluoxetine and trazodone) developed serotonin syndrome perioperatively when undergoing outpatient procedures. Both experienced acute loss of consciousness and generalized myoclonus after receiving fentanyl. In one patient, the serotonin syndrome promptly resolved after naloxone administration. In the other patient, the onset of serotonin syndrome was delayed and manifested after discharge, most likely attributed to the intraoperative use of midazolam for sedation. CONCLUSION: Even small doses of fentanyl administered to patients taking multiple serotonergic medications and herbal supplements may trigger serotonin syndrome. Prompt reversal of serotonin toxicity in one patient by naloxone illustrates the likely opioid-mediated pathogenesis of serotonin syndrome in this case. It also highlights that taking serotonergic agents concomitantly can produce the compounding effect that causes serotonin syndrome. The delayed presentation of serotonin syndrome in the patient who received a large dose of midazolam suggests that outpatients taking multiple serotonergic drugs who receive benzodiazepines may require longer postprocedural monitoring.

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

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

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

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

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

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

A combination of hypothalamic phospholipid liposomes with trazodone for treatment of depression. An open controlled study.

In an open controlled trial of 48 patients with major depression illness (according to DSM-III), the patients were randomly assigned to 2 groups. One group of 25 patients was treated with 200-300 mg/day of trazodone and a second group of 23 patients was treated with 200-300 mg/day trazodone plus 1 ampoule (corresponding to 1000 gamma of lipidic phosphorous) twice daily of hypothalamic phospholipids (HPL). The effectiveness of treatment was evaluated by the Hamilton Rating Scale for Depression (HRSD). Side effects of treatment with trazodone were looked for by measuring systolic and diastolic blood pressure and heart rate and from EEG made before and on the 7th and 30th days of treatment. Combination with HPL shortened the typical latency of action of the antidepressant trazodone, definitely improved the subjective symptoms, especially the psychosomatic symptoms, on the HRDS and decreased the incidence of such side effects of trazodone as hypertension, reflex tachycardia and asthenia.