Evaluation of efficacy and tolerability of dothiepin hydrochloride in the management of major depression in patients suffering from rheumatoid arthritis.

Several studies have shown that 20 to 66.2% of patients with rheumatoid arthritis have associated psychiatric comorbidity especially depression. Dothiepin hydrochloride is a well-established and effective antidepressant in patients with depressive symptoms of varying severity and co-existing anxiety. To document the efficacy and tolerability of dothiepin hydrochloride in the management of major depressive disorder (MDD) in rheumatoid arthritis patients a phase IV, open, single arm, prospective study was initiated with dothiepin hydrochloride in the dose of 75 mg/day, duration of therapy was 6 weeks. Twenty-five rheumatoid arthritis patients suffering from co-morbid MDD completed the 6-week dothiepin hydrochoride treatment and were considered for final analysis. There was significant reduction (p < 0.05) in mean HAM-D scores at week 2 (13.92 +/- 5.45), week 4 (9.28 +/- 4.13) and week 6 (5.72 +/- 3.26) compared to baseline (21.64 +/- 5.93). There was significant reduction (p < 0.05) in mean HAM-A scores at week 2 (6.52 +/- 3.34), week 4 (4.0 +/- 2.25) and week 6 (2.76 +/- 1.59) compared to baseline (10.68 +/- 3.68). The global impression of efficacy at the end of 6 weeks of dothiepin hydrochloride treatment was rated by the clinician (psychiatrist) as marked and moderate improvement in 20 (80%) and 5 patients (20%) respectively. Only 2 patients reported dry mouth as an adverse event in the study. The overall assessment of tolerability at the end of 6 weeks of dothiepin hydrochloride treatment was rated by the clinician (psychiatrist) as good and fair in 19 (76%) and 6 patients (24%) respectively. Dothiepin hydrochloride was found to be an effective and well-tolerated drug in the management of MDD and anxiety in patients suffering from rheumatoid arthritis.

The Effect of Tricyclic Antidepressant(Dothiepin) on Sleep in Depressed Patients: A Polysomnographic Study / 신경정신의학

OBJECTIVE: This study was designed to investigate 1) sleep changes after antidepressant(dothiepin) treatment, and 2) sleep variables which seem to be associated with clinical response in the depressed patients. METHODS: The subjects consisted of 16 patients who fullfilled the criteria for major depression by the Diagnostic and Statistical Manual,(4th edition). Their sleep was recorded using polysomnography at the baseline and after one week and three weeks of dothiepin treatment. All subjects were further interviewed using Hamilton Rating Scale for Depression (HRSD) to rate the severity of their depression. High response to the drug was defined as a reduction of more than 50% of the HRSD score. Result : The results were as follows : 1) Depressed patients after dothiepin treatment showed more total sleep time(p=0.019), shorter sleep latency(p=0.05), less awake time(p=0.033), more sleep efficiency(p=0.018), more stage 2 sleep(p=0.002), less REM time(p=0.000), and longer REM sleep latency(p=0.004) than before treatment. 2) There were no differences in sleep variables between those who received 1 week and 3 weeks of dothiepin treatment except of th shortening of sleep latency after 3 weeks(p<0.05). 3) Depressive symptom scores on HRSD were reduced after 1 week and 3 weeks of dothiepin treatment as compared with the baseline. 4) High responers showed a tendency of increased wake time(p=0.054), while their stage 4 sleep decreased after 1 week of dothiepin treatment as compared with the low responders(p=0.0136). Conclusions : These results suggest that sleep of the depressed patients after dothiepin treatment tends to be nomalized and sleep chages seem to appear early in the treatment phase. In addition, clinical response might be associated with greater wake time at the baseline and lesser atage 4 sleep 1 week of dothiepin treatment.

Comparison between Dothiepin-Sertraline Combination and Dothiepin Alone Therapy in the Treatment of Depressive Disorder

The dysfunction of either or both noradrenaline and serotonin system are important in the pathophysiology of depression. Previous reports have suggested that there may be an important interaction between these two systems. Recently, some investigators have suggested that the combination of tricyclic antidepressants(TCAs and selective serotonin reuptake inhibitors(SSRIs would produce a rapid synergistic effect on down-regulation of either or both of these two systems and that this combination may produce a more rapid and absolute antidepressant effect. We compared the treatment efficacy, treatment associated side effects, treatment satisfaction, and the quality of life between the combination therapy of dothiepin-sertraline as well as the therapy of dothiepin alone in the treatment of major depressive disorder and dysthymic disorder. In our study, the combination therapy of dothiepin and sertraline produced a more rapid and absolute antidepressant effect than dothiepin alone. And the patients with combination therapy experienced relatively high treatment satisfaction than the patients with dothiepin therapy. The patients quality of life improved more rapidly in the combination therapy, especially, in the health perception, social behavior, and life satisfaction, that dothiepin alone. These results support the hypothesis that the combination of TCA an SSRI may produce a rapid synergistic effect on either or both norepinephrine and serotonin system, and more rapid antidepressant effect and high treatment satisfaction.

Evaluation of testicular histology and micronucleus test in mice treated by bromocryptine mesylate and dothipen hydrochloride

The present study aimed to evaluate and compare the genotoxicity and morphological changes in mouse testis after short term chronic administration of either BCM or DPH. They were administered by daily oral doses [1/10 LD 50] for 4 weeks, then the treatment was stopped for another 4 weeks to study the effects of the drugs. 100 male mice were used and classified into 3 groups, a control group and 2 groups for testing the effects of BCM and DPH. The seminiferous tubules showed disorganization, hypospermtogenesis and spermatogenic arrest. Their lumina contained desquamated spermatogenic cells or necrotic tissue. The inter-tubular spaces contained dilated blood vessels and an exudate. In DPH treated group the nuclei of germ cells appeared pyknotic at the 4th week. There were marked improvement in testicular structure after cessation of BCM treatment. While the DPH-treated group needed longer period to attain its original architecture. The micronucleated PCEs were significantly increased at the 3rd and 4th weeks of BCM treatment and their numbers declined when the treatment was stopped for another 4 weeks

Effects of ECT-dothiepin combination on learning in rats.

Electroconvulsive therapy (ECT) and antidepressant drugs are each known to impair learning and memory. No information is available on their effects on cognition when used concurrently in the treatment of depression, as is frequent in India. In the present study, therefore, the effects of electro-convulsive shocks (ECS) and dothiepin, separately and in combination, were studied in an animal model employing a complex maze operant learning paradigm. ECS were given on alternate days (3/week) for 2 weeks. Dothiepin (10 mg/kg, ip) was administered once daily for 2 weeks. Learning was assessed on days 2-10 post-treatment ECS produced greater initial impairment in learning while dothiepin produced a more sustained impairment. While impairment was maximum in the combined treatment group, the statistical significances that emerged to proscribed the combination were but weak.

Effect of dothiepin on nociceptive response in diabetic rats.

In alloxan-diabetic rats of 4 wk duration with blood glucose levels of about 300 mg/100 ml, the tail flick reaction time (TFRT) to thermal stimuli was significantly elevated (P less than 0.25), indicating hypoalgesia. Intraperitoneal dothiepin, injections of 25 mg & 50 mg/kg body weight per day did not significantly alter the TFRT, either in control or in diabetic rats, following either acute (one dose), or short term (once a day for five days) administration. It is concluded that at least in the dosage schedule used herein, dothiepin does not influence hypoalgesia of diabetic neuropathy.