Acute Effect of Single Oral Administration of Nefazodone and Trazodone of Psychomotor Performance: A Duble-Blind Cross-Over Comparison in Healthy Volunteers / 대한정신약물학회지

OBJECTIVE: New antidepressant, nefazodone is classified as a serotonin -2 antagonist/reuptake inhibitor like old antidepressant, trazodone. Nefazodone, however, differs from trazodone in that it lacks anti-histaminergic properties and in that it has some norepinephrine reuptake inhibitory properties. These differences may account for the differences between the two drugs in the side effect profiles. This study was conducted to compare the acute effects of nefazodone on the psychomotor performance with those of trazodone. METHODS: The subjects were 12 healthy male volunteers aged between 20-40 years. A single, oral starting dose of nefazodone or trazodone was administered in a double-blind, randomized latin-square design with a 1-week interval between each drug switch. Psychomotor performances were assessed at 1 hour before and at 2 hours after administration of nefazodone 50 mg, nefazodone 100 mg or trazodone 50 mg. The measures of psychomotor performance included Vienna Determination Unit for complex choice reaction time, Critical Flicker Fusion Test, and Grooved Pegboard Test. RESULTS: In the Vienna Determination Unit, when 'within drug effect' (pre- vs. post-medication) was analyzed, nefazodone 100 mg decreased complex choice reaction time in both subtest 2 and subtest 3. Nefazodone 50 mg also decreased the reaction time in subtest 3 but not in subtest 2 which was more difficult and demanding task than subtest 3. On the other hand, no significant changes in the reaction time were observed with trazodone 50 mg in either subtest 2 or subtest 3. When 'between drug effect' was analyzed, however, the differences between drugs were not found to reach statistically significant level. No significant 'between drug effect' or 'within drug effect' was observed in Critical Flicker Fusion Test and Grooved Pegboard Test. CONCLUSION: Although the differences between nefazodone and trazodone did not reach statistically significant level, the results on the complex choice reaction time suggest that al least a single starting dose of nefazodone up to 100 mg does not impair psychomotor performances and it might have a less detrimental effect than trazodone on the psychomotor performance.

A Multicenter Study on Effects of Nefazodone(Serzone TM) on Depression, Anxiety, Sleep, Sexual Functions, and Quality of Life in Patients with Depression / 대한정신약물학회지

OBJECTIVE: The aim of this study is to determine effects of nefazodone on depression, anxiety, sleep and sexual function in depressive patients. SUBJECTS AND METHODS: This is an open, non-comparative, multi-center study. Antidepressant and other clinical effects of nefazodone were evaluated in 230 patients of 26 centers, aged 14 years or more, who met DSM-IV criteria to major depressive disorder or dysthymic disorder and didn't have other psychiatric disorders and were physically healthy. The clinical efficacy was assessed at week 1, 2, 4 and 8 using Clinical Global Improvement (CGI), Hamilton Depression Scale (HAM-D), Beck Depression Inventory (BDI), State and Trait Anxiety Inventory-State Anxiety (STAI-SA). Other clinical effects were assessed with Weekly Sleep Questionnaire, Sexual Functioning Questionnaire and GHQ-QOL-12, a scale for quality of life. Adverse drug reactions were checked with a questionnaire. Post-treatment effects of drug were compared with pre-treatment baseline condition. RESULTS: The response rates by Clincal Grobal Improvement and HAM-D after 8 weeks treatment were 62.4% and 75.2% respectively. Comparing to baseline, nefazodone was proved to have significantly higher antidepressant and antianxiety effects in depressive patients and it improved also sleep, sexual functions and quality of life. Both patients and physicians satisfied with the effects of drug. Adverse drug reactions were a few and not serious, and most of them disappeared as treatment continued. CONCLUSION: These results suggest that not only nefazodone has antidepressant effects and antianxiety effects, but also it improves sleep disturbance, sexual dysfunction and the quality of life in depressive patients. Adverse drug reactions were a few and not serious.

Coadministration of Nefazodone and Benzodiazepine in the Early Phase of Treatment of Depression / 대한정신약물학회지

OBJECTIVE: The purpose of this study was to examine the efficacy and safety of coadministration of nefazodone (NEF) and benzodiazepine (BZD) in the clinical setting, particularly during the initial period of treatment. METHODS: This study was based on data collected in an open, multi-center, 8-week, clinical trial of NEF in depressed patients and focused on the first 2 weeks of treatment and the concurrent use of two BZDs: alprazolam (ALP), metabolized largely by the same cytochrome P450-3A4 isoform that metabolizes NEF and lorazepam (LOR), eliminated by conjugation with glucuronic acid and less likely to interact with NEF. Patients receiving NEF alone (NEF-mono group, n=) and those receiving adjunctive BZD therapy (BZD-combi group, n=) were selected and their data were reviewed for demographic and clinical characteristics at baseline and various outcome measures at weeks 1 and 2. The BZD-combi group consisted of patients receiving alprazolam (ALP-combi subgroup, n=) and those receiving lorazepam (LOR-combi subgroup, n=). Efficacy was analysed according to the individual groups and subgroups. In addition, the efficacy at each time point was compared between NEF-mono and BZD-combi groups as well as between ALP-combi and LOR-combi subgroups. Safety and tolerability were judged by reported adverse effects and were compared. RESULTS: In NEF-mono and BZD-combi groups, the mean daily dose for NEF was less than 200 mg/day (range, 50-500 mg/day) and did not differ between groups and subgroups. The mean daily doses for BZDs were 0.61 mg/day (range, 0.25-1.5 mg/day) for ALP and 1.49 mg/day (range, 0.5-2.5 mg/day) for LOR. Sleep, anxiety and depression in both NEF-mono and BZD-combi groups were, in general, significantly improved compared to baseline. Furthermore, BZD-combi group showed greater improvement in anxiety and sleep but not in depression compared to NEF-mono group. Within the BZD-combi group, there was no significant difference in clinical effects between ALP-combi and LOR-combi subgroups. In terms of safety and tolerability, there was no evidence to suggest that BZD combination caused daytime sedation or any other particular adverse events more severely than NEF alone. Also, there was no significant difference in the side effect profiles of ALP-combi and LOR-combi subgroups. CONCLUSION: These results suggest that combining low doses of ALP or LOR with NEF is beneficial for the control of insomnia and anxiety without substantial adverse effects, at least during the early period of treatment of depression when therapeutic dosages of NEF are not yet reached.

Nefazodone and Associated Perceptual Disturbance : A Report of Four Cases

Nefazodone, a newer antidepressant is a phenylpiperazine derivative that inhibits the reuptake of both norepinephrine and serotonin, and antagonizes 5-HT2A and alpha1 adrenergic receptors. Compared with SSRIs nefazodone caused the fewer activating symptoms, adverse gastrointestinal effects(nausea, diarrhea, anorexia) and adverse effects of sexual function, but is associated with the more dizziness, dry mouth, constipation, visual disturbances and confusion. We report on 4 cases of visual disturbances and hallucinations in patients taking nefazodone. 1) Nefazodone, as a 5-HT2A antagonist, might induce visual disturbances. 2) mCPP, metabolite of nefazodone might contribute to the hallucination through action on 5-HT receptor. 3) Dopaminergic enhancing activity of nefazodone might cause hallucination. The case report raises the possibility that dose-related perceptual disturbances may exist with nefazodone. The fact emphasizes the need to pay close attention to all possible drug interactions, particularly in patients treated with multiple psychoactive agents, older patients, and patients with decreased hepatic function.