Korean J Psychopharmacol.  2001 Sep;12(3):222-232.

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

Affiliations
  • 1Department of Neuropsychiatry & Research Institute of Medical Science, Chonnam National University Medical School, Kwangju, Korea. jsyoon@chonnam.ac.kr

Abstract


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.

Keyword

Nefazodone; Benzodiazepine; Coadministration; Depression

MeSH Terms

Alprazolam
Anxiety
Benzodiazepines*
Cytochromes
Depression*
Glucuronic Acid
Humans
Lorazepam
Outcome Assessment (Health Care)
Sleep Initiation and Maintenance Disorders
Alprazolam
Benzodiazepines
Cytochromes
Glucuronic Acid
Lorazepam
Full Text Links
  • KJP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr