Should we consider prescribing a benzodiazepine in persons with major depressive disorder with anxiety symptoms?
It is being done commonly
1. Newly starting an antidepressant
Of commercially insured adults in the US with a diagnosis of a depressive disorder, 11% are started on an antidepressant and a benzodiazepine simultaneously (Bushnell et al., 2017).
2. Prevalence in those taking an antidepressant
In a mood disorders psychopharmacology unit of a university network (Rizvi et al., 2015), 25% of persons with major depressive disorder were regularly taking a benzodiazepine. Those who were taking a benzodiazepine were more likely to be female, to be unemployed, to have a history of child abuse, and to have comorbid panic disorder.
In a community survey, as many as 49% of those who had major depressive episode in the previous 12 months and were taking an antidepressant were also taking a benzodiazepine (Sanyal et al., 2011).
Of course, it is not clear from these studies whether the benzodiazepine was prescribed for a comorbid anxiety disorder or for anxiety symptoms of the major depression itself.
A meta-analysis of all the randomized, controlled clinical trials done to that point (Furakawa et al., 2002) found that persons with major depressive disorder who received a benzodiazepine along with an antidepressant are:
– Less likely to discontinue treatment (relative risk 0.63)
– Less likely to discontinue treatment due to side effects (relative risk 0.53). The risk was reduced by almost half!
Does adding a benzodiazepine also lead to greater improvement in depression?
– More likely to show improvement in depression at one week (relative risk 1.63). This shows that many more patients feel better sooner–in just one week.
– More likely to show improvement in depression at four weeks (relative risk 1.38)
– Not more likely show improvement in depression at six or eight weeks.
– The person can have any of the usual potential side effects of benzodiazepines
– Risk of benzodiazepine abuse or dependence
– Persons with major depressive disorder who were taking a benzodiazepine were more likely to have anhedonia (Rizvi et al., 2015) but a cause and effect relationship has not been shown.
– Animal studies have raised concern that benzodiazepines may counteract the increase in neurogenesis that antidepressants may produce (e.g., Sun et al., 2013; Boldrini et al., 2014).
Since the benefit is mainly or entirely in the first four weeks and there are significant potential drawbacks in the longer run, I recommend that we should start slowly tapering off the benzodiazepine after the first few weeks, once the antidepressant is well-established (i.e., the initial side effects have been dealt with), the anxiety is signficantly less, and, hopefully, the depression is starting to get better.
Boldrini M, Butt TH, Santiago AN, Tamir H, Dwork AJ, Rosoklija GB, Arango V, Hen R, Mann JJ. Benzodiazepines and the potential trophic effect of antidepressants on dentate gyrus cells in mood disorders. Int J Neuropsychopharmacol. 2014 Dec;17(12):1923-33. PubMed PMID: 24969726; PubMed Central PMCID: PMC4374628.
Bushnell GA, Stürmer T, Gaynes BN, Pate V, Miller M. Simultaneous Antidepressant and Benzodiazepine New Use and Subsequent Long-term Benzodiazepine Use in Adults With Depression, United States, 2001-2014. JAMA Psychiatry. 2017 Jul 1;74(7):747-755. PubMed PMID: 28593281; PubMed Central PMCID: PMC5710248.
Fulone I, Silva MT, Lopes LC. Factors Associated with the Combined Use of Antidepressants and Benzodiazepines in Major Depression: A Case-Control Study. Basic Clin Pharmacol Toxicol. 2016 Sep;119(3):273-7. PubMed PMID: 26998968.
Furukawa TA, Streiner DL, Young LT. Antidepressant and benzodiazepine for major depression. Cochrane Database Syst Rev. 2002;(1):CD001026. Review. PubMed PMID: 11869584.
Rizvi SJ, Sproule BA, Gallaugher L, McIntyre RS, Kennedy SH. Correlates of benzodiazepine use in major depressive disorder: The effect of anhedonia. J Affect Disord. 2015 Nov 15;187:101-5. PubMed PMID: 26331683.
Sanyal C, Asbridge M, Kisely S, Sketris I, Andreou P. The utilization of antidepressants and benzodiazepines among people with major depression in Canada. Can J Psychiatry. 2011 Nov;56(11):667-76. PubMed PMID: 22114921.
Sun Y, Evans J, Russell B, Kydd R, Connor B. A benzodiazepine impairs the neurogenic and behavioural effects of fluoxetine in a rodent model of chronic stress. Neuropharmacology. 2013 Sep;72:20-8. PubMed PMID: 23639432.
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