Evidence-Based Reviews

Benzodiazepines: A versatile clinical tool

Current Psychiatry. 2012 April;11(4):54-64

Evidence supports their use for alcohol withdrawal, insomnia, anxiety disorders, and other conditions

References

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Since the discovery of chlordiazepoxide in the 1950s, benzodiazepines have revolutionized the treatment of anxiety and insomnia, largely because of their improved safety profile compared with barbiturates, formerly the preferred sedative-hypnotic.¹ In addition to their anxiolytic and sedative-hypnotic effects, benzodiazepines exhibit anterograde amnesia, anticonvulsant, and muscle relaxant properties.¹ Psychiatrists use benzodiazepines to treat anxiety and sleep disorders, acute agitation, alcohol withdrawal, catatonia, and psychotropic side effects such as akathisia. This article highlights the evidence for using benzodiazepines in anxiety and other disorders and why they generally should not be used for obsessive-compulsive disorder and posttraumatic stress disorder (Box 1).

Box 1

When not to use benzodiazepines: OCD and PTSD

Current evidence indicates little support for using benzodiazepines for obsessive-compulsive disorder (OCD). The American Psychiatric Association (APA) and the World Federation of Biological Psychiatry do not recommend benzodiazepines for treating OCD because of a lack of evidence for efficacy.^a,b An earlier study suggested clonazepam monotherapy was effective for OCD^c; however, a more recent study did not show a benefit on rate of response or degree of symptom improvement.^d Augmentation strategies with benzodiazepines also do not appear to be beneficial for OCD management. A recent double-blind, placebo-controlled study failed to demonstrate faster symptom improvement by augmenting sertraline with clonazepam, although the study had a small sample size and high drop-out rate.^e

Because benzodiazepines have negligible action on core posttraumatic stress disorder (PTSD) symptoms (re-experiencing, avoidance, and hyperarousal), selective serotonin reuptake inhibitors and other agents largely have supplanted them for PTSD treatment.^f Use of benzodiazepines for PTSD is associated with withdrawal symptoms, more severe symptoms after discontinuation, and possible disinhibition, and may interfere with patients’ efforts to integrate trauma experiences. Although benzodiazepines may reduce distress associated with acute trauma, there is evidence—in clinical studies and animal models—that early benzodiazepine administration fails to prevent PTSD and may increase its incidence.^g The International Consensus Group on Depression and Anxiety, the APA, and the British Association for Psychopharmacology all highlight the limited role, if any, for benzodiazepines in PTSD.^h-j

References

Bandelow B, Zohar J, Hollander E, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the pharmacological treatment of anxiety, obsessive-compulsive and post-traumatic stress disorders - first revision. World J Biol Psychiatry. 2008;9(4):248-312.
American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Arlington, VA: American Psychiatric Publishing, Inc.; 2007.
Hewlett WA, Vinogradov S, Agras WS. Clomipramine, clonazepam, and clonidine treatment of obsessive compulsive disorder. J Clin Psychopharmacol. 1992;12(6):420-430.
Hollander E, Kaplan A, Stahl SM. A double-blind, placebo-controlled trial of clonazepam in obsessive-compulsive disorder. World J Biol Psychiatry. 2003;4(1):30-34.
Crockett BA, Churchill E, Davidson JR. A double-blind combination study of clonazepam and sertraline in OCD. Ann Clin Psychiatry. 2004;16(3):127-132.
Argyropoulos SV, Sandford JJ, Nutt DJ. The psychobiology of anxiolytic drugs. Part 2: pharmacological treatments of anxiety. Pharmacol Ther. 2000;88(3):213-227.
Matar MA, Zohar J, Kaplan Z, et al. Alprazolam treatment immediately after stress exposure interferes with the normal HPA-stress response and increases vulnerability to subsequent stress in an animal model of PTSD. Eur Neuropsychopharmacol. 2009;19(4):283-295.
Ballenger JC, Davidson JR, Lecrubier Y, et al. Consensus statement update on posttraumatic stress disorder from the international consensus group on depression and anxiety. J Clin Psychiatry. 2004;65(suppl 1):55-62.
Ursano RJ, Bell C, Eth S, et al. Practice guideline for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Am J Psychiatry. 2004;161(11 suppl):3-31.
Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2005;19(6):567-596.

Pharmacokinetic properties

Most benzodiazepines are considered to have similar efficacy; therefore, selection is based on pharmacokinetic considerations. Table 1 compares the indication, onset, and half-life of 12 commonly used benzodiazepines.^2-6 Although Table 1 lists approximate equivalent doses, studies report inconsistent data. These are approximations only and should not be used independently to make therapy decisions.

Table 1

Oral benzodiazepines: Indications, onset, half-life, and equivalent doses

Drug	FDA-approved indication(s)	Onset of action	Approximate half-life (hours) in healthy adults	Approximate equivalent dose (mg)^a	Comments
Alprazolam	Anxiety disorders, panic disorder	Intermediate	6.3 to 26.9 (IR), 10.7 to 15.8 (XR)	0.5	Increased risk for abuse because of greater lipid solubility
Chlordiazepoxide	Anxiety disorders, acute alcohol withdrawal, preoperative apprehension and anxiety	Intermediate	24 to 48	10	Risk for accumulation because of long-acting metabolites (desmethyldiazepam, oxazepam)
Clonazepam	Seizure disorders, panic disorder	Intermediate	18 to 50	0.25 to 0.5	Use caution in patients with liver disease
Clorazepate	Anxiety, seizures, acute alcohol withdrawal	Fast	40 to 50	7.5	Risk for accumulation because of long-acting metabolites (desmethyldiazepam, oxazepam)
Diazepam	Anxiety disorders, acute alcohol withdrawal, muscle spasms, convulsive disorders	Very fast	20 to 100	5	Risk for accumulation because of long-acting metabolites (temazepam, desmethyldiazepam, oxazepam). Increased risk for abuse because of quick onset
Estazolam	Insomnia	Intermediate	10 to 24	0.3 to 2	None
Flurazepam	Insomnia	Intermediate	47 to 100	30	Avoid in geriatric patients or patients with liver impairment
Lorazepam	Anxiety	Intermediate	10 to 20	1	Preferred for patients with liver impairment and geriatric patients
Oxazepam	Anxiety, acute alcohol withdrawal	Slow to intermediate	5 to 20	30	Preferred for patients with liver impairment and geriatric patients
Quazepam	Insomnia	Intermediate	39 to 73	5 to 15	Risk for accumulation because of long-acting metabolites (desmethyldiazepam, oxazepam)
Temazepam	Insomnia	Intermediate	3.5 to 18.4	30	Preferred for patients with liver impairment and geriatric patients
Triazolam	Insomnia	Fast	1.5 to 5.5	0.25	Lacks active metabolites
IR: immediate release; XR: extended release ^aInterpret with caution, conflicting data exist Source: References 2-6