A diverse range of indications
Alcohol withdrawal. Benzodiazepines are the treatment of choice for alcohol withdrawal syndrome, particularly to prevent seizures.7 Research supports symptom-triggered therapy using the revised Clinical Institute Withdrawal Assessment for Alcohol. Benzodiazepines reduce CNS sympathetic hyperactivity to mitigate withdrawal from alcohol by decreasing tachycardia, tremor, insomnia, agitation, and anxiety. Furthermore, these agents provide prophylaxis against serious sequelae such as seizures and delirium.
Insomnia. The American Academy of Sleep Medicine considers benzodiazepine receptor agonists (BzRAs, which include benzodiazepines and non-benzodiazepines) and ramelteon first-line pharmacotherapy for primary insomnia.8 However, pharmacologic treatment should be short-term. Agents with short to intermediate half-lives and rapid onset, such as triazolam, can aid sleep initiation. Those with longer half-lives, such as temazepam, could address sleep maintenance. If a patient does not respond to the initial agent, try another medication within the same class, because patients may respond differently. Use lower starting doses in geriatric patients.9 Closely monitor for adverse effects, rebound insomnia, and potential abuse or tolerance. Identify comorbid conditions and medications that may impair sleep, and address them accordingly.
Psychological and behavioral treatments given over 4 to 8 weeks can yield stable sleep improvements for up to 2 years. If available, these interventions may be considered first-line for treating insomnia because of their lasting effects compared with BzRAs.10
Generalized anxiety disorder (GAD). Benzodiazepines effectively treat GAD because they work quickly and are well tolerated. However, there are better first-line treatment options when considering efficacy studies and dependence and tolerance concerns. One effect-size comparison of 21 double-blind, placebo-controlled trials showed that the efficacy of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and pregabalin are comparable to benzodiazepines.11 Benzodiazepines can be used in the first 2 to 3 weeks after initiating antidepressants to alleviate and prevent worsening of anxiety that may occur at the start of antidepressant therapy. Recent treatment guidelines recommend benzodiazepines as a second-line treatment or for treatment-resistant GAD in patients who do not have a substance abuse history.12,13
Panic disorder. Efficacy of benzodiazepines for panic disorder is comparable to SSRIs, SNRIs, and tricyclic antidepressants (TCAs). SSRIs and SNRIs are considered first-line treatments for panic disorder because of their favorable side effect profile.14 In practice, benzodiazepines often are combined with SSRIs, SNRIs, or TCAs. A randomized controlled trial demonstrated that paroxetine and clonazepam (mean dose 1.6 mg/d at 5 weeks) resulted in a more rapid response compared with paroxetine alone, although this difference lasted only a few weeks.15 Furthermore, this study suggested that brief treatment with clonazepam followed by a taper is as effective as sustained treatment with paroxetine and clonazepam.15
There is a lack of high-quality data on combining cognitive-behavioral therapy (CBT) and benzodiazepines for panic disorder, although a Cochrane Review found that adding a benzodiazepine to CBT did not lead to a significant difference in response compared with psychotherapy alone.16 A recent randomized controlled trial demonstrated that tapering benzodiazepines combined with CBT was associated with successful discontinuation of the drug and prevented return of panic symptoms.17
Social anxiety. A meta-analysis found that for treating social anxiety, benzodiazepines have better efficacy than SSRIs, monoamine oxidase inhibitors, and anticonvulsants.18 Longer-acting benzodiazepines may be more effective than shorter-acting agents. One study of patients with social anxiety showed a 38% response rate for alprazolam vs 20% for placebo over 12 weeks, and a similar 10-week study demonstrated a 73% recovery rate with clonazepam vs 22% for placebo.19 In addition, studies have observed that patients can be maintained on clonazepam for up to 2 years without symptom relapse and will tolerate slow-taper discontinuation.18,20 Sedation and drowsiness can be lessened by limiting clonazepam doses to 2 to 3 mg/d.
Akathisia and tremor. Akathisia, a syndrome of motor restlessness and inner turmoil, is associated with antipsychotics but can occur with SSRIs. Reducing the dosage or switching to another, usually less potent agent often can relieve akathisia. When these remedies are not tenable, consider benzodiazepines along with other medications—including beta blockers and anticholinergic agents—with demonstrated efficacy in reducing akathisia symptoms. Lorazepam, diazepam, and clonazepam have demonstrated efficacy for relieving akathisia in comparison studies with placebo, propranolol, and diphenhydramine.21,22
Drug-induced postural tremor can occur with several psychotropics, including lithium, valproic acid, antidepressants, and antipsychotics. A tremor is considered mild if a patient can drink a glass of water with 1 hand without spilling and severe if holding a glass with 2 hands is difficult. Propranolol is most commonly prescribed for these tremors, but alprazolam and clonazepam have demonstrated efficacy, either as monotherapy or coadministered with a beta blocker.23