What are non-benzodiazepine options for anxiolysis?

From the Guidelines

Non-benzodiazepine options for anxiolysis include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), buspirone, antihistamines, beta-blockers, pregabalin, and gabapentin, which are effective alternatives to benzodiazepines for managing anxiety. These medications work through various mechanisms, including modulating neurotransmitters like serotonin, norepinephrine, and GABA, or by reducing sympathetic nervous system activity, providing alternatives to benzodiazepines which can cause dependence and tolerance with long-term use 1.

Key Medications

• SSRIs like sertraline (50-200 mg daily), escitalopram (10-20 mg daily), and fluoxetine (20-80 mg daily) are first-line treatments for most anxiety disorders, though they typically take 2-4 weeks to reach full effectiveness.
• SNRIs such as venlafaxine (75-225 mg daily) and duloxetine (30-120 mg daily) are also effective, particularly for anxiety with comorbid pain.
• Buspirone (15-60 mg daily in divided doses) can be helpful for more immediate relief, working within 1-2 weeks.
• Certain antihistamines like hydroxyzine (25-100 mg up to four times daily) provide rapid anxiolysis.
• Beta-blockers such as propranolol (10-40 mg as needed) effectively manage physical symptoms of anxiety, especially performance anxiety.
• Pregabalin (150-600 mg daily in divided doses) and gabapentin (300-3600 mg daily in divided doses) can treat anxiety, particularly with neuropathic pain.

Considerations

• The choice of medication should be informed by side-effect profiles, interactions, response, patient age, and preference, as recommended by recent guidelines 1.
• Interventions with short-term duration should be considered, and patients should be monitored regularly for adherence, side effects, and adverse events.
• Tricyclic antidepressants and certain atypical antipsychotics may be used in specific cases but carry more side effects, and their use should be carefully considered based on the individual patient's needs and medical history.

From the FDA Drug Label

Buspirone hydrochloride tablets, USP are an antianxiety agent that is not chemically or pharmacologically related to the benzodiazepines, barbiturates, or other sedative/anxiolytic drugs. Non-benzodiazepine options for anxiolysis include buspirone, which is an antianxiety agent that is not related to benzodiazepines.

• Key points about buspirone:
  • Not chemically or pharmacologically related to benzodiazepines
  • Used as an antianxiety agent
  • Available in various doses, including 5 mg, 10 mg, 15 mg, and 30 mg tablets 2

From the Research

Non-Benzodiazepine Options for Anxiolysis

• Buspirone is a non-benzodiazepine anxiolytic with a unique chemical structure, as evidenced by a study published in 1986 3.
• It has been shown to be effective in treating generalized anxiety disorder, with a similar efficacy to benzodiazepines such as diazepam and clorazepate, but with fewer side effects like sedation 3, 4.
• Buspirone's mechanism of action is not fully understood, but it is thought to act as a midbrain modulator, exerting selective anxiolytic activity 4.
• Another option is hydroxyzine, an antihistamine medication that has been used to treat anxiety, with some evidence suggesting it is more effective than placebo for generalized anxiety disorder 5.
• Hydroxyzine has been shown to be equivalent in terms of efficacy, acceptability, and tolerability to other anxiolytic agents like benzodiazepines and buspirone 5.
• Buspirone has also been used to treat anxiety disorders and comorbid alcohol abuse, with a case report suggesting it is an effective alternative for patients with underlying hematological conditions 6.
• The pharmacokinetics of anxiolytic drugs, including buspirone and hydroxyzine, have been reviewed, highlighting the need for a more balanced assessment of the benefits and risks associated with their use 7.