What medications can be used instead of benzodiazepines (BZDs) for anxiety?

Non-Benzodiazepine Medications for Anxiety

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) should be considered first-line pharmacotherapy options for anxiety disorders instead of benzodiazepines due to their efficacy, safety profile, and lack of dependency issues. 1, 2, 3

First-Line Medications

• SSRIs: Escitalopram, sertraline, paroxetine, and fluvoxamine are effective first-line treatments for anxiety disorders with strong evidence supporting their use 4
• SNRIs: Venlafaxine is recommended as a first-line treatment with efficacy comparable to SSRIs 4, 3
• Pregabalin: An anticonvulsant that modulates calcium channels, effective for generalized anxiety disorder and considered a first-line option in some guidelines 3, 5

Second-Line Medications

• Buspirone: An azapirone that acts as a partial agonist at 5-HT1A receptors, useful for generalized anxiety disorder, particularly when added to antidepressants 2, 6
• Tricyclic antidepressants: Effective for anxiety disorders but less well-tolerated than SSRIs/SNRIs due to anticholinergic and other side effects 3
• Gabapentin: An anticonvulsant with anxiolytic properties, used off-label for anxiety disorders 5

Other Options

• Alpha-2 adrenergic agonists: Clonidine and guanfacine can be used for anxiety management, particularly when there's a component of autonomic hyperarousal 4, 5
• Beta-blockers: Propranolol can be helpful for performance anxiety and physical symptoms of anxiety 4, 5
• Hydroxyzine: An antihistamine with anxiolytic properties that can be used for short-term management of anxiety symptoms 5
• Atypical antipsychotics: May be considered in treatment-resistant cases, though their use should be limited due to metabolic and other side effects 6

Non-Pharmacological Approaches

• Cognitive Behavioral Therapy (CBT): Highly effective for anxiety disorders and should be considered either alone or in combination with medication 4, 3
• Self-help with support: Based on CBT principles, can be effective for those who don't want face-to-face therapy 4

Clinical Considerations

• SSRIs and SNRIs may take 2-4 weeks to show full therapeutic effect, so patient education about delayed onset is important 2
• After achieving remission, medications should be continued for 6-12 months to prevent relapse 2
• When switching from benzodiazepines to alternative treatments, a gradual taper is recommended to avoid withdrawal symptoms 4
• Common side effects of SSRIs/SNRIs include initial anxiety, nausea, sexual dysfunction, and sleep disturbances, but these often improve with time 3

Special Populations

• For children and adolescents with anxiety and intellectual disability, SSRIs (particularly fluoxetine and sertraline) are preferred over benzodiazepines due to potential disinhibition effects in this population 4
• In elderly patients, start with lower doses of medications and titrate slowly to minimize side effects 6
• In patients with cancer and anxiety, SSRIs are widely used for both anxiety and depression symptoms 4

Common Pitfalls to Avoid

• Abrupt discontinuation of SSRIs/SNRIs can lead to withdrawal symptoms; always taper gradually 3
• Benzodiazepines should be avoided when possible, especially in patients with a history of substance abuse 4
• Combining benzodiazepines with opioids significantly increases the risk of respiratory depression and should be avoided whenever possible 4
• Treatment resistance should prompt reevaluation of diagnosis and consideration of comorbid conditions 6