Non-Benzodiazepine Medications for Anxiety

First-Line Medications

The American Academy of Neuropsychopharmacology recommends SSRIs, such as escitalopram, sertraline, paroxetine, and fluvoxamine, as effective first-line treatments for anxiety disorders with strong evidence supporting their use 1, 2, 3
The American Academy of Neuropsychopharmacology recommends SNRIs, such as venlafaxine, as a first-line treatment with efficacy comparable to SSRIs 2, 3

The American Academy of Child and Adolescent Psychiatry suggests alpha-2 adrenergic agonists, such as clonidine and guanfacine, can be used for anxiety management, particularly when there's a component of autonomic hyperarousal 4
The American Thoracic Society recommends beta-blockers, such as propranolol, for performance anxiety and physical symptoms of anxiety 5

The American Academy of Neuropsychopharmacology recommends Cognitive Behavioral Therapy (CBT) as highly effective for anxiety disorders and should be considered either alone or in combination with medication 1, 2
The American Academy of Neuropsychopharmacology suggests self-help with support, based on CBT principles, can be effective for those who don't want face-to-face therapy 2

The Centers for Disease Control and Prevention recommends a gradual taper when switching from benzodiazepines to alternative treatments to avoid withdrawal symptoms 6

The American Academy of Child and Adolescent Psychiatry recommends SSRIs, particularly fluoxetine and sertraline, for children and adolescents with anxiety and intellectual disability due to potential disinhibition effects in this population 4, 7
The National Comprehensive Cancer Network recommends SSRIs for patients with cancer and anxiety, as they are widely used for both anxiety and depression symptoms 8, 9

The Centers for Disease Control and Prevention warns that benzodiazepines should be avoided when possible, especially in patients with a history of substance abuse, and that combining benzodiazepines with opioids significantly increases the risk of respiratory depression and should be avoided whenever possible 6

The American College of Neuropsychopharmacology recommends SSRIs, including escitalopram, sertraline, paroxetine, and fluvoxamine, as effective first-line treatments for various anxiety disorders 10
SSRIs are particularly effective for social anxiety disorder with a Number Needed to Treat (NNT) of 4.70 11
Common side effects of SSRIs include somnolence, dizziness, nausea, and potential serotonin syndrome which requires monitoring 12
Venlafaxine is suggested as an effective first-line treatment with efficacy comparable to SSRIs (NNT = 4.94) 10, 11
SNRIs have similar dropout rates to placebo, suggesting good tolerability 11

The American Academy of Sleep Medicine suggests that sedating antidepressants like trazodone, amitriptyline, doxepin, and mirtazapine can be considered when first-line treatments are unsuccessful 13
These medications have the added benefit of helping with comorbid insomnia due to their sedating properties 13

The American Geriatrics Society recommends that benzodiazepines should be avoided in older adults due to increased risk of falls, cognitive impairment, and delirium 14
When treating anxiety in older adults, start with lower doses of SSRIs or SNRIs and titrate slowly 14

The American Academy of Sleep Medicine recommends that short-term hypnotic treatment should be supplemented with behavioral and cognitive therapies 13
For treatment-resistant anxiety, consider combining medications from different classes after monotherapy trials 13
Medication selection should be guided by symptom pattern, treatment goals, past treatment responses, comorbid conditions, contraindications, and potential drug interactions 13