What medications can be used to control anxiety without benzodiazepines (BZDs)?

Non-Benzodiazepine Medications for Anxiety Management

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are the first-line medications recommended for anxiety management without benzodiazepines due to their established efficacy and favorable safety profile. 1, 2

First-Line Medications

SSRIs

• SSRIs including escitalopram, sertraline, paroxetine, and fluvoxamine are recommended as effective first-line treatments for various anxiety disorders 1, 3
• These medications have the highest level of evidence supporting their use in anxiety disorders and do not cause dependency issues 4
• SSRIs are particularly effective for social anxiety disorder with a Number Needed to Treat (NNT) of 4.70 3
• Common side effects include somnolence, dizziness, nausea, and potential serotonin syndrome which requires monitoring 3

SNRIs

• Venlafaxine is suggested as an effective first-line treatment with efficacy comparable to SSRIs (NNT = 4.94) 3
• SNRIs have similar dropout rates to placebo, suggesting good tolerability 3
• Venlafaxine can be particularly useful when both anxiety and depression are present 2

Second-Line Medications

Sedating Antidepressants

• Trazodone, amitriptyline, doxepin, and mirtazapine can be considered when first-line treatments are unsuccessful 3
• These medications have the added benefit of helping with comorbid insomnia due to their sedating properties 3

Anti-Epileptic Medications

• Gabapentin and pregabalin can be effective for anxiety management, particularly in patients with comorbid pain conditions 2, 5
• These medications work through GABA mechanisms but without the dependency issues associated with benzodiazepines 5

Alpha-2 Adrenergic Agonists

• Clonidine and guanfacine can be used for anxiety management, particularly when there's a component of autonomic hyperarousal 1
• These medications help reduce physical symptoms of anxiety like increased heart rate and blood pressure 1

Situational Anxiety Options

Beta-Blockers

• Propranolol can be effective for performance anxiety and physical symptoms of anxiety (tremor, tachycardia) 1
• These are particularly useful for situational anxiety rather than chronic anxiety disorders 1

Buspirone

• Can be an alternative for generalized anxiety disorder 6
• Has a delayed onset of action (2-3 weeks) and lacks the immediate relief provided by benzodiazepines 2

Special Considerations

Older Adults

• Benzodiazepines should be avoided in older adults due to increased risk of falls, cognitive impairment, and delirium 3
• When treating anxiety in older adults, start with lower doses of SSRIs or SNRIs and titrate slowly 3

Patients with Substance Use History

• SSRIs and SNRIs are preferred in patients with history of substance abuse as they lack abuse potential 1
• Avoid medications with dependency potential in patients with history of substance abuse 1

Common Pitfalls and Caveats

• Antidepressants may take 2-4 weeks to show full therapeutic effect for anxiety, unlike the immediate relief from benzodiazepines - patients should be educated about this delay 2
• Risk of serotonin syndrome when combining multiple serotonergic agents (SSRIs, SNRIs, tramadol, triptans) 7
• SSRIs can cause initial activation or increased anxiety in some patients; starting at lower doses can help mitigate this effect 7
• Abrupt discontinuation of SSRIs or SNRIs can lead to withdrawal symptoms; gradual tapering is recommended 7
• Monitoring for suicidal ideation is important, especially during the initial treatment phase with antidepressants 7

Combination Approaches

• Pharmacotherapy should be combined with cognitive behavioral therapy (CBT) when possible for optimal outcomes 1
• Short-term hypnotic treatment should be supplemented with behavioral and cognitive therapies 3
• For treatment-resistant anxiety, consider combining medications from different classes after monotherapy trials 3

Remember that medication selection should be guided by symptom pattern, treatment goals, past treatment responses, comorbid conditions, contraindications, and potential drug interactions 3.