What medications, other than benzodiazepines (BZDs), are used to treat anxiety?

Non-Benzodiazepine Medications for Anxiety Treatment

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are the first-line medications for treating anxiety disorders when benzodiazepines are not an option. 1

First-Line Medications

SSRIs

SSRIs have demonstrated high efficacy with favorable safety profiles for anxiety disorders:

• Fluvoxamine - Covered by national health insurance for social anxiety disorder in Japan 1
• Paroxetine - Covered by national health insurance for social anxiety disorder in Japan 1
• Escitalopram - Covered by national health insurance for social anxiety disorder in Japan 1
• Sertraline - Effective for anxiety disorders though not covered by insurance in some countries 1

SSRIs show a high treatment response rate (NNT = 4.70) with dropout rates similar to placebo, indicating good tolerability 1.

SNRIs

SNRIs are also effective for anxiety disorders:

• Venlafaxine - Particularly effective for social anxiety disorder 1
• Duloxetine - FDA-approved for generalized anxiety disorder in children and adolescents 7 years and older 1

SNRIs have shown comparable efficacy to SSRIs (NNT = 4.94) with similar safety profiles 1.

Second-Line Options

When SSRIs and SNRIs are ineffective or not tolerated, consider:

Anticonvulsants/Mood Stabilizers

• Carbamazepine
• Lamotrigine
• Valproate

These anticonvulsants have not generally been associated with severe arrhythmias 1.

Other Antidepressants

• Mirtazapine (NaSSA) - May provide benefits across anxiety disorders 2
• Tricyclic antidepressants (TCAs) - Effective but with more side effects than newer options 2

Cautions and Monitoring

QT Prolongation Risk

• Monitor ECG in patients with risk factors when using SSRIs, particularly citalopram and escitalopram 1
• Use caution in patients with congenital long QT syndrome, history of QT prolongation, or family history of sudden cardiac death 3

Common Side Effects

• SSRIs/SNRIs: Nausea, headache, insomnia, sexual dysfunction
• TCAs: Anticholinergic effects (dry mouth, constipation, blurred vision)

Special Populations

• Elderly: Greater risk of hyponatremia with SSRIs and SNRIs 3
• Patients with diabetes: Monitor glycemic control as SSRIs may alter blood sugar levels 3

Augmentation Strategies

For partial response to SSRIs/SNRIs, consider augmentation with:

• Buspirone - Non-benzodiazepine anxiolytic 4
• Beta blockers - Particularly for performance anxiety 4
• Pregabalin - GABA analog effective for anxiety 1

Implementation Tips

1. Start with low doses of SSRIs/SNRIs and gradually increase to minimize initial side effects
2. Allow adequate trial duration (8-12 weeks) before concluding treatment failure
3. Consider cognitive behavioral therapy (CBT) as an adjunct to medication for all patients 1
4. For SNRIs like venlafaxine extended release, single daily dosing is usually sufficient 1

Common Pitfalls to Avoid

1. Abrupt discontinuation: SSRIs and SNRIs should be tapered slowly to avoid withdrawal symptoms 3
2. Inadequate dosing: Some patients require higher doses than typical starting doses
3. Overlooking drug interactions: SSRIs can interact with other medications that affect serotonin levels
4. Ignoring comorbidities: Anxiety often co-occurs with depression and other conditions that may influence treatment choice

By following this approach, clinicians can effectively manage anxiety disorders without relying on benzodiazepines, reducing risks of dependency and other adverse effects associated with benzodiazepine use.