Explore treatment options for Generalized Anxiety Disorder
Overview
As a clinical pharmacist, it's essential to recognize that about 1 in 13 adults in the US will be diagnosed with generalized anxiety disorder (GAD) in their lifetime. Recommend cognitive behavioral therapy or medications as the initial treatment for GAD, as their efficacy seems similar. Be ready to use a stepwise approach if medications are preferred.
Management approach
First-Line Medications for GAD
SSRIs/SNRIs: Continue to prescribe one of these as the first-line medication, based on overall evidence for generalized anxiety disorder. Plus, they’re preferred for common comorbidities, such as depression. Keep in mind, there’s not one “best” SSRI or SNRI; often choose escitalopram, sertraline, duloxetine, or venlafaxine. Limited data suggest these provide a better balance of efficacy and tolerability.
- Start with low doses, such as sertraline (Lustral, Serpass) 25 mg/day, and titrate to limit early side effects (worsening anxiety, insomnia).
- Explain to patients that it can take about 2 to 4 weeks to start seeing some benefits and up to 12 weeks for maximum effects.
Alternative Treatment Options
Buspirone (Buspar, Seropar, Neurobus): Consider this if an SSRI or SNRI isn’t tolerated or as an add-on if they aren’t enough. Start with 7.5 mg BID and titrate up to 60 mg/day if needed, divided BID or TID. Keep in mind, buspirone doesn't work PRN for anxiety; it usually takes about 2 weeks to start seeing some effect.
Pregabalin (Lyrica): Think of this as an alternative or add-on. It may start working as early as 1 week, but weigh concerns about misuse and side effects (drowsiness, dizziness, weight gain, etc.).
Hydroxyzine (Atarax): Consider this as an alternative, especially if a quick-onset medication or “PRN” option is needed. However, hydroxyzine has limited evidence and anticholinergic effects (dry mouth, urinary retention, constipation, etc.) often occur.
Benzodiazepines and Cautionary Measures
Benzodiazepines: Save these as an add-on for just a few weeks until an SSRI or SNRI starts working or for severe anxiety disorders. Avoid alprazolam if a benzodiazepine is needed; its short half-life can cause rebound anxiety and withdrawal. Choose a longer-acting option instead, such as clonazepam, to possibly ease discontinuation.
Be alert for medications that may worsen anxiety, such as stimulants for ADHD, and select alternatives. Also, be ready to treat other conditions that may contribute to anxiety, such as alcohol use disorder.
Read our note, Think of BUSPirone as 2nd option for managing anxiety, and "see table 1" for medication therapy of anxiety..
| Table (1). Pharmacology of medicines for treatment of adults with generalized anxiety disorder (GAD) | ||
|---|---|---|
| Medication | Dose | Comments |
| SSRIs/SNRIs | ||
| Escitalopram | 10-20 mg/day | Lower risk of insomnia/agitation and few drug interactions |
| Sertraline | 25-200 mg/day | More likely to cause GI side effects and initial anxiety than other antidepressants. |
| Duloxetine | 30-60 mg/day | Greater risk of insomnia/agitation |
| Venlafaxine | 75-225 mg/day | Nausea, insomnia, increased BP |
| Buspirone | 7.5-60 mg/day | Useful for treating anxiety Sx related to GAD; not as effective in pts who have been on BZDs in past; does not cause tolerance or dependence; takes 4-6 wks to reach maximal effectiveness. |
| Pregabalin | 150-600 mg/day | Dizziness, drowsiness, weight gain |
| Hydroxyzine | 25-100 mg/day | Anithistamine used to treat anxiety. May cause sedation, anticholinergic side effects, delirium in elderly/demented pts. Can be used instead of benzodiazepines for PRN treatment of anxiety Sxs. |
| Benzodiazepines | ||
| Clonazepam | 0.5-4 mg/day | Rapid acting, long half-life BZD, FDA-approved for treatment of PD, less likely to cause rebound anxiety Sx when tapered. |
| Alprazolam | 0.25-2 mg/day | Rapid acting, short half-life BZD, FDA-approved for treating panic Sx, has more abuse potential than longer acting BZDs. |
References
- Szuhany KL, Simon NM. Anxiety Disorders: A Review. JAMA. 2022;328(24):2431-2445.
- Fagan HA, Baldwin DS. Pharmacological Treatment of Generalised Anxiety Disorder: Current Practice and Future Directions. Expert Rev Neurother. 2023;23(6):535-548.
- DeGeorge KC, Grover M, Streeter GS. Generalized Anxiety Disorder and Panic Disorder in Adults. Am Fam Physician. 2022;106(2):157-164.
