Explore treatment options for Generalized Anxiety Disorder

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 in their lifetime. Recommend cognitive behavioral therapy or meds as the initial treatment for generalized anxiety disorder, efficacy seems similar. Be ready to use a stepwise approach if meds are preferred...

  • SSRIs/SNRIs. Continue to prescribe one of these as the 1st-line med, 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 or sertraline, or 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 to see some benefit and up to 12 weeks for max effects.
  • 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 med or “PRN” option is needed. But hydroxyzine has limited evidence and anticholinergic effects (dry mouth, urinary retention, constipation, etc) often occur.
  • Benzodiazipines. 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 benzo 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 meds 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.

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.

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