What are the recommended medications for treating severe anxiety?

Recommended Medications for Severe Anxiety

SSRIs and SNRIs are the first-line pharmacological treatments for severe anxiety disorders due to their established efficacy, favorable safety profiles, and low risk of dependence. 1, 2, 3

First-Line Medications

Selective Serotonin Reuptake Inhibitors (SSRIs)

• SSRIs demonstrate high treatment response rates with number needed to treat (NNT) = 4.70 and dropout rates similar to placebo, indicating good efficacy and tolerability 1
• Specific SSRIs with strong evidence for anxiety disorders include:
  • Sertraline - well-tolerated with low potential for pharmacokinetic drug interactions 4
  • Paroxetine - effective but associated with higher risk of discontinuation syndrome 1
  • Fluoxetine - longer half-life allowing for less frequent dosing 1
  • Escitalopram/Citalopram - may have least effect on CYP450 isoenzymes and lower propensity for drug interactions 1
• Important considerations with SSRIs:
  • Initial adverse effects may include increased anxiety or agitation; consider starting with subtherapeutic "test" dose 1
  • Response typically follows logarithmic model with clinically significant improvement by week 6 and maximal improvement by week 12 1

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

• SNRIs show similar efficacy to SSRIs with NNT = 4.94 and comparable safety profile 1
• Venlafaxine has the most robust evidence among SNRIs for anxiety disorders 1, 5
• SNRIs may offer potential clinical advantages over SSRIs in some patients with anxiety disorders 5

Second-Line Medications

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

Benzodiazepines

• Recommended for rapid anxiety relief in short-term use 2, 6
• Alprazolam is FDA-approved for generalized anxiety disorder and panic disorder 6
• Caution: Not recommended for routine or long-term use due to risk of dependence and tolerance 2, 3

Anticonvulsants

• Pregabalin has demonstrated efficacy as a second-line treatment 2
• Gabapentin may be beneficial, particularly in patients with comorbid pain conditions 2

Other Options

• Buspirone - alternative for generalized anxiety disorder 3, 7
• Tricyclic antidepressants (TCAs) - effective but less well-tolerated than SSRIs/SNRIs 3, 7
• Mirtazapine, trazodone, nefazodone - considered second-line based on open-label studies 8

Treatment Approach

Medication Initiation and Titration

• Start with low doses and increase gradually:
  • For shorter half-life SSRIs (sertraline, citalopram): increase at 1-2 week intervals 1
  • For longer half-life SSRIs (fluoxetine): increase at 3-4 week intervals 1
  • Faster titration may be indicated for more severe anxiety presentations 1

Combination Therapy

• Consider combination of medication with Cognitive Behavioral Therapy (CBT) for optimal outcomes 2
• For children and adolescents, combination treatment (CBT plus SSRI) is suggested over monotherapy 1

Important Precautions

• Monitor for initial worsening of anxiety symptoms when starting SSRIs 1
• Avoid paroxetine in patients at risk for suicidal ideation 1
• Avoid citalopram doses exceeding 40mg/day due to risk of QT prolongation 1
• Avoid concomitant use of MAOIs with SSRIs due to risk of serotonin syndrome 1
• After achieving remission, continue medications for 6-12 months to prevent relapse 3

Special Considerations

• For rapid symptom relief while waiting for SSRIs/SNRIs to take effect, short-term benzodiazepine use may be considered 7
• In treatment-resistant cases, augmentation with atypical antipsychotics may be beneficial 8
• Regular monitoring by a physician with expertise in anxiety disorders is essential for evaluating treatment response 2