What are non-controlled medication options for treating anxiety?

Non-Controlled Medication Options for Anxiety

Start with escitalopram (10-20 mg/day) or sertraline (50-200 mg/day) as first-line treatment for anxiety disorders, as these SSRIs have the strongest evidence for efficacy and tolerability among non-controlled medications. 1

First-Line Pharmacotherapy: SSRIs and SNRIs

Preferred SSRIs

• Escitalopram and sertraline are the top-tier first-line agents due to their established efficacy, favorable side effect profiles, and lower risk of discontinuation symptoms compared to other SSRIs 2, 1
• Start escitalopram at 5-10 mg daily and titrate by 5-10 mg increments every 1-2 weeks to a target of 10-20 mg/day 1
• Start sertraline at 25-50 mg daily and titrate by 25-50 mg increments every 1-2 weeks to a target of 50-200 mg/day 1, 3
• Fluoxetine and fluvoxamine are effective alternatives, with fluoxetine's longer half-life being advantageous for patients who occasionally miss doses 1

Alternative SSRIs (Second-Tier)

• Paroxetine and fluvoxamine are equally effective but carry higher risks of discontinuation symptoms and should be reserved for when first-tier SSRIs fail 2, 1
• Avoid paroxetine as initial therapy due to increased risk of discontinuation syndrome and potentially higher suicidal thinking compared to other SSRIs 1

SNRIs as First-Line Alternatives

• Venlafaxine extended-release (75-225 mg/day) is effective for generalized anxiety disorder, social anxiety disorder, and panic disorder 2, 1, 4
• Requires blood pressure monitoring due to risk of sustained hypertension, particularly at higher doses 1
• Duloxetine (60-120 mg/day) is particularly beneficial for patients with comorbid pain conditions 1
• Start duloxetine at 30 mg daily for one week to minimize nausea, then increase to 60 mg 1

Second-Line Non-Controlled Options

Pregabalin and Gabapentin

• Consider pregabalin or gabapentin when SSRIs/SNRIs are ineffective or not tolerated, particularly for patients with comorbid pain conditions 1, 5
• These anticonvulsant analogs have demonstrated efficacy in generalized anxiety disorder 2

Buspirone

• Buspirone (5 mg twice daily, maximum 20 mg three times daily) is useful for mild to moderate anxiety symptoms 5
• Critical pitfall: Buspirone requires 2-4 weeks to become fully effective, which must be communicated to patients to prevent premature discontinuation 5
• This is NOT an as-needed medication despite being non-controlled 5

Beta-Blockers (Limited Role)

• Propranolol is NOT recommended as primary treatment for anxiety disorders but may help with physical symptoms (tremor, tachycardia, sweating) in situational anxiety 5
• The Canadian guideline specifically deprecates beta blockers (atenolol, propranolol) for social anxiety disorder based on negative evidence 2
• Use caution in patients with asthma, diabetes, or cardiac conditions 5

Treatment Algorithm

Initial Treatment Selection

• Begin with escitalopram or sertraline at low doses to minimize initial anxiety/agitation that can occur with SSRIs 1
• If patient has comorbid pain, consider duloxetine or venlafaxine as first choice 1
• Titrate gradually over 1-2 weeks to minimize side effects 1

Monitoring Response

• Expect statistically significant improvement within 2 weeks, clinically significant improvement by week 6, and maximal improvement by week 12 or later 1
• Assess response using standardized anxiety rating scales (e.g., HAM-A) 1
• Monitor for common side effects: nausea, sexual dysfunction, headache, insomnia, dry mouth, diarrhea, somnolence, and dizziness 1
• Most adverse effects emerge within the first few weeks of treatment 1

If First SSRI Fails

• After 8-12 weeks at therapeutic doses with inadequate response, switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) 1
• Alternatively, switch to an SNRI (venlafaxine or duloxetine) 1
• Consider adding cognitive behavioral therapy if not already implemented 1

If Second Trial Fails

• Switch to pregabalin or gabapentin as third-line option 1, 5
• Consider buspirone for patients with mild to moderate symptoms who cannot tolerate SSRIs/SNRIs 5

Critical Warnings and Pitfalls

Medications to Avoid

• Tricyclic antidepressants should be avoided due to unfavorable risk-benefit profile, particularly cardiac toxicity 1
• Benzodiazepines are controlled substances and not appropriate for this question, though they remain commonly prescribed 6, 7
• Beta blockers are not effective as primary treatment for most anxiety disorders 2, 5

Discontinuation Considerations

• Never abruptly discontinue any anxiety medication, even non-controlled ones, to prevent rebound symptoms 5
• Discontinue gradually, particularly with shorter half-life SSRIs like sertraline and paroxetine 1
• After remission, continue medications for 6-12 months before attempting discontinuation 6
• Stopping medication within the first year increases relapse risk 7

Special Monitoring Requirements

• Monitor blood pressure with venlafaxine, especially at doses above 150 mg/day 1
• Screen for nausea with duloxetine and consider starting at 30 mg for one week 1
• Assess for discontinuation symptoms when switching between SSRIs, particularly from paroxetine 1

Combination with Psychotherapy

• Combining medication with cognitive behavioral therapy targeting anxiety patterns provides optimal outcomes 1, 6
• CBT has demonstrated efficacy comparable to or exceeding pharmacotherapy alone for anxiety disorders 2, 4
• Individual CBT is prioritized over group therapy due to superior clinical and health-economic effectiveness 2