What medication is recommended for a patient with anxiety, considering potential substance abuse history and severity of symptoms?

Medication for Anxiety

For patients with anxiety, SSRIs—specifically escitalopram or sertraline—are the first-line pharmacological treatment, even in those with a history of substance abuse, as benzodiazepines should be avoided due to risks of dependence and tolerance. 1

First-Line Medication Recommendations

Start with escitalopram (5-10 mg daily) or sertraline (25-50 mg daily) as these agents have the most favorable evidence for efficacy and tolerability across anxiety disorders. 1

• Escitalopram has the lowest risk of drug interactions (minimal CYP450 inhibition) and lower discontinuation syndrome compared to other SSRIs. 1
• Sertraline offers excellent tolerability, low potential for pharmacokinetic drug interactions (unlike fluoxetine, fluvoxamine, and paroxetine), and proven efficacy across multiple anxiety disorders. 2
• Both medications demonstrate treatment response with NNT = 4.70, meaning approximately 1 in 5 patients will respond who would not have responded to placebo. 3

Dosing Strategy

• Begin with subtherapeutic doses to minimize initial anxiety or agitation that commonly occurs with SSRI initiation. 1
• Titrate sertraline by 25-50 mg increments every 1-2 weeks, targeting 50-200 mg/day. 1
• Titrate escitalopram by 5-10 mg increments every 1-2 weeks, targeting 10-20 mg/day. 1
• Allow 12 weeks for full therapeutic response, though statistically significant improvement may begin by week 2 and clinically meaningful improvement by week 6. 1

Alternative First-Line Options

If escitalopram or sertraline are unavailable or not tolerated:

• Fluvoxamine (50 mg twice daily, titrated to 150 mg twice daily) is effective but has greater potential for drug-drug interactions through multiple CYP450 pathways and higher discontinuation syndrome risk. 3, 1
• Paroxetine (10 mg daily, titrated to 40 mg/day) is effective but carries the highest risk of discontinuation syndrome and potentially increased suicidal thinking compared to other SSRIs. 1
• Fluoxetine (5-10 mg daily, titrated to 20-40 mg/day) has a longer half-life that may benefit patients who occasionally miss doses, but is a potent CYP2D6 inhibitor requiring caution with drug interactions. 1, 4

Second-Line Treatment: SNRIs

If inadequate response after 8-12 weeks at therapeutic SSRI doses, switch to an SNRI:

• Venlafaxine extended-release (75-225 mg/day) has demonstrated efficacy comparable to SSRIs (NNT = 4.94) but requires blood pressure monitoring due to risk of sustained hypertension. 3, 1
• Duloxetine (60-120 mg/day) is effective for GAD and offers additional benefits for patients with comorbid pain conditions; start at 30 mg daily for one week to reduce nausea. 1

Critical Considerations for Substance Abuse History

Benzodiazepines should be avoided as first-line treatment in patients with substance abuse history due to risks of dependence, tolerance, and withdrawal, and should be reserved only for short-term use in acute situations. 1, 5

• While some evidence suggests benzodiazepines do not necessarily induce relapse in former substance abusers 6, the consensus guideline position prioritizes SSRIs/SNRIs for chronic anxiety management to avoid addiction potential. 1
• SSRIs and SNRIs have no dependence potential and low risk of lethality in overdose, making them safer in this population. 2

Monitoring and Safety

Monitor closely for suicidal thinking and behavior, especially in the first months and following dose adjustments, with pooled absolute rates of 1% versus 0.2% for placebo (NNH = 143). 1, 7

Watch for these warning signs requiring immediate contact with provider:

• New or worsening depression, anxiety, or panic attacks
• Agitation, restlessness, irritability, or hostility
• Impulsivity or acting on dangerous impulses
• Insomnia or increased activity/talking 7, 4

Common side effects (typically emerging within first few weeks and resolving with continued treatment):

• Nausea, diarrhea, dry mouth, heartburn
• Headache, dizziness, somnolence or insomnia
• Sexual dysfunction, nervousness, tremor 1, 7

Assess response monthly until symptoms stabilize using standardized scales (GAD-7 or HAM-A), then every 3 months. 1

Treatment Duration

Continue effective medication for minimum 9-12 months after achieving remission to prevent relapse. 1

Taper gradually when discontinuing to avoid withdrawal symptoms (anxiety, irritability, mood changes, restlessness, headache, sweating, nausea, dizziness, electric shock-like sensations), particularly with shorter half-life SSRIs like sertraline and paroxetine. 1, 7

Combination Treatment

Combining medication with cognitive behavioral therapy (CBT) provides superior outcomes compared to either treatment alone, particularly for moderate to severe anxiety. 1

• Individual CBT is preferred over group therapy for superior clinical and cost-effectiveness. 1
• Structured physical activity and cardiovascular exercise provide moderate to large reductions in anxiety symptoms as adjunctive treatment. 1

Common Pitfalls to Avoid

• Do not escalate doses too rapidly—allow 1-2 weeks between increases to assess tolerability and avoid overshooting the therapeutic window. 1
• Do not abandon treatment prematurely—full response requires 12+ weeks at therapeutic doses. 1
• Do not use bupropion for anxiety—it is contraindicated as it is activating and can exacerbate anxiety symptoms. 1
• Do not use tricyclic antidepressants—they have unfavorable risk-benefit profiles, particularly cardiac toxicity. 1