What are the recommended medications and therapies for treating anxiety in patients, considering factors like substance abuse history and potential for dependence?

Medications for Anxiety

Start with an SSRI—specifically sertraline (25-50 mg daily) or escitalopram (5-10 mg daily)—as first-line pharmacological treatment for anxiety disorders, avoiding benzodiazepines entirely in patients with substance abuse history due to high dependence risk. 1, 2

First-Line Pharmacotherapy

Preferred SSRIs

• Sertraline and escitalopram 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. 1, 2
• Start sertraline at 25-50 mg daily and titrate by 25-50 mg increments every 1-2 weeks as tolerated, targeting 50-200 mg/day. 1
• Start escitalopram at 5-10 mg daily and titrate by 5-10 mg increments every 1-2 weeks, targeting 10-20 mg/day. 1
• Escitalopram has the least effect on CYP450 isoenzymes, resulting in lower propensity for drug interactions and lower risk of discontinuation syndrome. 1

Alternative SSRIs

• Paroxetine and fluvoxamine are equally effective but carry higher risks of discontinuation symptoms and should be reserved for when first-tier SSRIs fail. 1
• Critical warning: Paroxetine has a higher risk of discontinuation syndrome and potentially increased suicidal thinking compared to other SSRIs. 1
• Fluoxetine has a longer half-life that may be beneficial for patients who occasionally miss doses, but requires slower titration starting at 5-10 mg daily. 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 but requires blood pressure monitoring due to risk of sustained hypertension. 1, 2
• Duloxetine (60-120 mg/day) has demonstrated efficacy in GAD and has additional benefits for patients with comorbid pain conditions; start at 30 mg daily for one week to reduce nausea. 1

Expected Timeline and Monitoring

Response Pattern

• SSRI response follows a logarithmic model with statistically significant improvement within 2 weeks, clinically significant improvement by week 6, and maximal improvement by week 12 or later. 1
• Do not abandon treatment prematurely—full response may take 12+ weeks, and gradual dose escalation prevents overshooting the therapeutic window. 1

Critical Monitoring

• All SSRIs carry a boxed warning for suicidal thinking and behavior, with pooled absolute rates of 1% versus 0.2% for placebo (NNH = 143). 1, 3
• Monitor closely for suicidal thinking, especially in the first months and following dose adjustments. 1, 3
• Assess response using standardized anxiety rating scales (e.g., GAD-7, HAM-A) monthly until symptoms stabilize, then every 3 months. 1
• Common side effects include nausea, sexual dysfunction, headache, insomnia, dry mouth, and diarrhea, with most adverse effects emerging within the first few weeks and typically resolving with continued treatment. 1, 3

Medications to AVOID in Substance Abuse History

Benzodiazepines

• Benzodiazepines should be avoided entirely as first-line treatment due to risks of dependence, tolerance, and withdrawal—reserve only for very short-term use if absolutely necessary. 1, 2
• This is especially critical in patients with substance abuse history, where benzodiazepines pose unacceptable addiction risk. 1

Tricyclic Antidepressants

• TCAs should be avoided due to their unfavorable risk-benefit profile, particularly cardiac toxicity. 1

Bupropion

• Bupropion is contraindicated for anxiety disorders because it is activating and can exacerbate anxiety symptoms, agitation, and nervousness. 1

Second-Line Options

When First SSRI Fails

• If inadequate response after 8-12 weeks at therapeutic doses with good adherence, switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) or an SNRI. 1
• Cross-taper by reducing the first SSRI by 25-50 mg every 1-2 weeks while simultaneously starting the new medication at a low "test" dose to minimize initial anxiety or agitation. 1

Pregabalin/Gabapentin

• Consider pregabalin or gabapentin when first-line treatments are ineffective or not tolerated, particularly for patients with comorbid pain conditions. 1

Combination with Psychotherapy

Cognitive Behavioral Therapy

• Combining medication with CBT provides superior outcomes compared to either treatment alone, particularly for moderate to severe anxiety (large effect size: Hedges g = 1.01 for GAD). 1, 4
• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness. 1
• Recommend 12-20 CBT sessions for significant symptomatic and functional improvement. 1

CBT Components

• Education on anxiety, cognitive restructuring to challenge distortions, relaxation techniques, and gradual exposure when appropriate. 1

Treatment Duration

• Continue effective medication for a minimum of 9-12 months after achieving remission to prevent relapse. 1, 2
• For recurrent anxiety, longer-term or indefinite treatment may be beneficial. 2
• Discontinue medication gradually to avoid withdrawal symptoms, particularly with shorter half-life SSRIs like sertraline and paroxetine. 1, 3

Adjunctive Non-Pharmacological Strategies

• Structured physical activity and exercise provide moderate to large reduction in anxiety symptoms. 1
• Breathing techniques, progressive muscle relaxation, grounding strategies, visualization, and mindfulness are useful adjunctive strategies. 1
• Avoid excessive caffeine and alcohol as both can exacerbate anxiety symptoms. 1
• Sleep hygiene education can address insomnia which commonly co-occurs with anxiety. 1

Critical Clinical Pitfalls

• Rule out medical causes before initiating treatment: hyperthyroidism, caffeinism, hypoglycemia, asthma exacerbations, cardiac arrhythmias, and other endocrine disorders. 1
• Rule out substance-induced anxiety and ensure symptoms are not caused by drugs of abuse, pharmaceuticals, or other medical conditions. 1
• Screen for comorbid conditions (depression, substance use, other psychiatric disorders) as approximately one-third of anxiety patients have comorbidities. 1
• Patients with anxiety pathology commonly avoid follow-through on referrals—proactively assess and address barriers to treatment adherence. 1
• Monitor for low sodium levels in blood, especially in elderly patients, which can present as headache, weakness, confusion, or memory problems. 3