What are the guidelines for prescribing medication to a patient with anxiety, considering factors such as age, medical history, and potential comorbidities?

Guidelines for Anxiety Medication

First-Line Pharmacotherapy

SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin-norepinephrine reuptake inhibitors) are the recommended first-line medications for anxiety disorders, with escitalopram and sertraline being the preferred SSRIs due to their superior safety profiles and lower discontinuation symptoms. 1

Preferred SSRI Options

• Escitalopram (5-10 mg daily, titrate to 10-20 mg/day): Has the least effect on CYP450 enzymes, resulting in minimal drug interactions and lower risk of discontinuation syndrome 1
• Sertraline (25-50 mg daily, titrate to 50-200 mg/day): Equally effective with favorable tolerability profile 1, 2
• Fluoxetine (5-10 mg daily, titrate to 20-40 mg/day): Longer half-life beneficial for patients who occasionally miss doses, though more drug interactions than escitalopram 1

Alternative SSRIs (Second-Tier)

• Paroxetine and fluvoxamine are effective but carry higher risks of discontinuation symptoms and should be reserved for when first-tier SSRIs fail 1
• Paroxetine has significant anticholinergic properties and higher risk of suicidal thinking compared to other SSRIs 1

SNRI Options

• Duloxetine (60-120 mg/day): Particularly beneficial for patients with comorbid pain conditions 1
• Venlafaxine extended-release (75-225 mg/day): Effective for generalized anxiety disorder, social anxiety disorder, and panic disorder, but requires blood pressure monitoring due to risk of sustained hypertension 1, 2

Treatment Algorithm by Patient Factors

Age Considerations

Adults (18-65 years):

• Start with escitalopram 10 mg daily or sertraline 50 mg daily 1
• Titrate every 1-2 weeks based on tolerability 1
• Target therapeutic doses by weeks 4-6 1

Elderly Patients (>65 years):

• Start low and go slow: Begin sertraline at 25 mg daily (half the standard adult dose) or escitalopram at 5 mg daily 3
• Titrate at 1-2 week intervals for shorter half-life SSRIs, extending to 3-4 weeks for longer half-life agents 3
• Avoid paroxetine and fluoxetine in older adults due to higher rates of adverse effects, anticholinergic properties, and extensive drug interactions 3
• Escitalopram and sertraline are preferred due to favorable safety profiles and low drug interaction potential 3

Medical History Considerations

Comorbid Pain Conditions:

• Prioritize duloxetine (60-120 mg/day) or pregabalin/gabapentin as these provide dual benefits 1

Cardiovascular Disease:

• Avoid tricyclic antidepressants due to cardiac toxicity 1
• Monitor blood pressure if using venlafaxine 1
• If using citalopram in patients >60 years, avoid doses >20 mg daily due to QT prolongation risk 3

Multiple Medications (Polypharmacy):

• Choose escitalopram due to minimal CYP450 interactions 1, 3
• Review all current medications for potential interactions, particularly CYP450 substrates 3

Pregnancy or Reproductive Planning:

• Excluded from standard guidelines; requires specialized consultation 4

Comorbidity Considerations

Comorbid Depression:

• SSRIs/SNRIs address both conditions simultaneously 1, 2
• Prioritize treatment of depressive symptoms or use unified CBT protocol 3

Comorbid Bipolar Disorder, Schizophrenia, Substance Use Disorders:

• These patients are excluded from standard anxiety treatment guidelines and require specialized psychiatric management 4

Comorbid Developmental Disorders or Intellectual Disabilities:

• Excluded from standard guidelines; require specialized approach 4

Suicidal Risk:

• Patients at obvious risk of self-harm require immediate psychiatric evaluation and are excluded from routine outpatient anxiety treatment protocols 4

Expected Timeline and Monitoring

Response Timeline

• Week 2: Statistically significant improvement may begin 1
• Week 6: Clinically significant improvement expected 1
• Week 12 or later: Maximal therapeutic benefit achieved 1
• Full response may take 12+ weeks; do not abandon treatment prematurely 1

Monitoring Schedule

• Initial phase: Assess response at 4 weeks and 8 weeks using standardized scales (GAD-7 or HAM-A) 1, 3
• Stabilization phase: Monthly reassessment until symptoms stabilize, then every 3 months 1
• Monitor for: Common side effects (nausea, sexual dysfunction, headache, insomnia), suicidal thinking (especially first months and after dose changes), and functional improvement 1

Treatment Adjustment Strategy

If inadequate response after 8-12 weeks at therapeutic doses:

• Switch to a different SSRI (e.g., sertraline to escitalopram or vice versa) 1
• Consider switching to an SNRI (venlafaxine or duloxetine) 1
• Add cognitive behavioral therapy if not already implemented 1

Second-Line Medications

Pregabalin/Gabapentin:

• Consider when first-line treatments are ineffective or not tolerated 1
• Particularly useful for patients with comorbid pain conditions 1

Buspirone:

• Suitable for mild to moderate anxiety in relatively healthy patients 3
• Start at 5 mg twice daily, maximum 20 mg three times daily 3
• Takes 2-4 weeks to become effective 3

Medications to Avoid

Benzodiazepines (e.g., alprazolam, lorazepam):

• Should be avoided as first-line treatment due to risks of dependence, tolerance, withdrawal, cognitive impairment, falls (especially in elderly), and potential to worsen PTSD 1, 5
• Reserve only for short-term use in acute situations 1
• In elderly patients, benzodiazepines increase risk of cognitive impairment, delirium, falls, and fractures even at low doses 3
• Physical dependence can develop even after relatively short-term use (0.75-4 mg/day) 5
• Withdrawal symptoms include seizures (life-threatening), heightened sensory perception, paresthesias, muscle cramps, and rebound anxiety 5

Tricyclic Antidepressants:

• Avoid due to unfavorable risk-benefit profile, particularly cardiac toxicity and ease of overdose 1

Bupropion:

• Contraindicated for anxiety disorders as it is activating and can exacerbate anxiety symptoms, agitation, and nervousness 1

Beta-blockers (atenolol, propranolol):

• Deprecated for chronic social anxiety disorder based on negative evidence 1
• May be used off-label for acute performance anxiety only 1

Treatment Duration

• First episode: Continue effective medication for minimum of 9-12 months after achieving remission to prevent relapse 1
• Recurrent anxiety: Longer-term or indefinite treatment may be beneficial 3
• Discontinuation: Taper gradually over 10-14 days to avoid discontinuation syndrome (dizziness, paresthesias, anxiety, irritability) 3
• Decrease dosage by no more than 25-50 mg every 1-2 weeks for shorter half-life SSRIs 1

Combination with Psychotherapy

Cognitive Behavioral Therapy (CBT) is the psychotherapy with the highest level of evidence for anxiety disorders and should be offered alongside or instead of medication based on patient preference. 1, 2

• Individual CBT is prioritized over group therapy due to superior clinical and cost-effectiveness 1
• Recommended duration: 12-20 sessions for significant symptomatic and functional improvement 1
• Combination treatment (SSRI/SNRI + CBT) provides superior outcomes compared to either treatment alone, particularly for moderate to severe anxiety 1, 2

Critical Warnings and Pitfalls

Suicidal Thinking:

• All SSRIs carry FDA boxed warning for suicidal thinking and behavior, with pooled absolute rates of 1% versus 0.2% for placebo (NNH = 143) 1
• Monitor closely, especially in first months and following dose adjustments 1

Initial Activation:

• SSRIs can cause initial anxiety, agitation, or activation symptoms in first 1-2 weeks 1, 3
• Start with low doses and titrate gradually to minimize this effect 1

Discontinuation Syndrome:

• Never discontinue SSRIs abruptly 3
• Shorter half-life SSRIs (sertraline, paroxetine) have higher risk than longer half-life agents (fluoxetine) 1

Drug Interactions:

• Review all medications before prescribing, particularly in elderly or those on polypharmacy 3
• Paroxetine and fluoxetine have extensive CYP450 interactions 1, 3

Treatment Adherence:

• Patients with anxiety commonly avoid follow-through on referrals; proactively assess and address barriers 1
• Most adverse effects emerge within first few weeks and typically resolve with continued treatment 1

Adjunctive Non-Pharmacological Strategies

• Provide psychoeducation to patient and family members about anxiety symptoms and treatment 1
• Recommend structured physical activity/exercise (provides moderate to large reduction in anxiety symptoms) 1
• Teach breathing techniques, progressive muscle relaxation, grounding strategies, and mindfulness 1
• Address sleep hygiene, avoid excessive caffeine and alcohol 1
• Consider treatment for parents/caregivers who struggle with anxiety themselves 1