What is the first-line treatment for generalized anxiety disorder?

First-Line Treatment for Generalized Anxiety Disorder

For adults with generalized anxiety disorder, initiate treatment with either an SSRI (escitalopram, sertraline, or paroxetine) or an SNRI (venlafaxine or duloxetine) as first-line pharmacotherapy, with escitalopram being particularly preferred due to its favorable safety profile and low drug interaction potential. 1, 2, 3, 4

Pharmacological Treatment Approach

First-Line Medications

SSRIs and SNRIs are the established first-line pharmacological treatments for GAD, with high-certainty evidence demonstrating superiority over placebo. 5

• Escitalopram 10 mg once daily is the recommended starting dose, with demonstrated efficacy in multiple placebo-controlled trials and FDA approval for GAD 1, 2, 3
• Sertraline, paroxetine, duloxetine, and venlafaxine are equally effective alternatives with robust evidence 2, 3, 4
• Antidepressants show a 41% greater treatment response rate compared to placebo (number needed to treat = 7), with high-certainty evidence 5

Dosing Strategy

• Start with 10 mg daily of escitalopram (or equivalent SSRI dose) 1
• If dose escalation is needed to 20 mg, wait at least one week before increasing 1
• For elderly patients or those with hepatic impairment, maintain 10 mg daily without escalation 1
• Consider starting with a subtherapeutic "test dose" if the patient is particularly anxious, as SSRIs can initially worsen anxiety 6

Cognitive Behavioral Therapy

CBT specifically designed for anxiety disorders should be offered as first-line treatment, either alone or in combination with pharmacotherapy. 6, 7

• Structure treatment as approximately 14 individual sessions over 4 months, with each session lasting 60-90 minutes 6
• Individual therapy is preferred over group therapy due to superior clinical and cost-effectiveness 6
• For patients refusing face-to-face CBT, offer self-help with therapist support as an alternative 6

Combination Therapy Consideration

For patients with moderate-to-severe GAD, combination treatment (CBT plus SSRI) demonstrates superior outcomes compared to monotherapy. 6, 7

• Combination therapy improves primary anxiety symptoms, global functioning, treatment response rates, and remission rates compared to either treatment alone 6
• This approach is particularly beneficial for patients ages 6-18 years, though the evidence extends to adults 6, 7

Treatment Duration and Monitoring

• Continue treatment for at least 4-12 months after symptom remission for first episodes 7
• For recurrent GAD, consider longer-term or indefinite treatment 7
• Systematically assess treatment response using standardized symptom rating scales 6
• Periodically re-evaluate the need for continued pharmacotherapy 1

Alternative Pharmacological Options

If first-line SSRIs/SNRIs are ineffective or not tolerated:

• Pregabalin has robust evidence as a second-line agent with rapid anxiety reduction and low abuse potential 3, 8
• Quetiapine (low-dose atypical antipsychotic) shows efficacy similar to SSRIs but with lower overall tolerability 3, 8
• Benzodiazepines, buspirone, and hydroxyzine are FDA-approved but should be reserved for specific situations due to dependence concerns 8

Critical Safety Considerations

Discontinuation Management

• Never abruptly discontinue SSRIs/SNRIs - taper gradually to avoid withdrawal symptoms including vertigo, paresthesias, anxiety, and agitation 6
• Shorter-acting SSRIs (paroxetine, sertraline) carry higher discontinuation syndrome risk than longer-acting agents (fluoxetine) 6
• If intolerable symptoms occur during taper, resume the previous dose and decrease more gradually 1

Monitoring Requirements

• Screen for personal or family history of bipolar disorder before initiating antidepressants to avoid precipitating mania 1
• Monitor for suicidal ideation and behavior, particularly in patients under age 24 6
• For SNRIs, monitor blood pressure and pulse due to risk of sustained hypertension 6
• With duloxetine specifically, monitor for hepatic dysfunction (abdominal pain, hepatomegaly, elevated transaminases) and discontinue if jaundice develops 6

Drug Interactions

• Allow at least 14 days between discontinuing an MAOI and starting an SSRI/SNRI, and vice versa 1
• Do not initiate SSRIs in patients receiving linezolid or IV methylene blue due to serotonin syndrome risk 1

Common Pitfalls to Avoid

• Starting with full therapeutic doses can worsen anxiety initially; consider subtherapeutic test doses 6
• Expecting immediate response - SSRIs/SNRIs require 2-4 weeks before symptom relief begins 2
• Inadequate treatment duration - many patients require several months beyond acute response for sustained remission 1
• Abrupt discontinuation - always taper gradually, especially with shorter-acting agents 6, 1