What medications are used to treat anxiety?

Medications for Anxiety Disorders

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are the first-line pharmacological treatments for anxiety disorders due to their established efficacy and favorable safety profiles. 1, 2

First-Line Medications

SSRIs

• SSRIs are suggested as first-line pharmacotherapy for anxiety disorders including generalized anxiety disorder, social anxiety disorder, panic disorder, and separation anxiety 2, 1
• Commonly prescribed SSRIs include:
  • Fluvoxamine 2
  • Paroxetine 2
  • Escitalopram 2
  • Sertraline 3, 4
  • Fluoxetine 5
  • Citalopram 2

SNRIs

• SNRIs such as venlafaxine are also suggested as first-line treatments 2, 1
• Other SNRIs include duloxetine and desvenlafaxine 2
• SNRIs work by inhibiting the presynaptic reuptake of both serotonin and norepinephrine 2

Medication Selection Considerations

Efficacy

• Meta-analyses show SSRIs and SNRIs have small to medium effect sizes compared to placebo:
  • For generalized anxiety disorder: standardized mean difference -0.55 1
  • For social anxiety disorder: standardized mean difference -0.67 1
  • For panic disorder: standardized mean difference -0.30 1
• Sertraline has demonstrated efficacy in treating panic disorder, reducing severity and frequency of panic attacks 3
• In a 12-week trial for generalized anxiety disorder, sertraline showed significantly greater improvement than placebo with 63% response rate versus 37% for placebo 6

Pharmacokinetic Considerations

• SSRIs vary in their half-lives, affecting dosing schedules:
  • Shorter half-life SSRIs (sertraline, citalopram): dose adjustments at 1-2 week intervals 2
  • Longer half-life SSRIs (fluoxetine): dose adjustments at 3-4 week intervals 2
• Sertraline has an elimination half-life of 22-36 hours, allowing for once-daily dosing 7
• Citalopram/escitalopram may have the least effect on CYP450 isoenzymes compared to other SSRIs, potentially resulting in fewer drug interactions 2

Adverse Effects and Precautions

Common Adverse Effects

• SSRIs and SNRIs can cause:
  • Anxiety and insomnia (12-16% for fluoxetine vs. 7-9% for placebo in depression trials) 5
  • Gastrointestinal symptoms (nausea, vomiting, diarrhea) 2, 5
  • Sexual dysfunction 2, 5
  • Altered appetite and weight changes 5
  • Headache, dizziness, and somnolence 2

Serious Adverse Effects

• Increased risk of bleeding events, especially when combined with NSAIDs, aspirin, or anticoagulants 5
• Hyponatremia, particularly in elderly patients or those taking diuretics 5
• Activation of mania/hypomania (0.1-0.8% in clinical trials) 5
• Serotonin syndrome when combined with other serotonergic medications 2
• QT prolongation with citalopram at doses exceeding 40 mg/day 2

Drug Interactions

• Concomitant use of SSRIs with MAOIs is contraindicated due to risk of serotonin syndrome 2
• Fluoxetine, paroxetine, and sertraline may interact with drugs metabolized by CYP2D6 2
• Fluvoxamine may interact with drugs metabolized by multiple CYP enzymes (CYP1A2, CYP2C19, CYP2C9, CYP3A4, CYP2D6) 2
• Sertraline has minimal inhibitory effects on major cytochrome P450 enzymes, resulting in fewer drug-drug interactions 7

Dosing and Administration

Initiation and Titration

• Start with a subtherapeutic "test" dose, as initial adverse effects can include increased anxiety or agitation 2
• For mild to moderate anxiety:
  • Increase dose as tolerated within therapeutic range 2
  • Use smallest available increments 2
  • For shorter half-life SSRIs: adjust at 1-2 week intervals 2
  • For longer half-life SSRIs: adjust at 3-4 week intervals 2
• For severe anxiety, faster up-titration may be indicated as tolerated 2

Discontinuation

• A discontinuation syndrome can occur with missed doses or abrupt discontinuation, particularly with shorter-acting SSRIs like paroxetine, fluvoxamine, and sertraline 2
• Symptoms may include dizziness, fatigue, headaches, nausea, sensory disturbances, anxiety, and irritability 2

Special Populations

Children and Adolescents

• Combination treatment (CBT and an SSRI) could be offered preferentially over monotherapy for children and adolescents with anxiety disorders 2
• Parental oversight of medication regimens is crucial in pediatric populations 2

Alternative and Adjunctive Treatments

Psychotherapy

• Cognitive Behavioral Therapy (CBT) is the psychotherapy with the most evidence of efficacy for anxiety disorders 1
• CBT has shown large effect sizes for generalized anxiety disorder (Hedges g = 1.01) and small to medium effects for social anxiety disorder and panic disorder 1
• For social anxiety disorder, structured CBT with individual sessions by a skilled therapist is suggested 2

Other Medication Classes

• Benzodiazepines, beta blockers, antiepileptics, antipsychotics, and MAOIs have not been as extensively studied for anxiety disorders 2
• These alternative medication classes should be considered when first-line treatments are ineffective or contraindicated 2