What are the top 3 medications for treating anxiety?

Top 3 Medications for Anxiety

The top 3 medications for treating anxiety are SSRIs (particularly sertraline), SNRIs (particularly venlafaxine), and benzodiazepines (such as alprazolam), with SSRIs being the first-line treatment due to their established efficacy and favorable safety profile. 1, 2

First-Line Treatment: SSRIs

SSRIs are the most extensively studied and recommended first-line medications for anxiety disorders:

• SSRIs have demonstrated significant improvement in anxiety symptoms compared to placebo, with moderate strength of evidence and a number needed to treat (NNT) of 4.70 1, 2
• They improve primary anxiety symptoms, response to treatment, remission rates, and global functioning 1
• Sertraline is particularly well-supported by evidence and FDA-approved for multiple anxiety disorders including social anxiety disorder, panic disorder, and PTSD 3, 2
• Other effective SSRIs include:
  • Paroxetine - effective for social anxiety disorder but has higher risk of discontinuation syndrome 4
  • Escitalopram - effective with potentially fewer drug interactions 4
  • Fluoxetine - longer half-life allowing for once-daily dosing 1, 4

Dosing and Administration

• Start with lower doses and increase gradually:
  • Shorter half-life SSRIs (sertraline, citalopram): increase at 1-2 week intervals
  • Longer half-life SSRIs (fluoxetine): increase at 3-4 week intervals 1
• Consider starting with subtherapeutic "test" doses as initial adverse effects may include increased anxiety 1

Adverse Effects

• Common side effects include dry mouth, nausea, diarrhea, headache, somnolence, insomnia, and sexual dysfunction 1
• Serious but uncommon adverse effects include suicidal thinking (through age 24), behavioral activation, hypomania/mania, and serotonin syndrome 1
• Discontinuation syndrome is more common with shorter-acting SSRIs, particularly paroxetine 1, 4

Second-Line Treatment: SNRIs

SNRIs are effective alternatives when SSRIs are not tolerated or ineffective:

• SNRIs have demonstrated efficacy similar to SSRIs with an NNT of 4.94 1
• They inhibit the reuptake of both serotonin and norepinephrine, which may help with both anxiety and pain symptoms 5
• Venlafaxine (extended release) has the most evidence among SNRIs for anxiety disorders 1, 4
• Duloxetine is the only SNRI with FDA approval for generalized anxiety disorder in children and adolescents (7 years and older) 1

Adverse Effects

• Common side effects include diaphoresis, dry mouth, abdominal discomfort, nausea, fatigue, dizziness, headache, and somnolence 1
• SNRIs may cause increased blood pressure and heart rate, requiring monitoring 1
• Venlafaxine appears to have more cardiovascular effects and discontinuation issues compared to duloxetine 5

Third-Line Treatment: Benzodiazepines

Benzodiazepines can be effective for short-term or as-needed use:

• Alprazolam has demonstrated superiority to placebo in multiple clinical trials for panic disorder and anxiety 6
• Benzodiazepines provide rapid relief of anxiety symptoms but have significant limitations 7, 8
• They should be used cautiously due to risks of dependence, tolerance, and withdrawal 8

Limitations and Concerns

• Not recommended for long-term use due to potential for dependence and tolerance 7
• May worsen depression or PTSD symptoms in some patients 8
• Risk of cognitive impairment, especially in elderly patients 7

Combination Therapy

• Combining CBT with medication (particularly an SSRI) is often more effective than either treatment alone 1
• Combination treatment has shown superior outcomes for response rates and remission of anxiety disorders 1

Special Considerations

• Patient factors that influence medication selection include:
  • Prior response to medications
  • Comorbid conditions (depression, pain disorders)
  • Risk of drug interactions
  • Tolerability concerns 2
• For patients with comorbid depression, SSRIs and SNRIs are particularly advantageous 9
• Patients with chronic pain may benefit more from SNRIs than SSRIs 5

Treatment Algorithm

1. Start with an SSRI (sertraline preferred) unless contraindicated
2. If ineffective or poorly tolerated after adequate trial (8-12 weeks), switch to another SSRI or an SNRI
3. If second medication trial fails, consider combination therapy with CBT
4. Reserve benzodiazepines for short-term use during acute anxiety or as adjuncts while waiting for SSRI/SNRI effects 2, 7