What is the step-wise approach to medication for patients with anxiety disorders, including the use of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), benzodiazepines, and other anxiolytics?

From the Guidelines

The stepwise approach to medication for anxiety disorders typically begins with selective serotonin reuptake inhibitors (SSRIs) as first-line treatment due to their efficacy and favorable safety profile. Common SSRIs include sertraline (starting at 25-50mg daily, increasing to 50-200mg), escitalopram (5-10mg daily, up to 20mg), and fluoxetine (10-20mg daily, up to 80mg) 1. These medications usually require 4-6 weeks for full effect and should be continued for at least 6-12 months after symptom improvement. If SSRIs are ineffective or poorly tolerated, serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine (37.5-75mg daily, up to 225mg) or duloxetine (30mg daily, up to 120mg) are typically tried next 1. Some key points to consider when prescribing SNRIs include:

• Duloxetine is the only SNRI to have an FDA indication for the treatment of any anxiety disorder (specifically, generalized anxiety disorder in children and adolescents 7 years old) 1
• The choice of medication for anxiety within the SNRI class may also be governed by other considerations such as pharmacokinetics, pharmacodynamics, tolerability, cost, insurance formularies, and unique risks leading to warnings or precautions 1
• Limited data are available on drug pharmacokinetics and pharmacodynamics of SNRIs for young people, and most SSRIs have sufficiently long elimination half-lives to permit single daily dosing 1 For patients with severe symptoms requiring immediate relief, benzodiazepines such as lorazepam (0.5-2mg), alprazolam (0.25-0.5mg), or clonazepam (0.5-1mg) may be prescribed short-term (2-4 weeks) alongside an SSRI/SNRI while waiting for the antidepressant to take effect. However, benzodiazepines should be used cautiously due to risks of dependence, tolerance, and withdrawal. Alternative anxiolytics for patients who don't respond to or cannot tolerate first-line treatments include buspirone (7.5-15mg twice daily), pregabalin (150-600mg daily in divided doses), hydroxyzine (25-100mg up to four times daily), and certain atypical antipsychotics or tricyclic antidepressants. Treatment should be individualized based on anxiety subtype, comorbidities, previous medication response, and side effect profiles, with regular monitoring for effectiveness and adverse effects. Medication should ideally be combined with cognitive-behavioral therapy or other psychotherapeutic approaches for optimal outcomes.

From the Research

Step-Wise Approach to Medication for Anxiety Disorders

The treatment of anxiety disorders typically involves a step-wise approach, with the selection of medication depending on the severity of symptoms, patient preferences, and potential side effects.

• First-Line Treatments: Selective serotonin reuptake inhibitors (SSRIs) are commonly used as first-line treatments for anxiety disorders, including generalized anxiety disorder, social anxiety disorder, and panic disorder 2, 3, 4. SSRIs have been shown to be effective in reducing symptoms of anxiety and have a relatively favorable side effect profile.
• Second-Line Treatments: For patients who do not respond to SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs) may be considered as second-line treatments 3, 5. SNRIs have been shown to be effective in reducing symptoms of anxiety and may be particularly useful for patients with comorbid depression.
• Alternative Treatments: Benzodiazepines may be used as alternative treatments for anxiety disorders, particularly for patients who require rapid relief from symptoms 3, 5, 6. However, benzodiazepines can be associated with risks of tolerance and dependence, and their use should be carefully monitored.
• Other Anxiolytics: Other anxiolytics, such as buspirone and hydroxyzine, may also be used to treat anxiety disorders 3, 5. These medications may be particularly useful for patients who have not responded to other treatments or who have contraindications to SSRIs or SNRIs.
• Combination Therapies: Combination therapies, involving the use of multiple medications, may be considered for patients with severe or treatment-resistant anxiety disorders 3, 5. However, the use of combination therapies should be carefully monitored, as they can be associated with increased risks of side effects.

Key Considerations

When selecting a medication for anxiety disorders, several key considerations should be taken into account, including:

• Efficacy: The medication should be effective in reducing symptoms of anxiety.
• Side Effects: The medication should have a relatively favorable side effect profile.
• Potential for Abuse: The medication should have a low potential for abuse, particularly for patients with a history of substance use disorders.
• Patient Preferences: The patient's preferences and values should be taken into account when selecting a medication.
• Comorbid Conditions: The presence of comorbid conditions, such as depression or substance use disorders, should be considered when selecting a medication.