What are alternative treatments for acute anxiety in the absence of benzodiazepines (BZDs)?

Alternative Treatments for Acute Anxiety Without Benzodiazepines

First-line treatment for acute anxiety when benzodiazepines are not an option should be selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), with paroxetine being particularly effective for social anxiety disorder. 1, 2

Pharmacological Options

First-Line Medications

• SSRIs (such as paroxetine, fluvoxamine, escitalopram) are recommended as first-line pharmacological treatment for anxiety disorders due to their efficacy and favorable side effect profile 1
• SNRIs (such as venlafaxine, duloxetine) offer dual action on both serotonin and noradrenaline systems, which may provide advantages in certain anxiety disorders 3
• Paroxetine has demonstrated significant superiority over placebo in treating social anxiety disorder at doses of 20-50 mg daily 2

Second-Line Medications

• Antipsychotics may be considered for severe anxiety with agitation:

  • Haloperidol 0.5-1 mg orally at night and every 2 hours as required (maximum 10 mg daily, 5 mg in elderly) 1
  • Quetiapine 25 mg (immediate release) orally every 12 hours if needed 1
  • Olanzapine 2.5-5 mg orally or subcutaneously (caution: risk of oversedation) 1

• Other options include:

  • Hydroxyzine (an antihistamine) has shown efficacy over placebo for generalized anxiety disorder, though evidence quality is limited 4
  • Buspirone (5-HT1A receptor partial agonist) may be effective for generalized anxiety disorder 3
  • Pregabalin has evidence for anxiety treatment and lacks the dependence potential of benzodiazepines 5

For Specific Situations

• For anxiety in palliative care settings when benzodiazepines are contraindicated:

  • Levomepromazine (methotrimeprazine) 5-12.5 mg orally or subcutaneously every 2 hours as needed 1
  • Haloperidol in lower doses (0.25-0.5 mg) for elderly or frail patients 1

• For breathlessness-associated anxiety:

  • Low-dose morphine may be considered (if not contraindicated): 2.5-10 mg PO every 2 hours as needed 1
  • In renal impairment (GFR <30 mL/min), use oxycodone instead of morphine 1

Non-Pharmacological Approaches

• Cognitive Behavioral Therapy (CBT) has the highest level of evidence among psychological interventions 1, 5

• Other effective psychological interventions include:

  • Mindfulness-based cognitive therapy 1
  • Acceptance and commitment therapy 1
  • Relaxation techniques and stress management 1

• Physical comfort measures:

  • Use of fans and cooler temperatures for anxiety with breathlessness 1
  • Educational, psychosocial, and emotional support for the patient 1

Treatment Algorithm

1. Assess severity and context of anxiety:

   • For mild-moderate anxiety: Start with non-pharmacological approaches
   • For moderate-severe anxiety: Consider medication plus non-pharmacological approaches 5

2. First medication choice:

   • Start with an SSRI (paroxetine 20mg daily) or SNRI 2, 5
   • Note: These medications may take 2-4 weeks for full effect

3. For immediate symptom relief while waiting for SSRI/SNRI effect:

   • Consider hydroxyzine 25-50mg as needed 4
   • Or low-dose antipsychotic for severe agitation (haloperidol 0.5-1mg) 1

4. For treatment-resistant anxiety:

   • Consider augmentation with second-generation antipsychotics at low doses 1
   • Consider pregabalin as an alternative 5

Important Considerations and Pitfalls

• Avoid NSAIDs in patients with heart failure as they increase fluid retention and risk of worsening heart failure 1

• Caution with antipsychotics:

  • Monitor for extrapyramidal side effects, especially with haloperidol 1
  • Use lower doses in elderly patients or those with hepatic impairment 1
  • Beware of QTc prolongation with certain antipsychotics 1

• Medication duration:

  • After remission, medications should be continued for 6-12 months to prevent relapse 5
  • For long-term treatment, regularly re-evaluate the need for continued medication 2

• Special populations:

  • In elderly patients: Start with lower doses of all medications 1
  • In renal impairment: Avoid morphine and use oxycodone if opioids are needed 1
  • In patients with COPD: Use caution with respiratory depressants 1