What non-controlled substances are effective for managing anxiety?

Non-Controlled Substances for Anxiety Management

SSRIs (selective serotonin reuptake inhibitors) are the first-line non-controlled pharmacological treatment for anxiety disorders, with escitalopram and sertraline being the preferred agents based on efficacy and tolerability. 1

Primary Pharmacological Options

First-Line: SSRIs

The following SSRIs have the strongest evidence base for anxiety treatment:

• Escitalopram: Recommended as first-line by NICE guidelines and listed as a standard drug in German S3 guidelines 1
• Sertraline: First-line per NICE guidelines with favorable side effect profile and low drug interaction potential 1, 2
• Fluvoxamine: Effective for anxiety disorders with similar efficacy to other SSRIs 1
• Paroxetine: Effective but considered second-line by NICE due to discontinuation symptoms 1

Key prescribing considerations: SSRIs demonstrate high treatment response rates (NNT = 4.70) with dropout rates similar to placebo, indicating excellent tolerability 1. Treatment should continue for 6-12 months after remission to prevent relapse 3.

Second-Line: SNRIs

• Venlafaxine: Listed as a standard drug in multiple international guidelines with efficacy comparable to SSRIs (NNT = 4.94) 1

Important caveat: While effective, venlafaxine may have more discontinuation symptoms than some SSRIs 1.

Alternative Non-Controlled Options

Anticonvulsant Analogs

• Pregabalin: Listed as first-line in Canadian guidelines for social anxiety disorder 1
• Gabapentin: Considered second-line per Canadian guidelines, particularly useful when comorbid conditions exist (neuropathic pain, insomnia) 4

Other Agents with Limited Evidence

• Buspirone (azapirone): Can be considered for generalized anxiety disorder, though evidence is less robust than SSRIs 3, 5
• Hydroxyzine (antihistamine): May have utility in GAD but limited high-quality evidence 5

Non-Pharmacological First-Line Treatment

Cognitive Behavioral Therapy (CBT) should be offered as first-line treatment, either alone or combined with pharmacotherapy 1, 4, 3. Structured CBT consists of approximately 14 individual sessions over 4 months (60-90 minutes each) 1.

Treatment Algorithm

1. Initial approach: Start with SSRI (escitalopram or sertraline preferred) OR CBT, depending on patient preference and availability 1, 4

2. If inadequate response after 12 weeks: Switch to alternative SSRI or add CBT if not already implemented 1, 3

3. If multiple SSRI failures: Consider venlafaxine (SNRI) or pregabalin 1

4. Comorbid conditions guide selection:

   • Depression present: Prioritize antidepressant (SSRI/SNRI) over other options 5
   • Neuropathic pain/insomnia: Consider gabapentin or pregabalin 4

Critical Safety Warnings

Monitor for serious adverse reactions with SSRIs/SNRIs including serotonin syndrome, neuroleptic malignant syndrome, and common side effects like somnolence, dizziness, and nausea 1. Dose adjustments may be necessary in elderly patients or those with renal impairment (eGFR <30 mL/min) 1.

What to Avoid

Beta blockers (atenolol, propranolol) are specifically not recommended based on negative evidence in anxiety disorders 1. While benzodiazepines are effective, they are controlled substances and carry dependence risks, making them inappropriate for routine or long-term use 1, 4, 3.