Pharmacotherapy of Anxiety Disorders

Anxiolytics Overview - Pill Power Intro

• Major Anxiolytic Classes:
  • SSRIs & SNRIs (Often first-line)
  • Benzodiazepines (BZDs) (Rapid relief, short-term)
  • Buspirone (Non-sedating, delayed onset)
  • Beta-blockers (Performance anxiety, e.g., Propranolol)
  • TCAs & MAOIs (Reserved due to side effects/interactions)
• Indications for Pharmacotherapy:
  • Moderate to severe symptoms, functional impairment.
  • Patient preference or inadequate psychotherapy response.
• General Principles:
  • Start low, go slow.
  • Adequate trial: 4-8 weeks at therapeutic dose.
  • Taper gradually on discontinuation to prevent withdrawal.

⭐ SSRIs are generally first-line for most anxiety disorders due to better tolerability and safety profile.

SSRIs & SNRIs - Serotonin Soothers

• MOA: SSRIs selectively inhibit 5-HT reuptake; SNRIs inhibit 5-HT & NE reuptake.
• Examples (Anxiety Doses):
  • SSRIs: Fluoxetine (20-60mg), Sertraline (50-200mg), Paroxetine (20-50mg), Escitalopram (10-20mg).
  • SNRIs: Venlafaxine XR (75-225mg), Duloxetine (60-120mg).
• Uses: First-line for GAD, Panic Disorder, Social Anxiety Disorder, PTSD, OCD.
• Side Effects: GI upset, sexual dysfunction, initial ↑anxiety, sleep issues. Serotonin Syndrome (agitation, hyperthermia, hyperreflexia).
• Key Notes:
  • Therapeutic effect: 2-4 weeks (up to 6-8).
  • Discontinuation 📌 FINISH: Flu-like symptoms, Insomnia, Nausea, Imbalance, Sensory disturbances, Hyperarousal.

⭐ SSRIs are first-line for most anxiety disorders due to better tolerability.

Benzodiazepines - Rapid Relaxers

• MOA: Positive allosteric modulators of GABA-A receptors; ↑ frequency of $Cl^-$ channel opening, enhancing GABAergic inhibition.
• Classification & Examples:
  • Short-acting: Midazolam, Triazolam.
  • Intermediate-acting: Alprazolam, Lorazepam, Oxazepam, Temazepam. (📌 Mnemonic 'LOT': Lorazepam, Oxazepam, Temazepam - safer in liver disease/elderly).
  • Long-acting: Diazepam, Clonazepam, Chlordiazepoxide.
• Indications: Acute anxiety, panic attacks, insomnia (short-term), procedural sedation, alcohol withdrawal, status epilepticus.
• Adverse Effects: Sedation, drowsiness, psychomotor impairment, anterograde amnesia, respiratory depression (⚠️ risk with opioids), dependence, tolerance, withdrawal syndrome.
• Antidote: Flumazenil.

⭐ Flumazenil reverses BZD overdose but must be used cautiously in chronic users due to risk of precipitating seizures.

Other Anxiolytics - Backup Brigade

• Buspirone: 5-HT1A partial agonist, D2 antagonist. Delayed onset (2-4 weeks). No dependence/withdrawal. For GAD; not panic disorder.

  ⭐ Buspirone has a delayed onset of anxiolytic action, typically 2-4 weeks, and is not effective for acute anxiety or panic attacks.

• Beta-blockers (e.g., Propranolol): For performance anxiety (social phobia), managing peripheral somatic symptoms (tremor, tachycardia). Propranolol 10-40 mg prior to event.
• Pregabalin: Binds to $\alpha2\delta$ subunit of voltage-gated Ca$^{2+}$ channels. Anxiolytic in GAD, faster onset than SSRIs. Potential for misuse.
• Antihistamines (e.g., Hydroxyzine): Sedative/anxiolytic via H1 antagonism. Short-term anxiety, insomnia.
• TCAs & MAOIs: Imipramine (panic), Clomipramine (OCD), Phenelzine. Use limited by side effects/dietary restrictions (MAOIs).

Anxiety Rx Algorithms - Smart Steps

• Core Strategy: SSRIs/SNRIs are first-line for GAD, Panic Disorder, SAD, PTSD, OCD.
• Benzodiazepines (BZDs) for initial severe symptoms (short-term bridge).
• GAD/Panic Disorder Flow:

• OCD: Higher SSRI doses often needed; Clomipramine is effective.
• PTSD: Prazosin for nightmares.
• Duration: Maintain treatment 6-12 months post-remission before slow taper.

⭐ For most anxiety disorders, SSRIs or SNRIs are the initial pharmacotherapy of choice due to their efficacy and tolerability profile.

High‑Yield Points - ⚡ Biggest Takeaways

• SSRIs (Escitalopram, Sertraline) are first-line for GAD, panic, social anxiety, and PTSD.
• SNRIs (Venlafaxine, Duloxetine) are also first-line, especially with comorbid pain or if SSRIs fail.
• Benzodiazepines offer rapid relief but are for short-term/SOS use only due to high dependence risk.
• Buspirone is a non-BZD anxiolytic for GAD; delayed onset (2-4 weeks), no abuse potential.
• Beta-blockers (Propranolol) manage performance anxiety by reducing peripheral autonomic symptoms.
• TCAs/MAOIs are older agents, typically third-line due to side effects and interactions_._