II. Precautions

  1. Anxiety Non-pharmacologic Management is a cornerstone to Anxiety Management
    1. Medications should be adjunctive to non-medication therapy
  2. Benzodiazepines are best limited to short-term Anxiety Management
    1. Consider in severe anxiety while bridging to longterm strategies (e.g. SNRI and CBT)
    2. Longterm use risks dependency and abuse

III. Management: First-Line Agents

  1. Indicated as primary agents for anxiety as well as for concurrent depression
    1. Start at low dose and titrate to effective dose (warn patients of delayed effect over 2-4 weeks)
    2. Switch medications or add adjunctive agents if not effective after 4-6 weeks at optimal dose
    3. Continue medications for at least 12 months before tapering dose
  2. Specific precautions in children
    1. SSRI and SNRI have FDA black box warnings for Suicidality in children and teens
    2. Continue medications for 6 to 12 months after symptoms resolve and plan to taper during stress-free times (e.g. summer)
  3. Serotonin-Norepinephrine Reuptake Inhibitors
    1. Venlafaxine (Effexor ER)
      1. Excellent first-line agent with good efficacy, and generally well tolerated in Anxiety Disorder
      2. Starting dose: 37.5 mg/day (of extended release)
    2. Duloxetine (Cymbalta)
      1. FDA approved for Generalized Anxiety Disorder for ages 7 years and older
      2. Strawn (2015) J Am Acad Child Adolesc Psychiatry 54(4):283-93 +PMID: 25791145 [PubMed]
  4. Selective Serotonin Reuptake Inhibitors or SSRIs
    1. Escitalopram (Lexapro) or Citalopram (Celexa)
    2. Sertraline (Zoloft)
    3. Paroxetine (Paxil)
      1. Other agents are preferred due to severe Antidepressant Withdrawal symptoms

IV. Management: Adjunctive - Benzodiazepines

  1. Precautions
    1. Use short-term for severe anxiety until SSRI or SNRI reaches effectiveness
    2. Consider longer-term only with caution and Consultation if severe anxiety refractory to non-Benzodiazepines
    3. Consider Hydroxyzine as an alternative
  2. Short-acting Benzodiazepines
    1. Lorazepam (Ativan)
      1. Indicated when a Benzodiazepine cannot be avoided in the elderly or with decreased Creatinine Clearance
    2. Avoid Alprazolam
      1. Higher risk of abuse and withdrawal (rapid onset, short Half-Life)
  3. Long Acting Benzodiazepines
    1. Clonazepam (Klonopin)
      1. Less abused than the shorter acting agents (but still, abuse is common)

V. Management: Adjunctive Pharmacotherapy - Second Line

  1. Precautions
    1. No evidence of benefit when most adjunctive drugs are added to Antidepressants in treatment resistant anxiety
    2. Agents lacking evidence include Benzodiazepines, Buspar, Atypical Antipsychotics
    3. Patterson (2017) Focus 15(2): 219-26 [PubMed]
  2. Hydroxyzine (Atarax, Vistaril)
    1. Sedating Antihistamine with rapid onset that may be used as needed
    2. As effective as Benzodiazepines in limited studies
      1. Guaiana (2010) Cochrane Database Syst Rev (12):CD006815 [PubMed]
  3. Buspirone (Buspar)
    1. Start at 7.5 mg orally twice daily (and may titrate up to 30 mg twice daily)
    2. Use on scheduled basis (too long of delayed onset to be used as needed)
    3. Positive effects are delayed at least 2 weeks from drug onset
    4. More effective than Placebo in Generalized Anxiety Disorder
    5. Not effective in Panic Disorder
  4. Pregabalin (Lyrica)
    1. Second-line agent after Antidepressants have been tried
    2. Relieves Anxiety Symptoms with similar efficacy to SSRIs and Benzodiazepines
    3. Minimum threshold effective dose is 200 mg per day
    4. Adverse effects include drowsiness, Dizziness and weight gain
    5. Risks for misuse and abuse (as with Gabapentin)
    6. Bech (2007) Pharmacopsychiatry 40(4): 163-8 [PubMed]
  5. Gabapentin (Neurontin)
    1. Has also been used instead of Pregabalin (Lyrica)
  6. Atypical Antipsychotics
    1. Quetiapine (Seroquel)
  7. Tricyclic Antidepressants (may be useful in transitioning off Benzodiazepines)
    1. Imipramine (Tofranil)
    2. Desipramine (Norpramin)

VI. Management: Adjunctive Pharmacotherapy - Third Line

  1. MAO Inhibitors
    1. Indicated for concurrent Phobia
    2. Phenelzine (Nardil)
    3. Tranylcypromine (Parnate)
  2. Cardiovascular agents (excessive autonomic symptoms)
    1. Clonidine (Catapres)
    2. Beta Blockers
      1. Indicated for excessive autonomic symptoms
      2. Propranolol (Inderal)
      3. Atenolol (Tenormin)

VII. Management: Herbals and Supplements Used in Anxiety Disorder

  1. Agents that appear effective
    1. Ashwagandha (Withania somnifera)
      1. Well tolerated other than mild gastrointestinal side effects
      2. Contraindicated in Hormone-sensitive Prostate Cancer
      3. Contraindicated in pregnancy (risk of Preterm Labor)
      4. Risk of sedation when taken with Benzodiazepines
    2. Chamomile Extract
      1. Well tolerated
    3. Lavender Extract (Lavandula angustifolia)
      1. Well tolerated other than increased sedation when combined with Opioids or Sedatives
    4. Magnesium
      1. Well tolerated
      2. May cause Diarrhea in higher doses
  2. Possibly effective agents
    1. Kava Kava (Piper methysticum)
      1. Hepatotoxicity (rare, low risk)
      2. Rare Headaches
  3. Inconclusive effectiveness
    1. Passion Flower (Passiflora incarnata)
      1. May cause Ataxia and CNS depression or sedation
      2. Risk of Prolonged QTc with higher doses
    2. St. John's Wort (Hypericum perforatum)
      1. Serotonin Syndrome risk when combined with serotinergic medications (e.g. SSRIs)
      2. Gastrointestinal side effects (e.g. Nausea) or Headache may occur
    3. Valerian (Valeriana officinalis)
      1. Well tolerated other than gastrointestinal side effects, Headaches
      2. Hepatotoxicity (rare, low risk)
    4. 5-Hydroxytryptophan
      1. Gastrointestinal side effects
      2. Serotonin Syndrome risk when combined with serotinergic medications (e.g. SSRIs)
  4. References
    1. DeGeorge (2022) Am Fam Physician 106(2): 157-64 [PubMed]

VIII. Management: Children

  1. Cognitive Behavioral Therapy (most important single intervention)
  2. Selective Serotonin Reuptake Inhibitors (SSRI)
    1. SSRIs combined with CBT are 80% effective in pediatric anxiety
    2. Fluoxetine (Prozac)
    3. Citalopram (Celexa)
    4. Sertraline (Zoloft)
    5. Avoid Paroxetine (Paxil) due to withdrawal risk
  3. Serotonin Norepinephrine Reuptake Inhibitors (SNRI)
    1. Venlafaxine (Effexor)
  4. Other agents with specific indications
    1. Clomipramine indications
      1. Inadequate effect with CBT and SSRI or SNRI
      2. Obsessive-Compulsive Disorder
    2. Benzodiazepine indications
      1. Short-term as needed use for severe anxiety and panic while initiating other therapy
  5. Precautions
    1. Avoid Tricyclic Antidepressants due to low efficacy in pediatric anxiety
  6. References
    1. (2013) Presc Lett 20(5): 29
    2. Todd (2012) Child Adolesc Psychiatr Clin N Am 21(4):789-806 [PubMed]

IX. Complications: Medications in the Elderly

  1. Ataxia with risk of falls and secondary Fracture
  2. Decreased cognition

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