Psychopharmacology of Anxiety Disorders I: GAD & SAD

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This PPT is part 1 of 2 lectures given to second year pharmacy students in a pharmacology & toxicology class.

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Psychopharmacology of Anxiety Disorders I: GAD & SAD

  1. 1. Anxiety I: Agents for GAD and SAD Brian J. Piper, Ph.D., M.S. January 30, 2013
  2. 2. Objectives• Anxiety overview• Generalized Anxiety Disorder (GAD)• Panic Disorder• Social Anxiety Disorder (SAD)• Premenstrual Dysphoric Disorder (PMDD)
  3. 3. Terminology• Fear = current; Anxiety = future• Disorder = – personal distress – social or occupation impairment
  4. 4. Comorbid ConditionsAnxiety frequently occurs with substance abuse, ADHD, bipolar, pain & sleep disordersStahl, S. (2008). Essential Psychopharmacology, p. 722.
  5. 5. Neurobiology of Anxiety ---------- CRH: Corticotropin Releasing Hormone; ACTH: Adrenocorticotropin Hormone; CORT: cortisolStahl, S. (2008). Essential Psychopharmacology, p. 727.
  6. 6. Comparison of % Time With Symptoms• High--|-----------|-----------------|----------------|--Low GAD PTSD/OCD Panic Disorder SAD
  7. 7. Most Common of Psychiatric Disorders Lifetime Prevalence Onset Age Onset Age (5%/95%) (50%) OCD 1.6% 19 10 / 54 Panic Disorder 4.7% 24 6 / 56 GAD 5.7% 31 8 / 66 PTSD 6.8% 23 6 / 61 Phobia 12.5% 7 4 / 91 MDD 16.6% 32 12 / 64Kessler et al. (2005). Archives of General Psychiatry, 62, 592 – 602.
  8. 8. Dramatized Example (0:30-1:40): http://www.youtube.com/watch?v=3mOkkCkajsI
  9. 9. All SRI’s Are Not EqualDrug 2D6 3A4escitalopramF weak 0citalopram weak 0fluoxetineF strong moderateparoxetineF strong weaksertraline 0 moderateFFDA approved for GAD 0: negligible Spina et al. (2008). Clinical Therapeutics, 30(7), 1206-1227.
  10. 10. All SRIs Are Not Equal fluoxetine sertraline escitalopram paroxetine citalopram  weakStahl, S. (2008). Essential Psychopharmacology, p. 511 – 541.
  11. 11. SNRI Venlafaxine XR DuloxetineMechanism of Action SRI > NRI SRI > NRIHalf-Life 12 5 (10)Adverse Effects sexual dysfunction sexual dysfunction nausea nausea somnolence dry mouthContraindications MAO-Is MAO-Is
  12. 12. Benzodiazepines & GAD• MOA: ↑ frequency of GABAA α1, α2, α3, α5 Cl-• Onset: rapid (hours) versus 2+ weeks for SRI/SNRI• Recommendation: Addiction concerns indicate tertiary use• Reality: very commonly used
  13. 13. Ashton’s Recommendations of Benzo Withdrawal • Frequency: 30%? • Symptoms: flu-like, sweating, flushing, convulsions, muscle ache, pain, fatigue, energy, stiffness, depression, seizures • Strategy – gradual/individualized dosage recommendation – anti-depressants may be needed (SRIs) – psychological supportAshton, H. (1994). Addiction, 89, 1535-1541.
  14. 14. Future: A More Selective Benzo? • Determination of which GABAA α subunit is required for anxiolytic effect of benzodiazepines. • Mice with α2 subunit modified so diazepam doesn’t bind completed behavioral testingLow et al. (2004). Science, 290(5489), 131-134.
  15. 15. Future: A More Selective Benzo? • Determination of which GABAA α subunit is required for anxiolytic effect of benzodiazepines. • Mice with α2 subunit modified so diazepam doesn’t bind completed behavioral testingLow et al. (2004). Science, 290(5489), 131-134.
  16. 16. Buspirone• MOA: 5-HT1A agonist, D2 (moderate)• Indications: FDA approved for GAD, 3rd-line• Adverse Effects: sedation ( < benzos)• Contraindications: MAO-Is
  17. 17. GAD Summary • GAD treatment was focused on acute symptom management (Benzo). Recent focus is on prevention (SSRI). • SSRIs show 60% response, 30% remission • Benzos continue to be commonly prescribed as a first-line in primary care settingsReinhold et al. (2011). Expert Opinion in Pharmacotherapy, 12(16), 2457-2467.
  18. 18. Panic Disorder• Panic Attacks: – Psychological: sudden, intense anxiety/terror, depersonalization/derealization – Physical: labored breathing, heart palpitations, chest pain, sweating, chills, trembling• Criteria – May co-occur with agoraphobia – Recurrent uncued panic attacks – At least 1 month of concern about future attacksKring, A. (2012). Abnormal Psychology, p. 179.
  19. 19. Contrast • APA recommends: – 1) SSRI: fluoxetine, sertraline, paroxetine – 2) SNRI: venlafaxine ER – 3) TCA: imipramine – 4) Benzos: alprazolam • Benzos continue to be very common for long- term Panic Disorder treatmenthttp://psychiatryonline.org/content.aspx?bookid=28&sectionid=1680635
  20. 20. Social Anxiety Disorder (Social Phobia) • Marked & disproportionate fear consistently triggered by exposure to potential social scrutiny • Trigger situations are avoided or endured with intense anxiety • Symptoms persist for at least 6 monthsDescription (2 min): http://www.youtube.com/watch?v=Gk2hm3bqO1gKring, A. (2012). Abnormal Psychology, p. 178.
  21. 21. Melton, S. & Kirkwood, C. (2011). In DiPiro’s Pharmacotherapy, p. 1223.
  22. 22. Kava Kava • Piper methysticum • MOA: ?, GABAA • Pronounced acute anxiolytic effects • Liver toxicity cases (N > 100)Sarris, et al. (2011). Australian & New Zealand Journal of Psychiatry, 45, 27-35.
  23. 23. Summary• Anxiety disorders are extremely common psychiatric conditions.• Although Benzodiazepines are commonly used for their acute anxiolytic effects, practice guidelines consistently recommend SSRI/SNRI as first line pharmacotherapies for long-term symptomatic management for GAD, SAD, and Panic Disorder.
  24. 24. Prementrual Dysphorphic Disorder • In most menstrual cycles during the past year, at least 5 in the final week before menses: – Affective lability – Irritability – Anxiety – Diminished interest in usual activities – Sleeping too much or too little – Physical symptoms: breast tenderness, joint/muscle pain, bloating • SSRIs are FDA approvedKring, A. (2012). Abnormal Psychology, p. 134.

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