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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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Anxiety I: Agents for GAD and SAD
Brian J. Piper, Ph.D., M.S.
January 30, 2013
Objectives
• Anxiety overview• Generalized Anxiety Disorder (GAD)• Panic Disorder• Social Anxiety Disorder (SAD)• Premenstrual Dysphoric Disorder (PMDD)
Terminology
• Fear = current; Anxiety = future• Disorder = – personal distress– social or occupation impairment
Comorbid Conditions
Stahl, S. (2008). Essential Psychopharmacology, p. 722.
Anxiety frequently occurs with substance abuse, ADHD, bipolar, pain & sleep disorders
Neurobiology of Anxiety
----------
Stahl, S. (2008). Essential Psychopharmacology, p. 727.
CRH: Corticotropin Releasing Hormone; ACTH: AdrenocorticotropinHormone; CORT: cortisol
Comparison of % Time With Symptoms
• High--|-----------|-----------------|----------------|--Low GAD PTSD/OCD Panic Disorder SAD
Most Common of Psychiatric DisordersLifetime Prevalence Onset Age
(50%)Onset Age (5%/95%)
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 / 64
Kessler et al. (2005). Archives of General Psychiatry, 62, 592 – 602.
Dramatized Example (0:30-1:40): http://www.youtube.com/watch?v=3mOkkCkajsI
All SRI’s Are Not EqualDrug 2D6 3A4escitalopramF weak 0
citalopram weak 0
fluoxetineF strong moderate
paroxetineF strong weak
sertraline moderate 0
Spina et al. (2008). Clinical Therapeutics, 30(7), 1206-1227.0: negligibleFFDA approved for GAD
All SRIs Are Not Equalfluoxetine sertraline escitalopram
paroxetine citalopram
Stahl, S. (2008). Essential Psychopharmacology, p. 511 – 541.
weak
SNRI
Venlafaxine XR Duloxetine
Mechanism of Action SRI > NRI SRI > NRIHalf-Life 5 (10) 12
Adverse Effects sexual dysfunctionnauseasomnolence
sexual dysfunctionnauseadry mouth
Contraindications MAO-Is MAO-Is
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
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 support
Ashton, H. (1994). Addiction, 89, 1535-1541.
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 testing
Low et al. (2004). Science, 290(5489), 131-134.
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 testing
Low et al. (2004). Science, 290(5489), 131-134.
Buspirone
• MOA: 5-HT1A agonist, D2 (moderate)• Indications: FDA approved for GAD, 3rd-line• Adverse Effects: sedation ( < benzos)• Contraindications: MAO-Is
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 settings
Reinhold et al. (2011). Expert Opinion in Pharmacotherapy, 12(16), 2457-2467.
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
attacks
Kring, A. (2012). Abnormal Psychology, p. 179.
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 treatment
http://psychiatryonline.org/content.aspx?bookid=28§ionid=1680635
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 months
Kring, A. (2012). Abnormal Psychology, p. 178.Description (2 min): http://www.youtube.com/watch?v=Gk2hm3bqO1g
Melton, S. & Kirkwood, C. (2011). In DiPiro’s Pharmacotherapy, p. 1223.
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.
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.
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 approved
Kring, A. (2012). Abnormal Psychology, p. 134.