9. All SRI’s Are Not Equal
Drug 2D6 3A4
escitalopramF weak 0
citalopram weak 0
fluoxetineF strong moderate
paroxetineF strong weak
sertraline 0
moderate
FFDA approved for GAD 0: negligible
Spina et al. (2008). Clinical Therapeutics, 30(7), 1206-1227.
10. All SRIs Are Not Equal
fluoxetine sertraline escitalopram
paroxetine citalopram
weak
Stahl, S. (2008). Essential Psychopharmacology, p. 511 – 541.
11. SNRI
Venlafaxine XR Duloxetine
Mechanism of Action SRI > NRI SRI > NRI
Half-Life 12
5 (10)
Adverse Effects sexual dysfunction sexual dysfunction
nausea nausea
somnolence dry mouth
Contraindications MAO-Is MAO-Is
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. 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.
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 testing
Low et al. (2004). Science, 290(5489), 131-134.
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 testing
Low et al. (2004). Science, 290(5489), 131-134.
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 settings
Reinhold et al. (2011). Expert Opinion in Pharmacotherapy, 12(16), 2457-2467.
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
attacks
Kring, A. (2012). Abnormal Psychology, p. 179.
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 treatment
http://psychiatryonline.org/content.aspx?bookid=28§ionid=1680635
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 months
Description (2 min): http://www.youtube.com/watch?v=Gk2hm3bqO1g
Kring, A. (2012). Abnormal Psychology, p. 178.
21. Melton, S. & Kirkwood, C. (2011). In DiPiro’s Pharmacotherapy, p. 1223.
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. 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. 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.
Anxiety’s final common pathway involves over-activity of the HPA axis or a failure of negative feedback to turn off this system.
Interview conducted with a large (N=9000) nationally representative sample. Notice tremendous individual differences in onset age.
Good general description (2 min): http://www.youtube.com/watch?v=NPWFXZJ59JsAnxiety is out of proportion from the concern.
Paroxetine is a moderate antagonist of muscarinic (M1) receptors. R-citalopram is also a weak anti-histamine inhibitor.
Low dose venlafaxine has more pronounced effects on SRI than NRI. The NRI effects become more pronounced with higher doses. The half-life of venlafaxine is 5 hours but its metabolite desvenlafaxine is twice as long.Duloxetine moderately inhibits 2D6.
Seizures are rare but have been reported. For a video from Heather Ashton, see: http://www.youtube.com/watch?v=UsjhqdE7-6AApproximately 1/3rd of long-term benzo users will have difficulties with withdrawal. The dose reduction process can last months or even years. She recommends a plan that is developed in collaboration between patient and their health care provider. This could involve 1 mg diazepam/2 weeks.
This is a very subtle modification which involves going to the drug binding site and replacing a the amino acid Histidine (H) with an Arginine (A).
This is a very subtle modification which involves going to the drug binding site and replacing a the amino acid Histidine (H) with an Arginine (A).
Metabolized by 3A4.
Cued panic attack (e.g. snakes) = phobia.
DSM-IVTR refers to Social Phobia but this will be changed to Social Anxiety Disorder for DSM 5. SAD has high rates of alcohol dependence (20%).
Symptoms typically improve with a few days of menses. PMDD may occur in 3-5% of women.