PSYC 7950 Anxiety Disorders Panic Disorder Module 3

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PSYC 7950 Anxiety DisordersPanic Disorder
Module 3

• W Klugh Kennedy, PharmD, BCPP, FASHP, FCCP
• Clinical Professor of Pharmacy Practice
• Professor of Psychiatry
• Mercer University
• Savannah, Georgia
• klughkennedy_at_kennedy-kps.com

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Objectives

• Essential target features of Panic Disorder for
  pharmacotherapeutic treatment.
• Pharmacotherapy and the evidence in Panic
  Disorder

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Panic DO Diagnostic Criteria

• A. Both (1) and (2)
• 1. recurrent unexpected Panic Attacks
• 2. at least one of the attacks has been followed
  by 1 month (or more) of one (or more) of the
  following
• a. persistent concern about having additional
  attacks
• b. worry about the implications of the attack or
  its consequences (e.g., losing control, having a
  heart attack, going crazy)
• c. a significant change in behavior related to
  the attacks
• B. Absence of Agoraphobia
• C. The Panic Attacks are not due to the direct
  physiological effects of a substance (e.g., a
  drug of abuse, a medication) or a general medical
  condition (e.g., hyperthyroidism).
• D. The Panic Attacks are not better accounted for
  by another mental disorder, such as Social Phobia
  (e.g., occurring on exposure to feared social
  situations), Specific Phobia (e.g., on exposure
  to a specific phobic situation),
  Obsessive-Compulsive Disorder (e.g., on exposure
  to dirt in someone with an obsession about
  contamination), Posttraumatic Stress Disorder
  (e.g., in response to stimuli associated with a
  severe stressor), or Separation Anxiety Disorder
  (e.g., in esponse to being away rom home or
  close relatives).

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Panic Attack

• A discrete period of intense fear or discomfort,
  in which four (or more) of the following
  symptoms developed abruptly and reached a peak
  within 10 minutes
• 1. palpitations, pounding heart, or accelerated
  heart rate
• 2. sweating
• 3. trembling or shaking
• 4. sensations of shortness of breath or
  smothering
• 5. feeling of choking
• 6. chest pain or discomfort
• 7. nausea or abdominal distress
• 8. feeling dizzy, unsteady, light-headed, or
  faint
• 9. derealization (feelings of unreality) or
  depersonalization (being detached from oneself)
• 10. fear of losing control or going crazy
• 11. fear of dying
• 12. paresthesias (numbness or tingling
  sensations)
• 13. chills or hot flushes

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Agoraphobia

• A. Anxiety about being in places or situations
  from which escape might be difficult (or
  embarrassing) or in which help may not be
  available in the event of having panic-like
  symptoms. Fears typically involve characteristic
  clusters of situations like being outside the
  home alone in a crowd on a bridge or traveling
  in a bus, train, or automobile.
• Note
• Consider the diagnosis of Specific Phobia if the
  avoidance is limited to one or only a few
  specific situations, or Social Anxiety Disorder
  if the avoidance is limited to social situations.
• B. Situations are avoided or else are endured
  with marked distress or with anxiety about having
  a Panic Attack or panic-like symptoms, or require
  the presence of a companion.
• C. Not better accounted for by another mental
  disorder, such as Social Anxiety Disorder,
  Specific, Obsessive-Compulsive Disorder (e.g.,
  avoidance of dirt in someone with an obsession
  about contamination), Posttraumatic Stress
  Disorder (e.g., avoidance of stimuli associated
  with a severe stressor), or Separation Anxiety
  disorder (e.g., avoidance of leaving home or
  relatives).

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Panic - Epidemiology

• Lifetime prevalence of a panic attack is 15
• Lifetime prevalence of panic disorder is 2
• Age of onset is generally in the 20s
• Comorbid
• ¼ to ½ with agoraphobia
• 1 in 3 with clinical depression
• Higher morbidity and mortality
• Costly in lost work, healthcare utilization, etc.

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Panic Etiology and Risk

• Environment may become triggers
• Learned avoidance ? agoraphobia?
• Genetics 1st degree relative at least 8x more
  likely
• Pathophysiology similar theories to GAD

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Genetics of Panic DO

• trkC gene?
• linkage studies to map the relevant loci have
  implicated several chromosomal regions, including
  1q(14), 2q(15), 4q31-q34(16, 17), 7p(18, 19),
  9q(17, 20), 12q(21), 13q(17, 22),14q(17, 23),
  15q(15), and 22q(17, 24). linkage analyses for PD
  have shown little consistency.
• Only the Val158Met polymorphism of the
  catechol-O-methyltransferase (COMT) gene has been
  implicated in susceptibility to PD by several
  studies independently. Association analyses have
  implicated several genes that are essentially
  classical candidate genes by examined more than
  350 candidate genes, but results were
  inconsistent, negative, or not clearly
  replicated.
• There is a huge amount of published data but no
  consistent candidate SNPs emerge.

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Panic DO Pathophysiology

• Reduced volume in amygdala
• Decrease metabolism in amygdala, hippocampus, and
  thalamus
• Reduced BZD receptor density in peri-hippocampal
  and amygdala areas
• Reductions in 5HT1A receptor concentrations

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Panic DO Pathophysiology

• Noradrenergic Model locus ceruleus
  hypersensitive ? alpha 2 noradrenergic receptors
  down regulated
• Catecholamine Genetic polymorphism decreases
  the effect of COMT? Then why do SSRIs work in
  Panic DO?
• GABA receptor Model inhibitory neurotransmitter
• Serotonin differences, which receptors or is it
  reuptake transporters or is it metabolism?

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Panic DO Rating Scales

• PDSS with or without agoraphobia
• PAS 2 versions 1 for patient
• SPRAS heavily weighted toward somatic effects,
  patient self assessment
• PRIME-MD clinician rated, primary care setting

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Panic Disorder - Nonpharmacologic

• Evidence for efficacy of CBT is excellent
• Combined psychotherapy pharmacotherapy
• Again little data to support, need studies
• All guidelines suggest it.
• I like it

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Panic DisorderPharmacologic Treatment- first line

• SSRIs effect by week 4
• SNRI venlafaxine, duloxetine also 4 week
• Benzodiazepines are commonly required as
  augmenting agents on a scheduled basis.

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Dosing for Panic Disorder
Starting Dose and Incremental Dose (mg/day) Usual Therapeutic Dose (mg/day)
SSRIs
Citalopram 10 2040
Escitalopram 510 1020
Fluoxetine 510 2040
Fluvoxamine 2550 100200
Paroxetine 10 2040
Sertraline 25 100200
SNRIs
Duloxetine 2030 60120
Venlafaxine ER 37.5 150225
TCAs
Imipramine 10 100300
Clomipramine 1025 50150
Nortriptyline 25 50150
Benzodiazepines
Alprazolam 0.751.0 26
Clonazepam 0.51.0 12
Lorazepam 1.52.0 48
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Panic Pharmacotherapy other/alternate

• MAO-Is positive evidence, some confusing
  evidence
• Mirtazapine evidence positive (non-inferiority
  with paroxetine), adverse effects
• Bupropion contradictory evidence, increased
  anxiety
• Trazodone weak contradictory evidence
• Buspirone lack of efficacy as monotherapy or
  augmentation
• Carbamazepine Negative evidence
• Valproate positive from one open-label study
• Gabapentin, Pregabalin, Vigabatrin,
  Levetiracetam, Tiagabine sparse, weak, positive
  evidence
• 2nd Generation Antipsychotics some positive
  evidence for risperidone and olanzapine but more
  rigorous studies needed
• Antihypertensives
• Beta-blockers ineffective, inferior to
  benzodiazepines
• Pindolol weak positive evidence as augmenter
  for SSRI
• Clonidine mild transient effects if any
• Calcium Channel Blockers - mild transient effects
  if any

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Monitoring guidelines

• Baseline laboratory studies CBC, CMP, TSH, UDS
• psychiatric assessment, medical history and
  referral for laboratory or medical evaluation.
• Inquiry about sleep hygiene, lifestyle issues,
  activation syndrome and medication side effects
  should take place at each visit.
• Possible anxiety ADE at start of therapy with
  antidepressants includes increased anxiety,
  jitteriness, shakiness, and agitation. Start at
  one-half the usual dose and slowly titrate.
• Assessment of response goals of treatment
• Decrease frequency and severity of panic attacks
• Reduce anticipatory anxiety, fear-driven
  avoidance, and impaired functioning
• Definition of remission Free of panic attacks,
  no or mild agoraphobic avoidance no or minimal
  anxiety, no or mild functional disability, and no
  depressive symptoms
• Patient input
• Patients should be monitored weekly at onset of
  treatment
• Daily diary of panic symptoms (time, location,
  nature, intensity of panic symptoms)
• Patients on chronic benzodiazepine therapy (gt 3
  months) should consent to a controlled substance
  agreement.

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Questions?

• Questions? Consults? Want to talk?
• IDEAL
• chat sessions so everyone can benefit
• Alternately
• email me at klughkennedy_at_kennedy-kps.com
• Call me at the cell number in the syllabus