Transcript Practice Guideline for the Treatment of Patients with

Treating Resistant Anxiety Disorders
(Resource: www.healthyminds.org)
Lorrin M. Koran, M.D.
Professor of Psychiatry, Emeritus
Stanford University Medical Center
Panic Disorder without Agoraphobia:
Diagnostic Criteria
• Recurrent unexpected panic attacks
• ≥ 1 month of worry re recurrence,
implications, consequences
• ≥ 1 month of changed behavior
• Not due to substance or medical disorder
• Not better accounted for by other psych dx,
e.g., PTSD, OCD, social phobia
Epidemiology of Panic Disorder
• Prevalence: 1.6%-2.2%, F/M = 2/1
• Age at onset typically 20s
• Runs in families:
– Risk = 4-7x higher in first degree relatives
• Comorbidities:
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Major depression - 50%-60%
Alcohol/substance
GAD, OCD, PTSD
Bipolar I and II - 11%-22%
Panic Disorder: Differential Dx
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Caffeinism
Hyperthyroidism
COPD
Stimulant abuse
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Hypoparathyroidism
Vestibular problem
TLE
Cardiac arrhythmia
Steroids
Bronchodilators
Pheochromocytoma
Hypoglycemia
First-line Treatments for Panic Disorder
• CBT (~ 65% much, very much improved)
• SSRI (50-65% panic free, vs 40-55% placebo)
– Sertraline ≥ 100 mg. Paroxetine 40 mg > 20 mg
– Citalopram 20-30 mg > 40-60 mg (drop outs)
• Benzodiazepine (60-75% panic free)
• Add CBT later to SSRI (starting both
simultaneously may lead to poorer long-term
outcome)
• Patient education
Possible Treatments for Rx-Resistant
Panic Disorder
• Add to an SSRI:
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CBT (controlled trials)
high-potency benzodiazepine (dbl.blind trials)
Pindolol (2.5 mg tid) (open trial)
Pramipexole (0.251.5 mg/d) (cases)
• Switch to a TCA (imipramine 75-150 mg)
• Switch to mirtazapine (1 small trial)
• Add or switch to an atypical antipsychotic
Generalized Anxiety Disorder:
Diagnostic Criteria
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Excessive worry re many events/activities
Difficult to control (unlike normal worry)
≥ 50% of days in past 6 months
≥ 3 of:
– Muscle tension, restlessness, mental tension,
– Fatigue, irritability, poor concentration
• Causes signif. distress or impairment
Epidemiology of Generalized Anxiety Disorder
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Prevalence 1 year: 3%, lifetime: 5%
F/M = 2/1
Onset ≥ 50% in childhood/adolescence
Less than 50% remit without Rx
About 8% of patients in primary care
Comorbidities:
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Major depression 63%, dysthymia 40%
Panic disorder, Social Anxiety Disorder, OCD
Sedative, anxiolytic drug abuse
Fibromyalgia, irritable bowel, chest pain, headache
First-line Treatments for
Generalized Anxiety Disorder
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SSRI - sexual SEs
SNRI - venlafaxine, duloxetine
Benzodiazepines - differences among them
Buspirone - onset 2-4 weeks. 20-60 mg
Hydroxyzine - 50 mg/day, 12-week trial
CBT - self-monitor; relaxation; cognitive
therapy; rehearse skills via imagery
Possible Treatments for Rx-Resistant
Generalized Anxiety Disorder
• Take a caffeine history
• Consider treatment alliance, comorbid conditions,
adherence, secondary gain, stressors, family
• Add CBT to drug or vice versa (sparse data)
• Add an SSRI or SNRI to a benzodiazepine (?)
• Add to an SSRI or SNRI:
– A benzodiazepine (experts suggest)
– pregabalin (dbl-blnd studies)
– an atypical antipsychotic (case reports)
Social Anxiety Disorder:
Diagnostic Criteria
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Marked, persistent fear of social situations
Fear of embarrassment, humiliation
Excessive anxiety in the feared situation
Avoids, or endures with great distress
Impaired function or marked distress
If under age 18, duration ≥ 6 months
Not due to BDD, panic, stuttering, anorexia
Epidemiology of Generalized Social Anxiety
Disorder
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Prevalence 1 yr: 8%; lifetime 13%
F/M = 1.4/1
Onset usually childhood/adolescence
Spontaneous remission in only 20%
Comorbidities
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Major depression - 60% lifetime
Agoraphobia - 47%
Alcohol abuse - 25%-35%
GAD - 20%, panic disorder - 10%
Body dysmorphic disorder - 11%
First-line Treatments for
Social Anxiety Disorder
• SSRI (50%-80% response [≥ 50%  in
LSAS score])
• Venlafaxine (44%-69% response)
• Benzodiazepine (doesn’t Rx comorbid MDD)
• CBT (50%-66% response)
– Individual format better than group format
– ? More durable than meds after discontinuation
– Doesn’t add to SSRI efficacy in studies, but may help
a given individual
Possible Treatments for Rx-Resistant
Social Anxiety Disorder
• Add to an SSRI or SNRI (expert opinion):
– CBT (individual, not group)
– A benzodiazepine
– Gabapentin or Pregabalin
• Switch to an MAOI (controlled trial)
Evidence for Anticonvulsants in Anxiety Disorders
Mula et al., J Clin Psychopharmacol 2007;27:263-272
Drug
GAD
Gabapentin
Panic Disorder
SAD
2?
2
Levetiracetam
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3
Pregabalin
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2
Tiagabine
3
Topiramate
Valproic acid
3
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3
Level 1 = meta-analysis and replicated RCTs; Level 2 = ≥ 1 RCT;
Level 3 = uncontrolled trial with ≥ 10 subjects
APA Practice Guideline
Work Group on OCD
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Lorrin M. Koran, M.D., Chair
Gregory L. Hanna, M.D.
Eric Hollander, M.D.
Gerald Nestadt, M.D.
Helen Blair Simpson, M.D., Ph.D.
APA Staff
• Robert Kunkle, M.A., Senior Program Manager
• Amy B. Albert, B.A., Project Manager
• Laura J. Fochtmann, M.D., Medical Editor
Disclosures
• L. Koran, M.D.
– Cypress Bioscience, Eli Lilly, Forest
Laboratories, Jazz Pharmaceuticals, Ortho
McNeil, Somaxon,
• E. Hollander, M.D.
– Abbott, Eli Lilly, Forest Laboratories,
GlaxoSmithKline, Janssen, Pfizer, Somaxon,
Wyeth
APA Guideline for Obsessive-Compulsive Disorder:
Psychiatric Management
• Establish a therapeutic alliance.
• Assess symptoms and differentiate them from
those of other disorders.
• Consider using rating scales.
• Enhance the safety of the patient and others.
• Set treatment goals (e.g., to improve symptoms,
functioning, QOL; enhance cooperation, coping;
educate the patient and family).
• Enhance treatment adherence.
Choosing an Initial Treatment
• First-line treatments: CBT, SRI, or SRI + CBT.
• CBT alone is recommended for a patient who is
not too depressed, anxious, or severely ill to
cooperate with treatment, or who prefers not to
take medications.
• An SRI alone is recommended for a patient who
has previously responded well to a given drug or
who prefers treatment with an SRI alone.
Combined Treatment
• More effective than monotherapy for some
patients, but not necessary for all.
• Consider for patients with an unsatisfactory
response to monotherapy, for those with cooccurring psychiatric conditions for which
SRIs are effective, and for those who wish
to limit the duration of SRI treatment.
• Also consider for patients with severe OCD.
Comorbid Conditions in OCD
Treatment Implications
e.g., of tics/Tourette’s
Axis I Comorbidity in OCD Subjects
Brown Longitudinal Obsessive-Compulsive Study (N=293)
Lifetime
Current
DSM-IV Diagnosis
n
%
n
%
OCD only
27
9.2
170
58.0
217
74.1
48
16.4
197
67.2
44
15.0
8
2.7
2
0.7
8
2.7
6
2.0
154
52.6
111
38.0
Panic disorder
54
18.4
21
7.2
Social phobia
81
27.6
55
18.8
Specific phobia
53
18.1
43
14.7
Generalized anxiety disorder
22
7.5
22
7.5
75
25.6
17
5.8
Any mood disorder
Major depressive disorder (MDD)
Bipolar disorder
Any psychotic disorder
Any anxiety disorder
Any substance use disorder
Pinto A, et al. J Clin Psychiatry. 2006;67:703-711.
Pharmacotherapy for OCD
• Clomipramine, fluoxetine, fluvoxamine,
paroxetine, and sertraline are FDA-approved.
• An SSRI is preferred for a first medication trial
because the SSRIs have a less troublesome side
effect profile than clomipramine.
• All SSRIs (including citalopram and escitalopram)
appear to be equally effective. Consider side
effects, drug interactions, past treatment response,
and co-occurring general medical conditions.
CBT and Other Psychotherapies
• CBT utilizing primarily behavioral techniques
such as exposure and response prevention (ERP)
is recommended because it has the best
evidentiary support.
• Some data support Cognitive Therapy.
• Psychodynamic psychotherapy may help patients
overcome resistance to treatment or address
interpersonal consequences of OCD.
• Motivational interviewing and family therapy may
be useful.
Implementing Pharmacotherapy
• Initiate at the dose recommended by the
manufacturer and titrate to the maximum tolerated
dose.
• Continue for 8-12 weeks, including 4-6 weeks at a
maximum tolerated dose.
• Manage side effects (e.g., insomnia, fatigue,
sweating, bruxism, sexual dysfunction).
• Follow-up may vary from a few days to 2 weeks
after starting a new medication.
Implementation of CBT
• The literature and expert opinion suggest that an
adequate trial for most patients is 13-20 weekly
sessions with daily homework (or 3 weeks of
weekday daily CBT).
• CBT can be delivered in individual, group, or
family formats, with session lengths from <1 hour
to 2 hours.
• Consider booster sessions after response.
• Self-help treatment guides are OK to use.
• Refer patients to www.ocfoundation.org.
Changing Treatment: General Principles
• First treatments rarely produce freedom from all
OCD symptoms.
• Patients may be willing to accept residual
symptoms. But consider whether depressed mood
is diminishing hopefulness or illness is associated
with secondary gain.
• Consider contribution of other factors such as
problems in the therapeutic alliance, interference
of co-occurring conditions, inadequate adherence,
psychosocial stressors, or family accommodation.
Changing Treatment: Strategies
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Augment SSRI with CBT (or CT) or vice versa.
Augment SSRI with an atypical antipsychotic.
Switch to a different SSRI or to clomipramine.
Switch to venlafaxine or to mirtazpine.
Augment with buspirone, once-weekly morphine,
inositol, or a glutamate antagonist.
• Switch to d-amphetamine, tramadol, ondansetron,
or an MAOI.
• Consider rTMS, deep brain stimulation, ablative
neurosurgery.
Discontinuing Treatment
• Continue medication for 1-2 years, then consider a
gradual taper (10%-25% q 1-2 months).
• Follow successful CBT with monthly booster
sessions for 3-6 months or more.
• Relapse rates are high. Most patients require
continued treatment of some form.
• Some data suggest “relapse” 4-6 months after
CBT is less likely than after medication has been
stopped.
Additional Information Available in
the Full-Text Guideline
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Disease definition
Epidemiology
Natural history and course
Genetics
Review of evidence regarding all treatments
Suggestions for future research
Published in Am J Psychiatry, July 2007, and
www.psychiatryonline.com.