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Pharmacologic Considerations in
the Treatment of Anxiety Disorders
Presented by: Ann M. Hamer, PharmD, BCPP
Date: 1/8/2015
Disclosures and Learning Objectives
• Learning Objectives
Be able to identify first-line treatment
recommendations for:
– Panic Disorder
– Generalized Anxiety Disorder
– Social Anxiety Disorder
– Obsessive Compulsive Disorder
– Post Traumatic Stress Disorder
Disclosures: Dr. Ann Hamer has nothing to disclose.
Pharmacologic Treatment of Anxiety
Disorders
• Review treatment recommendations for
• Panic Disorder
• Generalized Anxiety Disorder
• Social Anxiety Disorder
• Obsessive Compulsive Disorder
• Post Traumatic Stress Disorder
General Treatment Recommendations
• Recommendations from:
• World Federation of Biological Psychiatry
•
Complement to diagnostic guidelines prepared by
the World Health Organization (WHO) and
American Psychiatric Association (APA)
• Agency for Healthcare Research and Quality
• National Institute for Health and Clinical
Excellence
General Treatment Recommendations
Treatment selection is based upon:
•
•
•
•
•
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•
•
patient preference
severity of illness
co-morbidity
concomitant medical illnesses
complications like substance abuse or suicide risk,
history of previous treatments
cost issues
availability of types of treatment in a given area
Bandelow, et al. International Journal of Psychiatry in Clinical Practice, 2012; 16: 77–84
General Treatment Recommendations
Treatment options include both pharmacologic and
nonpharmacologic approaches
•
•
Prior to initiating pharmacologic treatment it is
recommended that patients are informed of
advantages and disadvantages
Treatment should continue for at least 6 – 24 months
after remission has occurred, in order to reduce the
risk of relapse, and may be stopped only if all, or
almost all, symptoms disappear.
Bandelow, et al. International Journal of Psychiatry in Clinical Practice, 2012; 16: 77–84
Pharmacologic Treatment
Recommendations
Drug Classes Studied in Anxiety Disorders
Drug Class
Panic
GAD
SAD
OCD
PTSD
SSRIs
X
X
X
X
X
SNRIs
X
X
X
TCAs
X
MAOIs
X
Ca Channel Modulators
Pregabalin
Gabapentin
Benzodiazepines
Atypical Antipsychotics
Risperdal
Quetiapine
Other
Mirtazapine
Hydroxyzine
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Guideline Recommendation Grade
Drug Class
Panic
SSRIs
Citalopram
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
1
1
1
1
1
1
GAD
1
1
1
SAD
OCD
3
1
5
1
1
1
1
1
1
1
1
Grade Key:
1=Category A evidence and good risk-benefit ratio
2=Category A evidence and moderate risk-benefit ratio
3=Category B evidence (limited positive evidence)
4=Category C evidence (evidence from uncontrolled studies or case reports
5=Category D evidence (inconsistent results)
PTSD
1
1
1
Guideline Recommendation Grade
Drug Class
Panic
GAD
SAD
SNRIs
Venlafaxine
Duloxetine
1
1
1
1
Grade Key:
1=Category A evidence and good risk-benefit ratio
2=Category A evidence and moderate risk-benefit ratio
3=Category B evidence (limited positive evidence)
4=Category C evidence (evidence from uncontrolled studies or case reports
5=Category D evidence (inconsistent results)
OCD
PTSD
1
Guideline Recommendation Grade
Drug Class
TCAs
Amitriptyline
Clomipramine
Imipramine
Panic
GAD
SAD
OCD
PTSD
3
2
2
1
Drug Class
Panic
GAD
MAOIs
Phenelzine
3
2
3
SAD
OCD
PTSD
2
5
5
Grade Key:
1=Category A evidence and good risk-benefit ratio
2=Category A evidence and moderate risk-benefit ratio
3=Category B evidence (limited positive evidence)
4=Category C evidence (evidence from uncontrolled studies or case reports
5=Category D evidence (inconsistent results)
Guideline Recommendation Grade
Drug Class
Ca Channel
Modulators
Pregabalin
Gabapentin
Panic
GAD
SAD
1
3
Grade Key:
1=Category A evidence and good risk-benefit ratio
2=Category A evidence and moderate risk-benefit ratio
3=Category B evidence (limited positive evidence)
4=Category C evidence (evidence from uncontrolled studies or case reports
5=Category D evidence (inconsistent results)
OCD
PTSD
Guideline Recommendation Grade
Drug Class
Benzodiazepines
Alprazolam
Clonazepam
Diazepam
Lorazepam
Panic
2
2
2
2
GAD
SAD
3
2
2
Grade Key:
1=Category A evidence and good risk-benefit ratio
2=Category A evidence and moderate risk-benefit ratio
3=Category B evidence (limited positive evidence)
4=Category C evidence (evidence from uncontrolled studies or case reports
5=Category D evidence (inconsistent results)
OCD
PTSD
Guideline Recommendation Grade
Drug Class
Panic
Atypical
Antipsychotics
Quetiapine
Risperidone
Drug Class
Other
Mirtazapine
Hydroxyzine
GAD
SAD
OCD
PTSD
1
3
Panic
GAD
SAD
2
Grade Key:
1=Category A evidence and good risk-benefit ratio
2=Category A evidence and moderate risk-benefit ratio
3=Category B evidence (limited positive evidence)
4=Category C evidence (evidence from uncontrolled studies or case reports
5=Category D evidence (inconsistent results)
OCD
PTSD
3
3
Dosing Ranges of Grade 1 Agents
Drug Class
Panic
SSRIs
Citalopram
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
20-60
10-20
20-40
100-300
20-60
50-150
SNRIs
Venlafaxine
Duloxetine
75-225
GAD
SAD
OCD
10-20
10-20
10-20
20-60
100-300
20-60
50-200
20-50
50-150
75-225
60-120
Ca Channel Modulators
Pregabalin
150-600
Atypical Antipsychotics
Quetiapine
50-300
100-300
20-50
50-150
75-225
PTSD
20-40
20-40
50-100
75-225
SSRIs
• Generally well tolerated
• Restlessness, jitteriness, increase in anxiety
symptoms, insomnia or headache in the first
few days/weeks of treatment may jeopardize
compliance
• Use low starting doses to minimize
overstimulation
• Anxiolytic effect may start with a delay of 2-4
weeks (in some cases up to 6 or 8 weeks)
SNRIs
• Generally well tolerated
• Similar to SSRIs, use low starting doses to
minimize overstimulation
• Anxiolytic effect may start with a delay of 2-4
weeks
• No evidence to support use in OCD
Pregabalin
• Anxioytic effects are attributed to its binding at
the α2-∂-subunit protein of voltage-gated
calcium channels in CNS tissues
• Binding reduces calcium influx at nerve terminal
and modulates the release of neurotransmitters
• Anxiolytic effect starts in first days of treatment
TCAs
• Well proven efficacy, however compliance may
be reduced due to adverse effects
• Concern with drug interactions and potential for
lethality
• SSRIs and SNRIs should be tried first
Benzodiazepines
• Associated with sedation, dizziness, and
prolonged reaction time
• After a couple of weeks or months of
continuous use, dependency may occur in a
substantial number of patients
• Can be helpful in first days/weeks of initiating
antidepressant treatment
• Anxiolytic effect starts within minutes
Atypical Antipsychotics
• Use typically reserved for non-responsive cases
• Significant adverse effects and higher cost
make these agents less favorable
Treatment Considerations
• Most patients will respond to low dose
antidepressants
•
OCD is the exception where higher doses are often
needed
• Start low and go slow
• Single daily doses enhance treatment
adherence
• In patients with hepatic impairment, consider
medications that are primarily renally cleared
Treatment Considerations
• Unless not tolerated, maintain an adequate
dose for 4-6 weeks (8-12 weeks in OCD or
PTSD) before switching agents
• Consider non-pharmacologic treatment
alternatives or enhancements
Treatment Considerations
• Panic disorder and agoraphobia
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Severe attacks may require short-acting
benzodiazepines
SSRIs and venlafaxine are first-line treatment
options
After remission, treatment should continue for at
least several months in order to prevent relapses
Combination CBT and medication has been shown
to have the best treatment outcomes
Treatment Considerations
• Generalized Anxiety Disorder (GAD)
•
•
First-line treatment options are SSRIs, SNRIs and
pregabalin
Benzodiazepines should only be used when other
drugs or CBT have failed (or short-term only)
Treatment Considerations
• Social Anxiety Disorder (SAD)
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•
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SSRIs and venlafaxine are first-line treatment
options
Benzodiazepines not extensively studied
No evidence for use of TCAs
Treatment Considerations
• Obsessive Compulsive Disorder (OCD)
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SSRIs and the TCA clomipramine are first-line
treatment options
Use doses in the medium to upper dose range
Requires long-term treatment at an effective doselevel
Treatment Considerations
• Post-Traumatic Stress Disorder (PTSD)
•
Evidence supports the efficacy of fluoxetine, paroxetine,
sertraline, topiramate, and venlafaxine for improving PTSD
symptoms
•
Insufficient evidence to recommend alpha blockers (e.g.
prazosin), anticonvulsants (other than topiramate),
antipsychotics (minimal evidence for risperidone),
benzodiazepines, TCAs or other second generation
antidepressants
•
Often a chronic disorder requiring long-term treatment for at
least 12-24 months
Psychological and Pharmacological Treatments for Adults With Posttraumatic Stress Disorder (PTSD). Comparative
Effectiveness Review No. 92. AHRQ Publication No. 13-EHC011-EF. Rockville, MD: Agency for Healthcare
Research and Quality; April 2013.
www.effectivehealthcare.ahrq.gov/reports/final.cfm.
Special Treatment Considerations
• Pregnancy
•
•
Risk of drug treatment must be weighed against the
risk of withholding treatment
Recommended to avoid paroxetine and alprazolam
• Breast-feeding
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SSRIs and TCAs generally OK (with the exception of
doxepin)
Typically not recommended with benzodiazepines
Special Treatment Considerations
• Children and Adolescents
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SSRIs recommended first-line
Careful monitoring recommended (increased risk of
suicidal ideation and behavior)
• Elderly
•
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SSRIs appear to be safe (start with low doses)
TCAs and benzodiazepines are less favorable
Special Treatment Considerations
• Patients with Severe Somatic Disease
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Primary or secondary causes of anxiety
Compounds the management and prognosis of
COPD, CAD/MI, DM or brain injury
TCAs best avoided in cardiac disease
SSRIs generally well tolerated (avoid high dose
citalopram and escitalopram)
Venlafaxine usually well tolerated (monitor blood
pressure in patients with hypertension)
The End!
Next Week:
Pharmacologic
Treatment
Recommendations
for Anxiety Part 2