Pharmacologic Considerations in the Treatment of Anxiety Disorders
Presented by: Ann M. Hamer, PharmD, BCPP
Date: 1/8/2015

Disclosures and Learning Objectives
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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
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General Treatment Recommendations
• 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:
• 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

Drug Classes Studied in Anxiety Disorders
Drug Class
SSRIs
SNRIs
TCAs
MAOIs
Ca Channel Modulators
Pregabalin
Gabapentin
Benzodiazepines
Atypical Antipsychotics
Risperdal
Quetiapine
Other
Mirtazapine
Hydroxyzine
Panic
X
X
X
X
GAD
X
X
X
X
X
SAD
X
X
X
OCD
X
X
X
PTSD
X
X
X
X
X
X
X
X
X X
X

Guideline Recommendation Grade
Drug Class
SSRIs
Citalopram
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
Panic
1
1
1
1
1
1
GAD
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)
SAD
1
1
1
3
1
5
OCD PTSD
1
1
1
1
1
1
1
1

Guideline Recommendation Grade
Drug Class
SNRIs
Venlafaxine
Duloxetine
Panic
1
GAD
1
1
SAD
1
OCD PTSD
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)

Guideline Recommendation Grade
Drug Class
TCAs
Amitriptyline
Clomipramine
Imipramine
Drug Class
MAOIs
Phenelzine
Panic
2
2
Panic
3
GAD
1
GAD
SAD
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
2
OCD
5
PTSD
3
3
PTSD
5

Guideline Recommendation Grade
Drug Class
Ca Channel
Modulators
Pregabalin
Gabapentin
Panic GAD
1
SAD OCD PTSD
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)

Guideline Recommendation Grade
Drug Class
Benzodiazepines
Alprazolam
Clonazepam
Diazepam
Lorazepam
Panic
2
2
2
2
GAD
2
2
SAD
3
OCD PTSD
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
Atypical
Antipsychotics
Quetiapine
Risperidone
Panic GAD
1
SAD
Drug Class
Other
Mirtazapine
Hydroxyzine
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
OCD
3
3
PTSD
3

Dosing Ranges of Grade 1 Agents
Drug Class
SSRIs
Citalopram
Escitalopram
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
SNRIs
Venlafaxine
Duloxetine
Ca Channel Modulators
Pregabalin
Atypical Antipsychotics
Quetiapine
Panic GAD SAD OCD PTSD
20-60
10-20
20-40
100-300
20-60
50-150
75-225
10-20
20-50
50-150
10-20
100-300
20-50
50-150
10-20
20-60
100-300
20-60
50-200
75-225
60-120
150-600
75-225
20-40
20-40
50-100
75-225
50-300

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
• 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)
• SSRIs and venlafaxine are first-line treatment options
• Benzodiazepines not extensively studied
• No evidence for use of TCAs

Treatment Considerations
• Obsessive Compulsive Disorder (OCD)
• 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
• SSRIs and TCAs generally OK (with the exception of doxepin)
• Typically not recommended with benzodiazepines

Special Treatment Considerations
• Children and Adolescents
• SSRIs recommended first-line
• Careful monitoring recommended (increased risk of suicidal ideation and behavior)
• Elderly
• SSRIs appear to be safe (start with low doses)
• TCAs and benzodiazepines are less favorable

Special Treatment Considerations
• Patients with Severe Somatic Disease
• 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!