Pharmacotherapy of Anxiety Disorders
Rakesh Jain, MD, MPH Clinical Professor Department of Psychiatry Texas Tech University School of Medicine Midland, Texas
ARS Questions
Pharmacotherapy of Anxiety Disorders
Rakesh Jain, MD, MPH Clinical Professor Department of Psychiatry Texas Tech University School of Medicine Midland, Texas
Disclosure Statement
• Consultant – Addrenex, Allergan, Lilly, Lundbeck, Merck, Otsuka, Pamlab, Pfizer, Shionogi, Shire, Sunovion, Takeda (Spouse: Pamlab & Otsuka)
• Speaker's Bureau – Addrenex, Allergan, Lilly, Lundbeck, Merck, Otsuka, Pamlab, Pfizer, Shionogi, Shire, Sunovion, Takeda
• Research Support – AstraZeneca, Allergan, Lilly, Lundbeck, Otsuka, Pfizer, Shire, Takeda
Anxiety Disorders are the Most Common Cluster of Psychiatric Disorders
50%
Risk of any disorder
46.4 %
>2 disorders
27.7 %
>3 disorders
17.3 %
40% 28.8%
30% 20.8% 20%
24.8%
14.6%
10% 0%
Substance Use
Mood Disorder
Disorder
Kessler RC, et al. Arch Gen Psychiatry. 2005;62:593-602.
Impulse-Control Disorder
Anxiety Disorder
Anxiety Disorders: Not Just Prevalent in Society, but Also in Our Clinical Practices 40
N=965
30 19.5 20 8.6 10
7.6
6.8
6.2
0 PTSD
GAD
Panic Disorder
Anxiety Disorder PTSD=posttraumatic stress disorder; GAD=generalized anxiety disorder. Kroenke K, et al. Ann Intern Med. 2007;146:317-325.
Social Anxiety Disorder
Any Anxiety Disorder
Impairment from GAD Is Similar to Major Depression (Further Worsened If Both Are Co-present) 1.5
Neither
1.6
GAD only
94.7
2.1
11.3 Past month’s work impairment (days) 0 1 or 2
MDD only 10
3–5
7.9
2.6 MDD & GAD
≥6
75.3
9.4
5.3
GAD=generalized anxiety disorder; MDD=major depressive disorder. Kessler RC, et al. Am J Psychiatry. 1995;155:1092-1096.
78.2
21.9
58.2
11.8 8.1
Anxiety Disorders: The ‘Old’ DSM-IV Classification Anxiety Disorders
Panic + Agoraphobia
Panic Disorder
Agoraphobia
Social Phobia
Specific Phobia
ASD
OCD
PTSD
GAD
Generalized Type
ASD = acute stress disorder; OCD = obsessive-compulsive disorder; PTSD = posttraumatic stress disorder; GAD = generalized anxiety disorder. Task Force on DSM-IV. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Textbook Revision). Arlington, VA: American Psychiatric Association; 2000.
Anxiety Disorders: The ‘New’ DSM-5 Classification Trauma and Stressor-Related Disorders
Anxiety Disorders
OC & Related Disorders
GAD
Panic Disorder
Agoraphobia
Separation Anxiety Disorder
Social Anxiety Disorder
Selective Mutism
Public Speaking
Specific Phobia
OCD
PTSD
Dissociative
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
DSM-5 Has Significant New Changes Pertaining to Anxiety Disorders The DSM-5 groups include: 1.
Neurodevelopmental Disorders
10. Feeding and Eating Disorders
2.
Schizophrenia Spectrum and Other Psychotic Disorders
11. Elimination Disorders
3.
Bipolar and Related Disorders
4.
Depressive Disorders
5.
Anxiety Disorders
6.
Obsessive-Compulsive Spectrum
7.
Trauma- and Stressor-Related Disorders
8.
Dissociative Disorders
9.
Somatic Symptom and Related Disorders
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
12. Sleep-Wake Disorders 13. Sexual Dysfunctions 14. Gender Dysphoria 15. Substance-Related and Addictive Disorders 16. Neurocognitive Disorders 17. Personality Disorders
DSM-5 - Anxiety Disorders Changes from DSM-IV: • Agoraphobia separate disorder (previously specifier of PD) • OCD removed from this category (Obsessive-Compulsive and Related Disorders) • PTSD removed from this category (Trauma- and Stressor-Related Disorders) • Panic Attack Specifier may occur with any anxiety disorder – – – – – – –
Separation Anxiety Disorder Specific Phobia Social Anxiety Disorder (Social Phobia) Panic Disorder Generalized Anxiety Disorder Substance/Medication-Induced Anxiety Disorder Anxiety Disorder due to Another Medical Condition
PD = panic disorder; OCD = obsessive-compulsive disorder. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
Obsessive-Compulsive and Related Disorders (NEW) •
Obsessive-Compulsive Disorder
•
Body Dysmorphic Disorder
•
Hoarding Disorder (NEW): – Persistent difficulty discarding possessions regardless of value
• Trichotillomania (hair-pulling disorder): – Repetitive and compulsive picking resulting in tissue damage
•
Excoriation (skin-picking) Disorder (NEW): - Constant and recurrent picking resulting in skin lesions
•
Other Specified and Unspecified ObsessiveCompulsive Related Disorders
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
Trauma- and Stressor-Related Disorders (NEW) • • • • •
PTSD Acute Stress Disorder Reactive Attachment Disorder Disinhibited Social Engagement Disorder Adjustment Disorder
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
DSM-5 Update on Post Traumatic Stress Disorder •
•
Language describing a person’s response to an event (intense fear, helplessness or horror) has been removed – not useful in predicting the onset of PTSD Symptom clusters revised and expanded: 1. 2. 3. 4.
Intrusion symptoms Avoidance symptoms Negative alterations in cognitions and mood Marked alterations in arousal and reactivity » New Subtype: PTSD 6 years and younger » New Specifiers: With dissociative symptoms and with delayed expression » Criteria persist >1 month » Significant impairment » Not attributable to another medical condition or substance
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.
“Right Questions to Ask” Clinical Technique To Employ Start with an Exploratory set of Questions (specific Qs for each AD) Positive
Negative
Move on to confirm the diagnosis using DSM-IV-TR criteria
No need to ask any further questions
“Over the last 2 weeks, how often have you been bothered by the following problems?” 1. Feeling nervous, anxious, or on edge 2. Not being able to stop or control worrying
AD=anxiety disorder. Kroenke K, et al. Ann Intern Med. 2007;146:317-325.
Treating Anxiety 2016 • Antidepressants • Benzodiazepines - Selective serotonin reuptake • Other Agents inhibitors (SSRIs) - Buspirone - Serotonin-norepinephrine - Beta-blockers and Alphareuptake inhibitors (SNRIs) blockers - Atypical antidepressants - Anticonvulsants - Tricyclic (TCAs) and - Atypical Antipsychoticsheterocyclic antidepressants specially agents with anti- Monoamine oxidase adrenergic properties inhibitors (MAOIs) • Cognitive-Behavioral Therapy • Psycho-surgery
FDA Anxiety Indications 2002 • GAD – Paroxetine – Venlafaxine ER – Escitalopram • PD – Fluoxetine – Paroxetine – Paroxetine CR – Sertraline – Venlafaxine ER – Alprazolam – Clonazepam • Social Anxiety Disorder
– Paroxetine – Paroxetine CR – Sertraline – Venlafaxine ER • PTSD – Paroxetine – Sertraline • OCD – Sertraline – Paroxetine – Fluoxetine – Fluvoxamine – Clomipramine
FDA Anxiety Indications 2016 • GAD – Paroxetine – Venlafaxine ER – Escitalopram – Duloxetine • PD – Fluoxetine – Paroxetine – Paroxetine CR – Sertraline – Venlafaxine ER – Alprazolam – Clonazepam
• Social Anxiety Disorder - Paroxetine - Paroxetine CR - Sertraline - Venlafaxine ER • PTSD – Paroxetine – Sertraline • OCD – Sertraline – Paroxetine – Fluoxetine – Fluvoxamine – Clomipramine
Algorithm: Panic Disorder Treating Patients with Panic Disorder Patient meets DSM-IV criteria for panic disorder
Is current alcohol abuse present?
Yes
Offer alcohol detoxification and maintenance program with follow-up to reassess panic disorder
No
Is rapid action needed for the patient to function?
Yes
No
Consider short-term therapy with a benzodiazepine while long-term therapy is initiated
Offer treatment with antidepressants or CBT (4–12 sessions) Reassess at 2 and 10 weeks to discuss effectiveness and side effects Is the patient panic free or functioning well? No
Offer additional treatment with another therapy, combination therapy, increased medication dosage, or additional CBT
CBT=cognitive-behavioral therapy. Ham P et al. Am Fam Physician. 2005;15:733-739.
Yes
Antidepressants:
Continue for 6 months and consider medication withdrawal with monthly follow-up for relapse
CBT:
Follow patient monthly for relapse after sessions are discontinued
Benzodiazepines:
Taper benzodiazepine. If unsuccessful, offer CBT during tapering period
Panic Disorder: Treatment Approaches SSRIs
TCAs
Acute panic attack
Benzodiazepines Others Alprazolam Lorazepam
Acute efficacy
Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine Sertraline
Clomipramine Imipramine
Alprazolam Clonazepam Diazepam Lorazepam
CBT Phenelzine Moclobemide* Mirtazapine* Venlafaxine Reboxetine Navalproate (Brofaromine) (Nefazodone)
Long-term efficacy
Citalopram Fluoxetine Paroxetine Sertraline
Clomipramine Imipramine
Alprazolam
Moclobemide* CBT
Relapse prevention
Fluoxetine Paroxetine Sertraline
Imipramine
CBT
Antidepressants (meta-analysis)
Benzodiazepines
Enhances the efficacy of Paroxetine psychological treatment Buspirone (meta-analysis)
* Comparator-controlled study only. Empty cell indicates absence of published placebo-controlled data. SSRIs=selective serotonin reuptake inhibitors; TCAs=tricyclic antidepressants; CBT=cognitive-behavioral therapy. Baldwin DS, et al. J Psychopharmacol. 2005;19:567-596.
Posttraumatic Stress Disorder: Treatment Approaches SSRIs
TCAs
Benzodiazepines Others
Prevention of posttraumatic symptoms?
Acute efficacy
Hydrocortisone Propranolol Trauma-focused CBT Fluoxetine
Amitriptyline
Paroxetine Sertraline
Imipramine
Long-term efficacy
Sertraline
Relapse prevention
Fluoxetine Sertraline
Alprazolam
Trauma-focused CBT EMDR Brofaromine Phenelzine Lamotrigine Mirtazapine Venlafaxine CBT?
Enhances the efficacy of psychological treatment After nonresponse
Olanzapine* Risperidone*
* Comparator-controlled augmentation study. Empty cell indicates absence of published placebo-controlled data. SSRIs=selective serotonin reuptake inhibitors; TCAs=tricyclic antidepressants; CBT=cognitive-behavioral therapy; EMDR=eye-movement desensitization and reprocessing. Baldwin DS, et al. J Psychopharmacol. 2005;19:567-596.
Algorithm: Posttraumatic Stress Disorder Signs and symptoms of an anxiety disorder History of trauma? Yes
Four or more symptoms positive on screening?
No
Meets DSM-IV criteria for PTSD? No
Yes
Provide support, monitor patient, and consider treating individual symptoms
Initiate treatment with an SSRI
Comorbid psychiatric illness?
Yes Treat comorbid substance abuse, mood disorders, or other anxiety disorders; provide support and patient education; consider referral for psychotherapy
No Monitor patient receiving SSRI, provide support and patient education, and consider referral for psychotherapy
PTSD=posttraumatic stress disorder; SSRI=selective serotonin reuptake inhibitor. Grinage BD. Am Fam Physician. 2003;15:2401-2409.
Algorithm: Treatment of Obsessive-Compulsive Disorder First-line treatments
CBT (ERP)
Is the response adequate after 13–20 weekly sessions of CBT? Yes
SSRI + CBT (ERP)
SSRI No
Is the response adequate after 8–12 total weeks of SSRI (4–6 weeks at maximal tolerable dose) or 13–20 weekly sessions of CBT or weekday daily CBT for 3 weeks? Yes
For medication: continue for 1–2 years, then consider gradual taper over several months or more For CBT: provide periodic booster sessions for 3–6 months after acute treatment
Yes Adequate response? No next slide
No
Strategies for Moderate Response • Augment with a second-generation antipsychotic or with CBT (ERP) if not already provided • Add cognitive therapy to ERP* Strategies for Little or No Response • Switch to a different SSRI (may try more than one trial) • Switch to clomipramine • Augment with a second-generation antipsychotic • Switch to venlafaxine • Switch to mirtazapine
CBT=cognitive-behavioral therapy; ERP=exposure and response prevention; SSRI=selective serotonin reuptake inhibitor. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Obsessive-Compulsive Disorder. 2007.
Algorithm: Treatment of Obsessive-Compulsive Disorder (Cont’d.) previous slide Adequate response? No
Strategies for Moderate and for Little or No Response • • • •
Switch to a different augmenting second-generation antipsychotic Switch to a different SSRI Augment with clomipramine* Augment with buspirone,* pindolol,* morphine sulfate,* inositol,* or a glutamate antagonist (e.g., riluzole, topiramate)*
Strategies Only for Little or No Response • • • •
Switch to D-amphetamine monotherapy* Switch to tramadol monotherapy* Switch to ondansetron monotherapy* Switch to an MAOI*
After first- and second-line strategies have been exhausted, other options that may be considered include transcranial magnetic stimulation,* deep-brain stimulation,* and ablative neurosurgery. Note: “moderate response” means clinically significant but inadequate response. * Treatment with little supporting evidence (eg, one or few small trials, case reports, or uncontrolled case series. SSRI=selective serotonin reuptake inhibitor; MAOI=monoamine oxidase inhibitor. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Obsessive-Compulsive Disorder. 2007.
Algorithm: Social Anxiety Disorder Diagnosis of social anxiety disorder Yes Initiate SSRI Yes
No Switch medication
Response
next slide
SSRI=selective serotonin reuptake inhibitor. Stein DJ, et al. Curr Psychiatry Rep. 2010;12:471-477.
Maintenance treatment
Algorithm: Social Anxiety Disorder
(Cont’d.)
previous slide
Optimize dose and duration Yes Response No Reassessment Yes Switch medications/ refer SSRI=selective serotonin reuptake inhibitor. Stein DJ, et al. Curr Psychiatry Rep. 2010;12:471-477.
Maintenance treatment
Treatment Choices for Generalized Anxiety Disorder Treatment for Acute Transient Anxiety BZDs Short-term, intermittent course of anxiolytic therapy, particularly for patients with episodic anxiety
SSRIs
Prolonged Treatment Indicated SSR! + 5HT1A
SNRI
CBT
Evaluate after 8 weeks of treatment Responsive 6 months to 1 year of treatment for medication and booster sessions for CBT
Nonresponsive • Reassess diagnosis • Examine for comorbidity • Assess for treatment compliance • Assess for adequate dose • Side effects intolerable
Treatment Options • Switch to another first-line treatment • Augmentation with CBT if on medication only or the reverse if started with CBT • Augmentation with a BZD • Augmentation with a second antidepressant • Low-dose augmentation with an antipsychotic
BZDs=benzodiazepines; SSRIs=selective serotonin reuptake inhibitors; SNRIs=serotonin norepinephrine reuptake inhibitors; CBT=cognitive-behavioral therapy. Rynn MA, Brawman-Mintzer O. CNS Spectr. 2004;9:716-723.
Generalized Anxiety Disorder: Treatment Approaches SSRIs
TCAs
Benzodiazepines Others
Acute efficacy
Vilazodone Imipramine Escitalopram Paroxetine Sertraline
Long-term efficacy
Escitalopram Paroxetine
CBT Venlafaxine
Relapse prevention
Paroxetine Escitalopram
CBT
Enhances the efficacy of psychological treatment
Alprazolam Diazepam
Venlafaxine CBT Buspirone Hydroxyzine Pregabalin Trifluoperazine (Abercarnil) (Opipramol)
Diazepam
After nonresponse
Empty cell indicates absence of published placebo-controlled data. Brackets indicate drug is not available for Clinical use. SSRIs=selective serotonin reuptake inhibitors; TCAs=tricyclic antidepressants; CBT=cognitive-behavioral therapy. Baldwin DS, et al. J Psychopharmacol. 2005;19:567-596.
Recommended Steps to Take with Treatment-Resistant GAD For Those with Partial Response to Standard Pharmacotherapy • Increasing the dose. Switch between classes of medications • Continuing treatment for 2–3 months • Pharmacologic augmentation o Benzodiazepines o Hypnotic medications: eszopiclone, zolpidem o Pregabalin o Antipsychotic medications – Aripiprazole – Quetiapine – Risperidone – Olanzapine – Ziprasidone • Augmentation with psychological treatment (e.g., cognitivebehavioral therapy) GAD=generalized anxiety disorder. Starcevic V, Hood S. Psychiatr Ann. 2001;13(2):78-88.
Side Effects: Short and Long Term Side effects with medications for the treatment of anxiety disorders are not uncommon; they are, if not managed well, a common reason for medication noncompliance Common Short-Term Side Effects • Nausea • Sedation • Insomnia • Agitation • Diarrhea
Common Long-Term Side Effects • Sexual dysfunction • Weight gain • Memory difficulties • Apathy • Addiction (with some anxiety medications) • Withdrawal symptoms (when stopped abruptly)
Example of SSRI Rx – Sertraline in PTSD
60
53
45 32 30
Placebo Sertraline
15
0 Week 12 Response Rate (%)
Brady K, et al. JAMA. 2000;283(14):1837-1844.
Off Label Rx Options in Refractory Patients: Olanzapine Augmentation of SSRI-Resistance: GAD RCT 75 65
Percent
55
Placebo, LVCF (n = 12) Olanzapine, LVCF (n = 9)
*
*
45 35 25 15 5
50% Reduction in HAM-A
CGI-Severity Score <3
OFF-LABEL- Olanzapine is not approved by FDA for the treatment of anxiety disorders *P < .05. Total N = 45. Patients with 1 postrandomization visit (N = 21). LVCF = last visit carried forward; HAM-A = Hamilton Rating Scale for Anxiety; CGI = Clinical Global Impressions Scale. Pollack MH, et al. Biol Psychiatry. 2006;59(3):211-215.
Efficacy of 3 Doses of Pregabalin vs Alprazolam in Reducing the HAM-A Total Score
Mean HAM-A Score
25
Placebo (n = 85) ALP 1.5 mg/day (n = 88) PGB 600 mg/day (n = 85) PGB 450 mg/day (n = 87) PGB 300 mg/day (n = 89)
20
*
15
* * 10
Base
Wk 1
Wk 2
Wk 3
OFF-LABEL – Pregabalin is not indiacated for Anxiety Disorder Rx in USA All medications dosed TID. *P ≤ .05 vs placebo (ANCOVA) for all medications. **P ≤ .05 vs placebo (ANCOVA) for PGB 300 mg/day and PGB 600 mg/day only. ALP = alprazolam; PGB = pregabalin; LOCF = last observation carried forward; ANCOVA = analysis of covariance. Rickels K, et al. Arch Gen Psychiatry. 2005;62(9):1022-1030.
** Wk 4
* LOCF-End
Pregabalin Augmentation for Partial SRI Response in GAD • Patients with GAD not responding to SRI Rx • Double-blind randomized addition of – Pregabalin (N = 180) [150-600 mg/day] – Placebo (N = 176) § 8 weeks of augmentation
• Well tolerated – Adverse effect-related discontinuations infrequent § Pregabalin (4%) vs. placebo (2%)
• HAM-A responder rates (<50% reduction) – Pregabalin (47.5%) vs. placebo (35.2%) § P = .0145
OFF-LABEL – Pregabalin is not indiacated for Anxiety Disorder Rx in USA Rickels K, et al. Int Clin Psychopharmacol. 2012;27(3):142-150.
Response and Remission in Patients with Insomnia and Comorbid GAD Treated with Placebo and Escitalopram or Eszopiclone and Escitalopram
Eszoplicone is not indicated for the treatment of anxiety disorders Pollack M, et al. Arch Gen Psychiatry. 2008;65(5):551-562.
For Refractory Patients – Consider MAOIs • Phenelzine 45-90 mg/day • Tranylcypromine 30-60 mg/day – Adverse effects: light-headedness, neurological symptoms, weight gain, sexual dysfunction, – Need for dietary and medication restrictions because of concerns RE: hypertensive crisis and serotonin syndrome – Risk of lethal overdose and toxicity
• Generally reserved for refractory cases • Efficacy: panic disorder, social phobia, PTSD, GAD
Vilazodone a SSRI + 5HT1A Antidepressant Is Showing Promise in GAD Trails • Three separate trials with Vilazodone were conducted in GAD patients – all are positive studies of Vilazodone in GAD • Two are flexible dose studies (20-40 mg /day) and one was fixed dose study with 20 and 40 mg arms with placebo arm present in three studies • Both flexible dose studies were statistically significant (p<.05), and the 40 mg arm in the fixed dose study separated from placebo (p<.05)
Gommoll C, et al. Int Clin Psychopharmacol. 2015;30(6):297-306. doi: 10.1097/YIC.0000000000000096. Gommoll C, et al. Depress Anxiety. 2015;32(6):451-9. doi: 10.1002/da.22365. Epub 2015 Apr 17. Durgam S, et al. J Clin. Psych (In press).
Vilazodone Has Demonstrated Positive Studies in GAD
A multicenter, double-blind, parallel-group, placebo-controlled, fixed-dose study in patients with GAD randomized (1:1:1) to placebo (n = 223), or vilazodone 20 mg/day (n = 230) or 40 mg/day (n = 227)
Gommel C, et al. Depression and Anxiety.2015; 32:451–459.
Prazosin – Emerging Role in PTSD Sixty-seven soldiers were randomly assigned to treatment with prazosin or placebo for 15 weeks. Drug was titrated based on nightmare response over 6 weeks to a possible maximum dose of 5 mg midmorning and 20 mg at bedtime for men and 2 mg midmorning and 10 mg at bedtime for women (CAPS - Clinician Administered PTSD Scale)
Medication was initiated at 1 mg at bedtime for 2 days and increased to 2 mg at bedtime for the next 5 days. The dosage was further increased at weekly intervals
Raskind MA, et al. Am J Psychiatry. 2013; 170:1003–1010.
For Refractory OCD – We Psychopharmacologists Need to Know of Neurosurgical Options ReclaimTm DBS Therapy for Obsessive Compulsive Disorder (OCD)
This device is indicated for bilateral stimulation of the anterior limb of the internal capsule, AIC, as an adjunct to medications and as an alternative to anterior capsulotomy for treatment of chronic, severe, treatment-resistant obsessive compulsive disorder (OCD) in adult patients who have failed at least three selective serotonin reuptake inhibitors (SSRIs)
http://www.accessdata.fda.gov/cdrh_docs/pdf5/H050003a.pdf Lapidus K. et.a la World Neurosurg. 2013. http://dx.doi.org/10.1016/j.wneu.2013.02.053
Cognitive-Behavioral Therapy in Anxiety Disorders
Key Elements of Cognitive-Behavioral Therapy Identifying dysfunctional thought patterns
Psychoeducation
Realistic goal setting
Communication skills training
Relaxation training
Relapse prevention Behavioral pacing
Bennett R, Nelson D. Nat Clin Pract Rheumatol. 2006;2:416-424.
CBT: Pros and Cons
• •
• • • •
Advantages It works (70% to 85% efficacy) It may have lower relapse rate than medication when discontinued Most people like it Time-limited Overall low price Few adverse effects
• • • • •
Disadvantages Harder to administer than medication Limited availability More effort than taking medication Lack of third-party coverage Not all patients willing/able – Initially “too anxious” – Severe or comorbid disorders – Cognitively impaired
American Psychiatric Association. Practice Guideline for the Treatment of Patients with Panic Disorder. January 2009. http://psychiatryonline.org/pdfaccess.ashx?ResourceID=243182&PDFSource=6. Accessed June 25, 2014. Ballenger JC. Biol Psychiatry. 1999;46(11):1579-1594. Fava GA, et al. Br J Psychiatry. 1995;166(1):87-92.
Advantages of Using Scales and Screeners
Improve patient outcomes
Avoid missing important pieces of information
Time efficient
Advantages of Using Scales & Screeners
Good sensitivity and specificity
Avoid making an incorrect diagnosis & missing comorbidities
Avoid potential catastrophic results (eg, hospitalization, suicide)
Generalized Anxiety Disorder 7-Item Scale
How to Use Patients circle one of the 4 numbers (representing severity) associated with 7 problems. If patients identify any problems, they indicate (by checking the appropriate box) the degree to which these problems made it difficult for them to work, take care of home responsibilities, or get along with people.
GAD-7
How to Score Add the values for each column, and then add the total for each column to get the total score. Total Score Interpretation >10
Probable diagnosis of GAD; confirm by further evaluation
5
Mild anxiety
10
Moderate anxiety
15
Severe anxiety
Spitzer RL, et al. Arch Intern Med. 2006;166:1092-1097.
Summary • Anxiety disorders are highly prevalent • Frequently comorbid – e.g., with MDD
• Multiple pharmacotherapeutic options available – Antidepressants remain a mainstay of treatment
• Adding cognitive-behavioral management to pharmacotherapy adds value – Improved acceptability and better outcomes
• Measurement-based care – Here to stay… lets all get with the plan!
Appendix Additional Resources
Obsessive-Compulsive Disorder: Treatment Approaches SSRIs
TCAs
Benzodiazepines Others
Acute efficacy
Citalopram Fluoxetine Fluvoxamine Paroxetine Sertraline
Clomipramine Imipramine
Clonazepam?
Long-term efficacy
Fluoxetine Sertraline
Clomipramine
Relapse prevention
Fluoxetine Paroxetine Sertraline
Enhances the efficacy of Fluvoxamine psychological treatment After nonresponse
CBT
CBT
Clomipramine Clonazepam
Another SSRI Haloperidol* Risperidone* Quetiapine* Pindolol*
* Placebo-controlled augmentation study. Empty cell indicates absence of published placebo-controlled data. SSRIs=selective serotonin reuptake inhibitors; TCAs=tricyclic antidepressants; CBT=cognitive-behavioral therapy. Baldwin DS, et al. J Psychopharmacol. 2005;19:567-596.
Obsessive-Compulsive Disorder: Dosing SSRIs
Starting Dose and Incremental Dose (mg/day)a
Usual Target Dose(mg/day)
Usual Maximum Dose (mg/day)
Occasionally Prescribed Maximum Dose (mg/day)b
Citalopram
20
4–60
80
120
Clomipramine
25
100–250
250
___c
Escitalopram
10
20
40
60
Fluoxetine
20
40–60
80
120
Fluvoxamine
50
200
300
450
Paroxetine
20
40–60
60
100
Sertralined
50
200
200
400
SSRI
a Some patients may need to start at half this dose or less to minimize undesired side effects, such as nausea, or to accommodate anxiety about taking medications. b These doses are sometimes used for rapid metabolizers or for patients with no or mild side effects and inadequate therapeutic response after >8 weeks at the usual maximum dose. c Combined plasma levels of clomipramine plus desmethylclomipramine 12 hours after the dose should be kept below 500 ng/ml to minimize risk of seizures and cardiac conduction delay. d Sertraline, alone among the SSRIs, is better absorbed with food. SSRIs=selective serotonin reuptake inhibitors. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Obsessive-Compulsive Disorder. 2007.
Social Anxiety: Treatment Approaches SSRIs
Acute efficacy
Escitalopram Fluoxetine Fluvoxamine Paroxetine Sertraline
Long-term efficacy
Escitalopram Fluvoxamine Paroxetine Sertraline
Relapse prevention
Escitalopram Paroxetine Sertraline
Enhances the efficacy of psychological treatment
TCAs
Benzodiazepin es Bromazepam Clonazepam Moclobemide Venlafaxine Gabapentin
Others CBT Phenelzine Pregabalin Olanzapine (Brofaromine) CBT Phenelzine Moclobemide Venlafaxine
Clonazepam
CBT
Sertraline
After nonresponse Empty cell indicates absence of published placebo-controlled data. SSRIs=selective serotonin reuptake inhibitor; TCAs=tricyclic antidepressants; CBT=cognitive-behavioral therapy. Baldwin DS, et al. J Psychopharmacol. 2005;19:567-596.
Panic Disorder: Dosing Antidepressants and Benzodiazepines
SSRIs
Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine Paroxetine CR Sertraline
Starting Dose and Incremental Dose (mg/day) 10 5–10 5–10 25–50 10 12.5 25
SNRIs
Duloxetine Venlafaxine ER Imipramine Clomipramine Desipramine Nortriptyline
20–30 37.5 10 10–25 25–50 25
60–120 150–225 100–300 50–150 100–200 50–150
0.75–1.0b 0.5–1.0c 1.5–2.0b
2–4b 1–2c 4–8b
TCAs
Benzodiazepines
Alprazolam Clonazepam Lorazepam
Usual Therapeutic Dose (mg/day)a 20–40 10–20 20–40 100–200 20–40 25–50 100–200
a Higher doses are sometimes used for patients who do not respond to the usual therapeutic dose. b Usually split into 3 or 4 doses given throughout the day. c Often split into 2 doses, given morning and evening. SSRIs=selective serotonin reuptake inhibitors; CR=controlled release; ER=extended release; SNRIs=serotonin norepinephrine reuptake inhibitors; TCAs=tricyclic antidepressants. APA Practice Guidelines: Practice Guidelines for the Treatment of Patients with Panic Disorder. 2nd ed. 2009.
ARS Questions
