Depression, Anxiety, PTSD: A Focus on Pharmacotherapy Robert L Page II, Pharm.D., MSPH, FHFSA, FCCP, FAHA Professor of Clinical Pharmacy Clinical Specialist, Division of Cardiology University of Colorado Schools of Pharmacy and Medicine Presenter Disclosure Financial Disclosure: There are no financial or other relationships to disclose related to this presentation Unlabeled/Unapproved Uses Disclosure: None Objectives Describe the types of psychologic disorders that heart failure patients may experience, including depression, anxiety, and PTSD. Discuss the various treatment options for psychologic disorders in the heart failure patient. 1
Depression Depression Across the Spectrum Trends in Cardiovascular Medicine 2015; 25(7): 614 622. Hypotheses of Depression in HF J Physiol Pharmacol 2006 ;57 Suppl 11:5-29. 2
Hypotheses of Depression in HF J Physiol Pharmacol 2006 ;57 Suppl 11:5-29. Prevalence of Depression in HF J Am Coll Cardiol 2006;48:1527 37. Prevalence of Depression in HF J Am Coll Cardiol 2006;48:1527 37. 3
Depression/HF/Mortality Effect sizes and 95% confidence intervals among studies reporting associations between depression and mortality and secondary events (8 studies) J Am Coll Cardiol 2006;48:1527 37. Depression/HF/Mortality Circ Heart Fail 2013; 6:387-94. Depression/HF/Mortality Circ Heart Fail 2015; 8: 464-472. 4
Depression/HF/Adherence Clin Nurs Res. 2014; 23(3): 231 244. Depression/HF/Adherence Medication adherent without depressive symptoms Medication adherent with depressive symptoms Medication nonadherent without depressive symptoms Medication nonadherent with depressive symptoms J Card Fail. 2013; 19(15): 317-324. J Am Coll Cardiol 2010; 56(9): 692 699. 5
SADHART-HF Change in HDRS from Baseline to Week 12 J Am Coll Cardiol 2010; 56(9): 692 699. SADHART-HF Fatal and Nonfatal Events Through Week 12 J Am Coll Cardiol 2010; 56(9): 692 699. SADHART-HF Fatal and Nonfatal Events Long Term J Am Coll Cardiol 2010; 56(9): 692 699. 6
MOOD-HF MOOD-HF 7
MOOD-HF MOOD-HF MOOD-HF 8
MOOD-HF MOOD-HF MOOD-HF 9
MOOD-HF Screening Tools Rated on a 4 point Likert Scale from 0 (not at all) to 3 (nearly every day): range 0-6 A cut off > 3 optimal balance between sensitivity and specificity for major depression disorder In cardiac patients, a cut-off >2 exhibits an optimal balance between sensitivity and specificity Treatment Phases http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf 10
Treatment Phases http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf Symptoms to Pharmacology Mechanism of Action 11
Receptor Serotonin Receptors Function 1A, 1B, 1D, 1E, 1F Anxiety, aggression, sexual behavior, appetite, vasoconstriction 2A, 2B, 2C 2A: inhibits dopamine release; mediates anxiety, agitation, hallucinations, sexual behavior, weight gain/loss 2B: Smooth muscle (GI tract), cardiovascular function 2C: inhibits dopamine and norepinephrine release; mediates appetite, anxiety, mood, GI motility, sexual behavior, thermoregulation, weight gain/loss 3 Chemoreceptor trigger zone, emesis, GI/bowel motility, nausea, memory 4 Cardiac repolarization (seizure susceptibility), respiration, gastric emptying, oesophageal peristalsis, appetite, anxiety 5A, 5B Locomotion, anxiety, sleep, cognition, thermoregulation, respiration, mood, memory 6 7 http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf Pharmacology 101 http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf Pharmacology 101 http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf 12
Cardiac Side Effects Progess Cardiovasc Dis 2016; 58 (5): 514-28. Cardiac Side Effects Inter J Cardiol. 2010; 140(1): 12-18. Drug-Drug Interactions Inhibition of Cytochrome P450 Progess Cardiovasc Dis 2016; 58 (5): 514-28. 13
Drug-Drug Interactions Progess Cardiovasc Dis 2016; 58 (5): 514-28. Drug-Disease Interactions Avoid with Congenital Long QTc Progess Cardiovasc Dis 2016; 58 (5): 514-28. Anxiety 14
Symptoms to Pharmacology Contribution to CVD Am J Cardiol 2016; 118 (4): 511-519. Guideline Recommendations Treatment Options First Line Medications SSRI and SNRI FDA approved Venlafaxine XR 75-225 daily Duloxetine 30-60 mg daily, max 120 mg/day Paroxetine 20 mg QHS, max 50 mg/day, max elderly 40mg/day, Escitalopram 10 mg daily, max 20 mg/day, max elderly 10 mg/day Not FDA approved Sertraline 50-200 daily Fluoxetine 20-80 daily Second Line Benzodiazepines Diazepam 2-10 mg BID-TID Alprazolam 0.25-0.5 mg TID, max 4 mg/day; elderly start 0.25 mg BID-TID Lorazepam 2-6 mg divided BID-TID, max 10 mg/day; elderly start 1-2 mg BID-TID Clonazepam 0.25-0.5 mg BID-TID, max 4 mg/day Non-Benzodiazepines Buspirone 20-30 mg divided BID-TID, max 60 mg/day https://www.adaa.org/resources-professionals/practice-guidelines-gad 15
Guideline Recommendations Treatment Options FDA approved Hydroxyzine Medications 50-100 q6h, max 600 mg Other Medications Augmentation Not FDA approved Imipramine 150-300 mg daily, elderly max 100 mg/day Trazodone 50-100 mg BID-TID, max 400/day Mirtazapine 15-40 mg daily Bupropion XL 150-300 mg daily Pregabalin 150-600 mg divided BID-TID Quetiapine 50-300 mg daily Vortioxetine 5 mg daily ot FDA approved) Olanzapine 5-10 mg daily Risperidone 0.5-1.5 mg daily Quetiapine see above Pregabalin see above https://www.adaa.org/resources-professionals/practice-guidelines-gad PTSD Symptoms to Pharmacology 16
DSM IV vs DSM V PTSD and Incident HF HR = 1.47; 95% CI:1.13-1.92 Am J Public Health. 2015;105:757 763 PTSD/HF/Risk Factors Age Diabetes Risk Factors Hypertension Overweight Obesity Combat Service 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 10 Odds Ratio Am J Public Health. 2015;105:757 763 17
Hypotheses of PTSD in HF Am J Physiol Regul Integr Comp Physiol 2015;309:R315-R321 Guideline Recommendations Pharmacotherapy For adult patients with PTSD, the panel suggests that clinicians offer one of the following (listed alphabetically): fluoxetine paroxetine sertraline venlafaxine There is insufficient evidence to recommend for or against clinicians offering the following medications (listed alphabetically) for treatment of adults with PTSD. risperidone topiramate For adult patients with PTSD, the panel recommends clinicians offering either venlafaxine ER or sertraline when both are being considered Strength of Recommendation Conditional Insufficient Strong For https://www.apa.org/about/offices/directorates/guidelines/ptsd.pdf 18
Conclusions and Questions 19