Psychiatry in Medical Settings Pharmacology Challenges in ... Challenge… · Antipsychotics that...
Transcript of Psychiatry in Medical Settings Pharmacology Challenges in ... Challenge… · Antipsychotics that...
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Psychiatry in Medical Settings Pharmacology Challenges in Consultation Psychiatry
Robert P. Bright, M.D.
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Disclosure
Relevant Financial Relationships
None
Off-Label/Investigational Uses
The off-label use of antipsychotic medications in the treatment of agitated delirium will be discussed
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Learning Objectives
• Increased understanding of factors influencing the choice of psychotropic medications in a patient with complex medical co-morbidities
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Altered Mental Status in a Young Patient with Cancer
• 34 year old SWF diagnosed 6 months ago with aplastic anemia, admitted after BIB EMS to ED for after “found down” outside her apartment by a neighbor. AMS upon arrival to ED.
• Consultation Question: Management of Agitated Delirium
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History
• Psych Hx: Depression and inpatient treatment for an eating disorder
• Medical Hx:
• Multiple childhood admissions for recurrent pneumonias
• Seen in ED 6 months ago for fatigue – viral syndrome? Pancytopenic. Bone marrow bx: hypocellularity (5%)
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Exam
• T 38.5. P 112 RR 12 BP 98/62
• Yelling and pulling at restraints, attempting to strike staff, demanding to leave
• Waxing and waning LOC, attention and concentration
• AVH, PI
• Oriented only to self
• Labs: WBC 1.7, Hgb 8.2, Plts 3,000
• ECG: QTc 515 msec
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Antipsychotics with Higher Risk for Causing QTc Prolongation
• IV Haloperidol > PO or IM
• Ziprasidone
• Chlorpromazine
• Thioridazine
• Droperidol
• Pimozide
• Iloperidone
Resource for Medications to Avoid with Prolonged QTc:
Crediblemeds.org
Credible Meds. Drugs to be avoided by congenital long QT patients. Available at: http://crediblemeds.org; Dietle A, QTC Prolongation With Antidepressants and
Antipsychotics. US Pharm. 2015; 40(11): HS34-HS40
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Antipsychotics that do not cause QTc Prolongation
• Aripiprazole
• Lurasidone
• Clozapine
• Loxapine
• Brexiprazole
Dietle A, QTC Prolongation With Antidepressants and Antipsychotics. US Pharm. 2015; 40(11): HS34-HS40
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Management of Psychosis and Agitation in Medically Ill Patients with (or at Risk for) Prolonged QTc
• For patients with risk factors, but no prolonged QT:
• First Tier Choice: Olanzapine po or IM, Aripiprazole po
• Second Tier Choice: Risperidone, Quetiapine, po or IM Haloperidol
• If the QTc is 450 – 499 msec
• Aripiprazole, Olanzapine, Risperidone, Quetiapine
• If the QTc is 500 msec +
• Aripiprazole, Valproate, Trazodone*, Benzodiazepines
Ries, R., & Sayadipour, A. (2014). Management of psychosis and agitation in medical-surgical
patients who have or are at risk for prolonged QT interval. J Psychiatr Pract, 20(5), 338-344. *Teply, R. M., Packard, K. A., White, N. D., Hilleman, D. E., & DiNicolantonio, J. J. (2016).
Treatment of Depression in Patients with Concomitant Cardiac Disease. Prog Cardiovasc Dis, 58(5), 514-528.
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General Considerations
• If risk factors, baseline and intermittent ECG, Quetiapine and olanzapine – sedating meds may make lower doses possible 1
• Avoid polypharmacy, combination with others that prolong QTc, monitor electrolytes 2
• FDA recommends cardiac monitoring for all patients receiving IV haloperidol 3
1 Beach, S. R., Celano, C. M., Noseworthy, P. A., Januzzi, J. L., & Huffman, J. C. (2013). QTc prolongation, torsades de pointes, and psychotropic medications.
Psychosomatics, 54(1), 1-13. 2 Nielsen, J., Graff, C., Kanters, J. K., Toft, E., Taylor, D., & Meyer, J. M. (2011). Assessing QT interval prolongation and its associated
risks with antipsychotics. CNS Drugs, 25(6), 473-490. 3 US Food and Drug Administration. Information for healthcare professionals: Haloperidol. FDA Alert
2007-9, September 2007 (available at http://www.fda.gov/Drugs/DrugSafety/ucm085203.htm)
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Antipsychotics that do not cause QTc Prolongation
• Aripiprazole
• Lurasidone
• Clozapine
• Loxapine
• Brexiprazole
Dietle A, QTC Prolongation With Antidepressants and Antipsychotics. US Pharm. 2015; 40(11): HS34-HS40
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Consult # 2
• Four days later, she has been treated for bacteremia/ sepsis and her mental status has cleared. She is A&O X 4, cooperative and has insight that she was confused. She has reported SI to the staff.
• Consultation Question: Evaluate for depression
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History and ROS
• FHx: Depression in 3 maternal relatives. No bipolar illness or psychosis
• Psych Hx: No suicide attempts, mania, psychosis, SIB. Inpatient X 2 for depression and anorexia nervosa, binge-eating/ purging type. No h/o mania/ hypomania
• Social History:
• No EtOH, rx or illicit substance abuse hx.
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Exam
• PHQ -9 = 27
• Depressed mood, hopeless re her prognosis and future, feels helpless and unworthy of treatment, no appetite, anergic, no motivation, hypersomnia, no libido, can’t concentrate. No psychosis.
• + SI with plan to ingest “poison”
• Affect: tearful, distraught, depressed
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What’s All the Fuss?
• SSRI’s are associated with a dose-dependent MODEST (+6.10 msec), but statistically significant, increase in QTc interval compared with placebo
Beach, S. R., Kostis, W. J., Celano, C. M., Januzzi, J. L., Ruskin, J. N., Noseworthy, P. A., & Huffman, J. C. (2014). Meta-analysis of selective serotonin
reuptake inhibitor-associated QTc prolongation. J Clin Psychiatry, 75(5), e441-449.
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What’s All the Fuss?
• “A comprehensive review of the published literature has concluded that there is little evidence that psychotropic drug – associated QTc interval prolongation by itself is sufficient to predict TdP.”
• At least one additional risk factor in 92% of cases
• In TdP cases
• 20% had QTc < 500 msec
• 75% at therapeutic drug doses Hasnain, M., & Vieweg, W. V. (2014). QTc interval prolongation and torsade de
pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review. CNS Drugs, 28(10), 887-920.
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Other Risk Factors
• Congenital Prolonged QTc
• Female
• Hypomagnesemia
• Hypokalemia
• Bradycardia
• Recent MI
• Co-administered QTc-prolonging meds
Beach, S. R., Celano, C. M., Noseworthy, P. A., Januzzi, J. L., & Huffman, J. C. (2013). QTc prolongation, torsades de pointes, and psychotropic medications.
Psychosomatics, 54(1), 1-13.
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Antidepressants with Higher Risk for Causing QTc Prolongation
• Amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline
• Citalopram, escitalopram, fluoxetine, paroxetine, sertraline
• Mirtazapine, trazodone, venlafaxine
Credible Meds. Drugs to be avoided by congenital long QT patients. Available at: http://crediblemeds.org; Dietle A, QTC Prolongation With Antidepressants and Antipsychotics. US Pharm. 2015; 40(11): HS34-HS40
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Antidepressants and QTc
• No QTc Prolongation:
• Cymbalta (duloxetine)
• Pristiq (desvenlafaxine)
• Fetzima (levomilnacipran)
• No clinically significant QTc Prolongation at Therapeutic Doses:
• Viibryd (vilazodone)
• Desyrel (trazodone)
• Wellbutrin (bupropion)
• Trintellix (vortioxetine)
Dietle A, QTC Prolongation With Antidepressants and Antipsychotics. US Pharm. 2015; 40(11): HS34-HS40
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Which would be the SAFEST antipsychotic medication for the management of her agitation?
1. Intravenous haloperidol
2. Oral quetiapine
3. Intramuscular olanzapine
4. Oral aripiprazole
5. Oral risperidone
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What would be the SAFEST antidepressant choice?
1. Sertraline
2. Nortriptyline
3. Desvenlafaxine
4. Mirtazapine
5. Bupropion
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Low-dose IV Haloperidol in the ICU
• 34 patients. Baseline QTc < 500 msec. Delirium, in ICU. Other risk factors not excluded.
• 1 mg IV q6h vs placebo, double blind. Telemetry + q 12h ECG.
• No significant difference in average rate of change of QTc over time, proportion of patients who developed QTc prolongation (8/34 H vs 14/34 P), a QTc > 500 msec (4/34 H vs 3/34 P) or increase QTc by > 60 msec 6/34 H vs 14/34 P)
• Need to study larger numbers and higher doses Duprey, M. S., Al-Qadheeb, N., Roberts, R., Skrobik, Y., Schumaker, G., & Devlin, J. W. (2016). The use of low-dose IV haloperidol is not associated with QTc prolongation: post hoc analysis of
a randomized, placebo-controlled trial. Intensive Care Med.
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Saphris (asenapine): Sublingual
• Mild effect on QTc, comparable to quetiapine
• 2 to 5 msec compared to placebo. No QTc increases ≥60 msec , no prolongation to QTc to ≥500 msec.
• 10 mg SL acute agitation in ER. Well tolerated. NNT comparable to IM ziprasidone 10-20 mg, IM olanzapine 10 mg, IM aripiprazole 9.75 mg, haloperidol 6.5 – 7.5 mg, IM lorazepam 2 mg
Citrome, L. (2014). Asenapine review, part II: clinical efficacy, safety and tolerability. Expert Opin Drug Saf, 13(6), 803-830.