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Clinical Pearls in Psychiatry: Disclosures Objectives Objectives 6/29/2018 #FSHP2018 Disclosures • At this time, I do not have any relevant financial/non- Clinical Pearls in Psychiatry: financial relationships with any proprietary interests Antipsychotics in Acute Care Joshua Caballero, PharmD, BCPP, FCCP Professor, Chair Clinical and Administrative Sciences Larkin University, College of Pharmacy #FSHP2018 Objectives Objectives • Discuss recent literature related to the treatment • Describe opportunities for pharmacists in the of the following: administration of long acting antipsychotic • Agitation/delirium in non-critically ill patients medications • Antipsychotics and CV adverse effects/QT changes • Apply practice strategies to monitor antipsychotic • De-prescribing strategies and algorithms for use for patients in the acute care setting antipsychotics #FSHP2018 #FSHP2018 Agitation vs. Delirium1-2 Delirium2-5 Agitation Delirium • Approximately 50% of older adults during hospital • Psychomotor disturbance • Acute decline in admission or stay may experience delirium characterized by a attention and cognition • Hospital delirium persisted at discharge in marked increase in both • Subtypes include: approximately 45% of cases motor and psychological • Hypoactive activities, often • Hyperactive* • Associated with higher morbidity and mortality accompanied by a loss of control of action and a • Mixed • Healthcare costs: over $160 billion annually disorganization of thought * Agitation is a component of hyperactive delirium #FSHP2018 #FSHP2018 1 6/29/2018 Delirium: Risk Factors3-6 Delirium: Medications that Increase Risk3,7-9 • Predisposing factors • Precipitating factors • Anticholinergics • Non-benzodiazepine • Dementia • Immobilizations • Anticonvulsants hypnotics • > 65 years of age • Medications • Antipsychotics • Opioids • Sensory/functional • Dehydration • Benzodiazepines • Sedative-hypnotics impairment • Pain • Corticosteroids • Comorbidities • Sleep deprivation • Histamine-2 (H ) blockers • Also consider alcohol • Depression • Urinary 2 and/or drug withdrawals • Renal/hepatic retention/constipation impairment • Acute illness #FSHP2018 #FSHP2018 Delirium: Anticholinergic Risk Scale10,11 Delirium: Prevention and Management Low Medium High • Rule out underlying cause(s) Carbidopa-levodopa Cetirizine Tolterodine Amitriptyline Promethazine • Medications Selegiline Cyclobenzaprine Amantadine Benztropine Oxybutynin • Infection • Electrolyte imbalance Metoclopramide Loperamide Loratadine Meclizine Imipramine Ranitidine Olanzapine Tizanidine Hydroxyzine • Manage symptoms Trazodone Desipramine Diphenhydramine • Non-pharmacologic options Quetiapine Baclofen Chlorpheniramine • Pharmacologic options #FSHP2018 #FSHP2018 Delirium: Non-Pharmacologic Options5,12 Delirium: Non-Pharmacologic Options13-17 • Multi-component protocols • Studies using non-pharmacologic/multicomponent • Goal: decrease risk factors (e.g., medication, environment) options show decreases in: • Requires interdisciplinary approach • Incidence • Targeted risk factors • Duration of delirium • Immobility • Length of hospital stay • Sensory (e.g., visual/hearing impairment) • Accidental falls • Dehydration • Mortality • Cognitive impairment Note: minimal effects on decreasing severity or recurrences • Sleep deprivation #FSHP2018 #FSHP2018 2 6/29/2018 Delirium: Pharmacologic Options Delirium: Efficacy of Antipsychotics18-20 • Currently, there are no FDA approved medications to Guidelines Examples on Treatment of Delirium treat delirium American Psychiatric Low dose haloperidol as first-line agent in symptomatic Association- APA (1999) management of delirium episodes National Institute for Consider short term haloperidol or olanzapine for Health and Clinical distressed person with delirium who is posing a risk to Excellence-NICE (2010) themselves or others May use antipsychotics at the lowest effective dose for American Geriatric Society-AGS (2015) the shortest possible duration for severely agitated patients who are threatening harm to self and/or others #FSHP2018 #FSHP2018 Delirium: Efficacy of Antipsychotics21 Delirium: Efficacy of Antipsychotics21 Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis • Conclusions (on post operative patients) Evaluate effectiveness of antipsychotics in preventing and Objective treating delirium (post-operative patients) • No improvement in incidence, severity, or duration • No improvement in length of stay Design Systematic review and meta-analysis • Hospital and intensive care unit Inclusion 19 studies (12 treatment + 7 prevention) First (haloperidol) and second generation (risperidone, Medications olanzapine, quetiapine) antipsychotics Note: Some good news with no association with mortality up to 30 days Delirium: incidence, severity, and duration Outcomes Length of stay: hospital and intensive care unit #FSHP2018 #FSHP2018 Delirium: Efficacy of Antipsychotic21-24 Delirium: Antipsychotic Adverse Effect Profile21-25 • Data on other populations with delirium • Anticholinergic: sedation, orthostasis, dizziness, falls, • Some benefits urinary incontinence • Decrease severity • Extrapyramidal symptoms • Decrease duration • Cardiovascular side effects • QTc prolongation (possible cutoff of > 450-500 msecs) • Ventricular arrythmias • Venous thromboembolism • … and increased mortality #FSHP2018 #FSHP2018 3 6/29/2018 Delirium: Antipsychotic Contraindications Delirium: Antipsychotic FDA Public Health Advisory26-28 "WARNING: Increased Mortality in Elderly Patients With Dementia-Related Psychosis” Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at • Second generation antipsychotics associated with an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration* of increased mortality (due to cardiovascular events and 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo- infections) in elderly patients with dementia (2005) treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the • First and second generation antipsychotics associated placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infections with increased mortality in elderly patients treated for (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical dementia-related psychosis (2008) antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies • Studies in elderly patients show higher rates for may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. [DRUG BRAND NAME (drug generic name)] is not approved for the cerebrovascular side effects and mortality treatment of patients with dementia-related psychosis." #FSHP2018 #FSHP2018 Delirium: Antipsychotic Final Recommendation5,6,19 Delirium: Antipsychotic Final Recommendation6,19,29,30 • Second generation antipsychotics should be reserved • Antipsychotics should be reserved as a last treatment as a last treatment option when option when • non-pharmacologic interventions have failed • non-pharmacologic interventions have failed • Symptoms cause the patient to be a threat to themselves • Symptoms cause the patient to be a threat to themselves or others or others • Accompanying severe aggressive behavior • Accompanying severe aggressive behavior • Second generation antipsychotics may be preferred • Risperidone, olanzapine, quetiapine, aripiprazole • Start low and go slow #FSHP2018 #FSHP2018 Delirium: Antipsychotic Final Recommendation 5,6,19,30 Delirium: Discontinuation of Antipsychotics31 • Discuss with family/caregivers risk vs. benefits and • A study on approximately 500 patients showed 30% of document patients were discharged on an initiated • Obtain electrocardiogram (ECG) when initiation and antipsychotic periodic ECG monitoring • Of those, fewer than 13% of discharge summaries had instructions on antipsychotic discontinuation • Aripiprazole may be preferred, if concerned • Evaluate need for continuing antipsychotic • Role for a residency project or APPE students to develop protocol? #FSHP2018 #FSHP2018 4 6/29/2018 Delirium: Discontinuation of Antipsychotics32 Long Acting Injectable Antipsychotics (Brand) Centers for Medicare and Medicaid Services (CMS) • Haloperidol decanoate (Haldol Decanoate) • PRN antipsychotics in long-term care facilities • Aripiprazole lauroxil (Aristada) • 14 day limitation and cannot be extended • Aripiprazole monohydrate (Abilify Maintena) • New order may be written if the prescriber: • Olanzapine pamoate (Zyprexa Relprevv) • DIRECTLY examines and assesses the patient and • Documents clinical rationale for the new order including: • Paliperidone palmitate-monthly (Invega Sustenna) • Benefit of the medication and • Paliperidone palmitate- 3 months (Invega Trinza) • Have symptoms improved as a result of the PRN medication? • Risperidone microsphere (Risperdal Consta) • Can be used as PRN in emergent situation #FSHP2018 #FSHP2018 Long Acting Injectable (LAI) Antipsychotics33 Long Acting Injectable (LAI) Antipsychotics33 Oral Supplement for Administration Oral Cross-titration Dose Adjustments Special considerations Missed
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