Dr. Cynthia Hadfield, Pharm.D. Director of Pharmacy for Employee, LTC & Retail Pharmacies Lead Clinical Pharmacist, Geriatric Specialist Citizens Memorial Healthcare Dr. Hadfield has no financial, other relationship or other support from the pharmaceutical industry Dr. Hadfield will be discussing off-label use of Psychoactive medications and other medications Prescribing of a medication for a condition other than its FDA approved indication Common practice allowed by FDA and Medical boards and often appropriate and beneficial FDA approval expensive >50% Cancer Drugs used off label All Anti-psychotic use for Behavioral and psychological Symptoms of Dementia (BPSD) in USA is off-label ◦ Risperdal is approved in Canada ◦ OIG report 2011—83% Antipsychotic use off label Outline CMS Regulations and initiatives related to use of Antipsychotics Understand how Antipsychotics work and why they can cause serious side effects Understand how Anti-anxiety and Hypnotic medications work and related side effects Understand effects and side effects of Antidepressants and Anticonvulsants Understand how analgesics and other main classes of medications affect cognition and behaviors Strategies to ensure safe and effective use of Psychoactive medications in Long Term Care and how to reduce Psychoactive medication use rates CMS reports by late 2014 nursing homes in the US had achieved a 19.4% reduction in Antipsychotic use >30,000 fewer residents on Antipsychotics All but 8 states have met or exceeded 15% reduction target Missouri Antipsychotic rate was25.5% in 2nd quarter of 2011 but rose to 26.1% in 4th Quarter of 2011, then dropped to to 20.7% in the 4th Quarter of 2014 ◦ 5.43% percentage point decrease, which translates to a 20.8 “% change” ◦ Excludes individuals with Schizophrenia, Tourette’s and Huntington’s disease CMH LTC overall rate is13% (11% if Schizophrenia, Tourette’s and Huntington’s Excluded) CMS and national organizations that are actively participating in the Partnership, recently announced an updated goal to achieve 30% reduction in the use of Antipsychotic medications nationally, no later than the end of CY2016 Feb 2015 CMS added two measures of Antipsychotic use (one for long stay residents and one for short stay) to the algorithm that is used to calculate each nursing home’s Five Star Rating System on CMS Nursing Home Compare website Chlorpromazine (Thorazine) Fluphenazine Haloperidol (Haldol) Loxapine Mesoridazine Molindone Perphenazine Promazine Thioridazine (Mellaril) Thiothixine Trifluperazine Triflupromazine Typical (first generation / conventional) Asenapine (Saphris) Aripiprazole (Abilify) Clozapine (Clozaril) Iloperidone (Fanapt) Lurasidone (Latuda) Olanzepine (Zyprexa) Paliperidone(Invega) Quetiapine (Seroquel) Riperidone(Risperdal) Ziprasidone(Geodon) Atypical (second generation) Psychotic symptoms (hallucinations, delusions) linked to abnormal dopamine release and function in the brain Antipsychotic Medications block Dopamine receptors in the brain causing dopamine to have less effect Older Antipsychotics (Typical) not particularly selective and also block dopamine receptors in other areas of the brain including the nigrostriatal pathway responsible for movement Newer Antipsychotics (Atypical) developed to be more selective but still have the same side effects • also affect serotonin receptors The “why” behind all of the regulations! General: anticholinergic effects , falls, sedation Cardiovascular: arrhythmias, orthostatic hypotension ◦ Perform orthostatic blood pressures every shift for the first week and again with dose increases ◦ ECG recommended with older agents Metabolic: Increase in total cholesterol and triglycerides, unstable or poorly controlled blood sugar, weight gain ◦ Fasting lipid profile and fasting blood glucose / A1c (prior to treatment, at 3 months, then annually) ◦ Weight, BMI waist circumference Esophageal dysmotility /Aspiration Lowers seizure threshold Neuroleptic malignant syndrome (NMS) Mental status changes Muscle rigidity Fever Impaired temperature regulation Worsened by heat exposure, dehydration and medications with anticholinergic properties Extrapyramidal Symptoms (EPS) ◦ Pseudo parkinsonism ◦ Acute dystonic reactions Dose related Higher risk in males and younger patients Akathesia Tardive Dyskinesia Inability to stay still, restlessness, feeling of crawling out of one’s skin Irreversible Tongue and facial movements Abnormal Involuntary Movement Scale (AIMS) test recommended prior to treatment then every 3 months while on antipsychotic Sternest warning from FDA that a medication can cary and still remain on the US market Indicating serious side effects or life threatening risks Thioridazine (Mellaril) All Antipsychotics ◦ QTC prolongation ◦ Dose related ◦ Should be avoided and reserved for patients with Schizophrenia who have failed other antipsychotics ◦ Elderly patients with dementia-related psychosis are at increased risk of death Cardiovascular (stroke, heart failure, sudden death) Infectious (pneumonia) Issued in 2005 ◦ Careful consideration of Risk versus Benefit Schizophrenia Bipolar Disorder Treatment Resistant Depression (Olanzapine, Aripirazole ) Major Depressive Disorder (Quetiapine) Tourettes (Pimozide) ICU Delirium (Quetiapine) Emphasis on Person Centered Care, especially for residents with dementia Same diagnosis and dosage limits Guidelines are just more defined Bottom line: If resident has dementia, the facility must: ◦ Do everything possible to manage behaviors without medication ◦ If medication is used, more than one person had better put a lot of thought into the selection of the medication ◦ Continual monitoring & documentation of the residents’ behaviors, medical conditions, social situation ◦ ◦ ◦ ◦ ◦ ◦ ◦ Schizophrenia Huntington’s Disease Tourette’s Disorder Schizo-affective disorder Schizophreniform disorder Delusional Disorder Moods Disorders ◦ ◦ ◦ ◦ Psychosis in the absence of dementia Hiccups (not induced by other medications) Nausea and vomiting associated with cancer or chemotherapy Medical illnesses with psychotic symptoms Bipolar Severe depression refractory to other therapies and/ or with psychotic features Neoplastic disease Treatment related psychosis (high dose steroids) Delirium BPSD Behavior or Psychological Symptoms of Dementia (BPSD) Also referred to as “Neuropsychiatric Symptoms” Describes behavior or other symptoms in individuals with dementia that cannot be attributed to a specific medical or psychiatric cause ◦ Agitation, Aberrant Motor behavior, Anxiety, Elation, Irritability, Depression, Apathy, Disinhibition, Delusions, Hallucinations, sleep and appetite changes NOT included in the defining criteria of dementia in the current classifications “Dementia with Behaviors” is the closest ICD code Diagnosis alone does NOT warrant the use of an Antipsychotic Identify the specific behavior Document all of the non- medication interventions tried and how they worked ◦ Must also be included in the care plan Describe how the behavior poses a threat to the resident or to others Describe how the behavior seriously impairs the resident’s quality of life Identify the behavior as related to mania or psychosis (hallucinations, delusions, paranoia, grandiosity) Wandering Confusion Agitation Uncooperative Resisting care Nervousness Restlessness fidgeting Indifference unsociability Poor self care Depression Impaired memory Insomnia Crying out (occasional) Yelling or screaming (occasional) Cannot Use Spitting, Biting, pinching Kicking, Punching Scratching, Slapping Extreme fear Frightful distress Inappropriate Sexual Behavior Continuous pacing Finger painting feces Throwing objects Purposeful vomiting Purposeful B/B inappropriately Tripping, Ramming, Pushing others Head banging Self inflicted injuries Hallucinations Delusions Paranoia Continuous and extreme crying out, yelling, screaming Can Use CNAs & CMTs should document every shift Charge Nurses should document a meaningful summary once per week Document before and after a PRN is administered Interdisciplinary team document every care plan Consultant Pharmacist: at least every quarter Physician: every month Document more often when behaviors occur or when medication is changed Documentation reminder comes up whenever an Antipsychotic Medication is ordered. CNAs document behaviors every shift for residents on Antipsychotics. Charge nurses complete detailed Antipsychotic Medication Documentation every week for residents on an Antipsychotic Weekly behavior documentation is done by both CNAs and Charge nurses for residents on any psychoactive medication Acute onset or exacerbation of symptoms Immediate threat to health or safety of resident or others Acute treatment is limited to 7 days AND Clinician and interdisciplinary team must evaluate and document the situation within 7 days to identify and address any contributing and underlying causes of the acute condition and verify the continuing need for antipsychotic medication Encourage Prescribers to only prescribe a one time dose for emergencies Limit PRN Antipsychotic orders to residents who occasionally exhibit very psychotic and dangerous behavior Only allow Charge nurse to administer PRN Antipsychotics ◦ Only after all non-medication and other medication interventions have been tried and failed ◦ Extensive documentation before and after dose administered Team follow up after each dose administered to confirm positive response and continued need for PRN dose Facility is responsible for pre-admission screening for mentally ill and intellectually disabled individuals AND obtaining physicians orders for resident’s immediate care. This screening (F285) should provide diagnosis for Antipsychotic use Other residents admitted on Antipsychotic must have use evaluated at time of admission and / or within 2 weeks of admission (initial MDS) ◦ Consider dose reduction or discontinuance of Antipsychotic Anticholinergic Medications Antiparkinson’s Medications Benzodiazepines Alcohol (including withdrawal) Cardiac Medications (especially digoxin) Corticosteroids Opioid Analgesics Stimulants Any medication can cause a psychiatric side effect in an individual patient ◦ always note new medications (even antibiotics and OTCs) Antihistamines Muscle Relaxants Urinary agents (Antimuscarinics) GI antispasmodics Tricyclic Antidepressant Antiparkinson Agents ◦ Hydroxyzine, diphenhydramine ◦ Cyclobenzaprine, Tizanidine ◦ Oxybutynin ◦ Dicyclomine, Atropine ◦ Amitriptyline, Doxepin ◦ Benztropine, Trihexyphenidyl Control pain which is a major cause of anxiety, irritability and behavior problems Anti-anxiety effect Help with shortness of breath a major cause of anxiety in COPD patients Improved quality of life BENEFITS Sedation Confusion Falls Insomnia Hallucinations (visual) Constipation Urinary retention POTENTIAL SIDE EFFECTS Significantly increase with age Generalized Anxiety Disorder (GAD) ◦ Diffuse constant anxiety and worry for >6 months 90% of presentations of late-life anxiety accounted for by Generalized Anxiety Disorder(GAD) or a specific phobia 10% are Obsessive-compulsive (OCD), post-traumatic Stress (PTSD) and panic disorders Increasing frailty, medical illness, and losses can contribute to feelings of vulnerability, fear and can reactivate anxiety disorders Agoraphobia (fear of being trapped in a place from which escape might be difficult) ◦ Afraid of being alone and unable to get help ◦ Fear of leaving home ◦ Fear of falling Rule out underlying causes Angina, arrhythmia, MI, Stroke Diabetes, low calcium, hyperthyroidism PUD, Pancreatic cancer, UTI Anemia, low blood sugar, low potassium, low sodium COPD, Pneumonia, Pulmonary Embolism Delirium, Dementia, hearing and visual impairment, Parkinson’s, Seizures, brain cancer PAIN Bronchodilators, Steroids, Theophylline Nasal decongestants, Antihistamines Caffeine Nicotine; benzodiazepine or alcohol withdrawal Opioid analgesic withdrawal Thyroid medication, Estrogen Digoxin Calcium channel blockers, alpha-blockers, betablockers Levodopa GAD Phobia PTSD OCD First Line SSRI, SNRI, Buspirone SSRI SSRI, TCA SSRI Second Line TCA SNRI SNRI SNRI Third Line/ Adjunct Benzodiazepine Benzodiazepine Benzodiazepine, Divalproex, Clonidine Benzodiazepine, Gabapentin Adapted from Cassidy, K.L., Rector, N.A. et al. SSRIs generally safest and most effective ◦ Celexa, Lexapro, Zoloft, Prozac, Luvox, Paxil Many residents also have depression May take up to 6 – 8 weeks to see full benefit at any given dose Nausea, diarrhea, tremor, increased anxiety can occur for the first few weeks ◦ Start with low dose Use of benzodiazepine in the short term may be beneficial ◦ Remember to get stop date Mechanism of Action unknown Most Common Adverse Effects Dose: 5 mg BID, increase by 5mg/day every 2-3 days as needed up to 20-30mg/day ◦ High affinity for serotonin receptors ◦ Moderate affinity for dopamine receptor ◦ Does NOT affect benzodiazepine-GABA receptors ◦ Dizziness ◦ Headache ◦ Nausea ◦ Maximum dose: 60 mg /day Not as effective on a PRN basis but is sometimes acceptable to use PRN Alprazolam (Xanax) Lorazepam (Ativan) Temazepam (Restoril) Oxazepam (Serax) Triazolam (Halcion) Estazolam Short Acting Clonazepam (Klonopin) Diazepam (Valium) Chlordiazepoxide (Librium) Clorazepate Flurazepam Quazepam Chlordiazepoxide – Amitriptyline ClidiniumChlordiazepoxide (Librax) Long Acting Sedation Respiratory depression Hypotension, dizziness Falls, Fractures Disinhibiting Akathesia, Ataxia, weakness Amnesia, headache Increased Risk of Dementia ◦ Prospective Population based study in France ◦ 1063 men & women, free of Dementia and did not start taking benzodiazepines until at least the 3rd year of follow-up ◦ 15 year follow up ◦ 50% increase in the risk of Dementia for patients that ever used a benzodiazepine versus those who never used Long acting agent should NOT be used unless shorter acting medication has failed Sleep cycle deteriorates with age Hypnotics provide minimal improvements on sleep latency and duration with high risk of adverse events Underlying causes for insomnia should always be addressed prior to starting medication ◦ ◦ ◦ ◦ Environmental (light, noise, temperature) Physical (Pain, shortness of breath) Medications (including caffeine intake) Persons life long sleep habits FDA labeled for Insomnia ◦ ◦ ◦ ◦ Lorazepam (Ativan) Oxazepam Estazolam Temazepam (Restoril) 7.5mg – 15 mg Capsules QHS Hard to dose reduce because 7.5 mg capsules are more expensive ◦ Triazolam (Halcion)----NOT RECOMMENDED Short half-life Increased risk of anterograde amnesia Inability to create new memories ◦ Alprazolam (Xanax)-off label Consider using same benzo for insomnia that is being used for anxiety to minimize polypharmacy Zolpidem (Ambien & Ambien CR, Intermezzo ◦ ◦ ◦ ◦ ◦ 5-10 mg (max 10mg) of immediate release 6.25-12.5 extended release Zolpimist Spray – 5 mg / actuation Should only be administered when patient is able to stay in bed a full night Intermezzo- 1.75 or 3.5 mg SL tab for middle of night (>4 hrs left) Zaleplon (Sonata) Eszopiclone (Lunesta) ◦ 5 mg-20 mg at bedtime (max. 10 mg in geriatrics) for 7-10 days ◦ High fat meals prolong absorption ◦ 1-3 mg (2 mg max for geriatrics) ◦ Do NOT take with or immediately after a high fat meal Rapid onset and should be administered when resident is already in bed and having difficulty sleeping Withdrawal can occur with abrupt discontinuance Chronic use >90 days NOT recommended Abnormal thinking & behavior Worsen depression CNS depression ◦ Decreased inhibition, aggression, agitation, hallucinations ◦ Suicidal ideation ◦ Impairment of physical and mental capabilities ◦ Respiratory depression (caution with COPD & apnea) Sedation, Delirium Falls, Fractures Angioedema and anaphylaxis Complex sleep-related behavior ◦ Driving, making phone calls, preparing food while asleep with no memory Trazodone ◦ Unlabeled but common use ◦ 25 mg – 150 mg at bedtime less than antidepressant dose of up to 600mg /day in divided doses ◦ Orthostatic hypotension & Syncope ◦ QT prolongation & tachycardia (less than SSRIs) Mirtazapine (Remeron) ◦ 7.5-15 mg QHS ◦ Also helpful with appetite ◦ Higher doses actually are less sedating and less effective for sleep and appetite Not recommended due to Anticholinergic side effects and adverse effect on sleep architecture Diphenhydramine (Benadryl) ◦ In Tylenol PM Hydroxyzine (Atarax, Vistaril) ◦ Safely used for anxiety in younger adults For a resident with allergies and anxiety consider Cetirizine (Zytrec) 5-10mg QHS ◦ Active metabolite of hydroxyzine with slightly less anticholinergic effect Increase the amount of Serotonin available in the Brain Citalopram (Celexa), Escitalopram (Lexapro), Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft), Fluvoxamine (Luvox) Most also FDA approved for Anxiety Adverse Effects: ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ EPS (movement disorders) Hypernatremia (low sodium) GI upset, nausea, GI bleeding Tremor, headache Decreased libido, sexual dysfunction Insomnia or somnolence Suicide (in early treatment, younger patients) Serotonin Syndrome Results from too much Serotonin in the brain Often occurs when more than one medication that increases serotonin ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ SSRIs (Prozac, Zoloft, Celexa etc…) SNRIs (Cymbalta, Effexor) Tramadol (Ultram) Buprenorphine (Butrans patch) Dextromethorphan (Robitussin DM) Buproprion (Wellbutrin, Zyban) Buspirone (Buspar) Anti –Migraine medicines (Triptans – Amerge, Zomig) TCAs (Amitriptyline, Nortriptyline) Lithium Ondansetron (Zofran) St. John’s Wart, Ginseng Or agents that impair metabolism of serotonin ◦ Linezolid (Zyvox), IV Methylene blue ◦ Marplan, Nardil (MOAI antidepressants) Mental Status Changes ◦ ◦ ◦ ◦ Hallucinations Agitation, increased anxiety Delirium Coma Autonomic Instability Neuromuscular changes GI Symptoms ◦ Tachycardia ◦ Labile blood pressure ◦ Diaphoresis, fever ◦ Tremor ◦ Rigidity ◦ Myoclonus ◦ Nausea / vomiting Seizures, coma, death Anxiety, Ankle clonus, agitation and tremor most common signs ◦ Tricyclic Antidpressants Amitriptyline (Elavil), Imipramine (Tofranil) Nortriptyline (Pamelor), Desipramine (Norpramin) Side Effects:Hypotension, sedation, cardiac arrhythmias Duloxetine (Cymbalta) ◦ Approved for anxiety ◦ Approved for fibromyalgia, diabetic neuropathy, chronic pain ◦ Nausea, dry mouth, dizziness ◦ Hypertension ◦ Reduce dose if CrCl 30-60ml/min and contraindicated if CrCl <30 ml/min Lithium ◦ ◦ ◦ ◦ More commonly used in Bipolar patients Narrow therapeutic index drug Adversely effects renal function and is cleared renaly High risk of toxicity with dehydration and with medications that affect sodium excretion (ACEIs, diuretics, NSAIDs) Anticonvulsants ◦ Divalproex (Valproic acid, Depakote) Most commonly used for behaviors in seniors Better tolerated than other mood stabilizers in older adults ◦ Carbamazepine (Tegretol) Lots of monitoring required: cbc, thyroid, LFTs ◦ Lamotrigine (Lamictal) ◦ Gabapentin (Neurontin) ◦ Topiramate (Topamax) helpful in patients that need to lose weight Side effects: Sedation, confusion, falls, Nausea, Low sodium, pancreatitis, low platelets, high ammonia levels Monitoring: CBC, Platelets, Liver function at baseline and every 6 months. Monitoring Serum levels for carbamazepine and valproic acid (every 6-12 months depending on dose) Maintain on minimum effective dose Seizure disorders Bipolar disorder Chronic pain Neuropathic pain ◦ ◦ ◦ ◦ Diabetic neuropathy Post-herpetic neuralgia Trigeminal neuralgia Post-Stroke pain Restless Leg Syndrome Watch for Polypharmacy with Gabapentin for neuropathic pain Antipsychotics ◦ Within the first year of admission or initiating of medication, attempt GDR during two separate quarters (with at least one month between attempts) ◦ Then at least annually thereafter ◦ Semi-annually if dementia with no behaviors ◦ More Aggressive Protocol: Consider GDR every quarter until behaviors emerge ◦ Limit PRN use to 1x doses or to 10 days when titrating routine doses Anti-Anxiety, Antidepressants, Anticonvulsants ◦ Within the first year of admission or initiating of medication, attempt GDR during two separate quarters (with at least one month between attempts) ◦ Then at least annually thereafter ◦ If used for pain dose reduction not recommended unless side effects Hypnotics ◦ Manufacturer Guidelines considered ◦ Attempt Quarterly GDRs May be clinically contraindicated if target symptoms returned or worsened after dose reduction or physician has well documented rationale How long it took to titrate to therapeutic dose and residents history of depression or anxiety Inherent physical dependence /withdrawal properties of the medication Dosage forms available, price, whether or not tablets can be split Number of different psychoactive medications resident is on and set priorities based on symptoms Is the resident experiencing side effects ◦ FALLS ◦ WEAKNESS ◦ TREMORS Behavioral health Committee or team ◦ Consultant Pharmacist, Psychologist, Medical Director, Administrator, D.O.N. ◦ Activities, Therapy, Social services ◦ Direct care staff (Nurses, RMTs, CNAs) Meet at least monthly to discuss dementia patients, residents on antipsychotics or residents with problematic behavior issues ◦ Look for underlying causes of behavior Pain, medication side effects, metabolic conditions, psychosocial factors ◦ Consider gradual dose reductions ◦ Ensure supportive documentation Educate Nursing Staff (including CNAs) regarding the use of Psychoactive Medications ◦ Which medications work for which symptoms ◦ Side effects to monitor ◦ Diagnosis and specific behaviors that must be documented to justify / support the use of the medication Consider implementing policy / Process ◦ No single nurse allowed to call and request and antipsychotic ◦ Psychoactive medications started by on-call physicians be reevaluated promptly by the behavior team Advanced Copy: Dementia Care in Nursing Homes: Clarification to Appendix P State Operations Manual (SOM) and appendix PP in the SOM for F309-Quality of Care and F329-Unnecessary Drugs. Accessed online August 2013 at: http://surveytraining.cms.hhs.gov Billioti de Gage, S.,Begaud, B., Bazin, F. et al. Benzodiazepine Use and Risk of Dementia Prospective Population Based Study. BMJ. Accessed online Sept. 2013 at: http//www.medscape.com/viewarticle/771934. Cassidy, k.L., Rector, Neil A. The Silent Geriatric Giant: Anxiety Disorders in Late Life. Geriatrics and Aging. 2008;11(3):150-156 Cerejeira, J., Lagarto, and Mukaetova-Ladinska, E.B., Behavioral and Psychological Symptoms of Demetia. Published online 201 May 7. frontiers in Neurology. Guide to the Management of Psychotic Disorders and Neuropsychiatric Symptoms of Dementia in Older Adults. October 2012. Accessed online Sept. 2013 at: http://dementia.americangeriatrics.org/GeriPsych_index.php Policy Statement. Use of Antipsychotic Medications in Nursing Facility Residents. Accessed online Sept. 2013 at: www.ascp.com The American Geriatrics Society 2012 Beers Criteria Update Expert Panel. American Geriatrics Society Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. JAGS 2012. Accessed online September 2013 at: www.americangeriatrics.org Lexicomp online drug information: www.online.lexi.com