Effective and Appropriate Use of Psychoactive Medications in Long Term Care Residents

1. Effective and Appropriate Use of Psychoactive Medications in Long Term Care Residents Dr. Cynthia Hadfield, Pharm.D. Director of Pharmacy for Employee, LTC & Retail Pharmacies Lead Clinical Pharmacist, Geriatric Specialist Citizens Memorial Healthcare

2. Faculty Disclosure • 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

3. Off-label Medication Use • 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

4. Objectives • 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

5. Some Good News • 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)

6. Focus on Antipsychotic Reduction Will Continue ! • 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

7. Antipsychotics • Chlorpromazine (Thorazine) • Fluphenazine • Haloperidol (Haldol) • Loxapine • Mesoridazine • Molindone • Perphenazine • Promazine • Thioridazine (Mellaril) • Thiothixine • Trifluperazine • Triflupromazine • Asenapine (Saphris) • Aripiprazole (Abilify) • Clozapine (Clozaril) • Iloperidone (Fanapt) • Lurasidone (Latuda) • Olanzepine (Zyprexa) • Paliperidone(Invega) • Quetiapine (Seroquel) • Riperidone(Risperdal) • Ziprasidone(Geodon) Typical (first generation / conventional) Atypical (second generation)

8. How Antipsychotics work • 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

9. Side Effects of Antipsychotics • 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

10. Side Effects of Antipsychotics • 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

11. Neurologic Side Effects of Antipsychotics • Extrapyramidal Symptoms (EPS) • Pseudo parkinsonism • Acute dystonic reactions • Dose related • Higher risk in males and younger patients • Akathesia • Inability to stay still, restlessness, feeling of crawling out of one’s skin • Tardive Dyskinesia • Irreversible • Tongue and facial movements • Abnormal Involuntary Movement Scale (AIMS) test recommended prior to treatment then every 3 months while on antipsychotic

12. Black Box Warnings for Antipsychotics • 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) • QTC prolongation • Dose related • Should be avoided and reserved for patients with Schizophrenia who have failed other antipsychotics • All 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

13. Antipsychotic FDA Approved Diagnosis • Schizophrenia • Bipolar Disorder • Treatment Resistant Depression (Olanzapine, Aripirazole ) • Major Depressive Disorder (Quetiapine) • Tourettes (Pimozide) • ICU Delirium (Quetiapine)

14. Changes to F309 & F329 Related to antipsychotics • 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

15. F329- Antipsychotic Indications for Use • Schizophrenia • Huntington’s Disease • Tourette’s Disorder • Schizo-affective disorder • Schizophreniform disorder • Delusional Disorder • Moods Disorders • Bipolar • Severe depression refractory to other therapies and/ or with psychotic features • 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 • Neoplastic disease • Treatment related psychosis (high dose steroids) • Delirium BPSD

16. 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

17. Clinical Indications in Meditech EMR for Antipsychotic use

18. Behavior Documentation • 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)

19. Specific Target Behaviors • 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) • 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 Cannot Use Can Use

20. How often to document • 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

21. CMH Behavior Documentation in Meditech • 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

22. Behavior Monitoring Intervention for Charge Nurses, CNAs & CMTs

23. Weekly Antipsychotic Medication Monitoring Intervention for Charge Nurses

24. Weekly Antipsychotic Medication Monitoring Intervention for Charge Nurses (continued…)

25. Weekly Antipsychotic Medication Monitoring Intervention for Charge Nurses (continued…)

26. Weekly Antipsychotic Medication Monitoring Intervention for Charge Nurses (continued…)

27. F329- Acute Situations / Emergency • 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

28. Acute Situations / PRN Antipsychotic Use • 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

29. PRN Reason Dictionary

30. Residents admitted on an Antipsychotic • 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

31. Common Medication causes of Psychotic symptoms and behaviors • 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)

32. Common Anticholinergic medications that worsen cognition and Behaviors with Dementia • Antihistamines • Hydroxyzine, diphenhydramine • Muscle Relaxants • Cyclobenzaprine, Tizanidine • Urinary agents (Antimuscarinics) • Oxybutynin • GI antispasmodics • Dicyclomine, Atropine • Tricyclic Antidepressant • Amitriptyline, Doxepin • Antiparkinson Agents • Benztropine, Trihexyphenidyl

33. How Opioid Analgesics affect Behavior • 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 • Sedation • Confusion • Falls • Insomnia • Hallucinations (visual) • Constipation • Urinary retention BENEFITS POTENTIAL SIDE EFFECTS

34. Anxiety Disorders • 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

35. Medical Conditions Associated with Late-Life Anxiety • 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

36. Medication causes of Anxiety • Bronchodilators, Steroids, Theophylline • Nasal decongestants, Antihistamines • Caffeine • Nicotine; benzodiazepine or alcohol withdrawal • Opioid analgesic withdrawal • Thyroid medication, Estrogen • Digoxin • Calcium channel blockers, alpha-blockers, beta-blockers • Levodopa

37. Pharmacological Treatment of Anxiety Adapted from Cassidy, K.L., Rector, N.A. et al.

38. SSRIs for Treatment of Anxiety • 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

39. Buspirone • Mechanism of Action unknown • High affinity for serotonin receptors • Moderate affinity for dopamine receptor • Does NOT affect benzodiazepine-GABA receptors • Most Common Adverse Effects • Dizziness • Headache • Nausea • Dose: 5 mg BID, increase by 5mg/day every 2-3 days as needed up to 20-30mg/day • Maximum dose: 60 mg /day • Not as effective on a PRN basis but is sometimes acceptable to use PRN

40. Benzodiazepines • Alprazolam (Xanax) • Lorazepam (Ativan) • Temazepam (Restoril) • Oxazepam (Serax) • Triazolam (Halcion) • Estazolam • Clonazepam (Klonopin) • Diazepam (Valium) • Chlordiazepoxide (Librium) • Clorazepate • Flurazepam • Quazepam • Chlordiazepoxide – Amitriptyline • Clidinium- Chlordiazepoxide (Librax) Short Acting Long Acting

41. Benzodiazepine Side Effects • 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

42. Insomnia and Use of hypnotics • 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

43. Benzodiazepines for Insomnia • 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

44. Non-benzodiazepine Hypnotics • 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) • 5 mg-20 mg at bedtime (max. 10 mg in geriatrics) for 7-10 days • High fat meals prolong absorption • Eszopiclone (Lunesta) • 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

45. Side Effects of hypnotic medications • Abnormal thinking & behavior • Decreased inhibition, aggression, agitation, hallucinations • Worsen depression • Suicidal ideation • CNS depression • 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

46. Use of sedating Antidepressants to help sleep • 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

47. Use of Antihistamines for Anxiety or Insomnia • 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

48. Selective Serotonin –Reuptake Inhibitors (SSRIs) • 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

49. 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 (Butranspatch) • 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)

50. Symptoms / Signs of Serotonin Syndrome • Mental Status Changes • Hallucinations • Agitation, increased anxiety • Delirium • Coma • Autonomic Instability • Tachycardia • Labile blood pressure • Diaphoresis, fever • Neuromuscular changes • Tremor • Rigidity • Myoclonus • GI Symptoms • Nausea / vomiting • Seizures, coma, death • Anxiety, Ankle clonus, agitation and tremor most common signs