Antipsychotic Use in the Elderly Presented by: Fatima M. Ali, PharmD, RPh, BCPS Clinical Consultant Pharmacist MediSystem Pharmacy, Kingston Originally Prepared by: Nicole Tisi BScPhm, RPh ACPR
Disclosure No conflict of interest to disclose
Objectives List at least three age-related physiologic changes in the elderly Differentiate between first generation antipsychotics (FGAs) and second generation antipsychotics (SGAs) or Atypicals Describe most common and severe adverse effects associated with antipsychotic therapy Identify monitoring parameters for antipsychotic therapy
Age-Related Physiologic Changes Amount of water in body, % of fat tissue Drugs dissolving in water reach HIGHER concentrations (less water to dilute them) Drugs dissolving in fat ACCUMULATE more (more fat tissue to store them) Decreased renal/hepatic function: Renal: less able to excrete drugs into urine Hepatic: less able to breakdown (metabolize) drugs
Bottom Line Medications are less readily removed from the body
Age-Related Physiologic Changes Slower gut motility more susceptible to constipation Decreased skeletal bone mass osteoporosis and increased fractures Decreased ability to taste decreased appetite, weight loss Elderly may over salt their food due to reduced ability to taste
SCHIZOPHRENIA
Epidemiology Affects 1% of the population Risk higher in those this family history 25-50% attempt suicide with 10% successful Affects men and women equally Onset usually late adolescent to young adulthood People with schizophrenia are the largest group of older people with severe mental health problems
Question What type(s) of symptoms do residents with schizophrenia experience?
Positive Symptoms Excess of normal functions: Delusions and hallucinations Distortions or exaggerations in language and communication (disorganized speech) Disorganized, catatonic or agitated behaviour Other disorders that can have positive symptoms bipolar disorder, psychotic depression and Alzheimer s disease
Negative Symptoms Reduction in normal functions Affective flattening restricted range and intensity of emotional expression Alogia restricted fluency and productivity of thought and speech Avolition restrictions in initiation of goal directed behaviour Anhedonia lack of pleasure Attentional impairment
Cognitive Symptoms Impaired attention and information processing verbal fluency (spontaneous speech) serial learning (list of items or sequence of events) executive functioning (focusing attention, concentration, prioritizing and modulating behaviour based on social cues) Also seen in post stroke dementia, autism, Alzheimer s disease
ANTIPSYCHOTIC THERAPY
Pharmacologic Therapy Antipsychotics First generation/ conventional antipsychotics Second generation/ atypical antipsychotics Augmentation therapies Mood stabilizers (i.e. lithium, valproic acid, carbamazipine) SSRI antidepressants (i.e. fluvoxamine, fluoxetine)
Question What is the difference between first & second generation antipsychotics? Examples?
Antipsychotics Dosage ranges in Schizophrenia First Generation Agents Recommended Dose Range (mg/day) Second Generation Agents Recommended Dose Range (mg/day) Chlorpromazine 300-1000 Aripiprazole 10-30 Fluphenazine 5-20 Clozapine 150-600 Perphenazine 16-64 Olanzapine 10-30 Trifluoperazine 15-50 Quetiapine 300-800 Haloperidol 5-20 Risperidone 2-8 Loxapine 30-100 Ziprasidone 120-200 **Effective doses are much higher than those used for treatment of BPSD**
Antipsychotic Medication Mechanism of Action All antipsychotics block dopamine 2 (D2) receptors in the mesolimbic dopamine pathway and act to diminish positive symptoms
Therapeutic Dilemma FGA distribute to and block all D2 receptors in the brain (not just the mesolimbic pathway) Also blocks DA in mesocortical pathway (negative symptoms) where DA may already be deficient Nigrostriatal pathway (movement disorders) And finally also leads to DA blockade in the tuberoinfundibular pathway (hyperprolactinemia)
Atypical / SGA Mechanism of Action Have both serotonin & dopamine blocking properties Serotonin inhibition reverses the effects of antipsychotics on the blockade of dopamine in 3/4 dopamine pathways Luckily, serotonin fails to reverse the effects of dopamine blockade in the mesolimbic pathway (responsible for positive symptoms)
Impact on the Endocrine System Increased prolactin levels Galactorrhea Gynecomastia Bone demineralization (postmenopausal women) Weight gain Change in drug warranted if weight gain 5% above baseline Substantial impact increased risk of cardiovascular disease Impaired glucose metabolism Increased incidence of diabetes in patients
Impact on the Cardiovascular System Orthostatic hypotension Especially noted with IM administration, elderly and diabetics with pre-existing cardiovascular disease Lipid changes Increased TG, Low HDL Electrocardiographic changes prolonged QT interval, ventricular arrhythmia, tachycardia Monitor for drug-drug interaction
Question What are some common medications that may cause QT prolongation?
Impact on Autonomic Nervous System Anticholinergic side effects dry mouth, constipation, tachycardia, blurred vision, urinary retention, impaired memory, confusion, delirium Incidence is 10-50% and occurs with both FGAs and SGAs More troublesome for older patients
Impact on Central Nervous System Extrapyramidal Symptoms Dystonia Prolonged tonic contraction ( muscle spasm ) Dramatic, painful and can be life threatening (i.e. pharyngeal-laryngeal dystonia) Akathisia Unable to sit still, inner restlessness or compulsion to move or remain in constant motion Occurs in most patients on FGAs but many can t verbalize the feeling or recognize akathisia as different from psychosis
Impact on Central Nervous System Extrapyramidal Symptoms Pseudoparkinsonism (most common form of EPS caused by FGAs) Akinesia, bradykinesia Tremor (predominate at rest) Cogwheel rigidity Postural abnormalities and instability
Impact on Central Nervous System Extrapyramidal Symptoms Tardive Dyskinesia - 5% of people per year on FGA Abnormal involuntary movements Occurs late in onset relative to starting treatment Possibly reversible and only if medication stopped/reduced early Risk factors: older age, acute EPS, poor drug response, diabetes, mood disorder and female
Impact on the Central Nervous System Sedation and Cognition Thermoregulation Neuroleptic Malignant Syndrome Body temp > 38, alterted LOC, tachycardia, labile BP, diaphoresis, tachypnea, urinary or fecal incontinence and rigidity Seizure
Management of EPS Medication Name Dose (mg/day) Target Extrapyramidal Side Effect Benztropine 0.5-6 Akathisia, dystonia, parkinsonism Trihexyphenidyl 1-15 Akathisia, dystonia, parkinsonism Amantadine 100-300 Akathisia, parkinsonism Propranolol 30-90 Akathisia Lorazepam 1-6 Akathisia Diphenhydramine 25-50 Akathisia, dystonia, parkinsonism
Impact on the Hematologic System Transient leukopenia during initial treatment (typically insignificant) Agranulocytosis (serious) Onset usually within first 8 weeks May initially present as local infection with sore throat, leukoplakia, erythema and ulcerations of the pharynx need immediate WBC count Limits clinical utility of clozapine
General Side Effects of Selected Antipsychotics EPS Prolactin Elevation Wg. Gain Glucose and lipid Sedation Hypotension Anticholinergic Thioridazine + ++ + +? ++ ++ ++ Perphenazine ++ ++ + +? + + 0 Haloperidol +++ +++ + 0 ++ 0 0 Clozapine 0 0 +++ +++ +++ +++ +++ Risperidone + +++ ++ ++ + + 0 Olanzapine 0 0 +++ +++ + + ++ Quetiapine 0 0 ++ ++ ++ ++ 0 Ziprasidone 0 + 0 0 0 0 0 Aripiprazole 0 0 0 0 + 0 0
CONSIDERATIONS IN THE ELDERLY
Considerations w/ Antipyschotics May only be effective for 1 in 5 dementia residents Only minimally effective for certain types of behavioral symptoms Non-pharmacologic therapy may be just as beneficial as antipsychotic therapy Adverse effects may include falls, increased mortality, and increased risk of stroke
Considerations Consider slow tapering / deprescribing for residents experiencing adverse effects Residents with more severe BPSD or psychiatric disorders may worsen with dose reduction or cessation of therapy Residents with no symptoms, controlled symptoms or significant improvement may benefit a slow taper trial Symptom free period of 3-6 months
Considerations for Treatment of Schizophrenia in the Elderly Age related changes in receptor sensitivity, absorption and metabolism may warrant lower dosing More susceptible to adverse effects (i.e reports of EPS with FGA after three years 60% in the elderly vs. 20 % in younger groups)
Considerations for Management of Non-psychotic Indications in Elderly Avoid antipsychotic medications whenever appropriate Avoid use as sleep-aid medication Consider using low dose trazodone when appropriate When warranted, use only for acute period for resolution of symptoms After acute phase and if controlled as described previously, taper slowly by 10-25% every 6-8 weeks and monitor for reoccurrence of symptoms
Summary When utilizing for psychotic indication: Start with second generation or atypical antipsychotics Reduced side effects and potentially better efficacy for negative symptoms Choose appropriate second generation agent based on side effect profiles Maintenance Phase: aim for lowest effective dose
Summary Monitor for EPS, weight gain, blood pressure, lipid abnormalities (especially with dosage changes and/or starting new agents) Rapidly dissolving formulations useful for people who cheek medications IM antipsychotics and/or benzodiazepines for acutely agitated patient to assist in calming (monitor for EPS) Avoid prolonged use
Summary When utilizing for NON-psychotic indication: Avoid antipsychotic therapy with appropriate When warranted: Use lowest effective doses for acute period Monitor for adverse effects Slowly taper after acute phase has resolved Deprescribe as soon as possible
Questions
References 1. Dipiro, J.T. "Pharmacotherapy : a Pathophysiologic Approach". APA (9th ed.) DiPiro, J. T. (2014). 2. Besdine, Richard W. Physical Changes with Aging. The Merck Manual, June 2009. 3. Chandler, D, Presenter. Managing Older Adults: High Risk Medications-Increasing Awareness and Working to Improve Patient Outcomes. University of Buffalo, May 2012. 4. The American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc 2015. 5. Steinman, M, and Hanlon, J. Managing Medications in Clinically Complex Elders. JAMA 2010; 304 (14): 1592-1601.
Antipsychotic Use in the Elderly Presented by: Fatima M. Ali, PharmD, RPh, BCPS Clinical Consultant Pharmacist MediSystem Pharmacy, Kingston Originally Prepared by: Nicole Tisi BScPhm, RPh ACPR