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Pharmacological Management of Behavioral Problems Should I give a medication… Or just take one myself? Dr. Gordon Thomas Geriatric Psychiatrist Royal Ottawa Mental Health Centre 1 Psychotropic drugs Part of the overall approach • Psychotropic: • Any drug capable of affecting the mind, emotions, and behavior • Examples • • • • • Antidepressants Antipsychotics Anxiolytics/Sedatives Mood stabilizers Cognitive stabilizers 2 Psychotropic drugs Part of the overall approach Behaviors that Do Not respond to Medication: Wandering / pacing Exit-seeking Sundowning Hoarding Rummaging Resistance to care Sexual disinhibition Inappropriate dressing/disrobing Inappropriate voiding/defecation Swearing Screaming/repetitive vocalizations Spitting 3 Psychotropic drugs Part of the overall approach Causes of behaviors that May respond to Medication: Anxiety Depression Mania Psychosis Sleep disruption General medical illness Infections Medication side effects Delirium Pain Aggression Frontal disinhibition Agitation 4 How the body handles drugs: PHARMACOKINETICS 5 Psychotropic drugs Use in the Elderly • Changes in how the body handles drugs • • • • Absorption Distribution Metabolism Elimination 6 Psychotropic drugs Use in the Elderly • Absorption • Slower in elderly patients • Decreased motility and gastric pH • No clinical significance without overt disease • Can be delayed by other medications • • • • Antacids Aluminum containing cathartics Calcium/Magnesium Fibre 7 Psychotropic drugs Use in the Elderly • Distribution (fat / water / protein bound) • Higher fat:muscle and fat:water ratios • • Lipid soluble medications stored and take longer to clear Most psychotropics are lipid soluble • Lower protein (albumin) levels • • Not clinically significant by itself Multiple medications bind protein and may compete 8 Psychotropic drugs Use in the Elderly • Metabolism • Phase I: oxidation before entering circulation • Decreased in elderly = more active drug in system • Phase II: conjugation/glucuronidation • • Relatively unaffected Other changes decrease this process • • Reduced liver blood flow (40-45%) Reduced liver mass • Some activate or deactivate the process • Decrease or increase levels of active drug 9 Psychotropic drugs Use in the Elderly • Elimination • Decreased renal function with age • • GFR decreases yearly from age 20 Calculated CrCl needed (eGFR is inaccurate) • Decreased response to volume changes • More likely to have abnormal electrolytes (SIADH) 10 Psychotropic drugs Use in the Elderly • Illnesses alter handling of drugs • • • • • Gastric surgery Heart failure Liver disease Renal disease Malnutrition 11 How the drugs affect the body: PHARMACODYNAMICS 12 Psychotropic drugs Use in the Elderly • Changes in how drugs affect the body • Increased sensitivity • • • Changes in receptor density Decreased responsiveness of regulatory systems Direct sensitivities (stroke, Parkinson’s, dementia) 13 Psychotropic drugs Use in the Elderly • Different approach to using medications • “Start low and go slow” • Overall therapeutic dose often unchanged • Longer time to get a clinical response • Can be toxic at “therapeutic levels” • More vulnerable to some side effects 14 The happy pill… ANTIDEPRESSANTS 15 Psychotropic drugs Antidepressants • Antidepressant usage • • • • • • Depression treatment/prevention Anxiety Sleep disruption Agitation Frontal symptoms / Behaviors Pain control 16 Psychotropic drugs Antidepressants • SSRI (Selective Serotonin Reuptake Inhibitor) • • • • Celexa (citalopram): few drug interactions Cipralex (escitalopram): few drug interactions Zoloft (sertraline): minor interactions Luvox (fluvoxamine): more interactions, sedating • Effective and well tolerated • Depression/anxiety, agitation, behaviors • Prozac (fluoxetine): half-life too long • Paxil (paroxetine): too anticholinergic 17 Psychotropic drugs Antidepressants • SNRI (Serotonin Noradrenaline Reuptake Inhibitor) • Effexor (venlafaxine) • Cymbalta (duloxetine) • Effective and well tolerated • Depression/anxiety, (behaviors) • Neuropathic pain • Nociceptive pain (new indication) 18 Psychotropic drugs Antidepressants • NaSSA (Noradrenergic and Selective Serotinergic Antidepressant) • Remeron (mirtazapine) • Effective and well tolerated • Depression/anxiety, sleep disturbance, appetite • (behavior), (pain) 19 Psychotropic drugs Antidepressants • NDRI (Norepinephrine-Dopamine Reuptake Inhibitor) • Wellbutrin (bupropion) • Effective and well tolerated • Depression • May worsen anxiety 20 Psychotropic drugs Antidepressants • TCA (Tri-Cyclic Antidepressant) • Nortriptyline, Desipramine • Amitriptyline, Imipramine • Effective but poorly tolerated • Cardiac effects (hypotension, tachycardia) • Increased fall risk • Anticholinergic effects • Dry mouth, confusion, constipation, confusion, urinary retention, confusion, blurred vision, confusion 21 Psychotropic drugs Antidepressants • MAOI (MonoAmine Oxidase Inhibitor) • Parnate, Nardil • Poorly tolerated due to need for diet (yuck!) • Mannerix (Moclobemide) • • No need for diet Less effective and poorly studied in elderly 22 Psychotropic drugs Antidepressants • Trazodone • Not used for depression (need high doses) • Used at low doses • • • • Sleep initiation Anxiety Agitation Frontal symptoms 23 Psychotropic drugs Antidepressants Class Side Effects to watch for: SSRI HANDS: Headache, Agitation, Nausea, Diarrhea, Dizziness, Sweating, Sedation SNRI Headache, Nausea, Hypertension, Agitation NaSSA Sleepiness, Dizziness, Constipation, Weight gain NDRI SHARES: Seizure, Headache, Agitation, Rash, Emesis, Sleep disturbance Trazodone Drowsiness, orthostatic hypotension, headache, tinnitus TCA Cardiovascular, Anticholinergic, Confusion 24 Psychotropic drugs Antidepressants Drug Typical initial doses Typical dose range Celexa (citalopram) 10 mg daily 20-40 mg daily Cipralex (escitalopram) 5 mg daily 10-20 mg daily Zoloft (sertraline) 25 mg daily 50-200 mg daily Luvox (fluvoxamine) 25 mg qhs 50-200 mg qhs Effexor XR (venlafaxine) 37.5 mg daily 150-300 mg daily Cymbalta (duloxetine) 30 mg daily 60-120 mg daily Remeron (mirtazepine) 15 mg qhs 30-45 mg qhs Wellbutrin XL (bupropion) 150 mg daily 300-450 mg daily Trazodone 25-50 mg qhs 12.5-25 mg tid 12.5–25 mg q4h prn 25-200 mg qhs 12.5-100 mg tid 12.5-50 mg q4h prn 25 Psychotropic drugs Antidepressants • Common questions • • • • • • When should the dose increase? When should the drug stop? How long does it take to work? What if it doesn’t work? What other options are there? What about ECT? 26 Psychotropic drugs Antidepressants • Common Uses • • • • • Depression and Anxiety Pain (Effexor & Cymbalta) Sleep (Remeron & Trazodone) Frontal Disinhibition Smoking Cessation (Wellbutrin) 27 The crazy pill… ANTIPSYCHOTICS 28 Psychotropic drugs Antipsychotics • Antipsychotic usage • • • • Schizophrenia / Delusional disorders Psychotic depression Delirium Dementia with behavioral problems These are not first choice medications 29 Psychotropic drugs Antipsychotics • Atypicals (newer medications) • • • • • Risperidone (Risperdal) Olanzapine (Zyprexa) Seroquel (Quetiapine) Zeldox (Ziprazidone) Abilify (Aripiprazole) • Fewer side effects than older medications • Still need to be used cautiously • Sedation, weight gain, risk of falls, risk of stroke • Small increase in mortality 30 Psychotropic drugs Antipsychotics • Typicals (older drugs) • Haldol, Perphenazine, Nozinan, Loxapine, Chlorpromazine, others… • More side effects, higher risks • Parkinsonian symptoms • Tremor, rigidity, bradykinesia, restlessness, falls • Cognitive blunting • Tardive dyskinesia • Increased mortality 31 Psychotropic drugs Antipsychotics Drug Typical doses Comments Risperidone 0.125-1.5 mg qhs Risk of parkinson symptoms at higher doses Less sedating Little weight gain Olanzapine 1.25–10 mg qhs Most sedating Large weight gain Can cause problems with diabetic control Seroquel 12.5–100 mg bid Sedating 12.5-50 mg tid/qid Hypotension can be problem Abilify 2-10 mg daily Not sedating Can increase anxiety or restlessness (rare) Seems to work well for mood symptoms Always need to use the lowest possible dose and review frequently Most patients need these medications only for short periods (few months) 32 Psychotropic drugs Antipsychotics • Common questions • • • • • • When should the dose increase? When should the drug stop? How long does it take to work? What if it doesn’t work? What other options are there? When should they not be used? 33 The sleepy pill… ANXIOLYTIC / SEDATIVE HYPNOTICS 34 Psychotropic drugs Anxiolytics • Anxiolytics / Sedative Hypnotic use • • • • • Use is controversial in elderly patients Sleep Anxiety Behavioral management Alcohol withdrawal 35 Psychotropic drugs Anxiolytics • Benzodiazepines • • • • Alprazolam (Xanax) Diazepam (Valium) Flurazepam (Dalmane) Clonazepam (Rivotril) • Lorazepam (Ativan) • Oxazepam (Serax) • Temazepam (Restoril) • Non-benzodiazepines • Zopiclone (Imovane) • Zolpidem (Ambien) • Zaleplon (Starnoc) 36 Psychotropic drugs Anxiolytics • Side effects • Drowsiness / fatigue • Memory impairment / confusion • • • • • • • • Chronic use can meet criteria for dementia Weakness Incoordination / ataxia Depression Disinhibition / behavior problems Paradoxial reactions Decreased sleep quality and worsened apnea Tolerance and withdrawal symptoms • Elderly (especially with dementia) are more sensitive 37 The steady pill… MOOD STABILIZERS 38 Psychotropic drugs Mood Stabilizers • Mood stabilizer use • Bipolar disorder (mania & depression) • Augmentation of antidepressants 39 Psychotropic drugs Mood Stabilizers • Lithium • • • • Effective for mania and depression Effective in lower doses for augmentation Water soluble and cleared by kidneys Serum levels must be monitored • • 0.4 – 0.7 mmol/L (not 0.8 – 1.5 mmol/L) Lower levels for augmentation (0.3 - 0.6 mmol/L) 40 Psychotropic drugs Mood Stabilizers • Lithium side effects • • • • nausea, anorexia, diarrhoea,vomiting weight gain, sedation subjective memory loss and slowing tremor, parkinsonism, ataxia • High serum levels are toxic • Increased side effects, delirium • Hold and check level if losing fluid 41 Psychotropic drugs Mood Stabilizers • Anticonvulsants • Valproic acid (Epival) • GI upset, somnolence, alopecia, tremor, weakness, increased liver enzymes, gait instability • Lamotragine (Lamictal) • Gabapentin (Neurontin) • Carbamazepine (Tegretol) • some evidence of cognitive impairment caused by these drugs 42 The memory pill… COGNITIVE STABILIZERS 43 Psychotropic drugs Cognitive Stabilizers • Cognitive Stabilizer use • Stabilizers not Enhancers • • • • • Preservation of Abilities Management of Behaviors Stabilization of Cognitive function Decrease caregiver time Delay Entry into LTC setting 44 Psychotropic drugs Cognitive Stabilizers • Cholinergic agents • Aricept (donepezil) • Reminyl (galantamine) • Exelon (rivastigmine) • Effective for Mild to Severe dementias • Stabilize cognition for 1-2 years • Still some benefits even when decline resumes 45 Psychotropic drugs Cognitive Stabilizers • Cholinergic agents • Side Effects (MIND) • • • • Muscle cramps Insomnia / nightmares Nausea *** Diarrhea • Caution with: • COPD, heart block, seizures, ulcers 46 Psychotropic drugs Cognitive Stabilizers • Glutaminergic agents • Ebixa (memantine) • Effective for Moderate to Severe dementias • Stabilize cognition for 1-2 years • • Small number have some improvement Small number get more confused • Not covered by ODB ($120 per month) 47 Psychotropic drugs Cognitive Stabilizers • Glutaminergic agents • Side Effects (CHECK) • • • • • Confusion Headache Equilibrium (dizziness) Constipation Kidney function • Dosage depends on CrCl (eGFR is not adequate) 48 Psychotropic drugs Cognitive Stabilizers • Who might benefit? • • • • • Alzheimer’s dementia Vascular dementia Mixed Dementia Lewy-Body Dementia Other neuropsychiatric disorders • i.e. Parkinsons-related Dementia Fronto-temporal dementia can get worse 49 Psychotropic drugs Cognitive Stabilizers Drug Starting dose Treatment dose Aricept (donepezil) 5 mg qam 5 or 10 mg qam Reminyl ER (galantamine) 8 mg qam 16-24 mg qam Exelon (rivastigmine) 1.5 mg bid 3-6 mg bid Patch 5 daily Patch 10 daily 5 mg qam 5 or 10 mg bid Exelon patch Ebixa (memantine) 50 Psychotropic drugs Cognitive Stabilizers • Common Questions • • • • • Which medication? When and how to switch medications? How to monitor? Are combinations useful? When should they be stopped? 51