Pharmacological Management of Behavioral Problems

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Should I give a medication…

Pharmacological Management of Behavioral Problems

Or just take one myself?Dr. Gordon ThomasGeriatric Psychiatrist

Royal Ottawa Mental Health Centre

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

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approach

Wandering / pacing Exit-seeking Sundowning Hoarding Rummaging Resistance to care Sexual disinhibition

Inappropriate dressing/disrobing

Inappropriate voiding/defecation

Swearing Screaming/repetitive

vocalizations Spitting

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Behaviors that Do Not respond to Medication:


approach

Anxiety Depression Mania Psychosis Sleep disruption

Aggression Frontal disinhibition

General medical illness

Infections Medication side

effects Delirium Pain

Agitation

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Causes of behaviors that May respond to Medication:

PHARMACOKINETICSHow the body handles drugs:

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Psychotropic drugs Use in the

Elderly• Changes in how the body handles drugs

• Absorption• Distribution• Metabolism• Elimination

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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

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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

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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

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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)

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Elderly• Illnesses alter handling of drugs

• Gastric surgery• Heart failure• Liver disease• Renal disease• Malnutrition

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PHARMACODYNAMICSHow the drugs affect the body:

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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)

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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

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ANTIDEPRESSANTSThe happy pill…

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Psychotropic drugs

Antidepressants• Antidepressant usage

• Depression treatment/prevention• Anxiety• Sleep disruption• Agitation• Frontal symptoms / Behaviors• Pain control

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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

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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)

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Psychotropic drugs

Antidepressants• NaSSA (Noradrenergic and Selective Serotinergic

Antidepressant)• Remeron (mirtazapine)

• Effective and well tolerated• Depression/anxiety, sleep disturbance,

appetite• (behavior), (pain)

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Psychotropic drugs

Antidepressants• NDRI (Norepinephrine-Dopamine Reuptake

Inhibitor)• Wellbutrin (bupropion)

• Effective and well tolerated• Depression• May worsen anxiety

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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

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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

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Psychotropic drugs

Antidepressants• Trazodone

• Not used for depression (need high doses)• Used at low doses

• Sleep initiation• Anxiety• Agitation• Frontal symptoms

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Psychotropic drugs

AntidepressantsClass Side Effects to watch for:SSRI HANDS:

Headache, Agitation, Nausea, Diarrhea, Dizziness, Sweating, Sedation

SNRI Headache, Nausea, Hypertension, AgitationNaSSA Sleepiness, Dizziness, Constipation, Weight gainNDRI SHARES:

Seizure, Headache, Agitation, Rash, Emesis, Sleep disturbance

Trazodone

Drowsiness, orthostatic hypotension, headache, tinnitus

TCA Cardiovascular, Anticholinergic, Confusion

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Psychotropic drugs

Antidepressants

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Drug Typical initial doses

Typical dose range

Celexa (citalopram) 10 mg daily 20-40 mg dailyCipralex (escitalopram) 5 mg daily 10-20 mg dailyZoloft (sertraline) 25 mg daily 50-200 mg dailyLuvox (fluvoxamine) 25 mg qhs 50-200 mg qhsEffexor XR (venlafaxine)

37.5 mg daily 150-300 mg daily

Cymbalta (duloxetine) 30 mg daily 60-120 mg dailyRemeron (mirtazepine) 15 mg qhs 30-45 mg qhsWellbutrin XL (bupropion)

150 mg daily 300-450 mg daily

Trazodone25-50 mg qhs12.5-25 mg tid12.5–25 mg q4h prn

25-200 mg qhs12.5-100 mg tid12.5-50 mg q4h prn

Psychotropic drugs

Antidepressants

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• 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?

Psychotropic drugs

Antidepressants

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• Common Uses• Depression and Anxiety• Pain (Effexor & Cymbalta)• Sleep (Remeron & Trazodone)• Frontal Disinhibition• Smoking Cessation (Wellbutrin)

ANTIPSYCHOTICSThe crazy pill…

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Psychotropic drugs

Antipsychotics• Antipsychotic usage

• Schizophrenia / Delusional disorders• Psychotic depression• Delirium• Dementia with behavioral problems

These are not first choice medications

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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

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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

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Psychotropic drugs

AntipsychoticsDrug Typical doses CommentsRisperidone

0.125-1.5 mg qhs

Risk of parkinson symptoms at higher dosesLess sedatingLittle weight gain

Olanzapine

1.25–10 mg qhs Most sedatingLarge weight gainCan cause problems with diabetic control

Seroquel 12.5–100 mg bid12.5-50 mg tid/qid

SedatingHypotension can be problem

Abilify 2-10 mg daily Not sedatingCan increase anxiety or restlessness (rare)Seems to work well for mood symptoms

Always need to use the lowest possible dose and review frequentlyMost patients need these medications only for short periods (few months)

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Psychotropic drugs

Antipsychotics

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• 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?

ANXIOLYTIC / SEDATIVE HYPNOTICS

The sleepy pill…

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Psychotropic drugs

Anxiolytics

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• Anxiolytics / Sedative Hypnotic use• Use is controversial in elderly patients• Sleep• Anxiety• Behavioral management• Alcohol withdrawal

Psychotropic drugs

Anxiolytics• Benzodiazepines

• Alprazolam (Xanax)• Diazepam (Valium)• Flurazepam

(Dalmane)• Clonazepam

(Rivotril)

• Non-benzodiazepines• Zopiclone (Imovane)• Zolpidem (Ambien)• Zaleplon (Starnoc)

• Lorazepam (Ativan)• Oxazepam (Serax)• Temazepam

(Restoril)

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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

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MOOD STABILIZERSThe steady pill…

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Psychotropic drugs Mood

Stabilizers• Mood stabilizer use

• Bipolar disorder (mania & depression)• Augmentation of antidepressants

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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)

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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

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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

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COGNITIVE STABILIZERSThe memory pill…

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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

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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

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Stabilizers• Cholinergic agents

• Side Effects (MIND)• Muscle cramps• Insomnia / nightmares• Nausea ***• Diarrhea

• Caution with:• COPD, heart block, seizures, ulcers

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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)

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Stabilizers• Glutaminergic agents

• Side Effects (CHECK)• Confusion• Headache• Equilibrium (dizziness)• Constipation• Kidney function

• Dosage depends on CrCl (eGFR is not adequate)

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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

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StabilizersDrug Starting dose Treatment doseAricept (donepezil) 5 mg qam 5 or 10 mg qamReminyl ER (galantamine)

8 mg qam 16-24 mg qam

Exelon (rivastigmine) 1.5 mg bid 3-6 mg bid Exelon patch Patch 5 daily Patch 10 dailyEbixa (memantine) 5 mg qam 5 or 10 mg bid

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Stabilizers• Common Questions

• Which medication?• When and how to switch medications?• How to monitor?• Are combinations useful?• When should they be stopped?

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Pharmacological Management of Behavioral Problems