Chapter 8 BPSD and the Use of Psychotropic Medications Dr. Ken Le Clair Dr. Marie-France Rivard

BPSD – Handbook for Family Physicians

BPSD – Handbook for Family Physicians

Chapter Index Introduction to Pharmacological Treatment of BPSD ............................. 1 Key Questions Related to the Use of Psychotropics in BPSD ............... 1 Main Indications for the Use of Psychotropics ........................................ 2 Important Basic Principles to Consider when Prescribing Medications for BPSD ................................................................................. 3 Selecting the Right Medication .................................................................. 4 Classes of medications commonly used in BPSD................................................... 5

Treatment of Depressive and Anxiety Disorders/Symptom Clusters .... 5 Duration of Antidepressant Treatment...................................................... 7 A Word about Benzodiazepines in the Treatment of Depressive & Anxiety Disorders........................................................................................ 8 Treatment of Persistent Psychotic Symptoms and Severe Agitation .. 10 The Newer Atypicals: Potential Concerns .............................................. 10 Treatment of Dementia: Cognitive Enhancers and Glutaminergic Agents ........................................................................................................ 11 Treatment of Severe Agitation Likely Due to Delirium .......................... 12 Treatment of Behavioural Problems Due to Lewy Body Dementia ...... 15 Treatment of Inappropriate Sexual Behaviour ....................................... 15 Treatment of Sleep Disturbances ............................................................ 15 High-Risk Situations: Capacity is an Issue and Psychotropics are Required .............................................................................................. 16 Conclusion ................................................................................................. 16 References ................................................................................................. 17

BPSD – Handbook for Family Physicians

BPSD – Handbook for Family Physicians

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Introduction to Pharmacological Treatment of BPSD The goal of this chapter is to assist family physicians in the effective use of psychotropics in the treatment of persons with BPSD. We will review how to: 1. Identify conditions that may be responsive to medications and those that will only respond to environmental or caregiving approaches. 2. Select the right medication for a particular situation and individual, minimizing the risk of side effects and maximizing its benefits. 3. Use recommended pharmacological treatments for specific clusters of BPSD. The U.R.A.F. problem-solving and collaborative care approach provides a vehicle for defining the problem and coming to a common understanding of the causes of each problem, their impact, and severity in the context of the patient and family, including the evaluation of RISKS. This foundation helps physicians to establish a shared set of goals, expected outcomes and specific roles for each care provider in regards to the actions that need to be taken and follow-up required. Key principles to keep in mind throughout this chapter are: •

Use psychotropics within the context of the overall clinical assessment framework, described in chapter 1 (U.R.A.F. and P.I.E.C.E.S.).

•

Use psychotropics with the appropriate non pharmacological approach(es).

•

Use psychotropics with an informed, involved patient and family working with an informed interdisplinary team or circle of care.

Key Questions Related to the Use of Psychotropics in BPSD The following questions have been used as part of the P.I.E.C.E.S. training to help health care professionals identify appropriate use of pharmacological treatments. Physicians, with the help of information provided by partners in care, are responsible for the identification of a clear indication for the use of medication (diagnosis), selection of the right medication and monitoring of response and side effects.

Three-Questions for Detecting, Selecting and Monitoring the Use, Risk and Benefits of Psychotropics 1. Detect: When should a psychotropic be used or considered? 2. Select: How do I contribute to the selection of the right medication? 3. Effect: How do I monitor the response and side effects?

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The P.I.E.C.E.S. educated health care providers can provide family physicians with information that will assist in identifying patients that may be responsive to psychotropics and establishing a baseline frequency and intensity of symptoms that will require monitoring during treatment. Monitoring of the benefits/response and emerging or troublesome side effects can also be done collaboratively through instruments contained in the Toolkit section.

Main Indications for the Use of Psychotropics Psychotropic medications may be considered during the course of dementia for: • •

•

Specific treatment for a mental disorder (e.g., a major depressive disorder, anxiety disorder or chronic psychotic or delusional disorder); Specific treatment for an associated behaviour or mental health problem in dementia (e.g. persistent agitation or psychosis not responsive to non-pharmacological interventions); Adjunctive, temporary treatment (e.g. delirium with significant agitation and psychosis where short-term use of an antipsychotic may be required).

Consider pharmacological treatment of BPSD when: 1. Behaviour is dangerous, distressing, disturbing, damaging to social relationships and persistent, AND 2. Has not responded to comprehensive non-pharmacological treatment plan including removal of possible offending drugs. OR 3. Requires emergency treatment to allow proper investigation of underlying problems.

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Important Basic Principles to Consider when Prescribing Medications for BPSD 1. Physicians need to try to correct or optimize treatment for underlying diagnosable medical conditions. For example, if the behavioural problems are clearly due to memory deficits due to dementia and do not seem related to any other diagnosable medical/psychiatric illness, one would consider treatment with a cholinesterase inhibitor. If the behavioural problems seem to be the result of depression, one would vigorously pursue antidepressant therapy. For problems that seem to be related to delirium or pain, one would try to find the cause(s) of the delirium or pain and correct these underlying medical problems first. Identifying medical problems, correcting them or optimizing their treatment will not only improve the well being of the person but also improve tolerability to psychotropic drugs that may be required. 2. Removing drugs that may be contributing to the BPSD: as noted previously, many drugs can worsen behavioural problems and should be removed (some gradually to avoid withdrawal symptoms). 3. Use one drug at a time, monitoring effect on target symptoms. It is usually possible to obtain the desired effect by utilizing only one medication. Combinations of drugs (haloperidol + lorazepam for example) tend to be less well tolerated (more side effects) and carry a much higher potential for harmful drug interactions than using a single medication. If side effects occur it may be difficult to sort out which element of the combination needs to be removed/decreased. 4. Start low, go slow but optimize the dose and duration of treatment to allow an adequate trial before switching to another medication. 5. Choose drugs that won’t worsen dementia or other medical problems of the patient, watching particularly for the anticholinergic load of the medication list of the patient. Within each class of psychotropic medications, we tend to chose drugs that have the least anticholinergic activity, as much as possible. Examples: avoid tricyclic antidepressants and choose SSRIs that have lower anticholinergic properties; within SSRIs, choose Citalopram over Paroxetine. 6. Check for potential drug-drug interactions before finalizing your choice. This is particularly important with antidepressants, given that most SSRIs have the potential to interact with drugs elderly patients commonly have to take, such as anticoagulants, other antidepressants, beta blockers, anti-arrhythmics, benzodiazepines and calcium channel blockers. In addition to identifying a clear indication for the use of a specific medication and its potential benefits, physicians usually have to explain to patients, substitute decisionmakers and care providers, the expected time to response, risks associated with and without treatment, targeted dose range and potential side effects that would prompt a dose reduction or discontinuation. Part of having the right indications for treatment includes the identification of those conditions that will not respond to pharmacological interventions.

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Behaviours NOT (Usually) Responsive to Medication 1. Aimless wandering 2. Inappropriate urination/defecation 3. Inappropriate dressing/undressing 4. Annoying perserverative activities 5. Vocally repetitious behaviour 6. Hiding/hoarding 7. Pushing wheelchair bound co-patient 8. Eating inedibles 9. Tugging at/removal of restraints Behaviours that May be Responsive to Medication 1. Physical aggression 2. Verbal aggression 3. Anxiety and restlessness 4. Sadness, crying, anorexia, insomnia and other symptoms indicative of depression 5. Withdrawal and apathy 6. Sleep disturbance 7. Wandering with agitation/aggression 8. Elation, pressured speech and hyperactivity (manic like symptoms) 9. Persistent delusions and hallucinations 10. Sexually inappropriate behaviour with agitation

Selecting the Right Medication The RISKS and severity of the presenting problems will help define the need for specific immediate interventions for those behaviours that may adversely affect the individual and/or caregiver. Physicians, by their training, are skilled at considering a full differential diagnosis, taking appropriate action (examination and investigations) to confirm most likely diagnoses that guide the selection of treatment. For example, the person is having significant sleep problems in the context of a depression complicating dementia: one would select an antidepressant (rather than a sedative) with low anticholinergic activity (to avoid worsening dementia), taking into account possible drug interactions with cholinesterase inhibitor and monitoring closely for gastrointestinal problems or side effects of the combined antidepressant + cholinesterase inhibitor.

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Classes of medications commonly used in BPSD 1. 2. 3. 4. 5.

Antidepressants Anxiolytic (mostly SSRIs and other antidepressants) Antipsychotic medications Cognitive enhancers Mood stabilizers

Tables regarding medications commonly used in the treatment of BPSD can be found in the Toolkit. They outline their main indications, usual starting dose, average and maximum recommended doses and main side effects to monitor for. Treatments used for depressive and anxiety disorders, persistent and distressing psychotic symptoms, delirium and dementia itself are summarized in these 2 tables.

Treatment of Depressive and Anxiety Disorders/Symptom Clusters When a diagnosis of depression is clear and meets the DSM IV criteria for a major depressive episode, antidepressant medications are recommended in addition to supportive psychotherapeutic interventions. For those patients who present with depressive symptoms that are clearly part of an adjustment reaction to a recent traumatic event and/or those for whom the diagnosis is not as clear, a period of observation and documentation of symptoms should be considered prior to pharmacological treatment. The length of the observational period may range from 2 to 8 weeks, but a decision should be made in a timely manner as to not delay treatment, particularly if symptoms are worsening. The full range of treatment modalities should be considered, including psychosocial interventions (e.g., education, participating in social events), psychotherapy, and pharmacological interventions. A full review of the treatment of depressive disorders, including depression occurring in the context of dementia is provided by the Canadian Coalition for Seniors’ Mental Health: Guidelines on the Assessment and Treatment of Depression and can be downloaded from the web: www.ccsmh.ca. Selection of an appropriate antidepressant medication should be based on: a) Previous response to antidepressant (avoiding medications that clearly failed or gave unacceptable side effects); b) Other medical comorbidities (e.g., selecting a drug that will not worsen dementia or worsen a vulnerability to urinary retention); c) Side effect profile of the antidepressant (e.g., avoiding drugs that may cause severe hypotension and falls and drugs that have high anticholinergic properties); d) Potential drug-drug interactions, considering other medications that have to be taken.

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The presence of dementia or cognitive impairment dictates that we select drugs that will not worsen the cognitive difficulties and therefore have low anticholinergic properties. Amongst current antidepressants available, the following have the lowest anticholinergic activity: • • • • • •

Venlafaxine (Effexor) Moclobemide (Manerix) Buproprion (Welbutrin) Citalopram (Celexa) Escitalopram (Cipralex) Sertraline (Zoloft) and Mirtazapine (Remeron) are also acceptable but probably have a bit more anticholinergic properties ( ref: Clinical Handbook of Psychotropic Drugs, 17th edition, 2007)

From the above choices, one has to determine which drug is best suited for the medical co-morbidities of the patient. For example, patients who have had difficult to stabilize hypertension may have problems with Venlafaxine and therefore an SSRI such as Citalopram is likely a better choice. On the other hand, patients who have significant problems with chronic pain may benefit from the noradrenergic activity of Effexor. Another example would be that patients who have Parkinson Disease may see a worsening of their Parkinsonian symptoms with a pure SSRI, although not necessarily so. If other choices are reasonable in the context of the health problems of the patient, then one would go to drugs that have dual action or more adrenergic activity such as Venlafaxine, Bupropion or Manerix for such a patient. Drug interactions are also important to consider. In the example above, if a patient with Parkinson Disease also takes Eldepryl, a MAO-B inhibitor, then utilizing Moclobemide would be difficult as a full MAOI diet would be required to allow its safe use. Several SSRIs are problematic to use in the elderly (e.g. fluoxetine, fluvoxamine, paroxetine) because of the potential for serious drug interactions with other medications elderly patients have to take. Initial dosage, average and maximum recommended doses are provided in the table on the following page. Patients who start on serotonergic antidepressants (e.g. Citalopram, Sertraline) should be monitored for common side effects such as nausea headaches and diarrhea, as well as less common but potentially serious ones, such as hyponatremia (leading to fatigue, malaise, delirium) or serotonin syndrome (with agitation, tachycardia, tremor, hyperreflexia). Venlafaxine can cause increased blood pressure when used in the higher dose range (beyond 150 mg daily). There is an increased risk of seizures with higher dosages of bupropion and weight gain is more common with mirtazapine. There is some evidence supporting the use of moclobemide as a first line agent, although this antidepressant is not commonly used in Canada. It is particularly well tolerated with a very acceptable side effect profile. Mirtazapine is available as a rapidly dissolving wafer (Remeron-RD) which may be useful for residents with swallowing problems. Escitalopram (the S-enantiomer of citalopram) is now available in Canada and may be a useful SSRI in seniors, although initial dosage has to be low. Tricyclic antidepressants (TCAs) may be used in the rare occasion where a patient with dementia has a “treatment-resistant” depression that has not responded to other adequate trials of other antidepressants. Nortriptyline and desipramine have lower anticholinergic BPSD – Handbook for Family Physicians

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properties and should be preferred over other tricyclics. Blood levels of these agents may be helpful to ensure that there has been an adequate therapeutic trial and should be done at least once to ensure the drug has not accumulated to a high (cardio-toxic) level because the patient is a “slow metabolizer” of tricyclic antidepressant medication. There is indeed a significant portion of the population that metabolizes these drugs much more slowly than others. Levels are also useful before concluding that the drug is not effective. TCAs should not be used in residents with significant cardiac conduction abnormalities. Clinicians should monitor patients on TCAs for postural hypotension, cardiac symptoms and anticholinergic side effects. Finally, one should keep in mind that electroconvulsive therapy may be a better option for patients with severe “treatment-resistant” depression or psychotic depression. Antidepressants can precipitate a manic or hypomanic episode in residents with a history of Bipolar Mood Disorder. This is less likely to occur if they are on a mood stabilizer. For patients who have known history of bipolar disorder prior to the onset of dementia, we recommend the continuation of their mood stabilizing drugs as much as feasible. The best mood stabilizer remains lithium although it requires careful monitoring, significant adjustment in dosing (lower doses and once a day dosing) and blood levels (0.4 o 0.7 MMol/L). Detailed recommendations regarding the use of lithium carbonate can be found in the National Guidelines for Seniors’ Mental Health: The Assessment and Treatment of Depression (2006). Other mood stabilizers include Sodium Valproate (Epival), Carbamazepine (Tegretol), Gabapentin (Neurontin, sometimes also used for neuropathic pain), Lamotrigine (Lamictal) and topiramate (Topamax). All can cause sedation, ataxia, nausea, bruising and rashes (Steven Johnson syndrome with Lamictal). Monitoring includes serum levels, liver function tests and CBC.

Duration of Antidepressant Treatment When initiating treatment with an antidepressant, titration according to therapeutic benefits and side effects will usually take at least one month, sometimes longer. An adequate trial is defined as having achieved a therapeutic response or having spent 4 weeks at maximum tolerated or recommended dose and there is no response. For patients who have a partial response after 4 weeks, there needs to be a further 4 weeks at maximum tolerated or recommended dose before concluding that there has been an adequate trial of this medication. There is some debate regarding the minimum recommended period for continuation therapy with antidepressants when a patient experiences a first depressive episode. The CPA/CANMAT guidelines (2001) suggest a minimum of 2 years in older persons (ref. Canadian Psychiatric Association (CPA), Canadian Network for Mood and Anxiety Treatments (CANMAT). Clinical guidelines for the treatment of depressive disorders. Can J Psychiatry 2001;46(Suppl 1):1-91S). Alexopoulos and colleagues’ (2001) Expert Consensus Guidelines on pharmacotherapy of depression endorse a minimum of 12 months (ref: Alexopoulos GS, Katz IR, Reynolds CF, Carpenter D, Docherty JP. The expert consensus guideline series: Pharmacotherapy of depressive disorders in older patients. A Postgrad Med Special Report. New York: McGraw-Hill; 2001). However, there is agreement that those persons who have recurrent depressive episodes should be treated indefinitely, given that the risks associated with relapsing depression is much higher than the risks of a well tolerated antidepressant therapy.

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Trazodone for agitation in patients with dementia A study comparing trazodone to haloperidol reported equal improvement in agitation (Sultzer DL, Gray et al., A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia. Am J Geriatr Psychiatry 1997;5(1):60-9). Trazodone is currently used mostly to provide sedation at bedtime, to help avoid sedatives and benzodiazepines. However, it is sometimes used during the day, in advanced stages of dementia, as an alternative to other pharmacological interventions. It can however cause postural hypotension, excessive sedation and rarely priapism.

A Word about Benzodiazepines in the Treatment of Depressive & Anxiety Disorders Benzodiazepines are no longer recommended for the long-term management of anxiety disorders or insomnia. Their side effect profile is particularly problematic in older individuals with dementia as they can cause confusion and memory loss, ataxia leading to falls and fractures, somnolence and disinhibited behaviour, particularly a concern for patients with frontal lobe impairment. The risks of worsening behavioural difficulties or causing unacceptable side effects far outweigh their benefits. Use may be considered in specific, short-term situations such as withdrawal from alcohol or punctual (not ongoing) relief of situation-specific anxiety (panic attack, catastrophic reaction to a new situation). On the next page you will find the table summarizing treatments most commonly utilized for depressive and anxiety disorders.

BPSD – Handbook for Family Physicians

10 mg

5 mg

25 mg

37.5 mg

15 mg

100 mg

150 mg

Citalopram (SSRI) +

Escitalopram (SSRI) +

Sertraline (SSRI) ++

Venlafaxine (SNRI) -

Mirtazapine(NASA) ++

Bupropion (NDRI) -/+

Moclobemide (RIMA) -

450 mg (A) 600 mg (M)

Wellbutrin SR (M=150mg) XL: M=150 BID

30 mg (A) 45 mg (M)

150 mg (A) 225 mg (new Max dose, 300 mg previously

100 mg (A) 200 mg (M)

10 mg (A) 20 mg (M)

20-30 mg (A) 40 mg/day (M)

Average (A) & Maximum (M) recommended doses Headache, Hyponatremia Agitation Nausea “H.A.N.D.S.” Diarrhea Sweating Somnolence Initially watch for increased agitation, sleeplessness, suicidal ideation and excessive drowsiness. Monitor serum sodium levels at baseline and in first month of treatment. Sertraline: mild anticholinergic activity Individuals usually do not feel subjectively better for 6-8 weeks

Monitor for hypotension. When combined with MAO-B (Eldepryl), MAOI diet/full precautions needed. Interactions: Carbamazepine, narcotics, Sympathomimetic

Seizures, Headaches, Agitation, Rash, Emesis, Sleep disturbance and possible increase in blood pressure

Dry mouth, Drowsiness, weight gain, dizziness, mild anticholinergic activity

Headaches, nausea, elevated BP with higher doses, may also cause hyponatremia

•

• • • • • • •

Monitoring response and side effects

Watch for hypotension

In doses up to 600 mg/day, no dietary precautions needed.

Advanced dementia also associated with increased seizure risk.

Watch for suicidal risk when “energy” increased but still despondent.

Other SSRIs: Paroxetine, fluoxetine, fluvoxamine have more common or severe drug interactions; prolonged side effects (weeks) with fluoxetine due to long elimination half-life

Notes

BPSD – Handbook for Family Physicians

SSRI: Selective Serotonin Reuptake Inhibitor, SNRI: Serotonin, Norepinephrine Reuptake Inhibitor, NASA: NorAdrenergic and specific Serotoninergic antidepressant; SARI: Serotonin-2 Antagonist/Reuptake Inhibitor; RIMA: Reversible Inhibitor of Monoamine Oxydase of type A

Usually not first line treatment: Tricyclics since they have more anticholinergic activity and are more likely to cause hypotension.

Trazodone (SARI) is currently used mostly for HS sedation rather than its antidepressant properties. Initial dose 25-50 mg HS. May need to be repeated as short duration of sedation. Occasionally used during the day in severe BPSD.

Usual starting dose

Preferred (first line) choices & anticholinergic activity - /+ to ++

relapse in recurrent or persistent mood and anxiety disorders.

Antidepressants Summary: Indicated when there is a depressive or anxiety disorder appearing or continuing during the course of dementia: to prevent

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Treatment of Persistent Psychotic Symptoms and Severe Agitation The newer atypical antipsychotic medications (Risperidone, Olanzapine, Quetiapine) are the preferred choice in BPSD with older neuroleptics seldom indicated, except for the very short-term treatment of delirium where haloperidol (Haldol) in small doses (0.25 mg to 1-3 mg daily) may be helpful (see chapter on delirium). These atypical antipsychotics appear to have good efficacy and have been studied in patients residing both in Long Term Care settings and the community. The best evidence from placebo-controlled trials in LTC homes supports the use of atypical antipsychotics for the treatment of persistent psychotic symptoms or severe agitation (Brodaty et al., J Clin Psychiatry 2003b;64:134-43; De Deyn et al., . Int J Geriatr Psychiatry. 2004 Feb;19(2):115-26). The studies compared olanzapine or risperidone to placebo. A recent Cochrane review of the effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease examined 16 placebo controlled trials and included 9 in the meta-analysis (Ballard & Waite, Cochrane Database Syst Rev. 2006 Jan 25;(1):CD003476). The review concluded that risperidone and olanzapine are useful in reducing aggression and risperidone reduces psychosis. Despite their modest efficacy, the significant number of adverse events (compared to placebo) suggested that neither risperidone nor olanzapine should be used routinely to treat residents with aggression or psychosis unless there is marked risk or severe distress. This is particularly true since all antipsychotics have been associated with a 1.6 fold increase of sudden death. Atypical antipsychotics bring their own set of side effects, as there is currently no perfect antipsychotic medication. One should therefore not use these medications without following proper indications, dosage, duration and monitoring of adverse reactions. In addition, specific evaluation of the RISKs of treatment needs to be weighted against the RISKs of not using these medications when indicated. These risks have to be discussed with capable individuals, either the patient or his/her Substitute Decision Maker (usually next of kin).

The Newer Atypicals: Potential Concerns •

Weight gain, diabetic dyscontrol, elevated cholesterol and increased risk for stroke.

•

Associated increase in cardiovascular events and instability, which need to be carefully weighed against the risks of not using an antipsychotic when needed. (Note that all antipsychotics have been associated with increased mortality rates but uncontrolled severe agitation may also lead to mortality and morbidity for the patient and others).

•

All may cause Dizziness, Akathisia, Somnolence, Hypotension (DASH)

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Newer Antipsychotics

Side Effects to Consider in Selection of Atypical Antipsychotics For all atypicals: Dizziness, Akathisia, Somnolence, Hypotension (DASH)

Olanzapine

Glucose watch! Weight gain Hypotension, significant anti-cholinergic effects if dose greater than 10 m per day

Risperidone

Extrapyramidal watch! Hypotension, Somnolence, at doses greater than 2 mg per day: EPS and akathisia (agitation)

Quetiapine

Sedation watch! Orthostatic hypotension, excessive somnolence

Treatment of Dementia: Cognitive Enhancers and Glutaminergic Agents There is evidence that cholinesterase inhibitors (e.g., donepezil, galantamine and rivastigmine) and memantine may delay the emergence of behavioural symptoms in Alzheimer’s disease and other dementias. A recent meta-analysis of cholinesterase inhibitors in older adults with Alzheimer’s disease suggested a small but statistically significant improvement in studies using the NPI (Neuropsychiatric Inventory) as an outcome measure and a trend towards benefit in studies using the ADAS-noncog (Trinh et al., 2003, Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer’s disease: a meta-analysis. JAMA 2003;289(2):210-6.) BPSD that are common in moderate to late stages of dementia can be minimized or delayed by the appropriate treatment of the underlying dementia. This particularly applies to the early stages of Alzheimer’s disease and Lewy Body Dementia. Currently available first line of treatment, ideally initiated when the dementia and cognitive losses are still mild, are cholinesterase inhibitors, namely donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl). Before cholinesterase inhibitors are initiated, one has to consider possible “contra-indications” such as asthma and seizure disorder, which can be worsened by these medications as well as low pulse and second degree atrio-ventricular blocks that could lead to syncopal episodes, falls and fractures.

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Cholinesterase Inhibitors Can Cause or Make these Problems Worse:

Asthma

Seizures

Supraventricular Dysfunction; Sick Sinus Syndrome

Low pulse (Bradycardia)

Nausea, and peptic ulcer (Should avoid NSAIDS)

Common side effects for cholinergic enhancers include Muscle cramp, Insomnia, Nausea, Diarrhea, summarized in the MIND acronym. However the most commonly reported side effects are gastro-intestinal side effects and vivid dreams. For Glutaminergic (NMDA) agents such as memantine, used in moderate stages of dementia and often in combination with a cholinesterase inhibitor, CHECK reminds us of common side effects: • Confusion, Headaches, Equilibrium, Constipation, Kidney function In monitoring the response to memantine, C - SHAPE may be a useful mnemonic: Cognitive improvement (awakening) Socialization: apathy and communication often seen at 1 month Household tasks: such as setting the table taking the garbage out, finding things ADL: such as using the toilet, washing, feeding oneself Persecutory ideation: delusions Excessive activity (agitation) Keep in mind that the expected therapeutic benefit is to maintain function and to improve and prevent onset of disabilities in the areas listed above.

Treatment of Severe Agitation Likely Due to Delirium When symptomatic pharmacological management of delirium is warranted, it is important use the lowest possible dose of medication. Unfortunately, the doses of psychotropics used during an acute delirium are often excessive and continued long beyond the desired treatment period: this leads to depressed sensorium and delays recovery from the delirium.

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Best evidence to date, summarized in the Canadian Coalition for Seniors’ Mental Health Guidelines on the Assessment and Treatment of Delirium (2006), suggests the use of low doses of haloperidol (0.25 – 1 mg IM per dose or 1-2 mg per day) for as short a period of time as possible (days) during acute delirium not due to withdrawal from alcohol or benzodiazepine. Baseline electrocardiogram is recommended, looking for QTC intervals greater than 450 msec or 25% over baseline as a reason to obtain cardiology consultation and/or consider discontinuation. While prolonged use of Haloperidol is very likely to cause unacceptable Parkinsonian symptoms, benztropine mesylate should not be used prophylactically due to its anticholinergic properties. Akathisia is another common and under recognized side effect of antipsychotics, which may be confused with continuing delirium or may make the delirium worse. However, haloperidol should be avoided entirely if the patient has a diagnosis of Lewy Body Dementia. While atypical antipsychotic drugs have become first line treatment in the management of severe and persistent agitation or psychosis in dementia, there is still limited data on their use for the specific treatment of agitation due to delirium. They may be considered as alternate agents in patients who already have Parkinson’s disease and for those who have a history of severe side effects with previous use of haloperidol. Dosage should be low (e.g. risperidone, 0.5 mg daily or quetiapine, 25 mg once or twice a day or olanzapine, 2.5 mg daily). In the presence of possible Lewy Body Dementia, Quetiapine (Seroquel) is preferred, as it seems less likely to cause EPS than Risperidone or Olanzapine. For acute alcohol or benzodiazepine withdrawal delirium, a shorter acting benzodiazepine such as lorazepam is the recommended choice for its ease of administration (parenterally and sub-lingually) and its elimination half-life will allow for safe titration to light somnolence while minimizing the risks of prolonged over-sedation. Antipsychotics may be added but only when the agitation and psychotic symptoms of alcohol withdrawal cannot be adequately controlled with benzodiazepines alone. It is important to note that some delirious patients become more agitated on benzodiazepines, and some delirious states (e.g. delirium due to hepatic failure) are worsened by benzodiazepines. It is therefore important to monitor response to treatment carefully. Cholinesterase inhibitors have been used with variable effect in the literature. There are reports of the successful use of donepezil in the treatment of super-imposed delirium in patients with pre-existing Alzheimer's Disease and cholinesterase inhibitors may be particularly useful in patients with Lewy Body Dementia who may present with repeated delirium-like episodes when no other physical problem is identified.

BPSD – Handbook for Family Physicians

5-7.5 mg (A) 10 mg (M) 1-2 mg (A) 5 mg/day (M)

0.5 mg

2.5 mg

0.5mg

Risperidone +/-

Olanzapine ++

Haloperidol USED IF ACUTE DELIRIUM SHORT-TERM

Extrapyramidal symptoms (rigidity, Pisa syndrome, shuffling gait, tremors, etc.) if used more than a few days.

Weight gain and increased vascular risk factors (lipid profile, diabetes). Hypotension, anticholinergic side effects (dry mouth, constipation, etc.).

Hypotension and extrapyramidal side effects.

Hypotension and oversedation, mild anticholinergic properties at higher doses, some weight gain. Sedation may occur early but full antipsychotic effect usually takes several weeks.

Monitoring response and side effects All atypical antipsychotics can cause side effects. However, side effects more common with specific medications are outlined below.

Used mostly in acute management of delirium when no Lewy Body Dementia. If possible LBD, consider quetiapine or trazodone for short-term sedation.

Beyond 10 mg daily, anticholinergic activity may worsen dementia and cause delirium.

Wide titration range. If no effect within 150 mg daily, may consider changing medication.

All have been noted to have increased associated mortality but may also prevent serious injury. Discuss risk/benefits for informed decision and consent.

Breathing problems (asthma, COPD) Peptic ulcers (esp. if ASA or NSAID is also taken) Seizures Syncope, bradycardia and second degree block on ECG (B-blockers) Heart disease (CHF, CAD) Drug interactions (anticholinergics decrease efficacy and some SSRIs can increase blood levels: e.g. paroxetine, fluoxetine and fluvoxamine

Not recommended if severe renal impairment Antacids may increase blood levels

Donepezil (Aricept)

Memantine (Ebixa)

Galantamine (Reminyl)

Rivastigmine (Exelon)

Risk evaluation and possible contra-indications

Choices

10 mg BID * 5 mg BID if CrCl less than 60

ER 24 mg Q AM

BPSD – Handbook for Family Physicians

5 mg daily X 1 week 5 mg BID X 1 week 10 mg AM and 5 mg in PM X 1 week 10 mg BID

ER 8 mg AM for 4 weeks then, 16 mg in AM for 4 weeks and 24 mg if no SE

6 mg BID with meals

10 mg daily

5 mg daily for 4 to 6 weeks 1.5 mg BID for 4 weeks, increase by 1.5 mg BID Q 4 weeks

Maximum recommended dose

Usual starting dose

Treatment of dementia: cognitive enhancers (donepezil, rivastigmine, galantamine and glutaminergic agents (memantine)

May improve cognition, socialization, ADLS and decrease BPSD in moderate to severe Alzheimer’s disease and vascular dementia Most common side effects: Confusion, Headaches, Agitation, Insomnia and Dizziness Urinary incontinence and UTIs can occur. Hallucinations if dose too high.

May improve cognition, socialization, prevent decline in ADLs. May save caregiver time. Watch for “MIND”: • Muscle cramps; • Insomnia and agitation • Nausea & vomiting (if titration too rapid); (consider propantheline 7.5-15 mg or domperidone 10 mg TID if severe) • Diarrhea • Weight loss with longer term use.

Monitoring and side effects.

Pharmacological treatment of delirium: Use haloperidol unless Lewy Body Dementia (see above notes) or withdrawal delirium from alcohol or benzodiazepines, when we recommend using a benzodiazeopine such as Lorazepam 1- 2 mg Q 2 hours initially until symptoms improve or sedation occurs. Re-assess Q 6-8 hours on the first day to adjust dosage, provide symptom control without oversedation and estimate daily dose to taper from. Take more than twice the time to taper the benzodiazepine than with younger patients.

Usually not first line treatment: Chlorpromazine is very anticholinergic and hypotensive. Continuation of older neuroleptics may however be warranted in some patients with schizophrenia, particularly when switching to newer (atypical) antipsychotic medication has failed to control schizophrenia. May consider Loxapine or Perphenazine if atypicals fail.

1 mg daily (A) 2-3 mg daily (M)

undetermined (A)(M)

25-50 mg

Quetiapine +

Average (A) & Maximum (M) recommended doses

Usual starting dose

Preferred (first line) choices & anticholinergic activity -/+ to ++

non-pharmacological interventions or 2. Continuation of treatment of schizophrenia and delusional disorders that preceded dementia.

Antipsychotic Medications Summary: for 1. Persistent and distressing psychotic symptoms or agitation that is not responsive to

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Treatment of Behavioural Problems Due to Lewy Body Dementia Antipsychotics should generally be avoided in residents with DLB as they may develop severe adverse effects. If an antipsychotic is absolutely necessary in residents with Parkinson’s disease, quetiapine may be less likely than other atypicals to exacerbate the motor symptoms (Friedman & Factor, Mov Disord; 15(2):201-11; 2000). One placebocontrolled RCT of rivastigmine (a cholinesterase inhibitor) in Dementia with Lewy Bodies (DLB) found benefits in behavioural symptoms including hallucinations (McKeith et al., Lancet 2000;356:2031-6). • • •

Cholinesterase inhibitors are now first line of treatment for BPSD of Lewy Body Dementia. Several weeks are needed to evaluate their therapeutic efficacy. If cholinesterase inhibitors are ineffective or it is too early in treatment, consider low doses of trazodone for sedation (watch BP). If antipsychotic medication is absolutely necessary, document risks with Substitute Decision Maker and consider low doses of quetiapine (Seroquel).

Treatment of Inappropriate Sexual Behaviour There is very limited evidence, primarily case reports, in support of pharmacological treatment for inappropriate sexual behaviour. In fact, it is rarely necessary to resort to medications for these problems and it is of utmost importance to utilize the framework outlined in previous chapters to ensure that the care team understands the causes of these behaviours before concluding that there is a need to decrease sexual drive. Options for treatment include Serotoninergic antidepressants (SSRIs), anti-psychotics or antiandrogens. Hormonal therapy may be considered for men who put others at risk when other interventions have failed. Common side effects of hormonal therapy include weight gain, breast pain, depression and oedema. There may be an increased risk of thromboembolism. Black and colleagues (Journal of Geriatric Psychiatry and Neurology; 2005; 18: 155-62) recently carried out a review of these behaviours and available treatments. In the management of inappropriate sexual behaviour, it is important to avoid (or remove) benzodiazepines, which cause disinhibition and worsens these difficulties. Furthermore, it is useful to remember that trazodone can occasionally cause priapism, which then gets misinterpreted as inappropriate sexual behaviour.

Treatment of Sleep Disturbances Before specific symptomatic treatment of sleep disturbances can be considered, one has to evaluate and understand the underlying factors and possible causes of discomfort and sleep disruption. The most common Physical causes are pain, nocturia and incontinence. One also needs to consider the possibility of sleep apnea, incipient heart failure, restless leg and periodic leg movement as well as REM Behavioural Disorder and seizures. In Long Term Care settings in particular, common causes would include insufficient physical activity, excessive daytime napping, noise or too much light in the environment at night. Other causes, such as specific psychiatric disorders such as depression or bipolar illness have to BPSD – Handbook for Family Physicians

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be considered. Treatment therefore starts by addressing these underlying contributing factors as specifically as possible. When pharmacological management is essential, it may be useful to consider Trazodone, 25 to 50 mg at bedtime for its sedating properties. It can however cause postural hypotension, which will need to be monitored. If depression is one of the underlying cause, one might consider the use of Mirtazapine for its sedating properties, taking care to remain in a low dose range to avoid anticholinergic activity. When the cause of the insomnia will clearly be temporary (a few days), and given no contraindication to their use (such as sleep apnea), low doses of short-acting benzodiazepines (Oxazepam, lorazepam) or Zopiclone may be considered , keeping in mind the possible risks of ataxia, falls, worsening confusion and disinhibition.

High-Risk Situations: Capacity is an Issue and Psychotropics are Required As clearly outlined in this chapter, pharmacological management of behavioural difficulties requires good knowledge of medications, including their appropriate use, indications and side effect profile. Physicians have to explain the risks and benefits to the capable patients or their Substitute Decision Makers or next of kin. When side effects are rare but serious, a discussion about the risks of harm to self and others if BPSD are not treated need to be weighed against the risks (e.g. increased risk of CVA or sudden death with antipsychotics). In this discussion, it will be important to outline possible alternatives and nonpharmacological interventions that have been tried to date. It is easier to engage families and Substitute Decisions Makers early rather than having to address their concerns about a prescription that has already been written, except of course in cases when emergency treatment was clearly required (such as in a delirium).

Conclusion Pharmacological management of BPSD requires a full understanding of the appropriate indications for the use of medications and reflecting on issues that may influence the need for their use. Except in emergency situations, pharmacological management should occur only after non-pharmacological approaches have been put in place, although medications will often be required if a specific psychiatric diagnosis is identified (e.g. depression or anxiety disorder). Non-pharmacological interventions need to be continued during the implementation of pharmacological treatment. For situations where medications are needed only for a limited period of time (e.g. psychotic symptoms or sleep disorders), it will be important to set an appropriate review date (3-6 months for persistent psychotic symptoms and 1-2 weeks for sleep problems) and attempt tapering or discontinuation when possible. On the other hand, some disorders will require ongoing maintenance treatment (such as recurrent depressive episodes or bipolar illness). Ongoing monitoring of these treatments will be required.

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References: Friedman JH, Factor SA. Atypical antipsychotics in the treatment of drug-induced psychosis in Parkinson's disease. Mov Disord 2000;15(2):201-11. McKeith I, Del Ser T, Spano P, Emre M, Wesnes K, Anand R, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 2000;356:2031-6 Black B, Muralee S, Tampi R. Sexually inappropriate behaviours. Journal of Geriatric Psychiatry and Neurology; 2005; 18: 155-62

BPSD – Handbook for Family Physicians

BPSD – Handbook for Family Physicians