Treatment for behavioural and psychological symptoms of dementia
Diagnosis and treatment of dementia
- Visual Hallucinations
- Motor restlessness
- Sleep disturbance
- Sexual behaviour
Relationship of treatment of BPSD to differential diagnosis
Whilst some BPSD are more common in vascular dementia (eg depression, lability and perhaps aggression), DLB (visual hallucinations, REM sleep behaviour disorder), or frontal lobe dementia (apathy, sexual disinhibition) the implications for drug and non-drug treatment implications of these are not generally different in the different diagnostic categories. Therefore, except where otherwise stated, the treatment options delineated in this section apply across diagnoses.
Non-pharmacological interventions of BPSD
Nonpharmacological interventions are the first line treatment of choice for most patients with non-cognitive disturbances (I).
Non-pharmacological interventions which merit consideration include the following (II):
- Staff training.
- Nursing care interventions, e.g. altering approach during intimate care and bathing.
- Environmental interventions, e.g. dementia safe and friendly environments, wandering paths, bright-light therapy (?).
- Activities, e.g. structured activity programmes, physical rehabilitation and physical exercises.
- Social contact, e.g. one-on-one interaction, pet therapy, simulated presence.
- Timalation (interaction in which the senses are the main focus for engagement rather than interactions which involve an intellectual or emotional component), e.g. music, aromatherapy, massage, dance and movement, multi-sensory approaches such as snoezelen.
- Standard psychological therapies, e.g. behavioural therapy, validation, resolution, reality orientation, reminiscence.
- Alternative therapies, e.g. art therapy.
A detailed account of these interventions and their effectiveness is given elsewhere in the EUROCODE report.
Principles of drug treatment of BPSD disturbance
During any drug treatment
- There should be a full discussion about the possible benefits and risks of treatment (I).
- The choice of drug should be made after an individual risk– benefit analysis (II).
- The dose should be low initially and then titrated upwards (I)
- At each stage, the possibility that concomitant medical illness may be exacerbating or causing the problem should be revisited (II)
- Because the underlying behaviour often fluctuates, an attempt should be made to withdraw any psychotropic drug given for BPSD after not more than 4-6 weeks (III). This is especially relevant when potentially sedating drugs are used, or when the behaviour in question has settled .
- Drugs which have not worked should be withdrawn before other drugs are tried (II).
- The possibility of drug interactions should be remembered (II). For example, the effects of cholinesterase inhibitors and SSRIs on appetite and nausea may be additive. Similarly, the sedative effects of psychotropic drugs (eg of trazodone and atypical antipsychotics) may be additive.
- Changes in target symptoms and cognition should be assessed and recorded regularly (II).
With two notable exceptions (quote CALM-AD, CATIE-AD), drug studies have been confined to identifying first line therapy rather than an algorithm. Because of this dearth of evidence or detailed previous guidance, and because of the great clinical importance of this area, a hierarchical sequence of treatment options is proposed: first line, second line, third line etc.
Assessment of agitation
The term ‘agitation’ is used in different ways by different authorities, which gives rise to confusion. Here, we define its core feature as increased arousal.
This increased arousal is commonly associated with (but is not the same as) anxiety, psychosis, aggression and motor restlessness.
It is helpful to define the contributions of these features to the agitation because, where such definition is possible, treatment strategy should be directed first at the dominant component. Where no such definition is possible, the strategy outlined for psychosis should be followed.
Anxiety may be an expression of many forms of cerebral impairment, arising from the sense of losing control. It may take the form of repetitive questioning, for example about upcoming appointments. Fear of abandonment is common. Anxiety may arise because of an underlying psychosis, in which case the treatment should be directed at the psychosis. Additional features of depression should also be actively sought and, if present, should determine the treatment.
It is also useful to distinguish between different types of psychosis for several reasons.
First, the presence of visual hallucinations and illusions ‘trumps’ other BPSD in determining which course of treatment to follow. (see sections on Assessment and treatment of visual hallucinations below)
Second, the presence of persistent suspiciousness is an important sign because antipsychotic use may be more appropriately used in such cases.
It is useful to distinguish suspiciousness from an unshakeable belief in an erroneous idea (delusion). Delusions in dementia take variable forms and are sometimes secondary to poor memory. Therefore, the presence of a delusion per se should never automatically trigger the prescription of an antipsychotic.
For example, the effect of dementia on memory means that patients often ‘live in the past’, (e.g. thinking that long-dead parents are still alive) and their sense that their home is not their own sometimes seems related to this. Although the phenomenon is also sometimes related to a primary sense of perplexity and unfamiliarity, it is, in practice, not useful to define these sorts of belief as delusions requiring antipsychotic treatment, even when they are unshakeable.
On the other hand, suspiciousness associated with the belief that someone has been replaced by an imposter, seems more likely to have its origins directly in a brain change and, particularly if associated with hostility may respond to an antipsychotic.
The belief that someone is stealing from them may be due to a combination of factors: premorbid personality, a tendency to hide things and poor memory for where they have placed things. Suspiciousness may also be an additional feature.
The term ‘aggressive’ can be applied to behaviours which range from occasional mild verbal irritability to frequent sustained physical assaults. A full description of the behaviour is therefore required, including an account of the predisposing factors, the precipitants, the behaviour itself (including the nature, severity, frequency, motivation, setting) and any perpetuating factors. Depression commonly underlies irritability. Hostility and psychosis are often linked.
Apathy is more common than restlessness in dementia of all forms. However, when patients do develop restlessness it typically persists for several years. Some patients go through a phase of trailing after caregivers. This may be driven by anxiety, poor memory, or a more basic drive to move. In severe dementia, the acrophase is shifted which means that such patients sometimes have a pattern of being at their most active in the early evening.
Treatment of Agitation
First line treatment
Increased arousal, anxiety, psychosis, aggression and restlessness are fluctuating symptoms which are very often dependent on psychosocial or physical health factors. First line management should therefore always be directed to changes in the approach of carers or to treatment of physical discomfort (see ’Non-pharmacological interventions’ above).
Second line treatment
A strategy of watchful waiting is then usually justified. The exception is those with serious violence and aggression (see below).
The duration of such waiting will be defined by the skill and resources of the caregivers, the duration of the behaviour before presentation, its severity and its impact on others.
Third line treatment
The vulnerability of patients with dementia to the side-effects of psychotropic medication means that where there is little to choose in terms of efficacy, drugs with better side-effect profiles should be used first. SSRIs are therefore a suitable first choice for drug therapy for use in primary care before referral to specialists.
If non-pharmacological strategies have been attempted and failed, and the agitation persists, an SSRI (e.g. citalopram (starting at 10mg and increasing up to 20mg daily) or sertraline (starting 50mg increasing to 150mg daily) or trazodone (starting dose 50mg daily increasing up to 100mg twice daily) is recommended for third line treatment of uncomplicated auditory hallucinations or delusional ideas with suspiciousness. This recommendation is made on the basis that the adverse side-effect profile of antidepressants is less clearcut than that of antipsychotics, there is evidence of efficacy of both, and there is evidence of no differential benefit in the two classes of drugs (52;53).
If non-pharmacological strategies have been attempted and failed, and the agitation persists, anxiety with additional features of depression such as ideas of hopelessness, guilt and diurnal variation should be treated first with an SSRI (eg citalopram or sertraline). However, anxiety without depression, particularly when associated with repetitiveness should be treated with a cholinesterase inhibitor.
If non-pharmacological strategies have been attempted and failed, trazodone (or an SSRI eg citalopram or sertraline) is widely used for aggression which necessitates an element of sedation. Trazodone may also be more useful if sedation at night is required. The starting dose of trazodone is 50mg od, increasing up to 100mg bd. Higher doses are occasionally needed but are usually oversedating.
Fourth line treatment
Psychosis or aggression
When auditory hallucinations or delusional ideas with suspiciousness have failed to respond to non-pharmacological and antidepressant strategies, then the antidepressant should be stopped. A cholinesterase inhibitor should then be tried. For those already taking a cholinesterase inhibitor, a low dose of an atypical antipsychotic is appropriate. Risperidone 0.5mg increasing to 1.5mg daily is suggested. Risperidone is ‘indicated for the short-term treatment (up to 6 weeks) of persistent aggression in patients with moderate to severe Alzheimer’s dementia unresponsive to non-pharmacological approaches and when there is a risk of harm to self or others’. Although quetiapine is ‘not approved for this indication’, it is widely used in doses starting at 25mg increasing up to 200mg. Caution is required in patients with cerebrovascular risk factors.
The manufacturers of olanzapine, aripiprazole and ziprasidone recommend that they are not used in dementia.
Antipsychotic medication in dementia
Antipsychotic medications as a group are associated with a number of severe adverse events, including increased risks for falls, death, cerebrovascular accidents, neuroleptic malignant syndrome, hyperlipidemia, weight gain, diabetes mellitus, sedation, parkinsonism, and worsening of cognition.
Even a few weeks of typical (first generation) antipsychotics can cause patients with dementia to develop tardive dyskinesia, particularly orofacial dyskinesia. This is commonly irreversible. Typical antipsychotics should therefore not be used in dementia.
Anticholinergic agents (benztropine (Cogentin) or trihexyphenidyl (Artane)) should not be used for the treatment of antipsychotic-induced extrapyramidalism in dementia since they exacerbate cognitive impairment.
If an SSRI has been unsuccessfully tried, it is unlikely that trazodone will be successful. The SSRI should be stopped. A cholinesterase inhibitor should then be tried.
If a cholinesterase inhibitor has been unsuccessfully tried, an SSRI or trazodone should be tried. Trazodone may be useful if sleep is disturbed and gait secure.
Fifth line treatment
Psychosis or aggression
If an atypical antipsychotic has not been successful, then it should usually be withdrawn. Mild persistent symptoms tend to improve on withdrawal of antipsychotics. Reassessment of physical health (especially extrapyramidal symptoms) and psychosocial factors is needed.
In cases of severe symptoms which have partially responded, it may be necessary to continue the antipsychotic.
A short course of shorter-acting minor tranquillisers may be tried, eg chlormethiazole, buspirone, lorazepam, oxazepam or alprazolam , oksazepam. These are not recommended for other than brief use because of risks of daytime sedation, tolerance, rebound insomnia, worsening cognition, falls, disinhibition, and delirium. Longer acting benzodiazepines such as diazepam should be reserved for cases where a valuable clinical response has been achieved with a shorter acting drug and the problem has re-emerged when it is stopped.
Sixth line treatment
Psychosis or aggression
The evidence for oxcarbazine and carbamazepine as a treatment for severe agitation in severe dementia is based on a single small RCT. Side-effects, particularly ataxia, are prominent and dose dependent, so low starting doses (eg 50mg twice daily, or even once daily) are important. Titration should be on the basis of clinical effect, not blood levels.
Atypical antipsychotics can be used for anxiety when other strategies have failed because, as mentioned above, anxiety can be associated with an underlying psychosis.
Seventh line treatment
Psychosis, aggression or anxiety
Memantine may occasionally be useful in the treatment of persistent severe symptoms, particularly when the patient has severe dementia and is declining rapidly. There is preliminary evidence that conjugated equine oestrogen up to 2.5mg daily may be helpful.
Eighth line treatment
Gradually withdraw all psychotropic medication.
Drugs which are not recommended for use in agitation
Propranolol is unlikely to be of benefit for treatment resistant psychosis or aggression.
Lithium is not recommended for treatment of aggression because of the side-effect profile. There is good evidence that valproate is ineffective.
Assessment of visual hallucinations
It is important to establish whether visual hallucinations are present because they are commonly (>80%) associated with other features which indicate a diagnosis of dementia with Lewy bodies (DLB) and are associated with more intense cholinergic deficits. Nevertheless, causes of delirium should always be actively sought and excluded before assuming that the visual hallucinations are arising solely as a result of the dementia.
Useful screening questions, which should lead to further exploration if answered in the affirmative, are ‘Does your imagination play tricks with you?’ and ‘Do you have vivid dreams at night – or day dreams?’ It is important to know about the duration, persistence and frequency of visual hallucinations in order to assess the benefits of any treatment.
Visual hallucinations do not always merit treatment. They may be infrequent. Patients also commonly recognise that the hallucinations are not real and are not particularly bothered by them. Sometimes, they find them comforting. More commonly however, other concomitant impairments also improve with treatment. These include fluctuations in cognitive and functional ability, and also the aggression and irritability which can occur, particularly when insight is lost.
For this reason, the presence of visual hallucinations should ‘trump’ that of other BPSD in determining the hierarchy to follow.
Treatment of visual hallucinations
Drugs which might be contributing to the generation of hallucinations, particularly anticholinergics such as benzhexol or procyclidine, dopamine agonists, L-DOPA or other antiparkinsonian medication should be rationalised as far as possible. Cessation of mildly anticholinergic drugs such as bladder stabilisers or very small doses of tricyclic antidepressants rarely seems to help.
Recurrent visual hallucinations are typically more likely to occur when the patient is unstimulated, tired, or when light levels are low. Increasing light levels or improving the patient’s eyesight (eg cataract removal) can occasionally be helpful. Soft furnishings which have elaborate patterns seem to promote illusions. Covering them with monochromatic material can occasionally be helpful.
A cholinesterase inhibitor should be considered early in the management of visual hallucinations.
Often the dose of ChEI attained may be higher and can be reached more quickly in patients with DLB/PDD than in those with AD.
However, in addition to the usual gastrointestinal symptoms, ChEIs may be particularly likely to cause hypersalivation, lacrimation, and urinary frequency in patients with DLB. A dose dependent exacerbation of extrapyramidal motor features may occur in a minority.
If ChEIs are ineffective or if more acute symptom control of behaviour is required, it may be difficult to avoid a cautious trial of an atypical antipsychotic. The clinician should warn both the carer and patient of the possibility of a severe sensitivity reaction. Quetiapine is usually the drug of choice because of its lower potential to cause extrapyramidalism.
In severe cases, the balance between ChEIs, L-DOPA and quetiapine can be very difficult to manage. Rivstigmine patches merit consideration if, as sometimes seems to be the case, the ability to swallow is dependent on adequate intake of ChEI.
This phenomenon is poorly understood and described. Pharmacological strategies usually fail and there is no consensus on which are valuable. Occasionally a very low dose of atypical antipsychotic such as risperidone can help.
Recent evidence suggests that a combination of bright light therapy and melatonin may be of limited benefit .
People with dementia who present with depression should be offered treatment for these symptoms.
Therapies demanding intense cognitive engagement are unlikely to be helpful in those with memory impairment. Non-pharmacological interventions such as social stimulation, activities, and counselling should therefore be used as first line treatment for people with dementia with comorbid depression. These are discussed in more detail elsewhere in the EuroCoDe report.
If non-pharmacological interventions are unsuccessful then anti-depressants should be offered.
Where antidepressants are chosen the following principles should be followed
- The choice of antidepressant should be carefully weighed against the side-effect profile and the symptoms of the patient.
- Drugs with anti-cholinergic effects should be avoided, particularly in DLB and PDD
- Careful explanation to the patient and carers should be made of need for compliance, withdrawal effects and the leg before symptom improvement
An SSRI should be tried. Citalopram and sertraline seem to be slightly better tolerated than other SSRIs.
The SNRIs mirtazapine and venlafaxine are recommended for second-line
If antidepressants are ineffective then a trial of cholinesterase inhibitors may be undertaken.
If the depressive symptoms do not resolve with pharmacological treatment, then patients with severe, treatment resistant depression, a course of ECT may be undertaken.
Sleep disturbance and disruption of circadian cycle
Assessment of sleep disturbance and disruption of circadian cycle
Depression is common in dementia. Therefore, in patients who complain of insomnia, other symptoms of depression, including early morning waking and diurnal variation in mood, should be actively sought.
As with other BPSD, enquiries about the patient’s sleep pattern should, where possible, involve discussion with an informant. Use of wrist actigraphy or external movement sensors may occasionally be useful when the extent of the disruption is not clear, for example when the quality of information from staff in institutional care is very poor, or when the patient lives alone at home.
Treatment of nocturnal sleep disturbance
Hypnotic drugs are sometimes used inappropriately. It may be preferable to allow the patient to be awake at night than to run the risks associated with hypnotic medication, all of which increase the risk of falls and increased confusion.
Sleep disorders markedly increase in the later stages of the disease, may result in a day/night reversal and can be resistant to treatment.
A regular daily routine which includes physical exercise and adequate light exposure should be instituted if at all possible. Daytime napping should be reduced in frequency and duration by maximising social interaction or other stimulating activity. Caffeinated drinks after mid-afternoon and any night-time drink can increase night-time wakings.
Sedating drugs are a common cause of circadian disruption. A trial without such drugs should be attempted.
Alternatively, the timing and dose of sedating medication may need adjusting. The slower absorption and metabolism of drugs in the elderly mean that occasionally hypnotic drugs should be given in the mid or early afternoon to achieve an effect at night-time.
Excessive daytime sleepiness commonly coexists with apathy. Apathy is commonly more of a problem for the carer than the patient. It should therefore only be treated when it is particularly severe or causing particular distress for the carer which then impacts on the patient. ChEIs improve apathy and motivation and should be tried where apathy is prominent.
Drugs which may improve sleep include trazodone (eg 50-250mg nocte), zolpidem (5mg), zopiclone (3.75-7.5mg), or zaleplon (5mg).
Benzodiazepines are not recommended for other than brief use because of risks of daytime sedation, tolerance, rebound insomnia, worsening cognition, falls, disinhibition, and delirium. A brief course of short acting benzodiazepines (Lorazepam 0.5-1mg) may occasionally break a cycle of nocturnal sleep disturbance and daytime napping.
Chlormethiazole is used as an alternative (1-3 capsules, 5-15mls)
Chloral hydrate and now rarely used.
Some advocate using such medication and alternating with other drugs every few weeks in an attempt to prevent the problems of tolerance which tend to develop.
Drugs which are not recommended for treatment of insomnia
Typical or atypical neuroleptics should not be used for the treatment of insomnia.
The management of behaviours which have, or appear to have, sexual connotations depends almost entirely on the context and the nature of the behaviour. This ranges from inappropriate but innocently intended sexualised remarks which are manifestations of disinhibition to more intrusive invitations, display behaviours, masturbation and sexually motivated touching and pursuit, or attempts at genital contact or penetration.
In severe dementia, this sexual behaviour is commonly associated with frontal lobe disinhibition. It can also occur with hyperdopaminergic states such as overuse of L-DOPA or other parkinson’s medication.
There are no RCTs restricted to this group of patients. An SSRI can sometimes effectively reduce libido and is the safest first option. A small dose of an atypical antipsychotic is sometimes helpful in more severe, persistent cases. The butyrophenone antipsychotic benperidol has an indication for antisocial sexual behaviour (not limited to dementia), but the balance of benefit means that an atypical is probably now preferred. Antiandrogenic medication should be the next step, the safest of which, in men, are conjugated oestrogens. Cyproterone and medroxyprogesterone should be reserved for the most serious, dangerous, treatment-resistant cases because they are generally very sedating.
Severe Violence and Aggression
People with dementia who display violence or aggression that present a risk to themselves or others should be treated in a low-stimulation environment to minimise this risk.
If a decision is made to use immediate sedation the following principles should be followed
- The lowest dose possible should be used
- Single agents rather than combinations should be used
- Oral agents should be used as first line therapy
- If oral agents are not appropriate then intramuscular injections are second choice, but long acting depot medication should not be used
- Intravenous agents should only be used in extreme circumstances due to the risks
- Where sedating agents have been used, people with dementia should be monitored closely for vital signs and signs of significant side effects
- The incident should be discussed with the caregivers of the person who was sedated and a clear explanation of the incident given
- If antipsychotics are used there should be close monitoring for extrapyramidal side-effects
Where drugs are chosen to treat severe violence and aggression in patients with dementia irrespective of the cause of the dementia, the following therapies are suggested.
First line treatment
Oral lorazepam 1-2mg
Add oral risperidone 1-2mg
Repeat oral lorazepam and risperidone
Intramuscular agents – lorazepam 1-2mg
Intramuscular haloperidol 3mg
Repeat intramuscular lorazepam and haloperidol
Drugs to be avoided
IM diazepam and IM chlorpromazine
The companies responsible for aripiprazole, olanzapine, ziprasidone specifically caution against their use in dementia.
Last Updated: Thursday 08 October 2009