Dementia: drugs used to relieve depression and behavioural symptoms

People with dementia may develop mood disorders such as depression, behavioural problems with symptoms such as restlessness or aggression, or psychiatric symptoms such as psychosis (delusions and hallucinations). This factsheet describes the different types of drugs that may be prescribed to treat these symptoms.

It is important to try to understand and address the underlying causes that may have triggered a person's symptoms. However, when behavioural or psychiatric symptoms are severe, extremely distressing, or causing risk to the person or others, and if psychological treatments have not worked, it may be necessary to prescribe medication.

The treatment of depression is slightly different, as depression has a major impact on people's functioning and quality of life. Mild depression can be treated with psychological treatments, but more severe clinically significant depression should be treated with antidepressant medication (see also Factsheet 444, Depression).

When should drugs be used?

Drugs should be avoided unless they are really necessary. Before any of the drugs mentioned in this factsheet are prescribed, it is essential to ensure that the person with dementia is physically healthy, comfortable and well cared for. Whenever possible, the person should be helped to lead an active life, with interesting and stimulating daily activities. In this way it is often possible to avoid the use of sedative drugs altogether.

Some symptoms should always be treated, including:

• pain, and any underlying medical conditions (such as infections), as these can often cause or worsen behavioural symptoms
• problems with eyesight or related medical problems, such as cataracts, as these can significantly contribute to the development of visual hallucinations and can increase their vulnerability
• hearing difficulty, as if left untreated this can make a person more confused.

Possible effects

Drugs will be more effective if they are taken exactly as prescribed by the doctor, in the correct dose, and are monitored regularly for side-effects.

• If symptoms are difficult to control, the GP may refer to a specialist for further advice.
• Do not expect immediate results. Benefits may take several weeks to appear, particularly with antidepressants and antipsychotics.
• Some drugs, such as antidepressants and antipsychotics (often called major tranquillisers or neuroleptics), need to be taken regularly to have an effect. These drugs are not helpful when given on an as-needed basis. This should only be done after discussion with the doctor.
• All drugs have side-effects that may worsen symptoms. Side-effects may occur early or late in the course of treatment, so it's important to ask the doctor what to expect.
• Side-effects are usually related to the dose. The doctor will usually 'start low and go slow', gradually increasing the dose until the desired effects are achieved.
• Bear in mind that certain combinations of drugs may counteract each other. Remind your doctor if other medications are being taken. All medications should be taken to clinic and hospital appointments.
• Don't assume that a drug that has proved to be useful at one time will continue to be effective. Dementia is a degenerative condition, so the chemistry and structure of the brain will change during the course of the illness.
• Once treatment has been established, it is important that it is reviewed regularly. In most circumstances, drugs for behavioural problems should not be prescribed for more than three months without a trial of stopping the treatment.
• Remember that many of the drugs taken to treat mood symptoms, behavioural problems and psychiatric symptoms can be dangerous if accidentally taken in large quantities, so make sure medicines are kept safe and secure.

What do drug names mean?

All drugs have at least two names − a generic name, which identifies the substance, and a proprietary (trade) name, which may vary depending upon the company that manufactured it. (For example, Aricept is the trade name for the Alzheimer's drug donepezil hydrochloride.) This factsheet uses generic names, but the section 'Commonly prescribed drugs', later in the factsheet, lists drugs in common use, giving both the generic and proprietary names.

Treating restlessness, aggression and psychotic symptoms

All good practice guidelines state clearly that non-pharmacological treatments should be tried before drugs for the treatment of aggression and restlessness, unless there is severe and persistent risk of harm to the person with dementia or others. Simple psychological interventions can be very beneficial, and can frequently prevent the need for drugs. These include:

• social interaction
• psychological therapies based on a detailed analysis of the problem
• other psychological approaches such as reminiscence therapy.

Antipsychotics

Antipsychotics (also known as neuroleptics or major tranquillisers) are drugs that were originally developed and are effective for the treatment of people with schizophrenia. They are the most commonly used drug treatments for the treatment of restlessness, aggression and psychiatric symptoms in people with dementia.

Combining the results of clinical trials suggests that this type of drug can reduce aggression and, to a lesser extent, psychotic symptoms over a period of three months. However, there is no evidence that these drugs improve restlessness or other non-aggressive behavioural symptoms (Ballard and Howard 2006, Schneider et al 2006). Longer-term clinical trials show that the benefits are very limited over longer periods (Cohen-Mansfield et al 1999, Schneider et al 2006, Ballard et al 2008). These drugs can be safely stopped after three months, with no worsening of behavioural symptoms in most people (Cohen-Mansfield et al 1999, Ballard et al 2008).

The two drugs with the best evidence of effectiveness are risperidone and aripiprazole (Ballard and Howard 2006, Schneider et al 2006). Until recently, antipsychotic drug treatments have been used 'off-licence' to treat people with Alzheimer's disease. Now, one of these treatments, risperidone, has been licensed specifically for the treatment of severe and persistent aggression in people with Alzheimer's disease that have not responded to other therapies.

There is no evidence of any beneficial effects of antipsychotic symptoms in people with dementia with Lewy bodies, and there are currently no clinical trials looking at these drugs in people with vascular dementia.

Side-effects and points to remember:

• Side-effects can include excessive sedation, dizziness, unsteadiness, and symptoms that resemble those of Parkinson's disease (shakiness, slowness and stiffness of the limbs), chest infections, ankle swelling and falls (Ballard and Howard 2006). More recently, there have been increasing concerns about the risk of serious side-effects such as stroke (Committee for the Safety of Medicines 2004, Ballard and Howard 2006) and premature death (Food and Drug Administration 2005, Schneider et al 2005), leading to warnings from the regulatory authorities about the safety of these treatments for people with dementia. The risk of these serious side-effects is quite low over short periods of treatment (up to three months), but becomes much higher over longer treatment periods.
• Antipsychotics may be particularly dangerous for people with dementia with Lewy bodies, possibly causing sudden death (McKeith et al 1992, Aarsland et al 2005). If a person with dementia with Lewy bodies must be prescribed an antipsychotic drug, this should be done with the utmost care, under constant supervision, and they should be reviewed regularly by the GP or consultant.
• Whichever drug is used, treatment with antipsychotics should be regularly reviewed and the dose reduced or the drug withdrawn if side-effects become unacceptable.
• Excessive sedation with antipsychotics may reduce symptoms such as restlessness and aggression at the expense of the person's mobility and coherence.
• Evidence is also beginning to accumulate to suggest that antipsychotics may accelerate the rate of decline in people with dementia (Ballard et al 2005, Schneider et al 2006), so there are particular concerns about the long-term use of these drugs.
• Side-effects and the risk of premature death are even greater if antipsychotics are combined with other sedative drugs (Hollis et al 2007). Combinations of different sedative drugs are strongly discouraged in people with dementia.

Anticonvulsant and antidepressant drugs

Anticonvulsant drugs, such as sodium valproate (Lonergan and Luxenberg 2007) and carbamazepine (Tariot et al 1998), and antidepressants such as trazadone (Sultzer et al 1997) and citalopram (Pollock et al 2007) are also sometimes used to reduce aggression and agitation. There is some evidence from several small clinical trials that these drugs can help these symptoms, but more evidence is needed, and the safety of these treatments used in this way for people with dementia has not been established in large or longer-term studies. These drugs should not usually be combined with each other or with antipsychotics.

Antidementia drugs

There is increasing evidence from re-analysis of clinical trials that the anti-dementia drug memantine may be an effective treatment for aggression and other symptoms of agitation (Gauthier et al 2005, Cummings et al 2006, Wilcock et al 2008). Memantine has the advantage of being a very safe treatment, with other benefits for function and memory, but further work from new, specific clinical trials is still needed to confirm how effective it is for treating aggression.

Cholinesterase inhibitors comprise the other class of dementia drugs, which include donepezil, rivastigmine and galantamine. They appear to be an effective treatment for psychotic symptoms in people with dementia with Lewy bodies and dementia related to Parkinson's disease (McKeith et al 2000, Emre et al 2004). In people with Alzheimer's disease they may delay the onset of psychiatric and behavioural symptoms (Tariot et al 2000), but it is not clear whether they are a helpful treatment once these symptoms occur (Howard et al 2007).

Treating depression

Symptoms of depression are common in dementia. In the early stages they may be a reaction to the person's awareness of their diagnosis. Depression may also be the result of reduced chemical transmitter function in the brain. Simple non-drug interventions, such as an activity or exercise programme (Teri et al 1997, 2003) or other types of psychological treatment can be very helpful − especially for mild depression.

The evidence from clinical trials is not entirely clear (Bains et al 2008), but the best evidence suggests that one of the newer SSRI antidepressants called sertraline is effective without any major side-effects (Lyketsos et al 2003).

Antidepressants may be helpful not only in improving persistently low mood but also in controlling the irritability and rapid mood swings that often occur in dementia and following a stroke. Once started, the doctor will usually recommend prescribing antidepressant drugs for a period of at least six months. In order for them to be effective, it is important that they are taken regularly without missing any doses.

Improvement in mood typically takes two-to-three weeks or more to occur. Side-effects may appear within a few days of starting treatment.

Side-effects

• Tricyclic antidepressants, such as amitriptyline, imipramine or dothiepin, which are commonly used to treat depression in younger people, are likely to increase confusion in someone with dementia. They might also cause a dry mouth, blurred vision, constipation, difficulty in urination (especially in men) and dizziness on standing, which may lead to falls and injuries. Newer antidepressants are preferable as first-line treatments for depression in dementia.
• Drugs such as fluoxetine, paroxetine, fluvoxamine, sertraline and citalopram (known as the selective serotonin re-uptake inhibitors, SSRI), or the selective noradrenaline re-uptake inhibitor (SNRI) mirtrazapine, do not have the side-effects of tricyclics, and are well-tolerated by older people. SSRIs can produce headaches and nausea − especially in the first week or two of treatment. The best evidence of effectiveness in people with dementia is for the SSRI sertraline. Venlafaxine, however, has many of the side-effects of tricyclic antidepressants, but can be very helpful in people who have not responded to other treatments.

Treating anxiety

Anxiety states, accompanied by panic attacks and fearfulness, may lead to demands for constant company. There is no research evidence about the treatment of anxiety in people with dementia, so recommendations made here are based on clinical experience.

Mild symptoms are usually helped by reassurance, adjustments to the environment or an improved structure to everyday life. For more persistent mild anxiety, psychological treatments can be helpful. More severe and persistent anxiety is often related to underlying depression, and will probably improve with antidepressant treatments. Benzodiazepines and antipsychotics are sometimes used to treat anxiety, but both of these types of drug should usually be avoided as treatments for anxiety in people with dementia.

Side-effects

• There are many different benzodiazepines − some with a short duration of action (such as lorazepam and oxazepam) and some with longer action (such as chlordiazepoxide and diazepam). All of these drugs may cause excessive sedation, unsteadiness and a tendency to fall, and may accentuate any confusion and memory deficits that are already present. These drugs can also cause dependency, and may lead to withdrawal symptoms when they are stopped.
• Antipsychotics (see above) are sometimes used for severe or persistent anxiety, but should be avoided for this purpose in people with dementia. If taken for long periods, these drugs can produce a side-effect called tardive dyskinesia, which is recognised by persistent involuntary chewing movements and facial grimacing, in addition to the side-effects described above.

Treating sleep disturbance

Sleep disturbance − in particular, persistent wakefulness and night-time restlessness − can be distressing for the person with dementia and difficult for the people around them. Many of the drugs commonly prescribed for people with dementia can cause excessive sedation during the day, leading to an inability to sleep at night. Increased stimulation during the day and avoiding caffeinated drinks late at night will reduce sleep problems. Aromatherapy with lavender can also help.

It is important to have realistic expectations about what duration of sleep should be expected. Older people rarely sleep for more than five-to-six hours at night, and in people with dementia this will often be spread out over a full 24 hours.

In care homes and nursing homes, the person's care plan must meet these 24-hour needs. In most circumstances, this should be achieved without the need for medication. When people are at home, pressure upon carers, or risks related to people getting up at night, can sometimes necessitate the use of medication − although there is no research evidence assessing the value of this approach.

If hypnotics (sleeping tablets) are used, the preference would be for one of the newer agents such as zopiclone or zolpidem, which have fewer side-effects, fewer hangover effects in the morning, and are less addictive than others. Another good option is a sedative antidepressant, such as trazadone. It is usually better to avoid benzodiazepines in people with dementia.

Hypnotics are generally more helpful in getting people off to sleep at bedtime than they are at keeping people asleep throughout the whole of the night. They are usually taken 30 minutes to one hour before going to bed.

Side-effects

• If excessive sedation is given at bedtime, the person may be unable to wake to go to the toilet and incontinence may occur − sometimes for the first time.
• If the person does wake up during the night despite sedation, increased confusion and unsteadiness may occur.
• Hypnotics are often best used intermittently, rather than regularly, when the carer and person with dementia feel that a good night's sleep is necessary for either or both of them. The use of such drugs should be regularly reviewed by the doctor.

Commonly prescribed drugs

This list includes the names of many (but not all) of the different medications available. New drugs are appearing all the time, and you may need to ask your doctor what type of medication is being prescribed. The generic name is given first, followed by some of the common proprietary (trade) names.

Antipsychotics

Amisulpride (Solian)
Aripiprazole (Abilify)
Chlorpromazine (Largactil)
Fluphenazine (Modecate)
Haloperidol (Haldol, Serenace)
Olanzapine (Zyprexa)
Promazine (Promazine)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Sulpiride (Dolmatil, Sulparex, Sulpitil)
Trifluoperazine (Stelazine)
Zotepine (Zoleptil)
Zuclopenthixol (Clopixol)

Antidepressants

Amitriptyline (Lentizol)
Amoxapine (Asendis)
Citalopram (Cipramil)
Dothiepin (Prothiaden)
Doxepin (Sinequan)
Fluoxetine (Prozac)
Fluvoxamine (Faverin)
Imipramine (Tofranil)
Lofepramine (Gamanil)
Mirtazipine (Zispin)
Nefazodone (Dutonin)
Nortriptyline (Allegron)
Paroxetine (Seroxat)
Reboxetine (Edronax)
Sertraline (Lustral)
Trazodone (Molipaxin)
Venlafaxine (Efexor)

Anxiety-relieving drugs

Alprazolam (Xanax)
Diazepam (Valium)
Lorazepam (Ativan)
Oxazepam (Oxazepam)

Hypnotics

Flurazepam (Dalmane)
Nitrazepam (Mogadon)
Temazepam (Temazepam)
Zopiclone (Zimovane)
Zolpidem (Stilnoct)

Antidementia drugs

Donepezil (Aricept)
Rivastigmine (Exelon)
Galantamine (Reminyl)
Memantine (Ebixa)

Anticonvulsant drugs

Sodium valproate (Epilim)
Carbamazepine (Tegretol)

Your local Alzheimer's Society branch will always be willing to talk to you and offer advice and information to support your needs.

For more information, Dementia Catalogue, our specialist dementia information resource, is available on the website at alzheimers.org.uk/dementiacatalogue

References

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Bains J, Birks J S, Dening T D (2008) 'Antidepressants for treating depression in dementia'. Cochrane Dementia and Cognitive Improvement Group, Cochrane Database of Systematic Reviews 1

Ballard C, Margallo-Lana M, Juszczak E, Douglas S, Swann A, Thomas A, O'Brien J, Everratt A, Sadler S, Maddison C, Lee L, Bannister C, Elvish R, Jacoby R (2005) 'Quetiapine and rivastigmine and cognitive decline in Alzheimer's disease: randomised double blind placebo controlled trial'. British Medical Journal 330: 874

Ballard C, Howard R (2006) 'Neuroleptic drugs in dementia: benefits and harm'. Nature Reviews Neuroscience 7: 492-500

Ballard C, Lana M M, Theodoulou M, Douglas S, McShane R, Jacoby R, Kossakowski K, Yu L-M, Juszczak E (2008) 'A randomised, blinded, placebo-controlled trial in dementia patients continuing or stopping neuroleptics (the DART-AD trial)'. Public Library of Science (PLoS) Medicine 5 (4): e76

Cohen-Mansfield J, Lipson S, Werner P, Billig N, Taylor L et al (1999) 'Withdrawal of haloperidol, thioridazine, and lorazepam in the nursing home: a controlled, double-blind study'. Archives of Internal Medicine 159: 1733-40

Committee for the Safety of Medicines (2004) Atypical antipsychotic drugs and stroke, London: Department of Health

Cummings J L, Schneider E, Tariot P N, Graham S M, for the Memantine MEM-MD-02 Study Group (2006) 'Behavioural effects of memantine in Alzheimer's disease patients receiving donepezil treatment'. Neurology 67: 57-63

Food and Drug Administration (2005) 'Deaths with antipsychotics in elderly patients with behavioral disturbances'. Washington DC: FDA Public Health Advisory, Centre for Drug Evaluation and Research

Gauthier S, Wirth Y and Möbius H J (2005) 'Effects of memantine on behavioural symptoms in Alzheimer's disease patients: an analysis of the Neuropsychiatric Inventory (NPI) data of two randomised, controlled studies'. International Journal of Geriatric Psychiatry 20: 459-464

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Lonergan E T, Luxenberg J (2007) 'Valproate preparations for agitation in dementia'. Cochrane Dementia and Cognitive Improvement Group Cochrane Database of Systematic Reviews 3

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Pollock B G, Mulsant B H, Rosen J, Mazumdar S, Blakesley R E, Houck P R, Huber K A (2007) 'A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia'. American Journal of Geriatric Psychiatry 15: 942-52

Schneider L S, Dagerman K S, Insel P et al (2005) 'Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials'. Journal of the American Medical Association 294: 1934-43

Schneider L S, Dagerman K, Insel P S (2006a) 'Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials'. American Journal of Geriatric Psychiatry 14: 191-210

Schneider L S, Tariot P N, Dagerman K S, Davis S M, Hsiao J K, Ismail M S, Lebowitz B D, Lyketsos C G, Ryan J M, Stroup T S, Sultzer D L, Weintraub D, Lieberman J A, CATIE-AD Study Group (2006b) 'Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease'. New England Journal of Medicine 355 (15): 1525-38

Sultzer D L, Gray K F, Gunay I, Berisford M A, Mahler M E (1997) 'A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia'. American Journal of Geriatric Psychiatry 5: 60-69

Tariot P N, Erb R, Podgorski C A, Cox C, Patel S, Jakimovich L, Irvine C (1998) 'Efficacy and tolerability of carbamazepine for agitation and aggression in dementia'. American Journal of Psychiatry 155: 54-61

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Factsheet 408

Last updated: September 2008
Last reviewed: September 2008

Reviewed by: Professor Clive Ballard, Director of Research, Alzheimer's Society