Is haloperidol good for people with dementia
Treatment of neuropsychiatric disorders in dementia with antipsychotics
Dementia syndrome is defined as a loss of cognitive performance. Affect and behavior disorders are nonetheless very common for patients and the environment and are often far more stressful than memory or orientation disorders. Typical symptoms are apathy, social withdrawal or anxiety, in advanced stages also delusional thoughts, irritability, disinhibition, constant walking around, aggressiveness or stereotypical behavior. Overall, behavior disorders occur in almost 90% of all dementia sufferers in the course of the disease. Various causes lead to the manifestation of dementia syndrome, of which Alzheimer's disease is the most common. Vascular encephalopathy is significantly less likely to cause dementia (vascular dementia).
If the frequency of behavioral disorders in dementia is considered together with the frequency of prescribing AP in this indication, it can be assumed that the need for treatment is to be assessed as high. Wittmann et al. (1) found in a survey in 30 German psychiatric clinics that 77% of inpatients with dementia received antipsychotics on the reference date, 49% of the patients received more than one AP at the same time. Dementia patients treated on an outpatient basis receive 10% AP, predominantly atypical ones. (2). Atypical AP are substances such as risperidone, olazapine, aripiprazole and clozapine, which in contrast to so-called typical or classic AP such as haloperidol cause extrapyramidal motor disorders less often.
Benefits of antipsychotics
The effectiveness of AP in the indication of neuropsychiatric symptoms in dementia has not been very well proven and is surprisingly low overall. The indication is based on the symptoms.
Risperidone (1 mg / d) (3) is particularly effective in agitated behavior / aggression, but also aripiprazole (2.5 to 15 mg / d). Quetiapine (up to 600 mg / day) and olanzapine (up to 10 mg / day) are not effective in agitated behavior / aggression (4). For the treatment of delusions and hallucinations, haloperidol (2 to 3 mg / day) and especially risperidone (up to 2 mg / day) are preferred. Quetiapine and olanzapine are not effective against delusions and hallucinations (3–5). The results for aripiprazole are contradicting in this indication.
Apathy is not amenable to treatment with AP. For other neuropsychiatric symptoms in dementia, such as constant walking, stereotypical movements, or screaming, the effectiveness of AP has not really been studied, apart from anecdotal reports.
In Germany, only risperidone for dementia in Alzheimer's disease is approved for the indication of neuropsychiatric symptoms in the indication a) severe chronic aggressiveness, through which the patients endanger themselves and others, and b) psychotic symptoms, through which the patients are significantly impaired.
Disadvantages of AP
Typical ADRs of the classic AP such as B. Haloperidol in higher doses are extrapyramidal movement disorders such as akathisia, Parkinson's syndrome and dyskinesia. Atypical AP have a significantly lower risk of extrapyramidal motor disorders. The lowest risk is assumed for clozapine and quetiapine. Sedation and fatigue can be a target of AP administration, but they can also be undesirable.
The significant advantages of atypical AP over classic AP were questioned when increased mortality due to increased cerebrovascular side effects including strokes became known. Banerjee (6) has summarized the data situation very clearly:
If 1000 patients with dementia behavioral disorders are treated with atypical neuroleptics, the result is that
- 91 to 200 experienced a significant improvement
- 10 additional deaths occur
- 18 additional cerebrovascular side effects occur, half of which can be severe.
These estimates are for up to twelve weeks of treatment. If AP is administered for more than two years, 167 additional deaths are likely and thus a very significant increase in risk (7; 8). The mortality risk is highest for haloperidol (NNH 26), followed by risperidone (NNH 27), olanzapine (NNH 40) and quetiapine (NNH 50). The mentioned AP increase mortality by 3.5% at higher doses (9).
Identify symptoms that need treatment
At the beginning of every treatment there is the definition of the target symptom. The indication for treatment is made to the patient, not to relatives or professional caregivers.
Analysis of the conditions
There is broad agreement (e.g. (10)) that pharmacotherapy does not come first in the case of neuropsychiatric symptoms in dementia. The first step must always be a behavior analysis. The spectrum of triggering and sustaining conditions ranges from poor lighting or spatial constriction to urinary retention and pain to long-lasting partner conflicts or staff shortages in nursing homes (8; 11). Structural or maintenance deficiencies cannot be neutralized by the administration of AP.
AP under strict therapy control
The definition of a target symptom is not only a prerequisite for the adequate selection of the therapeutic agent, but also for effective therapy control.
The duration of treatment must be limited in time; AP help quickly, usually within days, if symptoms are effective. If the defined target symptom is not eliminated, the AP administration will not be continued. Failure to follow this simple rule is likely to be one of the reasons why AP are given so persistently in many cases. A sufficiently high dosage is a prerequisite for assessing the effectiveness in individual cases. For the treatment of dementia patients, this is significantly lower than that of younger adults. It almost always makes sense and is possible to start with the lowest dose and then slowly increase the dose. On the basis of pragmatic considerations, if the applied AP is not effective, a treatment attempt with an alternative substance will be undertaken. There is no scientifically based ranking of drugs here.
The combination of several neuroleptics for the treatment of neuropsychiatric disorders in dementia cannot be justified and makes the assessment of possible ADRs more difficult. The short duration of the treatment can keep the risks low.
When it comes to the specific selection of an AP, there is unfortunately a clear contrast between effectiveness and safety. Quetiapine is considered to be relatively safe, but is not effective in the important indications. Risperidone and haloperidol are effective but have dangerous side effects including increased mortality. Ultimately, risperidone is still the drug of choice for behavioral disorders in dementia (12), followed by aripiprazole.
conclusion for practice
As treating physicians, we have to say goodbye to the widespread idea that antipsychotics (AP) are effective in treating behavioral disorders in dementia.
AP should only be used after all non-pharmacological intervention options have been exhausted. AP should be administered over a limited period of time, since the target symptoms usually also appear temporarily and can subside spontaneously. The drugs of choice are risperidone and, with restrictions, aripiprazole.
Conflicts of Interest
A conflict of interest is denied by the author.
1 Wittmann M, Hausner H, Hajak G, Haen E: [Antipsychotic treatment of dementia after publication of new risks]. Psychiatric Practice 2010; 37: 68-70.
2 Eichler T, Wucherer D, Thyrian JR et al .: Antipsychotic drug treatment in ambulatory dementia care: prevalence and correlates. J Alzheimers Dis 2015; 43: 1303-1311.
3 Ballard C, Waite J: The effectiveness of atypical antipsychotics for the treatment of aggression and psychosis in Alzheimer's disease. Cochrane Database Syst Rev 2006; Issue 1: CD003476.
4 Schneider LS, Dagerman K, Insel PS: Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry 2006; 14: 191-210.
5 Devanand DP, Marder K, Michaels KS et al .: A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease. Am J Psychiatry 1998; 155: 1512-1520.
6 Banerjee S: The use of antipsychotic medication for people with dementia: Time for action. A report for the Minister of State for Care Services: http://www.rcpsych.ac.uk/pdf/Antipsychotic%20Bannerjee%20Report.pdf. Department of Health, November 2009.
7 Ballard C, Hanney ML, Theodoulou M et al .: The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomized placebo-controlled trial. Lancet Neurol 2009; 8: 151-157.
8 Gertz HJ, Stoppe G, Muller-Oerlinghausen B et al .: [Antipsychotics for the treatment of neuropsychiatric disorders in dementia]. Neurologist 2013; 84: 370-373.
9 Mouse DT, Kim HM, Seyfried LS et al .: Antipsychotics, other psychotropics, and the risk of death in patients with dementia: number needed to harm. JAMA Psychiatry 2015; 72: 438-445.
10 German Society for Neurology (DGN), German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology (DGPPN): S3 guideline "Dementia": http://www.dgn.org/leitlinien/3176-leitlinie-diagnose-und- therapy-of-dementias-2016. AWMF registration number: 038/013; Status: January 24, 2016. Last checked: June 28, 2016.
11 Jessen F, Spottke A: [Therapy of psychological and behavioral symptoms in dementia]. Neurologist 2010; 81: 815-822.
12 Ballard C, Corbett A: Agitation and aggression in people with Alzheimer's disease. Curr Opin Psychiatry 2013; 26: 252-259.
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