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Supportive Care in Cancer : Official... Dec 2021Nausea and vomiting are a common clinical symptom in the advanced cancer patient. Pharmacologic management is important. Evidence for drug choices and guidelines are...
BACKGROUND
Nausea and vomiting are a common clinical symptom in the advanced cancer patient. Pharmacologic management is important. Evidence for drug choices and guidelines are needed to help clinicians manage nausea and vomiting in this population METHODS: Evidence from a systematic review published in 2010, initial MASCC guidelines developed from a systematic review of literature to 2015, and a new systematic review of randomized trials published between 2015 and February 2, 2021, was combined to establish a new guideline.
RESULTS
A search of the literature between 2015 and February 2, 2021, revealed 257 abstracts of which there was one systematic review and 4 randomized trials which were used to modify the guideline. The new guideline is as follows: First Line: Metoclopramide (II) multiple small RCTs including a placebo-controlled trial, haloperidol (II) multiple non-placebo-controlled RCTs, high consensus. Second line: Methotrimeprazine (II) 1 well-powered non-placebo-controlled RCT, olanzapine (II) 1 placebo-controlled pilot RCT, high consensus. Third line: Tropisetron (II) large unblinded lower quality non-placebo-controlled RCT, levosulpiride (II) 1 blinded non-placebo-controlled pilot RCT, high consensus.
DISCUSSION
Haloperidol, metoclopramide, methotrimeprazine, olanzapine tropisetron, and levosulpiride have been antiemetics used in randomized trials with antiemetic activity demonstrated. There are only three placebo-controlled randomized trials we could find in our literature review. Placebo responses varied significantly between two randomized trials. More randomized placebo-controlled trials with either metoclopramide or haloperidol rescue are needed to clarify antiemetic choices in advanced cancer.
CONCLUSION
First-line antiemetics for nausea and vomiting in advanced cancer are metoclopramide and haloperidol, and second-line medications are methotrimeprazine and olanzapine.
Topics: Antiemetics; Humans; Metoclopramide; Nausea; Neoplasms; Vomiting
PubMed: 34398289
DOI: 10.1007/s00520-021-06437-w -
The Cochrane Database of Systematic... Oct 2010Levomepromazine is an 'older' typical antipsychotic medication licensed for use in schizophrenia but sparingly prescribed in the United Kingdom. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Levomepromazine is an 'older' typical antipsychotic medication licensed for use in schizophrenia but sparingly prescribed in the United Kingdom.
OBJECTIVES
To determine the clinical effects and safety of levomepromazine compared with placebo or antipsychotic medications for schizophrenia and schizophreniform psychoses.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group's Register (December 2008) which is based on regular searches of, amongst others, BIOSIS, CENTRAL CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were inspected for further trials. We also contacted relevant pharmaceutical companies for additional information.
SELECTION CRITERIA
All randomised trials comparing levomepromazine with placebo or other antipsychotics for schizophrenia and schizophreniform psychoses were included.
DATA COLLECTION AND ANALYSIS
Data were extracted independently. For dichotomous outcomes, we calculated relative risk (RR) (random-effects model), 95% confidence intervals (CI) and, where appropriate, number needed to treat (NNT) was calculated. We avoided the use of number needed to harm (NNH), as an alternative we used number needed to treat for an additional beneficial outcome (NNTB) and number needed to treat for an additional harmful outcome (NNTH) to indicate the direction of effect. For continuous outcomes, we calculated weighted mean differences (WMD).
MAIN RESULTS
The review currently includes 4 RCTs with 192 participants. For our primary outcome of leaving the study early, levomepromazine was not significantly different compared with other antipsychotics. The levomepromazine arm was significantly better on CGI severity compared with chlorpromazine (n=38, 1 RCT, WMD -0.80 CI -1.51 to -0.09). Risperidone was better for CGI endpoint scores (n=42, 1 RCT, RR 2.33 CI 1.11 to 4.89, NNT 3 CI 2 to 10) compared with levomepromazine. Recipients given levomepromazine had a better BPRS endpoint score (n=38, 1 RCT, WMD -9.00, CI -17.46 to -0.54) and PANSS total score (n=38, 1 RCT, WMD -15.90, CI -30.30 to -1.50) than chlorpromazine. Risperidone recipients noticed a significant difference for the outcome 'at least 20% reduction' on BPRS endpoint score (n=42, 1 RCT, RR 3.33 CI 1.07 to 10.42, NNT 3 CI 2 to 14) compared with levomepromazine. Levomepromazine caused less tremor (n=41, 1 RCT RR 0.12 CI 0.02 to 0.87 NNTB 3 CI 2 to 8), less antiparkinsonian medication administration (n=79, 2 RCTs, RR 0.39 CI 0.17 to 0.90, NNTB 5, CI 2 to 21) compared with haloperidol. Levomepromazine caused less akathisia compared with chlorpromazine, but more hypotension compared with risperidone (n=42, 1 RCT, RR 2.50 CI 1.21 to 5.18, NNTH 3, CI 2 to 7). Dizziness was common with levomepromazine compared with other antipsychotic medications.
AUTHORS' CONCLUSIONS
Available data does not enable us to confidently comment on the effectiveness of levomepromazine for schizophrenia. Larger, more robust, studies comparing levomepromazine with other antipsychotics including clozapine are much needed.
Topics: Antipsychotic Agents; Chlorpromazine; Humans; Methotrimeprazine; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia
PubMed: 20927765
DOI: 10.1002/14651858.CD007779.pub2 -
The Cochrane Database of Systematic... Nov 2015This is an updated version of the original Cochrane Review published in Issue 4, 2013, on Levomepromazine for nausea and vomiting in palliative care.Nausea and vomiting... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane Review published in Issue 4, 2013, on Levomepromazine for nausea and vomiting in palliative care.Nausea and vomiting are common, distressing symptoms for patients receiving palliative care. There are several drugs which can be used to treat these symptoms, known as antiemetics. Levomepromazine is an antipsychotic drug is commonly used as an antiemetic to alleviate nausea and vomiting in palliative care settings.
OBJECTIVES
To evaluate the efficacy of, and adverse events associated with, levomepromazine for the treatment of nausea and vomiting in palliative care patients.
SEARCH METHODS
For this update we searched electronic databases, including those of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, up to February 2015. We searched clinical trial registers on 7 October 2015 for ongoing trials.
SELECTION CRITERIA
Randomised controlled trials of levomepromazine for the treatment of nausea or vomiting, or both, in adults receiving palliative care. We excluded studies in which symptoms were thought to be due to pregnancy or surgery.
DATA COLLECTION AND ANALYSIS
We assessed the potential relevance of studies based on titles and abstracts. We obtained copies of any study reports that appeared to meet the inclusion criteria for further assessment. At least two review authors read each paper to determine suitability for inclusion and discussed discrepancies in order to achieve a consensus.
MAIN RESULTS
In the original review, we identified 421 abstracts using the search strategy. We considered eight studies for inclusion but ultimately excluded them all from the review. We updated the search in February 2015 and identified 35 abstracts, but again none met the inclusion criteria. We identified two trials from clinical trial registers, one of which is ongoing and one of which was closed due to poor recruitment.
AUTHORS' CONCLUSIONS
As in the initial review, we identified no published randomised controlled trials examining the use of levomepromazine for the management of nausea and vomiting in adults receiving palliative care, and our conclusion (that further studies of levomepromazine and other antiemetic agents are needed to provide better evidence for their use in this setting) remains unchanged. We did, however, identify one ongoing study that we hope will contribute to the evidence base for this intervention in future updates of this review.
Topics: Adult; Antiemetics; Female; Humans; Methotrimeprazine; Nausea; Palliative Care; Pregnancy; Vomiting
PubMed: 26524693
DOI: 10.1002/14651858.CD009420.pub3 -
Journal of Applied Toxicology : JAT Apr 2023In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the... (Review)
Review
In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the treatment of schizophrenia, which is related to altered neurotransmission and dysregulation of neuronal autophagy. Thus, phenothiazine derivatives can impact autophagy. We identified 35 papers, where the use of the phenothiazines in the in vitro autophagy assays on normal and cancer cell lines, Caenorhabditis elegans, and zebrafish were discussed. Chlorpromazine, fluphenazine, mepazine, methotrimeprazine, perphenazine, prochlorperazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate autophagy. Stimulation of autophagy by phenothiazines may be either mammalian target of rapamycin (mTOR)-dependent or mTOR-independent. The final effect depends on the used concentration as well as the cell line. A further investigation of the mechanisms of autophagy regulation by phenothiazine derivatives is required to understand the biological actions and to increase the therapeutic potential of this class of drugs.
Topics: Animals; Antipsychotic Agents; Zebrafish; Promazine; Phenothiazines; Chlorpromazine; Mammals
PubMed: 36165981
DOI: 10.1002/jat.4397 -
The Cochrane Database of Systematic... Apr 2013Nausea and vomiting are common, distressing symptoms for patients receiving palliative care. There are several agents which can be used to treat these symptoms.... (Review)
Review
BACKGROUND
Nausea and vomiting are common, distressing symptoms for patients receiving palliative care. There are several agents which can be used to treat these symptoms. Levomepromazine is an antipsychotic drug which is commonly used to alleviate nausea and vomiting in palliative care settings.
OBJECTIVES
To evaluate the efficacy of and adverse events (both minor and serious) associated with the use of levomepromazine for the treatment of nausea and vomiting in palliative care patients.
SEARCH METHODS
We searched the electronic databases including CENTRAL, MEDLINE, and EMBASE using relevant search terms and synonyms in March 2013.
SELECTION CRITERIA
Randomised controlled trials of levomepromazine for the treatment of nausea or vomiting, or both, for adults receiving palliative care. Studies where symptoms were thought to be due to pregnancy or surgery were excluded.
DATA COLLECTION AND ANALYSIS
The potential relevance of studies was assessed based on titles and abstracts. Any study reports which appeared to meet the inclusion criteria were obtained for further assessment. All three authors read these papers to determine their suitability for inclusion and discussed discrepancies to achieve a consensus.
MAIN RESULTS
The search strategy identified 421 abstracts from which eight studies were considered but all were excluded from the review.
AUTHORS' CONCLUSIONS
No randomised controlled trials were identified examining the use of levomepromazine for nausea and vomiting in palliative care. Further studies of levomepromazine and other antiemetic agents are needed to provide better evidence for their use in this setting.
Topics: Adult; Antiemetics; Female; Humans; Methotrimeprazine; Nausea; Palliative Care; Pregnancy; Vomiting
PubMed: 23633372
DOI: 10.1002/14651858.CD009420.pub2 -
Supportive Care in Cancer : Official... Jun 2004To systematically review studies of antiemetics used in the treatment of nausea in patients with far-advanced cancer. (Review)
Review
OBJECTIVES
To systematically review studies of antiemetics used in the treatment of nausea in patients with far-advanced cancer.
DATA SOURCES
Randomized controlled trials (RCT) and uncontrolled studies identified by electronic and hand searching.
REVIEW METHODS
Identified studies were appraised for quality and effect size.
RESULTS
Of 21 studies included, 2 were systematic reviews, 7 were RCT and 12 were uncontrolled studies or case series. Differences in interventions and outcomes amongst the RCT precluded any quantitative data synthesis and all seven studies were prone to bias. Whereas uncontrolled studies indicated a high response rate to standard regimens (75-93% for both nausea and vomiting), RCT showed much lower response rates to these agents (23-36% for nausea, 18-52% for vomiting). The two methods of antiemetic choice (choice based either on the inferred mechanism or empirical) were equally effective. There is reasonably strong evidence for the use of metoclopramide in cancer-associated dyspepsia and steroids in malignant bowel obstruction. There was conflicting evidence about the efficacy of serotonin antagonists compared with standard treatments (e.g. metoclopramide, dopamine antagonists and dexamethasone). There was little or no evidence of the efficacy of some commonly used and seemingly effective drugs such as haloperidol, cyclizine, and methotrimeprazine.
CONCLUSION
Evidence supporting the existing consensus-based guidelines for management of nausea and vomiting in advanced cancer is sparse. Current approaches to treatment based on the neuropharmacology of the emetic pathway may be inappropriate in this setting. Well-designed studies of the impact of "standard" management and novel agents on nausea and vomiting in palliative populations are needed.
Topics: Antiemetics; Antineoplastic Agents; Disease Progression; Dose-Response Relationship, Drug; Humans; Nausea; Neoplasms; Palliative Care; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Research Design; Vomiting
PubMed: 15108099
DOI: 10.1007/s00520-004-0629-y -
The Cochrane Database of Systematic... Nov 2015Nausea and vomiting are common symptoms in patients with terminal, incurable illnesses. Both nausea and vomiting can be distressing. Haloperidol is commonly prescribed... (Review)
Review
BACKGROUND
Nausea and vomiting are common symptoms in patients with terminal, incurable illnesses. Both nausea and vomiting can be distressing. Haloperidol is commonly prescribed to relieve these symptoms. This is an updated version of the original Cochrane review published in Issue 2, 2009, of Haloperidol for the treatment of nausea and vomiting in palliative care patients.
OBJECTIVES
To evaluate the efficacy and adverse events associated with the use of haloperidol for the treatment of nausea and vomiting in palliative care patients.
SEARCH METHODS
For this updated review, we performed updated searches of CENTRAL, EMBASE and MEDLINE in November 2013 and in November 2014. We searched controlled trials registers in March 2015 to identify any ongoing or unpublished trials. We imposed no language restrictions. For the original review, we performed database searching in August 2007, including CENTRAL, MEDLINE, EMBASE, CINAHL and AMED, using relevant search terms and synonyms. Handsearching complemented the electronic searches (using reference lists of included studies, relevant chapters and review articles) for the original review.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) of haloperidol for the treatment of nausea or vomiting, or both, in any setting, for inclusion. The studies had to be conducted with adults receiving palliative care or suffering from an incurable progressive medical condition. We excluded studies where nausea or vomiting, or both, were thought to be secondary to pregnancy or surgery.
DATA COLLECTION AND ANALYSIS
We imported records from each of the electronic databases into a bibliographic package and merged them into a core database where we inspected titles, keywords and abstracts for relevance. If it was not possible to accept or reject an abstract with certainty, we obtained the full text of the article for further evaluation. The two review authors independently assessed studies in accordance with the inclusion criteria. There were no differences in opinion between the authors with regard to the assessment of studies.
MAIN RESULTS
We considered 27 studies from the 2007 search. In this update we considered a further 38 studies from the 2013 search, and two in the 2014 search. We identified one RCT of moderate quality with low risk of bias overall which met the inclusion criteria for this update, comparing ABH (Ativan®, Benadryl®, Haldol®) gel, applied to the wrist, with placebo for the relief of nausea in 22 participants. ABH gel includes haloperidol as well as diphenhydramine and lorazepam. The gel was not significantly better than placebo in this small study; however haloperidol is reported not to be absorbed significantly when applied topically, therefore the trial does not address the issue of whether haloperidol is effective or well-tolerated when administered by other routes (e.g. by mouth, subcutaneously or intravenously). We identified one ongoing trial of haloperidol for the management of nausea and vomiting in patients with cancer, with initial results published in a conference abstract suggesting that haloperidol is effective for 65% of patients. The trial had not been fully published at the time of our review. A further trial has opened, comparing oral haloperidol with oral methotrimeprazine (levomepromazine) for patients with cancer and nausea unrelated to their treatment, which we aim to include in the next review update.
AUTHORS' CONCLUSIONS
Since the last version of this review, we found one new study for inclusion but the conclusion remains unchanged. There is incomplete evidence from published RCTs to determine the effectiveness of haloperidol for nausea and vomiting in palliative care. Other than the trial of ABH gel vs placebo, we did not identify any fully published RCTs exploring the effectiveness of haloperidol for nausea and vomiting in palliative care patients for this update, but two trials are underway.
Topics: Antiemetics; Diphenhydramine; Gels; Haloperidol; Humans; Lorazepam; Nausea; Palliative Care; Randomized Controlled Trials as Topic; Vomiting
PubMed: 26524474
DOI: 10.1002/14651858.CD006271.pub3 -
The Annals of Pharmacotherapy Nov 2006To determine which antipsychotic is associated with the greatest efficacy and safety when used for the pharmacotherapeutic management of delirium in medically or... (Comparative Study)
Comparative Study Review
OBJECTIVE
To determine which antipsychotic is associated with the greatest efficacy and safety when used for the pharmacotherapeutic management of delirium in medically or surgically ill patients.
DATA SOURCES
MEDLINE, Current Contents, Cumulative Index of Nursing and Allied Health Literature, PsycINFO, Biological Abstracts, Cochrane Central Register of Controlled Trials, and EMBASE databases (all to July 2006) were searched for trials evaluating the pharmacologic treatment of delirium in medically or surgically ill patients. The key terms used included delirium, agitation, or acute confusion, and antipsychotics, phenothiazine, butyrophenone, perphenazine, fluphenazine, clozapine, trifluorophenazine, loxapine, thioridazine, pimozide, molindone, haloperidol, methotrimeprazine, chlorpromazine, prochlorperazine, droperidol, risperidone, quetiapine, ziprasidone, amisulpride, or olanzapine.
STUDY SELECTION AND DATA EXTRACTION
Prospective, randomized, controlled trials comparing the clinical effects of antipsychotic therapy with placebo or comparing 2 antipsychotic treatments in an acute care setting were selected. Studies involving dementia-associated delirium, Alzheimer's disease-associated delirium, emergency department-associated acute agitation, acute brain trauma-associated agitation, or agitation secondary to underlying psychiatric afflictions such as depression or schizophrenia were excluded. All studies were evaluated independently by the 3 authors using a validated evaluation tool. Outcomes related to both efficacy and safety were collected. Four prospective trials were included in this systematic review.
DATA SYNTHESIS
Antipsychotic agents, either atypical or typical, were effective compared with baseline for the treatment of delirium in medically or surgically ill patients without underlying cognitive disorders. Oral haloperidol was associated with more frequent extrapyramidal side effects, but overall, all agents were well tolerated. Interpretation of the published evidence is limited by the small sample sizes, varied patient populations, and comparative agents of the studies reviewed.
CONCLUSIONS
The comparative studies evaluated here suggest that antipsychotic drugs are efficacious, when compared with baseline, and safe for the treatment of delirium. Haloperidol remains the most studied agent. Recommendation of one antipsychotic over another as a first-line pharmacologic intervention in the treatment of hospital-associated delirium is limited by the quality and quantity of data available. Better designed and larger studies evaluating the addition of antipsychotic agents to nonpharmacologic treatments are needed to measure the true effect of pharmacologic treatment.
Topics: Antipsychotic Agents; Delirium; Haloperidol; Hospital Departments; Hospitalization; Humans; Surgery Department, Hospital
PubMed: 17047137
DOI: 10.1345/aph.1H241 -
The Cochrane Database of Systematic... Mar 2013Antipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in dementia, although the literature is sceptical about their long-term use for this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic agents are often used to treat neuropsychiatric symptoms (NPS) in dementia, although the literature is sceptical about their long-term use for this indication. Their effectiveness is limited and there is concern about adverse effects, including higher mortality with long-term use. When behavioural strategies have failed and drug therapy is instituted, regular attempts to withdraw these drugs are recommended. Physicians, nurses and families of older people with dementia are often reluctant to try to stop antipsychotics, fearing deterioration of NPS. Strategies to reduce antipsychotic use have been proposed, but a systematic review of interventions aimed at withdrawal of antipsychotic agents in older people with dementia has not yet been performed.
OBJECTIVES
To evaluate whether withdrawal of antipsychotic agents is successful in older people with dementia in community or nursing home settings, to list the different strategies for withdrawal of antipsychotic agents in older people with dementia and NPS, and to measure the effects of withdrawal of antipsychotic agents on behaviour.
SEARCH METHODS
ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, clinical trials registries and grey literature sources were searched on 23 November 2012. The search included the following terms: antipsychotic* or neuroleptic* or phenothiazines or butyrophenones or risperidone or olanzapine or haloperidol or prothipendyl or methotrimeprazine or clopenthixol or flupenthixol or clothiapine or metylperon or droperidol or pipamperone or benperidol or bromperidol or fluspirilene or pimozide or penfluridol or sulpiride or veralipride or levosulpiride or sultopride or aripiprazole or clozapine or quetiapine or thioridazine combined wither terms such as discontinu* or withdraw* or cessat* or reduce* or reducing or reduct* or taper* or stop*.ALOIS contains records from all major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), as well as from many clinical trials registries and grey literature sources.
SELECTION CRITERIA
Randomised, placebo-controlled trials comparing an antipsychotic withdrawal strategy to continuation of antipsychotics in people with dementia.
DATA COLLECTION AND ANALYSIS
Review authors independently assessed trials for inclusion, rated their risk of bias and extracted data.
MAIN RESULTS
We included nine trials with 606 randomised participants. Seven trials were conducted in nursing homes, one trial in an outpatient setting and one in both settings. In these trials, different types of antipsychotics prescribed at different doses were withdrawn. Both abrupt and gradual withdrawal schedules were used. The risk of bias of the included studies was generally low regarding blinding and outcome reporting and unclear for randomisation procedures and recruitment of participants.There was a wide variety of outcome measures. Our primary efficacy outcomes were success of withdrawal (i.e. remaining in study off antipsychotics) and NPS. Eight of nine trials reported no overall significant difference between groups on the primary outcomes, although in one pilot study of people with psychosis and agitation that had responded to haloperidol, time to relapse was significantly shorter in the discontinuation group (Chi(2) = 4.1, P value = 0.04). The ninth trial included people with psychosis or agitation who had responded well to risperidone therapy for four to eight months and reported that discontinuation led to an increased risk of relapse, that is, increase in the Neuropsychiatric Inventory (NPI)-core score of 30% or greater (P value = 0.004, hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.09 to 3.45 at four months). The only outcome that could be pooled was the full NPI-score, used in two studies. For this outcome there was no significant difference between people withdrawn from and those continuing on antipsychotics at three months (mean difference (MD) -1.49, 95% CI -5.39 to 2.40). These two studies reported subgroup analyses according to baseline NPI-score (14 or less versus > 14). In one study, those with milder symptoms at baseline were significantly less agitated at three months in the discontinuation group (NPI-agitation, Mann-Whitney U test z = 2.4, P value = 0.018). In both studies, there was evidence of significant behavioural deterioration in people with more severe baseline NPS who were withdrawn from antipsychotics (Chi(2) = 6.8; P value = 0.009 for the marked symptom score in one study).Individual studies did not report significant differences between groups on any other outcome except one trial that found a significant difference in a measure of verbal fluency, favouring discontinuation. Most trials lacked power to detect clinically important differences between groups.Adverse events were not systematically assessed. In one trial there was a non-significant increase in mortality in people who continued antipsychotic treatment (5% to 8% greater than placebo, depending on the population analysed, measured at 12 months). This trend became significant three years after randomisation, but due to dropout and uncertainty about the use of antipsychotics in this follow-up period this result should be interpreted with caution.
AUTHORS' CONCLUSIONS
Our findings suggest that many older people with Alzheimer's dementia and NPS can be withdrawn from chronic antipsychotic medication without detrimental effects on their behaviour. It remains uncertain whether withdrawal is beneficial for cognition or psychomotor status, but the results of this review suggest that discontinuation programmes could be incorporated into routine practice. However, two studies of people whose agitation or psychosis had previously responded well to antipsychotic treatment found an increased risk of relapse or shorter time to relapse after discontinuation. Two other studies suggest that people with more severe NPS at baseline could benefit from continuing their antipsychotic medication. In these people, withdrawal might not be recommended.
Topics: Aged; Antipsychotic Agents; Dementia; Humans; Mental Disorders; Psychomotor Agitation; Randomized Controlled Trials as Topic; Recurrence
PubMed: 23543555
DOI: 10.1002/14651858.CD007726.pub2