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The Cochrane Database of Systematic... Sep 2017The efficacy of chlorpromazine, a benchmark antipsychotic, has not been fully assessed in direct comparison with different individual antipsychotics. Penfluridol is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The efficacy of chlorpromazine, a benchmark antipsychotic, has not been fully assessed in direct comparison with different individual antipsychotics. Penfluridol is another old antipsychotic with a long half-life so one oral dose may last up to one week. This could confer advantage.
OBJECTIVES
To assess the clinical effects of chlorpromazine compared with penfluridol for adults with schizophrenia.
SEARCH METHODS
On 31 March 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, date, document type, or publication status limitations for inclusion of records in the register.
SELECTION CRITERIA
We included all randomised clinical trials focusing on chlorpromazine versus penfluridol for adults with schizophrenia or related disorders. Outcomes of interest were death, service utilisation, global state, mental state, adverse effects and leaving the study early. We included trials meeting our selection criteria and reporting useable data.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we planned to estimate the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
The review includes three studies with a total of 130 participants. Short-term results for hospital admissions showed no clear difference between chlorpromazine and penfluridol (1 RCT, n = 29, RR 0.19, 95% CI 0.01 to 3.60, low-quality evidence). No clear difference in the incidence of akathisia was found at medium term (2 RCTs, n = 85, RR 0.19, 95% CI 0.04 to 1.06, low-quality evidence), and similar numbers of participants - nearly half - from each treatment group left the study early (3 RCTs, n = 130, RR 1.21, 95% CI 0.83 to 1.77, low-quality evidence). The risk of needing additional antiparkinsonian medication was less in the chlorpromazine group (2 RCTs, n = 74, RR 0.70, 95% CI 0.51 to 0.95). No useable data reported clinically important change in global or mental state. No data were reported for relapse. No deaths were reported by the trials.
AUTHORS' CONCLUSIONS
Only three small studies provided data and the quality of reporting and evidence is low. Limited data indicate the efficacy and adverse effects profiles of chlorpromazine and penfluridol are generally similar. Penfluridol, however, may confer advantage by needing to be given only once per week. Firm conclusions are not possible without good-quality trials, and where these treatments are used, such trials are justified.
Topics: Adult; Akathisia, Drug-Induced; Antipsychotic Agents; Chlorpromazine; Humans; Length of Stay; Penfluridol; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 28940256
DOI: 10.1002/14651858.CD011831.pub2 -
The Cochrane Database of Systematic... Jul 2017Haloperidol used alone is recommended to help calm situations of aggression or agitation for people with psychosis. It is widely accessible and may be the only... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Haloperidol used alone is recommended to help calm situations of aggression or agitation for people with psychosis. It is widely accessible and may be the only antipsychotic medication available in limited-resource areas.
OBJECTIVES
To examine whether haloperidol alone is an effective treatment for psychosis-induced aggression or agitation, wherein clinicians are required to intervene to prevent harm to self and others.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (26th May 2016). This register is compiled by systematic searches of major resources (including AMED, BIOSIS CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings, with no language, date, document type, or publication status limitations for inclusion of records into the register.
SELECTION CRITERIA
Randomised controlled trials (RCTs) involving people exhibiting aggression and/or agitation thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes of interest included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects. We included trials meeting our selection criteria and providing useable data.
DATA COLLECTION AND ANALYSIS
We independently inspected all citations from searches, identified relevant abstracts, and independently extracted data from all included studies. For binary data we calculated risk ratio (RR), for continuous data we calculated mean difference (MD), and for cognitive outcomes we derived standardised mean difference (SMD) effect sizes, all with 95% confidence intervals (CI) and using a fixed-effect model. We assessed risk of bias for the included studies and used the GRADE approach to produce 'Summary of findings' tables which included our pre-specified main outcomes of interest.
MAIN RESULTS
We found nine new RCTs from the 2016 update search, giving a total of 41 included studies and 24 comparisons. Few studies were undertaken in circumstances that reflect real-world practice, and, with notable exceptions, most were small and carried considerable risk of bias. Due to the large number of comparisons, we can only present a summary of main results.Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n=220, RR 0.88, 95%CI 0.82 to 0.95, very low-quality evidence) and experienced dystonia (2 RCTs, n=207, RR 7.49, 95%CI 0.93 to 60.21, very low-quality evidence).Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n=473, RR 0.78, 95%CI 0.62 to 0.99, low-quality evidence). More people in the haloperidol group experienced dystonia (2 RCTs, n=477, RR 6.63, 95%CI 1.52 to 28.86, very low-quality evidence).Four trials (n=207) compared haloperidol with lorazepam with no significant differences with regard to number of participants asleep at one hour (1 RCT, n=60, RR 1.05, 95%CI 0.76 to 1.44, very low-quality of evidence) or those requiring additional injections (1 RCT, n=66, RR 1.14, 95%CI 0.91 to 1.43, very low-quality of evidence).Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n=67, RR 8.25, 95%CI 0.46 to 147.45, very low-quality of evidence).Addition of promethazine was investigated in two trials (n=376). More people in the haloperidol group were not tranquil or asleep by 20 minutes (1 RCT, n=316, RR 1.60, 95%CI 1.18 to 2.16, moderate-quality evidence). Acute dystonia was too common in the haloperidol alone group for the trial to continue beyond the interim analysis (1 RCT, n=316, RR 19.48, 95%CI 1.14 to 331.92, low-quality evidence).
AUTHORS' CONCLUSIONS
Additional data from new studies does not alter previous conclusions of this review. If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs are available, sole use of haloperidol for extreme emergency could be considered unethical. Addition of the sedating promethazine has support from better-grade evidence from within randomised trials. Use of an alternative antipsychotic drug is only partially supported by fragmented and poor-grade evidence. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries risk of additional harm.After six decades of use for emergency rapid tranquillisation, this is still an area in need of good independent trials relevant to real-world practice.
Topics: Aggression; Antipsychotic Agents; Dystonia; Haloperidol; Humans; Hypnotics and Sedatives; Placebos; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic; Sleep; Tranquilizing Agents
PubMed: 28758203
DOI: 10.1002/14651858.CD009377.pub3 -
The Cochrane Database of Systematic... May 2017Dementia is a clinical syndrome with a number of different causes which is characterised by deterioration in cognitive, behavioural, social and emotional functions.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dementia is a clinical syndrome with a number of different causes which is characterised by deterioration in cognitive, behavioural, social and emotional functions. Pharmacological interventions are available but have limited effect to treat many of the syndrome's features. Less research has been directed towards non-pharmacological treatments. In this review, we examined the evidence for effects of music-based interventions as a treatment.
OBJECTIVES
To assess the effects of music-based therapeutic interventions for people with dementia on emotional well-being including quality of life, mood disturbance or negative affect, behavioural problems, social behaviour, and cognition at the end of therapy and four or more weeks after the end of treatment.
SEARCH METHODS
We searched ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG) on 14 April 2010 using the terms: music therapy, music, singing, sing, auditory stimulation. Additional searches were also carried out on 3 July 2015 in the major healthcare databases MEDLINE, Embase, psycINFO, CINAHL and LILACS; and in trial registers and grey literature sources. On 12 April 2016, we searched the major databases for new studies for future evaluation.
SELECTION CRITERIA
We included randomized controlled trials of music-based therapeutic interventions (at least five sessions) for people with dementia that measured any of our outcomes of interest. Control groups either received usual care or other activities.
DATA COLLECTION AND ANALYSIS
Two reviewers worked independently to screen the retrieved studies against the inclusion criteria and then to extract data and assess methodological quality of the included studies. If necessary, we contacted trial authors to ask for additional data, including relevant subscales, or for other missing information. We pooled data using random-effects models.
MAIN RESULTS
We included 17 studies. Sixteen studies with a total of 620 participants contributed data to meta-analyses. Participants in the studies had dementia of varying degrees of severity, but all were resident in institutions. Five studies delivered an individual music intervention; in the others, the intervention was delivered to groups of participants. Most interventions involved both active and receptive musical elements. The methodological quality of the studies varied. All were at high risk of performance bias and some were at high risk of detection or other bias. At the end of treatment, we found low-quality evidence that music-based therapeutic interventions may have little or no effect on emotional well-being and quality of life (standardized mean difference, SMD 0.32, 95% CI -0.08 to 0.71; 6 studies, 181 participants), overall behaviour problems (SMD -0.20, 95% CI -0.56 to 0.17; 6 studies, 209 participants) and cognition (SMD 0.21, 95% CI -0.04 to 0.45; 6 studies, 257 participants). We found moderate-quality evidence that they reduce depressive symptoms (SMD -0.28, 95% CI -0.48 to -0.07; 9 studies, 376 participants), but do not decrease agitation or aggression (SMD -0.08, 95% CI -0.29 to 0.14; 12 studies, 515 participants). The quality of the evidence on anxiety and social behaviour was very low, so effects were very uncertain. The evidence for all long-term outcomes was also of very low quality.
AUTHORS' CONCLUSIONS
Providing people with dementia with at least five sessions of a music-based therapeutic intervention probably reduces depressive symptoms but has little or no effect on agitation or aggression. There may also be little or no effect on emotional well-being or quality of life, overall behavioural problems and cognition. We are uncertain about effects on anxiety or social behaviour, and about any long-term effects. Future studies should employ larger sample sizes, and include all important outcomes, in particular 'positive' outcomes such as emotional well-being and social outcomes. Future studies should also examine the duration of effects in relation to the overall duration of treatment and the number of sessions.
Topics: Aged; Aggression; Dementia; Depression; Humans; Mental Disorders; Music Therapy; Psychomotor Agitation; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 28462986
DOI: 10.1002/14651858.CD003477.pub3 -
The Cochrane Database of Systematic... Apr 2017Dementia is a common and serious neuropsychiatric syndrome, characterised by progressive cognitive and functional decline. The majority of people with dementia develop... (Review)
Review
BACKGROUND
Dementia is a common and serious neuropsychiatric syndrome, characterised by progressive cognitive and functional decline. The majority of people with dementia develop behavioural disturbances, also known as behavioural and psychological symptoms of dementia (BPSD). Several non-pharmacological interventions have been evaluated to treat BPSD in people with dementia. Simulated presence therapy (SPT), an intervention that uses video or audiotape recordings of family members played to the person with dementia, is a possible approach to treat BPSD.
OBJECTIVES
To assess the effects of SPT on behavioural and psychological symptoms and quality of life in people with dementia.
SEARCH METHODS
We searched ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), CENTRAL (The Cochrane Library) (9 February 2016), MEDLINE Ovid SP (1946 to 6 January 2017), Embase Ovid SP (1972 to 6 January 2017), PsycINFO Ovid SP (1806 to 6 January 2017), CINAHL via EBSCOhost (1980 to 6 January 2017), LILACS via BIREME (all dates to 6 January 2017), ClinicalTrials.gov (ClinicalTrials.gov) (all dates to 6 January 2017), and the World Health Organization (WHO) Portal (apps.who.int/trialsearch) (all dates to 6 January 2017). We also checked the reference lists of relevant articles to identify any additional studies.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials, including cross-over studies, that evaluated the efficacy of SPT, consisting of personalised audio or videotape recordings of family members, in people with any form of dementia.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies, assessed risk of bias and extracted data. No meta-analyses were conducted because of substantial heterogeneity among the included studies.
MAIN RESULTS
Three trials with 144 participants met the inclusion criteria. Two of the trials had a randomised cross-over design, one was a cross-over trial which we classified as quasi-randomised.Participants in the included studies were people with dementia living in nursing homes. They were predominantly women and had a mean age of over 80 years. SPT was performed using an audio or video recording prepared by family members or surrogates. It varied in its content, frequency of administration and duration. All the studies compared multiple treatments. In one study, SPT was compared with two other interventions; in the other two studies, it was compared with three other interventions. Specifically, SPT was compared to usual care, personalised music (two studies), a 'placebo' audiotape containing the voice of a person (two studies), and one-to-one social interaction performed by trained research assistants (one study). In terms of outcomes evaluated, one study considered agitation and withdrawn behaviour (both assessed with three methods); the second study evaluated verbal disruptive behaviour (assessed with three methods); and the third study evaluated physically agitated behaviour and verbally agitated behaviour (the method used was not clearly described).According to the GRADE criteria, the overall quality of the evidence was very low due to very small numbers of participants and risk of bias in the included studies; (none of the trials was at low risk of selection bias; all the trials were at high risk of performance bias; one trial was at high risk of attrition bias; and all had unclear selective reporting).Because of variation in the participants, the format of SPT, the comparison interventions, and the measures used to assess outcomes, we judged the results unsuitable for a meta-analysis.Within each trial, the effect of SPT on behaviour, compared to usual care, was mixed and depended on the measure used. Two trials which included a personalised music intervention reported no significant differences between simulated presence and music on behavioural outcomes. Because the overall quality of the evidence was very low, we were very uncertain regarding all the resultsNone of the studies evaluated quality of life or any of our secondary outcome measures (performance of activities of daily living, dropout and carer burden).
AUTHORS' CONCLUSIONS
We were unable to draw any conclusions about the efficacy of SPT for treating behavioural and psychological symptoms and improving quality of life of people with dementia. New high-quality studies are needed to investigate the effect of SPT.
Topics: Aged, 80 and over; Dementia; Depression; Family; Female; Humans; Male; Psychomotor Agitation; Randomized Controlled Trials as Topic; Tape Recording; Videotape Recording
PubMed: 28418586
DOI: 10.1002/14651858.CD011882.pub2 -
The Cochrane Database of Systematic... Apr 2017Aggression is a disposition, a willingness to inflict harm, regardless of whether this is behaviourally or verbally expressed and regardless of whether physical harm is... (Review)
Review
BACKGROUND
Aggression is a disposition, a willingness to inflict harm, regardless of whether this is behaviourally or verbally expressed and regardless of whether physical harm is sustained.De-escalation is a psychosocial intervention for managing people with disturbed or aggressive behaviour. Secondary management strategies such as rapid tranquillisation, physical intervention and seclusion should only be considered once de-escalation and other strategies have failed to calm the service user.
OBJECTIVES
To investigate the effects of de-escalation techniques in the short-term management of aggression or agitation thought or likely to be due to psychosis.
SEARCH METHODS
We searched Cochrane Schizophrenia Group's Study-Based Register of Trials (latest search 7 April, 2016).
SELECTION CRITERIA
Randomised controlled trials using de-escalation techniques for the short-term management of aggressive or agitated behaviour. We planned to include trials involving adults (at least 18 years) with a potential for aggressive behaviour due to psychosis, from those in a psychiatric setting to those possibly under the influence of alcohol or drugs and/or as part of an acute setting as well. We planned to include trials meeting our inclusion criteria that provided useful data.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. Two review authors inspected all abstracts of studies identified by the search process. As we were unable to include any studies, we could not perform data extraction and analysis.
MAIN RESULTS
Of the 345 citations that were identified using the search strategies, we found only one reference to be potentially suitable for further inspection. However, after viewing the full text, it was excluded as it was not a randomised controlled trial.
AUTHORS' CONCLUSIONS
Using de-escalation techniques for people with psychosis induced aggression or agitation appears to be accepted as good clinical practice but is not supported by evidence from randomised trials. It is unclear why it has remained such an under-researched area. Conducting trials in this area could be influenced by funding flow, ethical concerns - justified or not - anticipated pace of recruitment as well the difficulty in accurately quantifying the effects of de-escalation itself. With supportive funders and ethics committees, imaginative trialists, clinicians and service-user groups and wide collaboration this dearth of randomised research could be addressed.
Topics: Aggression; Behavior Control; Crisis Intervention; Humans; Psychomotor Agitation; Psychotic Disorders
PubMed: 28368091
DOI: 10.1002/14651858.CD009922.pub2 -
BMJ Open Mar 2017To provide an overview of non-pharmacological interventions for behavioural and psychological symptoms in dementia (BPSD). (Review)
Review
OBJECTIVE
To provide an overview of non-pharmacological interventions for behavioural and psychological symptoms in dementia (BPSD).
DESIGN
Systematic overview of reviews.
DATA SOURCES
PubMed, EMBASE, Cochrane Database of Systematic Reviews, CINAHL and PsycINFO (2009-March 2015).
ELIGIBILITY CRITERIA
Systematic reviews (SRs) that included at least one comparative study evaluating any non-pharmacological intervention, to treat BPSD.
DATA EXTRACTION
Eligible studies were selected and data extracted independently by 2 reviewers.The AMSTAR checklist was used to assess the quality of the SRs.
DATA ANALYSIS
Extracted data were synthesised using a narrative approach.
RESULTS
38 SRs and 129 primary studies were identified, comprising the following categories of non-pharmacological interventions: (1) sensory stimulation interventions (25 SRs, 66 primary studies) that encompassed: shiatsu and acupressure, aromatherapy, massage/touch therapy, light therapy, sensory garden and horticultural activities, music/dance therapy, dance therapy, snoezelen multisensory stimulation therapy, transcutaneous electrical nerve stimulation; (2) cognitive/emotion-oriented interventions (13 SRs; 26 primary studies) that included cognitive stimulation, reminiscence therapy, validation therapy, simulated presence therapy; (3) behaviour management techniques (6 SRs; 22 primary studies); (4) Multicomponent interventions (3 SR; four primary studies); (5) other therapies (5 SRs, 15 primary studies) comprising exercise therapy, animal-assisted therapy, special care unit and dining room environment-based interventions.
CONCLUSIONS
A large number of non-pharmacological interventions for BPSD were identified. The majority of the studies had great variation in how the same type of intervention was defined and applied, the follow-up duration, the type of outcome measured, usually with modest sample size. Overall, music therapy and behavioural management techniques were effective for reducing BPSD.
Topics: Aged; Aged, 80 and over; Anxiety; Cognitive Behavioral Therapy; Complementary Therapies; Dementia; Home Care Services; Humans; Phototherapy; Physical Therapy Modalities; Psychomotor Agitation; Review Literature as Topic
PubMed: 28302633
DOI: 10.1136/bmjopen-2016-012759 -
Clinical Interventions in Aging 2017Person-centered care is a holistic and integrative approach designed to maintain well-being and quality of life for people with dementia, and it includes the elements of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Person-centered care is a holistic and integrative approach designed to maintain well-being and quality of life for people with dementia, and it includes the elements of care, the individual, the carers, and the family.
AIM
A systematic literature review and meta-analysis were undertaken to investigate the effectiveness of person-centered care for people with dementia.
METHODS
Literature searches were undertaken using six databases including Medline, EMBASE, CINAHL, PsycINFO, Cochrane Database, and KoreaMed using the following keywords: cognition disorder, dementia, person-centered care, patient-centered care, client-centered care, relationship-centered care, and dementia care. The searches were limited to interventional studies written in English and Korean and included randomized controlled studies and noncontrolled studies for people with dementia living in any setting.
RESULTS
Nineteen interventional studies, including 3,985 participants, were identified. Of these, 17 studies were from long-term care facilities and two studies were from homecare settings. The pooled data from randomized controlled studies favored person-centered care in reducing agitation, neuropsychiatric symptoms, and depression and improving the quality of life. Subgroup analysis identified greater effectiveness of person-centered care when implemented for people with less severe dementia. For agitation, short-term interventions had a greater effect (standardized mean difference [SMD]: -0.434; 95% conference interval [CI]: -0.701 to -0.166) than long-term interventions (SMD: -0.098; 95% CI: -0.190 to 0.007). Individualized activities resulted in a significantly greater beneficial effect than standard care (SMD: 0.513; 95% CI: -0.994 to -0.032). However, long-term, staff education, and cultural change interventions had a greater effect on improving the quality of life for people with dementia (SMD: 0.191; 95% CI: 0.079 to 0.302).
CONCLUSION
This systematic review and meta-analysis provided evidence for person-centered care in clinical practice for people with dementia. Person-centered care interventions were shown to reduce agitation, neuropsychiatric symptoms, and depression and to improve the quality of life. Person-centered care interventions can effectively reduce agitation for a short term using intensive and activity-based intervention. However, an educational strategy that promotes learning and skill development of internal care staff is needed to enhance patient's quality of life and to ensure the sustainability of the effects of behavioral problems. The feasibility and effectiveness of the intervention, the severity of patient disease, and intervention type and duration should be considered as part of an intervention design.
Topics: Anxiety; Caregivers; Dementia; Depression; Family; Humans; Patient-Centered Care; Psychomotor Agitation; Quality of Life; Self Care; Severity of Illness Index
PubMed: 28255234
DOI: 10.2147/CIA.S117637 -
Social Science & Medicine (1982) Jun 2017To date global research on depression has used assessment tools based on research and clinical experience drawn from Western populations (i.e., in North American,... (Review)
Review
To date global research on depression has used assessment tools based on research and clinical experience drawn from Western populations (i.e., in North American, European and Australian). There may be features of depression in non-Western populations which are not captured in current diagnostic criteria or measurement tools, as well as criteria for depression that are not relevant in other regions. We investigated this possibility through a systematic review of qualitative studies of depression worldwide. Nine online databases were searched for records that used qualitative methods to study depression. Initial searches were conducted between August 2012 and December 2012; an updated search was repeated in June of 2015 to include relevant literature published between December 30, 2012 and May 30, 2015. No date limits were set for inclusion of articles. A total of 16,130 records were identified and 138 met full inclusion criteria. Included studies were published between 1976 and 2015. These 138 studies represented data on 170 different study populations (some reported on multiple samples) and 77 different nationalities/ethnicities. Variation in results by geographical region, gender, and study context were examined to determine the consistency of descriptions across populations. Fisher's exact tests were used to compare frequencies of features across region, gender and context. Seven of the 15 features with the highest relative frequency form part of the DSM-5 diagnosis of Major Depressive Disorder (MDD). However, many of the other features with relatively high frequencies across the studies are associated features in the DSM, but are not prioritized as diagnostic criteria and therefore not included in standard instruments. The DSM-5 diagnostic criteria of problems with concentration and psychomotor agitation or slowing were infrequently mentioned. This research suggests that the DSM model and standard instruments currently based on the DSM may not adequately reflect the experience of depression at the worldwide or regional levels.
Topics: Depression; Humans; Internationality
PubMed: 28069271
DOI: 10.1016/j.socscimed.2016.12.030 -
The Cochrane Database of Systematic... Dec 2016People experiencing acute psychotic illnesses, especially those associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People experiencing acute psychotic illnesses, especially those associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone antipsychotic, has been used for this purpose in several countries.
OBJECTIVES
To estimate the effects of droperidol, including its cost-effectiveness, when compared to placebo, other 'standard' or 'non-standard' treatments, or other forms of management of psychotic illness, in controlling acutely disturbed behaviour and reducing psychotic symptoms in people with schizophrenia-like illnesses.
SEARCH METHODS
We updated previous searches by searching the Cochrane Schizophrenia Group Register (18 December 2015). We searched references of all identified studies for further trial citations and contacted authors of trials. We supplemented these electronic searches by handsearching reference lists and contacting both the pharmaceutical industry and relevant authors.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) with useable data that compared droperidol to any other treatment for people acutely ill with suspected acute psychotic illnesses, including schizophrenia, schizoaffective disorder, mixed affective disorders, the manic phase of bipolar disorder or a brief psychotic episode.
DATA COLLECTION AND ANALYSIS
For included studies, we assessed quality, risk of bias and extracted data. We excluded data when more than 50% of participants were lost to follow-up. For binary outcomes, we calculated standard estimates of risk ratio (RR) and the corresponding 95% confidence intervals (CI). We created a 'Summary of findings' table using GRADE.
MAIN RESULTS
We identified four relevant trials from the update search (previous version of this review included only two trials). When droperidol was compared with placebo, for the outcome of tranquillisation or asleep by 30 minutes we found evidence of a clear difference (1 RCT, N = 227, RR 1.18, 95% CI 1.05 to 1.31, high-quality evidence). There was a clear demonstration of reduced risk of needing additional medication after 60 minutes for the droperidol group (1 RCT, N = 227, RR 0.55, 95% CI 0.36 to 0.85, high-quality evidence). There was no evidence that droperidol caused more cardiovascular arrhythmia (1 RCT, N = 227, RR 0.34, 95% CI 0.01 to 8.31, moderate-quality evidence) and respiratory airway obstruction (1 RCT, N = 227, RR 0.62, 95% CI 0.15 to 2.52, low-quality evidence) than placebo. For 'being ready for discharge', there was no clear difference between groups (1 RCT, N = 227, RR 1.16, 95% CI 0.90 to 1.48, high-quality evidence). There were no data for mental state and costs.Similarly, when droperidol was compared to haloperidol, for the outcome of tranquillisation or asleep by 30 minutes we found evidence of a clear difference (1 RCT, N = 228, RR 1.01, 95% CI 0.93 to 1.09, high-quality evidence). There was a clear demonstration of reduced risk of needing additional medication after 60 minutes for participants in the droperidol group (2 RCTs, N = 255, RR 0.37, 95% CI 0.16 to 0.90, high-quality evidence). There was no evidence that droperidol caused more cardiovascular hypotension (1 RCT, N = 228, RR 2.80, 95% CI 0.30 to 26.49,moderate-quality evidence) and cardiovascular hypotension/desaturation (1 RCT, N = 228, RR 2.80, 95% CI 0.12 to 67.98, low-quality evidence) than haloperidol. There was no suggestion that use of droperidol was unsafe. For mental state, there was no evidence of clear difference between the efficacy of droperidol compared to haloperidol (Scale for Quantification of Psychotic Symptom Severity, 1 RCT, N = 40, mean difference (MD) 0.11, 95% CI -0.07 to 0.29, low-quality evidence). There were no data for service use and costs.Whereas, when droperidol was compared with midazolam, for the outcome of tranquillisation or asleep by 30 minutes we found droperidol to be less acutely tranquillising than midazolam (1 RCT, N = 153, RR 0.96, 95% CI 0.72 to 1.28, high-quality evidence). As regards the 'need for additional medication by 60 minutes after initial adequate sedation, we found an effect (1 RCT, N = 153, RR 0.54, 95% CI 0.24 to 1.20, moderate-quality evidence). In terms of adverse effects, we found no statistically significant differences between the two drugs for either airway obstruction (1 RCT, N = 153, RR 0.13, 95% CI 0.01 to 2.55, low-quality evidence) or respiratory hypoxia (1 RCT, N = 153, RR 0.70, 95% CI 0.16 to 3.03, moderate-quality evidence) - but use of midazolam did result in three people (out of around 70) needing some sort of 'airway management' with no such events in the droperidol group. There were no data for mental state, service use and costs.Furthermore, when droperidol was compared to olanzapine, for the outcome of tranquillisation or asleep by any time point, we found no clear differences between the older drug (droperidol) and olanzapine (e.g. at 30 minutes: 1 RCT, N = 221, RR 1.02, 95% CI 0.94 to 1.11, high-quality evidence). There was a suggestion that participants allocated droperidol needed less additional medication after 60 minutes than people given the olanzapine (1 RCT, N = 221, RR 0.56, 95% CI 0.36 to 0.87, high-quality evidence). There was no evidence that droperidol caused more cardiovascular arrhythmia (1 RCT, N = 221, RR 0.32, 95% CI 0.01 to 7.88, moderate-quality evidence) and respiratory airway obstruction (1 RCT, N = 221, RR 0.97, 95% CI 0.20 to 4.72, low-quality evidence) than olanzapine. For 'being ready for discharge', there was no difference between groups (1 RCT, N = 221, RR 1.06, 95% CI 0.83 to 1.34, high-quality evidence). There were no data for mental state and costs.
AUTHORS' CONCLUSIONS
Previously, the use of droperidol was justified based on experience rather than evidence from well-conducted and reported randomised trials. However, this update found high-quality evidence with minimal risk of bias to support the use of droperidol for acute psychosis. Also, we found no evidence to suggest that droperidol should not be a treatment option for people acutely ill and disturbed because of serious mental illnesses.
Topics: Acute Disease; Aggression; Antipsychotic Agents; Benzodiazepines; Droperidol; Haloperidol; Humans; Midazolam; Olanzapine; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic
PubMed: 27976370
DOI: 10.1002/14651858.CD002830.pub3 -
The Cochrane Database of Systematic... Nov 2016Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such situations should ensure that the person becomes calm swiftly and safely.
OBJECTIVES
To examine whether haloperidol plus promethazine is an effective treatment for psychosis-induced aggression.
SEARCH METHODS
On 6 May 2015 we searched the Cochrane Schizophrenia Group's Register of Trials, which is compiled by systematic searches of major resources (including MEDLINE, EMBASE, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings.
SELECTION CRITERIA
All randomised clinical trials with useable data focusing on haloperidol plus promethazine for psychosis-induced aggression.
DATA COLLECTION AND ANALYSIS
We independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We found two new randomised controlled trials (RCTs) from the 2015 update searching. The review now includes six studies, randomising 1367 participants and presenting data relevant to six comparisons.When haloperidol plus promethazine was compared with haloperidol alone for psychosis-induced aggression for the outcome not tranquil or asleep at 30 minutes, the combination treatment was clearly more effective (n=316, 1 RCT, RR 0.65, 95% CI 0.49 to 0.87, high-quality evidence). There were 10 occurrences of acute dystonia in the haloperidol alone arm and none in the combination group. The trial was stopped early as haloperidol alone was considered to be too toxic.When haloperidol plus promethazine was compared with olanzapine, high-quality data showed both approaches to be tranquillising. It was suggested that the combination of haloperidol plus promethazine was more effective, but the difference between the two approaches did not reach conventional levels of statistical significance (n=300, 1 RCT, RR 0.60, 95% CI 0.22 to 1.61, high-quality evidence). Lower-quality data suggested that the risk of unwanted excessive sedation was less with the combination approach (n=116, 2 RCTs, RR 0.67, 95% CI 0.12 to 3.84).When haloperidol plus promethazine was compared with ziprasidone all data were of lesser quality. We identified no binary data for the outcome tranquil or asleep. The average sedation score (Ramsay Sedation Scale) was lower for the combination approach but not to conventional levels of statistical significance (n=60, 1 RCT, MD -0.1, 95% CI - 0.58 to 0.38). These data were of low quality and it is unclear what they mean in clinical terms. The haloperidol plus promethazine combination appeared to cause less excessive sedation but again the difference did not reach conventional levels of statistical significance (n=111, 2 RCTs, RR 0.30, 95% CI 0.06 to 1.43).We found few data for the comparison of haloperidol plus promethazine versus haloperidol plus midazolam. Average Ramsay Sedation Scale scores suggest the combination of haloperidol plus midazolam to be the most sedating (n=60, 1 RCT, MD - 0.6, 95% CI -1.13 to -0.07, low-quality evidence). The risk of excessive sedation was considerably less with haloperidol plus promethazine (n=117, 2 RCTs, RR 0.12, 95% CI 0.03 to 0.49, low-quality evidence). Haloperidol plus promethazine seemed to decrease the risk of needing restraints by around 12 hours (n=60, 1 RCT, RR 0.24, 95% CI 0.10 to 0.55, low-quality evidence). It may be that use of midazolam with haloperidol sedates swiftly, but this effect does not last long.When haloperidol plus promethazine was compared with lorazepam, haloperidol plus promethazine seemed to more effectively cause sedation or tranquillisation by 30 minutes (n=200, 1 RCT, RR 0.26, 95% CI 0.10 to 0.68, high-quality evidence). The secondary outcome of needing restraints or seclusion by 12 hours was not clearly different between groups, with about 10% in each group needing this intrusive intervention (moderate-quality evidence). Sedation data were not reported, however, the combination group did have less 'any serious adverse event' in 24-hour follow-up, but there were not clear differences between the groups and we are unsure exactly what the adverse effect was. There were no deaths.When haloperidol plus promethazine was compared with midazolam, there was clear evidence that midazolam is more swiftly tranquillising of an aggressive situation than haloperidol plus promethazine (n=301, 1 RCT, RR 2.90, 95% CI 1.75 to 4.8, high-quality evidence). On its own, midazolam seems to be swift and effective in tranquillising people who are aggressive due to psychosis. There was no difference in risk of serious adverse event overall (n=301, 1 RCT, RR 1.01, 95% CI 0.06 to 15.95, high-quality evidence). However, 1 in 150 participants allocated haloperidol plus promethazine had a swiftly reversed seizure, and 1 in 151 given midazolam had swiftly reversed respiratory arrest.
AUTHORS' CONCLUSIONS
Haloperidol plus promethazine is effective and safe, and its use is based on good evidence. Benzodiazepines work, with midazolam being particularly swift, but both midazolam and lorazepam cause respiratory depression. Olanzapine intramuscular and ziprasidone intramuscular do seem to be viable options and their action is swift, but resumption of aggression with subsequent need to re-inject was more likely than with haloperidol plus promethazine. Haloperidol used on its own without something to offset its frequent and serious adverse effects does seem difficult to justify.
Topics: Aggression; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Lorazepam; Midazolam; Promethazine; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic; Restraint, Physical
PubMed: 27885664
DOI: 10.1002/14651858.CD005146.pub3