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PloS One 2012Inappropriate medication prescription is a common cause of preventable adverse drug events among elderly persons in the primary care setting. (Review)
Review
BACKGROUND
Inappropriate medication prescription is a common cause of preventable adverse drug events among elderly persons in the primary care setting.
OBJECTIVE
The aim of this systematic review is to quantify the extent of inappropriate prescription to elderly persons in the primary care setting.
METHODS
We systematically searched Ovid-Medline and Ovid-EMBASE from 1950 and 1980 respectively to March 2012. Two independent reviewers screened and selected primary studies published in English that measured (in)appropriate medication prescription among elderly persons (>65 years) in the primary care setting. We extracted data sources, instruments for assessing medication prescription appropriateness, and the rate of inappropriate medication prescriptions. We grouped the reported individual medications according to the Anatomical Therapeutic and Chemical (ATC) classification and compared the median rate of inappropriate medication prescription and its range within each therapeutic class.
RESULTS
We included 19 studies, 14 of which used the Beers criteria as the instrument for assessing appropriateness of prescriptions. The median rate of inappropriate medication prescriptions (IMP) was 20.5% [IQR 18.1 to 25.6%.]. Medications with largest median rate of inappropriate medication prescriptions were propoxyphene 4.52 (0.10-23.30)%, doxazosin 3.96 (0.32 15.70)%, diphenhydramine 3.30 (0.02-4.40)% and amitriptiline 3.20 (0.05-20.5)% in a decreasing order of IMP rate. Available studies described unequal sets of medications and different measurement tools to estimate the overall prevalence of inappropriate prescription.
CONCLUSIONS
Approximately one in five prescriptions to elderly persons in primary care is inappropropriate despite the attention that has been directed to quality of prescription. Diphenhydramine and amitriptiline are the most common inappropriately prescribed medications with high risk adverse events while propoxyphene and doxazoxin are the most commonly prescribed medications with low risk adverse events. These medications are good candidates for being targeted for improvement e.g. by computerized clinical decision support.
Topics: Aged; Humans; Inappropriate Prescribing; Primary Health Care
PubMed: 22928004
DOI: 10.1371/journal.pone.0043617 -
The Cochrane Database of Systematic... May 2012The worldwide incidence of whooping cough (pertussis) has been estimated at 48.5 million cases and nearly 295,000 deaths per year. In low-income countries, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The worldwide incidence of whooping cough (pertussis) has been estimated at 48.5 million cases and nearly 295,000 deaths per year. In low-income countries, the case-fatality rate among infants may be as high as 4%. Much of the morbidity of whooping cough in children and adults is due to the effects of the paroxysmal cough. Cough treatments proposed include corticosteroids, beta 2-adrenergic agonists, pertussis-specific immunoglobulin, antihistamines and possibly leukotriene receptor antagonists (LTRAs).
OBJECTIVES
To assess the effectiveness and safety of interventions to reduce the severity of paroxysmal cough in whooping cough in children and adults.
SEARCH METHODS
We updated searches of the Cochrane Central Register of Controlled Trials (CENTRAL Issue 2, 2012), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, the Database of Abstracts of Reviews of Effects (DARE Issue 2, 2012) accessed from The Cochrane Library, MEDLINE (1950 to January 2012), EMBASE (1980 to January 2012), AMED (1985 to January 2012), CINAHL (1980 to January 2012) and LILACS (January 2012). We searched Current Controlled Trials to identify trials in progress.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) and quasi-RCTs of any intervention (excluding antibiotics and vaccines) to suppress the cough in whooping cough.
DATA COLLECTION AND ANALYSIS
Two review authors (SB, MT) independently selected trials, extracted data and assessed the quality of each trial for this review in 2009. Two review authors (SB, KW) independently reviewed additional studies identified by the updated search in 2012. The primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis (turning blue), development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay.
MAIN RESULTS
Ten trials were included of varying sample sizes (N = 9 to 135) from high-income countries. Study quality was generally poor. Included studies did not show a statistically significant benefit for any of the interventions. Only six trials including a total of 196 participants reported data in sufficient detail for analysis. Diphenhydramine did not change coughing episodes; the mean difference (MD) of coughing spells per 24 hours was 1.9; 95% confidence interval (CI) - 4.7 to 8.5. One study on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02) but no change in hospital stay (MD -0.7 days; 95% CI -3.8 to 2.4). Dexamethasone did not show a clear decrease in length of hospital stay (MD -3.5 days; 95% CI -15.3 to 8.4) and salbutamol showed no change in coughing paroxysms per 24 hours (MD -0.2; 95% CI -4.1 to 3.7). Only one trial comparing pertussis immunoglobulin versus placebo reported data on adverse events: 4.3% in the treatment group (rash) versus 5.3% in the placebo group (loose stools, pain and swelling at injection site).
AUTHORS' CONCLUSIONS
There is insufficient evidence to draw conclusions about the effectiveness of interventions for the cough in whooping cough.
Topics: Adult; Albuterol; Anti-Inflammatory Agents; Bordetella pertussis; Child; Cough; Dexamethasone; Diphenhydramine; Histamine H1 Antagonists; Humans; Immunoglobulins; Length of Stay; Randomized Controlled Trials as Topic; Whooping Cough
PubMed: 22592689
DOI: 10.1002/14651858.CD003257.pub4 -
The Cochrane Database of Systematic... Mar 2012Urticaria is a common skin disease characterised by itching weals or hives, which can occur almost anywhere on the body. There are a number of different subtypes and a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Urticaria is a common skin disease characterised by itching weals or hives, which can occur almost anywhere on the body. There are a number of different subtypes and a range of available treatment options. There is lack of agreement on the efficacy of H2-receptor antagonists used in the treatment of urticaria.
OBJECTIVES
To assess the safety and effectiveness of H2-receptor antagonists in the treatment of urticaria.
SEARCH METHODS
We searched the following databases up to 7 October 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2011, Issue 4), MEDLINE (from 2005), EMBASE (from 2007), and LILACS (from 1982). We also searched online trials registries for ongoing trials.
SELECTION CRITERIA
Randomised controlled trials of H2-receptor antagonists in people with a clinical diagnosis of urticaria of any duration or of any subtype. Studies including H1-antihistamines for chronic urticaria are the topic of a separate Cochrane review; thus, they were not included in this review.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial quality and extracted and analysed data.
MAIN RESULTS
Four studies of a relatively small size, involving 144 participants, were included in this review. A combination of ranitidine with diphenhydramine was more effective at improving the resolution of urticaria than diphenhydramine administered alone (risk ratio (RR) 1.59, 95% confidence interval (CI) 1.07 to 2.36). Although there was a similar improvement in itching, weal size, and intensity, cimetidine provided no statistically significant greater overall improvement in symptoms of urticaria when compared to diphenhydramine. However, a combination of these medications was more effective than diphenhydramine alone (RR 2.02, 95% CI 1.03 to 3.94). Adverse events were reported with several of the interventions, i.e. ranitidine and diphenhydramine, causing drowsiness and sedation, but there was no significant difference in the level of sedation from baseline with either famotidine or diphenhydramine.
AUTHORS' CONCLUSIONS
The very limited evidence provided by this review was based on a few old studies of a relatively small size, which we categorised as having high to unclear risk of bias. Thus, at present, the review does not allow confident decision-making about the use of H2-receptor antagonists for urticaria. Although some of these studies have reported a measure of relief of symptoms of urticaria and rather minimal clinical improvement in some of the participants, the evidence was weak and unreliable. We have emphasised the lack of precision and limitations in the reported data where appropriate in this review.
Topics: Cimetidine; Diphenhydramine; Drug Therapy, Combination; Famotidine; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Randomized Controlled Trials as Topic; Ranitidine; Urticaria
PubMed: 22419335
DOI: 10.1002/14651858.CD008596.pub2 -
The Cochrane Database of Systematic... Mar 2012Cough causes concern for parents and is a major cause of outpatient visits. It can impact on quality of life, cause anxiety and affect sleep in parents and children.... (Review)
Review
BACKGROUND
Cough causes concern for parents and is a major cause of outpatient visits. It can impact on quality of life, cause anxiety and affect sleep in parents and children. Several remedies, including honey, have been used to alleviate cough symptoms.
OBJECTIVES
To evaluate the effectiveness of honey for acute cough in children in ambulatory settings.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2011) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1950 to December week 4, 2011); EMBASE (1990 to January 2012); CINAHL (1981 to January 2012); Web of Science (2000 to January 2012); AMED (1985 to January 2012); LILACS (1982 to January 2012); and CAB abstracts (2009 to January 2012).
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing honey given alone, or in combination with antibiotics, versus nothing, placebo or other over-the-counter (OTC) cough medications to participants aged from two to 18 years for acute cough in ambulatory settings.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results for eligible studies and extracted data on reported outcomes.
MAIN RESULTS
We included two RCTs of high risk of bias involving 265 children. The studies compared the effect of honey with dextromethorphan, diphenhydramine and 'no treatment' on symptomatic relief of cough using the 7-point Likert scale.Honey was better than 'no treatment' in reducing frequency of cough (mean difference (MD) -1.07; 95% confidence interval (CI) -1.53 to -0.60; two studies; 154 participants). Moderate quality evidence suggests honey did not differ significantly from dextromethorphan in reducing cough frequency (MD -0.07; 95% CI -1.07 to 0.94; two studies; 149 participants). Low quality evidence suggests honey may be slightly better than diphenhydramine in reducing cough frequency (MD -0.57; 95% CI -0.90 to -0.24; one study; 80 participants).Adverse events included mild reactions (nervousness, insomnia and hyperactivity) experienced by seven children (9.3%) from the honey group and two (2.7%) from the dextromethorphan group; the difference was not significant (risk ratio (RR) 2.94; 95% Cl 0.74 to 11.71; two studies; 149 participants). Three children (7.5%) in the diphenhydramine group experienced somnolence (RR 0.14; 95% Cl 0.01 to 2.68; one study; 80 participants) but there was no significant difference between honey versus dextromethorphan or honey versus diphenhydramine. No adverse event was reported in the 'no treatment' group.
AUTHORS' CONCLUSIONS
Honey may be better than 'no treatment' and diphenhydramine in the symptomatic relief of cough but not better than dextromethorphan. There is no strong evidence for or against the use of honey.
Topics: Adolescent; Antitussive Agents; Apitherapy; Child; Child, Preschool; Cough; Dextromethorphan; Honey; Humans; Randomized Controlled Trials as Topic
PubMed: 22419319
DOI: 10.1002/14651858.CD007094.pub3 -
BMJ Clinical Evidence Oct 2011Up to 40% of older adults have insomnia, with difficulty getting to sleep, early waking, or feeling unrefreshed on waking. The prevalence of insomnia increases with age.... (Review)
Review
INTRODUCTION
Up to 40% of older adults have insomnia, with difficulty getting to sleep, early waking, or feeling unrefreshed on waking. The prevalence of insomnia increases with age. Other risk factors include psychological factors, stress, daytime napping, and hyperarousal.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug treatments for insomnia in older people? What are the effects of drug treatments for insomnia in older people? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 34 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antidepressants, benzodiazepines, cognitive behavioural therapy (CBT), diphenhydramine, exercise programmes, timed exposure to bright light, zaleplon, zolpidem, and zopiclone.
Topics: Cognitive Behavioral Therapy; Diphenhydramine; Evidence-Based Medicine; Humans; Prevalence; Sleep; Sleep Initiation and Maintenance Disorders
PubMed: 22030082
DOI: No ID Found -
Journal of Paediatrics and Child Health Feb 2012Based on concerns about safety and efficacy, international authorities have either advised against the use of cough and cold medication or considering such action. We... (Review)
Review
AIMS
Based on concerns about safety and efficacy, international authorities have either advised against the use of cough and cold medication or considering such action. We aimed to systematically review the evidence for the effectiveness and safety of cough and cold medicines in children.
METHODS
We conducted a systematic review to identify studies relating to the use of products to treat symptoms of the common cold, influenza or allergic rhinitis, and relating to poisoning or toxicity from unintentional ingestion or overdose in children (<12 years). Medline, Embase and the Cochrane database were searched. No meta-analysis was undertaken because of the paucity of evidence, multiple medicines available, and the need to consider both effectiveness and safety.
RESULTS
Seventy two relevant studies or clinical reports were identified. There was little support for the effectiveness of these medicines for acute cough or the common cold in children. However, the majority of these medicines do not appear to be highly toxic in children and are not a major cause of severe effects following unintentional poisoning. The common use of these agents does not appear to be responsible for increased deaths in young children. Many cases of toxicity from cough and cold medications in young children are a result of therapeutic error. Particular medications, including diphenhydramine and codeine, appear to be associated with a high frequency of severe adverse effects and toxicity.
CONCLUSION
Restriction of cough and cold medicines in children is supported by currently available evidence.
Topics: Antitussive Agents; Australia; Child; Child, Preschool; Common Cold; Cough; Drug and Narcotic Control; Histamine Antagonists; Humans; Infant; Nasal Decongestants
PubMed: 20598066
DOI: 10.1111/j.1440-1754.2010.01780.x -
The Cochrane Database of Systematic... Jun 2010Allergic and febrile non-haemolytic transfusion reactions (NHTRs) are the two most common forms of transfusion reaction. Pretransfusion medication with anti-inflammatory... (Review)
Review
BACKGROUND
Allergic and febrile non-haemolytic transfusion reactions (NHTRs) are the two most common forms of transfusion reaction. Pretransfusion medication with anti-inflammatory drugs is used in NHTR prevention, however its efficacy and safety remains unclear.
OBJECTIVES
To assess the clinical effects and safety of pharmacological interventions for preventing NHTR in patients with and without a history of transfusion reactions.
SEARCH STRATEGY
The search strategy included The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4, 2008), Cochrane Injuries Group's Specialised Register (December 17, 2008), MEDLINE (1950 to November (week 3) 2008), EMBASE (1988 to November (week 3) 2008), LILACS (1982 to January 12, 2009), CINAHL (1982 to December 2008), ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED): 1970 to December 2008). There was no language restriction.
SELECTION CRITERIA
Randomised controlled trials (RCTs) assessing the effectiveness of interventions for the prevention of NHTR.
DATA COLLECTION AND ANALYSIS
Authors independently selected studies, assessed the risks of bias and extracted data. Relative risks (RR) were estimated in RCTs with parallel design (PD). Odds ratio (OR) was estimated for one RCT with crossover design (CD). No meta-analysis was attempted due to differences in the pharmacotherapy of pre-transfusion medication and methodology between the studies; a per-protocol analysis was used.
MAIN RESULTS
This review includes three RCTs (two PD and one CD). The PD-RCTs employed disparate units of randomisation (UofR); patient or transfusion, while the CD-RCT applied the patient as the UofR. The PD-RCTs administered leukodepleted blood products. Both PD-RCTs compared acetaminophen plus diphenhydramine (ApD) at different regimens with placebo, while the CD-RCT contrasted hydrocortisone pharmacotherapy with diphenhydramine. Both PD-RCTs found no statistically significant difference in allergic reactions (RR 0.13, 95% confidence interval (CI) 0.01 to 2.39, RR 1.46, 95% CI 0.78 to 2.73) and febrile reactions (RR 0.52, 95% CI 0.22 to 1.26). The CD-RCT found a statistically significant difference in the odds of febrile reactions (OR 2.38, 95% CI 1.07 to 5.27). The trials did not report anaphylactic reactions, deaths related to transfusion reactions or other adverse events.
AUTHORS' CONCLUSIONS
None of the three studies found that medication prior to transfusion reduces NHTR. This applied regardless of the patient's history of NHTR and the use of leukodepleted blood products in the transfusion. However, this conclusion is based on three trials of moderate to low quality. A better-powered RCT is necessary to evaluate the role of pretransfusion medication in the prevention of NHTR. Inclusion criteria should be restricted to patients at high risk of developing NHTR, with no restriction by age, history of transfusion reactions and type of blood products (leukodepleted or not).
Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Diphenhydramine; Fever; Histamine H1 Antagonists; Humans; Hydrocortisone; Hypersensitivity; Premedication; Randomized Controlled Trials as Topic; Transfusion Reaction
PubMed: 20556779
DOI: 10.1002/14651858.CD007539.pub2 -
The Cochrane Database of Systematic... Jan 2010The worldwide incidence of whooping cough (pertussis) has been estimated at 48.5 million cases and nearly 295,000 deaths per year. In low-income countries, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The worldwide incidence of whooping cough (pertussis) has been estimated at 48.5 million cases and nearly 295,000 deaths per year. In low-income countries, the case-fatality rate among infants may be as high as 4%. Much of the morbidity of whooping cough in children and adults is due to the effects of the paroxysmal cough. Cough treatments proposed include corticosteroids, beta 2-adrenergic agonists, pertussis-specific immunoglobulin, antihistamines and possibly leukotriene receptor antagonists (LTRAs).
OBJECTIVES
To assess the effectiveness and safety of interventions to reduce the severity of paroxysmal cough in whooping cough in children and adults.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 1), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register and the Database of Abstracts of Reviews of Effects (DARE); MEDLINE (1950 to March 2009); EMBASE (1980 to March 2009); AMED (1985 to March 2009); CINAHL (1982 to March 2009) and LILACS (March 2009).
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs of any intervention (excluding antibiotics and vaccines) to suppress the cough in whooping cough.
DATA COLLECTION AND ANALYSIS
Two review authors (SB, MT) independently selected trials, extracted data and assessed the quality of each trial. The primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis (turning blue), development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay.
MAIN RESULTS
Ten trials were included of varying sample sizes (N = 9 to 135) from high-income countries. Study quality was generally poor. Included studies did not show a statistically significant benefit for any of the interventions. Diphenhydramine did not change coughing episodes; the mean difference of coughing spells per 24 hours was 1.9 (95% confidence interval (CI) - 4.7 to 8.5). One study on pertussis immunoglobulin reported a possible mean reduction of -3.1 whoops per 24 hours (95% CI -6.2 to 0.02) but no change in hospital stay (-0.7 days) (95% CI -3.8 to 2.4). Dexamethasone did not show a clear decrease in length of hospital stay (-3.5 days) (95% CI -15.3 to 8.4) and salbutamol showed no change in coughing paroxysms per 24 hours (-0.22) (95% CI -4.13 to 3.69).
AUTHORS' CONCLUSIONS
Insufficient evidence exists to draw conclusions about the effects of interventions for the cough in whooping cough.
Topics: Adult; Albuterol; Anti-Inflammatory Agents; Child; Cough; Dexamethasone; Diphenhydramine; Histamine H1 Antagonists; Humans; Immunoglobulins; Randomized Controlled Trials as Topic; Whooping Cough
PubMed: 20091541
DOI: 10.1002/14651858.CD003257.pub3 -
The Cochrane Database of Systematic... Oct 2008Whooping cough is an important cause of childhood morbidity and mortality. There are 20 to 40 million cases of whooping cough annually world-wide, 90% of which occur in... (Review)
Review
BACKGROUND
Whooping cough is an important cause of childhood morbidity and mortality. There are 20 to 40 million cases of whooping cough annually world-wide, 90% of which occur in developing countries, resulting in an estimated 200 to 300,000 fatalities each year. Much of the morbidity is due to the effects of the paroxysmal cough. Corticosteroids, salbutamol (beta 2 - adrenergic stimulant), and pertussis-specific immunoglobulin have been proposed as standard treatment for the cough. Antihistamines have also been administered. No systematic review of the effectiveness of any of these interventions or others has been performed.
OBJECTIVES
To assess the effectiveness and safety of interventions used to reduce the severity of the coughing paroxysms in whooping cough in children and adults.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2003, issue 2); MEDLINE (January 1966 to June 2003); EMBASE (1990 to June 2003) and LILACS (1982 to November 2001).
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of any intervention aimed at suppressing the cough in whooping cough; excluding antibiotics and vaccines.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data. Our primary outcome was frequency of paroxysms of coughing. Secondary outcomes were frequency of vomiting, frequency of whoop, frequency of cyanosis, development of serious complications, mortality from any cause, side effects due to medication, admission to hospital and duration of hospital stay. Disagreements were resolved by discussion.
MAIN RESULTS
Nine studies satisfied the inclusion criteria but four had insufficient data for meta - analysis of pre-specified outcomes. Studies were small and poorly reported. The largest study had a sample size of 49 and the smallest study 18. All studies were performed in industrialised settings.Eligible studies assessed diphenhyramine, pertussis immunoglobulin, dexamethasone and salbutamol. No statistically significant benefit was found for any of the interventions. Diphenhydramine did not change coughing spells (mean increase of coughing spells per 24 hours 1.9 with 95% CI - 4.7 to 8.5) and pertussis immunoglobulin no change in hospital stay (0.7 days, 95% CI -3.8 to 2.4), and a mean reduction of 3.1 whoops per 24 hours (95% CI -6.2 to 0.02). Dexamethasone did not show a clear decrease in hospital stay (-3.5 days, 95% CI - 15.3 to 8.4) and salbutamol showed no change in coughing paroxysms per 24 hours (-0.22, 95% CI - 4.13 to 3.69).
AUTHORS' CONCLUSIONS
Insufficient evidence exists to draw conclusions about the effects of any intervention for the cough in whooping cough.
Topics: Adult; Albuterol; Child; Dexamethasone; Diphenhydramine; Histamine H1 Antagonists; Humans; Immunoglobulins; Randomized Controlled Trials as Topic; Whooping Cough
PubMed: 18843643
DOI: 10.1002/14651858.CD003257.pub2 -
The Cochrane Database of Systematic... Jul 2008Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use,... (Review)
Review
BACKGROUND
Clozapine is widely used for people with schizophrenia. Although agranulocytosis, weight gain, and cardiac problems are serious problems associated with its use, hypersalivation, sometimes of a gross and socially unacceptable quantity, is also common (30-80%).
OBJECTIVES
To determine the clinical effects of pharmacological interventions for clozapine-induced hypersalivation.
SEARCH STRATEGY
We searched the Cochrane Schizophrenia Group Trials Register (March 2007), inspected references of all identified studies for further trials, contacted relevant pharmaceutical companies, drug approval agencies and authors of trials.
SELECTION CRITERIA
We included randomised controlled trials comparing pharmacological interventions, at any dose and by any route of administration, for clozapine-induced hypersalivation.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data (homogenous) we calculated relative risk (RR) with 95% confidence intervals (CI) and numbers needed to treat (NNT) on an intention-to-treat basis. We calculated weighted mean difference (WMD) for continuous data.
MAIN RESULTS
Of the 15 trials identified, 14 were conducted in China and 14 in hospitals. The quality of reporting was poor with no studies clearly describing allocation concealment and much data were missing or unusable. All results are vulnerable to considerable bias. Most frequently the primary outcome was the diameter of the wet patch on the pillow. Antimuscarinics (astemizole, diphenhydramine, propantheline, doxepin) were the most commonly evaluated drugs. For the outcome of 'no clinically important improvement' astemizole and diphenhydramine were more effective than placebo (astemizole: n=97, 2 RCTs, RR 0.61 CI 0.47 to 0.81 NNT 3 CI 2 to 5; diphenhydramine: n=131, 2 RCTs, RR 0.43 CI 0.31 to 0.58, NNT 2 CI 1.5 to 2.5), but the doses of astemizole used were those that can cause toxicity. Data involving propantheline were heterogeneous (I2= 86.6%), but both studies showed benefit over placebo. Adverse effects were poorly recorded. Of the other interventions, oryzanol (rice bran oil and rice embryo oil extract) showed benefit over the antimuscarinic doxepin in terms of 'no clinically important change' (n=104, 1 RCT, RR 0.45 CI 0.27 to 0.75, NNT 4 CI 2 to 7). The Chinese medicine suo quo wan (comprises spicebush root, Chinese yam and bitter cardamom) showed benefit over doxepin (n=70, 1 RCT, RR 'no clinically important change' 0.31 CI 0.16 to 0.59, NNT 3 CI 1.5 to 3.7).
AUTHORS' CONCLUSIONS
There are currently insufficient data to confidently inform clinical practice. The limitations of these studies are plentiful and the risk of bias is high. These trials, however, are invaluable guides for current and future study design. Well conducted randomised trials are possible. Some may be underway. Current practice outside of well designed randomised trials should be clearly justified.
Topics: Antipsychotic Agents; Clozapine; Drugs, Chinese Herbal; Muscarinic Antagonists; Phenylpropionates; Randomized Controlled Trials as Topic; Sialorrhea
PubMed: 18646130
DOI: 10.1002/14651858.CD005579.pub2