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Biomedical subjects

M Fenton

Publications and source records attributed to M Fenton.

At least 19 recordsLinked to original sources
PubMed2006

Zotepine for schizophrenia.

BACKGROUND: Zotepine is a relatively new antipsychotic often used for the treatment of people with schizophrenia. It is claimed to be particularly effective for negative symptoms. OBJECTIVES: To determine the effects of zotepine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: For the 2006 update we searched the Cochrane Schizophrenia Group's register of trials. SELECTION CRITERIA: We included all randomised clinical trials comparing zotepine with other treatments for people with schizophrenia or other psychoses. DATA COLLECTION AND ANALYSIS: We independently inspected citations and abstracts, ordered papers, re-inspected these and assessed their quality. For homogenous dichotomous data we calculated the relative risk (RR), 95% confidence intervals (CI) and, where appropriate, numbers needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We inspected all data for heterogeneity. MAIN RESULTS: The review currently includes 11 studies with 966 participants. Most outcomes were short term (4-12 weeks). We found no data for outcomes such as relapse, time in hospital, satisfaction with care and day-to-day functioning. Compared with placebo, mental state ratings favoured zotepine (n=106, 1 RCT, RR No 20% decrease in BPRS 0.44 CI 0.3 to 0.7, NNT 3 CI 2 to 6) using the last observation carried forward method. For the comparison with typical drugs, limited data suggest that zotepine may be as effective as these older medications. Mental state measures of 'no clinically important improvement' favour zotepine when compared with other active drugs (n=356, 4 RCTs, RR 0.77 CI 0.7 to 0.9, NNT 7 CI 4 to 22). About one third of people in both the zotepine and control groups left the studies before trial completion. Zotepine may result in less movement disorder adverse effects than typical antipsychotic drugs. Trials have not highlighted clear differences between zotepine and other atypical drugs. AUTHORS' CONCLUSIONS: Zotepine may be a valuable addition to the class of atypical antipsychotic drugs. However, more data from existing studies is urgently needed to increase confidence in the findings of this review. In addition to this, new data from well planned, conducted and reported long term pragmatic randomised trials are needed. Otherwise clinical use of zotepine will be based upon speculation of short explanatory trials for everyday practice.

Antipsychotic Agents↗
PubMed2006

Containment strategies for people with serious mental illness.

BACKGROUND: The management of acutely disturbed people during periods of psychiatric crisis poses a particular challenge for mental health professionals. The challenge is to maintain safety while providing a safe and therapeutic environment. Non-pharmaceutical methods currently used to accomplish this include special observations, de-escalation, behavioural contracts and locking doors. OBJECTIVES: To compare the effects of various strategies used to contain acutely disturbed people during periods of psychiatric crisis (excluding seclusion and restraint and the use of 'as prescribed medication). SEARCH STRATEGY: For the 2006 update of this review, we searched the Ovid interface of CINAHL, CENTRAL and The Schizophrenia Groups register, EMBASE, MEDLINE, PsycINFO. SELECTION CRITERIA: Relevant randomised controlled trials involving people hospitalised with serious mental illness, comparing any non-pharmacological interventions aimed at containing people who were at risk of harming themselves or others, (such as those approaches that change observation levels, lock wards, manage staff patient ratios, use de-escalation techniques or behavioural contracts). DATA COLLECTION AND ANALYSIS: Trials would have been reliably quality assessed and data extracted. Relative risks (RR) and 95% confidence intervals (CI) would have been calculated with a random effects model. Where possible, numbers needed to treat and harm (NNT, NNH) would have been estimated. MAIN RESULTS: The initial 1999 search identified over 2000 reports and the update search of 2006, an additional 2808 reports. Of these, only six seemed to have the potential to be relevant, but once they were obtained it was clear they could not be included. None focused upon non-pharmacological methods for containment of violence or self harm in people with serious mental illness. AUTHORS' CONCLUSIONS: Current non-pharmacological approaches to containment of disturbed or violent behaviour are not supported by evidence from controlled studies. Clinical practice is based on evidence that is not derived from trials and continued practice entirely outside of well designed, conducted and reported randomised studies is difficult to justify.

Aggression↗
PubMed2006

Psychological therapies for people with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is a relatively common personality disorder with a major impact on health services as those affected often present in crisis, often self-harming. OBJECTIVES: To evaluate the effects of psychological interventions for people with borderline personality disorder. SEARCH STRATEGY: We conducted a systematic search of 26 specialist and general bibliographic databases (December 2002) and searched relevant reference lists for further trials. SELECTION CRITERIA: All relevant clinical randomised controlled trials involving psychological treatments for people with BPD. The definition of psychological treatments included behavioural, cognitive-behavioural, psychodynamic and psychoanalytic. DATA COLLECTION AND ANALYSIS: We independently selected, quality assessed and data extracted studies. For binary outcomes we calculated a standard estimation of the risk ratio (RR), its 95% confidence interval (CI), and where possible the number need to help/harm (NNT/H). For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). MAIN RESULTS: We identified seven studies involving 262 people, and five separate comparisons. Comparing dialectical behaviour therapy (DBT) with treatment as usual studies found no difference for the outcome of still meeting SCID-II criteria for the diagnosis of BPD by six months (n=28, 1 RCT, RR 0.69 CI 0.35 to 1.38) or admission to hospital in previous three months (n=28, 1 RCT, RR 0.77 CI 0.28 to 2.14). Self harm or parasuicide may decrease at 6 to 12 months (n=63, 1 RCT, RR 0.81 CI 0.66 to 0.98, NNT 12 CI 7 to 108). One study detected statistical difference in favour of people receiving DBT compared with those allocated to treatment as usual for average scores of suicidal ideation at 6 months (n=20, MD -15.30 CI -25.46 to -5.14). There was no difference for the outcome of leaving the study early (n=155, 3 RCTs, RR 0.74 CI 0.52 to 1.04). For the outcome of interviewer-assessed alcohol free days, skewed data are reported and tend to favour DBT. When a substance abuse focused DBT was compared with comprehensive validation therapy plus 12-step substance misuse programme no clear differences were found for service outcomes (n=23, 1 RCT, RR imprisoned 1.09 CI 0.64 to 1.87) or leaving the study early (n=23, 1 RCT, RR 7.58 CI 0.44 to 132.08). When dialectical behaviour therapy-oriented treatment is compared with client centred therapy no differences were found for service outcomes (n=24, 1 RCT, RR admitted 0.33 CI 0.08 to 1.33). However, fewer people in the DBT group displayed indicators of parasuicidal behaviour (n=24, RR 0.13 CI 0.02 to 0.85, NNT 2 CI 2 to 11). There were no differences for outcomes of anxiety and depression (n=24, 1 RCT, RR anxiety BAI >/=10 0.60 CI 0.32 to 1.12; RR depression HDRS >/=10 0.43 CI 0.14 to 1.28) but people who received DBT had less general psychiatric severity than those in the control (MD BPRS at 6 months -7.41 CI -13.72 to -1.10). Finally this one relevant study reports skewed data for suicidal ideation with considerably lower scores for people allocated to DBT. When psychoanalytically oriented partial hospitalization was compared with general psychiatric care the former tended to come off best. People who received treatment in a psychoanalytic orientated day hospital were less likely to be admitted into inpatient care when measured at different time points (e.g. n=44, RR admitted to inpatient 24 hour care >18 to 24 months 0.05 CI 0.00 to 0.77, NNT 3 CI 3 to 10) Fewer people in psychoanalytically oriented partial hospitalization needed day hospital intervention in the 18 months after discharge (n=44, 1 RCT, RR 0.04 CI 0.00 to 0.59, NNT 2 CI 2 to 8). More people in the control group took psychotropic medication by the 30 to 36 month follow-up, than those receiving psychoanalytic treatment (n=44, 1 RCT, RR 0.44 CI 0.25 to 0.80, NNT 3 CI 2 to 7). Anxiety and depression scores were generally lower in the psychoanalytically oriented partial hospitalization group (n=44, 1 RCT, RR >/=14 on BDI 0.52 CI 0.34 to 0.80, NNT 3 CI 3 to 6), as are global severity scores. People receiving psychoanalytic care in a day hospital had better social improvement in social adjustment using the SAS-SR at 6 to 12 months compared with people in general psychiatric care (MD -0.70 CI -1.08 to -0.32). Rates of attrition were the same (n=44, 1 RCT, RR leaving the study early 1.00 CI 0.23 to 4.42). AUTHORS' CONCLUSIONS: This review suggests that some of the problems frequently encountered by people with borderline personality disorder may be amenable to talking/behavioural treatments but all therapies remain experimental and the studies are too few and small to inspire full confidence in their results. These findings require replication in larger 'real-world' studies.

Behavior Therapy↗
PubMed2006

Pharmacological interventions for people with borderline personality disorder.

BACKGROUND: Borderline Personality Disorder (BPD) is prevalent (2% in the general population, 20% among psychiatry in-patients) and has a major impact on health facilities as those affected often present in crisis but then make poor use of further attempts to help them. OBJECTIVES: To evaluate the effects of pharmacological interventions for people with borderline personality disorder. SEARCH STRATEGY: We conducted a systematic search of 26 specialist and general bibliographic databases (October 2002) and searched relevant reference lists for further trials. SELECTION CRITERIA: We included all randomised clinical trials comparing any psychoactive drugs with any other treatment for people with borderline personality disorder. DATA COLLECTION AND ANALYSIS: We independently selected, quality assessed and data extracted studies. For binary outcomes we calculated a standard estimation of the risk ratio (RR), its 95% confidence interval (CI), and where possible the number need to help/harm (NNT/H). For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were synthesised using a weighted mean difference (WMD). MAIN RESULTS: We found ten small (total n=554), short, randomised studies involving eight comparisons from which we could extract usable data. Studies comparing antidepressants with placebo were small (total n=79, 2 RCTs) but for ratings of anger fluoxetine may offer some improvement for those on antidepressant therapy over placebo (n=22, 1 RCT, RR anger not improved 0.30 CI 0.10 to 0.85, NNT 2 CI 2 to 9). The one small study investigating the important outcome of attempted suicide found no difference between mianserin and placebo (n=38, 1 RCT, RR 0.82 CI 0.44 to 1.54). Haloperidol may be better than antidepressants for symptoms of hostility and psychotism. There were few differences between MAOIs and placebo except that people given MAOIs were less hostile (n=62, 1 RCT, MD -9.19 CI -16.12 to -2.26). Although some ratings were statistically significant the comparison of MAOIs with antipsychotics did not show convincing differences. Antipsychotics may effect some mental state symptoms more effectively than placebo but results are difficult to interpret clinically and there is little evidence of advantage of one antipsychotic over another. Finally mood stabilisers such as divalporex may help mental state (n=16, 1 RCT, RR no improvement in mental state 0.58 CI 0.36 to 0.94, NNT 3 CI 2 to 17) but data are far from conclusive. AUTHORS' CONCLUSIONS: Pharmacological treatment of people with BPD is not based on good evidence from trials and it is arguable that future use of medication should be from within randomised trials. Current trials suggest that the positive effect of antidepressants, in particular, could be considerable. Well designed, conducted and reported clinically meaningful trials are possible and needed with, perhaps, the question of antidepressant versus placebo being addressed first.

Antidepressive Agents↗
PubMed2005

Olanzapine for schizophrenia.

BACKGROUND: Olanzapine is an atypical antipsychotic reported to be effective without producing disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. OBJECTIVES: To determine the clinical effects and safety of olanzapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. SEARCH STRATEGY: We updated the first search [Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and The Cochrane Schizophrenia Group's Register (October 2000)] in October 2004 using the Cochrane Schizophrenia's Group's register of trials. We also searched references of all included studies for further trials, and contacted relevant pharmaceutical companies and authors. SELECTION CRITERIA: We included all randomised clinical trials comparing olanzapine with placebo or any antipsychotic treatment for people with schizophrenia or schizophreniform psychoses. DATA COLLECTION AND ANALYSIS: We independently extracted data and, for homogeneous dichotomous data, calculated the random effects relative risk (RR), the 95% confidence intervals (CI) and the number needed to treat (NNT) on an intention-to-treat basis. For continuous data we calculated weighted mean differences. MAIN RESULTS: Fifty five trials are included (total n>10000 people with schizophrenia). Attrition from olanzapine versus placebo studies was >50% by six weeks, leaving interpretation of results problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (any dose, 2 RCTs n=418, RR 0.88 CI 0.8 to 0.1, NNT 8 CI 5 to 27). Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. The olanzapine group gained more weight. When compared with typical antipsychotic drugs, data from several small trials are incomplete. With high attrition in both groups (14 RCTs, n=3344, 38% attrition by six weeks, RR 0.81 CI 0.65 to 1.02) the assumptions included in all data are considerable. For the short term outcome of 'no important clinical response', olanzapine seems as effective as typical antipsychotics (4 RCTs, n=2778, RR 0.90 CI 0.76 to 1.06). People allocated olanzapine experienced fewer extrapyramidal adverse effects than those given typical antipsychotics. Weight change data for the short term are not statistically significant but results between three to 12 months suggest a clinically important average gain of four kilograms for people given olanzapine (4 RCTs, n=186, WMD 4.62, CI 0.6 to 8.64). Twenty three percent of people in trials of olanzapine and other atypical drugs left by eight weeks; 48% by three to12 months (11 RCTs, n=1847, RR 0.91 CI 0.82 to 1.00). There is little to choose between the atypicals, although olanzapine may cause fewer extrapyramidal adverse effects than other drugs in this category. Olanzapine produces more weight gain than other atypicals with some differences reaching conventional levels of statistical significance (1 RCT, n=980, RR gain at 2 years 1.73 CI 1.49 to 2.00, NNH 5 CI 4 to 7). There are very few data for people with first episode illness (1 RCT, duration 6 weeks, n=42). For people with treatment-resistant illness there were no clear differences between olanzapine and clozapine (4 RCTs, n=457). AUTHORS' CONCLUSIONS: The large proportion of participants leaving studies early in these trials makes it difficult to draw firm conclusions on olanzapine's clinical effects. For people with schizophrenia it may offer antipsychotic efficacy with fewer extrapyramidal adverse effects than typical drugs, but more weight gain. There is a need for further large, long-term randomised trials with more comprehensive data.

Antipsychotic Agents↗
PubMed2005

Olanzapine IM or velotab for acutely disturbed/agitated people with suspected serious mental illnesses.

BACKGROUND: People presenting with agitated or violent behaviour thought to be due to severe mental illness may require urgent pharmacological tranquillisation. Several preparations of olanzapine, an antipsychotic drug, are now being used for management of such agitation. OBJECTIVES: To estimate the effects of intramuscular, oral-velotab, or standard oral olanzapine compared with other treatments for controlling aggressive behaviour or agitation thought to be due to severe mental illness. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Issue 1, 2002), The Cochrane Schizophrenia Group's Register (November 2004) and reference lists. We contacted authors of trials and the manufacturers of olanzapine. SELECTION CRITERIA: Randomised clinical trials comparing oral-velotab or intramuscular, or standard oral olanzapine to any treatment, for agitated or aggressive people with severe mental illnesses. DATA COLLECTION AND ANALYSIS: We reliably selected, quality assessed and data extracted studies. For binary outcomes we calculated a fixed effects Risk Ratio (RR) and its 95% Confidence Interval (CI) with a weighted Number Needed to Treat/Harm statistic (NNT/H). For continuous outcomes, we preferred endpoint data to change data and synthesised non-skewed data from valid scales using a weighted mean difference (WMD). MAIN RESULTS: Four trials compared olanzapine IM with IM placebo (total n=769, 217 allocated to placebo). Fewer people given olanzapine IM had 'no important response' by 2 hours compared with placebo (4 RCTs, n=769, RR 0.49 CI 0.42 to 0.59, NNT 4 CI 3 to 5) and olanzapine IM was as acceptable as placebo (2 RCTs, n=354, RR leaving the study early 0.31 CI 0.06 to 1.55). When compared with placebo, people given olanzapine IM required substantially fewer additional injections following the initial dose (4 RCTs, n=774, RR 0.48 CI 0.40 to 0.58, NNT 4 CI 4 to 5). Olanzapine IM did not seem associated with extrapyramidal effects (4 RCT, n=570, RR experiencing any adverse event requiring anticholinergic medication in first 24 hours 1.27 CI 0.49 to 3.26). Two trials compared olanzapine IM with haloperidol IM (total n=482, 166 allocated to haloperidol). Studies found no differences between olanzapine IM and haloperidol by 2 hours for the outcome of 'no important clinical response' (2 RCTs, n= 482, RR 1.00 CI 0.73 to 1.38) neither was there a difference for needing repeat IM injections (2 RCTs, n=482, RR 0.99 CI 0.71 to 1.38). More people on haloperidol experienced akathisia over the five day oral period compared with olanzapine IM (1 RCT, n=257, RR 0.51 CI 0.32 to 0.80, NNT 6 CI 5 to 15) and fewer people allocated to olanzapine IM required anticholinergic medication by 24 hours compared with those given haloperidol IM (2 RCTs, n= 432, RR 0.20 CI 0.09 to 0.44, NNT 8 CI 7 to 11). Two trials compared olanzapine IM with lorazepam IM (total n=355, 119 allocated to lorazepam). For the outcome of 'no important clinical response' , there was no difference between people given olanzapine IM and those allocated to lorazepam at 2 hours (2 RCTs, n=355, RR 92 CI 0.66 to 1.30) but fewer people allocated to olanzapine IM required additional injections by 24 hours compared with those on lorazepam IM (2 RCTs, n=355, RR 0.68 CI 0.49 to 0.95, NNT 10 CI 6 to 59). People receiving IM olanzapine were less likely to experience any treatment emergent adverse events, than those on lorazepam (1 RCT, n=150, RR at 24 hours 0.62 CI 0.43 to 0.89, NNT 5 CI 4 to 17) and over the same time period there were no clear differences in the use of anticholinergic medication between groups (1 RCT, n=150, RR 1.16 CI 0.38 to 3.58).No studies reported outcomes related to hospital and service use. Nor did any report on issues of satisfaction with care or suicide, self-harm or harm to others. No studies evaluated the oro-dispersable form of olanzapine. AUTHORS' CONCLUSIONS: Data relevant to the effects of olanzapine IM are taken from some studies that may not be considered ethical in many places, all are funded by a company with a pecuniary interest in the result. These studies often poorly report outcomes that are difficult to interpret for routine care. Other important outcomes are not recorded at all. Nevertheless, olanzapine IM probably has some value in helping manage acute aggression or agitation, especially where it is necessary to avoid some of the older, better, known treatments. Olanzapine causes fewer movement disorders than haloperidol and more than lorazepam. The value of the oro-dipersable velotab preparation is untested in trials. There is a need for well designed, conducted and reported randomised studies in this area. Such studies are possible and, we argue, should be designed with the patient groups and clinicians in mind. They should report outcomes of relevance to the management of people at this difficult point in their illness.

Aggression↗
PubMed2004

Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses.

BACKGROUND: Medication used for acute aggression in psychiatry must have rapid onset of effect, low frequency of administration and low levels of adverse effects. Zuclopenthixol acetate is said to have these properties. OBJECTIVES: To estimate the clinical effects of zuclopenthixol acetate for the management of acute aggression or violence thought to be due to serious mental illnesses, in comparison to other drugs used to treat similar conditions. SEARCH STRATEGY: We supplemented past searches of Current Controlled Trials (10/2000), the Cochrane Library (1997) and MEDLINE (1966-1997) and appeals for unpublished data with an update search of the Cochrane Schizophrenia Group's Register of trials (September 2003). SELECTION CRITERIA: All randomised clinical trials involving people thought to have serious mental illnesses comparing zuclopenthixol acetate with other drugs. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers and cross-checked. We calculated fixed effects relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. Where possible, the number needed to treat/harm statistic (NNT/H) was calculated. We analyzed by intention-to-treat. Mean differences were used for continuous variables. MAIN RESULTS: We found no data for the primary outcome, tranquilisation. Compared with haloperidol, zuclopenthixol acetate was no more sedating at two hours (n=40, 1 RCT, RR 0.60 CI 0.27 to 1.34). People given zuclopenthixol acetate were not at reduced risk of being given supplementary antipsychotics (n=134, 3 RCTs, RR 1.49 CI 0.97 to 2.30) although additional use of benzodiazepines was less (n=50, 1 RCT, RR 0.03 CI 0.00 to 0.47, NNT 2 CI 2 to 4). People given zuclopenthixol acetate had fewer injections over seven days compared with those allocated to haloperidol IM (n=70, 1 RCT, RR 0.39 CI 0.18 to 0.84, NNT 4 CI 3 to 14). We found no data on more episodes of aggression or harm to self or others. One trial (n=148) reported no significant difference in adverse effects for people receiving zuclopenthixol acetate compared with those allocated haloperidol at one, three and six days (RR 0.74 CI 0.43 to 1.27). Compared with haloperidol or clotiapine, people allocated zuclopenthixol did not seem to be at more risk of a range of movement disorders (<20%). Three studies found no difference in the proportion of people getting blurred vision/ dry mouth (n=192, 2 RCTs, RR at 24 hours 0.90 CI 0.48 to 1.70). Similarly dizziness was equally infrequent for those allocated zuclopenthixol acetate compared with haloperidol (n=192, 2 RCTs, RR at 24 hours 1.15 CI 0.46 to 2.88). There was no difference between treatments for leaving the study before completion (n=522, RR 0.85 CI 0.31 to 2.31). REVIEWERS' CONCLUSIONS: Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis, or in preventing adverse effects than intramuscular haloperidol, and neither seemed to have a rapid onset of action. Well-conducted pragmatic randomised controlled trials are needed.

Acute Disease↗
PubMed2004

Psychological interventions for those who have sexually offended or are at risk of offending.

BACKGROUND: Sexual offending is both a social problem and a public health issue. To date, no positive treatment effects have been found in quasi-experimental institutional treatment programmes. OBJECTIVES: To evaluate effects of psychological interventions on target sexual acts, urges or thoughts for people who have been convicted, or cautioned, for sexual offences. SEARCH STRATEGY: 33 electronic databases including the Cochrane Controlled Trials Register (Issue 4, 2002) were searched. Relevant authors and organisations were contacted for additional data. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving adults treated in institutional or community settings for sexual behaviours that have resulted in conviction or caution for sexual offences, or offences or violent behaviours with a sexual element. Behavioural, cognitive-behavioural, psychodynamic, and psychoanalytic therapies were compared with each other, drug treatment, or standard care. DATA COLLECTION AND ANALYSIS: Independent assessors selected and assessed studies and extracted data. Data were excluded where more than 50% of participants were lost to follow-up. For binary outcomes, standard estimations of risk ratio (RR) and their 95% confidence intervals (CI) were calculated. Where possible, number-needed-to-treat or harm statistics (NNT, NNH) and their 95% CIs were calculated. MAIN RESULTS: We included nine RCTs with over 500 male offenders, 231 of whom have been followed up for a decade. Cognitive behavioural therapy (CBT) in groups may reduce re-offence at one year for child molesters when compared with standard care (n=155, 1 RCT, RR any sexual/violent crime - 0.41 CI 0.2 to 0.82, NNT 6 CI 3 to 20). However, when CBT was compared with a trans-theoretical counselling group therapy the former may have increased poor attitudes to treatment (corrected n=38, 1 RCT, RR 2.8 CI 1.26 to 6.22, NNH 2 CI 1 to 5). The largest trial compared broadly psychodynamic group therapy with no treatment for 231 men guilty of paedophilia, exhibitionism or sexual assault. Re-arrest over ten years was greater for those allocated to group therapy (result not statistically significant [n=231, 1 RCT, RR 1.87 CI 0.78 to 4.47]). REVIEWERS' CONCLUSIONS: Limited data make recommendations difficult. One study suggests that a cognitive approach results in a decline in re-offending after one year. Another large study shows no benefit for group therapy and suggests the potential for harm at ten years. The ethics of providing this still-experimental treatment to a vulnerable and potentially dangerous group of people outside of a well-designed evaluative study are debatable. This review proves such studies are possible.

Humans↗
PubMed2003

Toll-like receptor 4 signalling: new perspectives on a complex signal-transduction problem.

We previously reported that Toll-like receptor-2 (TLR2) agonists induce expression of a more limited repertoire of pro-inflammatory genes than TLR4 agonists. Murine macrophages stimulated with the TLR4 agonist, Escherichia coli lipopolysaccharide, induced signal transducer and activator of transcription 1 ('STAT1') tyrosine phosphorylation that was secondary to the autocrine/paracrine action of interferon (IFN)-beta, an immediate early gene. In contrast, TLR2 agonists failed to activate IFN-beta gene expression. TLR4-induced IFN-beta mRNA was found to be MyD88- and PKR (double-stranded RNA-dependent protein kinase)-independent, but TIRAP (Toll/interleukin-1 receptor domain-containing adapter protein)/Mal (MyD88-adapter-like)-dependent. In the present paper, we outline the recent controversy over the role of TIRAP/Mal in TLR2 and TLR4 signalling in the context of the current molecular tools used for such studies. Collectively, our findings provide the first mechanistic basis for differential patterns of gene expression activated by TLR4 and TLR2 agonists.

Animals↗
PubMed2001

Cellular senescence after single and repeated balloon catheter denudations of rabbit carotid arteries.

The hypothesis that increased cellular proliferation in the vasculature may lead to replicative senescence has been tested in a model of neointima formation. We have used a biomarker of replicative senescence, senescence-associated beta-galactosidase (SA-beta-gal), to detect senescence in rabbit carotid arteries subjected to single and double balloon denudations. We found an accumulation of senescent cells in the neointima and media of all injured vessels, in contrast to the near absence of such cells in control vessels. The relative area occupied by SA-beta-gal-positive cells was higher in vessels subjected to double denudation than in those subjected to single denudation, both in the neointima (0.99% versus 0.06%, respectively; P:<0.001) and in the media (0.11% versus 0.01%, respectively; P:<0.02). The majority of SA-beta-gal-positive cells were vascular smooth muscle cells, and a minority were endothelial cells. SA-beta-gal-positive cells showed no evidence of apoptosis by use of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling. Our results indicate that the proliferative response that follows intraluminal injury to the artery leads to the emergence of senescent endothelial and smooth muscle cells. The demonstration that vascular cell senescence can occur in vivo suggests that this process may be involved in cardiovascular pathologies that have a proliferative component.

Angioplasty, Balloon↗
PubMed2001

An audit of the ophthalmic division of the accident and emergency department of the Royal Victoria Eye and Ear Hospital, Dublin.

The objective was to study the patterns of emergency department visits and to make recommendations on ways of improving the service. Patients' demographic data, diagnoses, source of referral and follow-up were entered onto a database. Three thousand seven hundred consecutive patients' visits over a six-week period were entered. The average daily attendance ranged between 80-100 people. 54% of patients were self-referrals. 20% had a previous visit to the hospital. 17% were referred from a GP, 5% from another hospital and 3% from opticians. Superficial injury to the eye and ocular adnexae was the most common diagnostic category. 56% of patients were discharged at the first visit. 23% returned for review to casualty. 14% were referred to OPD, 3% directly to a consultant for review and 1% were admitted to hospital. Waiting times for consultation for patients was highly variable ranging from thirty minutes to five hours, mean two hours. The department provides a service far in excess of its defined function. Non urgent problems accounted for as much as 60-70% of all emergency department visits. Improvement of ophthalmic training of GPs, introduction of an ophthalmic triage system and expansion of outpatient services is recommended so that casualty remains a genuine emergency service and not a primary care service with uncontrollable numbers and unacceptable waiting times for patients.

Emergency Service, Hospital↗
PubMed2000

Zuclopenthixol acetate in psychiatric emergencies: looking for evidence from clinical trials.

BACKGROUND: Case series and reviews have suggested the effectiveness of zuclopenthixol acetate in the acute management of disturbed behaviour caused by serious mental illnesses. This review investigates the trial-based evidence for these suggestions. METHODS: All randomized clinical trials comparing zuclopenthixol acetate to other 'standard' treatments for the acute management of those with serious mental illnesses were identified and, if possible, their results summated. RESULTS: Six trials were identified. All had methodological problems and one did not meet the minimal methodological inclusion criteria. The summary data do not demonstrate that zuclopenthixol acetate is better than 'standard care' for altering behaviour, decreasing the need for supplementary medication, avoiding side-effects, or postponing early discharge against medical advice. One trial, however, presented data that suggested an earlier, more intense level of sedation. CONCLUSIONS: Recommendations of reviews and open studies for the use of zuclopenthixol acetate in preference to 'standard' treatments in the psychiatric emergency are not supported by evidence from randomized controlled trials.

Adolescent↗
PubMed2000

Zuclopenthixol acetate in the treatment of acute schizophrenia and similar serious mental illnesses.

BACKGROUND: People with schizophrenia or other psychotic illnesses may have delusions or hallucinations that may lead them to be aggressive or violent to themselves or others. Medication that is used in this context require the properties of rapid onset of effect (tranquillisation or at least initial sedation in order to quell aggressive or disorganised behaviour, but also antipsychotic effect), low frequency of administration and low levels of side effects, such as cardiological or neurological side effects, or pain at the injection site. Zuclopenthixol is the cis(Z)-isomer of clopenthixol, a neuroleptic of the thioxanthene group, used for treating people with psychotic symptoms. There is one oral preparation and two depot forms: zuclopenthixol acetate and zuclopenthixol decanoate. The acetate version does not stay in the body for very long (a single dose persists for only 72 hours) and is said to have these properties. OBJECTIVES: To estimate the effectiveness of zuclopenthixol acetate for the acute treatment of serious mental illnesses in comparison to other neuroleptic drugs. SEARCH STRATEGY: Searches of the Cochrane Schizophrenia Group's Register of Trials, The Cochrane Library, MEDLINE, abstracts of congresses and trial reference lists were performed. Appeals for unpublished data to the research community and to the Medical Information Department of Lundbeck Limited were also made. Attempts were made to contact relevant authors. SELECTION CRITERIA: Two reviewers independently assessed citations or papers and selected all randomised trials that included people with serious mental illnesses and compared zuclopenthixol acetate with other drug regimes. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Attempts were made to contact authors for additional or missing information. Odds-ratios (OR) and 95% confidence intervals (CI) were estimated for binary data. Where possible, OR were pooled using Peto method and intention-to-treat analysis undertaken. Mean differences were used for continuous variables. MAIN RESULTS: Pooled data shows no difference for the outcome 'no important improvement' in psychotic symptoms at the end of the follow-up period (OR 0.84 CI 0. 34-2.05). Sedation was evaluated using different instruments. Only one study presented data which suggested an earlier and more intense sedation in zuclopenthixol acetate users at 4 hours (OR 0.18 CI 0. 04-0.93). Use of additional antipsychotic medication was not avoided in the zuclopentixol acetate group (OR 2.18, CI 0.64-7.42) and data on total number of administrations was not obtainable. Side effect data were poorly reported but there is no evidence of a consistent difference between zuclopenthixol acetate and other 'standard drugs' for either the pattern of side effects or the wish to leave the study early. Hospital and service outcomes, number of aggressive incidents, satisfaction with care and economic outcomes were not addressed by any study. REVIEWER'S CONCLUSIONS: Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more effective in controlling aggressive/disorganised behaviour, acute psychotic symptoms, or preventing side effects. There were no data directly related to tranquillisation, but it may produce more earlier and intense sedation than oral haloperidol. Well conducted randomized controlled trials are needed to confirm claims related to the use of zuclopenthixol acetate in emergency psychiatry.

Acute Disease↗
PubMed2000

Sulpiride for schizophrenia.

BACKGROUND: The antipsychotic drug sulpiride was formulated over 20 years ago and was marked as having a low incidence of adverse effects and an effect on the negative symptoms of schizophrenia. This relatively inexpensive antipsychotic drug has a similar neuropharmacological profile to several novel atypical drugs. OBJECTIVES: To estimate the clinical efficacy and tolerability of sulpiride. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1997), CINAHL (1982-1998), Cochrane Schizophrenia Group's Register (March 1998), Cochrane Library (Issue 1, 1998), EMBASE (1980-1998), MEDLINE (1966-1998), PsycLIT (1974-1997), SIGLE (1994-1998), and Sociofile (1974-1997) were supplemented by reference searching, contacting authors and the manufacturers of sulpiride. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials focusing on the use of different doses of sulpiride or comparing sulpiride to (i) placebo; (ii) typical antipsychotic drugs; or (iii) atypical antipsychotic drugs, for those with schizophrenia or serious mental illness were selected. DATA COLLECTION AND ANALYSIS: Trials were reliably selected and quality rated. Data were independently extracted, by two reviewers (BGOS, MF), and analysed on an intention-to-treat basis. It was assumed that people who did not complete the follow up had no improvement. Authors of trials were contacted for additional and missing data. Relative risk (RR) and 95% confidence intervals (CI) of dichotomous data were calculated with the random effects model and weighted mean difference (WMD) was calculated for continuous data. MAIN RESULTS: The review currently includes 18 studies (30 citations). Studies are generally small and of poor quality. Limited evidence suggests that there is little difference between sulpiride and other drugs although the incidence of side effects may be less for sulpiride. There are no clear findings relating to negative symptoms. REVIEWER'S CONCLUSIONS: Sulpiride may be an effective antipsychotic drug but evidence is limited and data relating to claims for its value against negative symptoms is not trial-based.

Antipsychotic Agents↗
PubMed2000

Seclusion and restraint for people with serious mental illnesses.

BACKGROUND: Seclusion and restraint are interventions used in the treatment and management of disruptive and violent behaviours in psychiatry. The use of seclusion varies widely across institutions. The literature does offer numerous suggestions for interventions to reduce or prevent aggression. OBJECTIVES: 1. To estimate the effects of seclusion and restraint compared to the alternatives for those with serious mental illnesses. 2. To estimate the effects of strategies to prevent seclusion and restraint in those with serious mental illnesses. SEARCH STRATEGY: Electronic searches of The Cochrane Controlled Trials Register (Issue 1, 1999) and The Cochrane Schizophrenia Group's Register (January 1999) were supplemented with additional searches of Biological Abstracts (1989-1999), CINAHL (1982-1999), EMbase (1980-1999), MEDLINE (1966-1999), MEDIC (1979-1999), PsycLIT (1974-1999), Sociofile (1974-1999), SPRI & SWEMED (1982-1999), Social Sciences Citation Index (1996-1999), and WILP (1983-1999). In addition, trials were sought by hand searching the reference lists of all identified studies and conference abstracts and contacting the first author of each relevant study. SELECTION CRITERIA: Randomised controlled trials were included if they focused on the use (i) of restraint or seclusion; or (ii) of strategies designed to reduce the need for restraint or seclusion in the treatment of serious mental illness. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality rated and data extracted. For dichotomous data relative risks (RR) with 95% confidence intervals (CI) were estimated. Normal continuous data were summated using the weighted mean difference (WMD). MAIN RESULTS: 1. Effect of seclusion and restraint The search strategy yielded 2155 citations. Of these, the full articles for 35 studies were obtained. No studies met minimum inclusion criteria and no data were synthesised. Most of the 24 excluded studies focused upon the restraint of elderly, confused people and preventing them from wandering or falling. 2. Prevention of seclusion and restraint Work ongoing. REVIEWER'S CONCLUSIONS: No controlled studies exist that evaluate the value of seclusion or restraint in those with serious mental illness. There are reports of serious adverse effects for these techniques in qualitative reviews. Alternative ways of dealing with unwanted or harmful behaviours need to be developed. Continuing use of seclusion or restraint must therefore be questioned from within well-designed and reported randomised trials that are generalisable to routine practice.

Antipsychotic Agents↗
PubMed2000

Zuclopenthixol decanoate for schizophrenia and other serious mental illnesses.

BACKGROUND: There is a clear link between stopping antipsychotic medications and a relapse of psychotic symptoms. A series of long-acting intra-muscular preparations has been developed since the 1960s in the hope of reducing the frequency of relapse and, hence, overall disability. These depot preparations, active for weeks at a time, are frequently used for those who find taking oral medication on a regular basis difficult or unacceptable. It has, however, been a consistent concern that any reduction in relapse rate afforded by depot preparations may be offset by an increase in adverse effects such as drug-induced movement disorders. OBJECTIVES: To compare zuclopenthixol decanoate to oral zuclopenthixol and other antipsychotic preparations for the treatment of schizophrenia and similar serious mental illness. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1998), CINAHL (1982-1998), The Cochrane Library (Issue 2, 1998), The Cochrane Schizophrenia Group's Register (April 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) were searched. References of all eligible studies were searched for further trials. The manufacturer of zuclopenthixol was contacted. SELECTION CRITERIA: Inclusion criteria were that the clinical study should be randomised, focus on people with schizophrenia or other serious mental illness with psychotic symptoms, and compare the use of zuclopenthixol decanoate to oral zuclopenthixol or other antipsychotic preparations. DATA COLLECTION AND ANALYSIS: Data was extracted independently by two reviewers (EC, MF). Authors of trials were contacted for additional and missing data. Odds ratios (ORs) and 95% confidence intervals (CIs) of homogenous dichotomous data were calculated with the Peto method. Where possible the number needed to treat (NNT) and its 95% confidence interval was also calculated. MAIN RESULTS: Four studies relating to zuclopenthixol decanoate were included. All compared zuclopenthixol decanoate with other depot preparations. Zuclopenthixol decanoate prevented or postponed relapses when compared to other depots (NNT 8, CI 5-53). However, zuclopenthixol decanoate may induce more adverse effects (NNH 5, CI 3-31) although it decreases need for anticholinergic medication when compared to a group of other depot preparations (NNT 9, CI 5-38). For the risk of leaving the study early, there was also a trend for benefit to those allocated to zuclopenthixol decanoate. None of the studies reported outcomes on service utilisation, costs, or quality of life. REVIEWER'S CONCLUSIONS: Choice of which depot to use must always take into account clinical judgement and the preferences of the recipients of care and their carers. Limited trial data suggests, however, that there are real differences between zuclopenthixol decanoate and other depots and these differences largely favour the former. This review highlights the need for good controlled clinical trials to fully address the effects of zuclopenthixol decanoate for those with schizophrenia. Future studies should report service utilisation data, as well as satisfaction with care and economic outcomes. Duration of such trials should be of a longer duration than the included studies (12 months or more).

Administration, Oral↗
PubMed2000

Olanzapine for schizophrenia.

BACKGROUND: Olanzapine is an atypical antipsychotic that is reported to be effective without producing the disabling extrapyramidal side effects associated with the older, typical antipsychotic drugs. OBJECTIVES: To determine the clinical effects and safety of olanzapine as compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. SEARCH STRATEGY: The reviewers undertook electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), The Cochrane Schizophrenia Group's Register (September 1999), EMBASE (1980-1999), MEDLINE (1966-1999), and PsycLIT (1974-1999). References of all identified studies were searched for further trials, and the reviewers contacted relevant pharmaceutical companies and authors of trials. SELECTION CRITERIA: All randomised clinical trials comparing olanzapine to placebo or any antipsychotic treatment for those with schizophrenia or schizophreniform psychoses. DATA COLLECTION AND ANALYSIS: Data were independently extracted. For homogeneous dichotomous data the random effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data the reviewers calculated weighted mean differences. MAIN RESULTS: Twenty trials are included. Attrition from olanzapine versus placebo studies was so great (olanzapine - 61%, placebo - 73% by six weeks, RR 0.85 CI 0. 7-0.98, NNT 8 CI 5-40) that interpretation of results is problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (RR 0.88 CI 0.8-0.98, NNT 8 CI 5-27), but trial data regarding negative symptoms are equivocal for this comparison. Dizziness and dry mouth were more common in the olanzapine-treated group, and, although not statistically significant, the olanzapine group gained more weight. Data from several small trials are incomplete; but, for the short term outcome of 'no important clinical response', olanzapine seem as effective as typical antipsychotics (n=2778, RR 0.9 CI 0.76-1.06). Brief Psychiatric Rating Scale (BPRS) data tended to be equivocal but Positive and Negative Syndrome Scale (PANSS) rating of total score and negative and positive symptom sub-scores favoured olanzapine. With high attrition in both groups (olanzapine - 36%, typical drug - 49% by 6 weeks, n=2738, RR 0.85 CI 0.66-1.1; olanzapine - 83%, typical drug - 90% by 1 year, n=2738, RR 0.9 CI 0. 86-1.02), the assumptions included in all continuous data are considerable. Participants allocated olanzapine experienced fewer extrapyramidal side effects than people given haloperidol. Weight change data for the short term are not conclusive (n=2455, WMD 0.8kg CI -0.6-2.2) but the three to 12 month results suggest an average gain of four kilograms (n=233, WMD 4 CI 0.3-7.8). It is difficult to distinguish between olanzapine and other atypical drugs, although it may cause fewer extrapyramidal side effects than risperidone (n=339, RR 0.6 CI 0.4-0.9, NNH 8 CI 4-29). Olanzapine did cause more weight gain than its comparators but current data are not statistically significant (3-12 months, n=535, WMD 2.2kg CI -0.6-5). One study (n=180) found no clear differences between olanzapine and clozapine for people with treatment-resistant illness. REVIEWER'S CONCLUSIONS: For people with schizophrenia olanzapine may offer antipsychotic efficacy with fewer extrapyramidal side effects than typical drugs but more weight gain. The large proportions of participants leaving the studies early, in the large multi-centre trials makes it difficult to draw firm conclusions on clinical effects. Large, long-term randomised trials with participants, interventions and primary outcomes that are familiar to those wishing to help those with schizophrenia are long overdue.

Antipsychotic Agents↗