A systematic review of the public's knowledge and beliefs about antibiotic resistance.

OBJECTIVES: The objective of this study was to systematically review quantitative and qualitative studies on the public's knowledge and beliefs about antibiotic resistance. METHODS: We searched four databases to July 2014, with no language or study design restrictions. Two reviewers independently extracted data. We calculated the median (IQR) of the proportion of participants who agreed with each statement and synthesized qualitative data by identifying emergent themes. RESULTS: Of 3537 articles screened, 54 studies (41 quantitative, 3 mixed methods and 10 qualitative) were included (55 225 participants). Most studied adults (50; 93% studies) and were conducted in Europe (23; 43%), Asia (14; 26%) or North America (12; 22%). Some participants [median 70% (IQR 50%-84%); n = 8 studies] had heard of antibiotic resistance, but most [median 88% (IQR 86%-89%); n = 2 studies] believed it referred to changes in the human body. Many believed excessive antibiotic use [median 70% (IQR 59%-77%); n = 11 studies] and not completing antibiotic courses [median 62% (IQR 47%-77%); n = 8 studies] caused resistance. Most participants nominated reducing antibiotic use [median 74% (IQR 72%-85%); n = 4 studies] and discussing antibiotic resistance with their clinician (84%, n = 1 study) as strategies to reduce resistance. Qualitative data supported these findings and additionally identified that: participants believed they were at low risk from antibiotic resistance participants; largely attributed its development to the actions of others; and strategies to minimize resistance should be primarily aimed at clinicians. CONCLUSIONS: The public have an incomplete understanding of antibiotic resistance and misperceptions about it and its causes and do not believe they contribute to its development. These data can be used to inform interventions to change the public's beliefs about how they can contribute to tackling this global issue.

Not in my backyard: a systematic review of clinicians' knowledge and beliefs about antibiotic resistance.

OBJECTIVES: To systematically review clinicians' knowledge and beliefs about the importance and causes of antibiotic resistance, and strategies to reduce resistance. METHODS: Four databases were searched (until July 2014), without restrictions on language, setting or study design. Fixed responses (from surveys) were grouped into categories. The proportion of participants who agreed with each category was expressed as median, percentage and IQR. Qualitative data were coded into emergent themes. Quantitative categories and qualitative themes were grouped into four overarching categories that emerged from the data. RESULTS: There were 57 included studies (38 quantitative, 14 qualitative, 5 mixed methods) of 11593 clinicians. Most clinicians (69%, IQR 63%-72%, n=5 studies) had heard of antibiotic resistance and 98% (IQR 93%-99%, n=5 studies) believed it was serious. The proportion who believed it was a problem for their practice (67%, IQR 65%-74%, n=13 studies) was smaller than the proportion who believed it was a problem globally (89%, IQR 85%-97%, n=5 studies) or nationally (92%, IQR 88%-95%, n=21 studies). Most believed excessive antibiotic use (97%, IQR 91%-98%, n=12 studies) and patient non-adherence (90%, IQR 82%-92%, n=7 studies) caused resistance. Most knew of strategies to reduce resistance (e.g. clinician education, 90%, IQR 85%-96%, n=7 studies). Qualitative findings support these data: they attributed responsibility for antibiotic resistance to patients, other countries and healthcare settings; resistance was considered a low priority and a distant consequence of antibiotic prescribing. CONCLUSIONS: Clinicians believe antibiotic resistance is a serious problem, but think it is caused by others. This needs to be accommodated in interventions to reduce antibiotic resistance.

Rituximab for the first-line treatment of stage III-IV follicular lymphoma (review of Technology Appraisal No. 110): a systematic review and economic evaluation.

BACKGROUND: Follicular lymphoma (FL) is a non-Hodgkin's lymphoma which typically presents when the disease is at an advanced stage. The majority of patients receive first-line therapy of rituximab in combination with chemotherapy, with two-thirds receiving cyclophosphamide, vincristine and prednisolone. The clinical and cost-effectiveness of other chemotherapies in combination with rituximab in first-line therapy is not known. OBJECTIVE: To systematically evaluate and appraise the clinical effectiveness and cost-effectiveness of rituximab (MabThera(®), Roche Products) in combination with chemotherapy, compared with chemotherapy alone, for the first-line treatment of symptomatic stage III-IV FL. DATA SOURCES: A systematic review of literature and an economic evaluation were carried out. Key databases [including MEDLINE In-Process & Other Non-Indexed Citations; Cumulative Index to Nursing and Allied Health Literature (CINAHL); EMBASE; The Cochrane Library, including the Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED) and Health Technology Assessment (HTA) databases; Science Citation Index (SCI); and BIOSIS], plus research registers and conference proceedings, were searched for relevant studies from inception up to October 2010. REVIEW METHODS: One reviewer assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers and screened them against inclusion criteria. Data from included studies were extracted by one reviewer using a standardised data extraction form and checked by a second reviewer. The quality of included studies was assessed by one reviewer and checked by a second. A patient-level simulation model was developed to estimate the costs and quality-adjusted life-year (QALY) gains from the perspective of the UK NHS and Personal Social Services, with costs and benefits discounted at 3.5% annually. RESULTS: Four randomised controlled trials comparing rituximab plus chemotherapy (R-chemotherapy) with chemotherapy alone in untreated, symptomatic patients with stage III-IV FL were identified. R-chemotherapy compared with chemotherapy alone increased the likelihood of a response to treatment in all four trials, with no additional toxicity of clinical relevance. Overall response rates were significantly improved in all four trials, with a difference between the R-chemotherapy and chemotherapy arms of between 5% and 24%, respectively. Complete response rates were also improved, with a difference between the R-chemotherapy and chemotherapy arms of between 2% and 25%, respectively. Exploratory meta-analyses were conducted; the level of statistical heterogeneity was very high and thus we believe the response rates from the individual trials to be a more robust estimator of the efficacy of the specific R-chemotherapy regimens. Over a follow-up period of 4-5 years, R-chemotherapy significantly increased the overall survival rate compared with chemotherapy alone in three trials, although data for two trials were compromised owing to the use of additional treatments. The incremental cost-effectiveness ratio (ICER) for the addition of rituximab to CVP (cyclophosphamide, vincristine and prednisolone), CHOP (cyclophosphamide, doxorubicin/adriamycin, vincristine and prednisolone) and MCP [mitoxantrone, chlorambucil (Leukeran(®), Aspen) and prednisolone] was £7720, £10,834 and £9316 per QALY gained, respectively, when it was assumed that first-line rituximab maintenance was not used. A scenario analysis is also presented, assuming that responders to R-chemotherapy in first-line induction receive maintenance with rituximab, increasing the ICER to £14,959, £21,687 and £20,493 per QALY gained, respectively. LIMITATIONS: These relate to the sources of data used for the effectiveness in first and second line and the assumed utility values; there is uncertainty about the effect of salvage treatment on patients who had been previously treated with an anthracycline regimen. There is uncertainty whether or not rituximab is as effective in second-line treatment when patients have been previously treated with rituximab. CONCLUSIONS: The results from four randomised trials comparing R-chemotherapy with chemotherapy alone showed an improvement in clinical effectiveness outcomes, with minimal clinically relevant additional adverse events or toxicity. The cost per QALY gained is estimated to be < £25,000 for all three comparisons under our base-case assumption and is considerably lower if first-line rituximab maintenance is not assumed. More data on patients pre-treated with rituximab and on the effect of first-line maintenance with rituximab is required for future work. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Interventions to improve teamwork and communications among healthcare staff.

BACKGROUND: Concern over the frequency of unintended harm to patients has focused attention on the importance of teamwork and communication in avoiding errors. This has led to experiments with teamwork training programmes for clinical staff, mostly based on aviation models. These are widely assumed to be effective in improving patient safety, but the extent to which this assumption is justified by evidence remains unclear. METHODS: A systematic literature review on the effects of teamwork training for clinical staff was performed. Information was sought on outcomes including staff attitudes, teamwork skills, technical performance, efficiency and clinical outcomes. RESULTS: Of 1036 relevant abstracts identified, 14 articles were analysed in detail: four randomized trials and ten non-randomized studies. Overall study quality was poor, with particular problems over blinding, subjective measures and Hawthorne effects. Few studies reported on every outcome category. Most reported improved staff attitudes, and six of eight reported significantly better teamwork after training. Five of eight studies reported improved technical performance, improved efficiency or reduced errors. Three studies reported evidence of clinical benefit, but this was modest or of borderline significance in each case. Studies with a stronger intervention were more likely to report benefits than those providing less training. None of the randomized trials found evidence of technical or clinical benefit. CONCLUSION: The evidence for technical or clinical benefit from teamwork training in medicine is weak. There is some evidence of benefit from studies with more intensive training programmes, but better quality research and cost-benefit analysis are needed.

Open general medical wards versus specialist psychiatric units for acute psychoses.

BACKGROUND: As international healthcare policy has moved away from treating people with severe mental illness in large inpatient psychiatric institutions, beds for people with acute psychiatric disorders are being established in specialised psychiatric units in general hospitals. In developing countries, however, limited resources mean that it is not always possible to provide discrete psychiatric units, either in general hospitals or in the community. An alternative model of admission, used in the Caribbean, is to treat the person with acute psychosis in a general hospital ward. OBJECTIVES: To compare the outcomes for people with acute psychosis who have been admitted to open medical wards with those admitted to conventional psychiatric units. SEARCH STRATEGY: We searched The Cochrane Schizophrenia Group's study-based register (April 2007). This register is compiled from searches of BIOSIS, CINAHL, The Cochrane Library, EMBASE, LILACS, MEDLINE, PsycINFO, PSYNDEX, Sociofile, and many conference proceedings. SELECTION CRITERIA: We would have included all relevant randomised or quasi-randomised trials, allocating anyone thought to be suffering from an acute psychotic episode to either acute management on general medical wards, or acute management in a specialist psychiatric unit. The primary outcomes of interest were length of stay in hospital and relapse. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we would have calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based using a fixed effects model. MAIN RESULTS: We didnt identify any relevant randomised trials. AUTHORS' CONCLUSIONS: The Caribbean practice of treating people with severe mental illness on general medical wards has been influenced by socio-economic factors rather than evidence from randomised trials. This practice affords an opportunity for a well designed, well conducted and reported randomised trial, now impossible in many other settings.

Pimozide for schizophrenia or related psychoses.

BACKGROUND: Pimozide, formulated in the 1960s, continues to be marketed for the care of people with schizophrenia or related psychoses such as delusional disorder. It has been associated with cardiotoxicity and sudden unexplained deaths. Electrocardiogram monitoring is now required before and during use. OBJECTIVES: To assess the clinical effects of pimozide for people with schizophrenia, non-affective psychotic mental illness and delusional disorder. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (July 2005). SELECTION CRITERIA: We sought all relevant randomised clinical trials comparing pimozide with other treatments. DATA COLLECTION AND ANALYSIS: Working independently, we inspected citations, ordered papers, and then re-inspected and quality assessed the studies and extracted data. For homogeneous dichotomous data, we calculated the relative risk (RR), 95% confidence interval (CI), and, where appropriate, the number needed to treat (NNT) and the number needed to harm (NNH), on an intention-to-treat basis. We calculated weighted mean differences (WMD) for continuous data. We excluded data if loss to follow-up was greater than 50%. MAIN RESULTS: We found 35 relevant studies (total n=1348), all including people with schizophrenia but none with delusional disorder. 123 people were randomised to pimozide versus placebo. Data suggest that pimozide prevents relapse (2 RCTs, n=66, RR 0.45 CI 0.2 to 0.9, NNT 4 CI 3 to 22). Compared with typical antipsychotic drugs, pimozide has similar efficacy for outcomes of change in global functioning, mental state, relapse and leaving the study early. People allocated to pimozide did not have a higher mortality than those taking other antipsychotic drugs. Pimozide was more likely than typical antipsychotic drugs to cause tremor in the short-term (6 RCTs, n=192, RR 1.6 CI 1.1 to 2.3, NNH 6 CI 3 to 44) and lead to need for antiparkinsonian medication (4 RCTs, n=124, RR 1.8 CI 1.2 to 2.6, NNH 3 CI 2 to 5) than other drugs. In the medium-term, however, pimozide was less likely to cause sedation (5 RCTs, n=231, RR 0.6 CI 0.5 to 0.9, NNH 6 CI 4 to 16). AUTHORS' CONCLUSIONS: Although there are shortcomings in the data, there is enough overall consistency over different outcomes and time scales to confirm that pimozide is a drug with similar efficacy to other more commonly used antipsychotic drugs such as chlorpromazine for people with schizophrenia. There are no data to support or refute its use for those with delusional disorder.

Thioridazine for schizophrenia.

BACKGROUND: Thioridazine is an antipsychotic that can still be used for schizophrenia although it is associated with the cardiac arrhythmia, torsades de pointe. OBJECTIVES: To review the effects of thioridazine for people with schizophrenia. SEARCH STRATEGY: For this 2006 update, we searched the Cochrane Schizophrenia Group's Register (June 2006). SELECTION CRITERIA: We included all randomised clinical trials comparing thioridazine with other treatments for people with schizophrenia or other psychoses. DATA COLLECTION AND ANALYSIS: We reliably selected, quality rated and extracted data from relevant studies. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) on an intention-to-treat basis. MAIN RESULTS: This review currently includes 42 RCTs with 3498 participants. When thioridazine was compared with placebo (total n=668, 14 RCTs) we found global state outcomes favoured thioridazine (n=105, 3 RCTs, RR 'no change or worse' by 6 months 0.33 CI 0.2 to 0.5, NNT of 2 CI 2 to 3). Thioridazine is sedating (n=324, 3 RCTs, RR 5.37 CI 3.2 to 9.1, NNH 4 CI 2 to 74). Generally, thioridazine did not cause more movement disorders than placebo.Twenty-seven studies (total n=2598) compared thioridazine with typical antipsychotics. We found no significant difference in global state (n=743, 11 RCTs, RR no short-term change or worse 0.98 CI 0.8 to 1.2) and medium-term assessments (n=142, 3 RCTs, RR 0.99, CI 0.6 to 1.6). We found no significant differences in the number of people leaving the study early 'for any reason' (short-term, n=1587, 19 RCTs, RR 1.07 CI 0.9 to 1.3). Extrapyramidal adverse events lower for those allocated to thioridazine (n=1082, 7 RCTs, RR use of antiparkinsonian drugs 0.45 CI 0.4 to 0.6). Thioridazine did seem associated with cardiac adverse effects (n=74, 1 RCT, RR 'any cardiovascular adverse event' 3.17 CI 1.4 to 7.0, NNH 3 CI 2 to 5). Electrocardiogram changes were significantly more frequent in the thioridazine group (n=254, 2 RCTs, RR 2.38, CI 1.6 to 3.6, NNH 4 CI 3 to 10). Six RCTs (total n=344) randomised thioridazine against atypical antipsychotics. Global state rating did not reveal any short-term difference between thioridazine and remoxipride and sulpiride (n=203, RR not improved or worse 1.00 CI 0.8 to 1.3). Limited data did not highlight differences in adverse event profiles. AUTHORS' CONCLUSIONS: Although there are shortcomings, there appears to be enough consistency over different outcomes and periods to confirm that thioridazine is an antipsychotic of similar efficacy to other commonly used antipsychotics for people with schizophrenia. Its adverse events profile is similar to that of other drugs, but it may have a lower level of extrapyramidal problems and higher level of ECG changes. We would advocate the use of alternative drugs, but if its use in unavoidable, cardiac monitoring is justified.

Schizophrenia trials in China: a survey.

OBJECTIVE: China's biomedical research activity is increasing and this literature is becoming more accessible online. Our aim was to survey all randomized control schizophrenia trials (RCTs) in one Chinese bibliographic database. METHOD: Chinese Academic Journals was electronically searched for RCTs and all relevant citations were also sought on PubMed to ascertain global accessibility. RESULTS: The search identified 3275 records, of which 982 were RCTs relevant to schizophrenia. A total of 71% (699) could be found by using English phrases. All the main body of text of the 982 papers was in Mandarin. On average, these trials involved about 100 people, with interventions and outcome measures familiar to schizophrenia trialists worldwide. Four of the 982 records (<1%) were identified on PubMed. CONCLUSION: Those undertaking systematic reviews should search the Chinese literature for relevant material. Failing to do this will leave the results of systematic reviews prone to random error or bias, or both.

Chlorpromazine versus placebo for schizophrenia.

BACKGROUND: Chlorpromazine, formulated in the 1950s, remains a benchmark treatment for people with schizophrenia. OBJECTIVES: To evaluate the effects of chlorpromazine for schizophrenia in comparison with placebo. SEARCH STRATEGY: We updated previous searches of the Cochrane Schizophrenia Group Register (October 1999), Biological Abstracts (1982-1995), the Cochrane Library (1999, Issue 2), EMBASE (1980-1995), MEDLINE (1966-1995), PsycLIT (1974-1995), and the Cochrane Schizophrenia Group Register (June 2002), by searching The Cochrane Schizophrenia Group Trials Register (January 2007). We searched references of all identified studies for further trial citations. We contacted pharmaceutical companies and authors of trials for additional information. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing chlorpromazine with placebo for people with schizophrenia and non-affective serious/chronic mental illness irrespective of mode of diagnosis. Primary outcomes of interest were death, violent behaviours, overall improvement, relapse and satisfaction with care. DATA COLLECTION AND ANALYSIS: We independently inspected citations and abstracts, ordered papers, re-inspected and quality assessed these. BT and JR extracted data. CEA and GA independently checked a 10% sample for reliability. We analysed dichotomous data using fixed effects relative risk (RR) and estimated the 95% confidence interval (CI) around this. Where possible we calculated the number needed to treat (NNT) or number needed to harm (NNH) statistics. We excluded continuous data if more than 50% of participants were lost to follow up; where continuous data were included, we analysed this data using fixed effects weighted mean difference (WMD) with a 95% confidence interval. MAIN RESULTS: We inspected over 1000 electronic records. The review currently includes 302 excluded studies and 50 included studies. We found chlorpromazine reduces relapse over the short (n=74, 2 RCTs, RR 0.29 CI 0.1 to 0.8) and medium term (n=809, 4 RCTs, RR 0.49 CI 0.4 to 0.6) but data are heterogeneous. Longer term homogeneous data also favoured chlorpromazine (n=512, 3 RCTs, RR 0.57 CI 0.5 to 0.7, NNT 4 CI 3 to 5). We found chlorpromazine provided a global improvement in a person's symptoms and functioning (n=1121, 13 RCTs, RR 'no change/not improved' 0.80 CI 0.8 to 0.9, NNT 6 CI 5 to 8). Fewer people allocated to chlorpromazine left trials early (n=1780, 26 RCTs, RR 0.65 CI 0.5 to 0.8, NNT 15 CI 11 to 24) compared with placebo. There are many adverse effects. Chlorpromazine is clearly sedating (n=1404, 19 RCTs, RR 2.63 CI 2.1 to 3.3, NNH 5 CI 4 to 8), it increases a person's chances of experiencing acute movement disorders (n=942, 5 RCTs, RR 3.5 CI 1.5 to 8.0, NNH 32 CI 11 to 154), parkinsonism (n=1265, 12 RCTs, RR 2.01 CI 1.5 to 2.7, NNH 14 CI 9 to 28). Akathisia did not occur more often in the chlorpromazine group than placebo (n=1164, 9 RCTs, RR 0.78 CI 0.5 to 1.1). Chlorpromazine clearly causes a lowering of blood pressure with accompanying dizziness (n=1394, 16 RCTs, RR 2.37 CI 1.7 to 3.2, NNH 11 CI 7 to 21) and considerable weight gain (n=165, 5 RCTs, RR 4.92 CI 2.3 to 10.4, NNH 2 CI 2 to 3). AUTHORS' CONCLUSIONS: The results of this review confirm much that clinicians and recipients of care already know but aim to provide quantification to support clinical impression. Chlorpromazine's global position as a 'benchmark' treatment for psychoses is not threatened by the findings of this review. Chlorpromazine, in common use for half a century, is a well established but imperfect treatment. Judicious use of this best available evidence should lead to improved evidence-based decision making by clinicians, carers and patients.

Family intervention for schizophrenia.

BACKGROUND: People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families are now widely used. OBJECTIVES: To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared to standard care. SEARCH STRATEGY: We updated previous searches by searching The Cochrane Schizophrenia Group's Register (November 2002 and June 2005), searched references of all new included studies for further trial citations, and contacted authors of trials. SELECTION CRITERIA: We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. DATA COLLECTION AND ANALYSIS: We independently extracted data and calculated fixed effects relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: This 2005-6 update adds data of 15 additional trials (1765 participants, 43% of the total 4124). Family intervention may decrease the frequency of relapse (n=857, 16 RCTs, RR 0.71 CI 0.6 to 0.8, NNT 8 CI 6 to 11), although some small but negative studies may not have been identified by the search. Family intervention may also reduce hospital admission (8 RCTs, n=481, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13)--and this finding is a change to the previous equivocal data reported in 2002. Family intervention may also encourage compliance with medication (n=369, 7 RCTs, RR 0.74 CI 0.6 to 0.9, NNT 7 CI 4 to 19) but does not obviously affect the tendency of individuals/families to drop out of care (n=481, 6 RCTs, RR 0.86 CI 0.5 to 1.4). It may improve general social impairment and the levels of expressed emotion within the family. We did not find data to suggest that family intervention either prevents or promotes suicide. AUTHORS' CONCLUSIONS: Clinicians, researchers, policy makers and recipients of care cannot be confident of the effects of family intervention from the findings of this review. Further data from already completed trials could greatly inform practice and more trials are justified as long as their participants, interventions and outcomes are applicable to routine care.

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.

Anticholinergics for neuroleptic-induced acute akathisia.

BACKGROUND: Neuroleptic-induced akathisia is one of the most common and distressing early-onset adverse effects of first generation 'typical' antipsychotic drugs. It is associated with poor compliance with treatment, and thus, ultimately, with an increased risk of relapse. We assessed the role of anticholinergic drugs as an adjunct therapy to standard antipsychotic medication in the pharmacological treatment of this adverse effect. OBJECTIVES: To review anticholinergic drugs for neuroleptic-induced acute akathisia. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (October 1999), Biological Abstracts (1982-1999), CINAHL (1982-1999), Cochrane Library (Issue 4 1999), EMBASE (1980-1999), LILACS (1982-1999), MEDLINE (1966-1999) and PsycLIT (1974-1999). References of all identified studies were inspected for more trials and we contacted first authors. Each included study was sought as a citation on the Science Citation Index database. For this 2005-6 update, we searched the Cochrane Schizophrenia Group's Register (July 2005). SELECTION CRITERIA: We included all randomised clinical trials of adjunctive anticholinergic drugs in addition to antipsychotic medication compared with placebo, for people with neuroleptic-induced acute akathisia. DATA COLLECTION AND ANALYSIS: We quality assessed and extracted data independently. We calculated the fixed effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) for homogeneous dichotomous data on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: We identified no relevant randomised controlled trials. AUTHORS' CONCLUSIONS: At present, there is no reliable evidence to support or refute the use of anticholinergics for people suffering from neuroleptic-induced acute akathisia. Akathisia is a distressing movement disorder that remains highly prevalent in people with schizophrenia, both in the developed and developing world. This review highlights the need for well designed, conducted and reported clinical trials to address the claims of open studies as regards the effects of the anticholinergic group of drugs for akathisia.

Early intervention for psychosis.

BACKGROUND: Proponents of early intervention have argued that outcome might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection and phase-specific treatment. Both elements may be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia, but it is unclear how far early detection, phase-specific treatments, and the use of early intervention teams are underpinned by evidence of effectiveness. OBJECTIVES: To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first episode psychosis. SEARCH STRATEGY: We searched CINAHL (1982-2002), The Cochrane Controlled Trials Register (November 2001), The Cochrane Schizophrenia Group Register (July 2003), EMBASE (1980-2002), MEDLINE (1966-2002), PsycINFO (1967-2002), reference lists and contacted the European First Episode Network (2003). For the 2006 update we searched the Cochrane Schizophrenia Group's register. SELECTION CRITERIA: We included all randomised controlled trials designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first episode psychosis. Eligible interventions, alone and in combination, included early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). MAIN RESULTS: We included seven studies with a total of 941 participants. Six studies were small with numbers of participants ranging between 56 and 83, and one study randomised 547 people. None of the studies had similar interventions and therefore they were analysed separately. One small Australian trial (n=59) was concerned with a phase-specific intervention (low dose risperidone and cognitive behavioural therapy) for people with prodromal symptoms. This group were significantly less likely to develop psychosis at a six month follow up than people who only received care from a specialised team which did not involve phase-specific treatment (n=59, RR 0.27 CI 0.1 to 0.9, NNT 4 CI 2 to 20). This effect was not significant at 12 month follow up (n=59, 1 RCT, RR 0.54 CI 0.2 to 1.3). A UK-based study (EDIE) randomised 60 people with prodromal symptoms, to cognitive behavioural therapy (CBT) or a monitoring group. Only two outcomes were reported: leaving the study early and transition to psychosis, both sets of data were non-significant. A Chinese trial used a phase-specific intervention (family therapy) plus out patient care trial for people in their first episode of psychosis and found reduced admission rates care compared with those who received only outpatient care (n=83, RR 0.28 CI 0.1 to 0.6, NNT 3 CI 2 to 6). The applicability of this finding was, however, questionable. One Dutch study (n=76) comparing phase-specific intervention (family therapy) plus specialised team with specialised team for people in their first episode of schizophrenia found no difference between intervention and control groups at 12 months for the outcome of relapse (n=76, RR 1.05 CI 0.4 to 3.0). The large Scandinavian study (n=547) allocated people with first episode schizophrenia to integrated treatment (assertive community treatment plus family therapy, social skills training and a modified medication regime) or standard care. Global state outcome GAF significantly favoured integrated treatment (n=419, WMD -3.71 CI -6.7 to -0.7) by one year, but by two years data were non-significant. Rates of attrition were significantly lower (n=547, RR 0.59 CI 0.4 to 0.8, NNT 9 CI 6 to 18) for integrated treatment by one and two year follow-up. PRIME (USA) was the only double blind study and allocated people with prodromal symptoms to olanzapine or placebo. No significant differences were found between olanzapine and placebo in preventing conversion to psychosis by about 12 months (n=60, RR 0.58 CI 0.3 to 1.2). Clinical Global Impression change scores 'severity of illness' were equivocal by 12 months. Scale of Prodromal Symptoms (SOPS) scores were also equivocal and the PANSS, total, positive and negative outcomes were non-significant. There were no significant differences between the olanzapine and placebo group on adverse effects rating scales - SAS, BAS and AIMS scores; Weight gain was significantly higher in the olanzapine group (n=59, WMD 7.63 CI 4.0 to 11.2) by 12 months. Finally one more Australian study included people in their first episode of psychosis who were acutely suicidal and allocated people to phase-specific cognitively orientated therapy or standard care. Outcome data for leaving the study early and suicide were equivocal. AUTHORS' CONCLUSIONS: We identified insufficient trials to draw any definitive conclusions. The substantial international interest in early intervention offers an opportunity to make major positive changes in psychiatric practice, but making the most of this opportunity requires a concerted international programme of research to address key unanswered questions.

Neuroleptic reduction and/or cessation and neuroleptics as specific treatments for tardive dyskinesia.

BACKGROUND: Since the 1950s neuroleptic medication has been extensively used to treat people with chronic mental illnesses such as schizophrenia. These drugs, however, have been also associated with a wide range of adverse effects, including movement disorders such as tardive dyskinesia (TD). Various strategies have been examined to reduce a person's cumulative exposure to neuroleptics. These studies include dose reduction, intermittent dosing strategies such as drug holidays, and neuroleptic cessation. OBJECTIVES: To determine whether a reduction or cessation of neuroleptic drugs is associated with a reduction in TD, for people with schizophrenia (or other chronic mental illnesses) who have existing TD. Our secondary objective was to determine whether the use of specific neuroleptics for similar groups of people could be a treatment for TD that was already established. SEARCH STRATEGY: We updated previous searches of the Cochrane Schizophrenia Groups Register (1997), Biological Abstracts (1982-1997), EMBASE (1980-1997), LILACS (1982-1996), MEDLINE (1966-1997), PsycLIT (1974-1997), and SCISEARCH (1997) by searching the Cochrane Schizophrenia Groups Register (July 2003). We searched references of all identified studies for further trial citations. We also contacted the principal authors of trials for further unpublished trials. SELECTION CRITERIA: We included reports if they assessed people with schizophrenia or other chronic mental illnesses who had established neuroleptic-induced TD, and had been randomly allocated to (a) neuroleptic maintenance versus neuroleptic cessation (placebo or no intervention), (b) neuroleptic maintenance versus neuroleptic reduction (including intermittent strategies), and (c) specific neuroleptics for the treatment of TD versus, placebo or intervention. A post hoc decision was made to broaden comparison (c) to include specific neuroleptics versus other neuroleptics for the treatment of TD. DATA COLLECTION AND ANALYSIS: We (KSW, JR) independently inspected citations and, where possible, abstracts, ordered papers, and re-inspected and quality assessed these and extracted data. We analysed dichotomous data using random effects relative risk (RR) and estimated the 95% confidence interval (CI). Where possible we calculated the number needed to treat (NNT) or number needed to harm statistic (NNH). We excluded continuous data if more than 50% of people were lost to follow up, but, where possible, we calculated the weighted mean difference (WMD). It was assumed that those leaving the study early showed no improvement. MAIN RESULTS: We included five trials and excluded 102. One small two week study (n=18), reported on the 'masking' effects of molindone and haloperidol on TD, which favoured haloperidol (RR 3.44 CI 1.1 to 5.8). Two (total n=17) studies found no reduction in TD associated with neuroleptic reduction (RR 0.38 CI 0.1 to 1.0). One study (n=20) found no significant differences in oral dyskinesia (RR 2.45 CI 0.3 to 19.7) when neuroleptics were compared as a specific treatment for TD. Dyskinesia was found to be not significantly different (n=32, RR 0.62 CI 0.3 to 1.26) between quetiapine and haloperidol when these neuroleptics were used as specific treatments for TD, although the need for additional neuroleptics was significantly lower in the quetiapine group (n=47, RR 0.49 CI 0.2 to 1.0) than in those given haloperidol. AUTHORS' CONCLUSIONS: Limited data from small studies using neuroleptic reduction or specific neuroleptic drugs as treatments for TD did not provide any convincing evidence of the value of these approaches. There is a need for larger trials of a longer duration in order to fully investigate this area.

Non-neuroleptic catecholaminergic drugs for neuroleptic-induced tardive dyskinesia.

BACKGROUND: Tardive dyskinesia (TD) is a disabling movement disorder associated with the prolonged use of neuroleptic medication. Several strategies have been examined in the treatment of TD. Currently, however, there is no clear evidence of the effectiveness of these drugs in TD and they have been associated with many side effects. One particular strategy would be to use pharmaceutical agents which are known to influence the catecholaminergic system at various junctures. OBJECTIVES: To determine whether catecholaminergic drugs for people with schizophrenia or other chronic mental illnesses are associated with a reduction in neuroleptic-induced tardive dyskinesia. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's Register (January 1996), Biological Abstracts (1982-1995), EMBASE (1980-1995), LILACS (1982-1996), MEDLINE (1966-1995) and PsycLIT (1974-1995). We searched the Cochrane Schizophrenia Group's Register again in December 2002 and September 2005. We also searched references of all relevant studies for further trial citations and contacted principal authors of trials. SELECTION CRITERIA: We selected studies if they were randomised controlled trials focusing on people with schizophrenia or other chronic mental illnesses who also suffered from neuroleptic-induced tardive dyskinesia. We compared the use of catecholaminergic interventions versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: We independently extracted data. For homogenous dichotomous data, we calculated the random effects, relative risk (RR), and 95% confidence interval (CI) and, where appropriate, the numbers needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: We excluded 20 studies, mainly due to an inability to extract data from the first arm of the study crossover. One included study has shown that patients on placebo were no more likely to leave the study early than those on tiapride (n=24). The other included study (n=35) also reported equivocal data (RR 5.28 CI 0.3 to 102.6) for leaving the study early when participants were randomised to either celiprolol or placebo. However, in both studies, sample size was limited. AUTHORS' CONCLUSIONS: Although there has been a large amount of research in this area, most studies were excluded due to inherent problems in the nature of their crossover designs. Usually data are not reported before the crossover and the nature of TD and its likely response to treatments makes it imprudent to use this data. The review provides little usable information for service users or providers and more well designed and reported studies are indicated.

Benzodiazepines alone or in combination with antipsychotic drugs for acute psychosis.

BACKGROUND: Acute psychotic illness, especially when associated with agitated or violent behaviour, can require urgent pharmacological tranquillisation or sedation. In several countries, clinicians often use benzodiazepines (either alone or in combination with antipsychotics) for this outcome. OBJECTIVES: To estimate the effects of benzodiazepines, alone or in combination with antipsychotics, when compared to placebo or antipsychotics, to control disturbed behaviour and reduce psychotic symptoms. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register (October 2002 and April 2005), inspected reference lists of included and excluded studies and contacted authors of relevant studies. SELECTION CRITERIA: We included all randomised clinical trials comparing benzodiazepines, alone or in combination with antipsychotics, with placebo or sole use of antipsychotics, for people with acute psychotic illnesses. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality assessed them and extracted data. For binary outcomes we calculated standard estimates of relative risk (RR) and their 95% confidence intervals (CI), and weighted number needed to treat or harm (NNT/NNH) statistics. For continuous outcomes we estimated a weighted mean difference between groups. If heterogeneity was found, we used a random effects model. MAIN RESULTS: We included eleven studies with a total of 648 participants. When comparing benzodiazepines with placebo, sedation was equally prevalent (n=102, 1 RCT, RR 1.67 CI 0.4 to 6.6), however, fewer people allocated lorazepam remained excited at 24 hours (n=102, RR 0.62 CI 0.4 to 1.0, NNT 5 CI 3 to 59). The lorazepam and placebo group experienced similar non-significant, low levels of adverse effects. In the comparison of benzodiazepines versus use of antipsychotics without use of anticholinergics/antihistamines, people allocated benzodiazepines did not clearly need additional medication compared with those given antipsychotics (n=216, 2 RCTs, RR 1.28 CI 0.5 to 3.2). Numbers sedated were also equivocal between groups (n=324, 6 RCTs, RR 0.76 CI 0.5 to 1.2) as were mental state ratings. Extrapyramidal symptoms were significantly higher in the antipsychotic treatment group (n=391, 7 RCTs, RR 0.17 CI 0.1 to 0.4, NNT 6 CI 2 to 17). Two trials (total n=83) comparing lorazepam plus haloperidol with lorazepam alone found no clear difference for the need of additional medication (n=83, 2 RCTs, RR 1.02 CI 0.8 to 1.3) or 'not improved' at one hour (n=20, 1 RCT, RR 1.47 CI 0.66 to 3.25). There was no difference in the incidence of extrapyramidal symptoms (n=83, 2 RCTs, RR 1.94 CI 0.2 to 20.3). Finally when the benzodiazepine plus antipsychotic combination was compared with antipsychotics alone (2 RCTs, n=95) there was no difference between groups in the need for additional medications (n=67, 1 RCT, RR 0.95 CI 0.8 to 1.2) or for mental state measures. Extrapyramidal symptoms were significantly lower for people receiving both benzodiazepines and antipsychotics compared with those receiving antipsychotics alone (n=95, 2 RCTs, RR 0.45 CI 0.2 to 0.9, NNH 2 CI 1 to 5). There was no significant difference in the number of participants unfit for early discharge (n=28, 1 RCT, RR 0.90 CI 0.54 to 1.5). AUTHORS' CONCLUSIONS: There is insufficient data from these studies to support or refute the use of benzodiazepines with or without antipsychotics where emergency drugs are needed. The sole use of older antipsychotics unaccompanied by anticholinergic drugs may be problematic, but studies in this review are not large enough to identify any serious adverse effects of benzodiazepines such as respiratory depression. Larger, more informative studies are needed before definite conclusions can be drawn as to the efficacy of benzodiazapines.

Chinese herbal medicine for schizophrenia.

BACKGROUND: Traditional Chinese medicine (TCM) was the main form of treatment in China for psychiatric illnesses until the development of antipsychotic drugs in the 1950's. Antipsychotic drugs have become the primary intervention for schizophrenia, although herbal medicines can still form part of the treatment. OBJECTIVES: To review Chinese herbal medicine, used alone or as part of a TCM approach, for people with schizophrenia and related psychoses. SEARCH STRATEGY: We undertook electronic searches of the Cochrane Schizophrenia Group's register (December 2003), the Traditional Chinese Medical Literature Analysis and Retrieval Database (TCMLARS) (October 2003), Chinese Biomedical Database (CBM) (December 2003), China National Knowledge Infrastructure Database (May 2004), Complementary Medicine Database (AMED) (December 2003). We contacted the Chinese Cochrane Centre, the Cochrane Complementary Medicine Field and first authors of included studies and inspected reference lists for additional studies. SELECTION CRITERIA: We included all relevant randomised controlled trials involving people with schizophrenia-like illnesses, allocated to Chinese herbal medicine, including any Chinese herbs (single or mixture), compared with placebo/no treatment or antipsychotic drugs. DATA COLLECTION AND ANALYSIS: We independently extracted data and calculated fixed effects relative risk (RR), the 95% confidence intervals (CI) for homogeneous dichotomous data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: Only one small trial of the seven included studies truly evaluated TCM for schizophrenia. The other trials evaluated Chinese herbs for schizophrenia. We found one study comparing Chinese herbal medicine with antipsychotic drugs. Data for the global state outcome 'no change/worse' favoured people allocated to antipsychotic medication (n=90, RR 1.88 CI 1.2 to 2.9, NNH 4 CI 2 to 12). Six trials compared Chinese herbal medicine in combination with antipsychotic with antipsychotic drugs alone. One trial found global state 'not improved/worse' favoured the herbal medicine/antipsychotic combination (n=123, RR 0.19 CI 0.1 to 0.6, NNT 6 CI 5 to 11). Two studies (n=103) also found short-term data from the Clinical Global Impression scale favoured the herbal medicine plus antipsychotic group (WMD -0.46 CI -0.9 to -0.1) compared with those given only antipsychotics. Significantly fewer people in the experimental group left the study early compared with those given antipsychotics alone (n=1004, 6 RCTs, RR 0.30 CI 0.16 to 0.58, NNT 21 CI 18 to 35). Reports of constipation were significantly lower in the treatment group compared to those receiving antipsychotics (n=67, 1 RCT, RR 0.03 CI 0.0 to 0.5, NNH 2 CI 2 to 4). AUTHORS' CONCLUSIONS: Chinese herbal medicines, given in a Western biomedical context, may be beneficial for people with schizophrenia when combined with antipsychotics. Traditional Chinese medicine is also under-evaluated, but results from one pioneering study that attempted to evaluate TCM should encourage further trials.

Acupuncture for schizophrenia.

BACKGROUND: Acupuncture has been shown to be a relatively safe health care intervention with few adverse effects. In contrast ,antipsychotic drugs can have seriously disabling adverse effects. However, the benefits of acupuncture in the treatment of schizophrenia are unclear, and further evidence is needed to inform clinicians and people with schizophrenia of its efficacy in the treatment of schizophrenia. OBJECTIVES: To evaluate acupuncture for people with schizophrenia and related psychoses. SEARCH STRATEGY: We (JR, JX) undertook electronic searches of the Cochrane Schizophrenia Group's register (April 2005). We inspected reference lists and contacted the first author of each included study. SELECTION CRITERIA: We included all relevant randomised controlled trials involving people with schizophrenia-like illnesses, allocated to acupuncture, electro-acupuncture, laser-acupuncture, placebo, no treatment, or antipsychotic drugs produced by pharmaceutical companies were included. DATA COLLECTION AND ANALYSIS: We independently extracted the data. For homogeneous dichotomous data, the fixed 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, we calculated weighted mean differences with 95% CI. MAIN RESULTS: We included five trials. Two trials comparing acupuncture to antipsychotics were equivocal for global state and leaving the study early. Extrapyramidal adverse events were significantly lower in the acupuncture group (n=21, RR 0.05 CI 0.0 to 0.8, NNT 2 CI 2 to 8). Four out of the five trials also compared acupuncture combined with antipsychotics to antipsychotics alone. Global state outcomes and leaving the study early were equivocal. BPRS endpoint data (short term) favoured the combined acupuncture and antipsychotic group (n=109, RR -4.31 CI -7.0 to -1.6), although dichotomised BPRS data 'not improved' confounded this outcome with equivocal data. Depression scores HAMD (n=42, WMD -10.41 CI -12.8 to -8.0), HAMD 'not improved' (n=42, RR 0.17 CI 0.1 to 0.5, NNT 2 CI 2 to 3) and ZDS (n=42, WMD -24.25 CI -28.0 to -20.5) significantly favoured the combined acupuncture/antipsychotic treatment group, although results were from single, small studies. Treatment emergent adverse events scores were significantly lower in the acupuncture/antipsychotic group (n=40, WMD -0.50 CI -0.9 to -0.1), again from a single, small study. AUTHORS' CONCLUSIONS: We found insufficient evidence to recommend the use of acupuncture for people with schizophrenia. The numbers of participants and the blinding of acupuncture were both inadequate, and more comprehensive and better designed studies are needed to determine the effects of acupuncture for schizophrenia.

Depot perphenazine decanoate and enanthate for schizophrenia.

BACKGROUND: Antipsychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain. OBJECTIVES: To assess the effects of depot perphenazine decanoate and enanthate versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: We updated previous searches of the Cochrane Schizophrenia Group Register (June 1998), Biological Abstracts (1982-1998), the Cochrane Library (Issue 2, 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) by searching the Cochrane Schizophrenia Group Register (March 2004). References of all identified trials were also inspected for more studies and industry contacted. SELECTION CRITERIA: We compared randomised clinical trials focusing on people with schizophrenia where depot perphenazine decanoate and enanthate, oral antipsychotics or other depot preparations. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated them and extracted data. For dichotomous data we estimated the Relative Risk (RR) with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat. MAIN RESULTS: Only four studies (Ahlfors 1980, Eufe 1979, Knudsen 1985c, Tegeler 1979), randomising a total 313 people could be included in this review and this combined with an overall lack of usable data limits any interpretation of results. Perphenazine enanthate was not significantly any better or worse than other depot antipsychotics in most of the main outcomes such as global state, relapse or leaving the study early. We found some differences favouring the control groups for adverse effects. One study (Ahlfors 1980) of six months' duration (n=172), compared perphenazine enanthate to clopenthixol decanoate. There were no differences between the two groups for outcomes of global improvement, relapse and leaving the study early. More people in the perphenazine enanthate group, however, required anticholinergic drugs than those allocated to clopenthixol decanoate (RR 1.12 CI 1.0 to 1.2, NNT 10).A single study (n=64, duration six weeks) compared perphenazine enanthate and its longer acting decanoate ester. Data on relapse and leaving the study early failed to show convincing differences. The enanthate group, however, experienced more movement disorders (RR 1.36, CI 1.1 to 1.8 NNT 5) than those allocated the decanoate ester of the same drug and required more anticholinergic drugs (RR 1.47 CI 1.1 to 2.0, NNT 4). AUTHORS' CONCLUSIONS: Depot perphenazine is in clinical use in the Nordic countries, Belgium, Portugal and the Netherlands. At a conservative estimate, a quarter of a million people suffer from schizophrenia in those countries and could be treated with depot perphenazine. The total number of participants in the four trials with useful data is 313. None of the studies observed the effects of oral versus depot antipsychotic drugs. Until well conducted and reported randomised trials are undertaken clinicians will be in doubt as to the effects of perphenazine depots and people with schizophrenia should exercise their own judgement or ask to be randomised.