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Biomedical subjects

S Leucht

Publications and source records attributed to S Leucht.

At least 19 recordsLinked to original sources

Antidepressants for the negative symptoms of schizophrenia.

BACKGROUND: Negative symptoms are common in people with schizophrenia and are often difficult to treat with antipsychotic drugs. Treatment often involves the use of various add-on medications such as antidepressants. OBJECTIVES: To review the effects of the combination of antipsychotic and antidepressant drug treatment for management of negative symptoms in schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register (January 2004). We also contacted authors of included studies in order to identify further trials. SELECTION CRITERIA: We included all randomised controlled trials comparing antipsychotic and antidepressant combinations with antipsychotics alone for the treatment of prominent negative symptoms in schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Working independently, we selected and critically appraised studies, extracted data and analysed on an intention-to-treat basis. Where possible and appropriate we calculated the relative risk RR) and their 95% confidence intervals (CI), with the number needed to treat (NNT). MAIN RESULTS: We included five studies (all short-term, total N=190). We found no significant difference for 'leaving the study early for any reason' between the antipsychotic plus antidepressant combination and the control group (n=90, 3 RCTs, RR 3.0 CI 0.35 to 26.04). Leaving early due to adverse events (n=64, 2 RCTs, RR 5.0 CI 0.26 to 97.0) and leaving the study early due to inefficacy (n=34, 1 RCT, RR 3.0 CI 0.13 to 68.84) also showed no significant difference between the two treatment groups. In terms of clinical response, participants treated with the antipsychotic plus antidepressant medications showed a statistically significant greater improvement (n=30, 1 RCT, WMD -1.0 CI -1.61 to -0.39) and showed a significantly lower severity at endpoint (n=30, 1 RCT, WMD -0.9 CI -1.55 to -0.25) on the Clinical Global Impression Scale than those treated with antipsychotics alone. More people allocated to combination therapy had a clinically significant improvement in negative symptoms compared with those given antipsychotics and placebo (n=60, 2 RCTs, RR 0.56 CI 0.32 to 0.97, NNT 3 CI 3 to 34). Significant differences in favour of the combination therapy were seen in different aspects of negative symptoms: 'affective flattening' (n=30, 1 RCT, WMD -7.0 CI -10.37 to -3.63), 'alogia' (n=26, 1 RCT, WMD -3.00 CI -5.14 to -0.86) and 'avolition' (n=30, 1 RCT, WMD -3.0 CI -5.04 to -0.96). No statistically significant difference was found between treatment groups in regards to the outcome 'at least one adverse event' (n=84, 2 RCTs, RR 1.80 CI 0.66 to 4.90). For movement disorders and other adverse effects, no statistically significant differences were found in any of the studies that provided usable data on these outcomes. There are no data at all on outcomes such as compliance, cost, social and cognitive functioning, relapse, recurrence of negative symptoms, rehospitalisation or quality of life. There are no medium or long term data. AUTHORS' CONCLUSIONS: The combination of antipsychotics and antidepressants may be effective in treating negative symptoms of schizophrenia, but the amount of information is currently too limited to allow any firm conclusions. Large, pragmatic, well-designed and reported long term trials are justified.

Antidepressive Agents↗

Perazine for schizophrenia.

BACKGROUND: Perazine is an old phenothiazine derivative used for the treatment of people with schizophrenia and is reputed to have a low level of extrapyramidal adverse effects. As far as we are aware, its use is limited to Germany, Poland, the former Yugoslavia and the Netherlands. OBJECTIVES: To examine the effects of perazine for those with schizophrenia, and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register which includes relevant randomised controlled trials from the bibliographic databases Biological Abstracts, CINAHL, The Cochrane Library, EMBASE, MEDLINE, PsycLIT, LILACS, PSYNDEX, Sociological Abstracts and Sociofile (last update of the review March 2005). We searched references of all included studies for further trials. We contacted pharmaceutical companies and authors of trials. SELECTION CRITERIA: We selected all randomised controlled trials that compared perazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We independently (SL, BH) inspected citations and where possible abstracts and ordered papers for re-inspection and quality assessment. We independently extracted data. We excluded data if loss to follow up was greater than 50%. For homogeneous dichotomous data we calculated the Relative Risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). We inspected all data for heterogeneity. MAIN RESULTS: We included six trials with a total of 288 participants. In only one trial with 95 participants, perazine appeared superior to 'active placebo' (trimipramine) at five weeks for the outcome of 'no important global improvement' (n=95, RR 0.43 CI 0.2 to 0.8, NNT 4 CI 2 to 13), but there was no statistically significant difference in most measures of mental state. Perazine did not induce more general adverse events than placebo, but more participants received at least one dose of antiparkinson medication (n=95, RR 4.50 CI 1.0 to 19.5, NNH 6 CI 4 to 33). Five small trials comparing perazine with other antipsychotics, including in total only 193 participants, were incompletely reported and the outcomes were presented in various ways so that meta-analysis was not possible in most occasions. A similar number of participants receiving perazine or comparator antipsychotics left the studies early (n=193, RR 0.85, CI 0.5 to 1.4). The results on efficacy were controversial and need further assessment by randomised controlled trials. No obvious differences in adverse events between perazine and other antipsychotics could be derived from the limited data. Two haloperidol comparisons did not present extrapyramidal side-effects in a suitable way for use in meta-analysis, but three small comparisons with the atypical antipsychotics zotepine and amisulpride showed no higher risk of akathisia (n=111, RR 0.31 CI 0.1 to 1.1), dyskinesia (n=111, RR 0.47 CI 0.1 to 3.5), parkinsonism (n=81, RR 1.21 CI 0.5 2.8) or tremor (n=40, RR 0.80 CI 0.3 to 2.6) with perazine. AUTHORS' CONCLUSIONS: The number, size and reporting of randomised controlled perazine trials is insufficient to present firm conclusions about the properties of this antipsychotic. It is possible that perazine is associated with a similar risk of extrapyramidal side-effects as some atypical antipsychotics, and this should be clarified in larger, well-designed trials.

Antipsychotic Agents↗

The concepts of remission and recovery in schizophrenia.

OBJECTIVE: To examine the past and current research into the concepts of remission and recovery in schizophrenia. DATA SOURCES: An electronic literature search of studies published between January 1990-April 2005 examining the concepts of remission and recovery in schizophrenia and the treatment of schizophrenia with antipsychotic agents was performed using Medline and EMBASE. Primary research parameters were 'schizophrenia', 'remission', 'recovery', 'meta-analysis', 'antipsychotics', 'atypicals', 'conventional', 'cognition', 'function' and 'quality of life'. STUDY SELECTION: English language articles, original research articles, reviews and other articles of interest were reviewed. DATA EXTRACTION: Data quality was determined by publication in the peer-reviewed literature and the most important information was identified. DATA SYNTHESIS: A number of different definitions of remission and recovery have been previously used, which has made comparison of study results problematic. Recently, the first operational definition of remission, based on Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria (DSM-IV) for schizophrenia, was developed. It is hoped that this will provide a standard tool for assessing the effectiveness of treatments for schizophrenia. Recovery, which encompasses both symptom remission and more functional aspects of patient's well being, such as cognition, social functionality and quality of life, is still to be satisfactorily defined. Although recent studies on new generation antipsychotics have examined some proxy outcomes related to recovery, further research is required. CONCLUSIONS: Until the definition for 'recovery' is further elucidated, factors such as symptom control and remission, and functional aspects of recovery such as improvements in cognition and social functioning, which are quantifiable, should be used as measures of treatment outcome and markers of recovery.

Antipsychotic Agents↗

Standardized remission criteria in schizophrenia.

OBJECTIVE: Recent work has focussed on schizophrenia as a 'deficit' state but little attention has been paid to defining illness plasticity in terms of symptomatic remission. METHOD: A qualitative review of a recently proposed concept of remission [N.C. Andreasen, W.T. Carpenter Jr, J.M. Kane, R.A. Lasser, S.R. Marder, D.R. Weinberger (2005) Am J Psychiatry 162: 441] is presented. RESULTS: The proposed definition of remission is conceptually viable, and can be easily implemented in clinical trials and clinical practice. Its increasing acceptance may reset expectations of treatment to a higher level, improve documentation of clinical status and facilitate dialogue on treatment expectations. The availability of validated outcome measures based on remission will enhance the conduct and reporting of clinical investigations, and could facilitate the design and interpretation of new studies on cognition and functional outcomes. While useful as a concept, it is important to consider that remission is distinct from recovery. CONCLUSION: The introduction of standardized remission criteria may offer significant opportunities for clinical practice, health services research and clinical trials.

Chronic Disease↗

Shared decision making for in-patients with schizophrenia.

OBJECTIVE: Patients' participation in treatment planning is being increasingly advocated in mental health. The model of "Shared Decision Making" (SDM) is proposed as a promising method of engaging patients in medical decisions and improving health-related outcomes. In the present study, the feasibility and effects of SDM for in-patients with schizophrenia should be evaluated. METHOD: Randomized controlled trial comparing a SDM program with routine care (n = 107). RESULTS: The intervention studied was feasible for most of the patients and did not take up more of the doctors' time. Patients in the intervention group had a better knowledge about their disease (P = 0.01) and a higher perceived involvement in medical decisions (P = 0.03). The intervention increased the uptake of psychoeducation (P = 0.003). CONCLUSION: Sharing medical decisions with acutely ill in-patients with schizophrenia is in many cases possible and improves important treatment patterns. This might help in destigmatizing this group of patients and improving schizophrenia-related health outcomes.

Acute Disease↗

European psychiatric treatment guidelines: is the glass half full or half empty?

PURPOSE: We assessed the quality of European treatment guidelines in the field of mental health that have been produced by national psychiatric associations. The main focus was the question of whether the development process of the guidelines followed basic principles of evidence-based medicine. METHODS: Sixty-one European clinical practice guidelines from 14 countries, published between 1998 and 2003, were assessed using the 'Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument'. The domain score was calculated for each of the six domains of the AGREE instrument. The seven items of the domain "rigor of development" and one additional item concerning national particularities were assessed in detail. RESULTS: The mean scores in the six domains were rather low, although the quality varied among the different guidelines. The highest mean score was obtained in the domain clarity and presentation (70.8% S.D. 23.5), the lowest on editorial independence (19.7% S.D. 29.3). The recommendations of about half of the assessed guidelines could be considered to be evidence-based. CONCLUSION: The assessed guidelines showed a broad range of quality: some producers attached importance to an evidence-based development process; but in spite of this, a large number of guidelines were only of middling quality. As national particularities are only rarely mentioned and the development process of guidelines is complex, an international collaboration that aims toward the production of shareable guidelines might be promising.

Europe↗

Benperidol for schizophrenia.

BACKGROUND: Benperidol is a relatively old antipsychotic drug that has been marketed since 1966. It has been used in Germany for 30 years, but is also available in Belgium, Greece, Italy, the Netherlands and the UK. Benperidol is a butyrophenone antipsychotic, with the highest neuroleptic potency in terms of D2 receptor blockade. Those taking it are therefore reputed to be at high risk of extrapyramidal side effects, but benperidol's unusual profile may render it valuable to subgroups of people with schizophrenia. OBJECTIVES: To examine the clinical effects and safety of benperidol for those with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register (November 2004) for this update. SELECTION CRITERIA: We included all randomised controlled trials that compared benperidol with other treatments for people with schizophrenia, or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated them and extracted data. We independently extracted data but excluded data if loss to follow up was greater than 50%. 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. MAIN RESULTS: The update yielded no further studies for inclusion in the review. We identified only one unpublished poorly randomised controlled trial (N=40, duration 30 days, comparison perphenazine). Although benperidol was inferior to perphenazine (1 RCT, N=40, global state no better or worse RR 8.0 CI 2.1 to 30, NNH 1.4 CI 1 to 2) poor reporting suggests that an overestimate of effect is likely. It was not possible to report other outcomes. AUTHORS' CONCLUSIONS: Currently, there are insufficient data from randomised trials to assess the clinical effects of benperidol. This compound merits further research interest.

Antipsychotic Agents↗

Perphenazine for schizophrenia.

BACKGROUND: Perphenazine is an old phenothiazine antipsychotic with a potency similar to haloperidol. It has been used for many years and is popular in the northern European countries and Japan. OBJECTIVES: To examine the clinical effects and safety of perphenazine for those with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register (June 2001), references of all included studies and contacted pharmaceutical companies and authors of included studies in order to identify further trials. SELECTION CRITERIA: We included all randomised controlled trials that compared perphenazine with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. We excluded trials of depot formulations of perphenazine. DATA COLLECTION AND ANALYSIS: Two reviewers independently inspected citations and, where possible, abstracts. We ordered papers, inspected and quality assessed them. We extracted data, again working independently. If loss to follow up was greater than 50% we considered results as 'prone to bias'. For dichotomous data we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat/harm (NNT/H) on an intention-to-treat basis. For continuous data, we calculated weighted mean differences (WMD). MAIN RESULTS: The review currently includes 25 studies with 2478 patients, 2285 of whom had been randomised to interventions that were relevant for the review such as perphenazine, other antipsychotic drugs or placebo. The trials were carried out between 1961 and 1993. All but one trial were short term with a duration of between ten days and 12 weeks. Descriptions of allocation and blinding were usually incomplete. Six studies (n=300) compared perphenazine with placebo. Perphenazine was associated with fewer participants leaving the trials early due to relapse or worsening of symptoms (n=84, RR 0.1 CI 0.03 - 0.4, NNT 2 CI 1 to 20). Twenty studies compared perphenazine (n=738) with other antipsychotics (n=1278). Perphenazine seemed as effective as other antipsychotics ('global state unimproved or worse' n=1327, RR 1.0 CI 0.9 to 1.2). We found no clear differences in terms of specific aspects of efficacy, behaviour or tolerability. However, interpretation of findings of the review was limited by poor reporting and the use of 24 different comparator antipsychotics in the 20 trials. AUTHORS' CONCLUSIONS: Although perphenazine has been randomised for more than 40 years, incomplete reporting and the variety of comparators used make it impossible to draw clear conclusions. At best we can say that perphenazine showed similar effects and adverse events as several of the other pooled antipsychotic drugs. Since perphenazine is a relatively inexpensive and frequently used compound, further trials are justified to clarify the properties of this classical antipsychotic drug.

Antipsychotic Agents↗

Valproate for schizophrenia.

BACKGROUND: Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them valproate. OBJECTIVES: To review the effects of valproate for the treatment of schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane Schizophrenia Group's register (July 2002). This register is compiled of methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted a pharmaceutical company and authors of relevant studies in order to identify further trials. SELECTION CRITERIA: All randomised controlled trials comparing valproate to antipsychotics or to placebo (or no intervention), whether as the sole agent or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using relative risks (RR) and the 95% confidence intervals (CI). Continuous data were analysed using weighted mean differences. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. MAIN RESULTS: Five studies with a total of 379 participants were included. All trials examined the effectiveness of valproate as an adjunct to antipsychotics. With one exception the studies were small, short-term and incompletely reported. Adding valproate was as acceptable as adding placebo to antipsychotic drugs (n=130, RR leaving the study early 1.6 CI 0.8 to 3.1). No significant effect of using valproate as an adjunct to antipsychotic medication on the participants' global state or general mental state at the endpoint studies was evident. However, one study showed a quicker onset of action in the combination group. Participants receiving valproate more frequently experienced sedation than those in the placebo group. The effects of valproate on important subgroups such as those with schizophrenia and aggressive behaviour or those with schizoaffective disorder are unknown. REVIEWER'S CONCLUSIONS: Based on randomised trial-derived evidence which is currently available, there are no data to support or to refute the use of valproate as a sole agent for schizophrenia. There is some evidence for a more rapid improvement with valproate augmentation, but this effect vanished over time. Given this limited evidence, further large, simple well-designed and reported trials are necessary. These might focus on people with schizophrenia and violent episodes, on those with treatment resistant forms of the disorder and on people with schizoaffective disorders.

Antimanic Agents↗

Language bias in neuroscience--is the Tower of Babel located in Germany?

In internal medicine German authors tend to publish randomized controlled trials (RCTs) with non-significant findings in German journals, RCTs with significant findings in international journals. In the neurosciences a similar trend was seen but the findings were not statistically significant. The reason for this inconclusive finding might be the low number of RCTs published in German.

Germany↗

[Meta-analysis of effectiveness and tolerability of treatment of mild to moderate depression with St. John's Wort].

After anxiety, depression is one of the most common psychiatric diseases, showing a lifetime prevalence of 4.4 - 18 %. St. John's Wort is a herbal antidepressant combining a long tradition of use with well-proven medical research. We conducted a meta-analysis to review St. John's Wort's place in the treatment of depression. A comprehensive literature search was conducted for studies comparing effectiveness and tolerability of St. John's Wort with either placebo or synthetic antidepressant. Thirty studies met the inclusion as well as the quality criteria and were included in the meta-analysis. Four studies consisted of all three arms and were thus included in both analyses. Our results demonstrated a significant advantage for St. John's Wort compared to placebo (n = 2129, RR = 0.66, 95 % CI 0.57 - 0.78, p < 0.00001, NNT = 4.2 95 % CI 3.0 - 6.6, mean response: 53.3 vs. 32.7 %). Compared to synthetic antidepressants St. John's Wort demonstrated similar effectiveness (n = 2231, RR = 0.96, 95 % CI 0.85 - 1.08, p = 0.5, mean response: 53.2 % vs. 51.3 %). In the sub-group of mild to moderate depression, corresponding with the indication for St. John's Wort assigned by the German health authority, the herbal antidepressant showed better results against the synthetic antidepressants (n = 1166, RR = 0.85, 95 % CI 0.75 - 0.97, p = 0.01, NNT = 14.3, 95 % CI 8.3 - 100, mean response 59.5 vs. 52.9 %). This result viewed together with St. John's Wort's favourable side-effects profile, leading to a lower rate of drop-outs, suggests treatment with St. John's Wort should be attempted for milder forms of depression. Funnel plot analysis suggested publication bias could exist for the comparison with placebo. To put this in a perspective the fail-safe-N-test calculated that 423 studies with no effect would be needed to negate the presented result for placebo studies.

Antidepressive Agents↗

[Fugue and suicide].

The existence of dissociative fugue is doubted by many psychiatrists. We describe a 22-year-old patient who traveled about 600 km to Munich during a dissociative fugue and then exhibited an irreversible amnesia for a period of 24 h. There was a severe, clearly understandable conflict in the sense of a subjective stalemate situation which has been described as typical for dissociative fugue. The patient had a labile personality structure with insufficient coping strategies. It was possible to rule out other psychiatric or neurological disorders with sufficient certainty, and simulation was very unlikely. The conflict could not be satisfactorily solved, and the patient committed suicide 5 months later by jumping off a bridge.

Adult↗

Lithium for schizophrenia.

BACKGROUND: Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary antipsychotic drug treatment. In these cases, various add-on medications are used, among them lithium. OBJECTIVES: To review the effects of lithium for the treatment of schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane Schizophrenia Group's register (March 2002). This register is compiled by methodical searches of BIOSIS, CINAHL, Dissertation abstracts, EMBASE, LILACS, MEDLINE, PSYNDEX, PsycINFO, RUSSMED, Sociofile, supplemented with hand searching of relevant journals and numerous conference proceedings. We also contacted pharmaceutical companies and authors of relevant studies to identify further trials and to obtain original patient data. SELECTION CRITERIA: All randomised controlled trials comparing lithium to antipsychotics or to placebo (or no intervention), whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were extracted independently by at least two reviewers. Dichotomous data were analysed using relative risks (RR) and the 95% confidence interval (CI) estimated. Where possible the number needed to treat (NNT) or number needed to harm statistics were calculated. Continuous data were analysed using weighted mean differences (WMD). MAIN RESULTS: The review currently includes 20 studies with a total of 611 participants. Most studies were small, of short duration and incompletely reported, but a number of authors were willing to share their data with us. Three studies comparing lithium with placebo as the sole treatment showed no difference in any of the outcomes we analysed. In eight studies comparing lithium with antipsychotic drugs as the sole treatment more participants in the lithium group left the studies early (n=270, RR 1.8, CI 1.2 to 2.9, NNT 9, CI 5 to 33). Several of the outcomes relating to these studies suggested that lithium is less effective than antipsychotic drugs, but it was difficult to summarise the data, because a variety of rating scales were used in the studies. Eleven studies examined whether the augmentation of antipsychotic drugs with lithium salts is more effective than antipsychotic drugs alone. More participants who received lithium augmentation had a clinically significant response (n=244, RR 0.8, CI 0.7 to 0.96, NNT 8, CI 4 to 33). However, statistical significance became borderline when participants with schizoaffective disorders were excluded in a sensitivity analysis (n=120, RR 0.8, CI 0.6 to 1.0, p=0.07). Furthermore, more participants in the lithium augmentation groups left the studies early (n=320, RR 2.0 CI 1.3 to 3.1, NNT 7, CI 4 to 14), suggesting a lower acceptability of lithium augmentation compared to those on antipsychotics alone. No superior efficacy of lithium augmentation in any specific aspect of the mental state was found. While based on very little data, there were no differences between groups for adverse events. REVIEWER'S CONCLUSIONS: There is no randomised trial based evidence that lithium on its own is an effective treatment for people with schizophrenia. The evidence available on augmentation of antipsychotics with lithium is inconclusive, but it justifies further, large, simple and well-designed trials. These should concentrate on two target groups: 1) people with no affective symptoms, so that trialists can determine whether lithium has an effect on the core symptoms of schizophrenia, 2) people with schizoaffective disorders for whom lithium is widely used in clinical practice, although there is no evidence to support this use.

Antipsychotic Agents↗

New generation antipsychotics for first episode schizophrenia.

BACKGROUND: The new generation antipsychotics are associated with a lower risk of adverse effects compared with drugs such as haloperidol. Many treatment guidelines recommend the use of new generation ('atypical') antipsychotic drugs for people with a first episode of schizophrenia. OBJECTIVES: To examine the effects of the new generation antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. SEARCH STRATEGY: The reviewers searched the Cochrane Schizophrenia Group's register (March 2002) and the included and excluded studies tables of relevant Cochrane reviews, references of all relevant studies, contacted industry and authors of relevant studies to identify further trials. SELECTION CRITERIA: Randomised clinical trials comparing new generation antipsychotics (amisulpride, clozapine, olanzapine, quetiapine, risperidone, sulpiride, ziprasidone, zotepine) with conventional antipsychotics for people with a first episode of schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by three reviewers, papers ordered, re-inspected and quality assessed. We independently extracted data but excluded them if loss to follow up was greater than 50%. For homogeneous dichotomous data, we calculated the relative risk (RR), the 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT), on an intention-to-treat basis. For continuous data, reviewers calculated weighted mean differences (WMD). MAIN RESULTS: We include two short-term studies (total n=266), one of which was a report of a sub-group of a larger study. One compared risperidone with an average of 6 mg/day haloperidol and the other olanzapine with an average of 11 mg/day haloperidol. Compared with olanzapine, significantly more people receiving haloperidol left the study early (n=83, 1 RCT, RR 0.43 CI 0.3 to 0.7, NNH 3 CI 2 to 8). This was not so for the risperidone versus haloperidol comparison (n=183, 1 RCT, RR=0.7 CI 0.4 to 1.1). In terms of global effects, studies reported no differences between risperidone and haloperidol (n=183, RR not much improved 1.0 CI 0.6 to 1.5), and olanzapine and the same control (n=83, RR needing at least one dose of benzodiazepine 0.8 CI 0.5 to 1.1). More people allocated to olanzapine had clinically significant improvement in mental state compared with those given haloperidol (n=83, RR no 'clinically significant improvement' 0.45 CI 0.3 to 0.7, NNH 3 CI 2 to 6). In the risperidone study, however, no such difference was apparent (n=183, RR 'no clinically significant improvement in mental state' 0.85 CI 0.6 to 1.2). Significantly more people given haloperidol (4-16mg) experienced at least one adverse event when compared with risperidone (4-16mg) (n=183, RR 0.9 CI 0.8 to 0.98, NNH 8 CI 4 to 50). Use of anticholinergic medication for extrapyramidal adverse events was less prevalent for people allocated either olanzapine (n=83, RR 0.3 CI 0.2 to 0.7, NNH 4 CI 2 to 14) or risperidone (n=183, RR 0.7 CI 0.5 to 0.9, NNH 4 CI 3 to 9) compared with those given haloperidol. There are no data at all on outcomes such as compliance, cost, social and cognitive functioning, relapse, rehospitalisation, or quality of life. There are no medium to long-term data. Eight ongoing studies may provide more information. REVIEWER'S CONCLUSIONS: The results of this review are inconclusive. Whether the use of new generation antipsychotics really makes the treatment less off putting and enhances long-term compliance is unclear. Pragmatic, well-designed and reported long-term trials would be useful to answer this question.

Antipsychotic Agents↗

Shared decision making in psychiatry.

OBJECTIVE: In other medical fields, 'shared decision making' (a strategy for including patients in therapeutic decision processes) has been studied for several years now. This survey presents the potential of shared decision making for psychiatry. METHOD: Literature search. RESULTS: Research in other medical fields shows that shared decision making positively influences patients' satisfaction as well as health outcomes. The application of shared decision making to psychiatry is still in the initial stage. CONCLUSION: Evidence that shared decision making can be successfully practiced in psychiatry would contribute to an improved inclusion of psychiatric patients in therapeutic decisions and thereby help to implement basic rights of a group of patients who have not sufficiently benefited from consumer empowerment in other medical fields.

Antipsychotic Agents↗

Are the second-generation antipsychotics cost-effective? A critical review on the background of different health systems.

BACKGROUND: Despite clinical advantages over conventional compounds, second-generation antipsychotics are prescribed less frequently in some European countries than in the United States because of their higher acquisition price and the current cost-containment strategies of many European health systems. This has been criticized on the grounds that the higher acquisition costs of the new antipsychotics might be more than outweighed by savings in other fields, e. g., through a reduction in rehospitalizations or indirect costs. METHOD: In order to create an empirical basis for this discussion, a review of the results of pharmacoeconomic studies (mostly cost-effectiveness studies) comparing second-generation with conventional antipsychotics was undertaken. RESULTS: Of the 35 studies identified, most report at least cost-neutrality of the new antipsychotics (in many cases clozapine) that is due to reductions in hospitalization costs. These results cannot be generalized, however, because of methodological shortcomings such as small patient samples and study designs with low validity, and especially because of a lack of studies performed outside the U.S. It is shown that results from studies in the U.S. cannot be generalized to other health systems in Europe or in developing countries. Furthermore, only a few findings on newer second-generation antipsychotics other than clozapine are reported, and no study investigated indirect costs, which play a major role because of the early onset and chronicity of schizophrenia. CONCLUSION: Until now, there has been no sufficient evidence for the superior cost-effectiveness of atypical antipsychotics in European countries. Considering the importance of this topic for health politics, more cost-effectiveness studies in European countries are urgently needed. But even if economic superiority of the second-generation antipsychotics cannot be demonstrated in such studies, their use is nevertheless indicated with respect to patient's well-being.

Antipsychotic Agents↗