Maintenance treatment with antipsychotic drugs for schizophrenia.

BACKGROUND: The symptoms and signs of schizophrenia have been linked to high levels of dopamine in specific areas of the brain (limbic system). Antipsychotic drugs block the transmission of dopamine in the brain and reduce the acute symptoms of the disorder. An original version of the current review, published in 2012, examined whether antipsychotic drugs are also effective for relapse prevention. This is the updated version of the aforesaid review. OBJECTIVES: To review the effects of maintaining antipsychotic drugs for people with schizophrenia compared to withdrawing these agents. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials including the registries of clinical trials (12 November 2008, 10 October 2017, 3 July 2018, 11 September 2019). SELECTION CRITERIA: We included all randomised trials comparing maintenance treatment with antipsychotic drugs and placebo for people with schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CIs) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD) or standardised mean differences (SMD), again based on a random-effects model. MAIN RESULTS: The review currently includes 75 randomised controlled trials (RCTs) involving 9145 participants comparing antipsychotic medication with placebo. The trials were published from 1959 to 2017 and their size ranged between 14 and 420 participants. In many studies the methods of randomisation, allocation and blinding were poorly reported. However, restricting the analysis to studies at low risk of bias gave similar results. Although this and other potential sources of bias limited the overall quality, the efficacy of antipsychotic drugs for maintenance treatment in schizophrenia was clear. Antipsychotic drugs were more effective than placebo in preventing relapse at seven to 12 months (primary outcome; drug 24% versus placebo 61%, 30 RCTs, n = 4249, RR 0.38, 95% CI 0.32 to 0.45, number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 3; high-certainty evidence). Hospitalisation was also reduced, however, the baseline risk was lower (drug 7% versus placebo 18%, 21 RCTs, n = 3558, RR 0.43, 95% CI 0.32 to 0.57, NNTB 8, 95% CI 6 to 14; high-certainty evidence). More participants in the placebo group than in the antipsychotic drug group left the studies early due to any reason (at seven to 12 months: drug 36% versus placebo 62%, 24 RCTs, n = 3951, RR 0.56, 95% CI 0.48 to 0.65, NNTB 4, 95% CI 3 to 5; high-certainty evidence) and due to inefficacy of treatment (at seven to 12 months: drug 18% versus placebo 46%, 24 RCTs, n = 3951, RR 0.37, 95% CI 0.31 to 0.44, NNTB 3, 95% CI 3 to 4). Quality of life might be better in drug-treated participants (7 RCTs, n = 1573 SMD -0.32, 95% CI to -0.57 to -0.07; low-certainty evidence); probably the same for social functioning (15 RCTs, n = 3588, SMD -0.43, 95% CI -0.53 to -0.34; moderate-certainty evidence). Underpowered data revealed no evidence of a difference between groups for the outcome 'Death due to suicide' (drug 0.04% versus placebo 0.1%, 19 RCTs, n = 4634, RR 0.60, 95% CI 0.12 to 2.97,low-certainty evidence) and for the number of participants in employment (at 9 to 15 months, drug 39% versus placebo 34%, 3 RCTs, n = 593, RR 1.08, 95% CI 0.82 to 1.41, low certainty evidence). Antipsychotic drugs (as a group and irrespective of duration) were associated with more participants experiencing movement disorders (e.g. at least one movement disorder: drug 14% versus placebo 8%, 29 RCTs, n = 5276, RR 1.52, 95% CI 1.25 to 1.85, number needed to treat for an additional harmful outcome (NNTH) 20, 95% CI 14 to 50), sedation (drug 8% versus placebo 5%, 18 RCTs, n = 4078, RR 1.52, 95% CI 1.24 to 1.86, NNTH 50, 95% CI not significant), and weight gain (drug 9% versus placebo 6%, 19 RCTs, n = 4767, RR 1.69, 95% CI 1.21 to 2.35, NNTH 25, 95% CI 20 to 50). AUTHORS' CONCLUSIONS: For people with schizophrenia, the evidence suggests that maintenance on antipsychotic drugs prevents relapse to a much greater extent than placebo for approximately up to two years of follow-up. This effect must be weighed against the adverse effects of antipsychotic drugs. Future studies should better clarify the long-term morbidity and mortality associated with these drugs.

Training patients with schizophrenia to share decisions with their psychiatrists: a randomized-controlled trial.

PURPOSE: Many patients with schizophrenia have a desire for shared decision-making (SDM). However, in clinical practice SDM often does not take place. One cause might be that many patients behave passively in the medical encounter, therefore not facilitating SDM. It was the aim of the study to evaluate the effects of a patient directed SDM-training on patients' communicative behavior in the consultation, their attitudes towards decision-making and their long-term adherence. METHODS: Randomized-controlled trial comparing a five-session SDM-training for inpatients with schizophrenia with five sessions of non-specific group training. The SDM-training sessions included motivational (e.g. prospects of participation, patient rights) and behavioral aspects (e.g. role plays) and addressed important aspects of the patient-doctor interaction such as question asking or giving feedback. RESULTS: N = 264 patients were recruited in four psychiatric hospitals in Germany. The SDM-training yielded no group differences regarding the main outcome measure (treatment adherence) at 6 and 12 months after discharge. However, there were short-term effects on patients' participation preferences, their wish to take over more responsibility for medical decisions and (according to their psychiatrists' estimate) their behavior in psychiatric consultations. CONCLUSIONS: While there was no effect regarding treatment adherence, the shared decision-making training for inpatients with schizophrenia has been shown to increase patients' active behavior in psychiatric consultations during their inpatient treatment. When implemented it should be combined with complementary SDM interventions (decision support tools and communication training for professionals) to yield maximum effects.

A "Mental-Health-at-the-Workplace" Educational Workshop Reduces Managers' Stigma Toward Depression.

Stigma and discrimination are important factors hindering people with mental health conditions to stay employed or successfully make their careers. We surveyed 580 German managers before and after visiting a "mental-health-at-the-workplace" educational workshop using the Depression Stigma Scale. The workshop significantly reduced stigma toward depression. Managers at baseline already exhibited lower stigma toward depression compared with the general population. In addition, female gender and higher education predicted lower stigma, which is in line with findings from other studies. We conclude that an educational workshop giving practical guidance regarding "mental-health-at-the-workplace" reduces managers' stigma toward depression and improves knowledge regarding depression, its course, and its treatment.

Using films as a psychoeducation tool for patients with schizophrenia: a pilot study using a quasi-experimental pre-post design.

BACKGROUND: Relapses and, subsequently, readmissions are common in patients with schizophrenia. Psychoeducation has been shown to reduce the number and duration of readmissions. Yet, only little more than 20% of psychiatric patients in German speaking countries receive psychoeducation. Among other reasons, costs may be considered too high by hospitals. The objective of the present study was to test the feasibility of a new cost-efficient approach in the psychoeducation of patients with schizophrenia. In this study, films were used to impart knowledge about the illness to inpatients. METHODS: A total of 113 participants were initially included in the study, eleven of which were not included in the final analyses. Six films about the symptoms, diagnosis, causes, warning signs, treatment of schizophrenia and about the influence of family members and friends were shown in a group setting in the presence of nursing staff. All films combined facts, expert opinions, and personal experiences of peers. As the main outcome criterion of this feasibility pilot study, we measured the effects on knowledge. Secondary outcome measures included compliance, insight into illness, side effects, and quality of life. Data were collected directly after the intervention and about half a year afterwards. The number and the duration of readmissions to the hospital were recorded and compared to the number and duration of prior admissions. Patients were also asked to state their subjective opinion about the films. Main data analyses were done using paired t-tests and Wilcoxon signed-rank tests. Secondary analyses also involved ANOVAs and ANCOVAs. RESULTS: One hundred and two inpatients were included in the data analyses. Showing the films in the tested setting was shown to be feasible. Knowledge about schizophrenia (p < .001), compliance (ps < .01), insight into illness (p < .01), and quality of life (p < .001) all increased significantly after patients had watched the films and remained stable for at least half a year. A vast majority (84.9%) of the patients found the films to be interesting and informative. CONCLUSIONS: Using films to educate inpatients about schizophrenia is a feasible method that is cost- and time-efficient and well received by the patients.

Lithium for schizophrenia.

BACKGROUND: Many people with schizophrenia do not achieve a satisfactory treatment response with ordinary anti-psychotic drug treatment. In these cases, various add-on medications are used, among them lithium. OBJECTIVES: To assess whether:1. Lithium alone is an effective treatment for schizophrenia, schizophrenia-like psychoses and schizoaffective psychoses; and2. Lithium augmentation of antipsychotic medication is an effective treatment for the same illnesses. SEARCH METHODS: In July 2012, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. This search was updated on January 20, 2015. For the first version of the review, we also contacted pharmaceutical companies and authors of relevant studies to identify further trials and obtain original participant data. SELECTION CRITERIA: Randomised controlled trials (RCTs) of lithium compared with antipsychotics or placebo (or no intervention), whether as sole treatment or as an adjunct to antipsychotic medication, in the treatment of schizophrenia or schizophrenia-like psychoses or both. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data, we calculated random-effects meta-analyses, risk ratios (RRs), and 95% confidence intervals (CI) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD) and 95% confidence intervals. We used Grading of Recommendations Assessment, Development and Evaluation (GRADE) to create 'Summary of findings' tables and assessed risk of bias for included studies. MAIN RESULTS: The update search in 2012 detected two further studies that met our inclusion criteria. We did not find any further studies that met our inclusion criteria in the 2015 search. This review now includes 22 studies, with a total of 763 participants (median mean age: 35 years, range: 26 to 72 years). Most studies were small, of short duration, and incompletely reported. As we detected a high risk of bias in many studies, the overall methodological quality of the included sample was rather low.Three small 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 (eight RCTs; n = 270, RR 1.77, 95% CI 1.01 to 3.11, low quality evidence).Thirteen 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 (10 RCTs; n = 396, RR 1.81, 95% CI 1.10 to 2.97, low quality evidence). However, this effect became non-significant when we excluded participants with schizoaffective disorders in a sensitivity analysis (seven RCTs; n = 272, RR 1.64, 95% CI 0.95 to 2.81), when we excluded non-double-blind studies (seven RCTs; n = 224, RR 1.82, 95% CI 0.84 to 3.96), or when we excluded studies with high attrition (nine RCTs; n = 355, RR 1.67, CI 0.93 to 3.00). The overall acceptability of treatment (measured by the number of participants leaving the studies early) was not significantly different between groups (11 RCTs; n = 320, RR 1.89, CI 0.93 to 3.84, very low quality evidence). Few studies reported on side effects. There were no significant differences, but the database is too limited to make any judgement in this regard. For example, there were no data on thyroid dysfunction and kidney problems - two major and well-known side effects of lithium. AUTHORS' CONCLUSIONS: The evidence base for the use of lithium in schizophrenia is limited to 22 studies of overall low methodological quality. There is no randomised trial-based evidence that lithium on its own is an effective treatment for people with schizophrenia. There is some GRADE low quality evidence that augmentation of antipsychotics with lithium is effective, but the effects are not significant when more prone-to-bias open RCTs are excluded. Nevertheless, further large and well-designed trials are justified. 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, and (2) people with schizoaffective disorders for whom lithium is widely used in clinical practice, although there is no evidence to support this use.

Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis.

BACKGROUND: The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on the randomised evidence. We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs. METHODS: We did a Bayesian-framework, multiple-treatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation. FINDINGS: We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0·88, 0·73-1·03; amisulpride 0·66, 0·53-0·78; olanzapine 0·59, 0·53-0·65; risperidone 0·56, 0·50-0·63; paliperidone 0·50, 0·39-0·60; zotepine 0·49, 0·31-0·66; haloperidol 0·45, 0·39-0·51; quetiapine 0·44, 0·35-0·52; aripiprazole 0·43, 0·34-0·52; sertindole 0·39, 0·26-0·52; ziprasidone 0·39, 0·30-0·49; chlorpromazine 0·38, 0·23-0·54; asenapine 0·38, 0·25-0·51; lurasidone 0·33, 0·21-0·45; and iloperidone 0·33, 0·22-0·43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug (haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76 (haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from -0·09 for the best drug (haloperidol) to -0·74 for the worst drug (olanzapine), for prolactin increase 0·22 (aripiprazole) to -1·30 (paliperidone), and for QTc prolongation 0·10 (lurasidone) to -0·90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in meta-regressions and sensitivity analyses. INTERPRETATION: Antipsychotics differed substantially in side-effects, and small but robust differences were seen in efficacy. Our findings challenge the straightforward classification of antipsychotics into first-generation and second-generation groupings. Rather, hierarchies in the different domains should help clinicians to adapt the choice of antipsychotic drug to the needs of individual patients. These findings should be considered by mental health policy makers and in the revision of clinical practice guidelines. FUNDING: None.

Haloperidol versus low-potency first-generation antipsychotic drugs for schizophrenia.

BACKGROUND: Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between antipsychotic compounds, however, low-potency antipsychotic drugs are often clinically perceived as less efficacious than high-potency compounds, and they also seem to differ in their side-effects. OBJECTIVES: To review the effects in clinical response of haloperidol and low-potency antipsychotics for people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (July 2010). SELECTION CRITERIA: We included all randomised trials comparing haloperidol with first-generation low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data, we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD), again based on a random-effects model. MAIN RESULTS: The review currently includes 17 randomised trials and 877 participants. The size of the included studies was between 16 and 109 participants. All studies were short-term with a study length between two and 12 weeks. Overall, sequence generation, allocation procedures and blinding were poorly reported. We found no clear evidence that haloperidol was superior to low-potency antipsychotic drugs in terms of clinical response (haloperidol 40%, low-potency drug 36%, 14 RCTs, n = 574, RR 1.11, CI 0.86 to 1.44 lowquality evidence). There was also no clear evidence of benefit for either group in acceptability of treatment with equivocal difference in the number of participants leaving the studies early due to any reason (haloperidol 13%, low-potency antipsychotics 17%, 11 RCTs, n = 408, RR 0.82, CI 0.38 to 1.77, low quality evidence). Similar equivocal results were found between groups for experiencing at least one adverse effect (haloperidol 70%, low-potency antipsychotics 35%, 5 RCTs n = 158, RR 1.97, CI 0.69 to 5.66, very low quality evidence ). More participants from the low-potency drug group experienced sedation (haloperidol 14%, low-potency antipsychotics 41%, 2 RCTs, n = 44, RR 0.30, CI 0.11 to 0.82, moderate quality evidence), orthostasis problems (haloperidol 25%, low-potency antipsychotics 71%, 1 RCT, n = 41, RR 0.35, CI 0.16 to 0.78) and weight gain (haloperidol 5%, low-potency antipsychotics 29%, 3 RCTs, n = 88, RR 0.22, CI 0.06 to 0.81). In contrast, the outcome 'at least one movement disorder' was more frequent in the haloperidol group (haloperidol 72%, low-potency antipsychotics 41%, 5 RCTs, n = 170, RR 1.64, CI 1.22 to 2.21, low quality evidence). No data were available for death or quality of life. The results of the primary outcome were robust in several subgroup and sensitivity analyses. AUTHORS' CONCLUSIONS: The results do not clearly show a superiority in efficacy of haloperidol compared with low-potency antipsychotics. Differences in adverse events were found for movement disorders, which were more frequent in the haloperidol group, and orthostatic problems, sedation and weight gain, which were more frequent in the low-potency antipsychotic group. The quality of studies was low, and the quality of evidence for the main outcomes of interest varied from moderate to very low, so more newer studies would be needed in order to draw a definite conclusion about whether or not haloperidol is superior or inferior to low-potency antipsychotics.

Carbamazepine for schizophrenia.

BACKGROUND: Many people with schizophrenia do not achieve a satisfactory treatment response with just antipsychotic drug treatment and various adjunct medications are used to promote additional response. The antiepileptic carbamazepine is one such drug. OBJECTIVES: To examine whether carbamazepine or oxcarbazepine alone is an effective treatment for schizophrenia and schizoaffective psychoses and whether carbamazepine or oxcarbazepine augmentation of neuroleptic medication is an effective treatment for the same illnesses. SEARCH METHODS: For the original version we searched The Cochrane Schizophrenia Group's Register of Trials (December 2001), The Cochrane Library (Issue 3, 2001), MEDLINE (1966-2001), EMBASE (1980-2001), Biological Abstracts (1980-2001), PsycLIT (1886-2001) and PSYNDEX (1974-2001). For the most recent update we searched the Cochrane Schizophrenia Group's Register of Trials in July 2012. We also inspected references of all identified studies for further trials and contacted relevant pharmaceutical companies and authors for additional data. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing carbamazepine or compounds of the carbamazepine family with placebo or no intervention, whether as sole treatment or as an adjunct to antipsychotic medication for the treatment of schizophrenia and/or schizoaffective psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For homogenous dichotomous data we calculated fixed-effect, risk ratio (RR), with 95% confidence intervals (CIs) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). We assessed the risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS: The updated search did not reveal any further studies that met our inclusion criteria. The number of included studies therefore remains at 10 with the number of participants randomised still 283.One study comparing carbamazepine with placebo as the sole treatment for schizophrenia was abandoned early due to high relapse rate with 26 out of 31 participants relapsing by three months. No effect of carbamazepine was evident with no difference in relapse between the two groups (1 RCT n = 31, RR 1.07 CI 0.78 to 1.45). Another study compared carbamazepine with antipsychotics as the sole treatment for schizophrenia. No differences in terms of mental state were found when comparing 50% reduction in Brief Psychiatric Rating Scale (BPRS) scores (1 RCT n = 38, RR 1.23 CI 0.78 to 1.92). A favourable effect for carbamazepine was found when more people who received the antipsychotic (perphenazine) had parkinsonism (1 RCT n = 38, RR 0.03 CI 0.00 to 0.043). Eight studies compared adjunctive carbamazepine versus adjunctive placebo, we were able use GRADE for quality of evidence for these results. Adding carbamazepine to antipsychotic treatment was as acceptable as adding placebo with no difference between the numbers leaving the study early from each group (8 RCTs n = 182, RR 0.47 CI 0.16 to 1.35, very low quality evidence). Carbamazepine augmentation was superior compared with antipsychotics alone in terms of overall global improvement, but participant numbers were low (2 RCTs n = 38, RR 0.57 CI 0.37 to 0.88). There were no differences for the mental state outcome of 50% reduction in BPRS scores (6 RCTs n = 147, RR 0.86 CI 0.67 to 1.12, low quality evidence). Less people in the carbamazepine augmentation group had movement disorders than those taking haloperidol alone (1 RCT n = 20, RR 0.38 CI 0.14 to 1.02). No data were available for the effects of carbamazepine on subgroups of people with schizophrenia and aggressive behaviour, negative symptoms or EEG abnormalities or with schizoaffective disorder. AUTHORS' CONCLUSIONS: Based on currently available randomised trial-derived evidence, carbamazepine cannot be recommended for routine clinical use for treatment or augmentation of antipsychotic treatment of schizophrenia. At present large, simple well-designed and reported trials are justified - especially if focusing on people with violent episodes and people with schizoaffective disorders or those with both schizophrenia and EEG abnormalities.

Antipsychotic drugs versus placebo for relapse prevention in schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Relapse prevention with antipsychotic drugs compared with placebo in patients with schizophrenia has not been sufficiently addressed by previous systematic reviews. We aimed to assess the association between such drugs and various outcomes in patients with schizophrenia to resolve controversial issues. METHODS: We searched the Cochrane Schizophrenia Group's specialised register for reports published before Nov 11, 2008; and PubMed, Embase, and ClinicalTrials.gov for those before June 8, 2011. We also contacted pharmaceutical companies and searched the reference lists of included studies and previous reviews. Randomised trials of patients with schizophrenia continued on or withdrawn from any antipsychotic drug regimen after stabilisation were eligible. Our primary outcome was relapse between 7 and 12 months. We also examined safety and various functional outcomes. We used the random effects model and verified results for the primary outcome with a fixed effects model. Heterogeneity was investigated with subgroup and meta-regression analyses. FINDINGS: We identified 116 suitable reports from 65 trials, with data for 6493 patients. Antipsychotic drugs significantly reduced relapse rates at 1 year (drugs 27%vs placebo 64%; risk ratio [RR] 0·40, 95% CI 0·33-0·49; number needed to treat to benefit [NNTB] 3, 95% CI 2-3). Fewer patients given antipsychotic drugs than placebo were readmitted (10%vs 26%; RR 0·38, 95% CI 0·27-0·55; NNTB 5, 4-9), but less than a third of relapsed patients had to be admitted. Limited evidence suggested better quality of life (standardised mean difference -0·62, 95% CI -1·15 to -0·09) and fewer aggressive acts (2%vs 12%; RR 0·27, 95% CI 0·15-0·52; NNTB 11, 6-100) with antipsychotic drugs than with placebo. Employment data were scarce and too few deaths were reported to allow significant differences to be identified. More patients given antipsychotic drugs than placebo gained weight (10%vs 6%; RR 2·07, 95% CI 2·31-3·25), had movement disorders (16%vs 9%; 1·55, 1·25-1·93), and experienced sedation (13%vs 9%; 1·50, 1·22-1·84). Substantial heterogeneity in size of effect was recorded. In subgroup analyses, number of episodes, whether patients were in remission, abrupt or gradual withdrawal of treatment, length of stability before trial entry, first-generation or second-generation drugs, and allocation concealment method did not significantly affect relapse risk. Depot preparations reduced relapse (RR 0·31, 95% CI 0·21-0·41) more than did oral drugs (0·46, 0·37-0·57; p=0·03); depot haloperidol (RR 0·14, 95% CI 0·04-0·55) and fluphenazine (0·23, 0·14-0·39) had the greatest effects. The effects of antipsychotic drugs were greater in two unblinded trials (0·26, 0·17-0·39) than in most blinded studies (0·42, 0·35-0·51; p= 0·03). In a meta-regression, the difference between drug and placebo decreased with study length. INTERPRETATION: Maintenance treatment with antipsychotic drugs benefits patients with schizophrenia. The advantages of these drugs must be weighed against their side-effects. Future studies should focus on outcomes of social participation and clarify the long-term morbidity and mortality of these drugs. FUNDING: German Ministry of Education and Research.

Frequency and relevance of psychoeducation in psychiatric diagnoses: results of two surveys five years apart in German-speaking European countries.

BACKGROUND: Psychoeducation has been shown to reduce relapse rates in several psychiatric disorders. Studies investigating for which psychiatric diagnoses psychoeducation is offered and assessing its perceived relevance compared to other interventions are lacking. METHODS: A two-part questionnaire addressing these questions was sent to the heads of all psychiatric hospitals in Germany, Austria and Switzerland. Results were compared with those from a similar survey 5 years earlier. RESULTS: 289 of 500 (58%) institutions responded. Significantly (p = 0,02) more institutions (93%) offer any type of psychoeducation as compared to 5 years before (86%). Psychoeducation is mainly offered for schizophrenia (86%) and depression (67%) and less frequently for anxiety disorders (18%) and substance abuse (17%). For the following specific diagnoses it is offered by less than 10% of the institutions: Personality disorder, bipolar disorder, posttraumatic stress disorder, dementia, obsessive compulsive disorder, sleeping disorders, eating disorders, schizophrenia plus substance abuse, pain, attention deficit hyperactivity disorder and early psychosis. 25% offer diagnosis-unspecific psychoeducation. 'Pharmacotherapy' (99%), 'basic occupational therapy' (95%) and 'psychoeducation for patients' (93%) were the therapies being most often, 'light therapy' (24%) and 'sleep deprivation' (16%) the therapies being least often perceived as relevant by the respondents when asked about the value of different interventions offered in their hospitals. Art therapy (61%) and psychoanalytically oriented psychotherapy (59%), two therapies with a smaller evidence base than light therapy or sleep deprivation, were perceived as relevant by more than the half of the respondents. CONCLUSION: Psychoeducation for patients is considered relevant and offered frequently in German-speaking countries, however, mostly only for schizophrenia and depression. The ranking of the perceived relevance of different treatment options suggests that the evidence base is not considered crucial for determining their relevance.

Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses.

BACKGROUND: The efficacy of psychopharmacological treatments has been called into question. Psychiatrists are unfamiliar with the effectiveness of common medical drugs. AIMS: To put the efficacy of psychiatric drugs into the perspective of that of major medical drugs. METHOD: We searched Medline and the Cochrane Library for systematic reviews on the efficacy of drugs compared with placebo for common medical and psychiatric disorders, and systematically presented the effect sizes for primary efficacy outcomes. RESULTS: We included 94 meta-analyses (48 drugs in 20 medical diseases, 16 drugs in 8 psychiatric disorders). There were some general medical drugs with clearly higher effect sizes than the psychotropic agents, but the psychiatric drugs were not generally less efficacious than other drugs. CONCLUSIONS: Any comparison of different outcomes in different diseases can only serve the purpose of a qualitative perspective. The increment of improvement by drug over placebo must be viewed in the context of the disease's seriousness, suffering induced, natural course, duration, outcomes, adverse events and societal values.

Maintenance treatment with antipsychotic drugs for schizophrenia.

BACKGROUND: The symptoms and signs of schizophrenia have been firmly linked to high levels of dopamine in specific areas of the brain (limbic system). Antipsychotic drugs block the transmission of dopamine in the brain and reduce the acute symptoms of the disorder. This review examined whether antipsychotic drugs are also effective for relapse prevention. OBJECTIVES: To review the effects of maintaining antipsychotic drugs for people with schizophrenia compared to withdrawing these agents. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Specialised Register (November 2008), with additional searches of MEDLINE, EMBASE and clinicaltrials.gov (June 2011). SELECTION CRITERIA: We included all randomised trials comparing maintenance treatment with antipsychotic drugs and placebo for people with schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD) or standardised mean differences (SMD) again based on a random-effects model. MAIN RESULTS: The review currently includes 65 randomised controlled trials (RCT(s)) and 6493 participants comparing antipsychotic medication with placebo. The trials were published from 1959 to 2011 and their size ranged between 14 and 420 participants. In many studies the methods of randomisation, allocation and blinding were poorly reported. Although this and other potential sources of bias limited the overall quality, the efficacy of antipsychotic drugs for maintenance treatment in schizophrenia was clear. Antipsychotic drugs were significantly more effective than placebo in preventing relapse at seven to 12 months (primary outcome; drug 27%, placebo 64%, 24 RCT(s), n=2669, RR 0.40 CI 0.33 to 0.49, number needed to treat for an additional beneficial outcome (NNTB 3 CI 2 to 3). Hospitalisation was also reduced, however, the baseline risk was lower (drug 10%, placebo 26%, 16 RCT(s), n=2090, RR 0.38 CI 0.27 to 0.55, NNT 5 CI 4 to 9). More participants in the placebo group than in the antipsychotic drug group left the studies early due to any reason (at 7-12 months: drug 38%, placebo 66%, 18 RCT(s), n=2420, RR 0.55 CI 0.46 to 0.66, NNTB 4 CI 3 to 5) and due to inefficacy of treatment (at 7-12 months: drug 20%, placebo 50%, 18 RCT(s), n=2420, RR 0.36 CI 0.28 to 0.45, NNTB 3 CI 2 to 4). Quality of life was better in drug-treated participants (3 RCT(s), n=527, SMD -0.62 CI -1.15 to -0.09). Conversely, antipsychotic drugs as a group and irrespective of duration, were associated with more participants experiencing movement disorders (e.g. at least one movement disorder: drug 16%, placebo 9%, 22 RCT(s), n=3411, RR 1.55 CI 1.25 to 1.93, NNTH 25 CI 13 to 100), sedation (drug 13%, placebo 9%, 10 RCT(s), n=146, RR 1.50 CI 1.22 to 1.84, number needed to treat for an additional harmful outcome (NNTH) not significant) and weight gain (drug 10%, placebo 6%, 10 RCT(s), n=321, RR 2.07 CI 1.31 to 3.25, NNTH 20 CI 14 to 33). The results of the primary outcome were robust in a number of subgroup, meta-regression and sensitivity analyses, the main exception being that the drug-placebo difference in longer trials was smaller than in shorter trials. AUTHORS' CONCLUSIONS: The results clearly demonstrate the superiority of antipsychotic drugs compared to placebo in preventing relapse. This effect must be weighed against the side effects of antipsychotic drugs. Future studies should focus on outcomes of social participation and clarify the long-term morbidity and mortality associated with these drugs.

Do physicians' recommendations pull patients away from their preferred treatment options?

CONTEXT AND OBJECTIVE: Shared decision making is especially advocated for preference-sensitive decisions. We investigated whether physicians' recommendations pull patients away from their preferred treatment option when making a preference-sensitive decision. DESIGN, PARTICIPANTS AND METHODS: Inpatients (N = 102 with schizophrenia, N = 101 with multiple sclerosis) were presented with a hypothetical scenario (the choice between two drugs). They were first asked about their preferences concerning the two drugs and then they received a (fictitious) clinician's recommendation that was contrary to their preferences. Subsequently they made a final choice between the two drugs. MAIN OUTCOME MEASURES: The main outcome measure was whether the patient followed the physician's advice in the hypothetical scenario. Thereby patient's (pre-recommendation) preferences served as a baseline. RESULTS: In the decision scenario, about 48% of the patients with schizophrenia and 26% of the patients with multiple sclerosis followed the advice of their physician and thus chose the treatment option that went against their initial preferences. Patients who followed their physician's advice were less satisfied with their decision than patients not following their physician's advice (schizophrenia: t = 2.61, P = 0.01; multiple sclerosis: t = 2.67, P = 0.009). DISCUSSION AND CONCLUSIONS: When sharing decisions with patients, physicians should be aware that their advice might influence patients' decisions away from their preferred treatment option. They should encourage their patients to identify their own preferences and help to find the treatment option most consistent with them.

How should patients behave to facilitate shared decision making--the doctors' view.

OBJECTIVE: To study how physicians feel about patients' efforts to be engaged in shared decision making (SDM). STUDY SETTING AND DESIGN: Survey of physicians from distinctly different medical disciplines (238 psychiatrists and 169 vascular surgeons). Participants were requested to judge which patient behaviours they find helpful and which behaviours detrimental for SDM. RESULTS: Psychiatrists and surgeons had rather positive attitudes about active patient behaviours. However, there were quite a few patient behaviours (e.g. searching the Internet, being assertive towards the doctor) which provoked ambivalent or negative attitudes. DISCUSSION AND CONCLUSIONS: Physicians are generally quite open towards active patient behaviour in the consultation. They, however, do consider it as less helpful and become more annoyed if patients insist on their preferences and doubt their doctors' recommendations. Physicians must realize that SDM implies giving up decisional power and try to be more flexible in their interactions with patients.

How do patients from eastern and western Germany compare with regard to their preferences for shared decision making?

BACKGROUND: Increasing emphasis is being placed on involving patients in decisions concerning their health. This shift towards more patient engagement by health professionals and towards more desire by patients for participation may be partly based on socio-political factors. METHODS: To compare the preferences for shared decision making of patients from eastern and western Germany we analysed five patient samples (n = 2318) (general practice patients and schizophrenia patients from eastern and western Germany). Patients' role preferences for shared decisions were measured using the decision-making subscale of the Autonomy Preference Index. RESULTS: Patients resident in eastern Germany expressed lower preferences for shared decision making than patients in western Germany. This was true after controlling for socio-demographic variables and for patient group. CONCLUSION: The cultural imprint (e.g. western vs. former communist society) seems to have a significant influence on patients' expectations and behaviour in the medical encounter. Health services providers need to be aware that health attitudes within the same health system might vary for historical and cultural reasons. The engagement of patients in medical decisions might not be susceptible to a 'one size fits all' approach; doctors should instead aim to accommodate the individual patient's desire for autonomy.

Maintenance Treatment With Antipsychotic Drugs in Schizophrenia: A Cochrane Systematic Review and Meta-analysis.

Antipsychotic drugs are the mainstay of treatment of schizophrenia, and are known to reduce acute symptoms of the disorder. An original version of the current review, published in 2012, examined whether antipsychotics are effective for relapse prevention, compared to withdrawing these agents for people with schizophrenia or schizophrenia-like psychoses, based on evidence from randomized trials. The current report of the update of the review is focused on some newly investigated outcomes: rates of remission and recovery, change in social functioning and in quality of life. The updated review included 75 randomized controlled trials (RCTs) published from 1959 to 2017, involving 9145 participants. Although some potential sources of bias limited the overall quality, the efficacy of antipsychotic drugs for maintenance treatment in schizophrenia was clear and robust to a series of sensitivity analyses. Antipsychotic drugs were more effective than placebo in preventing relapse at 1 year (drug 24% versus placebo 61%, 30 RCTs, n = 4249, RR = 0.38, 95% CI = 0.32 to 0.45) and in reducing hospitalization (drug 7% versus placebo 18%, 21 RCTs, n = 3558, RR = 0.43, 95% CI = 0.32 to 0.57). Quality of life appeared to be better in drug-treated participants (7 RCTs, n = 1573, SMD = -0.32, 95% CI = -0.57 to -0.07); the same for social functioning (15 RCTs, n = 3588, SMD = -0.43, 95% CI = -0.53 to -0.34). Although based on data from fewer studies, maintenance treatment apparently increased the possibility to achieve remission of symptoms (drug 53%, placebo 31%; 7 RCTs, 867 participants; RR = 1.73, 95% CI = 1.20 to 2.48) and to sustain it over 6 months (drug 36%, placebo 26%; 8 RCTs, 1807 participants; RR = 1.67, 95% CI = 1.28 to 2.19). There were no data on recovery. Antipsychotic drugs as a group were associated with more participants experiencing side effects such as movement disorders (e.g., at least one movement disorder: drug 14% versus placebo 8%, 29 RCTs, n = 5276, RR 1.52, 95% CI = 1.25 to 1.85) and weight gain (drug 9% versus placebo 6%, 19 RCTs, n = 4767, RR = 1.69, 95% CI = 1.21 to 2.35, NNTH = 25, 95% CI = 20 to 50). For people with schizophrenia, the evidence suggests that maintenance on antipsychotic drugs does not only prevent relapses and rehospitalizations, but that patients also benefit in terms of quality of life, functioning and sustained remission. These positive effects must be weighed against the backdrop of the adverse effects of antipsychotics.

Evidence-based pharmacotherapy of schizophrenia.

We describe the pharmacological treatment of schizophrenia and have arranged the manuscript as a simple algorithm which starts from the choice of an antipsychotic drug for an acutely ill patient and concludes with the most important questions about maintenance treatment. In acutely ill patients the choice of drug is mainly based on pragmatic criteria. Among many strategies used for agitated patients, haloperidol plus promethazine is the best examined one. In case of persistent depression or negative symptoms treatment includes antidepressants, and some second-generation antipsychotic drugs (SGAs) have been found somewhat superior to first-generation antipsychotic drugs (FGAs) in these domains. If an antipsychotic is suspected to be ineffective, several factors need to be checked before action is taken. Few trials have addressed strategies such as switching the drug or increasing the dose in case of non-response. Clozapine remains the gold-standard for treatment-refractory patients, while none of the numerous augmentation strategies that have been examined by randomized controlled trials can be generally recommended. Maintenance treatment with antipsychotic drugs effectively reduces relapse rates. Small, not definitive, studies have shown that withdrawing antipsychotics from patients who have been stable for up to 6 yr leads to more relapses than continuing medication. In effect, continuous treatment is more effective than intermittent strategies. The identification of optimum doses for relapse prevention with FGAs has proven difficult, and there is little randomized data on SGAs. Although the randomized evidence on a superiority of depot compared to oral treatment is not ideal, this approach suggests obvious advantages in assuring compliance.

Risperidone versus other atypical antipsychotics for schizophrenia.

BACKGROUND: In many countries of the industrialised world second-generation ("atypical") antipsychotics (SGAs) have become the first line drug treatment for people with schizophrenia. The question as to whether and if so how much the effects of the various SGAs differ is a matter of debate. In this review we examined how the efficacy and tolerability of risperidone differs from that of other SGAs. OBJECTIVES: To evaluate the effects of risperidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. SEARCH STRATEGY: 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO.2. Reference searching We inspected the references of all identified studies for more trials.3. Personal contact We contacted the first author of each included study for missing information.4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. SELECTION CRITERIA: We included all randomised, blinded trials comparing oral risperidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD), again based on a random-effects model. MAIN RESULTS: The review currently includes 45 blinded RCTs with 7760 participants. The number of RCTs available for each comparison varied: four studies compared risperidone with amisulpride, two with aripiprazole, 11 with clozapine, 23 with olanzapine, eleven with quetiapine, two with sertindole, three with ziprasidone and none with zotepine. Attrition from these studies was high (46.9%), leaving the interpretation of results problematic. Furthermore, 60% were industry sponsored, which can be a source of bias.There were few significant differences in overall acceptability of treatment as measured by leaving the studies early. Risperidone was slightly less acceptable than olanzapine, and slightly more acceptable than ziprasidone in this regard.Risperidone improved the general mental state (PANSS total score) slightly less than olanzapine (15 RCTs, n = 2390, MD 1.94 CI 0.58 to 3.31), but slightly more than quetiapine (9 RCTs, n = 1953, MD -3.09 CI -5.16 to -1.01) and ziprasidone (3 RCTs, n = 1016, MD -3.91 CI -7.55 to -0.27). The comparisons with the other SGA drugs were equivocal. Risperidone was also less efficacious than olanzapine and clozapine in terms of leaving the studies early due to inefficacy, but more efficacious than ziprasidone in the same outcome.Risperidone produced somewhat more extrapyramidal side effects than a number of other SGAs (use of antiparkinson medication versus clozapine 6 RCTs, n = 304, RR 2.57 CI 1.47 to 4.48, NNH 6 CI 33 to 3; versus olanzapine 13 RCTs, n = 2599, RR 1.28 CI 1.06 to 1.55, NNH 17 CI 9 to 100; versus quetiapine 6 RCTs, n = 1715, RR 1.98 CI 1.16 to 3.39, NNH 20 CI 10 to 100; versus ziprasidone 2 RCTs, n = 822, RR 1.42 CI 1.03 to 1.96, NNH not estimable; parkinsonism versus sertindole 1 RCT, n = 321, RR 4.11 CI 1.44 to 11.73, NNH 14 CI 100 to 8). Risperidone also increased prolactin levels clearly more than all comparators, except for amisulpride and sertindole for which no data were available.Other adverse events were less consistently reported, but risperidone may well produce more weight gain and/or associated metabolic problems than amisulpride (weight gain: 3 RCTs, n = 585, MD 0.99 CI 0.37 to 1.61), aripiprazole (cholesterol increase: 1 RCT, n = 83, MD 22.30 CI 4.91 to 39.69) and ziprasidone (cholesterol increase 2 RCTs, n = 767, MD 8.58 CI 1.11 to 16.04) but less than clozapine (weight gain 3 RCTs n = 373, MD -3.30 CI -5.65 to -0.95), olanzapine (weight gain 13 RCTs, n = 2116, MD -2.61 CI -3.74 to -1.48), quetiapine (cholesterol increase: 5 RCTs, n = 1433, MD -8.49 CI -12. 23 to -4.75) and sertindole (weight gain: 2 RCTs, n = 328, MD -0.99 CI -1.86 to -0.12). It may be less sedating than clozapine and quetiapine, lengthen the QTc interval less than sertindole (QTc change: 2 RCTs, n = 495, MD -18.60 CI -22.37 to 14.83), produce fewer seizures than clozapine (2 RCTs, n = 354, RR 0.22 CI 0.07 to 0.70, NNT 14 CI 8 to 33) and less sexual dysfunction in men than sertindole (2 RCTs, n = 437, RR 0.34 CI 0.16 to 0.76, NNT 13 CI 8 to 33). AUTHORS' CONCLUSIONS: Risperidone seems to produce somewhat more extrapyramidal side effects and clearly more prolactin increase than most other SGAs. It may also differ from other compounds in efficacy and in the occurrence of other adverse effects such as weight gain, metabolic problems, cardiac effects, sedation and seizures. Nevertheless, the large proportion of participants leaving studies early and incomplete reporting of outcomes makes it difficult to draw firm conclusions. Further large trials, especially comparing risperidone with those other new drugs for which only a few RCTs are available, are needed.

'What would you do if you were me, doctor?': randomised trial of psychiatrists' personal v. professional perspectives on treatment recommendations.

BACKGROUND: If patients are unsure whether a specific treatment is really good for them, they often pose the question, 'What would you do if you were me, doctor?' Patients want their psychiatrists to put themselves in their shoes and not to give a 'standard recommendation'. AIMS: To study whether this question really leads psychiatrists to reveal their personal preferences. METHOD: Randomised experimental study with 515 psychiatrists incorporating two decision scenarios (depression scenario: antidepressant v. watchful waiting; schizophrenia scenario: depot v. oral antipsychotic) and three experimental conditions (giving a recommendation to a patient asking, 'What would you do if you were me, doctor?'; giving a regular recommendation to a patient without being asked this question; and imagining being ill and deciding for yourself). Main outcome measures were the treatments chosen or recommended by physicians. RESULTS: Psychiatrists choosing treatment for themselves predominantly selected other treatments (mostly watchful waiting and oral antipsychotics respectively) than what psychiatrists recommended to patients when asked in the 'regular recommendation role' (i.e. antidepressant and depot respectively). Psychiatrists in the 'what-would-you-do role' gave recommendations similar to the 'regular recommendation role' (depression scenario: χ(2) = 0.12, P = 0.73; schizophrenia scenario: χ(2) = 2.60, P = 0.11) but distinctly different from the 'self role'. CONCLUSIONS: The question 'What would you do if you were me, doctor?' does not motivate psychiatrists to leave their professional recommendation role and to take a more personal perspective. Psychiatrists should try to find out why individuals are asking this question and, together with the individual, identify the most appropriate treatment option.

Patient participation in antipsychotic drug choice decisions.

Patient inclusion in antipsychotic drug decisions is recommended by international treatment guidelines. For N=300 in patients with schizophrenia, we analysed patients' preferences for inclusion in decisions and physicians' estimates which patients actually participated in drug choice. Path analysis was used to examine the relationships between patients' preferences/actual participation and clinical variables measured. Forty percent of the patients expressed a wish to participate in clinical decisions. Those patients wishing to participate in medical decisions had less insight into the necessity of treatment. Psychiatrists gave better ratings of the doctor-patient relationship to those patients whom they rated as having participated in their drug choice. These patients had more positive attitudes towards antipsychotic medication. There was no relationship between the desire to participate and actual participation in the drug choice. When working with patients exhibiting poor insight and negative drug attitudes, psychiatrists use authoritative decision-making styles despite the patient's desire to participate.