Shared decision making and long-term outcome in schizophrenia treatment. The effect of fluphenazine upon social and vocational functioning in remitted schizophrenics. The dementia antipsychotic withdrawal trial (DART-AD): long-term follow-up of a randomised placebo-controlled trial. Effectiveness of psychoeducational intervention for rural Chinese families experiencing schizophrenia--a randomised controlled trial. Long-acting oral vs injectable antipsychotic drugs in schizophrenics: a one-year double-blind comparison in multiple episode schizophrenics. Nicotine transdermal patch and atypical antipsychotic medications for smoking cessation in schizophrenia. A randomized, placebo-controlled trial of the discontinuation of long-term antipsychotics in dementia. Effect of antipsychotic withdrawal on behavior and sleep/wake activity in nursing home residents with dementia: a randomized, placebo-controlled, double-blinded study. The Bergen District Nursing Home Study. Comparative effectiveness of fluphenazine decanoate injections every 2 weeks versus every 6 weeks. One-year, low-dose neuroleptic study of in-patients with chronic schizophrenia characterised by persistent negative symptoms. Amisulpride v. haloperidol. Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics.
Compliance with antipsychotic medication is a major issue in schizophrenia treatment, and noncompliance with antipsychotic treatment is closely related to relapse and rehospitalization. An enhanced involvement of patients with schizophrenia in treatment decisions ("shared decision making") is expected to improve long-term compliance and reduce rehospitalizations. The aim of the present analysis was to study whether shared decision making (SDM) in antipsychotic drug choice would influence long-term outcome.
                From February 2003 to January 2004, psychiatric state hospital inpatients with a diagnosis of schizophrenia (ICD-10; N = 107) were recruited for the trial using a cluster-randomized controlled design. An SDM program on antipsychotic drug choice consisting of a decision aid and a planning talk between patient and physician was compared with routine care with respect to long-term compliance and rehospitalizations (6-month and 18-month follow-up).
                On the whole, we found high rates of noncompliance and rehospitalization. There were no differences between intervention and control groups in the univariate analyses. However, when controlling for confounding factors in a multivariate analysis, there was a positive trend (p = .08) that patients in the SDM intervention had fewer rehospitalizations. Additionally, a higher desire of the patient for autonomy and better knowledge at discharge were associated with higher hospitalization rates.
                The intervention studied showed a positive trend but no clear beneficial effect on long-term outcomes. A more thorough implementation of SDM (e.g., iterative administration of decision aid) might yield larger effects. Those patients with higher participation preferences are at higher risk for poor treatment outcomes and therefore require special attention. Strategies to match these patients' needs might improve compliance and long-term outcomes. Thirty-six remitted schizophrenics who participated in an outpatient study of fluphenazine decanoate or oral fluphenazine vs placebo given for a year were examined for the effect of drug treatment upon social and vocational functioning. Only the period prior to any clinical relapse was evaluated. We found no difference between those on drug or placebo, and conclude that antipsychotic drugs, at least in the context of an aftercare clinic offering a rich spectrum of nonpharmacological services, and when combined with antiparkinson medication, do not interfere with social and vocational functioning. Data from 12-week placebo-controlled trials have led to mounting concerns about increased mortality in patients with Alzheimer's disease (AD) who are prescribed antipsychotics; however, there are no mortality data from long-term placebo-controlled trials. We aimed to assess whether continued treatment with antipsychotics in people with AD is associated with an increased risk of mortality.
                Between October, 2001, and December, 2004, patients with AD who resided in care facilities in the UK were enrolled into a randomised, placebo-controlled, parallel, two-group treatment discontinuation trial. Participants were randomly assigned to continue with their antipsychotic treatment (thioridazine, chlorpromazine, haloperidol, trifluoperazine, or risperidone) for 12 months or to switch their medication to an oral placebo. The primary outcome was mortality at 12 months. An additional follow-up telephone assessment was done to establish whether each participant was still alive 24 months after the enrollment of the last participant (range 24-54 months). Causes of death were obtained from death certificates. Analysis was by intention to treat (ITT) and modified intention to treat (mITT). This trial is registered with the Cochrane Central Registry of Controlled Trials/National Research Register, number ISRCTN33368770.
                165 patients were randomised (83 to continue antipsychotic treatment and 82 to placebo), of whom 128 (78%) started treatment (64 continued with their treatment and 64 received placebo). There was a reduction in survival in the patients who continued to receive antipsychotics compared with those who received placebo. Cumulative probability of survival during the 12 months was 70% (95% CI 58-80%) in the continue treatment group versus 77% (64-85%) in the placebo group for the mITT population. Kaplan-Meier estimates of mortality for the whole study period showed a significantly increased risk of mortality for patients who were allocated to continue antipsychotic treatment compared with those allocated to placebo (mITT log rank p=0.03; ITT p=0.02). The hazard ratio for the mITT group was 0.58 (95% CI 0.35 to 0.95) and 0.58 (0.36 to 0.92) for the ITT population. The more pronounced differences between groups during periods of follow up longer than 12 months were evident at specific timepoints (24-month survival 46%vs 71%; 36-month survival 30%vs 59%).
                There is an increased long-term risk of mortality in patients with AD who are prescribed antipsychotic medication; these results further highlight the need to seek less harmful alternatives for the long-term treatment of neuropsychiatric symptoms in these patients.
                UK Alzheimer's Research Trust. The aim of this study was to explore the characteristics and efficacy of psychoeducational family intervention for persons with schizophrenia in rural China.
                A cluster randomised controlled trial of psychoeducational family intervention for families experiencing schizophrenia (three groups, 326 cases) was conducted in Xinjin County, Chengdu. Treatment groups consisted of family intervention and medication, medication alone, and a control.
                The results showed a gain in knowledge, a change in the relatives' caring attitudes towards the patients, and an increase in treatment compliance in the psychoeducational family intervention group (p < 0.05, 0.001). Most importantly, the relapse rate over 9 months in this group (16.3 %) was half that of the drug-only group (37.8 %), and just over one-quarter of that of the control group (61.5 %) (p < 0.05). Antipsychotic drug treatment and families' attitudes towards patients after the 9-month follow-up were significantly associated with clinical outcome (p < 0.05).
                In rural China, family intervention should focus on improving the relatives' recognition of illness, the caring attitude towards the patients, treatment compliance, relapse prevention, and the training of the patients' social functioning. This trial, one of the largest in the literature, has shown that psychoeducational family intervention is effective and suitable for psychiatric rehabilitation in Chinese rural communities. Sixty patients meeting the criteria established for schizophrenia who attained a clinical plateau following hospital discharge were randomized to receive for one year either penfluridol, 20 to 160 mg orally once each week, or fluphenazine decanoate, 0.5 to 4 ml every two weeks. The relapse rate for both treatments was low and equal. The rate of recurrence of psychosis for patients receiving penfluridol was 7% and for those receiving fluphenazine decanoate 10%. A retrospective comparison of the penfluridol group was made to a similar group of patients assigned to placebo in an earlier study. Placebo-treated patients had a relapse rate of 68%. Penfluridol patients had statistically fewer psychotic relapses. Questions about the possible carcinogenicity of penfluridol in animals will have to be resolved before it can be widely used. This study demonstrates the feasibility of using an oral, long-acting antipsychotic agent. It would be a useful psychopharmacologic addition in the treatment of outpatient schizophrenics. Schizophrenic patients have high rates of cigarette smoking. The authors compared the outcomes of two group psychotherapy programs for smoking cessation in patients with schizophrenia or schizoaffective disorder who were also treated with the nicotine transdermal patch and with either atypical or typical antipsychotic medications.
                Forty-five subjects were randomly assigned to 1) the group therapy program of the American Lung Association (N=17) or 2) a specialized group therapy program for smokers with schizophrenia (N=28) that emphasized motivational enhancement, relapse prevention, social skills training, and psychoeducation. All subjects participated in 10 weeks of treatment with the nicotine transdermal patch (21 mg/day) and 10 weekly group therapy sessions and continued to receive their prestudy atypical (N=18) or typical (N=27) antipsychotic medications. Outcome variables included treatment retention, rate of smoking abstinence, and expired-breath carbon monoxide level.
                Smoking abstinence rates did not differ in the two group therapy programs. However, atypical antipsychotic agents, in combination with the nicotine transdermal patch, significantly enhanced the rate of smoking cessation (55.6% in the atypical agent group versus 22.2% in the typical group), which was reflected by a significant effect of atypical versus typical agents on carbon monoxide levels. Risperidone and olanzapine were associated with the highest quit rates.
                The results suggest that 1) smoking cessation rates with the nicotine transdermal patch are modest in schizophrenia, 2) specialized group therapy for schizophrenic patients is not significantly different from American Lung Association group therapy in its effect on smoking cessation, and 3) atypical agents may be superior to typical agents in combination with the nicotine transdermal patch for smoking cessation in schizophrenia. The objectives of this randomized clinical trial were to investigate the impact of the discontinuation of long-term antipsychotics in residents with dementia in chronic care institutions and to identify clinical predictors of safe discontinuation. Subjects included 34 residents with dementia who were on antipsychotics for more than 6 months and whose behavior was currently stable. Subjects were randomized to either continue receiving their regular dosage of antipsychotics or to receive placebo for 6 months. Early withdrawal from the study was not statistically different between the groups (relative risk [RR] = 1.57, 95% confidence interval [CI] 0.76-3.26), and though not significantly different, subjects in the placebo group were more likely to be withdrawn from the study because of worsening behavior (RR = 1.25, 95% Cl 0.33-4.76). Three subjects in the placebo group were withdrawn from the study due to worsening of extrapyramidal symptoms. The active treatment group had more behavioral problems (e.g., physical aggression towards others, p < .05) compared to the placebo group. The placebo group developed more apathy, but balancing this outcome was a relative improvement in cognitive functioning. Baseline antipsychotic dose was predictive of behavioral worsening upon discontinuation of long-term antipsychotic drugs. The primary limitation of the study was the small sample size. In conclusion, a trial of discontinuation of antipsychotics should be considered in this population. To explore the effect on sleep/wake activity and on behavioral and psychological symptoms of the withdrawal of antipsychotic medications from nursing home (NH) patients with dementia.
                Randomized, placebo-controlled, double-blind trial.
                NHs in Bergen, Norway.
                Thirty patients (mean age 83.5) taking haloperidol, risperidone, or olanzapine for nonpsychotic symptoms. Intervention: Study participants were randomly assigned to withdrawal (intervention group) or continued treatment with antipsychotic medications (reference group) for 4 consecutive weeks.
                Behavioral rating using the Neuropsychiatric Inventory Questionnaire (NPI-Q) and actigraphy.
                After antipsychotic withdrawal, behavioral scores remained stable or improved in 11 of 15 patients, whereas four had worsening scores. Actigraphy revealed decreased sleep efficiency after drug discontinuation and increased 24-hour and night activity in both groups. Actigraphy records of nighttime and daytime activity indicated sleep problems and restlessness, in terms of the NPI-Q. One patient was restarted on antipsychotics.
                Antipsychotic drug withdrawal affected activity and sleep efficiency over the short term. Increases in total activity and impaired sleep quality after drug discontinuation should be monitored, because the long-term effect of these changes is not known. The NPI-Q and actigraphy are feasible tools that disclose relevant changes occurring during antipsychotic withdrawal in NH patients with dementia. Their use in clinical practice should be substantiated by larger studies. Dose reduction strategies for the maintenance treatment of schizophrenia are designed to maintain the benefits of antipsychotic drug therapy while reducing risks. Previous strategies with decanoate preparations have been based on the use of lower doses per injection to achieve dose reduction; these strategies have achieved dose reduction but have resulted in some increase in symptoms. The authors tested a new dose reduction approach: increasing the interval between injections during intramuscular decanoate antipsychotic treatment.
                Fifty outpatients with schizophrenia or schizoaffective disorder were randomly assigned to receive 25 mg of fluphenazine decanoate intramuscularly either every 2 weeks or every 6 weeks for 54 weeks in a double-blind design.
                The two dose regimens did not differ significantly in relapse, symptom, or side effect measures. The every-6-weeks regimen was associated with a significant reduction in total antipsychotic exposure.
                The use of injections every 6 weeks instead of every 2 weeks may increase compliance and improve patients' comfort as well as decrease cumulative antipsychotic exposure, without increasing relapse rates or symptoms. Amisulpride is a potent substituted benzamide antipsychotic drug claimed to improve the negative symptoms of schizophrenia, particularly at low dosage.
                Sixty long-term in-patients with schizophrenia and selected for predominant negative symptoms were randomised to receive either haloperidol or amisulpride. Over a year there was systematic dose reduction, as symptoms allowed.
                There were no significant differences between the treatment groups in the proportion receiving low-dose treatment, the control of positive symptoms, or ratings of social behaviour, side-effects or tardive dyskinesia. For negative symptoms, there were consistent but non-significant trends in favour of amisulpride. The amisulpride patients required significantly less anticholinergic medication.
                In chronically-hospitalised in-patients with schizophrenia characterised by persistent negative symptoms, amisulpride was a well-tolerated maintenance antipsychotic medication. The drug had only a limited effect in reducing negative symptoms, which were relatively stable, enduring phenomena in this sample, despite dosage reduction. In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome.
                The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug.
                Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings.
                Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies.
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.