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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Evidence-based review of pharmacologic and nonpharmacologic treatments for older adults with schizophrenia

AD Van Citters, SI Pratt, SJ Bartels, and DV Jeste.

Review published: 2005.

CRD summary

This review assessed the efficacy and safety of pharmacological and non-pharmacological interventions for older adults with schizophrenia. The authors concluded that limited evidence suggests that these interventions can benefit older patients, but further research is required. The lack of a description of review methods and the use of multiple outcomes make it difficult to comment on the reliability of the evidence.

Authors' objectives

To evaluate the efficacy and safety of pharmacological and non-pharmacological interventions for older adults with schizophrenia.

Searching

Pharmacological studies were sought by searching PubMed, PsycINFO, CINAHL and BIOSIS Previews. The reference lists were screened and additional studies were sought using the related search facilities of PubMed and Web of Science. Non-pharmacological studies were sought by searching PubMed, PsycINFO and reference lists. Only English language reports were eligible for inclusion in the review. All searches were conducted through May 2005 and search terms for both types of studies were reported.

Study selection

Study designs of evaluations included in the review

Randomised controlled trials (RCTs), quasi-experimental studies and longitudinal studies with at least 100 patients were eligible for inclusion in the review of pharmacological interventions. Corresponding inclusion criteria for non-pharmacological interventions were not reported, but the included studies were of single-blind RCT, cohort and quasi-experimental designs.

Specific interventions included in the review

Studies that evaluated pharmacological or non-pharmacological treatments were eligible for inclusion. One eligible study that evaluated remoxipride was excluded since this drug had been withdrawn. The included studies evaluated a variety of different drugs: fluphenazine, thioridazine, haloperidol, clozapine, chlorpromazine, olanzapine, risperidone, unspecified typical or conventional antipsychotics, and antidepressant augmentation of antipsychotic agents. The drugs were given over time periods that ranged from 6 weeks to 1 year. The non-pharmacological interventions evaluated in the included studies were Cognitive Behavioral Social Skills Training (CBSST), Functional Adaptation Skills Training (FAST) and Skills Training and Health Management (ST+HM) for between 3 months and 1 year.

Participants included in the review

Studies in older adults with schizophrenia or schizoaffective disorder were eligible for inclusion. Pharmacological studies that evaluated only adults aged 50 years or older with schizophrenia or schizoaffective disorder were eligible for inclusion; the review excluded pharmacological studies that evaluated heterogeneous populations or patients with paraphrenia. Studies of non-pharmacological interventions in which at least 50% of the sample had been diagnosed with schizophrenia or schizoaffective disorder were eligible for inclusion, as were studies that reported the outcomes separately for middle-aged or older adults (aged 40 years or more) with the conditions of interest were eligible for inclusion.

Outcomes assessed in the review

Studies that assessed efficacy and safety were eligible for inclusion. However, one included study evaluated neither of these outcomes. The primary review outcomes were improvement in psychiatric symptoms, functioning and tolerability. The included studies used a variety of measures to assess symptoms and function (details were reported).

How were decisions on the relevance of primary studies made?

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

The authors reported that they assessed the strengths and weaknesses of the individual studies. The authors did not state how the validity assessment was performed.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction. For each study, findings were extracted as text.

Methods of synthesis

How were the studies combined?

The studies were grouped by type of intervention and combined in a narrative.

How were differences between studies investigated?

Double-blind pharmacological RCTs were discussed separately. Differences between the studies were noted in the text and other differences were apparent from the tables.

Results of the review

Thirteen studies (n=1,000) evaluating pharmacological interventions were included in the review: 5 double-blind RCTs (n=387), 2 open-label RCTs (n=86), 2 quasi-experimental studies (n=186) and 2 non-controlled prospective cohort studies (n=283) that evaluated antipsychotic agents and 2 RCTs (n=58) of other psychoactive agents.

Five studies (n=156) evaluated non-pharmacological interventions: 2 RCTs (n=91), 2 quasi-experimental studies (n=56) and one non-controlled prospective cohort study (n=9).

Pharmacological interventions.

Antipsychotic agents - double-blind RCTs (5 studies).

Conventional versus atypical antipsychotic agents (2 RCTs): one study reported that olanzapine was more effective and had less severe extrapyramidal symptoms than haloperidol; the other reported that clozapine and chlorpromazine were of similar efficacy.

Atypical antipsychotic agents versus each other (1 RCT): the study reported that olanzapine and risperidone had similar effects on cognitive and psychiatric measures, with the only difference in side-effects being greater weight gain with olanzapine.

Conventional antipsychotics versus each other (2 RCTs): these RCTs had small sample size and limited generalisability. The RCT that compared haloperidol with placebo did not report either side-effects or effectiveness.

Antipsychotic agents - open-label RCTs, quasi-experimental studies and large prospective single-agent studies. Methodological flaws included small sample sizes, lack of blinding and randomisation, absence of a control group and use of a retrospective design.

The open-label RCTs reported that olanzapine and risperidone were associated with less parkinsonism and improved negative and depressive symptoms in comparison with conventional antipsychotics (1 crossover RCT), and that olanzapine was associated with greater improvements on symptoms measures compared with haloperidol (1 RCT).

The results of the other studies were also reported.

Antidepressant augmentation of antipsychotic agents (2 RCTs): the RCTs reported improvements in some symptom measures with mianserin and trazodone compared with placebo (1 small double-blind RCT) and with citalopram compared with no citalopram (1 small single-blind RCT).

Non-pharmacological studies.

Three studies (2 RCTs and 1 non-controlled prospective cohort study) evaluated CBSST. The smaller pilot RCT reported greater improvements in positive and negative symptoms with CBSST compared with usual care. The other RCT reported significant improvements in some outcomes ('social functioning', cognitive insight and performance) but not others (symptoms, hospitalisations and living skills) in patients allocated to CBSST compared with usual care. The non-controlled cohort study evaluated only 9 patients.

One quasi-experimental study evaluated FAST and reported significant improvement in community functioning skills with FAST compared with usual care, but no difference in psychiatric symptoms between treatments.

One quasi-experimental study evaluated ST+HM and reported greater improvements in independent living skills and social functioning in patients allocated to ST+HM compared with HM alone.

Authors' conclusions

The authors' conclusion appears to be that limited evidence suggests that pharmacological and psychosocial interventions can benefit older patients with schizophrenia, but further research is required.

CRD commentary

The review question was defined broadly in terms of the participants, intervention and study design (for studies of pharmacological interventions); inclusion criteria for the outcomes were not specified, nor were inclusion criteria for the design of studies of non-pharmacological interventions. However, one study that evaluated discontinuation of antipsychotic treatment and did not evaluate any of the outcomes of interest was also included, which suggests that the inclusion criteria might not have been strictly adhered to when selecting studies. Several relevant sources were searched but no attempts were made to minimise either publication or language bias. The methods used to select studies and extract the data were not described, so it is not known whether any efforts were made to reduce reviewer error and bias. A formal assessment of validity was not reported, but some methodological limitations of the studies were discussed in the text.

Given the differences between the studies, a narrative synthesis that noted some of the methodological flaws was appropriate. The results for individual studies were reported as text and not as point estimates and variance of treatment differences, thus it is not possible to confirm the results reported in the text. Most of the studies assessed multiple outcomes. The lack of reporting of a clear strategy for selecting primary review outcome measures means that there is a potential for bias due to selective reporting. The lack of a description of review methods and the use of multiple outcomes make it difficult to comment on the reliability of the evidence underpinning the conclusions that older adults benefit from the interventions. In view of the limited evidence, the recommendations for further research appear appropriate.

Implications of the review for practice and research

Practice: The authors stated that older patients taking clozapine should be monitored for agranulocytosis.

Research: The authors stated that well-designed studies (including larger RCTs) are required to evaluate interventions (including psychosocial interventions) in different subgroups of older patients with schizophrenia. There is also a need for a systematic evaluation of serious adverse effects in older adults with schizophrenia who are taking atypical antipsychotics.

Funding

National Institutes of Mental Health, grant numbers K24 MH 66282 and P30 MH66248; U.S. Department of Veterans Affairs.

Bibliographic details

Van Citters A D, Pratt S I, Bartels S J, Jeste D V. Evidence-based review of pharmacologic and nonpharmacologic treatments for older adults with schizophrenia. Psychiatric Clinics of North America 2005; 28(4): 913-939. [PubMed: 16325735]

Indexing Status

Subject indexing assigned by NLM

MeSH

Aged; Antipsychotic Agents /therapeutic use; Humans; Psychotherapy /methods; Schizophrenia /drug therapy /therapy

AccessionNumber

12006000183

Database entry date

31/07/2007

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 16325735

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