Efficacy of Psychological Therapy in Schizophrenia: Conclusions From Meta-analyses

Abstract

Over the past years, evidence for the efficacy of psychological therapies in schizophrenia has been summarized in a series of meta-analyses. The present contribution aims to provide a descriptive survey of the evidence for the efficacy of psychological therapies as derived from these meta-analyses and to supplement them by selected findings from an own recent meta-analysis. Relevant meta-analyses and randomized controlled trials were identified by searching several electronic databases and by hand searching of reference lists. In order to compare the findings of the existing meta-analyses, the reported effect sizes were extracted and transformed into a uniform effect size measure where possible. For the own meta-analysis, weighted mean effect size differences between comparison groups regarding various types of outcomes were estimated. Their significance was tested by confidence intervals, and heterogeneity tests were applied to examine the consistency of the effects. From the available meta-analyses, social skills training, cognitive remediation, psychoeducational coping-oriented interventions with families and relatives, as well as cognitive behavioral therapy of persistent positive symptoms emerge as effective adjuncts to pharmacotherapy. Social skills training consistently effectuates the acquisition of social skills, cognitive remediation leads to short-term improvements in cognitive functioning, family interventions decrease relapse and hospitalization rates, and cognitive behavioral therapy results in a reduction of positive symptoms. These benefits seem to be accompanied by slight improvements in social functioning. However, open questions remain as to the specific therapeutic ingredients, to the synergistic effects, to the indication, as well as to the generalizability of the findings to routine care.

Introduction

Over the past years a need for supplementary psychological therapies in the treatment of schizophrenia spectrum disorders became apparent for various reasons. For one, pharmacotherapy—commonly considered as cornerstone in the treatment of schizophrenia—has limits. For example, relapse rates in schizophrenia remain substantial even when adherence to prescribed medication is monitored.¹ Furthermore, a considerable number of schizophrenic patients suffer from persistent positive symptoms despite an ongoing medication regimen,² and current neuroleptic drugs have little beneficial effect on negative symptoms, residual cognitive impairments, and social functioning.³ Finally, hospital treatment of schizophrenia has increasingly been replaced by community-based care. Thus, more responsibility for managing the burden of illness-related impairment was passed on to patients and their relatives, who in turn had to develop or improve adequate coping strategies. Therefore, many experts in the field advocate a multimodal treatment approach for schizophrenia.⁴

Most health-care systems, however, are challenged by serious financial constraints. Thus, decisions about what treatment to provide for whom must be based on evidence. Meta-analyses represent a reliable method to establish evidence-based clinical practice. They describe criteria for the selection and evaluation of employed sources, which allows for a replication of their findings. Summarizing data from different studies on the same subject by using a standardized quantified measure provides the possibility to estimate and compare interventions by the magnitude and significance of their effects. Meta-analyses also facilitate the explanation of the variance between the findings of different studies by testing statistical models including moderator variables. In doing so, they increase the statistical power of the original single studies and thereby enhance the validity of their findings.⁵ Although problems inherent to this method may compromise the validity of the results (eg, with regard to the inclusion and comparison of methodologically heterogeneous or flawed studies), meta-analyses became widely accepted as a primary tool to assess the efficacy of specific treatment approaches.

However, none of the existing meta-analyses summarizing the efficacy of psychological therapies in schizophrenia allows for a comprehensive and comparative review of the effects of psychological interventions. The meta-analysis by Pilling et al^6,7 represents the only systematic quantitative review of randomized controlled trials on the efficacy of different well-defined psychological interventions. Yet, the power to detect the effects on different types of outcome is limited in this meta-analysis due to the small number of included randomized controlled trials. Therefore, we intend to summarize the findings of all meta-analyses published between 1990 and 2005 in order to draw consistent conclusions regarding the effects of different psychological therapy approaches in the treatment of schizophrenia. This summary is supplemented by selected results from an own meta-analysis of randomized controlled trials on the efficacy of psychological therapies in schizophrenia, where these results were suited to add to the findings of the existing meta-analyses.

Materials and Methods

Search

Relevant meta-analyses and randomized trials were identified by searching several electronic databases (PsycINFO; MEDLINE; the Cochrane Schizophrenia Group's Register of Trials; PSYNDEX). The following search algorithm was used to identify randomized controlled trials:

• [schizophren* or psychosis or psychotic] and

• [(psychological or psychosocial or psychotherapeutic* or supportive or behavio* or cognitive or operant or contingent or social-learning or skills or assertive* or problem-solv* or self-control or self-instruction* or self-management or rational-emotive or psychoeducation* or education* or adherence or compliance or psychoanal* or psychodynamic* or insight-oriented or system* or gestalt or client-centered or person-centered or experiential) near

• (psychotherapy or therapy or intervention or treatment or training or rehabilitation or remediation or program* or modification or conditioning)] and

• [(random* or controlled or clinical or comparative or empirical or experimental or evaluation or efficacy or outcome or treatment-outcome or prospective or single-blind-method or double-blind-method) near

• (study or trial)]

In addition, references of all identified meta-analyses, reviews, and studies were hand searched.

Selection

For reasons of internal validity, the scope of our meta-analysis was limited to randomized controlled trials. All randomized controlled trials published in peer-reviewed journals up to 2005 were selected if they evaluated the impact of a specific psychological intervention compared with standard treatment or with an unspecific psychosocial treatment condition and if they included a homogeneous sample of standardized diagnosed schizophrenic patients and at least one standardized outcome measure. The identified studies were categorized according to the described psychological therapy approach and comparison group. To verify reliability of the selection process and categorization, a second coder reassessed a random sample (n = 40) drawn from all studies identified with the search strategy. The inclusion and categorization criteria checklist may be obtained from the authors upon request.

Data Analysis

In order to compare the findings of the existing meta-analyses, we extracted and transformed the reported effect sizes into Hedges g effect sizes where possible.

For our own meta-analysis, the data of the single studies were extracted and transformed into effect sizes for different types of outcomes. A mean effect size was calculated if several outcome measures were applied to the same type of outcome in a single study in order to avoid dependent data. Differences in effect sizes between the compared treatment and control conditions were calculated by dividing the mean pre-post difference (or pre–follow-up difference) by the pooled pre-post standard deviations (SDs) (or pre–follow-up SDs) for each condition and outcome variable. These calculations were based on an according-to-protocol analysis. The resulting effect sizes of the experimental and control condition were subtracted from each other. The differences in effect sizes in the individual studies were weighted by the inverse conditional variance and integrated by means of a categorical model of fixed effects. If the indication of means and SDs was missing, the effect sizes were estimated by F-, t-, U- or chi-square tests. In addition, 95% confidence intervals were estimated to test the significance of the effects, and heterogeneity tests were applied to evaluate the consistency of the resulting effect sizes regarding different types of outcomes and different categories of comparisons.

Data analyses were performed using an SPSS software package for calculating effect sizes developed by Rustenbach.⁸

Results

Meta-analyses of Efficacy Studies on Psychological Therapies in Schizophrenia

Between 1990 and 2005, a total of 21 meta-analyses of studies assessing the efficacy of various psychological therapies in schizophrenia became available (table 1). The most comprehensive of these was conducted by Mojtabai et al.⁹ It included a total of 106 studies published between 1966 and 1994 comparing any psychosocial therapy with a control condition. Each study was categorized according to treatment and control condition, respectively, and for each category obtained, a mean effect size was computed. On average, the studies comparing a combination of psychosocial and drug treatment with pharmacotherapy alone yielded an effect size of 0.39 in favor of the combined treatment. This can be interpreted as the magnitude of the additional effect of psychosocial treatment to pharmacotherapy. It indicates that the mean in effect variables between experimental and control conditions differs in 0.39 SDs. This implies that on average a patient receiving combined psychosocial and pharmacological treatment does better than 65% of patients with pharmacological treatment alone. By showing the additional effect of psychosocial treatment approaches to pharmacologic treatment, the meta-analysis by Mojtabai et al⁹ provided the first solid empirical basis of the multimodal treatment model. They also provided a comparison between different types of psychosocial interventions.

Table 1.

Meta-analyses of the Efficacy of Psychological Therapies in Schizophrenia

Therapy Approach	Meta-analysis	Inclusion Criteria	Number of Included Studies
Psychosocial interventions	Mojtabai et al9	Controlled studies	106
Wunderlich et al10	Controlled studies	31
Psychodynamic therapy	Malmberg and Fenton11	Randomized controlled studies	3
Hypnosis	Izquierdo de Santiago and Kahn54	Randomized controlled studies	3
Token economy	McMonagle and Sultana14	Randomized controlled studies	3
Social skills training	Pilling et al6,7	Randomized controlled studies	9
Cognitive remediation	5
Family interventions	18
Cognitive behavioral therapy	7
Social skills training	Benton and Schroeder16	Controlled studies	27
Corrigan17	Observational and controlled studies	73
Cognitive remediation of executive functions (Wisconsin Card Sorting Test)	Kurtz et al26	Laboratory and controlled studies	11
Cognitive remediation of attention	Suslow et al27	Laboratory and controlled studies	9
Cognitive remediation	Krabbendam and Aleman28	Controlled studies	12
Twamley et al29	Controlled studies	17
Hayes and McGrath30	Randomized controlled studies	3
Integrated Psychological Therapy	Müller et al31	Controlled studies	28
Family interventions	Pharoah et al40	Randomized controlled studies	28
Pitschel-Walz et al41	Controlled studies	25
Cognitive behavioral therapy	Jones et al58	Randomized controlled studies	19
Cognitive behavioral therapy of positive symptoms	Tarrier and Wykes49 and Tarrier50	Controlled studies	20
Gould et al51	Controlled studies	7
Rector and Beck52	Controlled studies	7
Zimmermann et al53	Controlled studies	14

In a similar way Wunderlich et al¹⁰ compared the effect sizes resulting from different psychosocial therapy approaches. Their meta-analysis included all controlled studies (n = 31) published in English or German language between 1955 and 1994 that contrasted a psychosocial experimental condition with a pharmacologically or nonspecifically treated control group.

The meta-analyses by Mojtabai et al and Wunderlich et al thus license a first quantitative evaluation of the comparative efficacy of different psychosocial interventions. However, the specific psychological therapies were not well defined in these meta-analyses. Yet, both analyses demonstrate that psychological interventions designed to reduce disorder-related impairments in cognitive functioning or social behavior as well as psychoeducational and behavioral interventions focusing on the coping resources of schizophrenic patients and their relatives achieve significantly larger effects than insight-oriented psychodynamic therapy methods. The lack of evidence for the efficacy of psychodynamic therapies in schizophrenia has also been confirmed by a recent meta-analysis of Malmberg and Fenton.¹¹ Therefore, the findings of meta-analyses seem to confirm the theoretical assumptions provided by the vulnerability-stress-coping models.¹² These models suggest that favorable outcomes may be expected from psychological approaches that, in combination with neuroleptics, aim to improve the resources of patients and relatives for the management of disorder-related impairments and social strain. Considering these interventions in view of their specific therapeutic content, 4 distinct psychological treatment approaches can be identified on the basis of the available meta-analyses:

1. Training of social skills

2. Cognitive remediation

3. Psychoeducational coping-oriented interventions with families and relatives' groups

4. Cognitive behavioral therapy of positive symptoms.

The theoretical background, the content, as well as the empirically supported efficacy of these approaches will be outlined in the following sections.

Social Skills Training

Schizophrenic patients in general exhibit deficits in social competence that are widely independent of the severity of prevailing symptoms.¹³ Poor social competence provokes cliff-hanging, stressful interactions with the social environment and leads to social isolation. In contrast, social competence generates social resources and improves community integration and role functioning. Social competence may, therefore, be viewed as an essential factor in the fragile balance between vulnerability and stressors. Consequently, it is seen as a key factor of outcome and serves as a target for therapeutic interventions.

Institutionalized token economy, based on operant conditioning, was the first psychological intervention focusing the social behavior of psychiatrically disabled persons. Despite the positive effects of token economy on negative symptoms,¹⁴ its significance for the treatment of schizophrenic patients has decreased because the effects did not extend beyond the therapeutic setting and the possibility for contingent reinforcement is limited in community-based care settings. Therefore, social skills training gained an important role in therapeutic efforts to improve social functioning. The training is based on the perspective that social competence is composed of a set of skills allowing to receive, process, and express socially relevant clues. Prototypical sequences of social interactions are broken down into their components. These components are then practiced mostly within group settings by employing techniques derived from operant and social learning theory.

During the 1980s and 1990s, training approaches were tailored to address common problems particularly relevant to schizophrenic patients. The most widely studied skills training approach are the training modules for Social and Independent Living Skills developed by Liberman et al.¹⁵ This training program consists of a series of training modules to practice specific disorder-related social and instrumental skills such as basic conversation, medication management, or community reentry.

Three meta-analyses have explored the efficacy of social skills training in schizophrenia so far. Overall, they show a rather inconsistent pattern of findings (table 2). Their results largely depend on the degree of rigor in the determination of the methodic quality of the individual studies included. The analyses by Benton and Schroeder¹⁶ and by Corrigan¹⁷ also included quasi-experimental studies. They revealed large effect sizes with regard to the acquisition of social skills and assertiveness and small to large effects regarding the reduction of psychopathology and hospitalization rates. In contrast, the meta-analysis by Pilling et al,⁷ which included only randomized controlled trials, did not support these findings.

Table 2.

Findings of the Meta-analyses Regarding the Effects of Social Skills Training

Meta-analysis	Outcome Variable	Effect Sizea (95% CI)	Heterogeneity Qb
Benton and Schroeder16	Skill acquisition	0.76 (0.59 to 93)	13.49 (P > .90)
Skill acquisition (follow-up)	1.13 (0.62 to 1.64)	NR
Assertiveness	0.69 (0.43 to 95)	13.52 (P > .10)
General psychopathology	0.32 (0.06 to 0.58)	8.87 (P > .20)
Hospitalization (follow-up)	0.47 (0.18 to 0.76)	2.54 (P > .30)
Corrigan17	Skill acquisition	1.43*	NR
Skill acquisition (follow-up)	1.40*	NR
Assertiveness	0.92*	NR
General psychopathology	1.08*	NR
Pilling et al7	Social functioning	Lack of data
Relapse	0.17 (−0.14 to 0.46)	3.71 (P = .29)

Note: CI, confidence interval; NR, not reported.

^aHedges g.

^bSum of squares.

^*t-test, P < .05.

In our meta-analysis, we identified a total of 108 randomized controlled trials on the efficacy of various psychological interventions with schizophrenic patients. Twenty-two of these had to be excluded from further analysis because they could not be assigned unequivocally to a specific psychological therapy approach. Of the remaining 86 randomized controlled trials, 19 evaluated the efficacy of a social skills training approach. The included studies and their assignment to a specific class of psychological therapies as well as the excluded ones are listed in Appendix. To be classified as social skills training, the intervention had to include a range of techniques founded on the operant or social learning theory to enhance social performance such as instructions, modeling, role-play, reinforcement, corrective feedback, and in vivo exercises by homework assignments.

Our meta-analysis confirms a large, homogeneous and enduring effect on the acquisition of social skills by schizophrenic patients as measured in role-play tests and a short-term enhancement of their assertiveness (table 3). In addition, social skills training consistently leads to a moderate but significant and stable improvement in social functioning, slightly reduces general psychopathology, and considerably decreases the hospitalization rate at follow-up. However, the latter finding is based on only 2 randomized controlled trials.

Table 3.

Significant and Homogeneous Effects of Social Skills Training Across Various Control Groups

Outcome variable	Number of Included Studies	Number of Included Patients	Effect Size (95% CI)	Heterogeneity Qa
Posttreatment
Skill acquisition	14	688	0.77 (0.62 to 0.93)	16.54 (P = .22)
Assertiveness	5	160	0.43 (0.11 to 0.76)	2.63 (P = .62)
Social functioning	6	342	0.39 (0.19 to 0.59)	1.22 (P = .94)
General psychopathology	8	349	0.23 (0.01 to 0.44)	13.25 (P = .07)
Follow-up
Skill acquisition	6	295	0.52 (0.28 to 0.77)	5.57 (P = .35)
Social functioning	3	210	0.32 (0.08 to 0.56)	0.90 (P = .64)
Hospitalization	2	110	0.48 (0.11 to 0.86)	0.02 (P = .89)

Note: CI, confidence interval.

^aSum of squares.

Cognitive Remediation

The vast majority of schizophrenic patients demonstrate poor performance in different aspects of cognitive processing, most often reported in the domains of processing speed, sustained attention, working memory, verbal learning, executive functioning, and social cognition. 85% of the individuals suffering from schizophrenia score 1.3–2 SDs below the mean of samples drawn from mentally healthy populations. This is equivalent to scoring lower than 90% of healthy controls. Cognitive impairments tend to be relatively stable over the course of the disorder and are apparent even if psychotic symptoms remit. Mild cognitive impairments in schizophrenic patients are also observed before the onset of the disease as well as in a subgroup of their first-degree relatives.¹⁸ This indicates that cognitive impairment in part represents a stable vulnerability marker of schizophrenia.

Most important, certain cognitive dysfunctions clearly have been identified as rate-limiting factors impairing learning in psychosocial therapy and rehabilitation programs, as well as social and vocational functioning.¹⁹ Impairment of long-term verbal memory or sustained attention has been shown to limit the ability to acquire social and instrumental skills. Repeatedly, correlations were identified between impaired executive functioning and long-term verbal memory on the one hand and reduced social and vocational adaptation on the other hand.²⁰ Therefore, cognitive impairments are now recognized as a core feature of schizophrenia and are considered an important therapeutic target.

Over the past decade, several cognitive training approaches have been developed to improve cognitive deficits in schizophrenic patients by means of the following methods.

1. Repetitive exercise of cognitive tasks presented in a computerized or paper and pencil version.

2. Establishing compensatory strategies, which imply the learning of strategies to organize information (eg, categorization), or adaptive strategies, which involve prompts and other aids in the environment (environmental engineering) of the patient such as posting reminders, placing pills, or clothes boxes, etc.

3. Behavioral and didactic learning techniques, such as instructions, positive reinforcement or “errorless learning.” Errorless learning is based on the premise that learning is improved in the absence of errors and includes the following components: (1) the task is broken down into a set of hierarchically ordered components, (2) training begins on the simplest component and proceeds stepwise to more complex ones, (3) each component is overlearned through repeated practice, and (4) previously used prompts, cues, and instructions are slowly faded.

These methods have been employed alone or in various combinations in a series of training programs, which are summarized under the terms cognitive remediation or cognitive adaptation. Examples are the cognitive subprograms of the Integrated Psychological Therapy (IPT) developed by Brenner and coworkers,²¹ the Cognitive Remediation Therapy (CRT) by Delahunty and Morice,²² the Neuropsychological Educational Approach to Rehabilitation (NEAR) by Medalia et al,²³ the Cognitive Enhancement Therapy (CET) of Hogarty et al,²⁴ or the Cognitive Adaptation Training (CAT) by Velligan et al.²⁵

A number of laboratory trials have demonstrated change on neurocognitive tests used in training or close parallels. In addition, these studies indicate that various learning strategies differ in their positive effects on different cognitive functions. By now, a series of controlled clinical studies have also been conducted. Clinical investigations have examined the impact of cognitive remediation on functional outcome and neurocognitive measures that are independent of the tasks used in training.

Presently, the studies on the efficacy of cognitive remediation are covered by 6 meta-analyses. Two of them included laboratory and quasi-experimental studies evaluating the efficacy of cognitive training on executive functioning as assessed by the Wisconsin Card Sorting Test (WCST)²⁶ or attention tasks.²⁷ Four meta-analyses included controlled clinical trials.^7,28–30 Another meta-analysis evaluated the efficacy of the IPT program.³¹ The findings of this analysis will be discussed in detail in a separate contribution to this issue.

Again, findings are inconsistent with respect to the specific cognitive function that is evaluated and the rigor of the inclusion criteria (table 4). Suslow et al²⁷ show heterogeneous results with regard to improvements in various attention tasks, whereas Kurtz et al²⁶ demonstrate large effects on the performance in the WCST. The meta-analyses including only randomized controlled clinical trials^7,30 again do not support evidence for the clinical benefit of cognitive remediation. However, the meta-analyses of Krabbendam and Aleman²⁸ as well as the one of Twamley et al,²⁹ which also included quasi-experimental clinical trials, demonstrate small to medium effects on general cognitive functioning and indicate a possible transfer of these effects to social functioning.

Table 4.

Findings of the Meta-analyses Regarding the Effects of Cognitive Remediation

Meta-analysis	Outcome Variable	Effect Sizea (95% CI)	Heterogeneity Qb
Kurtz et al26	Executive functioning	0.98 (0.80 to 1.16)	17.6 (P = .61)
Suslow et al27	Attention	NR	NR
Krabbendam and Aleman28	Cognitive functioning	0.45 (0.26 to 0.64)	14.3 (P = .43)
Twamley et al29	Cognitive functioning	0.32 (NR)	NR
Social functioning	0.51 (NR)	NR
General psychopathology	0.26 (NR)	NR
Hayes and McGrath30	Cognitive functioning	Lack of data
Social functioning	Lack of data
General psychopathology	Lack of data
Pilling et al7	Attention	0.11 (−0.31 to 0.53)	NR
Verbal memory	0.14 (−0.23 to 0.50)	NR
Visual memory	0.34 (−0.23 to 0.92)	NR
Executive functioning	NR	NR
General psychopathology	0.23 (−0.20 to 0.66)	NR

Note: CI, confidence interval; NR, not reported.

^aHedges g.

^bSum of squares.

Our meta-analysis included 19 randomized controlled trials on cognitive remediation. Cognitive remediation was defined as an intervention that focuses on improving cognitive functioning by applying repeated practice of cognitive tasks or by the training of strategies for compensating cognitive impairments.

The findings provide support for the generalization of training effects to attention, executive functioning, memory, and social cognition. It demonstrates small to medium, but robust beneficial effects on these functions (table 5). It also supports the finding of a moderate transfer effect on social functioning and demonstrates small reductions in overall psychopathology and negative symptoms.

Table 5.

Significant and Homogeneous Effects of Cognitive Remediation Across Various Control Groups

Outcome Variable (posttreatment)	Number of Included Studies	Number of Included Patients	Effect Size (95% CI)	Heterogeneity Qa
Attention	13	539	0.32 (0.15 to 0.49)	7.67 (P = .81)
Memory	12	704	0.36 (0.20 to 0.51)	15.77 (P = .17)
Executive functioning	10	606	0.28 (0.12 to 0.44)	6.24 (P = .72)
Social cognition	3	228	0.40 (0.13 to 0.68)	0.28 (P = .87)
Social functioning	7	306	0.49 (0.27 to 0.70)	10.82 (P = .09)
General psychopathology	9	452	0.20 (0.01 to 0.38)	5.01 (P = .76)
Negative symptoms	9	394	0.24 (0.04 to 0.44)	13.52 (P = .09)

Note: CI, confidence interval.

^aSum of squares.

Psychoeducational Coping-Oriented Interventions With Families and Relatives' Groups

Over the past decades, psychoeducational interventions with families that focus on the improvement of disorder- and stress-related coping strategies of patients and their relatives have gained particular relevance. The finding of a consistent relation between family interactions characterized by high-expressed emotion and the risk for recidivism was an important trigger for their development.³² This type of intervention was introduced in various treatment settings including single families,^33–36 multiple family groups³⁷ and relatives' groups without patients,³⁸ or bifocal groups with patients and relatives in separate sessions.³⁹

Despite some variability as to the treatment setting, the psychoeducational and coping-oriented family interventions share 2 basic features. They usually start with psychoeducation providing information on the disorder based on the vulnerability-stress models to patients and their relatives. Particular emphasis is given to the instruction of patients as regards medication and treatment adherence. In addition, they intend to improve the ability to cope with stressors arising from illness-related symptoms or from the social environment. This is accomplished by means of various cognitive behavioral interventions that aim to improve dealing with early warning signs, problem-solving capacity, and communication skills.

No other psychological treatment approach for schizophrenic patients has been investigated as intensively during recent years. Since the end of the 1970s, a considerable number of controlled, longitudinal studies on the efficacy of these approaches have been conducted. The findings of these studies were summarized in 3 meta-analyses,^6,40,41 which consistently demonstrate that schizophrenic patients with relatives taking part in such interventions suffer from significantly fewer relapses and hospitalizations during follow-up (table 6). Pitschel-Walz et al⁴¹ found a 20% average decrease in relapse or hospitalization rates due to these interventions. In addition, psychoeducational family interventions lead to an improvement in the patients' adherence to medication.^6,40 Long-term interventions with families have significantly more impact on relapse and hospitalization rates than short-term interventions with relatives' groups.^6,41

Table 6.

Findings of the Meta-analyses Regarding the Effects of Psychoeducational Interventions With Families or Relatives

Meta-analysis	Outcome Variable	Effect Sizea (95% CI)	Heterogeneity Qb
Pharoa et al40	Relapse (at 12 months follow-up)	0.30 (0.14 to 0.46)	26.40 (P = .002)
Relapse (at 24 months follow-up)	0.26 (0.02 to 0.50)	16.28 (P = .006)
Hospitalization (at 12 months follow-up)	0.15 (−0.08 to 0.38)	9.39 (P = .15)
Hospitalization (at 18 months follow-up)	0.62 (0.31 to 0.94)	0.65 (P = .72)
Days in hospital	Lack of data
General psychopathology	NR	NR
Social functioning	0.78 (0.35 to 1.21)	4.05 (P = .04)
Compliance with medication	0.34 (0.11 to 0.56)	4.19 (P = .65)
Expressed emotion	0.67 (0.29 to 1.04)	6.24 (P = .04)
Burden	Lack of data
Quality of life	Lack of data
Pilling et al6	Relapse (first 12 months)	0.25 (0.08 to 0.43)	23.04 (P < .01)
Relapse (1 to 2 years)	0.17 (−0.12 to 0.45)	17.93 (P < .01)
Hospitalization (first 12 months)	0.31 (0.00 to 0.61)	11.79 (P < .01)
Hospitalization (1 to 2 years)	0.28 (0.10 to 0.46)	15.60 (P < .01)
Compliance with medication	0.25 (0.01 to 0.50)	2.48 (P = .65)
Pitschel-Walz et al41	Relapse and hospitalization (overall)	0.41 (0.28 to 0.56)	3.45 (P > 0.10)
Relapse and hospitalization (during first year)	0.39 (NR)	NR
Relapse and hospitalization (during second year)	0.52 (NR)	NR
Relapse and hospitalization (intervention lasting 3 months or less)	0.28 (0.12 to 0.45)	3.85 (P > .50)
Relapse and hospitalization (intervention lasting 9 to 24 months)	0.63 (0.39 to 0.90)	2.73 (P > .50)

Note: CI, confidence interval; NR, not reported.

^aHedges g.

^bSum of squares.

This is in line with the findings of our meta-analysis, which is based on 31 randomized controlled trials. For an intervention to be classified as a psychoeducational coping-oriented intervention with family or relatives' groups, it had to include psychoeducation and problem solving or crisis management.

The results of our meta-analysis additionally indicate that psychoeducational interventions foster a better knowledge of the disorder among the relatives of the patients and lead to a considerable shift from high- to low-expressed emotion, a substantial improvement in the social adjustment of the patients, a decline of inpatient treatment, and an overall reduction of psychopathology during the follow-up (table 7).

Table 7.

Significant and Homogeneous Effects of Psychoeducational Interventions With Families or Relatives Across Various Control Groups

Outcome Variable	Number of Included Studies	Number of Included Patients	Effect Size (95% CI)	Heterogeneity Qa
Posttreatment
Relatives' knowledge about the disorder	8	3662	0.39 (0.31 to 0.46)	2.04 (P = .96)
Patients' social functioning	6	3362	0.38 (0.30 to 0.46)	2.84 (P = .72)
High-expressed emotion	7	284	0.59 (0.36 to 0.83)	3.56 (P = .74)
Days in hospital	3	3197	0.27 (0.18 to 0.36)	0.39 (P = .82)
Follow-up
General psychopathology of patients	4	178	0.40 (0.10 to 0.70)	2.10 (P = .56)
Days in hospital	2	127	0.71 (0.35 to 1.06)	1.70 (P = .19)
6–12 months follow-up
Relapse	14	3838	0.42 (0.35 to 0.49)	16.58 (P = .22)
Hospitalization	13	3789	0.22 (0.14 to 0.29)	12.35 (P = .42)
18–24 months follow-up
Hospitalization	8	445	0.51 (0.32 to 0.70)	6.83 (P = .45)

Note: CI, confidence interval.

^aSum of squares.

Cognitive Behavioral Therapy of Positive Symptoms

Despite continuous pharmacological treatment, one fourth to up to one half of all schizophrenic patients suffer from persisting delusions and/or hallucinations.⁴² Therefore, cognitive behavioral therapy approaches for the treatment of positive symptoms have gained great attention over the last decade. One reason for this is the increasing importance of cognitive models for the description and understanding of delusions and hallucinations. It is now widely accepted that nonpsychotic and psychotic experiences can be modeled along a continuum. This assumption is supported by the observation that under certain conditions—for example, through hypnosis, sensory deprivation, sleep deprivation, or severe stress—psychotic experiences can be induced in healthy subjects. Cognitive explanatory models are essentially based on the assumption that irrational beliefs, misinterpretations, and misattributions form the foundation of delusions and hallucinations. These misjudgments could originate from impaired social cognition like theory of mind or self-monitoring deficits, which in turn may hamper the discrimination between external stimuli and internal intentions.⁴³

These assumptions open up the possibility to apply cognitive therapy methods in the treatment of psychotic symptoms. Presently, groups from England,^42,44,45 Scandinavia,⁴⁶ and Australia⁴⁷ have elaborated specific therapy models. A key feature of cognitive behavioral therapy for psychosis involves the development of a reasonable, “normalizing” explanation of the patients' symptoms. Therapy is based on an analysis of the quality of psychotic symptoms (ie, their frequency, intensity, and duration), their triggering events, and their maintaining conditions. The subjectively presumed consequences of delusions and hallucinations as well as their individual meaning are then targeted by means of cognitive interventions. Cognitive restructuring employs verbal challenge, empirical reality testing, or reappraisal. Another aspect of cognitive behavioral therapy for psychosis involves the enhancement of the patient's coping strategies. Cognitive behavioral therapies of positive symptoms are usually tailored to the specific situation of an individual patient and thus are conducted in single therapy settings. Lately, however, group therapy approaches have been conceived and evaluated as well.⁴⁸

The existing set of meta-analyses^49–53 generally demonstrates medium to large effect sizes with regard to the severity of positive symptoms (table 8).

Table 8.

Findings of the Meta-analyses Regarding the Effects of Cognitive Behavioral Therapy of Positive Symptoms

Meta-analysis	Outcome Variable	Effect Sizea (95% CI)	Heterogeneity Qb
Gould et al51	Positive symptoms	0.65 (0.56 to 0.71)	NR
Positive symptoms (follow-up)	0.93 (NR)	NR
Rector and Beck52	Positive symptoms	0.68 (NR)	NR
Positive symptoms (follow-up)	0.84 (NR)	NR
Negative symptoms	0.61 (NR)	NR
Negative symptoms (follow-up)	0.80 (NR)	NR
Tarrier and Wykes49 and Tarrier50	General psychopathology	0.37 (NR)	NR
Zimmermann et al53	Positive symptoms	0.35 (0.23 to 0.47)	21.45 (P > .05)
Positive symptoms (3–12 months follow-up)	0.40 (0.24 to 0.57)	12.80 (P > .05)
Positive symptoms (>12 months follow-up)	0.33 (0.14 to 0.51)	2.77 (P > .05)

Note: CI, confidence interval; NR, not reported.

^aGlass' Δ (Gould et al), pre-post effect size differences between cognitive behavioral therapy and supportive therapy (Rector and Beck), and Hedges g (Tarrier and Wykes and Tarrier; Zimmernann et al).

^bSum of squares.

Our meta-analysis underscores this finding. It included 17 randomized controlled trials on the efficacy of interventions targeting positive symptoms by cognitive restructuring methods and coping enhancement strategies.

However, consistent significant effects could only be established in trials on cognitive behavioral therapy of persistent positive symptoms (table 9). Compared with various control groups, cognitive behavioral therapy leads to a substantial decline of psychopathology at posttreatment assessments and attains a substantial and stable decrease of persistent positive symptoms. A considerable reduction in the severity of hallucinations is achieved at the time of completion of the therapy, but this gain is lost at follow-up. In contrast, a significant weakening of the impact of persistent delusions cannot be observed until follow-up.

Table 9.

Significant and Homogeneous Effects of Cognitive Behavioral Therapy of Persistent Positive Symptoms Across Various Control Groups

Outcome Variable	Number of Included Studies	Number of Included Patients	Effect Size (95% CI)	Heterogeneity Qa
Posttreatment
General psychopathology	11	477	0.45 (0.27 to 0.62)	7.41 (P = .69)
Positive symptoms	12	486	0.47 (0.29 to 0.65)	7.82 (P = .73)
Hallucinations	6	259	0.34 (0.09 to 0.58)	1.86 (P = .87)
Follow-up
Positive symptoms	9	335	0.39 (0.17 to 0.61)	4.51 (P = .81)
Delusions	5	196	0.47 (0.18 to 0.75)	2.02 (P = .73)

Note: CI, confidence interval.

^aSum of squares.

Discussion

It remains difficult to draw consistent conclusions from the existing literature on the efficacy of psychological interventions in the therapy of schizophrenic patients. On the one hand, there is sound evidence for the efficacy of these approaches at a general level, suggesting their implementation into routine care. This evidence is based on numerous studies that have been summarized in a series of meta-analyses over the past 2 decades. On the other hand, several important questions are still awaiting an answer. There are marked discrepancies between the results from meta-analyses in the field that only included randomized controlled trials, compared with those that also allowed for observational or quasi-experimental studies. The methodological quality of the included studies is likely to affect the effect sizes as pointed out by Tarrier and Wykes.⁴⁹ There is also some concern about the homogeneity of the therapeutic approaches included in those reviews.

We intended to give an overview of the results from presently available meta-analyses and tried to relate their findings to different specific psychological approaches in the treatment of schizophrenia. In the case of ambiguous results, we complemented them by selected findings from an own recent, but as yet unpublished, meta-analysis. We paid special attention to the methodological homogeneity of the included studies by focusing on randomized controlled trials and to the homogeneity with regard to the contents of the different specific psychological therapy approaches in our meta-analysis. In this way, we also intended to stimulate the discussion on possible fruitful directions of future psychotherapy research in the field.

From the meta-analyses that became available over the past 15 years, 4 distinct strands of psychological therapies for schizophrenic patients have emerged: social skills trainings, cognitive remediation, psychoeducational interventions with families and relatives, and cognitive behavioral therapy of psychotic symptoms. Other approaches still failed to provide a sufficient evidence base (eg, psychodynamic psychotherapy,¹¹ hypnosis⁵⁴).

For social skills training, significant and consistent positive effects on skills acquisition, assertiveness, social functioning, and general psychopathology—which were only reported by those meta-analyses that also included quasi-experimental and observational studies^16,17—were confirmed by our own analysis. This is in contrast to the negative findings in the analysis by Pilling et al,⁷ who also included only randomized controlled trials. The conflicting results might be explained by the higher number of randomized controlled studies we were able to include.

A crucial question regarding social skills training still remains the transfer of the verifiable gains in social skills to general social adjustment and role fulfillment of schizophrenic patients in their daily living environment. In recent years, training approaches such as the “Partners in Autonomous Living” approach or the “In Vivo Amplified Skills Training” were developed, which either include relatives or friends of the patient in order to provide opportunities, encourage, and contingently reinforce the patient's use of acquired skills in daily living or where training became an integral part of a case management program.⁵⁵ However, the data do not yet allow for a final conclusion regarding the additional benefits from these refined approaches. Moreover, findings indicate that the effects of social skills training on social functioning may be enhanced by an increase in cognitive functioning achieved by cognitive remediation.⁵⁶ Thus, further questions arise regarding the synergistic effects of combining social skills training with cognitive remediation or integrating it into the framework of interventions for psychosocial rehabilitation such as supported employment.

Systematic reviews covering cognitive remediation again reveal differences between the analyses that included only randomized controlled trials and those with less stringent inclusion criteria. Whereas no consistent positive effect of cognitive remediation could be found in the analyses that included only randomized trials, we demonstrated small to medium effects on cognitive functioning for this approach in our own analysis.

Because the available studies on cognitive remediation are based on short periods of observation, the question for the durability of these achievements in cognitive functions cannot be answered. Moreover, the strategies and techniques of the different cognitive remediation approaches vary considerably. Therefore, it may not be justified to summarize them under the same label. For future research there is a clear need to evaluate the functional relevance of specific cognitive profiles for certain instrumental and social requirements of daily life. This may help define the corresponding treatment targets and identify the essential common therapeutic components regarding the strategies and techniques of cognitive remediation that relate to these contents. Because the influence of neurocognition on social functioning seems to be widely mediated by social cognition and other metacognitive parameters, these variables may preferably be taken as a target of cognitive remediation. In addition, future training should place strong emphasis on individual profiles of cognitive deficits as not all schizophrenic patients suffer from the same cognitive impairments. Consideration should also be given to motivational factors because there is some evidence that a patient's level of motivation is associated with a beneficial treatment response.⁵⁷

The efficacy of psychoeducational family interventions in reducing relapse and hospitalization rates bas been empirically established by a large number of studies. Results from our own meta-analysis are well in line with the findings of previous systematic reviews. However, as to their implementation in routine care settings, some questions are still unanswered. There is uncertainty about the (cost-)effectiveness and the most efficient treatment format for these approaches. In addition, there is only limited knowledge about what specific components are effective in these approaches. For example, relapse rates seem to depend strongly on the patients' adherence to prescribed medication. To date, investigations have rarely addressed the issue of whether and to what extent the efficacy of psychoeducational coping-oriented therapy approaches may be mainly the consequence of improved medication compliance. It also remains unclear whether the intended improvements in the coping behavior of patients and their relatives play the supposed pivotal role in the efficacy of these interventions.

With regard to cognitive behavioral therapy of psychotic symptoms, the findings of our own meta-analysis in general support the positive findings at hand. But again, specific therapeutic ingredients within the overall toolbox of cognitive behavioral therapy for positive symptoms still need to be identified. Another unanswered question relates to differential indication of cognitive behavioral therapy because the benefits of approaches that are not specifically directed to a reduction of the severity of positive symptoms have not been clearly demonstrated.^6,58 For example, the application of cognitive behavioral therapy in early intervention programs has not yet proven effective.^47,59,60 Moreover, all the present efficacy studies on cognitive behavioral therapy of positive symptoms excluded a considerable number of patients. One main reason for nonacceptance was the patients' refusal to talk about their symptoms.⁶¹

Conclusions

The present state of research provides sound evidence for the efficacy of psychological therapy in the treatment of schizophrenia. However, many questions remain unanswered. These relate to the most efficient treatment setting and to the differential indication of the various psychological interventions. Moreover, the specific therapeutic ingredients still have to be identified. Future research must also focus on the synergistic effects of combinations of psychological interventions with pharmacotherapy or psychosocial rehabilitation programs. The present gaps in knowledge hamper the implementation of effective psychological interventions into routine mental health-care settings because they prevent therapy planning from being economically tailored to the specific needs and resources of individual patients. These gaps in knowledge result from a neglect to study the association between therapy processes and treatment outcomes as well as from the prevailing tendency to regard the efficacy of psychological therapy as independent of the general framework of the mental health-care system. Therefore, it seems essential that future psychotherapy research in schizophrenia will focus on process-outcome relations as well as on (cost-)effectiveness of psychological therapy. Otherwise, budgetary constraints may prevent these promising therapeutic approaches from being implemented into standard mental health care.

Appendix

Included Studies

Social Skills Training

Anzai, N, Yoneda, S, Kumagai, N, Nakamura, Y, Ikebuchi, E, Liberman, RP. Training persons with schizophrenia in illness self-management: a randomized controlled trial in Japan. Psychiatr Serv 2002. ;53545–547. Bellack, AE, Turner, SM, Hersen, M, Luber, RF. An examination of the efficacy of social skills training for chronic schizophrenic patients. Hosp Community Psychiatry 1984. ;351023–1028. Brown, MA and Munford, AM. Life skills training for chronic schizophrenics. J Nerv Ment Dis 1983. ;171466–470. Chien, HC, Ku, CH, Lu, RB, Chu, H, Tao, YH, Chou, KR. Effects of social skills training on improving social skills of patients with schizophrenia. Arch Psychiatr Nurs 2003. ;17228–236. Dobson, DJ, McDougall, G, Busheikin, J, Aldous, J. Effects of social skills training and social milieu treatment on symptoms of schizophrenia. Psychiatr Serv 1995. ;46376–380. Daniels, L. A group cognitive-behavioral and process-oriented approach to treating the social impairment and negative symptoms associated with chronic mental illness. J Psychother Prac Res 1998. ;7167–176. Eckman, TA, Wirshing, WC, Marder, SR, et al. Technique for training schizophrenic patients in illness self-management: a controlled trial. Am J Psychiatry 1992. ;1491549–1555. Marder, SR, Wirshing, WC, Mintz, J, et al. Two-year outcome of social skills training and group psychotherapy for outpatients with schizophrenia. Am J Psychiatry 1996. ;1531585–1592. Finch, BE and Wallace, CJ. Successful interpersonal skills training with schizophrenic inpatients. J Consult Clin Psychol 1977. ;45885–890. Granholm, E, McQuaid, JR, McClure, FS, et al. A randomized, controlled trial of cognitive behavioral social skills training for middle-aged and older outpatients with chronic schizophrenia. Am J Psychiatry 2005. ;162520–529. Hayes, RL, Halford, WK, Varghese, FT. Social skills training with chronic schizophrenic patients: effects on negative symptoms and community functioning. Behav Ther 1995. ;26433–449. Hogarty, GE, Anderson, CM, Reiss, DJ, et al. Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. I. One-year effects of a controlled study on relapse and expressed emotion. Arch Gen Psychiatry 1986. ;43633–642. Hogarty, GE, Anderson, CM, Reiss, DJ, et al. Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. II. Two-year effects of a controlled study on relapse and adjustment. Arch Gen Psychiatry 1991. ;48340–347. Kopelowicz, A, Wallace, CJ, Zarate, R. Teaching psychiatric inpatients to re-enter the community: a brief method of improving the continuity of care. Psychiatr Serv 1998. ;491313–1316. Kopelowicz, A, Zarate, R, Gonzalez Smith, V, Mintz, J, Liberman, RP. Disease management in Latinos with schizophrenia: a family-assisted skills training approach. Schizophr Bull 2003. ;29211–227. Liberman, RP, Wallace, CJ, Falloon, IRH, Vaughn, CE. Interpersonal problem-solving therapy for schizophrenics and their families. Compr Psychiatry 1981. ;22627–630. Wallace, CJ and Liberman, RP. Social skills training for patients with schizophrenia: a controlled clinical trial. Psychiatr Res 1985. ;15239–247. Lukoff, D, Wallace, CJ, Liberman, RP, Burke, K. A holistic program for chronic schizophrenic patients. Schizophr Bull 1986. ;12274–282. Liberman, RP, Wallace, CJ, Blackwell, G, Kopelowicz, A, Vaccaro, JV, Mintz, J. Skills training versus psychosocial occupational therapy for persons with persistent schizophrenia. Am J Psychiatry 1998. ;1551087–1091. Miller, TW, Wilson, GC, Dumas, MA. Development and evaluation of social skills training for schizophrenic patients in remission. J Psychiatr Nurs Ment Health Serv 1979. ;1742–46. Smith, TE, Hull, JW, Romanelli, S, Fertuck, E, Weiss, KA. Symptoms and neurocognition as rate limiters in skills training for psychotic patients. Am J Psychiatry 1999. ;1561817–1818. Tsang, HW and Pearson, V. Work-related social skills training for people with schizophrenia in Hong Kong. Schizophr Bull 2001. ;27139–148. Wallace, CJ, Liberman, RP, MacKain, SJ, Blackwell, G, Eckman, TA. Effectiveness and replicability of modules for teaching social and instrumental skills to the severely mentally ill. Am J Psychiatry 1992. ;149654–658.

Cognitive Remediation

Bell, M, Bryson, G, Greig, T, Corcoran, C, Wexler, BE. Neurocognitive enhancement therapy with work therapy: effects on neuropsychological test performance. Arch Gen Psychiatry 2001. ;58763–768. Bell, M, Bryson, G, Wexler, BE. Cognitive remediation of working memory deficits: durability of training effects in severely impaired and less severely impaired schizophrenia. Acta Psychiatr Scand 2003. ;108101–109. Bellucci, DM, Glaberman, K, Haslam, N. Computer-assisted cognitive rehabilitation reduces negative symptoms in the severely mentally ill. Schizophr Res 2003. ;59225–232. Benedict, RH, Harris, AE, Markow, T, McCormick, JA, Nuechterlein, KH, Asarnow, RF. Effects of attention training on information processing in schizophrenia. Schizophr Bull 1994. ;20537–546. Funke, B, Reinecker, H, Commichau, A. Grenzen kognitiver Trainingsmethoden bei schizophrenen Langzeitpatienten. Nervenarzt 1989. ;60750–756. Hadas, LN, Katz, N, Tyano, S, Weizman, A. Effectiveness of dynamic cognitive intervention in rehabilitation of clients with schizophrenia. Clin Rehab 2001. ;15349–359. Hermanutz, M and Gestrich, J. Computer-assisted attention training in schizophrenics: a comparative study. Eur Arch Psychiatry Clin Neuroscience 1991. ;240282–287. Hogarty, GE, Flesher, S, Ulrich, R, et al. Cognitive enhancement therapy for schizophrenia. Effects of a 2-year randomized trial on cognition and behavior. Arch Gen Psychiatry 2004. ;61866–876. Kraemer, S, Sulz, KH, Schmid, R, Laessle, R. Kognitive Therapie bei standardversorgten schizophrenen Patienten. Nervenarzt 1987. ;5884–90. Medalia, A, Aluma, M, Tryon, W, Merriam, AE. Effectiveness of attention training in schizophrenia. Schizophr Bull 1998. ;24147–152. Medalia, A, Revheim, N, Casey, M. Remediation of memory disorders in schizophrenia. Psychol Med 2000. ;301451–1459. Medalia, A, Revheim, N, Casey, M. The remediation of problem-solving skills in schizophrenia. Schizophr Bull 2001. ;27259–267. Medalia, A, Revheim, N, Casey, M. Remediation of problem-solving skills in schizophrenia: evidence of a persistent effect. Schizophr Res 2002. ;57165–171. Sartory, G, Zorn, C, Groetzinger, G, Windgassen, K. Computerized cognitive remediation improves verbal learning and processing speed in schizophrenia. Schizophr Res 2005. ;75219–223. Spaulding, WD, Reed, D, Sullivan, M, Richardson, C, Weiler, M. Effects of cognitive treatment in psychiatric rehabilitation. Schizophr Bull 1999. ;25657–676. Van der Gaag, M, Kern, RS, van den Bosch, RJ, Liberman, RP. A controlled trial of cognitive remediation in schizophrenia. Schizophr Bull 2002. ;28167–176. Vauth, R, Barth, A, Stieglitz, RD. Evaluation eines kognitiven Strategietrainings in der ambulanten beruflichen Rehabilitation Schizophrener. Z Klin Psychol Psychother 2001. ;30251–258. Vauth, R, Corrigan, PW, Clauss, M, et al. Cognitive strategies versus self-management skills as adjunct to vocational rehabilitation. Schizophr Bull 2005. ;3155–66. Velligan, DI, Bow-Thomas, CC, Huntzinger, C, et al. Randomized controlled trial of the use of compensatory strategies to enhance adaptive functioning in outpatients with schizophrenia. Am J Psychiatry 2000. ;1571317–1323. Velligan, DI, Prihoda, TJ, Ritch, JL, Maples, N, Bow-Thomas, CC, Dassori, A. A randomized single-blind pilot study of compensatory strategies in schizophrenia outpatients. Schizophr Bull 2002. ;28283–292. Wykes, T, Reeder, C, Corner, J, Williams, C, Everitt, B. The effects of neurocognitive remediation on executive processing in patients with schizophrenia. Schizophr Bull 1999. ;25291–307. Wykes, T, Reeder, C, Williams, C, Rice, C, Everitt, B. Are the effects of cognitive remediation therapy (CRT) durable? Results from an exploratory trial in schizophrenia. Schizophr Res 2003. ;61163–174.

Psychoeducational Coping-Oriented Interventions With Families and Relatives' Groups

Bäuml, J, Kissling, W, Meurer, C, Wais, A, Lauter, H. Informationszentrierte Angehörigengruppen zur Complianceverbesserung bei schizophrenen Patienten. Psychiatr Prax 1991. ;1848–54. Buchkremer, G, Schulze Mönking, H, Holle, R, Hornung, WP. The impact of therapeutic relatives' groups on the course of illness of schizophrenic patients. Eur Psychiatry 1995. ;1017–27. Chien, WT and Chan, SWC. One-year follow-up of a multiple-family-group intervention for Chinese families of patients with schizophrenia. Psychiatr Serv 2004. ;551276–1284. Dyck, DG, Short, RA, Hendryx, MS, et al. Management of negative symptoms among patients with schizophrenia attending multiple-family groups. Psychiatr Serv 2000. ;51513–519. Dyck, DG, Hendryx, MS, Short, RA, Voss, WD, McFarlane, WR. Service use among patients with schizophrenia in psychoeducational multiple-family group treatment. Psychiatr Serv 2002. ;53749–754. Falloon, IR, Boyd, JL, McGill, CW, Razani, J, Moss, HB, Gilderman, AM. Family management in the prevention of exacerbations of schizophrenia: a controlled study. New Engl J Med 1982. ;3061437–1440. Falloon, IR, Boyd, JL, McGill, CW, et al. Family management in the prevention of morbidity of schizophrenia. Clinical outcome of a two-year longitudinal study. Arch Gen Psychiatry 1985. ;42887–896. Falloon, IR, McGill, CW, Boyd, JL, Pederson, J. Family management in the prevention of morbidity of schizophrenia: social outcome of a two-year longitudinal study. Psychol Med 1987. ;1759–66. Glynn, SM, Randolph, ET, Eth, S, et al. Schizophrenic symptoms, work adjustment, and behavioral family therapy. Rehab Psychol 1992. ;37323–338. Randolph, ET, Eth, S, Glynn, SM, et al. Behavioural family management in schizophrenia. Outcome of a clinic-based intervention. Br J Psychiatry 1994. ;164501–506. Goldstein, MJ, Rodnick, EH, Evans, JR, May, PR, Steinberg, MR. Drug and family therapy in the aftercare of acute schizophrenics. Arch Gen Psychiatry 1978. ;351169–1177. Hogarty, GE, Anderson, CM, Reiss, DJ, et al. Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. I. One-year effects of a controlled study on relapse and expressed emotion. Arch Gen Psychiatry 1986. ;43633–642. Hogarty, GE, Anderson, CM, Reiss, DJ, et al. Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. II. Two-year effects of a controlled study on relapse and adjustment. Arch Gen Psychiatry 1991. ;48340–347. Hornung, WP, Holle, R, Schulze-Mönking, H, Klinberg, S, Buchkremer, G. Psychoedukativ-psychotherapeutische Behandlung von schizophrenen Patienten und ihren Bezugspersonen Ergebnisse einer 1-Jahres-Katamnese. Nervenarzt 1995. ;66828–834. Buchkremer, G, Klingberg, S, Holle, R, Schulze-Mönking, H, Hornung, WP. Psychoeducational psychotherapy for schizophrenic patients and their key relatives or care-givers: results of a 2-year follow-up. Acta Psychiatr Scand 1997. ;96483–491. Leff, J, Kuipers, L, Berkowitz, R, Eberlein-Vries, R, Sturgeon, D. A controlled trial of social intervention in the families of schizophrenic patients. Br J Psychiatry 1982. ;141121–134. Leff, J, Kuipers, L, Berkowitz, R, Sturgeon, D. A controlled trial of social intervention in the families of schizophrenic patients: two-year follow-up. Br J Psychiatry 1985. ;146594–600. Leff, J, Berkowitz, R, Shavit, N, Strachan, A, Glass, I, Vaughn, C. A trial of family therapy vs. a relatives group for schizophrenia. Br J Psychiatry 1989. ;15458–66. Leff, J, Berkowitz, R, Shavit, N, Strachan, A, Glass, I, Vaugh, C. A trial of family therapy versus a relatives' group for schizophrenia. Two-year follow-up. Br J Psychiatry 1990. ;157571–577. Leff, J, Sharpley, M, Chisholm, D, Bell, R, Gamble, C. Training community psychiatric nurses in schizophrenia family work: a study of clinical and economic outcomes for patients and relatives. J Ment Health U K 2001. ;10189–197. Linszen, DH, Dingemans, PMAJ, Van der Does, AJW, et al. Treatment, expressed emotion and relapse in recent onset schizophrenic disorders. Psychol Med 1996. ;26333–342. Nugter, MA, Dingemans, PMAJ, Linszen, DH, Van der Does, AJW, Gersons, BP. Parental communication deviance: its stability and the effect of family treatment in recent-onset schizophrenia. Acta Psychiatr Scand 1997. ;95199–204. McFarlane, WR, Lukens, ELB, Dushay, R, et al. Multiple-family groups and psychoeducation in the treatment of schizophrenia. Arch Gen Psychiatry 1995. ;52679–687. McFarlane, WR, Link, B, Dushay, R, Marchal, J, Crifly, J. Psychoeducational multiple family groups: four-year relapse outcome in schizophrenia. Fam Process 1995. ;34127–144. Merinder, LB, Viuff, AG, Laugesen, HD, Clemmensen, K, Misfelt, S, Espensen, B. Patient and relative education in community psychiatry: a randomized controlled trial regarding its effectiveness. Soc Psychiatry Psychiatr Epidemiol 1999. ;34287–294. Montero, I, Asencio, A, Hernandez, I, et al. Two strategies for family intervention in schizophrenia: a randomized trial in a Mediterranean environment. Schizophr Bull 2001. ;27661–670. Mingyuan, Z, Heqin, Y, Chengde, Y, et al. Effectiveness of psychoeducation of relatives of schizophrenic patients: a prospective cohort study in five cities of China. Int J Ment Health 1993. ;2247–59. Posner, CM, Wilson, KG, Kral, MJ, Lander, S, McIlwraith, RD. Family psychoeducational support groups in schizophrenia. Am J Orthopsychiatry 1992. ;62206–218. Ran, MS, Xiang, MZ, Chan, CLW, et al. Effectiveness of psychoeducational intervention for rural Chinese families experiencing schizophrenia. A randomised controlled trial. Soc Psychiatry Psychiatr Epidemiol 2003. ;3869–75. Schooler, NR, Keith, SJ, Severe, JB, et al. Relapse and rehospitalization during maintenance treatment of schizophrenia. The effects of dose reduction and family treatment. Arch Gen Psychiatry 1997. ;54453–463. Shimodera, S, Inoue, S, Mino, Y, Tanaka, S, Kii, M, Motoki, Y. Expressed emotion and psychoeducational intervention for relatives of patients with schizophrenia: A randomized controlled study in Japan. Psychiatry Res 2000. ;96141–148. Smith, JV and Birchwood, MJ. Specific and non-specific effects of educational intervention with families living with a schizophrenic relative. Br J Psychiatry 1987. ;150645–652. Szmukler, GI, Herrman, H, Colusa, S, Benson, A, Bloch, SA. A controlled trial of a counselling intervention for caregivers of relatives with schizophrenia. Soc Psychiatry Psychiatr Epidemiol 1996. ;31149–155. Tarrier, N, Barrowclough, C, Vaughn, C, et al. The community management of schizophrenia. A controlled trial of a behavioural intervention with families to reduce relapse. Br J Psychiatry 1988. ;153532–542. Tarrier, N, Barrowclough, C, Vaughn, C, et al. Community management of schizophrenia: A two-year follow-up of a behavioral intervention with families. Br J Psychiatry 1989. ;154625–628. Tomaras, V, Mavreas, V, Economou, M, Ioannovich, E, Karydi, V, Stefanis, C. The effect of family intervention on chronic schizophrenics under individual psychosocial treatment: a 3-year study. Soc Psychiatry Psychiatr Epidemiol 2000. ;35487–493. Vaughan, K, Doyle, M, McConaghy, N, Blaszczynski, A, Fox, A, Tarrier, N. The Sydney intervention trial: a controlled trial of relatives' counselling to reduce schizophrenic relapse. Soc Psychiatry Psychiatr Epidemiol 1992. ;2716–21. Xiang, M, Ran, M, Li, S. A controlled evaluation of psychoeducational family intervention in a rural Chinese community. Br J Psychiatry 1994. ;165544–548. Xiong, W, Phillips, MR, Hu, X, et al. 1994 Family-based intervention for schizophrenic patients in China. A randomised controlled trial. Br J Psychiatry 1994. ;165239–247. Zastowny, TR, Lehman, AF, Cole, RE, Kane, C. Family management of schizophrenia: a comparison of behavioral and supportive family treatment. Psychiatr Q 1992. ;63159–186. Zhang, M, Wang, M, Li, J, Phillips, MR. Randomised-control trial of family intervention for 78 first-episode male schizophrenic patients. An 18-month study in Suzhou, Jiangsu. Br J Psychiatry 1994. ;165suppl 2496–102.

Cognitive behavioral therapy of positive symptoms

Cather, C, Penn, D, Otto, MW, Yovel, I, Mueser, KT, Goff, DC. A pilot study of functional cognitive behavioral therapy (fcbt) for schizophrenia. Schizophr Res 2004. ;74201–209. Durham, RC, Guthrie, M, Morton, RV, et al. Tayside-Fife clinical trial of cognitive-behavioural therapy for medication-resistant psychotic symptoms: results to 3-month follow-up. Br J Psychiatry 2003. ;182303–311. Drury, V, Birchwood, M, Cochrane, R, MacMillan, F. Cognitive therapy and recovery from acute psychosis: a controlled trial. I. Impact on psychotic symptoms. Br J Psychiatry 1996. ;169593–601. Drury, V, Birchwood, M, Cochrane, R, MacMillan, F. Cognitive therapy and recovery from acute psychosis: a controlled trial. II. Impact on recovery time. Br J Psychiatry 1996. ;169602–607. Haddock, G, Tarrier, N, Morrison, AP, Hopkins, R, Drake, R, Lewis, S. A pilot study evaluating the effectiveness of individual inpatient cognitive-behavioural therapy in early psychosis. Soc Psychiatry Psychiatr Epidemiol 1999. ;34254–258. Jenner, JA, Nienhuis, FJ, Wiersma, D, van de Willige, G. Hallucination focused integrative treatment: a randomized controlled trial. Schizophr Bull 2004. ;30133–145. Kuipers, E, Garety, P, Fowler, D, et al. London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. I: effects of the treatment phase. Br J Psychiatry 1997. ;171319–327. Kuipers, E, Fowler, D, Garety, P, et al. London-East Anglia randomised controlled trial of cognitive-behavioural therapy for psychosis. III: follow-up and economic evaluation at 18 months. Br J Psychiatry 1998. ;17361–68. Levine, J, Barak, Y, Granek, I. Cognitive group therapy for paranoid schizophrenics: applying cognitive dissonance. J Cognit. Psychother 1998. ;123–12. Lewis, S, Tarrier, N, Haddock, G, et al. Randomised controlled trial of cognitive-behavioural therapy in early schizophrenia: acute-phase outcomes. Br J Psychiatry 2002. ;181suppl 4391–97. Pinto, A, La Pia, S, Mennella, R, Giorgio, D, DeSimone, L. Cognitive-behavioral therapy and clozapine for clients with treatment-refractory schizophrenia. Psychiatr Serv 1999. ;50901–904. Rector, NA, Seeman, MV, Segal, ZV. Cognitive therapy for schizophrenia: a preliminary randomized controlled trial. Schizophr Res 2003. ;631–11. Sensky, T, Turkington, D, Kingdon, D, et al. A randomized controlled trial of cognitive-behavioral therapy for persistent symptoms in schizophrenia resistant to medication. Arch Gen Psychiatry 2000. ;57165–172. Startup, M, Jackson, MC, Bendix, S. North Wales randomized controlled trial of cognitive behaviour therapy for acute schizophrenia spectrum disorders: outcomes at 6 and 12 months. Psychol Med 2004. ;34413–422. Tarrier, N, Beckett, R, Harwood, S, Baker, A, Yusupoff, L, Ugarteburu, I. A trial of two cognitive-behavioural methods of treating drug-resistant residual psychotic symptoms in schizophrenic patients. I: outcome. Br J Psychiatry 1993. ;162524–532. Tarrier, N, Yusupoff, L, Kinney, C, et al. Randomised controlled trial of intensive cognitive behaviour therapy for patients with chronic schizophrenia. BMJ 1998. ;317303–307. Tarrier, N, Wittkowski, A, Kinney, C, McCarthy, E, Morris, J, Humphreys, L. Durability of the effects of cognitive-behavioural therapy in the treatment of chronic schizophrenia: 12-month follow-up. Br J Psychiatry 1999. ;174500–504. Tarrier, N, Kinney, C, McCarthy, E, Humphreys, L, Wittkowski, A, Morris, J. Two-year follow-up of cognitive-behavioral therapy and supportive counseling in the treatment of persistent symptoms in chronic schizophrenia. J Consult Clin Psychol 2000. ;68917–922. Tarrier, N, Lewis, S, Haddock, G, et al. Cognitive-behavioural therapy in first-episode and early schizophrenia: 18-month follow-up of a randomised controlled trial. Br J Psychiatry 2004. ;184231–239. Trower, P, Birchwood, M, Meaden, A, Byrne, S, Nelson, A, Ross, K. Cognitive therapy for command hallucinations: randomised controlled trial. Br J Psychiatry 2004. ;184312–320. Turkington, D and Kingdon, D. Cognitive behavioural techniques for general psychiatrists in the management of patients with psychoses. Br J Psychiatry 2000. ;177101–106. Valmaggia, LR, van der Gaag, M, Tarrier, N, Pijnenborg, M, Slooff, CJ. Cognitive-behavioural therapy for refractory psychotic symptoms of schizophrenia resistant to atypical antipsychotic medication. Br J Psychiatry 2005. ;186324–330. Wiersma, D, Jenner, JA, Nienhuis, FJ, van de Willige, G. Hallucination focused integrative treatment improves quality of life in schizophrenia patients. Acta Psychiatr Scand 2004. ;109194–201.

Excluded studies

Bach, P and Hayes, SC. The use of acceptance and commitment therapy to prevent the rehospitalization of psychotic patients: a randomized controlled trial. J Consult Clin Psychol 2002. ;701129–1139. Barrowclough, C, Tarrier, N, Lewis, S, et al. Randomised controlled effectiveness trial of a needs-based psychosocial intervention service for carers of people with schizophrenia. Br J Psychiatry 1999. ;174505–511. Bechdolf, A, Knost, B, Kuntermann, C, et al. A randomized comparison of group cognitive-behavioural therapy and group psychoeducation in patients with schizophrenia. Acta Psychiatr Scand 2004. ;11021–28. Bradshaw, W. Integrating cognitive-behavioral psychotherapy for persons with schizophrenia into a psychiatric rehabilitation program: results of a three year trial. Community Ment Health J 2000. ;36491–500. De-Giacomo, P, Pierri, G, Santoni, RA, Buonsante, M. Schizophrenia: a study comparing a family therapy group following a paradoxical model plus psychodrugs and a group treated by the conventional clinical approach. Acta Psychiatr Scand 1997. ;95183–188. Fries, A, Pfammatter, M, Andres, K, Brenner, HD. Wirksamkeit und Prozessmerkmale einer psychoedukativen bewältigungsorientierten Gruppentherapie für schizophren und schizoaffektiv Erkrankte. Verhaltenstherapie 2003. ;13237–243. Gumley, A, O'Grady, M, McNay, L, Reilly, J, Power, K, Norrie, J. Early intervention for relapse in schizophrenia: results of a 12-month randomized controlled trial of cognitive behavioural therapy. Psychol Med 2003. ;33419–431. Herz, MI, Lamberti, JS, Mintz, J, et al. A program for relapse prevention in schizophrenia: a controlled study. Arch Gen Psychiatry 2000. ;57277–283. Hogarty, GE, Kornblith, SJ, Greenwald, D, et al. Three-year trials of personal therapy among schizophrenic patients living with or independent of family. I: description of study and effects on relapse rates. Am J Psychiatry 1997. ;1541504–1513. Hogarty, GE, Greenwald, D, Ulrich, RF, et al. Three-year trials of personal therapy among schizophrenic patients living with or independent of family. II: effects on adjustment of patients. Am J Psychiatry 1997. ;1541514–1524. Lamontagne, Y, Audet, N, Elie, R. Thought-stopping for delusions and hallucinations: a pilot study. Behav Psychother 1983. ;11177–184. Leclerc, C, Lesage, AD, Ricard, N, Lecomte, T, Cyr, M. Assessment of a new rehabilitative coping skills module for persons with schizophrenia. Am J Orthopsychiatry 2000. ;70380–388. Lecompte, D and Pelc, I. A cognitive-behavioral program to improve compliance with medication in patients with schizophrenia. Int J Ment Health 1996. ;2551–56. Lecomte, T, Cyr, M, Lesage, AD, Wilde, J, Leclerc, C, Ricard, N. Efficacy of a self-esteem module in the empowerment of individuals with schizophrenia. J Nerv Ment Dis 1999. ;187406–413. Malm, U. The influence of group therapy on schizophrenia. Acta Psychiatr Scand 1982. ;65suppl 2971–65. Malm, U, Ivarsson, B, Allebeck, P, Falloon, IRH. Integrated care in schizophrenia: a 2-year randomized controlled study of two community-based treatment programs. Acta Psychiatr Scand 2003. ;107415–423. Meichenbaum, D and Cameron, R. Training schizophrenics to talk to themselves: a means of developing attention controls. Behav Ther 1973. ;4515–534. Norman, RM, Malla, AK, McLean, TS, et al. An evaluation of a stress management program for individuals with schizophrenia. Schizophr Res 2002. ;58293–303. O'Donnell, C, Donohoe, G, Sharkey, L, et al. Compliance therapy: a randomised controlled trial in schizophrenia. BMJ 2003. ;3271–4. Turkington, D, Kingdon, D, Turner, T. Effectiveness of a brief cognitive-behavioural therapy intervention in the treatment of schizophrenia. Br J Psychiatry 2002. ;180523–527. Vallina-Fernandez, O, Lemos-Giraldez, S, Roder, V, et al. Controlled study of an integrated psychological intervention in schizophrenia. Eur J Psychiatry 2001. ;15167–179. Weinman, B, Gelbart, P, Wallace, M, Post, M. Inducing assertive behavior in chronic schizophrenics: a comparison of socioenvironmental, desensitization, and relaxation therapies. J Consult Clin Psychol 1972. ;39246–252. Weingaertner, AH. Self-administered aversive stimulation with hallucinating hospitalized schizophrenics. J Consult Clin Psychol 1971. ;36422–429.