Cognitive-behavioral therapy for negative symptoms of A systematic review and meta-analysis

Authors: Feifei Xu, Sheng Xu

Abstract

Background:

Cognitive-behavioral intervention techniques are increasingly demonstrating their efficacy in preventing relapses and managing problems in patients with schizophrenia. There is still variation in its effectiveness for negative symptoms, such as mood-related symptoms and motivation to engage socially.

Methods:

A systematic search was conducted in PubMed, Web of Science for English literature on cognitive-behavioral therapy (CBT) interventions in patients with schizophrenia. The search included randomized controlled trials and nonrandomized controlled trials. The search period extended from the inception of the databases to September 30, 2022. Two researchers independently performed quality assessment and data extraction based on predefined inclusion and exclusion criteria.

Results:

Discrepancies were resolved through discussion or consultation with a third researcher. Initially, 169 articles were retrieved through database searches and other means. After applying the inclusion and exclusion criteria, 10 randomized controlled studies were included in the final analysis. The intervention group comprised a total of 680 patients with schizophrenia, while the control group included 686 patients with schizophrenia. Meta-analysis results demonstrated a statistically significant difference in negative symptom reduction between the CBT intervention group (WMD = −1.19, 95% CI [−1.73, −0.66], P < .0001) and the control group.

Conclusion:

We have analyzed the effectiveness of CBT based on our previous research, CBT was found to effectively improve negative symptoms in individuals diagnosed with schizophrenia.

1. Introduction

Schizophrenia is a severe mental disorder that has a profound impact on the patient’s physical and psychological well-being, causing lifelong disability.^[1]^ Clinically, positive symptoms such as hallucinations and delusions, negative symptoms including emotional retardation and social withdrawal, and cognitive dysfunction are commonly observed and considered the core symptoms of schizophrenia.^[2,3]^ These long-term psychiatric symptoms ultimately result in reduced social functioning for the patient, affecting both their recovery and overall quality of life.^[4,5]^ While antipsychotic medications have been proven effective in alleviating positive symptoms and reducing the risk of relapse.^[6,7]^ They do not effectively address negative symptoms or cognitive impairment, and may even lead to deterioration in cognitive function.^[8,9]^ Therefore, it is of utmost importance to address the negative symptoms and cognitive function of patients given their significant impact on their lives.^[10]^

As a result, psychosocial treatment has evolved from its pessimistic beginnings (which believed that personality disorganization was an unavoidable consequence of psychotic cognitive deficits, thus preventing the use of psychotherapy) to a wide range of interventions aimed at rehabilitating patients. Today, psychosocial strategies are recognized as an important component of schizophrenia treatment, particularly when medications have limited effectiveness in improving negative symptoms.^[11]^ Although these symptoms are less noticeable than the positive symptoms, they are the most reliable long-term indicator of disease-related disability and impact the patient’s ability to function in daily life.^[12–14]^ In recent years, cognitive-behavioral therapy (CBT) has emerged as a psychotherapeutic approach in the clinical treatment of schizophrenic patients and has been recommended as a standard treatment for schizophrenic patients in Western countries.^[15,16]^ Cognitive-behavioral intervention techniques are increasingly demonstrating their efficacy in preventing relapses^[17]^ and managing problems in patients with schizophrenia^[18]^; They promote recovery and community integration by targeting key aspects of functioning such as symptom stability, independent living, employment, and social functioning. Studies have shown that CBT is generally effective in improving positive symptoms of schizophrenia, such as hallucinations and delusions,^[19,20]^ However, there is still variation in its effectiveness for negative symptoms, such as mood-related symptoms and motivation to engage socially.^[21,22]^ Conducting a meta-analysis can help researchers find reliable evidence from a multitude of studies. This study aimed to summarize and analyze previous studies through meta-analysis to determine the efficacy of CBT on negative symptoms of schizophrenia. This will provide a more reliable basis for the clinical application of CBT.

2. Materials and methods

This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This review has been registered in PROSPERO (Registration Number: CRD42023421071). This study is a review article and the ethical statement is not applicable.

2.1. Data sources and retrieval

An inclusive literature was searched in PubMed and web of science databases, respectively, from the date of establishment to September 30, 2022. The search terms were (schizophrenia) and (CBT) and (randomized controlled study). Foreign language database search (psychosis OR psychotic OR schizophrenia) AND (cognitive therapy OR cognitive behavior therapy OR CBT) AND (Randomized Controlled Trial) and Manual search for published literature.

Effect sizes (Cohen d) of each study and overall were calculated under a random-effect model with 95% confidence intervals.

2.2. Inclusion and exclusion criteria of the literature

2.2.1. Inclusion criteria

The type of study in the literature was an independent randomized controlled study; patients with schizophrenia according to DSM-5 diagnostic criteria; and able to directly extract or calculate the sample content, mean and standard deviation of positive and negative syndrome scale (PANSS) scale scores.

2.2.2. Exclusion criteria

Studies in which patients with schizophrenia had other types of disorders such as brain injury or more severe cognitive impairment; studies related to schizophrenia symptoms such as reviews, case reports, conference abstracts, and research plans; studies in which the study population, study type, interventions, and outcome indicators did not meet the inclusion criteria; studies in which the full text was not available, valid data could not be extracted, or the original data could not be requested; and studies with duplicate reports; quality assessment and data extraction.

2.3. Quality assessment and data extraction

Two researchers conducted literature screening and data extraction according to the inclusion and exclusion criteria, and cross-checked after completion. The screening included title, abstract, study subjects, study instruments, study parameters, and full-text screening. Two evaluators independently assessed the included literature according to the risk of bias assessment tool provided in the Cochrane Handbook version 5.1.0. The main criteria random sequence generation; allocation concealment; blinding of investigators and subjects; blinding of outcome evaluators; data integrity; selective reporting bias; and other biases. If all of these criteria are met, the risk of bias is minimal and the assessment level is A. If these criteria are partially met, the risk of bias is moderate and the assessment level is B. If these criteria are not met at all, the risk of bias is highest and the assessment level is C.

2.4. Statistical analysis

Meta-analysis was performed using Review Manager 5.3 software. Heterogeneity among the included literature was tested by Q test and I^2^ test, and if P ≥ .1 and I^2^ ≤ 50%, a fixed-effect model was used for meta-analysis, and when P < .1 and/or I^2^ > 50%, a random-effect model was selected for meta-analysis, and subgroup analysis was performed to explore the sources of heterogeneity. The impact of publication bias on the results was evaluated using funnel plots for qualitative evaluation and quantitative analysis of reporting bias, respectively, and sensitivity analysis was performed using the subtraction method.

Effect indicators for measures were expressed as mean difference (MD) or weighted mean difference (WMD) with 95% CI; if the same measurement tool was used to evaluate the same outcome, the combined effect statistic was expressed as weighted mean difference WMD; if different measurement tools were used, the combined effect statistic was expressed as If different instruments were used, the combined effect statistic was expressed as standardized mean difference.

3. Results

3.1. Results of the literature search

A total of 169 articles were retrieved from the database as well as other means, and were further screened according to the inclusion and exclusion criteria, and 10 randomized controlled studies were finally included, including a total of 680 patients with schizophrenia in the intervention group, and a total of 686 patients with schizophrenia in the control group, and the process of the screening of the literature and the results are shown in Figure 1

3.2. Basic characteristics and quality assessment of the included literature

A total of 10 English-language papers were included, and all studies used the PANSS scale to assess negative symptoms in patients with schizophrenia. Five studies were short term interventions (T < 16 weeks) and 5 studies were long-term interventions (T > 16weeks). CBT was used in the intervention group in all studies, and TAU, ST, SC, and CR were used in the control group. The literature was evaluated for quality using the scale Cochrane Handbook version 5.1.0. The included literature ended up with 3 A grades and 7 B grades. The basic characteristics and quality assessment of the included literature (Table 1).

3.3. Results of meta-analysis

3.3.1. Heterogeneity test

The heterogeneity test was performed on the 10 selected papers, and it was found that the heterogeneity among these papers was weak (I^2^ = 33%). So fixed effect model was chosen for meta-analysis. Negative symptoms in CBT intervention group (WMD = −1.19, 95% CI: [−1.73, −0.66], P < .0001) showed that there was an decrease in the negative symptoms in the intervention group as compared to the control group and it was statistically significant (Fig. 2).

3.3.2. Publication bias

The funnel plot of the 10 included papers found that 9 papers were essentially symmetrical and only 1 was biased, allowing further sensitivity analysis (Fig. 3).

3.3.3. Sensitivity analysis

The sensitivity analysis revealed that this study of Preethi Premkumar^[23]^ was different from other studies in that there was no mention of whether the experiment was double-blind or not in the literature. The meta-analysis was done after excluding this study and the resulting combined effect size (WMD = −1.08, 95% CI: [−1.63, −0.54], Z = 3.89, P = .0001) showed that CBT therapy combined with conventional therapy was more effective than conventional therapy alone, and the difference was statistically significant. Its heterogeneity results and combined effect size test (Fig. 4).

3.3.4. Subgroup analysis

Subgroup analysis based on intervention time showed that symptom changes were statistically different in both subgroups. Short term intervention (WMD = −1.08, 95% CI: [−1.80, −0.35], P = .004), long-term intervention (WMD = −1.34, 95% CI: [−2.13, −0.54], P = .001) (Fig. 5).

4. Discussion

CBT has been shown to be significantly effective in treating the positive symptoms of schizophrenia, but its impact on improving negative symptoms varies. This study conducted a meta-analysis of 10 papers and found that CBT therapy is more effective than single conventional treatment in improving negative symptoms of schizophrenia. Furthermore, it was observed that shorter interventions (<16 weeks) were also effective in improving negative symptoms compared to longer interventions (>16 weeks).

Negative symptoms are characterized by deficits or reductions in mood, as well as social and behavioral impairments. They are considered 1 of the core symptoms of schizophrenia and are among the most important predictors of its quality of life and functional outcomes.^[24,25]^ Additionally, negative symptoms can be transient or a result of antipsychotic medication.^[26,27]^ The treatment of negative symptoms in schizophrenia presents significant challenges to mental health care providers. Therefore, researchers must consider medication side effects in their studies and strive to balance the number of treatments so that the intervention outweighs the medication side effects as much as possible. It is possible that CBT accelerates symptom recovery by promoting cognitive changes, as supported by recent research findings. However, there is still a lack of research on negative symptoms in clinical settings, and the effectiveness of CBT can only be fully understood through large-sample randomized controlled trials.^[28]^ If the negative symptoms of psychiatric patients remain unresolved for a prolonged period, they may develop into other psychiatric disorders such as depression,^[29]^ causing significant impairment to their lives and social functioning.

The results of the sensitivity analysis revealed heterogeneity (I^2^ = 33%). Subsequent analysis revealed that the study by Premkumar^[23]^ did not mention whether it was double-blind or not in terms of the experimental methodology. This suggests that the rigor of the experimental design could influence the effect of the intervention. Additionally, this study had a smaller sample size compared to others, which may contribute to the heterogeneity. After removing this literature, the remaining 9 studies were still heterogeneous (I^2^ = 10%). From the analysis of the included studies, it can be concluded that the low quality of the study design and the inconsistency of the diagnostic criteria could be important factors affecting the results. Therefore, future studies and clinical treatments should prioritize rigorous experimental design, the professionalism of doctors, and the selection of intervention methods. The mechanism of action of CBT is still unclear, making it necessary to determine personalized intervention methods based on the patients’ individual situations. Inappropriate use of the therapy may result in ineffective or adverse effects.^[30]^ From the current study, contemporary CBT-based interventions usually focus more on overall treatment goals. For example, interventions have been studied for both positive and negative symptoms together, rather than being targeted to address patient-specific issues.^[31]^ The duration of intervention greatly influences its effectiveness, so the frequency and duration of the intervention should be carefully regulated to achieve better results.

Different etiological mechanisms may require tailored and individualized treatments, thus necessitating further assessment. Cognitive-behavioral interventions aimed at addressing negative symptoms and changing irrational beliefs that strongly impact symptoms are crucial. These negative beliefs may include feelings of social isolation, low self-esteem, and pessimistic expectations for happiness and success. Additionally, negative beliefs triggered by positive symptoms should also be considered.^[32]^ For instance, a patient experiencing negative symptoms predominantly rooted in dysfunctional beliefs regarding their work ability (in the absence of severe objective cognitive impairment) could benefit from CBT emphasizing exposure and behavioral activation. Behavioral activation has demonstrated effectiveness in reducing depression and may also alleviate adverse symptoms in individuals diagnosed with schizophrenia who share these dysfunctional beliefs.^[33]^ However, it is important to consider the patient’s acceptance of these techniques to avoid any potential adverse effects. In cases where a patient may not find the above methods acceptable, alternative interventions must be explored.

Studies have shown that CBT is effective in improving psychiatric symptoms by targeting patients’ cognition, disease prognosis, and overall treatment. The therapeutic effect of CBT was still evident even after 3 months posttreatment.^[32]^ However, due to its mechanism of action and potential subjectivity in its implementation, there are various challenges in controlling clinical research. In this particular study, the literature search focused solely on the PANSS scale as a measurement tool, overlooking the frequent use of the scale for assessment of negative symptoms scale in clinical research. Hence, future studies should be more precise and consider different measurement tools and diagnostic criteria. This study has several firstly, there was significant variation in study design and target population among the different meta-analyses included, despite attempts to examine studies specifically involving patients with negative symptoms alone. However, the advantage of meta-analysis lies in its ability to combine and analyze diverse studies to obtain more generalized results. Secondly, most studies did not specifically aim to reduce negative symptoms and therefore did not select patients based on the severity of these symptoms. Moreover, the majority of studies focused on overall symptom scores rather than specific subdimensions, which could be improved in future research to explore the sensitivity of CBT therapy towards negative symptoms. Thirdly, the choice of measurement tools used in this study also influenced the results, with concerns raised about the outdated item content and sensitivity to change of both the PANSS and scale for assessment of negative symptoms. Hence, more sensitive measures should be identified to assess symptoms in individuals with schizophrenia. Lastly, it was not possible to isolate the effects of antipsychotic medications in the CBT trial.

In summary, CBT does have better efficacy on negative symptoms of schizophrenia patients, and the improvement of negative symptoms is extremely important for patients, and the improvement of negative symptoms can enhance the social function of patients, which is of great significance for the prognosis of patients’ rehabilitation and slowing down the development of the disease.

Author contributions

Conceptualization: Sheng Xu.

**Data ** Feifei Xu.

**Funding ** Feifei Xu, Sheng Xu.

Methodology: Sheng Xu.

**Project ** Feifei Xu, Sheng Xu.

Software: Feifei Xu.

Supervision: Feifei Xu.

Validation: Sheng Xu.

Visualization: Feifei Xu.

**Writing – original ** Feifei Xu.

**Writing – review & ** Sheng Xu.