Computerized cognitive behavioral therapy with sertraline in schizophrenia with depressive episodes: A 12-week randomized controlled trial

Abstract

BACKGROUND

Schizophrenia is commonly associated with comorbid depression, which exacerbates cognitive impairments and negatively impacts quality of life. Despite the high prevalence and burden of these comorbidities, effective treatment options, particularly for cognitive dysfunction, remain limited.

AIM

To evaluate the efficacy of computerized cognitive behavioral therapy (CCBT) with sertraline vs sertraline monotherapy in improving depressive symptoms, cognitive function, and quality of life in schizophrenia and depressive episodes.

METHODS

In this single-center, randomized controlled trial, 68 adults [mean age (SD) = 36.5 (10.0), 57.4% male] with schizophrenia and depressive symptoms were randomly assigned to receive either CCBT with sertraline or sertraline monotherapy during a 4-week hospitalization. The CCBT intervention involved 45-60-minute sessions twice weekly for four weeks. Outcomes included comparisons of depressive symptoms (Calgary depression scale for schizophrenia), cognitive function [MATRICS consensus cognitive battery (MCCB)], and quality of life (36-item short form survey) between the groups.

RESULTS

The experimental group showed greater improvements in depressive symptoms at 4, 8, and 12 weeks compared to the controls, with the most notable difference at 12 weeks [mean difference (MD) = -1.7; P < 0.001; Cohen’s d = 0.9]. Cognitive function improved across all MCCB domains in the experimental group, with higher processing speed scores (MD = 4.1; P = 0.043; Cohen’s d = 0.5) and social cognition scores (MD = 4.9; P = 0.006; Cohen’s d = 0.7) than in the control group. Quality of life, particularly in mental health, was significantly better in the experimental group.

CONCLUSION

CCBT with sertraline was more effective than sertraline monotherapy for patients with schizophrenia and depressive episodes, supporting its use as an adjunctive therapy.

Key Words: Schizophrenia with depressive episode; Computerized cognitive behavioral therapy; Sertraline; Cognitive function; Quality of life; Randomized controlled trial

Core Tip: This randomized controlled trial demonstrates that combining computerized cognitive behavioral therapy (CCBT) with sertraline is more effective than sertraline alone in improving depressive symptoms, cognitive function, and quality of life in patients with schizophrenia and depressive episodes. Notably, CCBT significantly enhanced processing speed and social cognition. These findings support CCBT as a scalable, accessible, and effective adjunct to pharmacotherapy in this challenging population.

INTRODUCTION

Schizophrenia is a chronic and severe mental disorder characterized by positive symptoms, negative symptoms, and cognitive impairment. Psychiatric comorbidities are highly prevalent among individuals with schizophrenia, with depression being the most common, affecting up to 50% of patients[1-3]. The presence of comorbid depression significantly exacerbates cognitive impairment, worsens functional outcomes including social, vocational, and interpersonal domains, reduces overall quality of life, and increases the risk of suicide[4-7]. Despite the substantial burden associated with these comorbidities, treatment options for depression in schizophrenia remain limited, particularly in addressing cognitive dysfunction[8-10].

Recent studies indicate that cognitive behavioral therapy (CBT) is a promising intervention for addressing both depressive symptoms and cognitive impairments in schizophrenia[11,12]. However, its implementation in this population is limited by practical barriers, including patient engagement and accessibility[13]. Computerized CBT (CCBT) presents an alternative strategy that enables large-scale delivery with minimal clinician involvement, making it a feasible adjunct to pharmacotherapy[14,15]. Furthermore, CCBT has demonstrated efficacy in treating various mental disorders, including schizophrenia, and has been shown to improve both depressive symptoms and cognitive function[16,17]. A systematic review has highlighted the benefits of antidepressants, particularly sertraline, for individuals with schizophrenia and comorbid depression[18,19].

To the best of our knowledge, this clinical trial is the first to evaluate the comparative efficacy of CCBT combined with sertraline vs sertraline monotherapy. The primary aim is to assess the effectiveness of CCBT in combination with sertraline in improving depressive symptoms, cognitive function, and quality of life in patients with schizophrenia and comorbid depression. We hypothesize that the combined intervention will result in superior outcomes compared to sertraline monotherapy.

MATERIALS AND METHODS

Study design and protocol

We conducted a single-center, randomized controlled trial at the Second General Hospital of Fuzhou Neuropsychiatric Prevention and Treatment Hospital, Fuzhou, China, from September 2023 to January 2025. The trial was approved by the Ethics Committee of Fuzhou Second Hospital, Mental Health and Disease Prevention Institute [(2023) Ethics Review No. 16]. Participants and their guardians provided written informed consent. The study followed the Consolidated Standards of Reporting Trials reporting guideline.

Participants

Inclusion criteria: (1) Age between 18 and 60 years; (2) A diagnosis of schizophrenia according to ICD-10, in a stable condition (defined as the absence of acute symptom exacerbation and no change in antipsychotic medication type or dosage exceeding 20% within the past four weeks), and with significant depressive symptoms [defined as a Calgary depression scale for schizophrenia (CDSS) score ≥ 7]; and (3) Sufficient cognitive ability to understand and participate in the CCBT intervention.

Exclusion criteria: (1) Severe mental disorders not related to schizophrenia (e.g., schizoaffective disorder, major depressive disorder with psychotic features); (2) Uncontrolled medical conditions (e.g., symptomatic heart failure, uncontrolled diabetes); (3) Allergy or contraindication to sertraline; (4) Current or past participation in another intervention trial or psychological intervention; and (5) Pregnancy or breastfeeding.

Sample size calculation

The sample size was estimated using G*Power based on a randomized controlled trial comparing CBT and supportive therapy[20], which reported a between-group effect size of Cohen’s d = 0.64. For our calculation, we used Cohen’s d = 0.7. A total sample size of 34 is required to detect this effect with a power of 0.80 and a two-tailed alpha level of 0.05.

Randomization

Eligible participants were randomly allocated in a 1:1 ratio to either the experimental group (CCBT combined with sertraline) or the control group (sertraline monotherapy). Simple randomization was conducted using a computer-generated number sequence created by an independent researcher who was not involved in recruitment, treatment, or outcome assessment. Odd numbers were assigned to the experimental group, and even numbers to the control group. Allocation was concealed from the recruiter. After informed consent was obtained, the recruiter contacted the principal investigator to obtain the participant’s group assignment. The psychiatrist delivering the intervention was aware of the group allocation due to the nature of the treatment. However, outcome assessments were performed by trained assessors who were blinded to the treatment assignment.

Intervention

To ensure treatment adherence, continuous monitoring, and stability of daily routines, all participants were hospitalized for four weeks to receive the assigned treatment. Participants continued their antipsychotic medications without restrictions on the type used and were monitored from baseline to 12 weeks post-intervention.

In the control group, participants received sertraline (50 mg orally once daily after meals) in addition to their prescribed antipsychotic regimen. After the first week, the sertraline dosage could be titrated up to a maximum of 200 mg per day, depending on symptom severity and at the discretion of the attending physician and principal investigator. During hospitalization, all patients received standard psychiatric care from the attending physician, including medication management, clinical monitoring, and supportive interactions as needed.

Participants in the experimental group received the same treatment as the control group, with the addition of the CCBT intervention. The CCBT system used in this study was originally developed by Beijing Huilongguan Hospital and was specifically adapted for individuals with schizophrenia and comorbid depressive symptoms. The intervention comprised six structured modules, as outlined in Table 1, and was delivered via an interactive multimedia platform incorporating text, illustrations, audio instructions, and demonstration videos to enhance comprehension and engagement. Notably, the version used in this study did not include artificial intelligence or natural language processing components.

Table 1 Computerized cognitive behavioral therapy modules.

Module	Module title	Content description
1	Psychoeducation and self-assessment	Introduction to the structure and objectives of CCBT. Includes completion of mood and cognition self-assessments, and identification of target symptoms and treatment goals
2	Relaxation and stress regulation	Training in abdominal breathing, progressive muscle relaxation, and guided imagery. Includes multimedia demonstrations and interactive practice tasks
3	Behavioral activation	Education on the relationship between behavior and mood. Activity scheduling tasks to promote engagement in enjoyable or meaningful routines, with daily tracking tools
4	Cognitive restructuring	Explanation to negative automatic thoughts and common cognitive distortions. Includes interactive exercises to identify and challenge maladaptive beliefs
5	Homework assignments	Review and reinforcement of prior modules through structured tasks. Examples include mood logs, thought records, and activity diaries, with feedback and reminders
6	Relapse prevention	Review of core skills. Identification of early warning signs for relapse. Development of personalized prevention plans. Includes future-oriented coping strategies

CCBT: Computerized cognitive behavioral therapy.

All sessions were conducted during inpatient hospitalization using offline hospital-provided tablets or workstations, without requiring internet access. Each session lasted 45-60 minutes and was administered twice weekly over a four-week period. The structured inpatient environment, along with consistent supervision by psychiatrists trained in CCBT delivery, facilitated a nearly 100% module completion rate. Psychiatrists spent 10-15 minutes before each session to orient participants, address technical or content-related issues, and provide brief guidance. Following each session, they offered feedback, reinforced CBT principles, ensured proper platform use, and supported patient motivation and adherence throughout the intervention.

Outcomes

Outcomes were measured using CDSS at baseline, 2, 4, 8, and 12 weeks; MATRICS consensus cognitive battery (MCCB) at baseline and 12 weeks; and 36-item short form survey (SF-36) at baseline and 12 weeks. CDSS is a recommended tool for assessing depressive symptoms in patients with schizophrenia[21]. It consists of nine items, each scored from 0 to 3, with a total score ranging from 0 to 27. Higher scores indicate more severe depression. MCCB was developed to assess cognitive function in schizophrenia and covers seven cognitive domains: Processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem-solving, and social cognition[22]. A higher MCCB score indicates better cognitive function, while a score below 40 suggests cognitive impairment. The 36-item short form health survey (SF-36) is widely used to evaluate patients' quality of life[23,24]. Each SF-36 item is scored from 0 to 100, with higher scores indicating better health status.

The primary outcomes were comparisons of CDSS, MCCB, and SF-36 scores between the experimental and control groups. All tools were used to compare scores at baseline and the 12-week follow-up, while CDSS was also assessed at 2, 4, and 8 weeks. The secondary outcomes evaluated changes in CDSS, MCCB, and SF-36 scores from baseline to follow-up within the same groups. CDSS was assessed at 4, 8, and 12 weeks, while MCCB and SF-36 were compared between baseline and 12 weeks.

Statistical analysis

Categorical variables were reported as frequencies and percentages [n (%)], while continuous variables were expressed as mean ± SD or median (interquartile range). The χ² test was employed to compare categorical variables. The primary outcome of interest was the difference in CDSS, MCCB, and SF-36 scores, reported as the mean difference (MD) between the experimental and control groups, and analysed using an independent samples t-test or Mann-Whitney U test. The secondary outcome of interest was the change in mean CDSS, MCCB, and SF-36 scores from baseline to follow-up, assessed using a paired samples t-test. MDs were reported with 95% confidence intervals (95%CIs). Effect sizes were calculated using Cohen’s d, where values of 0.2, 0.5, and 0.8 were interpreted as small, medium, and large effect sizes, respectively.

All statistical analyses were conducted using SPSS Statistics (IBM SPSS Statistics for Windows, Version 29.0.2.0, Armonk, NY, United States). All P values were two-sided, with P values < 0.05 considered statistically significant. All data were analyzed according to the intention-to-treat principle.

RESULTS

Participants

A total of 68 patients were recruited and randomly assigned to either the experimental group (CCBT combined with sertraline) or the control group (sertraline monotherapy), with 34 participants in each group (Figure 1). The mean age was 36.5 ± 10.0 years, and 39 participants (57.4%) were male. Age, gender, years of education, marital status, family history, disease duration, and sertraline dosage were comparable between the two groups. Detailed baseline characteristics are summarized in Table 2.

Figure 1 Study flow chart. CCBT: Computerized cognitive behavioral therapy.

Table 2 Sociodemographic and clinical data.

Characteristic	All patients (n = 68)	Experimental group (n = 34)	Control group (n = 34)	P value
Age, mean ± SD, years	36.54 ± 9.96	36.18 ± 9.33	36.91 ± 10.68	0.763
Gender, n (%)				0.806
Male	39 (57.4)	19 (55.9)	20 (58.8)
Female	29 (42.6)	15 (44.1)	14 (41.2)
Year of education, mean ± SD, years	10.50 ± 2.64	10.32 ± 2.78	10.68 ± 2.52	0.585
Marital status, n (%)				0.314
Single	42 (61.8)	20 (58.8)	22 (64.7)
Married	18 (26.5)	8 (23.5)	10 (29.4)
Divorced	8 (11.8)	6 (17.6)	2 (5.9)
Family history, n (%)	12 (17.6)	6 (17.6)	6 (17.6)	1.000
Disease duration, mean ± SD, years	13.62 ± 6.44	13.52 ± 6.42	13.72 ± 6.57	0.902
Sertraline dosage at 4 weeks, median (IQR), mg	150 (100-150)	150 (100-150)	150 (100-150)	0.509
Sertraline dosage at 12 weeks, median (IQR), mg	150 (100-150)	150 (100-150)	150 (100-150)	0.314

Depressive symptom

The experimental and control groups exhibited similar baseline CDSS scores, indicating balanced allocation. Both groups showed significant symptom improvement, as evidenced by a decrease in CDSS scores at the 4-week, 8-week, and 12-week follow-ups compared to baseline (P < 0.001 for all comparisons). Additionally, the MDs increased over time, suggesting a progressive reduction in depressive symptoms (Supplementary Table 1).

At the 4-week, 8-week, and 12-week follow-ups, the experimental group had significantly lower CDSS scores than the control group (8.3 ± 1.8 vs 9.7 ± 1.7, 6.9 ± 1.4 vs 8.4 ± 1.4, and 4.0 ± 2.1 vs 5.7 ± 1.7, respectively). The differences between groups became more pronounced over time, with MD = -1.3 (95%CI: -2.2 to -0.5; P = 0.003; Cohen’s d = 0.7) at 4 weeks, MD = -1.5 (95%CI: -2.2 to -0.9; P < 0.001; Cohen’s d = 1.1) at 8 weeks, and MD = -1.7 (95%CI: -2.6 to -0.8; P < 0.001; Cohen’s d = 0.9) at 12 weeks (Table 3). These findings suggested that the experimental group experienced greater and sustained reductions in depressive symptoms compared to the control group.

Table 3 Comparison of Calgary depression scale for schizophrenia scores between experimental and control groups.

Outcome	Experimental group (n = 34)	Control group (n = 34)	MD (95%CI)	P value	Cohen’s d1
Baseline	12.32 ± 2.67	12.12 ± 2.90	0.21 (-1.14, 1.56)	0.762	-
2-week follow up	10.15 ± 2.73	10.91 ± 2.09	-0.76 (-1.94, 0.41)	0.200	-
4-week follow up	8.32 ± 1.84	9.65 ± 1.72	-1.32 (-2.19, -0.46)	0.003	0.74
8-week follow up	6.88 ± 1.43	8.41 ± 1.35	-1.53 (-2.20, -0.86)	< 0.001	1.10
12-week follow up	4.00 ± 2.10	5.68 ± 1.70	-1.68 (-2.60, -0.75)	< 0.001	0.88

¹Effect sizes are shown when t-tests are significant; small effect (> 0.2), medium effect (> 0.5), large effect (> 0.8).

95%CI: 95% confidence interval.

Cognitive function

At baseline, MCCB scores were similar between the two groups. Over the 12-week follow-up, the experimental group demonstrated significant cognitive improvements, with increased MCCB scores across all domains and total scores compared to baseline (P < 0.001). In contrast, the control group showed significant improvements in only three domains including attention/vigilance, visual learning, and reasoning/problem solving, along with total scores.

At 12 weeks, the experimental group had significantly higher MCCB scores in processing speed and social cognition than in the control group (47.0 ± 7.9 vs 43.0 ± 8.4; MD = 4.1; 95%CI: 0.1-8.0; P = 0.043; Cohen’s d = 0.5, and 39.8 ± 6.9 vs 34.9 ± 7.2; MD = 4.9; 95%CI: 1.5-8.3; P = 0.006; Cohen’s d = 0.7, respectively; Table 4). These results suggest that the experimental group experienced greater overall cognitive improvements from baseline. However, when directly compared to the control group, significantly greater improvements were observed in only two of the seven MCCB domains: Processing speed and social cognition.

Table 4 Comparison of MATRICS consensus cognitive battery scores between experimental and control groups.

Outcome	Pre-treatment (baseline)					Post-treatment (12 weeks)
	Experimental group (n = 34)	Control group (n = 34)	MD (95%CI)	P value	Cohen’s d1	Experimental group (n = 34)	Control group (n = 34)	MD (95%CI)	P value	Cohen’s d1
ProcSpeed	42.35 ± 9.07	42.21 ± 8.89	0.15 (-4.20, 4.49)	0.946	-	47.03 ± 7.85	42.97 ± 8.35	4.06 (0.13, 7.98)	0.043	0.50
AttnVig	41.65 ± 9.21	39.71 ± 10.10	1.94 (-2.74, 6.62)	0.411	-	45.76 ± 8.25	44.76 ± 6.58	1.00 (-2.61, 4.61)	0.583	-
WorkMem	40.15 ± 9.22	41.06 ± 7.88	-0.91 (-5.07, 3.24)	0.663	-	46.62 ± 7.96	42.74 ± 8.91	3.88 (-0.21, 7.97)	0.063	-
VerbLrn	42.00 ± 9.95	41.94 ± 10.25	0.06 (-4.83, 4.95)	0.981	-	46.09 ± 8.57	43.50 ± 5.56	2.59 (-0.91, 6.08)	0.144	-
VisLrn	41.44 ± 8.77	40.29 ± 8.22	1.15 (-2.97, 5.26)	0.580	-	46.56 ± 6.33	46.47 ± 6.76	0.09 (-3.08, 3.26)	0.956	-
ProbSolv	42.62 ± 6.56	43.24 ± 11.08	-0.62 (-5.63, 4.39)	0.806	-	46.00 ± 7.60	44.79 ± 8.11	1.21 (-2.60, 5.01)	0.529	-
SocCog	33.38 ± 9.02	34.26 ± 8.89	-0.88 (-5.22, 3.45)	0.686	-	39.82 ± 6.92	34.91 ± 7.21	4.91 (1.49, 8.33)	0.006	0.70
Total	40.47 ± 8.96	40.38 ± 8.82	0.09 (-4.22, 4.39)	0.967	-	45.35 ± 7.57	42.85 ± 6.87	2.50 (-1.00, 6.00)	0.159	-

¹Effect sizes are shown when t-tests are significant; small effect (> 0.2), medium effect (> 0.5), large effect (> 0.8).

95%CI: 95% confidence interval; ProcSpeed: Processing speed; AttnVig: Attention vigilance; WorkMem: Working memory; VerbLrn: Verbal learning; VisLrn: Visual learning; ProbSolv: Reasoning and problem solving; SocCog: Social cognition.

Quality of life

Baseline SF-36 scores were comparable between the two groups. Over the 12-week follow-up, quality of life significantly improved in the experimental group, with higher SF-36 scores in all four domains (P < 0.001). Similarly, the control group showed significant improvements in all domains except for mental health.

At 12 weeks, the experimental group had significantly higher SF-36 scores across all domains than the control group, with the most pronounced difference observed in the mental health domain (70.9 ± 12.0 vs 62.8 ± 9.2; MD = 8.1; 95%CI: 2.9-13.2; P = 0.003; Cohen’s d = 0.8; Table 5). These findings suggested that the experimental group had a superior impact on quality of life improvement compared to the control group.

Table 5 Comparison of 36-item short form survey scores between experimental and control groups.

Outcome	Pre-treatment (baseline)					Post-treatment (12 weeks)
	Experimental group (n = 34)	Control group (n = 34)	MD (95%CI)	P value	Cohen’s d1	Experimental group (n = 34)	Control group (n = 34)	MD (95%CI)	P value	Cohen’s d1
Physical function	73.56 ± 13.19	74.12 ± 13.89	-0.56 (-7.12, 6.00)	0.865	-	84.47 ± 6.97	78.85 ± 11.96	5.62 (0.88, 10.36)	0.021	0.57
Vitality	53.82 ± 11.95	53.38 ± 12.44	0.44 (-5.46, 6.35)	0.882	-	64.26 ± 8.52	58.82 ± 11.41	5.44 (0.56, 10.32)	0.029	0.54
Social function	60.32 ± 13.31	60.03 ± 12.89	0.29 (-6.05, 6.64)	0.927	-	73.44 ± 8.35	68.74 ± 8.37	4.71 (0.66, 8.76)	0.023	0.56
Mental health	62.12 ± 14.89	61.79 ± 14.28	0.32 (-6.74, 7.39)	0.927	-	70.88 ± 11.96	62.82 ± 9.24	8.06 (2.88, 13.23)	0.003	0.75

¹Effect sizes are shown when t-tests are significant; small effect (> 0.2), medium effect (> 0.5), large effect (> 0.8).

95%CI: 95% confidence interval.

DISCUSSION

This randomized controlled trial provides preliminary evidence supporting the efficacy of combining CCBT with sertraline in reducing depressive symptoms, enhancing cognitive function, and improving quality of life in patients with schizophrenia and comorbid depressive episodes. For depressive symptom, evaluated by CDSS, the experimental group experienced significantly greater reductions in depressive symptoms compared to the control group. The differences between groups became increasingly pronounced over time, with the most substantial improvement observed at the 12-week follow-up. These findings are consistent with previous research suggesting that CBT, including its computerized adaptation, is effective in alleviating depressive symptoms in individuals with schizophrenia[25,26].

Furthermore, CCBT has been shown to address negative cognitive biases and promote adaptive coping strategies, which are particularly important for individuals with schizophrenia, as they frequently experience distorted thought patterns[27]. The integration of CCBT with pharmacotherapy may enhance both pharmacological and psychological treatment components, resulting in more robust and sustained improvements in depressive symptoms compared to pharmacotherapy alone[28,29]. This corresponds with increasing evidence demonstrating the benefits of combining pharmacological treatments with psychological interventions to improve depressive symptoms in schizophrenia[30-32].

In addition to improvements in depressive symptoms, the experimental group also showed notable cognitive improvements, particularly in processing speed and social cognition, as measured by the MCCB. This finding is impactful because cognitive deficits, especially in processing speed and social cognition domains, are core features of schizophrenia and are associated with poor functional outcomes[33,34]. However, their management remains inadequately addressed[35]. Previous research on cognitive remediation therapies, such as CCBT, has similarly shown significant improvements in cognitive function in patients with schizophrenia[36-38].

Moreover, the quality of life in the experimental group, particularly in the mental health domain as assessed by the SF-36, has significantly improved. Individuals with schizophrenia generally experience a poor quality of life, highlighting the necessity of addressing both depressive symptoms and cognitive deficits to enhance functional outcomes[39,40]. The substantial improvements in mental health observed in the experimental group suggest that the combination of sertraline and CCBT effectively enhanced psychological well-being and overall functional outcomes. These findings align with previous studies emphasizing the importance of addressing both mental health and cognitive functioning in schizophrenia to improve quality of life[41-43].

The findings of this study are consistent with previous research on the efficacy of combining psychotherapy with pharmacological treatment in schizophrenia[44-46]. Studies have demonstrated that such combinations can result in greater and more sustained improvements in both mood and cognition compared to monotherapy[47]. This study highlights the potential of CCBT as an adjunct to pharmacological treatment in schizophrenia, as its computerized format offers several advantages beyond its proven efficacy. These advantages include broader accessibility, cost-effectiveness, and the ability to deliver treatment remotely, which can help overcome barriers associated with traditional psychotherapy[48-50].

However, this study has several limitations. First, the sample size was small, and the findings should be considered preliminary. Second, the study relied on ICD-10-based clinical diagnoses of schizophrenia without the use of structured diagnostic interviews such as the structured clinical interview for DSM disorders or the mini-international neuropsychiatric interview, which may affect diagnostic validity. Third, differentiating co-morbid depression in schizophrenia from negative symptoms or schizoaffective disorder is challenging and ideally requires comprehensive phenomenological evaluation beyond routine clinical assessments. Our inclusion criteria were designed to reflect real-world clinical practice, where such distinctions are often limited, which may have introduced diagnostic heterogeneity. Fourth, the study included only patients aged 18-60 with stable schizophrenia and depression, and all treatments were administered in an inpatient setting, which may limit the generalizability of the findings. Lastly, the study did not assess the long-term effects of the intervention beyond 12 weeks, making it difficult to determine the sustainability of the observed improvements. Future studies should include a larger and more diverse patient population, deliver CCBT in outpatient settings, and assess its long-term efficacy.

CONCLUSION

In conclusion, this study provides strong evidence that CCBT combined with sertraline is more effective than sertraline monotherapy in improving depressive symptoms, cognitive function, and quality of life in patients with schizophrenia and depressive episodes. These findings support the integration of CCBT as an adjunctive therapy to pharmacological treatment in this patient population.