Cognitive Behavioral Therapy Added to Risperidone for Schizophrenia (CBT-BDNF-SCZ)

Effectiveness of Cognitive Behavioral Therapy as Adjunctive Therapy on Cognitive Function and Serum Brain-Derived Neurotrophic Factor Levels in Patients With Schizophrenia Receiving Risperidone Therapy

This study evaluated whether cognitive behavioral therapy (CBT), when added to risperidone treatment, improves cognitive function and serum brain-derived neurotrophic factor (BDNF) levels in patients with schizophrenia. Participants were adults with stable-phase schizophrenia who were receiving risperidone therapy. They were assigned to either a control group receiving risperidone alone or an intervention group receiving risperidone plus 10 weekly CBT sessions.

Cognitive function was assessed using the Indonesian version of the Cognitive Assessment Interview (CAI-Ina). Serum BDNF levels were measured from blood samples using an enzyme-linked immunosorbent assay (ELISA). Measurements were performed at baseline and after 10 weeks. The study was conducted at Rumah Sakit Khusus Daerah Dadi, South Sulawesi, Indonesia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Risperidone 4 to 6 mg/day; Behavioral: Cognitive Behavioral Therapy

Detailed Description

Schizophrenia is a chronic psychiatric disorder associated not only with psychotic symptoms but also with persistent cognitive impairment. Cognitive deficits may affect attention, working memory, verbal memory, processing speed, reasoning, problem solving, and social cognition. These impairments can interfere with daily functioning and long-term recovery. Although risperidone is commonly used as an antipsychotic treatment for schizophrenia, its effect on cognitive function may be limited. Cognitive behavioral therapy (CBT) may provide additional benefit by helping patients identify maladaptive beliefs, develop coping strategies, improve insight, and strengthen adaptive behavior.

This study was designed to evaluate the effect of CBT as an adjunctive therapy to risperidone on cognitive function and serum BDNF levels in patients with schizophrenia. BDNF is a neurotrophic factor involved in neuroplasticity, synaptic function, learning, and memory. Lower BDNF levels have been associated with cognitive impairment in schizophrenia. The study assessed whether adding CBT to risperidone therapy was associated with improvement in cognitive function and changes in serum BDNF levels.

This was an interventional, randomized, single-blind, rater-blind study. Participants were patients with stable-phase schizophrenia treated at Rumah Sakit Khusus Daerah Dadi, South Sulawesi, Indonesia. Eligible participants were adults aged 20 to 50 years with schizophrenia diagnosed according to DSM-5 and PPDGJ-III criteria, illness onset of 5 years or less, stable clinical condition, and ongoing risperidone therapy.

Participants were assigned to two groups. The control group received risperidone therapy. The intervention group received risperidone therapy plus CBT. The CBT intervention consisted of 10 sessions delivered once weekly over 10 weeks, with each session lasting approximately 30 minutes. The CBT sessions included engagement and assessment of target problems, cognitive formulation, exploration of appraisals, evaluation of beliefs, gentle reality testing, development of alternative explanations, behavioral experiments, coping strategy enhancement, insight building, relapse prevention, and future planning.

Cognitive function was measured using the Indonesian version of the Cognitive Assessment Interview (CAI-Ina), an interview-based instrument for assessing cognitive function in patients with schizophrenia. Serum BDNF levels were measured from peripheral blood samples using ELISA. Assessments were performed at baseline and at week 10. The main objective was to compare changes in cognitive function and serum BDNF levels between the risperidone-only group and the risperidone plus CBT group.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Indonesia
  • South Sulawesi
    • Makassar, South Sulawesi, Indonesia, 90113
      • Rumah Sakit Khusus Daerah (RSKD) Dadi Provinsi Sulawesi Selatan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with schizophrenia according to DSM-5 and PPDGJ-III criteria.
• Illness onset of schizophrenia ≤ 5 years since the first appearance of symptoms.
• Age 20 to 50 years.
• Clinically stable phase, defined as PANSS score 30 to 60.
• Receiving risperidone therapy at a dose of 4 to 6 mg/day.
• Minimum educational level of senior high school.
• Willing to participate in the study and sign informed consent.

Exclusion Criteria:

• Presence of organic comorbid conditions, such as neurological disorders, severe endocrine or metabolic disorders, chronic liver or kidney disease, or systemic infection, that may affect cognitive function or serum BDNF levels.
• History of substance use before hospital admission, except caffeine and nicotine.
• Use of anti-inflammatory drugs, antibiotics, or antioxidant medications.
• Intellectual disability or mental retardation.
• Unwilling to attend cognitive behavioral therapy sessions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group; Participants received risperidone therapy without cognitive behavioral therapy.	Drug: Risperidone 4 to 6 mg/day; Risperidone was administered as antipsychotic therapy for patients with schizophrenia. Participants in both study groups received risperidone therapy according to the study protocol.
Experimental: Intervention Group; Participants received risperidone therapy plus 10 weekly sessions of cognitive behavioral therapy over 10 weeks. Each CBT session lasted approximately 30 minutes.	Drug: Risperidone 4 to 6 mg/day; Risperidone was administered as antipsychotic therapy for patients with schizophrenia. Participants in both study groups received risperidone therapy according to the study protocol.; Behavioral: Cognitive Behavioral Therapy; Cognitive behavioral therapy was delivered as an adjunctive intervention to risperidone therapy. The intervention consisted of 10 weekly sessions over 10 weeks, with each session lasting approximately 30 minutes. Sessions included engagement, cognitive formulation, appraisal exploration, belief evaluation, gentle reality testing, alternative explanations, behavioral experiments, coping strategy enhancement, insight building, relapse prevention, and future planning.; Other Names: CBT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cognitive Function Assessed by CAI-Ina Total Score	Cognitive function was assessed using the Indonesian version of the Cognitive Assessment Interview (CAI-Ina). The CAI-Ina evaluates cognitive function in patients with schizophrenia, including processing speed, attention, working memory, verbal memory, reasoning and problem solving, and social cognition. Higher scores indicate greater cognitive impairment. The outcome was the change in total CAI-Ina score from baseline to week 10.	Baseline and week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Brain-Derived Neurotrophic Factor Level	Serum brain-derived neurotrophic factor (BDNF) level was measured from peripheral blood samples using enzyme-linked immunosorbent assay (ELISA). The outcome was the change in serum BDNF level from baseline to week 10. Values were reported in pg/mL.	Baseline and week 10

Collaborators and Investigators

• Sponsor: Hasanuddin University
• Investigators: Principal Investigator: Maya Angela Lisal, Medical Doctor, Hasanuddin University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Actual): January 31, 2026
• Study Completion (Actual): January 31, 2026

Study Registration Dates

• First Submitted: May 20, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Psychosis; Risperidone; CBT; Cognitive Behavioral Therapy; BDNF; Cognitive Function; Brain-Derived Neurotrophic Factor; Cognitive Assessment Interview; CAI-Ina
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Psychotic Disorders; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Cognitive Behavioral Therapy
• Other Study ID Numbers: UH25090757; 807/UN4.6.4.5.31/PP36/2025 (Other Identifier: Hasanuddin University Research Ethics Committee)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared because no IPD sharing plan was specified in the approved study protocol, and participant confidentiality will be maintained according to the ethics approval and informed consent procedures.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No