Supportive Psychotherapy as Adjunct to Risperidone for Cognitive Function and Inflammation in Schizophrenia (SUPPORT-SCZ)

Supportive Psychotherapy As An Adjunct To Risperidone Improves Cognitive Function And Reduces High-Sensitivity C-Reactive Protein (Hs-CRP) In Schizophrenia: A Randomized Controlled Trial

This study examined whether adding structured supportive psychotherapy to risperidone treatment is more effective than risperidone alone in improving cognitive function and reducing inflammation in patients with schizophrenia.

Forty-six male patients with schizophrenia were randomly assigned to two groups: the intervention group (n=23) received risperidone 4 mg/day plus 12 sessions of structured supportive psychotherapy over 6 weeks. The control group (n=23) received risperidone 4 mg/day alone for 6 weeks.

Cognitive function was measured using the Montreal Cognitive Assessment - Indonesian version (MoCA-Ina) and inflammation was measured using serum high-sensitivity C-reactive protein (hs-CRP) levels, both assessed at baseline (Week 0) and after treatment (Week 6).

NOTE: This trial was retrospectively registered. The study was conducted from December 2024 to February 2025 and received ethical clearance (No. 1009/UN4.6.4.5.31/PP36/2024) from the Biomedical Research Ethics Committee, Faculty of Medicine, Universitas Hasanuddin, prior to study initiation. Registration was performed after study completion due to the investigator's initial unawareness of prospective registration requirements. No outcome measures, study design, or statistical analysis plan were modified following data collection.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Cognitive Dysfunction; Inflamation
• Intervention / Treatment: Behavioral: Structured Supportive Psychotherapy; Drug: Risperidone 2 mg

Detailed Description

This double-blind randomized controlled trial was conducted at Dadi Psychiatric Hospital (RSJ Dadi), South Sulawesi Province, Makassar, Indonesia, from December 2024 to February 2025.

BACKGROUND:

Schizophrenia is associated with cognitive impairment and elevated inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP). Supportive psychotherapy has been proposed as an adjunctive intervention to pharmacotherapy to address these deficits. However, evidence on the combined effect of supportive psychotherapy and risperidone on both cognitive function and inflammation remains limited.

INTERVENTION:

The intervention group received risperidone 4 mg/day (2 mg twice daily) plus structured supportive psychotherapy consisting of 12 sessions delivered twice weekly over 6 weeks (15-30 minutes per session). The control group received risperidone 4 mg/day monotherapy for 6 weeks. To minimize expectation bias, supportive psychotherapy was described to all participants as "standard supportive counseling," thereby preventing identification of group allocation.

RANDOMIZATION AND BLINDING:

Participants were randomly allocated in a 1:1 ratio using a simple random number generator by an independent researcher not involved in clinical recruitment. Allocation concealment was achieved using the Sequentially Numbered Opaque Sealed Envelope (SNOSE) method, prepared by a separate research assistant and disclosed only after informed consent and baseline assessments were completed. Participants 1-23 were assigned to the intervention group and participants 24-46 to the control group. The study employed a double-blind design in which both participants and outcome assessors were blinded to group allocation. Outcome assessors evaluating MoCA-Ina scores and laboratory personnel measuring serum hs-CRP levels were fully blinded to group allocation throughout the study period.

OUTCOME MEASURES:

Primary outcomes were: (1) change in cognitive function assessed by Montreal Cognitive Assessment - Indonesian version (MoCA-Ina) from baseline to Week 6; and (2) change in serum hs-CRP level from baseline to Week 6. Secondary outcome was the correlation between delta hs-CRP and delta MoCA-Ina within each group at Week 6.

ETHICAL APPROVAL:

This study was approved by the Biomedical Research Ethics Committee, Faculty of Medicine, Universitas Hasanuddin (No. 1009/UN4.6.4.5.31/PP36/2024) and conducted in accordance with the Declaration of Helsinki. All participants provided written informed consent prior to enrollment.

NOTE: This trial was retrospectively registered. The study was conducted from December 2024 to February 2025 and received ethical clearance prior to study initiation. Registration was performed after study completion due to the investigator's initial unawareness of prospective registration requirements. No outcome measures, study design, or statistical analysis plan were modified following data collection.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• Indonesia
  • South Sulawesi
    • Makassar, South Sulawesi, Indonesia, 90245
      • Dadi Psychiatric Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male patients diagnosed with schizophrenia according to DSM-5 criteria
• Aged 20-45 years
• Disease onset less than one year
• Insight level grade 4
• PANSS-EC score 14 or less
• Total PANSS score 60-70
• No febrile conditions, jaundice, or hepatosplenomegaly
• Willing and able to attend supportive psychotherapy sessions
• Receiving risperidone at fixed dose of 4 mg per day
• South Sulawesi ethnic origin

Exclusion Criteria:

• Organic comorbid diseases
• History of substance abuse within previous six months except caffeine and nicotine
• Comorbid personality disorders
• Obesity
• Active infectious diseases
• Use of anti-inflammatory agents, antibiotics, or antioxidant supplements
• Female sex

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supportive Psychotherapy plus Risperidone; Participants received risperidone 4 mg/day (2 mg tablet twice daily, oral administration) plus structured supportive psychotherapy consisting of 12 sessions delivered twice weekly over 6 weeks (15-30 minutes per session). Supportive psychotherapy was delivered using a validated module by the principal investigator.	Behavioral: Structured Supportive Psychotherapy; Structured supportive psychotherapy using the Supportive Psychotherapy Module for Schizophrenia (Suhuyanli et al.), nationally validated in the Indonesian population. Consisting of 12 structured sessions delivered twice weekly over 6 weeks (15-30 minutes per session), organized into initial (sessions 1-3), middle (sessions 4-9), and termination phases (sessions 10-12). Sessions were delivered by three trained psychiatrists supervised by a consultant in medical psychotherapy. To minimize expectation bias, the intervention was described to all participants as "standard supportive counseling."; Drug: Risperidone 2 mg; Risperidone 4 mg/day (2 mg tablet twice daily, oral administration) for 6 weeks. Administered to both the intervention group (in combination with supportive psychotherapy) and the control group (as monotherapy).
Active Comparator: Risperidone Monotherapy; Participants received risperidone 4 mg/day (2 mg tablet twice daily, oral administration) monotherapy for 6 weeks without any structured psychotherapy intervention.	Drug: Risperidone 2 mg; Risperidone 4 mg/day (2 mg tablet twice daily, oral administration) for 6 weeks. Administered to both the intervention group (in combination with supportive psychotherapy) and the control group (as monotherapy).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cognitive Function (MoCA-Ina Score)	Change in cognitive function assessed by the Montreal Cognitive Assessment - Indonesian version (MoCA-Ina) from baseline to Week 6. Score range 0-30; higher scores indicate better cognitive function. Inter-rater reliability kappa=0.820.	Baseline (Week 0) and post-intervention (Week 6)
Change in Serum hs-CRP Level	Change in serum high-sensitivity C-reactive protein (hs-CRP) level from baseline to Week 6, measured by Sandwich-ELISA (Elabscience Human hs-CRP ELISA Kit, Cat. No. E-EL-H5134; detection range 15.63-1000 pg/mL; sensitivity 9.38 pg/mL).	Baseline (Week 0) and post-intervention (Week 6)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between Delta hs-CRP and Delta MoCA-Ina	Correlation between change in serum hs-CRP level (delta hs-CRP) and change in cognitive function score (delta MoCA-Ina) within each group at Week 6. Analyzed using Spearman or Pearson correlation coefficient based on normality test (Shapiro-Wilk). Delta values calculated as Week 6 minus Week 0 for each measure.	Week 6 (end of intervention)

Collaborators and Investigators

• Sponsor: Hasanuddin University
• Investigators: Principal Investigator: Agus Durman, MD, Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia; Study Chair: Indrawaty Suhuyanli, MD, Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Actual): February 28, 2025
• Study Completion (Actual): February 28, 2025

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 13, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 13, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Inflammation; Schizophrenia; C-Reactive Protein; Randomized Controlled Trial; Risperidone; Cognitive Function; Supportive Psychotherapy
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Cognition Disorders; Pathological Conditions, Signs and Symptoms; Schizophrenia; Cognitive Dysfunction; Inflammation; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pyrimidinones; Risperidone
• Other Study ID Numbers: AGUS-SP-RIS-SCZ-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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