A Pilot Study of Adjunctive Structured Supportive Psychotherapy in Schizophrenia

NCT07671040 | Completed

• 1 other identifier: PILOT-HSCRP-2025
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot randomized controlled trial examined whether adding structured supportive psychotherapy to risperidone treatment is more effective than risperidone alone in improving cognitive function and reducing peripheral inflammation in stabilized inpatients with schizophrenia. Forty-four male and female inpatients with schizophrenia were randomly assigned to two groups: the intervention group (n=22) received risperidone 4 mg/day plus 12 individual sessions of structured supportive psychotherapy (45-60 minutes per session, once weekly) over 12 weeks. The control group (n=22) received risperidone 4 mg/day plus 12 sessions of unstructured supportive conversation (attention-matched) over the same 12-week period. 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 12). NOTE: This pilot randomized controlled trial was retrospectively registered. The study was conducted from March 2025 to June 2025 and received ethical clearance (PROTOKOL-UH24100793) from Komite Etik Penelitian 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.

Conditions

Schizophrenia; Cognitive and Executive Dysfunction; Neuroinflammation

Keywords

Schizophrenia; Psychotherapy; Cognition; C-Reactive Protein; Neuroinflammation

Outcome Measures

Primary Outcomes (2)

• 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 12. Score range 0-30; higher scores indicate better cognitive function. The MoCA-Ina is a World Health Organization (WHO)-aligned, nationally validated instrument with substantial inter-rater reliability (Cohen's kappa, κ = 0.820) and domain-level inter-rater agreement (κ = 0.817-1.000). Scores ≥26 indicate normal cognitive function.

  Baseline (Week 0) and post-intervention (Week 12)

• Change in Serum hs-CRP Level

  Change in serum high-sensitivity C-reactive protein (hs-CRP) level (mg/L) from baseline to Week 12, quantified using a sandwich Enzyme-Linked Immunosorbent Assay (ELISA) kit (Elabscience® Human hs-CRP ELISA Kit, catalog no. E-EL-H5134; detection range 15.63-1000 pg/mL; sensitivity 9.38 pg/mL; intra-assay coefficient of variation (CV) 4.47-4.64%; inter-assay CV 6.44-8.95%).

  Baseline (Week 0) and post-intervention (Week 12)

Secondary Outcomes (2)

• Correlation Between Delta hs-CRP and Delta MoCA-Ina

  Week 12 (end of intervention)

• Change in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores

  Baseline (Week 0) and Week 12 (end of intervention)

Study Arms (2)

Structured Supportive Psychotherapy plus Risperidone

EXPERIMENTAL

The intervention arm additionally underwent 12 individual structured supportive psychotherapy sessions delivered once weekly over 12 weeks, each lasting 45-60 minutes (total therapist contact time approximately 540-720 minutes), conducted by three board-certified psychiatrists each with over five years of psychotherapy experience, using the nationally validated Indonesian supportive psychotherapy module for schizophrenia.

Behavioral: Structured supportive psychotherapy; Drug: Risperidone

Unstructured Supportive Conversation plus Risperidone

ACTIVE COMPARATOR

The active control arm received an equivalent number of individual sessions over the same 12-week period (12 sessions, once weekly, each lasting 45-60 minutes), delivered by three board-certified psychiatrists with equivalent clinical experience, yielding comparable total therapist contact time of approximately 540-720 minutes per participant. Control sessions consisted of unstructured supportive conversation without a session manual, predetermined therapeutic modules, structured psychoeducation, or a fidelity protocol.

Drug: Risperidone; Behavioral: Unstructured Supportive Conversation

Interventions

Structured supportive psychotherapy BEHAVIORAL

Structured supportive psychotherapy using the Supportive Psychotherapy Module for Schizophrenia, nationally validated in the Indonesian population. Sessions progressed across three structured phases: Sessions 1-3 established therapeutic alliance and clinical formulation; Sessions 4-9 addressed psychoeducation, coping strategies, reality testing, and adherence reinforcement; and Sessions 10-12 consolidated treatment gains and planned relapse prevention. Protocol fidelity required completion of at least 10 of 12 sessions, monitored by an independent rater using a structured checklist (inter-rater agreement κ = 0.84).

Structured Supportive Psychotherapy plus Risperidone

Risperidone DRUG

Risperidone 4 mg/day (2 mg tablet twice daily, oral administration) for 12 weeks

Structured Supportive Psychotherapy plus Risperidone; Unstructured Supportive Conversation plus Risperidone

Unstructured Supportive Conversation BEHAVIORAL

Participants in the active control arm received an identical schedule of individual sessions over the 12-week period, administered by three board-certified psychiatrists of comparable clinical expertise. This design ensured an equivalent total contact time of approximately 540-720 minutes per participant, consisting strictly of Standard Clinical Care with Active Control

Unstructured Supportive Conversation plus Risperidone

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female inpatients diagnosed with schizophrenia according to DSM-5-TR criteria
• Aged 20 to 45 years
• In a post-acute stabilized residual phase
• Total PANSS score between 60 and 70
• Receiving risperidone at a fixed dose of 4 mg per day
• Willing and able to attend individual psychotherapy sessions throughout the 12-week trial period

You may not qualify if:

• Febrile conditions at time of screening
• Organic comorbid diseases
• Active infectious diseases
• Obesity (body mass index ≥ 30 kg/m²)
• Comorbid personality disorders
• Concurrent use of anti-inflammatory medications or antioxidant supplements
• Substance use disorder within the preceding 6 months

Sponsors & Collaborators

• Hasanuddin University: lead

Study Sites (1)

Department of Psychiatry, Faculty of Medicine, Hasanuddin University

Makassar, South Sulawesi, 90245, Indonesia

Location

MeSH Terms

Conditions

Schizophrenia; Neuroinflammatory Diseases

Interventions

Risperidone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Indrawaty Suhuyanli, MD

  Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia

  PRINCIPAL INVESTIGATOR

• Agus Durman, MD

  Department of Psychiatry, Faculty of Medicine, Hasanuddin University, Makassar, South Sulawesi, Indonesia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: June 26, 2026
• Study Start: March 1, 2025
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: June 30, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)