Efficacy of ISST in Schizophrenia

Efficacy of "Integrated Social Cognitive and Behavioral Skills Therapy" (ISST) in Improving Functional Outcome in Schizophrenia

University Hospital, Bonn, University Hospital of Cologne, University Hospital Tuebingen, Zentralinstitut für Seelische Gesundheit Mannheim, University of Cologne, Rheinhessen-Fachklinik Alzey, Vivantes Klinikum am Urban

The ISST study investigates whether integrated social cognitive remediation and social behavioral skills therapy is more efficacious in improving functional outcome and treatment adherence than an active control treatment comprising drill-and-practice oriented neurocognitive remediation.

Deficits in social functioning are a defining, very burdening feature of schizophrenia precluding patients from participating in a satisfying life. Traditional drug and psychosocial therapy and available specific treatment strategies that directly target single key determinants of functional outcome like neurocognition, social cognition, and social behavioral skills have produced only moderate effects leaving an urgent need for further optimization. The present trial aims to more efficaciously improve functional outcome by integrating social behavioral and social cognitive treatment strategies. Six months of "Integrated Social Cognitive and Behavioral Skills Therapy (ISST)" will be compared with "Neurocognitive Remediation Therapy (NCRT)" as active control condition in a randomized multicenter clinical trial using a two group pre-post design with 2x90 patients in the remitted early phase of schizophrenia. Beyond "all-cause-discontinuation" as common primary outcome of all clinical trials of the ESPRIT-consortium, measures of functional outcome and subjective quality of life, patient experience as well as neurocognitive, social-cognitive and social behavioral measures will be assessed at baseline (V0), after completion of treatment (V6), and after 6 months follow-up (V12). ISST is expected to reduce the one-year discontinuation rate by 20% compared with NCRT, and to be superior in functional outcome measures by an effect size of at least d=0.42.

The Integrated Social Cognitive and Behavioral Skills Therapy (ISST) shall target expressive and interactional behavior skills together with those social cognitive domains (facial and prosodic affect recognition, social perception, theory-of-mind) known to be most impaired (Savla, 2012) and most closely associated with functional outcome (Fett, 2012) in schizophrenia.

The Neurocognitive Remediation Therapy (NCRT) shall target impairments in attention, memory, and executive functions as an active comparator to the ISST.

The Integrated Social Cognitive and Behavioral Skills Therapy (ISST) is a newly developed treatment program. It is based on the Training of Affect Recognition (Wölwer et al. 2005) and common social skills trainings, which are combined in an integrated rather than a sequenced manner. ISST uses both repeated practice and strategy-based training, and consists of 12 individual sessions, 5 group sessions and 1 individual final session over a period of 6 months.

The Neurocognitive Remediation Program (NCRT) is based on a neurocognitive training already used as active control condition in our earlier studies (Wölwer et al. 2005, Klingberg et al. 2011). The present version of NCRT is matched in dose, mode and scheme of application to the ISST, but differs from the ISST regarding targeted cognitive domains and preferred training strategy (predominantly drill and practice based). The NCRT provides the same amount of group interaction and companionship as well as the same amount of guided community activity as in the ISST, but is structured in such a way that interactional behavior is secondary (e.g. by competition-like tasks rather than cooperative tasks). Thus therapeutic attention and commitment are held constant across study conditions.

All Cause Discontinuation is defined as 1) not keeping appointments to treatment or diagnostic sessions as scheduled for more than 6 weeks and/or (2) not being traceable despite extensive efforts by the intervention team to reengage the patient throughout the entire intended treatment period and/or (3) withdrawal of consent by the patient (4) rater induced discontinuation of the study treatment (eg. for safety criteria) (5) not taking psychotropic drugs as prescribed for more than 14 consecutive days and/or (6) relevant worsening of symptoms.

CDSS (Calgary Depression Rating Scale for Schizophrenia, Addington, Addington & Maticka-Tyndale 1993)

Assessed every 4-6 weeks from date of randomization until 1 year or until discontinuation (whatever came first)

Assessed every 4-6 weeks from date of randomization until 1 year or until discontinuation (whatever came first)

Inclusion Criteria: Written informed consent DSM-IV-TR diagnosis of schizophrenia (295.10-30, 295.90) PANSS at baseline: total score ≤ 75 Proficiency in German language. Exclusion Criteria: Lack of accountability Positive urine drug-screening for illicit drugs at screening (except cannabinoids and benzodiazepines) Serious suicidal risk at screening visit Other relevant axis 1-diagnoses according to diagnostic interview (MINI); Other relevant neurological or somatic disorders Verbal IQ<80 (MWT-B)

Data shall be shared within the German research network ESPRIT (Enhancing Schizophrenia Prevention and Recovery through Innovative Treatments) as well as with other German research networks funded by the BMBF (call "Psychische Erkrankungen").

Wolwer W, Frommann N, Lowe A, Kamp D, Weide K, Bechdolf A, Brockhaus-Dumke A, Hurlemann R, Muthesius A, Klingberg S, Hellmich M, Schmied S, Meyer-Lindenberg A; ISST study group. Efficacy of Integrated Social Cognitive Remediation vs. Neurocognitive Remediation in Improving Functional Outcome in Schizophrenia: Concept and Design of a Multicenter, Single-Blind RCT (The ISST Study). Front Psychiatry. 2022 Jun 21;13:909370. doi: 10.3389/fpsyt.2022.909370. eCollection 2022.