Edited by: Fergus Gracey, University of East Anglia, United Kingdom
Reviewed by: Jude Uzoma Ohaeri, University of Nigeria, Nsukka, Nigeria; Elizabeth Kuipers, King's College London, United Kingdom
This article was submitted to Public Mental Health, a section of the journal Frontiers in Public Health
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Schizophrenic psychoses are severe mental disorders, with a heterogeneous combination of symptoms and a lifetime prevalence of around one per cent (
The treatment of schizophrenic psychoses remains a challenge; only around half of the patients show substantial clinical improvement (
In the past few decades, psychological interventions have been shown to be effective when used in conjunction with pharmacological treatment (
The Integrated Psychological Therapy (IPT) for patients with schizophrenia is one of the first manualized integrated cognitive remediation therapy programs for groups, combining social skills, neuro- and social cognition in a single therapy (
Although both INT and IPT seem to be effective treatments for patients with schizophrenia; the therapeutic approaches differ in terms of the symptoms they address, together with how the intervention is delivered (
Generally, outpatients are less severely ill (
Therefore, we plan to conduct a single-blind, randomized, controlled trial comparing INT, IPT, and CGP in patients with schizophrenia requiring hospitalization for treatment; to assess the efficacy and feasibility of INT as a treatment programme for such patients. The main outcomes for the assessment of efficacy are changes in symptom load and functionality, together with cognitive performance. Outcomes for feasibility are retention, switch rates, and overall therapy attendance.
We have designed an 8-week, randomized, controlled, assessor-blind, three-parallel-arm trial for patients diagnosed with a schizophrenic psychosis. All patients with the diagnosis of a schizophrenic psychosis (according to the DSM 5 Diagnostic criteria) are eligible to participate. In order to allow the participation of chronic and low-functioning patients, the inclusion criteria were deliberately broad (see
Inclusion and Exclusion criteria.
Participants are competent to give informed consent, as determined by the referring physician or psychiatrist. |
Diagnosis of Schizophrenia or Schizoaffective Disorder according to DSM-5 ( |
Participants are between 18 and 65 years of age. |
Completion of regular compulsory education. |
German language proficiency as a native speaker or level B1 Common European Framework of Reference for Languages (CEFRL) ( |
Unwilling or unable to comply with study instructions. |
Low Intelligence as confirmed by failure to complete regular compulsory education. |
Currently in another psychotherapeutic treatment, either in individual or group sessions. |
Current consumption of alcohol or illicit drugs. |
The Center for Integrative Psychiatry [ZIP: (German) Zentrum für Integrative Psychiatrie], is part of the Psychiatric University Hospital of Zurich specializes in treating “heavy-users,” i.e., those patients with frequent or long-term hospitalizations for whom outpatient treatment is often insufficient. Participants will be recruited among the patients hospitalized for treatment in the Unit for Psychotic Disorders of the ZIP.
Cogpack is a computer-based neuropsychological cognitive training program, covering seven domains: visual-motor skills; processing speed; vigilance; executive functions; memory; verbal comprehension and problem- solving (
Integrated Psychological Therapy (IPT) is a manualized psychological intervention consisting of five modules (
Integrated Neurocognitive Therapy (INT) is a manualized psychological intervention consisting of four modules. Each module consists of neuro- and social-cognitive elements, together with stress and emotional regulation domains. The complexity of the modules increases successively as do the emotional demands. INT has a strategy-based-learning and a drill-and-practice approach, where the same didactic structure is applied to each domain (
Taking into account the usual length of stay in our unit, together with current recommendations, we have adapted both IPT and INT to 20 session programmes comprising the contents of all modules, whilst respecting the specifications and recommendations of the manuals. Cogpack modules are analogous to those of INT. For an overview of the parallel interventions according to TIDieR (see
Content and chedule of Interventions (ToM: Theory of Mind).
Sesion 1 | Card sorting | Information processing | Information processing |
Sesion 2 | Verbal concept | Attention/vigilance | Attention |
Sesion 3 | Verbal concept | Perception of emotions | Attention |
Sesion 4 | Search strategies | Perception of emotions | Vigilance |
Sesion 1 | Information collection | Verbal and visual learning | Verbal and visual learning |
Sesion 2 | Interpretation and discussion | Memory | Memory |
Sesion 3 | Interpretation and discussion | Social perception (ToM) | Memory |
Sesion 4 | Title finding | Social perception (ToM) | Verbal and visual learning |
Sesion 1 | Repetition/paraphrasing | Thinking / problem solving | Thinking / problem solving |
Sesion 2 | Questions and answers | Problem-solving | Thinking / problem solving |
Sesion 3 | Asking questions | Problem-solving | Thinking / problem solving |
Sesion 4 | Focussed communication | Problem-solving | Thinking / problem solving |
Sesion 1 | Cognitive processing | Social schemata | Thinking / problem solving |
Sesion 2 | Cognitive Processing | Social schemata | Thinking / problem solving |
Sesion 3 | Role-playing games | Working memory | Working memory |
Sesion 4 | Role-playing games | Working memory | Working memory |
Sesion 1 | Problem identification | Attribution | Working memory |
Sesion 2 | Generating solutions | Attribution | Working memory |
Sesion 3 | Generating solutions | Attribution | Working memory |
Sesion 4 | Implementing solutions | Emotion regulation | Working memory |
Following baseline assessment, patients will be randomly assigned (1:1:1 fashion) to either IPT or INT (active interventions) or Cogpack (control intervention). We expect six to eight participants in each treatment arm. Through randomization, there is the possibility that some participants will experience difficulties with their assigned treatment group. In such cases, patients will be permitted to switch to another treatment arm after 2 weeks. The sole criterion for switching intervention arm is patient preference due to excessive, respectively insufficient demands. We have chosen not to formulate explicit criteria for switching intervention arm for two reasons; first of all to empower patients in their commitment to therapy; second to prevent bias through the delayed selection of participants.
After participation in a minimum of 16 sessions (60–90 min each) in one treatment arm, the intervention will be completed; follow-up assessments will be carried out at 6 and 12 months. For a Study- Flow diagram (see
Schedule of enrolment, interventions, and assessments.
Eligibility screen | X | ||||||
Informed consent | X | ||||||
Allocation | X | ||||||
Switch | X | ||||||
INT | |||||||
IPT | |||||||
Cogpack | |||||||
Demographic data | X | X | |||||
Psychopathology | X | X | X | X | X | ||
Psychosocial functionality | X | X | X | X | X | ||
Neurocognition | X | X | X | X | X | ||
Medication | X | X | X | X | X | ||
Safety | X | X |
Study flow chart.
The study will be conducted in Switzerland in accordance with current regulations. The ethics committee of the Canton of Zurich approved the study protocol (BASEC Nr.: 2017- 01351). The study protocol was registered in
Study measurement and outcomes will be assessed by raters blinded regarding group allocation and treatment of the participants. Raters have a psychology degree and training in research methods. All raters have been systematically trained in the use of the study instruments. To ensure raters are blind to treatment arm, they will have no access to patient or study records beyond the strict requirements for rating.
Furthermore, rating sessions will be conducted outside the ward and treatment facilities. In the case of a participant revealing treatment arm allocation to the rater this will be documented. Following the completion of the study, such violations of blinding will be analyzed to determine whether they modified the results.
Primary outcomes are change in symptom load as measured by the Positive and Negative Syndrome Scale (PANSS) (
Outcome measurements.
Positive and Negative Syndrome Scale (PANSS) | The PANSS is a semi-structured interview designed to measure the severity of psychopathology in adult patients with a psychotic disorder, mainly schizophrenia and schizoaffective disorder ( |
Mini ICF—APP | The Mini-ICF-APP was developed ( |
MATRICS Consensus Cognitive Battery (MCCB) | The MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery was developed to provide a relatively brief evaluation of key cognitive domains relevant to schizophrenia and related disorders ( |
Clinical Global Impression (CGI) | The CGI scale is a brief, easy to use and pragmatic tool for the assessment of psychiatric illness severity and changes over time ( |
Global Assessment of Functioning (GAF) | The GAF is an observer-rated, 100-point single item scale that rates overall functioning on a continuum from mental health to mental illness ( |
Health of the Nation Outcome Scales (HoNOS) | The HoNOS is an observer-rated scale and consists of 12 items with a five-point Likert scale response format from 0 (no problems) to 4 (severe/very severe problems). Scores above two are considered clinically significant. The items were combined into four dimensions; each subject can be evaluated on items, subscale scores and the total score ( |
We calculated our required sample size using G*Power 3.1 (
All data sets of participants will be analyzed, on an intention to treat basis. Data at baseline, second week and after the intervention, as well as at 6 and 12-months post-intervention will be considered (see
Drop-outs will be replaced until the calculated number of participants has completed the intervention; all enrolled participants will be allowed to complete the intervention. Patient switching therapeutic arm will be considered as drop-outs and will be replaced correspondingly; however, they will be allowed to complete the intervention and outcomes will be assessed as scheduled. For all dropouts, an additional intention to treat, and last observation carried forward analysis will be performed.
In contrast to drop-outs the assessment of outcomes and observation of participants switching groups will be continued. Data prior to switching will be analyzed and reported separately in order to avoid bias duplication of results for a particular participant.
The outcomes of those participants who completed the intervention after switching groups will undergo a
If a participant withdraws from the study, his data will be anonymized, and his name will be deleted permanently from the study.
After completion of the study, a report for publication in a peer-reviewed journal will be prepared. The manuscript will be edited/compiled according to the CONSORT statement recommendation (
We expect all treatment arms to show similar overall rates of improvement; with differences in specific domains. Regarding symptom load, we do not expect any treatment arm to perform significantly better than the others. Regarding psychosocial functioning, we expect INT and IPT to be superior to CGP. Regarding cognitive abilities, we expect that patients participating in INT will perform better than both CGP and IPT participants.
Regarding the feasibility and implementation of the treatment arms, we expect similar retention rates in all treatment arms. Moreover, we anticipate that chronic and lower functioning participants will switch to CGP; whereas higher functioning participants may switch to INT, with lower fluctuation in IPT. Consequently, we anticipate slightly higher retention rates for IPT, followed by INT and CGP. For an overview of the expected outcomes (see
Expected outcomes.
Overall improvement (CGI) | + | + | + |
Overall functionality (GAF) | +++ | ++ | + |
Prescribed medication | + | ++ | +++ |
Drop out-switch of treatment group | +++ | ++ | + |
Completion of therapy | ++ | ++ | +++ |
Symptom load (PANSS) | + | + | + |
Symptom perception (BSI) | ++ | ++ | + |
Psychosocial functioning (mini ICF) | ++ | ++ | + |
Psychosocial functioning (HoNOS) | ++ | ++ | + |
Neurocognitive performance (MCCB) | +++ | + | ++ |
Speed of processing | ++ | + | +++ |
Verbal learning | +++ | ++ | + |
Working memory (non- verbal) | ++ | + | ++ |
Working memory (verbal) | ++ | ++ | + |
Reasoning and problem solving | +++ | ++ | ++ |
Visual learning | ++ | + | +++ |
Social cognition | ++ | ++ | + |
Attention/Vigilance | +++ | ++ | +++ |
Schizophrenia is a severe chronic disorder; those affected are frequently not able to cope with everyday challenges. Despite advances in treatment and an increase in treatment options the proportion of patients with schizophrenia who fully recover remains practically unchanged, this holds especially true for those requiring hospitalization for treatment (
The implementation of a new treatment intervention in clinical practice and moreover in an inpatient setting is a major challenge presenting a number of methodological and logistic problems. Firstly, patients hospitalized for treatment are generally more heterogeneous, with several co-morbid conditions, as well as being more severely affected than those typically included in studies. Especially patients with psychotic disorders who are more severely affected tend to have less insight and treatment motivation; consequently, they are less likely to enroll in therapy. Furthermore, the very negative and cognitive symptoms which require treatment may themselves interfere with treatment. Participants may, therefore, be unable to cope with the demands of therapy, leading to demotivation and frustration, which may lead to drop-out from therapy. We have therefore chosen to compare three treatment interventions with similar therapeutic targets and approaches, but differing participation (for patients) and implementation (for therapists) thresholds.
In clinical practice, factors relating to a patient which may affect the therapeutic outcome are considered before initiating treatment. This procedure is, however, incompatible with a randomized assignment of treatment. Furthermore, it makes it impossible to determine if a treatment is really feasible for a group of participants. Therefore, we chose to allow a switch of treatment groups after four sessions, a challenging methodological alternative which should, however, facilitate participants finding the appropriate therapy whilst allowing us to achieve our study goals. The decision to switch from one intervention to another is entirely the participant's choice. This approach strengthens the commitment of participants toward the therapy (
Taking into account that participants switching treatment arms will continue their treatment, we have decided to continue the assessment of outcomes. Baseline severity will, in such cases, correspond to the time when the main therapy began. This has as a consequence that in addition to the three original treatment arms other treatment arms emerge, namely those of switching from one treatment to another. Since we are not able to accurately foresee how many participants will use this option, and if so to which treatment option they will switch, we have decided to include this in a
The assessment of outcomes uses a variety of instruments measuring symptom load, neuro-cognitive performance and psychosocial functionality since we expect each treatment arm to show a unique response profile (
We anticipate an overall improvement in all participants, regardless of group allocation. This may be attributable to pharmacological treatments administered to the participants. For the same reason, we do not anticipate significant differences in symptom load. However, we do not exclude to find differences in dose equivalents of administered medication, primarily antipsychotics and benzodiazepines. Furthermore, we hope for a reduction of polypharmacy. In order to quantify this effect; medication, respectively dose and dose equivalents, will be taken into account as possible confounders (
The allocation of a patient to a treatment arm which does not meet his needs is considered to be unacceptable and may have detrimental effects. To avoid this situation, we have decided to allow participants to switch groups under particular conditions. We consider this approach to be both appropriate and compatible with the trial objectives since we are also interested in evaluating feasibility. In order to minimize the effect of group changes on the primary and secondary outcomes of the study, and to have similar treatment duration and number of sessions, we have chosen to conduct a second assessment prior to a (potential) change of groups. We consider 2 weeks, respectively four sessions, sufficient to determine the suitability and safety of a therapy. INT in outpatient setting shows low drop-out rates and high rates of attendance which indicates a high level of acceptance and motivation and lends support feasibility (
Another challenge of this trial was the adaptation of a treatment (INT) designed for outpatients to an inpatient setting (
Lower functioning patients with low functioning, including those with chronic schizophrenia, seem to benefit from higher frequency psychotherapy (
We considered this to be compatible with the average length of stay in our unit, since some patients remain in treatment for more than 8 weeks. Participants are also encouraged to continue participation after discharge. Although we consider that the completion of a treatment programme to be an important factor determining response, evidence suggests that response is not associated with treatment duration and number of sessions (
There is reason to believe that the three treatment arms will differ from one another due to top-down and integration effects on multiple domains. In respect of social- and neuro-cognition, we expect INT and IPT to outperform CGP (
In our study, we wish to evaluate the feasibility of a psychotherapeutic intervention in a unit specialized for the treatment of chronic and low functioning patients with a schizophrenic psychosis. Therefore, the effort required to implement such regular group psychotherapy will also be taken into account. The IPT treatment programme is manualized and has traditionally been delivered by nursing staff after an introductory seminar and workshop (
MR wrote the manuscript. DM contributed to the study design and manuscript. ES, SV, and SE contributed to the study design, study protocol and manuscript. All authors contributed to the article and approved the submitted version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Lorna McBroom: for language editing and proofreading.