Design and validation of standardized clinical and functional remission criteria in schizophrenia

Abstract

Background

International Remission Criteria (IRC) for schizophrenia were developed recently by a group of internationally known experts. The IRC detect only 10%–30% of cases and do not cover the diversity of forms and social functioning. Our aim was to design a more applicable tool and validate its use – the Standardized Clinical and Functional Remission Criteria (SCFRC).

Methods

We used a 6-month follow-up study of 203 outpatients from two Moscow centers and another further sample of stable patients from a 1-year controlled trial of atypical versus typical medication. Diagnosis was confirmed by International Classification of Diseases Version 10 (ICD10) criteria and the Mini-International Neuropsychiatric Interview (MINI). Patients were assessed by the Positive and Negative Syndrome Scale, including intensity threshold, and further classified using the Russian domestic remission criteria and the level of social and personal functioning, according to the Personal and Social Performance Scale (PSP). The SCFRC were formulated and were validated by a data reanalysis on the first population sample and on a second independent sample (104 patients) and in an open-label prospective randomized 12-month comparative study of risperidone long-acting injectable (RLAI) versus olanzapine.

Results

Only 64 of the 203 outpatients (31.5%) initially met the IRC, and 53 patients (26.1%) met the IRC after 6 months, without a change in treatment. Patients who were in remission had episodic and progressive deficit (39.6%), or remittent (15%) paranoid schizophrenia, or schizoaffective disorder (17%). In addition, 105 patients of 139 (51.7%), who did not meet symptomatic IRC, remained stable within the period. Reanalysis of data revealed that 65.5% of the patients met the SCFRC. In the controlled trial, 70% of patients in the RLAI group met the SCFRC and only 19% the IRC. In the routine treatment group, 55.9% met the SCFRC and only 5.7% the IRC. Results of the further independent sample demonstrated that 35% met the IRC, 65% the SCFRC, and 56% of patients met both the symptomatic and functional criteria. In the controlled trial of RLAI and olanzapine, 40% and 35% of patients, respectively, met the IRC, while 70% and 55%, respectively, met the SCFRC.

Conclusion

In schizophrenia outpatients, a greater proportion of stable cases is detected in remission by SCFRC in comparison with IRC. The SCFRC were more sensitive to the full spectrum of schizophrenia. The SCFRC appear to be valid as a tool and clinically useful as they produce a comprehensive assessment of treatment effectiveness for a wide range of patients.

Keywords:

• schizophrenia
• schizoaffective disorder
• remission criteria
• PANSS
• PSP
• long-acting risperidone (RLAI)

Acknowledgments

The authors thank the executive chief doctors of Moscow Psychiatric Outpatient Services #21 (Dr Larisa Burygina) and #1 (Dr Irina Zabelina), as well as all the medical personnel for their help in organizing and facilitating this study. The authors are also very thankful to Professor Steven Hirsch and to Dr Timothy Brow for the language editing and professional advice as well as to Ms Emma Brow and Dr Dkhaval Mavani for their English editing and technical support.

Author contributions

SNM provided the idea and the design of the study, participated in the study organization, patient consulting, data analysis, and drafting of the manuscript. AVP performed clinical assessments, including the scale rating and cognitive testing, statistical analysis, and participated in text drafting. UVU, as a district psychiatrist at Moscow Psychiatric Outpatient Service #21, was responsible for patient recruitment, diagnosing, and treatment. AAS and ABK were independent raters in validation studies and performed all assessments at Moscow Psychiatric Out patient Service #1 and in a comparative open-label randomized 12-month study of RLAI and olanzapine. All authors contributed toward data analysis, drafting, and revising the manuscript. All authors read and approved the final manuscript.

Disclosure

SNM has been a consultant or/and a free speaker for AstraZeneca, Bristol-Myers Squibb, Janssen-Cilag, Eli Lilly and Company, Lundbeck, Pfizer, and Sanofi-Aventis. UVU has been a free speaker for Janssen-Cilag. AVP, AAS, and ABK report no conflicts of interest in this work.

Supplementary materials

Glossary

Deficit syndrome

An observed state in a patient following acute psychotic illness whereby the patient has marked negative symptoms as described by the IRC and/or new personality traits (changes or shift in personality) and/or cognitive deficit, including thought disturbances, loosening of associations, etc. So the term resembles the contemporary notion of primary negative symptoms and marked cognitive disturbances acquired during the illness process (in the older Kraepelinian sense of “defect”).

Disbulia

Weakness and uncertainty of volition, any disturbance of the will or of the mental processes that lead to purposeful action (hyperbulia, hypobulia, abulia, or parabulia), usually related to Verschrobener personality changes.

Pseudopsychopathic

A variant of syndromic remission with predominant acquired personality changes following an acute psychotic episode and demonstrating symptoms and signs relating to typical psychopathy as measured on the Psychopathy Check List -Revised (PCL-R) but without necessarily premorbid evidence of personality disorder.⁴⁴

Verschrobener-like

Eccentric, quirky, peculiar, odd, strange, queer, crank, extravagant, with unpredictable behavior, usually a consequence of personality changes or shift after an acute psychotic episode (a relatively light variant of pseudopsychopathic deficit syndrome).

Clinical typology of remission in schizophrenia as observed for the SCFRC

Symptomatic, with the participation of positive symptoms

In the treated paranoid type remission patients, there was a delusional component of varying severity. The most characteristic feature was that, despite the presence of encapsulated and actively produced delusions, patients were fully or partially compensated socially; this was observed from historical data for at least 6 months. The same characteristic feature in remission patients was seen with hallucinatory and hallucinatory-paranoid types.

Hypochondria remission was characterized by persistent somatic complaints, followed by a continuous desire to be treated and the presence of senestopatii (somatesthesia) with emotional flattening, isolation, and introversion.

In patients of the obsessive remission type, signs of anankastic temperament, pedantic, unchanging commitment to the daily routine, rituals, propensity to household rechecking, and transient obsessive flashes (blasphemous thoughts, contrasting obsessions, obsessive doubts) were observed.

The thymopathic type of remission was characterized by the presence of mood change, such as of postschizophrenic depression (F20.4, ICD10), or cyclothymia, hyperthymia, or depression, which developed during recovery in affective and delusional episodes.

Syndromic, with predominant negative symptoms and personality changes – “deficit syndrome”

Asthenic remission patients were defined by the presence of elevated reactivity, vulnerability, fragility, lability, hyperesthesia, and rapid exhaustion. They were prone to feebleness and weakness. Thus, they were often observed to be more or less closed and had reduced social contact.

The sthenic variants were characterized by well-known tenacity and perseverance in achieving their goals, were productive in their contact with others, and prudent in their work. Despite their focus, they lacked situational understanding and flexibility. They had narrow interests, were emotionally labile, sharp, self-centered, coldly calculating – while being excessively pedantic.

In cases with apathetic remission, the patients were characterized by flattening of emotional displays to the point of emotional dullness, with lack of interests, weak motivation, poor accessibility, lack of friends, and passivity. In some, there was a complete indifference to the environment. These patients not only stayed at home, but they could perform simple household work, while either partially or completely taking care of themselves.

The clinical features of pseudopsychopathic-type remission included emotional and volitional impairment and, in particular, the inability to inhibit desires and to submit to the demands of others, with a lack of a sense of duty, responsibility, and persistent successive interests, and the presence of affective flatness, emotional shallowness, and moral coarsening, excessive egocentrism, explosive, combustible, and inability to empathize. In remission of the dependent personality type, Verschroben-like, and autistic changes were characteristic features, which included a reduced need for social contact and emotional attachment. These patients were shut off from the outside world, inaccessible, isolated, “unsociable”, and “gloomy”. They were also characterized by an autistic tendency, demonstrating vagueness of judgment, pedantry, and pretentiousness.