Department of Psychiatry and Psychotherapy, University of Cologne
Department of Psychiatry and Psychotherapy, University of Bonn
Department of Psychiatry and Psychotherapy, University of Düsseldorf
Department of Psychiatry and Psychotherapy, University of Munich
Department of Psychiatry and Psychotherapy, University of Cologne
Department of Psychotherapy, University of Bonn
Department of Psychiatry and Psychotherapy, University of Cologne, Germany
Correspondence: Dr Andreas Bechdolf, Early Recognition and Intervention Centre for Mental Crisis (FETZ), Department of Psychiatry and Psychotherapy, University of Cologne, Kerpenerstrasse 62, 50924 Cologne, Germany. Tel: +49 221 478 3869; fax: +49 221 478 6030; e-mail: andreas.bechdolf{at}uk-koeln.de
Declaration of interest The study on the late initial prodromal state is co-funded by a research grant from SanofiSynthelabo Germany.
* Paper presented at the Third International Early Psychosis Conference,
Copenhagen, Denmark, September 2002.
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ABSTRACT |
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Aims To present the concept of the intervention studies, and to provide an interim report of the recruitment procedure.
Method Comprehensive cognitivebehavioural therapy has been developed for patients in the early initial prodromal state. For patients in the late initial prodromal state the atypical neuroleptic amisulpride is explored. Both interventions are evaluated in randomised controlled trials using clinical management as the control condition.
Results Between January 2001 and March 2003, 1212 individuals seeking help for mental health problems were screened for putative prodromal symptoms at four university centres. More than 388 individuals fulfilled criteria for both interventions and 188 (48.5%) gave informed consent to participate in the trials.
Conclusions The screening procedure appears to be feasible and trial participation seems to be acceptable to a relevant proportion of people at increased risk of developing psychosis.
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INTRODUCTION |
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An awareness programme (Köhn et al, 2002) is ongoing for psychiatric and primary healthcare services, families of patients with schizophrenia, several youth support services and the general population. It provides information about early symptoms of schizophrenia and the need for early intervention. The aims of the programme are to promote help-seeking help-seeking and engagement with early intervention services for individuals at-risk of psychosis.
A two-step approach has been created in order to identify individuals at-risk for psychosis. A checklist (Häfner et al, 2004) has been used which serves as a low-threshold screening instrument for people who have approached general practitioners or counselling services, etc. because of mental health problems. The checklist includes criteria which indicate that a contact or a referral to one of the early intervention centres should be made. At the centre, a detailed assessment is made using a specially designed instrument, the Early Recognition Inventory (ERIraos; Maurer et al, 2004). The ERIraos indicates whether the individual at-risk of psychosis is in an early initial prodromal state or a late initial prodromal state (see below), as defined by the GRNS.
When there is evidence of an early initial prodromal state (EIPS), the at-risk individual is invited to participate in a randomised controlled trial (RCT) on psychological early intervention. However, an at-risk person with evidence of a late initial prodromal state (LIPS) is asked if they will take part in an RCT with pharmacological intervention, using amisulpride. In addition to psychopathological and psychosocial psychosocial assessments, individuals are asked to take part in GRNS neurobiological research projects. These comprise neuropsychological and neurophysiological assessments, brain imaging and molecular genetics (Maier et al, 2002). Furthermore, the effect of the awareness programme is investigated by pre- and post-assessments and comparison with regions in which the awareness programme does not operate (Köhn et al, 2002) (Fig. 1). Each study was approved by the respective local ethics committees.
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INTERVENTIONS IN THE INITIAL PRODROMAL STATES |
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The LIPS criteria are similar to the ultra-high-risk measures used by current controlled intervention studies (McGorry et al, 2002; Woods et al, 2003; Morrison et al, 2004) (Appendix). Patients fulfilling LIPS criteria are highly symptomatic, functionally compromised (Miller et al, 2003) and have a risk between 36% and 54% of developing psychosis within 12 months (Miller et al, 2002; Yung et al, 2003, 2004; Mason et al, 2004). Taking this into account and also the significantly improved tolerability of the new neuroleptics, it seemed appropriate to investigate the possible benefits of pharmacological interventions for these patients. In the LIPS study, amisulpride was chosen for several reasons: at a low dose there are beneficial effects on depressive and negative symptoms, probably because of its primarily dopaminergic properties in the low-dosage range. At a higher dose it is an effective antipsychotic and data from schizophrenia studies lead us to anticipate very good tolerability with a side-effect rate no different from placebo at low doses and, not least, low weight gain (Ruhrmann et al, 2003).
Aims of both intervention studies are: (a) improvement of present prodromal symptoms; (b) prevention of social decline/stagnation; and (c) prevention or delay of progression to psychosis.
Intervention in the EIPS
Design
Patients meeting EIPS criteria are randomised to receive either
comprehensive CBT treatment or clinical management for 12 months.
Interventions in both conditions follow a detailed manual, which defines the
aims of the sessions, examples of interventions and gives model responses for
the therapist (Bechdolf et al,
2002). The recruitment period is 3 years. Assessments take place
pre- and post-treatment (12 months) and at 24-month follow-up. After the
intervention period, monthly telephone interviews are conducted to check if
there is transition to psychosis. Main rating instruments are the Early
Recognition Inventory (ERIraos; Maurer
et al, 2004), Positive and Negative Syndrome Scale
(PANSS; Kay et al,
1987), DSMIV Global Assessment of Functioning Scale
(GAFF; American Psychiatric
Association, 1994) and the MontgomeryÅsberg
Depression Rating Scale (MADRS; Montgomery
& Åsberg, 1979). At yearly intervals, the Social
Adjustment ScaleII (SASII;
Schooler et al, 1979)
is administered. Transition to psychosis is defined by commonly used criteria
(e.g. McGorry et al,
2002; Morrison et al,
2004), such as the presence of at least one psychotic symptom from
a list for brief limited intermittent psychiatric symptoms (BLIPS, see
Appendix) for longer than 6 days. In accordance with our differential
intervention approach the presence of inclusion criteria for the LIPS served
as additional exit criteria from the EIPS intervention trial.
CBT intervention
The experimental intervention is based on a CBT model
(Larsen et al, 2003). Individual therapy forms the central part of the early intervention programme.
A combination of psychoeducation, symptom, stress and crisis management
modules is adapted to the specific needs of each client. Although putative
prepsychotic symptoms serve as inclusion criteria for therapy, the
interventions are problem-oriented, collaborative, educational and involve the
therapist and the client working together on an agreed problem list. This may
also include problems other than basic symptoms, such as anxiety, depression,
family or occupational problems. Apart from the treatment of the
psychopathological symptoms, one major treatment aspect focuses on
attributional styles that underpin symptoms. Psychoeducation and cognitive
techniques are used to challenge self-stigmatisation and self-stereotypes,
helping the person to protect and enhance self-esteem, and to come to terms
with understanding the illness and pursuing life goals. A special group
intervention, cognitive remediation and a short psychoeducational multi-family
intervention are also parts of the programme
(Table 1).
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Intervention in the LIPS
Design
The LIPS project is a pharmacological phase III study conforming to good
clinical practice and has a controlled, open-label, randomised, parallel group
design. In the first condition, patients receive a psychologically advanced
clinical management programme, including, where necessary, crisis
intervention, family counselling, etc. Its primary aim is providing very
focused, supportive care for the patients acute needs (psychotherapy is
not allowed). In the second condition, similar clinical management is combined
with amisulpride. The dose can range between 50 mg and 800 mg per day, the
increase in dose follows an algorithm based on clinical improvement and
minimal time periods between changes of dosage. The treatment period is 2
years with weekly visits during the first 4 weeks, then bi-weekly until week
12, and monthly, thereafter.
Main rating instruments are ERIraos, PANSS, GAFF and, at yearly intervals, SASII. Among other instruments are the MADRS, the Extrapyramidal Symptom Rating Scale (ESRS; Chouinard et al, 1980) and the UKU Side Effect Rating Scale (UKU; Lingjaerde et al, 1987).
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RECRUITMENT |
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DISCUSSION |
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In the first 2 years of the project over 1200 help-seeking individuals were screened for at-risk mental state and almost 190 patients in the initial prodromal phase were recruited and assessed with regard to psychopathology, psychosocial and neurobiological parameters at four recently established Early Detection and Intervention centres. With almost 50% of the at-risk individuals, a high number of participants have been recruited for the psychological and pharmacological intervention trials.
Baseline assessments within the two studies indicated that help-seeking individuals with prodromal symptoms, who were randomised to receive a clinical intervention, were clinically symptomatic and functionally compromised (Ruhrmann et al, 2003; Häfner et al, 2004; Bechdolf et al, 2005a). First interim evaluations of both interventions are promising as the two approaches seem to be successful regarding the first two aims of the interventions: (1) improvement of early or late prodromal symptoms; and (2) improvement of social or occupational functioning (Ruhrmann et al, 2003; Häfner et al, 2004; Bechdolf et al, 2005a). A preliminary analysis of the EIPS study indicated advantages of CBT regarding transition to late initial prodromal state and psychosis (Häfner et al, 2004).
In summary, the GRNS Early Detection and Intervention programme, including awareness campaigns and a two-stage screening approach, appears to be feasible and effective in recruiting at-risk individuals with putatively prodromal symptoms for interventions in the initial prodromal phase. The programme will be completed by the end of 2005 and will provide a sound data-set regarding the efficacy of intervening in the initial prodromal state, the prediction of psychosis, putative underlying neurobiological variables and the effects of awareness campaigns.
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APPENDIX |
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and/or
Reduction in the DSMIV Global Assessment of Functioning score of at
least 30 points (within the past year) and at least one of the following risk
factors:
Late initial prodromal state
Presence of at least one of the following attenuated psychotic symptoms
(APS) within the last 3 months, appearing several times per week for a period
of at least 1 week:
and/or
Brief limited intermittent psychotic symptoms (BLIPS), defined as
appearance of one of the following psychotic symptoms for less than 1 week
(interval between episodes of at least 1 week), resolving spontaneously:
Exclusion and exit criteria
APS or BLIPS (early initial prodromal state).
Present or past diagnosis of a schizophrenic, schizophreniform, schizoaffective, delusional or bipolar disorder according to DSMIV.
Present or past diagnosis of a brief psychotic disorder according to DSMIV with a duration equal to or of more than 1 week or within the last 4 weeks regardless of its duration.
Diagnosis of delirium, dementia, amnestic or other cognitive disorder, mental retardation, psychiatric disorders due to a somatic factor or related to psychotropic substances according to DSMIV.
Alcohol or drug misuse within the last 3 months prior to inclusion according to DSMIV.
Diseases of the central nervous system (inflammatory, traumatic, epilepsy, etc.).
Aged <18 years and <36 years.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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