Projects

Title: Prevention of psychosis with a cognitive behavioural intervention in help-seeking young people with an at risk mental state for developing psychosis

 

Background:

Prospective longitudinal studies have found that Psychotic-like experiences (PLEs) are quite prevalent in the population. These PLEs are transient in nature and only develop into florid psychosis when persistent and combined with other risk factor such as urbanisation, trauma or cannabis use. Studies have examined the possibility of detecting individuals in the prodromal stage, prior to the development of florid psychosis. McGorry and colleagues have developed operational criteria to identify a group among help-seeking young people of an 'at risk mental state' (ARMS). Such an ARMS makes this group at ultra high risk for developing a psychosis within a year time.

Three innovative studies have been undertaken to intervene in the ARMS group to reduce the transition rate into psychosis. The Melbourne study compared needs-based intervention with low dose risperidone (1.3 mg/d) and CBT combined (n=67). The results were that 35% of needs-based intervention developed a psychotic episode versus 10% in the risperidone CBT group. The Manchester trial compared treatment as usual with CBT (n=58). In the TAU group 26% developed a DSM-IV psychosis diagnosis while the CBT group showed only 6 % transitions into psychosis. The Copenhagen trial compared integrated treatment with standard treatment (n=79). After 12 months 33% was diagnosed with psychotic disorder in schizophrenia spectrum in the standard care group and 8% in the integrated treatment group. These are encouraging results in the short term.

 

Aims:

The study aims to reduce the number of transitions into psychosis in a group of people who are in an at risk mental state. This is done with a specialised cognitive behavioural therapy.

Other aims are:

1) Implementation of screening with the Prodromal Questionnaire [23] for all people in the age range from 18 to 35,

a. Who seek psychotherapeutic help at the mental health services in The Hague, Leiden and Friesland and

b. Who are referred to a specialised clinic on suspect of development of psychosis in Amsterdam

2) Implementation of the CAARMS in the services in The Hague, Leiden, Friesland and Amsterdam to discriminate between below threshold ARMS, ARMS, and psychosis.

3) Implementation of a CBT intervention that is specifically adapted to treat ARMS with a co-morbid disorder.

4) Test the reduction of persistence of PLEs over an 18-month period.

5) Test the transition rates of different genotypes

6) Develop materials and training packages to facilitate spread of these services to other mental health facilities.

 

Methods:

All consecutive referrals to the mental health services in the age from 18 to 35 years in The Hague (PsyQ), Leiden (Rivierduinen), mental health services Friesland and the referrals from the mental health services of Amsterdam to the specialised Adolescent Clinic in the age of 18 to 35 years will be screened with the Prodromal Questionnaire.

The ARMS group will be selected for the intervention study. In the selected group, the transition rate will probably be 35 percent to psychosis over an 18-month period and about 40 percent will have persistent PLEs. The intervention will aim top reduce the transitions to 17 percent and the persistence as an important risk factor for later transition to 20 percent.

Furthermore, measurements have been matched with the EDIE-2 trial: a comparable study in Britain in Manchester, Birmingham, Glasgow, Cambridge and Norfolk. This will allow us to compare the results of the UK trial and the Dutch trial. It would be possible for certain analysis to combine data to allow greater statistical power. We will request permission with the sponsor of the UK study who owns the British data.

 

Inclusion criteria:

Group 1: Vulnerability Group. This criterion identifies young people at risk of psychosis due to the combination of a trait risk factor and a significant deterioration in mental state and/or functioning.

Group 2: Attenuated Psychotic Symptoms Group. This criterion identifies young people at risk of psychosis due to a sub threshold psychotic syndrome. That is, they have symptoms which do not reach threshold levels for psychosis due to sub threshold intensity (the symptoms are not severe enough) or they have psychotic symptoms but at a sub threshold frequency (the symptoms do not occur often enough).

Group 3: BLIPS Group. This criterion identifies young people at risk of psychosis due to a recent history of frank psychotic symptoms that resolved spontaneously (without antipsychotic medication) within one week.

 

Intervention:

The effective intervention is the Dutch translation of the protocol as developed by French and Morrison and was demonstrated to be effective. This is a formulation driven cognitive behavioural intervention directed at reducing symptoms and normalising psychotic-like experiences and preventing that a catastrophising appraisal will occur. Such an appraisal is a next step on the road to psychosis. The control condition is treatment as usual at PsyQ in The Hague, Leiden and Friesland and monitoring in Amsterdam.

 

Primary outcome:

Rate of transitions to psychosis as defined in with the CAARMS criteria. The prescription of antipsychotic medication will be considered as a transition as well. At the transition to psychosis the PANSS and the PSYRATS will be administered and the SCID interview to diagnose the patient.

 

Secondary outcome measures and other products:

1) BDI (Beck Depression Inventory)

2) SIAS (Measure of social anxiety)

3) EQ5D (Health Questionnaire)

4) PBIQ-R (personal beliefs about illness)

5) MANSA (quality of life)

6) Medication check

7) Genetic material for genotyping at a later point in development. We expect higher transitions rates in people with the val/val genotype of the COMTval158met polimorsime, and the BDNFval166met met/met genotype.

The first six measures are identical to the EDIE-2 study that now runs at Manchester, Birmingham, Glasgow, Cambridge and Norfolk. At the transition to psychosis the PANSS and the PSYRATS will be administered and the SCID interview to diagnose the patient.

8) Implementation of screening of all people in the age range from 18 to 35 that seek psychotherapeutic help at the mental health services in The Hague with the Prodromal Questionnaire.

9) Implementation of the CAARMS in the services in The Hague and Amsterdam to discriminate between normal, ARMS, and psychosis.

10) Implementation of a CBT intervention that is specifically adapted to treat ARMS with a co-morbid disorder.

11) Develop materials and training packages to facilitate spread of these kinds of services to other mental health facilities.

 

Timetable:

Month 0 to 2: Preparation of the sites. Training of the CAARMS raters. Training of the therapists in the targeted CBT protocol.

Month 3 to 26: Inclusion of patients. 6-month intervention stage (targeted CBT or TAU and 18 month since inclusions follow-up).

Months 27 to 44: Last therapies of 6-month envelope and 18 month follow-up period.

Months 45 to 48: Analysis and report.

 

Staff and partners:

Prof. dr. Mark van der Gaag (principal investigator VU/Parnassia)

Prof. dr. Pim Cuijpers (administrator VU)

Prof. dr. Erik Hoencamp (Parnassia BAVO Group)

Dr. Kees Korrelboom (PsyQ)

Prof. dr. Don Linszen (UvA)

 

Trial manager:

Marion Bruns (Parnassia)

 

PhD students:

Judith Rietdijk (VU)

Sara Dragt (AMC/UvA)

Helga Ising (Parnassia)

Rianne Klaassen (Rivierduinen)

 

Senior researchers:

Nynke Boonstra (ggz Friesland)

Dorien Nieman (AMC/UvA)

Lex Wunderink (ggz Friesland)

 

Therapists:

David van den Berg (Parnassia)

Petra Bervoets (Parnassia)

Sarah Eussen (Rivierduinen)

Gitty de Haan (Parnassia)

Mischa van der Helm (Parnassia)

Martijn Huijgen (AMC/UvA)

Lianne Kampman (ggz Friesland)

Aaltsje Malda (ggz Friesland

Carin Meijer (AMC)

Julia Meijer (AMC)

Bianca Raijmakers (Parnassia)

Annelies van Strater (Rivierduinen)

Zhenya Tatkova (Parnassia)

Swanny Wierenga (Rivierduinen)

 

Research assistants:

Sven van Amstel (Rivierduinen)

Roeline Nieboer (ggz Friesland)

Marleen Rietveld (Parnassia)

Nadia van der Spek (PsyQ Amsterdam)

Tinie van de Tang (Rivierduinen)

Jenny van der Werf (Parnassia)

Annemieke Zwart (ggz Friesland)

 

Advice and collaboration:

Dr. Lucia Valmaggia: Institute of Psychiatry London, United Kingdom

Prof. Alison Yung: University of Melbourne, Australia

Prof. Tony Morrison, dr. Paul French: University of Manchester, United Kingdom

Prof. Jim van Os, dr. Ph. Delespaul: University of Maastricht, Netherlands

 

Publications:

 

Rietdijk, J., van Os, J., de Graaf, R., Delespaul, Ph., van der Gaag, M. (2009). Are social phobia and paranoia related, and which comes first? Psychosis 1(1), 29–38.

 

De Koning, M.B., Bloemen, O.J.N., van Amelsvoort, T.A.M.J., Becker, H.E., Nieman, D.H., van der Gaag, M., Linszen, D. (2009). Early intervention in patients at ultra high risk of psychosis: benefits and risks. Acta Psychiatrica Scandinavica, 119, 426-442.

 

Rietdijk, J., Dragt, S., Klaassen, R., Ising, H., Nieman, D.H., Wunderink, L., Delespaul, Ph., Cuijpers, P., Linszen, D.H., Van der Gaag, M. (2010). Rietdijk et al.: A single blind randomized controlled trial of cognitive behavioural therapy in a help-seeking population with an At Risk Mental State for psychosis: the Dutch Early Detection and Intervention Evaluation (EDIE-NL) trial. Trials 2010 11:30.

 

van den Berg, D., van der Gaag, M. (2010). Cognitieve gedragstherapie bij het voorkomen van ernstige psychiatrische klachten. Psychopraktijk, 2 (1), 7-10.

 

Ising, H., van der Gaag, M. (2010). De vroegdetectie van psychose via screening.  Psychopraktijk 2 (2), 34-37.

 

Abstracts of presentations:

Rietdijk, J., van Os, J., Graaf, R. de, van der Gaag, M. (2008) Is social anxiety disorder a precursor or a consequence of paranoid state? Early Intervention in Psychiatry, 2, suppl 1, a61.

 

Van der Gaag, M., Rietdijk, J., Dragt, S., Wunderink, L. (2008). Prodromal questionnaire in a help-seeking population as a self-report instrument preceeding the CAARMS. Early Intervention in Psychiatry, 2, suppl 1, a61.

 

Van der Gaag, M., Rietdijk, J., Dragt, S., Klaassen, R. (2009). Preventing psychosis in a help-seeking population with distressing symptoms: preliminary results. European Archives of Psychiatry and Clinical Neuroscience, 259, (suppl 1), S25.

 

Van der Gaag, M., Stant, D., Wolters, K., Wiersma, D. (2009). The cost-effectiveness of cognitive behavioral therapy for persistent and recurrent psychosis. European Archives of Psychiatry and Clinical Neuroscience, 259, (suppl 1), S58.