Comparing Different Treatments in Reducing Dissociative Seizure Occurrence

NCT02325544 | Completed DMC

• 1 other identifier: CSP 136836
• Study Type: interventional
• Target: 368
• Locations: 1 country
• Sites: 40

Brief Summary

The study will test the hypothesis that Cognitive Behavioural Therapy plus Standardised Medical Care (SMC) will have greater clinical and cost effectiveness than SMC alone in treating adult patients with dissociative seizures which had not initially ceased after diagnosis. About 12-20% of patients who attend neurology or specialist epilepsy clinics because of seizures do not in fact have epilepsy. Most of these people have what are referred to as dissociative (non-epileptic) seizures (DS). This means that they have episodes that resemble epileptic seizures but which have no medical reason for their occurrence and instead are due to psychological factors. In younger adults DS are about four times more common in women than men. A high percentage of these people will have other psychological or psychiatric problems and may have other medically unexplained symptoms. It is generally thought that people with DS will benefit from psychological treatments. However, studies on this have been small or have not compared the psychological therapy with the treatment people normally receive (standardised medical care). There is some evidence that cognitive behavioural therapy (CBT), which is a widely accepted talking therapy that focuses on the person's thoughts, emotions and behaviour, as well as considering the physical reactions and sensations that may occur in people's bodies, may lead to a reduction in how often people have DS. The investigators have previously developed a CBT package for people with DS. In a relatively small study by our group, published in 2010, people receiving CBT overall showed greater reduction in how often they had their DS. The investigators are now conducting a larger study, across several different hospitals, to obtain more definite results about the effectiveness of our CBT approach for DS. The investigators aim to invite \~ 500 adult patients with DS (but without current active epilepsy), who have been given their diagnosis by a neurologist or specialist in epilepsy, to take part in their study. Up to 698 might be invited if insufficient patients are progressing to the RCT. The investigators will collect initial information about these people and ask them to keep a record of how often they have their DS following diagnosis. Three months after the diagnosis, those who have agreed to take part in the study will be seen by a psychiatrist, who will undertake a psychiatric assessment and ask them about factors which may have led to the development of their DS. Patients who have continued to have DS in the previous 8 weeks and who meet other eligibility criteria and are willing to take part in the trial, will be randomly allocated to standardised medical care or CBT (plus standardised medical care) as further treatment for their seizures. These people will be asked to continue to complete seizure diaries and questionnaires, provide regular seizure frequency data following receipt of DS diagnosis and will need to be willing to attend weekly/fortnightly sessions if allocated to CBT. The investigators initially aim to randomise 298 people (149 to each study arm) although now allow for up to 356 to account for loss to follow-up.

Conditions

Convulsion, Nonepileptic; Conversion Disorder; Dissociative Disorder

Keywords

dissociative seizures,; psychogenic nonepileptic seizures

Outcome Measures

Primary Outcomes (1)

• Change in seizure frequency

  Monthly DS frequency

  Outcome assessed at 12 month post randomisation,

Secondary Outcomes (12)

• Change in informant rating

  Outcome assessed at 12 month post randomisation only

• Change in self-rated seizure severity

  Outcome assessed at 12 month post randomisation only

• Seizure freedom

  Outcome assessed at 12 month post randomisation only

• >50% reduction in seizure frequency

  Outcome assessed at 12 month post randomisation only

• Change in Quality of life (QoL)

  Outcome assessed at 12 month post randomisation only

Study Arms (2)

CBT+SMC

EXPERIMENTAL

12 sessions of Cognitive Behavioural Therapy adapted for DS (plus one booster session) plus standardised medical care

Behavioral: Cognitive Behavioral Therapy; Behavioral: Standardized Medical Care

SMC

ACTIVE COMPARATOR

Standardised medical care provide by neurologist and/or psychiatrist

Behavioral: Standardized Medical Care

Interventions

Cognitive Behavioral Therapy BEHAVIORAL

12 sessions of CBT (over 4-5 months) +1 booster session. Guided by a therapy manual and patient handouts; will involve setting homework tasks. Although treatment is manualised, it allows treatment to be formulation-based i.e. tailored to the person. Standardised medical as described in other intervention.

CBT+SMC

Standardized Medical Care BEHAVIORAL

Delivered by neurologists/ psychiatrists - both will be involved in discussing diagnosis. It will Include an information sheet about dissociative seizures and direction to self-help websites, general information provision about management of DS and support, consideration of psychiatric comorbidities / associated drug treatment and general review but no CBT techniques.

Also known as: Treatment as usual

CBT+SMC; SMC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adults (≥18yrs) with DS that have continued to occur within the previous 8 weeks and have been confirmed by video EEG telemetry or, where not achievable, clinical consensus; patients who have chronic DS can be included if they have been seen by the relevant Study Neurologist who has reviewed their diagnosis and communicated this to them according to the Study protocol
• ability to complete seizure diaries and questionnaires;
• willingness to complete seizure diaries regularly and undergo psychiatric assessment 3 months after DS diagnosis;
• no documented history of intellectual disabilities;
• ability to give written informed consent.
• adults (≥18yrs) with DS initially recruited at point of diagnosis;
• willingness to continue to complete seizure diaries and questionnaires;
• provision of regular seizure frequency data following receipt of DS diagnosis;
• willingness to attend weekly/fortnightly sessions if randomised to CBT
• both clinician and patient think that randomisation is acceptable
• ability to give written informed consent.

You may not qualify if:

• having a diagnosis of current epileptic seizures as well as DS. Patients with both DS and ES have been included in small studies but there is no method for verifying that patients can accurately differentiate between epileptic seizures and DS;
• inability to keep seizure records or complete questionnaires independently;
• meeting DSM-IV criteria for current drug/alcohol dependence;
• insufficient command of English to later undergo CBT without an interpreter or to complete questionnaires independently. Reasons for this include the need to self-rate secondary outcomes using scales not validated for non-English speaking populations, the considerable cost and uncertainty of being able reliably to engage sufficiently competent interpreters, and the need to demonstrate the delivery of therapy in terms of quality and manual adherence.
• having previously undergone a CBT-based treatment for dissociative seizures at a trial participating centre
• currently having CBT for another disorder, if this will not have ended by the time that the psychiatric assessment takes place.
• current epileptic seizures as well as DS, for reasons given above;
• not having had any DS in the 8 weeks prior to the psychiatric assessment, 3 months post diagnosis;
• having previously undergone a CBT-based treatment for dissociative seizures at a trial participating centre
• currently having CBT for another disorder
• active psychosis;
• meeting DSM-IV criteria for current drug/alcohol dependence; this may exacerbate symptoms/alter psychiatric state and health service use and affect recording of seizures;
• current benzodiazepine use exceeding the equivalent of 10mg diazepam/day;
• the patient is thought to be at imminent risk of self harm, after (neuro)psychiatric assessment or structured psychiatric assessment by the Research Worker with the MINI, followed by consultation with the psychiatrist.
• known diagnosis of Factitious Disorder

Sponsors & Collaborators

• King's College London: lead
• University of Edinburgh: collaborator
• University of Sheffield: collaborator
• University of Sussex: collaborator
• South London and Maudsley NHS Foundation Trust: collaborator

Study Sites (40)

Derbyshire Community Health Services Nhs Trust

Bakewell, DE45 1AD, United Kingdom

Location

Birmingham and Solihull Mental Health Nhs Foundation Trust

Birmingham, B1 3RB, United Kingdom

Location

University Hospital Birmingham Nhs Foundation Trust

Birmingham, B15 2TH, United Kingdom

Location

Berkshire Healthcare Nhs Foundation Trust

Bracknell, RG12 1LD, United Kingdom

Location

Brighton and Sussex University Hospitals Nhs Trust

Brighton, BN2 5BE, United Kingdom

Location

Cambridge University Hospitals Nhs Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

Cambridgeshire and Peterborough Nhs Foundation Trust

Cambridge, CB21 5EF, United Kingdom

Location

East Kent Hospitals University Nhs Foundation Trust

Canterbury, CT1 3NG, United Kingdom

Location

Cardiff and Vale University Local Health Board

Cardiff, CF14 4XW, United Kingdom

Location

Chesterfield Royal Hospital Nhs Foundation Trust

Chesterfield, S44 5BL, United Kingdom

Location

Dartford and Gravesham Nhs Trust

Dartford, DA2 8DA, United Kingdom

Location

Derbyshire Healthcare Nhs Foundation Trust

Derby, DE22 3LZ, United Kingdom

Location

NHS Lothian

Edinburgh, EH4 2XU, United Kingdom

Location

Medway Nhs Foundation Trust

Gillingham, ME7 5NY, United Kingdom

Location

Leeds Partnerships Nhs Foundation Trust

Leeds, LS15 8ZB, United Kingdom

Location

Leeds Teaching Hospitals Nhs Trust

Leeds, LS9 7TF, United Kingdom

Location

Barts and the London Nhs Trust

London, E1 1BB, United Kingdom

Location

East London Nhs Foundation Trust

London, E1 6LP, United Kingdom

Location

University College London Hospitals Nhs Foundation Trust

London, NW1 2PG, United Kingdom

Location

Royal Free Hampstead Nhs Trust

London, NW3 2QG, United Kingdom

Location

Guy'S and St Thomas' Nhs Foundation Trust

London, SE1 9RT, United Kingdom

Location

Lewisham Healthcare Nhs Trust

London, SE13 6LH, United Kingdom

Location

South London and Maudsley NHS Foundation Trust

London, SE5 8AZ, United Kingdom

Location

King'S College Hospital Nhs Foundation Trust

London, SE5 9RS, United Kingdom

Location

St George'S Healthcare Nhs Trust

London, SW17 0QT, United Kingdom

Location

South West London and St George'S Mental Health Nhs Trust

London, SW17 7DJ, United Kingdom

Location

Imperial College Healthcare Nhs Trust

London, W2 1NY, United Kingdom

Location

Maidstone and Tunbridge Wells Nhs Trust

Maidstone, ME16 9QQ, United Kingdom

Location

The Newcastle Upon Tyne Hospitals NHS Trust

Newcastle, NE1 4LP, United Kingdom

Location

Northumberland Tyne and Wear NHS Foundation Trust

Newcastle upon Tyne, NE6 4QD, United Kingdom

Location

Royal Berkshire Nhs Foundation Trust

Reading, RG1 5AN, United Kingdom

Location

East Sussex Healthcare Nhs Trust

Saint Leonards-on-Sea, TN37 7PT, United Kingdom

Location

Sheffield Health and Social Care Nhs Foundation Trust

Sheffield, S10 3TH, United Kingdom

Location

Sheffield Teaching Hospitals Nhs Foundation Trust

Sheffield, S5 7AU, United Kingdom

Location

University Hospital Southhampton NHS Trust

Southampton, SO16 6YD, United Kingdom

Location

Croydon Health Services Nhs Trust

Thornton Heath, CR7 7YE, United Kingdom

Location

West London Mental Health Nhs Foundation Trust

Uxbridge, UB1 3EU, United Kingdom

Location

Kent and Medway Nhs and Social Care Partnership Trust

West Malling, ME19 4AX, United Kingdom

Location

Western Sussex Hospitals Nhs Trust

Worthing, BN11 2DH, United Kingdom

Location

Sussex Partnership Nhs Foundation Trust

Worthing, BN13 3EP, United Kingdom

Location

Related Publications (12)

• Goldstein LH, Chalder T, Chigwedere C, Khondoker MR, Moriarty J, Toone BK, Mellers JD. Cognitive-behavioral therapy for psychogenic nonepileptic seizures: a pilot RCT. Neurology. 2010 Jun 15;74(24):1986-94. doi: 10.1212/WNL.0b013e3181e39658.

  PMID: 20548043 BACKGROUND

• Goldstein LH, Mellers JD, Landau S, Stone J, Carson A, Medford N, Reuber M, Richardson M, McCrone P, Murray J, Chalder T. COgnitive behavioural therapy vs standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): a multicentre randomised controlled trial protocol. BMC Neurol. 2015 Jun 27;15:98. doi: 10.1186/s12883-015-0350-0.

  PMID: 26111700 BACKGROUND

• Robinson EJ, Goldstein LH, McCrone P, Perdue I, Chalder T, Mellers JDC, Richardson MP, Murray J, Reuber M, Medford N, Stone J, Carson A, Landau S. COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): statistical and economic analysis plan for a randomised controlled trial. Trials. 2017 Jun 6;18(1):258. doi: 10.1186/s13063-017-2006-4.

  PMID: 28587649 BACKGROUND

• Jordan H, Feehan S, Perdue I, Murray J, Goldstein LH. Exploring psychiatrists' perspectives of working with patients with dissociative seizures in the UK healthcare system as part of the CODES trial: a qualitative study. BMJ Open. 2019 May 9;9(5):e026493. doi: 10.1136/bmjopen-2018-026493.

  PMID: 31072856 BACKGROUND

• Goldstein LH, Robinson EJ, Reuber M, Chalder T, Callaghan H, Eastwood C, Landau S, McCrone P, Medford N, Mellers JDC, Moore M, Mosweu I, Murray J, Perdue I, Pilecka I, Richardson MP, Carson A, Stone J; CODES Study Group. Characteristics of 698 patients with dissociative seizures: A UK multicenter study. Epilepsia. 2019 Nov;60(11):2182-2193. doi: 10.1111/epi.16350. Epub 2019 Oct 13.

  PMID: 31608436 BACKGROUND

• Goldstein LH, Robinson EJ, Mellers JDC, Stone J, Carson A, Chalder T, Reuber M, Eastwood C, Landau S, McCrone P, Moore M, Mosweu I, Murray J, Perdue I, Pilecka I, Richardson MP, Medford N; CODES Study Group. Psychological and demographic characteristics of 368 patients with dissociative seizures: data from the CODES cohort. Psychol Med. 2021 Oct;51(14):2433-2445. doi: 10.1017/S0033291720001051. Epub 2020 May 11.

  PMID: 32389147 BACKGROUND

• Wilkinson M, Day E, Purnell J, Pilecka I, Perdue I, Murray J, Hunter EM, Goldstein LH. The experiences of therapists providing cognitive behavioral therapy (CBT) for dissociative seizures in the CODES randomized controlled trial: A qualitative study. Epilepsy Behav. 2020 Apr;105:106943. doi: 10.1016/j.yebeh.2020.106943. Epub 2020 Feb 18.

  PMID: 32078929 BACKGROUND

• Read J, Jordan H, Perdue I, Purnell J, Murray J, Chalder T, Reuber M, Stone J, Goldstein LH. The experience of trial participation, treatment approaches and perceptions of change among participants with dissociative seizures within the CODES randomized controlled trial: A qualitative study. Epilepsy Behav. 2020 Oct;111:107230. doi: 10.1016/j.yebeh.2020.107230. Epub 2020 Jul 5.

  PMID: 32640411 BACKGROUND

• Stone J, Callaghan H, Robinson EJ, Carson A, Reuber M, Chalder T, Perdue I, Goldstein LH. Predicting first attendance at psychiatry appointments in patients with dissociative seizures. Seizure. 2020 Jan;74:93-98. doi: 10.1016/j.seizure.2019.11.014. Epub 2019 Nov 28.

  PMID: 31869756 BACKGROUND

• Goldstein LH, Robinson EJ, Mellers JDC, Stone J, Carson A, Reuber M, Medford N, McCrone P, Murray J, Richardson MP, Pilecka I, Eastwood C, Moore M, Mosweu I, Perdue I, Landau S, Chalder T; CODES study group. Cognitive behavioural therapy for adults with dissociative seizures (CODES): a pragmatic, multicentre, randomised controlled trial. Lancet Psychiatry. 2020 Jun;7(6):491-505. doi: 10.1016/S2215-0366(20)30128-0. Epub 2020 May 20.

  PMID: 32445688 RESULT

• Goldstein LH, Robinson EJ, Chalder T, Stone J, Reuber M, Medford N, Carson A, Moore M, Landau S. Moderators of cognitive behavioural therapy treatment effects and predictors of outcome in the CODES randomised controlled trial for adults with dissociative seizures. J Psychosom Res. 2022 Jul;158:110921. doi: 10.1016/j.jpsychores.2022.110921. Epub 2022 Apr 19.

  PMID: 35617911 DERIVED

• Goldstein LH, Robinson EJ, Pilecka I, Perdue I, Mosweu I, Read J, Jordan H, Wilkinson M, Rawlings G, Feehan SJ, Callaghan H, Day E, Purnell J, Baldellou Lopez M, Brockington A, Burness C, Poole NA, Eastwood C, Moore M, Mellers JD, Stone J, Carson A, Medford N, Reuber M, McCrone P, Murray J, Richardson MP, Landau S, Chalder T. Cognitive-behavioural therapy compared with standardised medical care for adults with dissociative non-epileptic seizures: the CODES RCT. Health Technol Assess. 2021 Jun;25(43):1-144. doi: 10.3310/hta25430.

  PMID: 34196269 DERIVED

Related Links

• CODES study website

MeSH Terms

Conditions

Seizures; Conversion Disorder; Dissociative Disorders; Psychogenic Nonepileptic Seizures

Interventions

Cognitive Behavioral Therapy; Therapeutics

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Somatoform Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Laura H Goldstein, PhD MPhil

  King's College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2014
• First Posted: December 25, 2014
• Study Start: October 1, 2014
• Primary Completion: May 31, 2017
• Study Completion: June 1, 2018
• Last Updated: October 9, 2020

Record last verified: 2016-02

Locations

GB (40)