Cognitive behavioural therapy vs standardised medical care for dissociative non-epileptic seizures
| ISRCTN | ISRCTN05681227 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN05681227 |
| ClinicalTrials.gov number | NCT02325544 |
| Secondary identifying numbers | 5.0; HTA 12/26/01 |
- Submission date
- 02/03/2014
- Registration date
- 05/03/2014
- Last edited
- 07/06/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
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 have other psychological or psychiatric problems and may have other medically unexplained symptoms. It is generally thought that people with DS 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. A CBT package has been developed for people with DS. In a relatively small study, people receiving CBT overall showed greater reduction in how often they had their DS. This is a larger study across several different hospitals to obtain more definite results about the effectiveness of the CBT approach for DS.
Who can participate?
Adult patients with DS (but without current epilepsy), who have been given their diagnosis by a neurologist or specialist in epilepsy
What does the study involve?
Initial information is collected 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 are seen by a psychiatrist, who undertakes a psychiatric assessment and asks them about factors which may have led to the development of their DS. Those people who have continued to have DS in the previous 8 weeks are randomly allocated to standardised medical care or CBT (plus standardised medical care) as further treatment for their seizures. These people continue to complete seizure diaries and questionnaires, provide regular seizure frequency data following receipt of DS diagnosis and are willing to attend weekly/fortnightly sessions if allocated to CBT.
What are the possible benefits and risks of participating?
By taking part in the study, people receive information leaflets about their condition as a minimum before they receive any further assessment and treatment. This gives them access to information to which they can refer at a later date. By taking part in the comparison between treatments they will help to find out about treatments that are effective in helping people with DS as it is not known at this stage which of the two treatments will help the most. If the CBT plus standardised medical care is found to be more effective, this may affect what treatments are offered to people in the future by the NHS. In terms of risks, when people are seen by a psychiatrist, attend CBT sessions (if they are allocated to that part of the study) and fill in some of the questionnaires, they may end up thinking and talking more about their feelings and about things that have happened to them as well as about their seizures. For some people, this may be upsetting. However, psychiatrists and CBT therapists are used to helping people in distress and may be able to help patients manage these feelings. Patients are not entered into the comparison study if they and their doctor do not feel this is suitable for them. In addition, completing questionnaires, attending CBT and research interviews all take people's time.
Where is the study run from?
Institute of Psychiatry, King's College London (UK)
When is the study starting and how long is it expected to run for?
June 2014 to March 2020
Who is funding the study?
National Institute of Health Research (NIHR) (UK)
Who is the main contact?
Prof. Laura H. Goldstein
laura.goldstein@kcl.ac.uk
Contact information
Scientific
Department of Psychology
PO77, Henry Wellcome Building
Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
United Kingdom
 ORCID ID |
0000-0001-9387-3035 |
|---|
Scientific
P1.16 Henry Wellcome Building
Department of Psychology PO77
Institute of Psychiatry, Psychology and Neuroscience
De Crespigny Park
Denmark Hill
London
SE5 8AF
United Kingdom
| ORCID ID |
0000-0001-7350-4873 |
|---|---|
| Phone | +44 (0)207 848 0665 |
| izabela.pilecka@kcl.ac.uk |
Study information
| Study design | Initial observational phase followed by a parallel group two-arm multi-centre pragmatic randomised controlled trial (interventional phase) |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | COgnitive behavioural therapy vs standardised medical care for adults with Dissociative non-Epileptic Seizures: a multicentre randomised controlled trial (CODES) |
| Study acronym | CODES |
| Study hypothesis | The study sets out to 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 following diagnosis. |
| Ethics approval(s) | NRES Committee London - Camberwell St Giles, 18/12/2013, ref. 13/LO/1595 |
| Condition | Dissociative seizures (also referred to as psychogenic nonepileptic seizures) |
| Intervention | How the CBT will be delivered: CBT will be delivered over 12 sessions (each approximately one hour in length) over a 4-5 month period with one booster session at 9 months post randomisation. The model has been developed from a single case study, trialled in an open label study and then in a Pilot RCT. Thus, based on the Pilot RCT a 12-session (plus one booster session) package of CBT specifically modified for treating DS will be assessed. The model is based on the two-process fear escape-avoidance model and conceptualises DS as dissociative responses to cues (cognitive/emotional/physiological or environmental) that may (but not in all cases) have been associated with profoundly distressing or life-threatening experiences, such as abuse or trauma, at an earlier stage in the persons life and which have previously produced intolerable feelings of fear and distress. There are essentially five stages to the treatment; engagement and rationale giving; teaching and use of seizure control techniques; reducing avoidance exposure technique; dealing with seizure-related cognitions and emotions; and relapse prevention. The treatment is manualised, which is important for subsequent rollout, but the structure allows treatment to be formulation-based so that particular issues raised in therapy that might be maintaining seizure occurrence (e.g. trauma-related issues) can be addressed. Written handouts supplement the content of face-to face therapy sessions. We will record therapy sessions and undertake treatment fidelity ratings. Therapists will receive training prior to treating study patients. SMC will be provided to study patients by neurologists and psychiatrists. Neurologists will have a key role in delivering the initial diagnosis of DS, when they will: 1. Explain the disorder: i) what patients do not have (epilepsy) and why (explanation of diagnosis, i.e. a restatement of why tests have not shown organic basis, drawing attention to positive aspects of the diagnosis); ii) what they do have (describing dissociation/switching off) 2. Reassure the patient: i) they are not suspected of 'putting on' the attacks - DS are real events; ii) the disorder is common 3. Explain causes of DS: i) relation to 'stress' may not be immediately apparent; ii) the best understanding of the disorder is that there is an underlying psychological mechanism; this is a complex matter and does not simply reflect a reaction to immediate stresses 4. Regarding treatment: i) explain that AED withdrawal should be gradual; ii) many people may lose their DS following diagnosis alone; iii) cognitive behavioural therapy may be helpful for some people but not yet clear for whom 5. Provide the patient with an information sheet including direction to self-help information. Psychiatrists' provision of SMC of patients begins post diagnosis. The initial pre-randomisation clinical psychiatric assessment will include the following components and partly have a psychoeducational function: 1. Explanation of any psychiatric comorbidity and its psychopharmacological treatment 2. Reiteration of the points covered by the neurologist at diagnosis 3. Discussion of factors emerging from the clinical history that seem to have aetiological significance: relevance of predisposing, precipitating and perpetuating factors in their case if apparent 4. Acknowledge fears about a psychiatric label 5. Provision of an information sheet including direction to self-help information (as above) 6. General information provision about distraction but not specific techniques and not discussed repeatedly so that this does not become therapy. Further SMC by psychiatrists will include support, consideration of psychiatric comorbidities and any associated drug treatment and general review but no CBT techniques. The trialists will allow for some local variation in the number of neurology and psychiatry SMC sessions after randomisation. |
| Intervention type | Other |
| Primary outcome measure | Monthly DS frequency at 12 months post-randomisation. This is a continuous variable that comprises a count of seizures over a four-week exposure period and therefore will reflect all participants' outcomes, whether they improve or not during the study. Seizure frequency has been used as an outcome measure in other studies of psychological interventions for DS. Added 31/03/2020: Frequency will also be measured at baseline and 6 months post-randomisation but the outcome will be assessed at 12 months post-randomisation. |
| Secondary outcome measures | Added 31/03/2020: The following secondary outcome measures are collected at baseline, 6- and 12-month follow up (unless otherwise specified). The assessment of the outcomes is at 12 months only. 1. A rating by an informant as to whether, compared to study entry (i.e. time of diagnosis) the patient's seizure frequency is worse, the same, better or whether they are seizure free 2. Self-rated seizure severity and bothersomeness, measured using two items from the Seizure Severity Scale (Cramer et al., 2002), asking how severe and bothersome DS were in the past month 3. Seizure freedom: patients' self-reported longest period of seizure freedom in days, measured between the 6- and 12-month follow-up (and previous 6 months at baseline); and whether or not the patient is seizure free in the last 3 months of the trial 4. The number of patients in each group who at the 6- and 12-month follow-up show >50% reduction in seizure frequency, compared to baseline 5. Quality of life (QoL): a generic measure of health-related QoL, the SF-12v2 (Ware et al.,1996) to allow more direct comparison to be made with other disorders. This will also allow the calculation of QALYs, although the principal measure for doing that in this study is the EQ-5D-5L (EuroQol group, 1990), a 5-domain, 5-level, multi-attribute scale which will also be used. Added 31/03/2020: Relevant summary measures will be: SF-12v2 Physical Composite Scale (PCS), SF-12v2 Mental Health Composite Scale (MCS), and EQ-5D-5L visual analogue scale (VAS) of health today 6. Psychosocial functioning: the 5-item Work and Social Adjustment Scale (WSAS) (Mundt et al., 2002) to measure patients' own perceptions of the impact of DS on their functioning in terms of work, home management, social leisure and private leisure activities, family and other relationships 7. Psychiatric symptoms and psychological distress: anxiety, depression and somatisation measured with the GAD7 (Spitzer et al., 2006), PHQ9 (Kroenke et al., 2001) and an extended PHQ15 (Kroenke et al., 2002; Sharpe et al., 2010), derived from the Patient Health Questionnaire which reflects DSM-IV diagnoses. The GAD7 is a 7-item anxiety scale with good internal consistency (Cronbach's alpha = 0.92), test-retest reliability (intraclass correlation = 0.83), sensitivity (89%), specificity (82%) criterion, construct and factorial validity. The PHQ9 is a 9-item depression scale that can be used to diagnose major depression (DSM-IV). It has good internal consistency (Cronbach's alpha = 0.86-0.89) and test-retest reliability (r=0.84); sensitivity and specificity and construct validity are good. The PHQ15 has been shown to have high internal validity (Cronbach's alpha = 0.8) and strong convergent and discriminant validity. A general measure of psychological distress, the CORE-10 (Connell & Barkham, 2007), is also used to assess self-reported global psychological distress 8. Patients' self-rated global outcome and satisfaction with treatment. The Clinical Global Impression (CGI) (Guy 1976) change score yields a self-rated global measure of change and has been used in previous trials of CBT interventions (baseline N/A) 9. The CGI change scale rated by CBT therapists at the end of session 12 and by the SMC doctor at the 12-month follow-up (baseline N/A) 10. Health service use (including hospital attendances and admissions, GP contacts), informal care, lost work time and financial benefits (which will be used as predictors of outcome in our analysis) measured via the self-report Client Service Receipt Inventory (Beecham & Knapp, 2001) 11. Objective measure of health service use; linkage data sets from NHS Health and Social Care Information Centre (Hospital Episode Statistics) eDRIS (NHS National Services Scotland Information Services Division (ISD) and Wales (NHS Wales Informatics Service) to allow quantification of objective measures of hospital attendances and admissions pre-randomisation and during follow-up using ICD-10 codes |
| Overall study start date | 01/06/2014 |
| Overall study end date | 31/03/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Target: observational phase 501; interventional phase 298; Final: observational phase 698; interventional phase 368; please note that 368 is a subset of the 698 not an additional sample |
| Total final enrolment | 368 |
| Participant inclusion criteria | Current inclusion criteria as of 14/05/2015: Inclusion criteria applied at the initial recruitment stage: 1. Adults (≥18 years) 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 2. Ability to complete seizure diaries and questionnaires 3. Willingness to complete seizure diaries regularly and undergo psychiatric assessment 3 months after DS diagnosis 4. No documented history of intellectual disabilities 5. Ability to give written informed consent Inclusion criteria evaluated at the randomisation stage: 1. Adults (≥18 years) with DS initially recruited at point of diagnosis; 2. Willingness to continue to complete seizure diaries and questionnaires; 3. Having provided regular seizure frequency data to research team following receipt of DS diagnosis; 4. Willingness to attend weekly/fortnightly sessions if randomised to CBT 5. Both clinician and patient agree that randomisation is acceptable 6. Ability to give written informed consent; Previous inclusion criteria: Inclusion criteria applied at the initial recruitment phase: 1. Adults (≥18 years) with DS confirmed by video EEG telemetry or, where not achievable, clinical consensus 2. 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 3. Ability to complete seizure diaries and questionnaires 4. Willingness to complete seizure diaries regularly and undergo psychiatric assessment 3 months after DS diagnosis 5. No documented history of intellectual disabilities 6. Ability to give written informed consent Inclusion criteria evaluated at the randomisation phase: 1. Adults (≥18 years) with DS initially recruited at point of diagnosis 2. Willingness to continue to complete seizure diaries and questionnaires 3. Provision of regular seizure frequency data following receipt of DS diagnosis 4. Willingness to attend weekly/fortnightly sessions if randomised to CBT 5. Both clinician and patient think that randomisation is acceptable 6. Ability to give written informed consent |
| Participant exclusion criteria | Current exclusion criteria as of 14/05/2015: Exclusion criteria applied at the initial recruitment stage: 1. Having a diagnosis of current epileptic seizures as well as DS 2. Inability to keep seizure records or complete questionnaires independently 3. Meeting DSM-IV criteria for current drug/alcohol dependence 4. Insufficient command of English to later undergo CBT without an interpreter or to complete questionnaires independently 5. Having previously undergone a CBT-based treatment for dissociative seizures at a trial participating centre 6. Currently having CBT for another disorder, if this will not have ended by the time that the psychiatric assessment takes place Exclusion criteria evaluated at the randomisation stage: 1. Current epileptic seizures as well as DS, for reasons given above 2. Not having had any DS in the 8 weeks prior to the psychiatric assessment, 3 months post diagnosis 3. Having previously undergone a CBT-based treatment for dissociative seizures at a trial participating centre 4. Currently having CBT for another disorder 5. Active psychosis 6. 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 7. Current benzodiazepine use exceeding the equivalent of 10mg diazepam/day 8. The patient is thought to be at imminent risk of self-harm, after psychiatric assessment or structured psychiatric assessment by the Research Worker with the MINI, followed by consultation with the psychiatrist 9. Known diagnosis of Factitious Disorder Previous exclusion criteria: Exclusion criteria applied at the initial recruitment phase: 1. Having a diagnosis of current epileptic seizures as well as DS 2. Inability to keep seizure records or complete questionnaires independently 3. Meeting DSM-IV criteria for current drug/alcohol dependence 4. Insufficient command of English to later undergo CBT without an interpreter or to complete questionnaires independently Exclusion criteria evaluated at the randomisation phase: 1. Current epileptic seizures as well as DS, for reasons given above 2. Not having had any DS in the 8 weeks prior to the psychiatric assessment, 3 months post diagnosis 3. Having previously undergone a CBT-based treatment for dissociative seizures at a trial participating centre 4. Currently having CBT for another disorder 5. Active psychosis 6. 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 7. Current benzodiazepine use exceeding the equivalent of 10 mg diazepam/day 8. The patient is thought to be at imminent risk of self-harm, after (neuro)psychiatric assessment and structured psychiatric assessment by the Research Worker with the MINI 9. Known diagnosis of Factitious Disorder |
| Recruitment start date | 01/10/2014 |
| Recruitment end date | 31/05/2017 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
United Kingdom
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NE1 4LP
United Kingdom
NE6 4QD
United Kingdom
SO16 6YD
United Kingdom
Sponsor information
University/education
c/o Professor Reza Razavi
Vice President & Vice Principal (Research)
Room 5.31, James Clerk Maxwell Building
57 Waterloo Road
London
SE1 8WA
England
United Kingdom
| Website | http://www.kcl.ac.uk/index.aspx |
|---|---|
"ROR" |
https://ror.org/0220mzb33 |
Hospital/treatment centre
c/o Ms Jennifer Liebscher
Joint SLaM/IoP R&D Office
Institute of Psychiatry
De Crespigny Park
London
SE5 8AF
England
United Kingdom
| Website | http://www.slam.nhs.uk/ |
|---|---|
|
"ROR" |
https://ror.org/015803449 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2020 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | The trialists intend to publish the main trial findings in a high-impact peer-reviewed journal around 1 year after the overall trial end date. 2020 video in https://www.youtube.com/watch?v=pUFKbYH7BcQ (added 29/09/2020) |
| IPD sharing plan | At present anonymised data from the clinical dataset generated during and/or analysed during the RCT may be available from around 22/11/2021 until 21/05/2023 upon reasonable request. In the first instance at that point contact Prof. Laura Goldstein (laura. goldstein@kcl.ac.uk) when access criteria will be specified and further information will be available. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 27/06/2015 | Yes | No | |
| Other publications | statistical and economic analysis plan | 06/06/2017 | Yes | No | |
| Other publications | qualitative study | 09/05/2019 | 13/05/2019 | Yes | No |
| Other publications | baseline characteristics | 01/11/2019 | 28/10/2019 | Yes | No |
| Results article | results | 01/06/2020 | 22/05/2020 | Yes | No |
| Other publications | participant characteristics | 11/05/2020 | 08/10/2020 | Yes | No |
| Other publications | participant experiences | 01/10/2020 | 08/10/2020 | Yes | No |
| Other publications | psychiatrists' perspectives | 09/05/2019 | 08/10/2020 | Yes | No |
| Results article | 01/06/2021 | 05/07/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
07/06/2023: Internal review.
05/07/2021: Publication reference added.
08/10/2020: Publication references and IPD sharing statement added.
29/09/2020: The publication and dissemination plan was updated.
26/05/2020: PubMed address added.
22/05/2020: Publication reference added.
31/03/2020: The primary and secondary outcome measures fields were updated to clarify the timepoints.
28/10/2019: The overall trial end date was changed from 31/12/2019 to 31/03/2020, publication references added.
08/07/2019: Total final enrolment numbers added.
05/07/2019: The following changes were made to the trial record:
1. The overall trial end date was changed from 31/07/2018 to 31/12/2019.
2. The intention to publish date was changed from 31/07/2019 to 31/12/2020.
3. The total final enrolment number was added.
13/05/2019: Publication reference and ClinicalTrials.gov number added.
28/03/2019: Mr Iain Purdue <iain.perdue@kcl.ac.uk> has been removed as a scientific contact and Dr Izabela Pilecka <izabela.pilecka@kcl.ac.uk> has been added as a scientific contact.
24/08/2018: Sponsor details updated.
04/07/2017: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/02/2018 to 31/05/2017.
2. Publication and dissemination plan and IPD sharing statement added.
3. The Newcastle Upon Tyne Hospitals NHS Trust, Northumberland Tyne and Wear NHS Foundation Trust and University Hospital Southampton NHS Trust were added to the trial participating centres.
08/06/2017: Publication reference added.
