Neuropsychiatry

J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2019-321926 on 5 November 2020. Downloaded from http://jnnp.bmj.com/ on August 6, 2022 by guest. Protected by
Review

Systematic review of psychotherapy for adults with

functional neurological disorder
Myles Gutkin  ‍ ‍,1,2 Loyola McLean  ‍ ‍,3,4 Richard Brown  ‍ ‍,5,6
Richard A Kanaan  ‍ ‍1

►► Additional material is ABSTRACT well as neuroplastic changes in emotion processing

published online only. To view, Functional neurological disorder (FND) is a common and agency perception.4 Heightened precon-
please visit the journal online
and disabling disorder that is often considered difficult
(http://d​ x.​doi.o​ rg/​10.​1136/​ scious emotional responsiveness, affective arousal,
jnnp-​2019-​321926). to treat, particularly in adults. Psychological therapies disrupted affect regulation and altered interocep-
are often recommended for FND. Outcome research tion of bodily emotional responses in people with
1
Department of Psychiatry, The on psychological therapies for FND has grown in FND are thought to contribute directly to the
University of Melbourne, Austin
recent years but has not been systematically evaluated generation of FND symptoms, through limbic influ-
Health, Heidelberg, Victoria,
Australia since 2005. This study aims to build on that by ences on awareness and control of sensory, motor
2
Consultation–Liaison Psychiatry systematically reviewing the evidence-­base for individual and behavioural functions, with early or prolonged
Department, Royal North Shore outpatient cognitive behavioural and psychodynamic psychosocial adversity being a common driver of
Hospital, Saint Leonards, New psychotherapies for FND. Medical databases were these alterations.5 Cognitive (eg, symptom-­focused
South Wales, Australia
3
Brain and Mind Centre, systematically searched for prospective studies of attention) and behavioural (eg, avoidance) factors
The University of Sydney, individual outpatient psychotherapy for FND with at are also thought to play a key role in maintaining
Camperdown, New South least five adult participants. Studies were assessed for the condition.6
Wales, Australia methodological quality using a standardised assessment
4 Psychological therapy is usually recommended
Westmead Psychotherapy
tool. Results were synthesised, and effect sizes calculated for all forms of FND, with different therapies
Program for Complex Traumatic
Disorders, Cumberland Hospital, for illustrative purposes. The search strategy identified targeting different factors in the development and
North Paramatta, New South 131 relevant studies, of which 19 were eligible for maintenance of the disorder. We group the two
Wales, Australia
5
inclusion: 12 examining cognitive behavioural therapy main types of therapies as psychodynamic therapy

copyright.
Division of Psychology and (CBT) and 7 investigating psychodynamic therapy (PDT).
Mental Health, The University of (PDT) and cognitive behavioural therapy (CBT).
Manchester, Manchester, UK Eleven were pre–post studies and eight were randomised There are several different ‘brands’ of PDT that
6
Greater Manchester Mental controlled trials. Most studies recruited a single differ in their emphases, but which share a number
Health NHS Foundation Trust, symptom-­based subtype rather than all presentations of characteristic intervention components7 that
Manchester, UK of FND. Effect sizes, where calculable, showed generally are collectively referred to as PDT here. All aim to
medium-­sized benefits for physical symptoms, mental connect FND symptoms with emotional and inter-
Correspondence to health, well-­being, function and resource use for both
Dr Myles Gutkin, Consultation– personal conflicts and experiences in the past or
Liaison Psychiatry Department, CBT and PDT. Outcomes were broadly comparable across present. A key aim in each case is to increase the
Royal North Shore Hospital, the two therapy types, although a lack of high-­quality ability to acknowledge, tolerate and communicate
Saint Leonards NSW 2065, New controlled trials of PDT is a significant limitation, as is
about difficult experiences and to manage asso-
South Wales, Australia; ​myles.​ the lack of long-­term follow-­up data in the majority
gutkin@​unimelb.​edu.​au ciated stressors more effectively. There is a large
of identified CBT trials. In conclusion, both CBT and theoretical literature on the psychodynamic treat-
Received 26 August 2019 PDT appear to potentially offer some benefit for FND, ment of FND, which can ultimately be traced to
Revised 10 September 2020 although better quality studies are needed.
its origins in Freudian psychoanalysis and related
Accepted 23 September 2020
Published Online First 5 approaches (eg, Janet).8
November 2020 CBT for FND typically focuses on reducing
INTRODUCTION symptoms by challenging maladaptive beliefs and
Functional neurological disorder (FND) is char- reversing avoidance and other unhelpful illness
acterised by distressing or disabling neurolog- behaviours.4 An active, empirical approach is
ical symptoms that are inconsistent with other adopted, with an emphasis on behaviour change
recognised neurological conditions. It is the most and hypothesis testing. We use the term broadly in
common single diagnosis in first presentations to this article to refer to all therapies with their theo-
outpatient neurology clinics and the second most retical origins in cognitive psychology, including
common neurological presenting symptom after those designed to identify and challenge unhelpful
headache.1 It is also associated with high rates of appraisals and behaviours9 (so-­ called ‘second
© Author(s) (or their
comorbid mental illness and disability.2 Although wave’ CBT) and those targeting specific cognitive
employer(s)) 2021. No
commercial re-­use. See rights FND presents with many different symptoms, and processes, such as perseverative cognition or threat
and permissions. Published there may be distinct variants with epidemiolog- monitoring (so-­called ‘third wave’ approaches).
by BMJ. ical differences (such as psychogenic non-­epileptic Unlike PDT, CBT focuses on cognitive and
To cite: Gutkin M, McLean L, seizures, PNES), it is generally thought of as a single behavioural factors that are maintaining distress and
Brown R, et al. J Neurol disorder with a core set of underlying processes.3 disability in the here and now, with relatively little
Neurosurg Psychiatry Contemporary explanations for FND empha- emphasis on emotional and interpersonal processes.
2021;92:36–44. sise dissociative and attentional mechanisms as The decreased emphasis on the historical origins of
36 Gutkin M, et al. J Neurol Neurosurg Psychiatry 2021;92:36–44. doi:10.1136/jnnp-2019-321926
 Neuropsychiatry

J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2019-321926 on 5 November 2020. Downloaded from http://jnnp.bmj.com/ on August 6, 2022 by guest. Protected by
METHODS
A systematic search strategy (online supplemental appendix
1) was applied to three major online databases (MEDLINE,
PsycINFO and Embase) to identify all prospective treatment
studies conducted on adults with any FND subtype with at least
five participants in the psychotherapy arm. Treatment had to be
psychological therapy administered to individuals in an outpa-
tient setting. Both controlled and uncontrolled studies were
included. Outcome variables measured had to include at least
one of: physical symptoms, mental health symptoms, quality
of life, function, treatment satisfaction and healthcare use.
Results were limited to articles in English published from the
1st of January 1980 (the year of publication of Diagnostic and
Statistical Manual of Mental Disorders, Third Edition (DSM-­
III), when the diagnosis of FND was revised) to the 1st of June
2020. Additional studies were identified from the reference lists
of identified studies and reviews. Abstracts were examined for
compliance with predetermined inclusion criteria by a single
reviewer and full-­length articles were obtained where relevance
was uncertain from the abstract (figure 1).
All studies that met inclusion criteria were assessed for quality
using the National Heart, Lung and Blood Institute study
quality assessment tools, standardised quality assessment tools
which identify potential sources of bias specific to controlled
Figure 1  Study selection flowchart. and uncontrolled intervention studies (available at www.​nhlbi.​
nih.​gov/​health-​topics/​study-​quality-​assessment-​tools). The tools
consist of 14 (controlled) or 12 (pre–post) items for evaluating
FND symptoms and the potential role of childhood adversity, potential flaws in study methods or implementation, including
which can be sources of conflict and resistance in therapy,10 sources of bias, confounding, study power, the strength of
mean that it may be more palatable for some patients than PDT. causality in the association between interventions and outcomes,
One potential disadvantage of this emphasis on illness beliefs and other factors. A final quality rating (good, fair or poor) was

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and behaviours is that potentially important emotional and inter- assigned for each study and reasons for a rating of poor were
personal factors may go unrecognised and unaddressed. PDT, noted.
in contrast, is particularly suited to addressing these emotional Where possible, Cohen’s d effect sizes for relevant outcome
and interpersonal aspects,7 although it may not be helpful for measures were generated by calculating the mean difference
patients who are unable or unwilling to examine their problems between groups and dividing by the pooled standard deviation.
from this perspective. Where possible, baseline measures were compared with end-­
A systematic review of psychosocial interventions for FND in of-­treatment measures and to each reported follow-­up measure
200511 concluded that all the available interventions should be separately. This included the treatment arm of controlled studies.
viewed as experimental, with only slight evidence in favour of For controlled studies, outcome measures were compared
help rather than harm. At that time, only studies of paradox- between treatment and control arms at end of treatment and
ical intention therapy and hypnosis were eligible for inclusion, at each follow-­ up time point. No quantitative synthesis was
neither of which are commonly used in the treatment of FND undertaken due to variability in outcome measures and interven-
now. Changes in diagnostic and management approaches since tions. The review complied with the 2009 Preferred Reporting
then have made diagnosis and recruitment of patients with FND Items for Systematic Reviews and Meta-­ Analyses statement
easier, contributing to an increase in psychological intervention and was registered on the PROSPERO database (registration
studies. A recent meta-­analysis of 16 studies suggests that CBT CRD42018104727).
is potentially beneficial for the subtype of PNES,12 with 47% of
eligible participants being seizure free at treatment completion,
and 82% experiencing a reduction in seizure frequency of 50% RESULTS
or more. Similar analyses have not yet been conducted on CBT We identified 19 relevant studies,13–31 the characteristics and
treatments for the broader diagnosis of FND, the potential bene- full author list of which are outlined in table 1. Elsewhere these
fits of which are less well understood. Several recent studies have studies are referred to by the first author’s surname followed by
also investigated outcomes following PDT for different types of the year of publication. Outcomes were divided into physical
FND but there has been no published attempt to summarise symptoms, mental health symptoms, well-­being (which includes
this literature, meaning that the efficacy of this approach also quality of life and measures of general health), function (which
remains uncertain. includes global, physical and occupational functional measures)
In this paper, we systematically review the evidence for outpa- and resource use (which includes medical and other healthcare
tient individual psychotherapy for adults with FND, with a service use).
focus on the evidence for PDT and CBT. Primarily psychoedu- Tables 2 and 3 display the effect sizes generated by comparing
cational, behavioural and hypnotic interventions were excluded baseline measures to end-­ of-­
treatment measures and to each
in order to focus on the utility of interventions specifically based reported follow-­ up measure separately for PDT and CBT,
on psychological theories about the aetiology and treatment of respectively. Table 4 shows effect sizes produced by comparing
FND. outcome measures between treatment and control arms at end
Gutkin M, et al. J Neurol Neurosurg Psychiatry 2021;92:36–44. doi:10.1136/jnnp-2019-321926 37
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J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2019-321926 on 5 November 2020. Downloaded from http://jnnp.bmj.com/ on August 6, 2022 by guest. Protected by
Table 1  Characteristics of identified studies
Author/s and year Location Population Sample size Study Intervention Follow-­up NHLBI quality
Goldstein et al 200413 London, UK PNES 20 B+A CBT 6 months Good (9/12)
(FEA)
LaFrance et al 200914 Rhode Island, USA PNES 21 B+A CBT Treatment end Good (10/12)
(ES-­MDD)
Goldstein et al 201015 London, UK PNES 33 CBT+SMC RCT CBT 6 months Good (11/14)
33 SMC (FEA)
LaFrance et al 201416 Rhode Island, USA PNES 9 CBT RCT CBT Treatment end Fair (9/14)
9 SSRI (ES-­MDD)
10 CBT+SSRI
10 SC
Dallocchio et al 201617 Verona, Italy Motor FND 11 CBT RCT CBT Treatment end Fair (10/14)
8 SC (FEA)
10 CBT+APA
Baslet et al 201518 Chicago, USA PNES 6 B+A CBT Treatment end Poor (6/12)
(FEA+MBT)
Sharpe et al 201119 Edinburgh and All FND 64 CBT RCT CBT 6 months Good (12/14)
Glasgow, UK 63 SC (GSH)
Myers et al 201720 Pennsylvania, USA PNES +PTSD 18 B+A CBT Treatment end Fair (9/12)
(PE)
Graham et al 201821 Leeds, UK All FND 8 B+A CBT Treatment end Fair (9/12)
(ACT)
Tolchin et al 201922 Boston, USA PNES 31 CBT #RCT CBT Treatment end Good (12/14)
29 CBT+MI (FEA±MI)
Baslet et al 202023 Boston, USA PNES 49 B+A CBT Treatment end Poor (6/12)
(FEA+MBT)
Goldstein et al 202024 England, Scotland and PNES 186 CBT+SMC RCT CBT 12 months Good (12/14)
Wales, UK 181 SMC (FEA)
Hinson et al 200625 Chicago, USA Motor FND 10 B+A PDT Treatment end Fair (9/12)
(STDP)
Reuber et al 200726 Sheffield, UK All FND 91 B+A PDT 6 months Fair (9/12)
(PIT)
Mayor et al 201027 Sheffield, UK PNES 47 B+A PDT 31–65 months Poor (7/12)
(PIT)

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Kompoliti et al 201428 Chicago, USA Motor FND 7 immediate RCT PDT 6 months Poor (8/14)
8 delayed (STDP)
Hubschmid et al 201529 Lausanne, Switzerland All FND 11 treatment RCT PDT 12 months Fair (10/14)
12 control (PIT)
Russell et al 201630 Nova Scotia, Canada PNES 28 B+A PDT 3 years Poor (7/12)
(STDP)
Santos et al 201431 Sao Paolo, Brazil PNES 37 B+A PDT Treatment end Poor (7/12)
(PA)
#RCT=RCT analysed as B+A in this review.
ACT, acceptance and commitment therapy; APA, adjunctive physical activity; B+A, before and after study; CBT, cognitive behavioural therapy; ES-­MDD, CBT for epilepsy and major depressive disorder; FEA, fear-­escape
avoidance model; FND, functional neurological disorder; GSH, guided self-­help; MBT, mindfulness-­based therapy; MI, motivational interviewing; NHLBI, National Heart, Lung and Blood Institute; PA, psychoanalysis; PDT,
psychodynamic therapy; PE, prolonged exposure; PIT, psychodynamic interpersonal therapy; PNES, psychogenic non-­epileptic seizures; PTSD, post-­traumatic stress disorder; RCT, randomised controlled trial; SC, standard
care; SMC, standardised medical care; SSRI, selective serotonin reuptake inhibitor; STDP, short-­term dynamic psychotherapy.

of treatment and at each follow-­up time point in the controlled three (Mayor 2010, Hubshmid 2015 and Russell 2016) collected
studies. Where effect sizes provided by the publication were long-­term follow-­up data for a year or more. Russell 2016 was
used, or where effect sizes could not be calculated using the stan- a substudy of PNES as part of a larger trial, and was judged to
dard technique above, this was noted in the table. be of poor quality due to a lack of detail about patient selection
The 19 studies identified were divided into those based on and the post-­hoc nature of the analysis, including introducing
CBT and those based on PDT. A description of the different new outcome measures over the course of the trial. Santos 2014
approaches used in each of the studies is provided in online was rated as poor quality due to selection bias from self-­selection
supplemental appendix 2.32–37 Where effects were associated into the treatment group (11 of 48 refused to participate and
with worse outcomes, the effect size was presented in the table were excluded) and a single self-­report outcome measure which
as a negative number. Where effect sizes were calculated using introduced reporting bias.
an odds ratio, this was indicated with an asterisk (*) after the Regarding the two larger studies, Reuber 2007 was an uncon-
number, or where this led to a non-­numerical result of infinity, trolled practice-­based evaluation of a modified form of psycho-
this was represented by an asterisk with no number. Where rele- dynamic interpersonal therapy (PIT) treating all FND that
vant data were provided in the publication but could not be trans- reported statistically significant benefits in all domains measured,
formed into effect sizes, this was represented as not calculable. which were sustained at 6 months. Mayor 2010 was also an
Of the seven studies that investigated PDT, three treated uncontrolled practice-­based trial of modified PIT, however, this
PNES, two treated all FND and two treated motor FND. The study treated PNES only. No measures were collected at treat-
majority were small (median n=28 range=10–91), although ment end, but outcomes at an average of 42 months showed
two were considerably larger (Reuber 2007 and Mayor 2010; significant benefit in all domains measured except for economic
n=91 and n=47, respectively). All but two (Hinson 2006 and activity. Effect sizes could not be calculated due to the non-­
Santos 2014) collected follow-­up data for at least 6 months, and normal distribution of the measures reported. The quality of this
38 Gutkin M, et al. J Neurol Neurosurg Psychiatry 2021;92:36–44. doi:10.1136/jnnp-2019-321926
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J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp-2019-321926 on 5 November 2020. Downloaded from http://jnnp.bmj.com/ on August 6, 2022 by guest. Protected by
Table 2  Effect sizes for pre–post comparisons in PDT studies
Effect sizes (pre–post)
12-­month
Domain Study Measure Population Sample Treatment end 6-­month follow-­up follow-­up
Physical symptoms Reuber 200726 PHQ-15 All FND 91 0.12 0.17
Hinson 200625 PMDRS Motor FND 10 1.26
Mayor 201027 PHQ-15 PNES 47 NC
Seizure freq.   NC
Mayor 201027 SF-36 (P)   NC
Hubschmid 201529 SDQ-20 All FND 11 0.84* 1.07* *
Mental health Reuber 200726 CORE All FND 91 0.27 0.31
Russell 201630 BSI PNES 28 0.69
Hinson 200625 Ham-­D Motor FND 10 2.08
BAI   1.99
Mayor 201027 CORE PNES 47 NC
SF-36 (M)   NC
Kompoliti 201428 Ham-­D Motor FND 7 0.51 0.57
BAI   0.70 1.52
Hubschmid 201529 CGI All FND 11 −0.16* 0.22* 0.73*
BDI   0.54* 0.06* 0.28*
MADRS   −0.24* −0.19* 0.14*
SF-36 (M)   0.83 1.35 2.09
Well-­being Reuber 200726 SF-36 All FND 91 0.32 0.41
Hubschmid 201529 SF-36 All FND 11 0.53 −1.37 1.04
Function Hinson 200625 PMDRS (F) Motor FND 10 1.08
GAF   0.91
Mayor 201027 Employment PNES 47 NC
Hubschmid 201529 Rankin All FND 11 0.69* 1.16* 0.97*
Employment   0.24 0.82 2.71

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Resource use Mayor 201027 Healthcare use PNES 47 NC
Hubschmid 201529 Hospital days All FND 11 −1.68 * *
A&E use   1.56 * *
Russell 201630 Doctor visits PNES 28 0.32
Doctor cost   0.35
Hospital visits   0.55
Hospital days   0.42
Hospital cost   0.42
*Calculated using OR.
A&E, Accident and Emergency; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; BSI, Brief Symptom Inventory; CGI, Clinical Global Impression; CORE, Clinical Outcomes in Routine
Evaluation; FND, functional neurological disorder; GAF, Global Assessment of Function; Ham-­D, Hamilton Depression Rating Scale; MADRS, Montgomery-­Asberg Depression Rating Scale; NC, not
calculable; PDT, psychodynamic therapy; PHQ-15, 15-­item Patient Health Questionnaire; PMDRS, Psychogenic Movement Disorders Rating Scale (F=function subscore); PNES, psychogenic non-­
epileptic seizures; SDQ-20, 20-­item Strengths and Difficulties Questionnaire; SF36, 36-­item Short Form health survey (M=mental health subscore/P=physical subscore).

study was rated as poor due to selection bias from participants conclusions cannot be drawn from the data. Hubschmid 2015
self-­selecting for treatment, and reporting bias from only 47 of reported statistically significant improvements following PIT for
66 providing follow-­up data from a mailed-­out questionnaire. all FND in the majority of measures of physical and psychiatric
Across PDT studies, all calculable pre–post (within-­ group) symptoms, as well as well-­being and some measures of healthcare
effect sizes were positive at the final time point, and generally use and no significant harms. All final pre–post (within group)
moderate to large in size although there were time points at effect sizes were positive and large (except Montgomery-­Asberg
which the effect varied substantially in Hubschmid 2015. At Depression Rating Scale and Beck Depression Inventory which
treatment end, the median pooled pre–post effect size for PDT were small), however while most final effect sizes were positive
was 0.69 with a range from −1.68 to 2.08, and at the final or neutral when calculated between groups, two showed large
follow-­up (excluding treatment end) it was 0.49 with a range negative effects (36-­item Short Form health survey and Rankin).
from 0.14 to 2.71. Closer examination reveals that, while randomisation was
There were only two controlled studies of PDT, both small. carried out, there were worse scores in the intervention group
Kompoliti 2014 reported on a randomised delayed treatment at baseline across every measure (except Clinical Global Impres-
crossover study of short-­term dynamic psychotherapy for motor sion) that were not taken into account. Coupled with the small
FND. Although beneficial effects were found in all measures sample size this precludes meaningful interpretation of between-­
when compared before and after, and between groups, the group effect sizes in this study. At treatment end, the median
authors reported that the benefit was associated with time rather pooled between group effect size for PDT was −0.03 with a
than treatment assignment. The small sample size, high dropout range from −0.99 to 3.76 and at the final follow-­up (excluding
rate, potential for selection bias and lack of intention-­to-­treat treatment end) it was 0.11 with a range from −1.28 to 0.98.
analysis led to a rating of poor quality and mean that firm Non-­numerical effect sizes were excluded.
Gutkin M, et al. J Neurol Neurosurg Psychiatry 2021;92:36–44. doi:10.1136/jnnp-2019-321926 39
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Table 3  Effect sizes for pre–post comparisons in CBT studies
Effect sizes (pre–post)
12-­month
Domain Study Measure Population Sample Treatment end 6-­month follow-­up follow-­up
Physical symptoms Goldstein 200413 Seizure freq. PNES 20 0.44 0.45
Sharpe 201119 PHQ-15 All FND 64 0.38 0.48
Dallocchio 201617 PMDRS Motor FND 11 1.46
PMDRS (M)   1.44
PHQ-15   1.56
Baslet 2015 Seizure freq. PNES 6 0.77
LaFrance 201416 Seizure freq. PNES 9 0.48*
Baslet 202023 Seizure freq. PNES 49 NC
  PHQ-15   0.19
Goldstein 202024 Seizure freq. PNES 186 NC NC
  Seizure severity   0.46 0.53
  Bothersome   0.69 0.71
Mental health Sharpe 201119 HADS (A) All FND 64 0.11 0.45
HADS (D)   0.45 0.17
LaFrance 200914 Ham-­D PNES 21 0.41
BDI   0.70
DTS   0.69
DES   0.49
SCL-90   0.48
CGI   1.95
Dallocchio 201617 Ham-­D Motor FND 11 2.12
BAI   1.35
Goldstein 200413 HADS (A) PNES 20 0.40 0.31
HADS (D)   0.54 0.48
Baslet 2012 BDI PNES 6 0.44

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DASS-A
­   0.21
Goldstein 201015 HADS (A) PNES 33 0.21 0.33
HADS (D)   0.13 0.22
Myers 2017 PDS PNES+PTSD 18 2.11
BDI   1.65
Graham 201821 CORE-10 All FND 8 1.70
Baslet 202023 BDI PNES 49 0.16
  DASS-­A   0.05
  DES   0.03
Goldstein 202024 SF-12 (M) PNES 186 0.22 0.30
  GAD-7   0.24 0.23
Well-­being LaFrance 200914 QOLIE-31 PNES 21 0.74
Tolchin 201922 QOLIE-10 PNES 31 0.21
  29+MI 0.76
Baslet 202023 QOLIE-10 PNES 49 0.19
Goldstein 202024 EQ5D5L PNES 186 0.11 0.20
Function Goldstein 200413 WSAS PNES 20 0.66 0.70
Sharpe 201119 SF-12 (F) All FND 64 0.08 0.33
LaFrance 200914 GAF PNES 21 0.86
OHS   0.18
LIFE-­RIFT   0.49
Dallocchio 201617 PMDRS (F) Motor FND 11 1.32
Goldstein 201015 WSAS PNES 33 0.76
Graham 201821 WSAS All FND 8 1.02
Goldstein 202024 SF-12 (F) PNES 186 0.08 0.08
  WSAS   0.4 0.52
*Calculated using OR.
BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; CBT, cognitive behavioural therapy; CGI, Clinical Global Impression; CORE-10, 10-­item Clinical Outcomes in Routine Evaluation;
DASS-­A, Depression Anxiety Stress Scale anxiety subscore; DES, Dissociative Experiences Scale; DTS, Davidson Trauma Scale; EQ5D5L, EuroQol 5 Dimension 5-­Level Scale; FND, functional
neurological disorder; GAD-7, 7-­item Generalised Anxiety Disorder Scale; GAF, Global Assessment of Function; HADS, Hamilton Anxiety and Depression Score (A=anxiety subscore/D=depression
subscore); Ham-­D, Hamilton Depression Rating Scale; LIFE-­RIFT, Longitudinal Interval Follow-­up Evaluation-­Range of Impaired Functioning Tool; MI, motivational interviewing; NC, not calculable;
OHS, Oxford Handicap Scale; PDS, Post-­traumatic Diagnosis Scale; PHQ-15, 15-­item Patient Health Questionnaire; PMDRS, Psychogenic Movement Disorders Rating Scale (M=motor subscore/
F=function subscore); PNES, psychogenic non-­epileptic seizures; PTSD, post-­traumatic stress disorder; QOLIE-31/10, 31/10-­item Quality of Life in Epilepsy score; SCL-90, 90-­item Symptom Checklist;
SF-12, 12-­item Short Form health survey (M=mental health subscore/F=function subscore); WSAS, Work and Social Adjustment Scale.

40 Gutkin M, et al. J Neurol Neurosurg Psychiatry 2021;92:36–44. doi:10.1136/jnnp-2019-321926

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Table 4  Effect sizes for comparisons of PDT with control and CBT with control
Effect sizes (compared with control)
6-­month 12-­month
Domain Study Measure Population Sample Control Type Treatment end follow-­up follow-­up
Physical Hubschmid 201529 SDQ-20 All FND 11 12 SC PDT 0.84* 0.38* *
symptoms Sharpe 201119 PHQ-15 All FND 64 63 SC CBT 0.25 0.13
Dallocchio 201617 PMDRS Motor FND 11 8 SC CBT 1.41
PMDRS (M) 1.99
PHQ-15 1.83
Goldstein 201015 Seizure freq. PNES 33 33 SMC CBT 0.75† 0.42†
Goldstein 202024 Seizure freq. PNES 186 182 SMC CBT NC NC
Seizure severity 0.29 0.17
Bothersome 0.39 0.34
Mental health Hubschmid 201529 BDI All FND 11 12 SC PDT 0* −0.52* 0*
MADRS −0.09* −0.41* 0*
SF-36 (M) −0.05 0.24 0.98
CGI −0.32* −0.12* 0.22*
Kompoliti 201428 Ham-­D Motor FND 7 8 SC PDT 0.59
BAI 0.53
Dallocchio 201617 Ham-­D Motor FND 11 8 SC CBT 1.58
BAI 1.31
Sharpe 201119 HADS (A) All FND 64 63 SC CBT 0.36 0.36
HADS (D) 0.29 0.32
Goldstein 201015 HADS (A) PNES 33 33 SMC CBT 0.20 0.20
HADS (D) 0.19 0.32
Goldstein 202024 SF-12 (M) PNES 186 182 SMC CBT 0.32 0.16
GAD-7 0.38 0.18
Well-­being Hubschmid 201529 SF-36 All FND 11 12 SC PDT −0.92 −2.22 −1.28
Goldstein 202024 EQ5D5L PNES 186 182 CBT 0.33 0.33

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Function Sharpe 201119 SF-12 (F) All FND 64 63 SC CBT 0.25 0.47
Hubschmid 201529 Rankin All FND 11 12 SC PDT −0.09* 0.31* −0.57*
Employment 3.76* 1.74* 0.26*
Dallocchio 201617 PMDRS (F) Motor FND 11 8 SC CBT 1.44
Goldstein 201015 WSAS PNES 33 33 SMC CBT 0.59 0.64
Goldstein 202024 SF-12 (F) PNES 186 182 CBT 0.22 0.27
WSAS 0.39 0.36
Resource use Hubschmid 201529 Hospital days All FND 11 12 SC PDT −0.99 * *
A&E use 0.41 * *
*Calculated using OR.
†Effect size provided by authors.
A&E, Accident and Emergency; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; CBT, cognitive behavioural therapy; CGI, Clinical Global Impression; EQ5D5L, EuroQol 5 Dimension
5-­Level Scale; FND, functional neurological disorder; GAD-7, 7-­item Generalised Anxiety Disorder Scale; HADS, Hamilton Anxiety and Depression Score (A=anxiety subscore/D=depression subscore);
Ham-­D, Hamilton Depression Rating Scale; MADRS, Montgomery-­Asberg Depression Rating Scale; NC, not calculable; PDT, psychodynamic therapy; PHQ-15, 15-­item Patient Health Questionnaire;
PMDRS, Psychogenic Movement Disorders Rating Scale (M=motor subscore/F=function subscore); PNES, psychogenic non-­epileptic seizures; SC, standard care; SDQ-20, 20-­item Strengths and
Difficulties Questionnaire; SF-12/36, 12/36-­item Short Form health survey (M=mental health subscore/F=function subscore); SMC, standardised medical care; WSAS, Work and Social Adjustment
Scale.

Among the Twelve studies of CBT identified, five were two focusing on PNES (Tolchin 2019 and Goldstein 2020;
controlled (Goldstein 2010 and 2020, Sharpe 2011, LaFrance n=60 and 367, respectively) and one on all FND (Sharpe 2011;
2014 and Dallochio 2016). Four of the twelve provided follow-­up n=127).
data after the end of treatment (Goldstein 2004; 2010 and 2020, The largest study (Goldstein 2020), the Cognitive Behavioural
and Sharpe 2011). Most (nine) treated only PNES (with one of Therapy for Dissociative non-­Epileptic Seizures (CODES) trial,
these, Myers 2017, treating only PNES with comorbid post-­ found no significant benefit of CBT for PNES on the primary
traumatic stress disorder (PTSD)). Of the others, two treated measure of seizure frequency compared with a standardised
all FND (Sharpe 2011 and Graham 2018) and one (Dallocchio psychiatric consultation control condition. However, there
2016) treated only motor FND. Quality ratings were generally were statistically significant benefits of CBT on longest period
higher for the CBT studies, with only two being rated as poor of seizure freedom, psychosocial functioning, self-­ rated and
quality, Baslet 2015 due to a lack of detail about enrolment, clinician-­rated global change, and healthcare treatment satisfac-
inadequate power and outcome measures which changed over tion compared with the control condition. The primary outcome
the course of the study and Baslet 2020 due to self-­selection, low effect size was not able to be calculated due to the non-­normal
rates of completion (55%) and high loss to follow-­up. distribution of the measures used; among secondary measures of
Although most had small samples sizes (median n=29; range physical symptoms, however, beneficial effects were moderate
6–367) there were three with moderate-­to-­large sample sizes, to large when compared before and after, and small to moderate
Gutkin M, et al. J Neurol Neurosurg Psychiatry 2021;92:36–44. doi:10.1136/jnnp-2019-321926 41
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when comparing to controls in reported seizure severity and The most recently published study, the multisite CODES trial,
bothersomeness. In the domains of mental health, well-­being contributes enormously to the quality of the evidence for CBT
and function, beneficial effects were small to moderate when for PNES due to its size and robust design. On the one hand,
compared before and after and between groups, however, this allows for a more confident assessment of the value of this
between group differences reduced modestly with time. modality for this subset of patients, which may be generalisable
The majority of CBT studies showed statistically significant to other subtypes of FND to an extent; on the other hand, it
benefits on measures of physical symptoms but were inconsistent allows for a more confident assessment of the limitations of
on other measures. Effect sizes which were able to be calculated CBT for PNES. Indeed, results suggest that the PNES-­specific
were mostly moderate to large for physical symptoms and small CBT intervention used was no more effective at reducing seizure
to moderate on measures of mental health, function and quality frequency than standard medical care, with only a minority of
of life. At treatment end, the median pooled pre–post effect size participants being seizure free at 12 months (20% with CBT vs
for CBT was 0.49 with a range from 0.03 to 2.12, and at the 12% of controls); measures of anxiety and depression were also
final follow-­up (excluding treatment end) it was 0.33 with a not significantly different between groups. The most important
range from 0.08 to 0.71. At treatment end, the median pooled positive outcome was that psychosocial functioning was
between group effect size for CBT was 0.67 with a range from improved significantly, perhaps reflecting the underlying theo-
0.19 to 1.99 and at the final follow-­up (excluding treatment end) retical model and the focus on avoidance behaviour in the treat-
it was 0.32 with a range from 0.13 to 0.64. ment. It may be that a CBT intervention specifically targeting
Comparing the pre–post medians of the pooled effect sizes distress and wider mental health issues (eg, PTSD) would be
at treatment end and at follow-­up, the median effect size of more effective. Heterogeneity within the patient group may also
PDT is higher on both occasions at 0.69 and 0.49, respectively, have contributed to the relatively modest effects observed in this
compared with those for CBT at 0.49 and 0.33, respectively. study.
However, when comparing treatment with control, the picture The lower quality of evidence for PDT for FND does not
is very different with the pooled median effect sizes for PDT at necessarily equate to the inferiority of this modality, and may
treatment end and end of follow-­up being much lower for PDT reflect the relative immaturity of the treatment literature in that
at −0.03 and 0.11, respectively, compared with 0.67 and 0.32, area. There is a clear need for more treatment research on PDT,
particularly in light of the inconclusive findings of the CODES
respectively. The exclusion of non-­calculable and non-­numerical
trial. In the absence of trials comparing the two approaches it is
results has a large impact on the between group median effect
impossible to say which is the most effective treatment for FND;
size for PDT, which limits the utility of this comparison.
moreover, research on psychotherapies for other mental health
conditions suggests that there is greater merit in studying which
patients should receive which treatment rather than attempting

copyright.
DISCUSSION
to identify gross differences in overall treatment efficacy.
This review identified seven studies of PDT and eleven studies of
CBT for FND. The relative preponderance of CBT studies may
be related to the empirical tradition within that literature and Applying this review to clinical practice
possibly the relative ease of studying CBT, which may be more This review supports the ongoing use of psychotherapy for FND
easily manualised and taught than some forms of PDT. Pre– in clinical practice.
post effect sizes suggest that people with FND report moderate Both CBT and PDT are dependent on the patient accepting
improvements in their mental and physical health, well-­being the possibility of psychological factors having an impact on
and functioning after both treatments, supporting their use in their symptoms in order to engage in treatment. Some types of
clinical practice. The majority of the studies identified had small PDT (particularly psychoanalysis) take many years and require
numbers of participants and most were uncontrolled, such that prolonged training and supervision. This is not true for some
spontaneous resolution, placebo/non-­specific effects and regres- contemporary PDTs but, taken together, PDT is probably more
sion to the mean cannot be excluded as explanations for the expensive than CBT.
positive clinical outcomes. The lack of high-­quality controlled Because PDT involves identifying emotional and interpersonal
studies of PDT in particular means that its efficacy compared patterns, patients need to be willing to explore these with the
with no treatment remains to be determined. therapist. Some patients with FND initially attribute their symp-
There have been more well-­ conducted controlled studies toms to non-­psychological causes, which may make it harder
pointing to the efficacy of CBT with different types of FND, in to address difficult underlying emotions. The association with
particular PNES. The greater proportion of studies on PNES may alexithymia and dissociation as well as frequent mental health
be because PNES is relatively homogeneous and more diagnosti- stigma and experiences of feeling dismissed by physicians among
cally straightforward compared with other subtypes of FND. We patients with FND may all contribute to increased resistance to
have treated them as part of the broader group of FND in our this task, limiting the acceptability of PDT for some patients.
analysis, though there is some debate as to whether PNES should
be considered a separate condition.3 One reason for ‘splitting’ Future directions
PNES off would be if treatment was different,38 which may be An important target for future research is identifying patient
the case in some respects; psychotherapeutic interventions for characteristics that might predict better responses to psycho-
inherently paroxysmal PNES may be more likely to focus on trig- therapy or that might guide selection of a particular treatment
gers, for example, rather than sustaining factors. In terms of effi- modality in order to improve patient outcomes. For CBT, this
cacy, however, there is no reason to assume that psychotherapy might include maladaptive beliefs and behaviours (eg, activity
would be more effective in any one subtype of FND (particularly avoidance) that are thought to be maintaining symptoms; for
if combined with physical therapies where indicated, such as in PDT, it may be emotional avoidance or maladaptive interper-
motor FND), and this review supports that assertion by demon- sonal patterns, including those that arise in relationships with
strating comparable outcomes across a range of subtypes. doctors and other care providers. The high rates of personality
42 Gutkin M, et al. J Neurol Neurosurg Psychiatry 2021;92:36–44. doi:10.1136/jnnp-2019-321926
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