Original Article

Journal of Child Neurology

2023, Vol. 38(6-7) 394-406
Caregivers’ Perspectives on the Impact of © The Author(s) 2023

Cannabidiol (CBD) Treatment for Dravet and Article reuse guidelines:

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Lennox-Gastaut Syndromes: A Multinational DOI: 10.1177/08830738231185241

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Qualitative Study

Jade Marshall, MEng, MSc1, Hanna Skrobanski, MSc, PhD2,

Lisa Moore-Ramdin, MBBS, MRCPCH, DPM, MFPM1, Klaudia Kornalska, MSc2,
Paul Swinburn, MRes2, and Sally Bowditch, MPH, BSc1

Abstract
Objective: To increase understanding of the impact of cannabidiol (CBD) on outcomes beyond seizure control among individ-
uals with Dravet syndrome or Lennox-Gastaut syndrome.
Methods: Qualitative interviews were conducted with caregivers of individuals with Dravet syndrome or Lennox-Gastaut syn-
drome treated with plant-derived, highly purified CBD medicine (Epidiolex in the USA; Epidyolex in Europe; 100 mg/mL oral
solution). Symptoms and impacts of Dravet syndrome and Lennox-Gastaut syndrome on individuals were explored, as were
the effects of CBD. Data were analyzed using thematic analysis.
Results: Twenty-one caregivers of individuals with Dravet syndrome (n = 14) and Lennox-Gastaut syndrome (n = 7) aged 4-22
years participated. Health-related quality of life improvements associated with CBD included cognitive function, communication,
behavior, mobility, and participation in daily activities. Seizure frequency reduction was commonly reported (n = 12), resulting in
caregivers having greater freedom and family life being less disrupted. Adverse events were reported by 10 caregivers.
Conclusion: In addition to reduced seizure frequency, CBD may have a wide range of beneficial effects beyond seizure control
that warrant further investigation.

Keywords
antiseizure drugs, behavior, epilepsy, quality of life, seizures

Received August 23 2022; Received revised May 3 2023; Accepted for publication June 7 2023.

Introduction
Dravet syndrome and Lennox-Gastaut syndrome are rare, severe
developmental and epileptic encephalopathies.1–4 Both syndromes
have early childhood onset and impact mortality.1–3,5–8 Dravet
syndrome and Lennox-Gastaut syndrome also exhibit multiple
seizure types and a high degree of treatment resistance.3,4,9
Health-related quality of life is considerably impacted in patients
with Dravet syndrome and with Lennox-Gastaut syndrome,10–12
and their caregivers.12,13 In addition to epileptic seizures, factors
that may contribute to lowered patient health-related quality of
life include affected mobility,1,11–14 cognitive impairment,1,11,15
and eating difficulties or reduced appetite.15,16
Highly purified cannabidiol (CBD; Epidiolex in the United
States and Epidyolex in the United Kingdom and European
Union [GW Pharma (International) BV, now part of Jazz
Pharmaceuticals, Inc]) has demonstrated efficacy for seizure
control with an acceptable safety profile in patients with Dravet
syndrome and Lennox-Gastaut syndrome in 4 randomized con-
trolled trials.17–20 However, there is limited evidence of CBD
effects beyond seizure control for patients with Dravet syndrome
and Lennox-Gastaut syndrome, and their caregivers.
Evidence from open-label studies of CBD in patient popula-
tions with treatment-resistant epilepsy suggests that CBD has
positive impacts on health-related quality of life independent
of reduced seizure frequency effects.21,22 Retrospective
studies have also found that caregivers and patients with
treatment-resistant epilepsy report improved sleep, mood, com-
munication, language use, and behavior/alertness after patient
treatment with CBD-enriched cannabis or oral cannabis
extracts.23–25 Similarly, a recent observational clinical audit at
2 UK neurology centers found positive effects of CBD on
1
Jazz Pharmaceuticals, Inc, London, UK
2
Acaster Lloyd Consulting Ltd, London, UK
Corresponding Author:
Sally Bowditch, Jazz Pharmaceuticals, Inc, 1 Cavendish Place, London, W1G
0QF, UK.
Email: sally.bowditch@jazzpharma.com
Marshall et al
cognition, particularly regarding language, in adults with
Dravet syndrome, even without significant reduction in
seizures.26
Quality of life, adaptive behavior, and cognition measures
were included as secondary endpoint variables in the CBD clin-
ical trials.17–20 However, in the largest pivotal trials of CBD in
Dravet syndrome and Lennox-Gastaut syndrome, the numbers
of patients who completed quality of life and adaptive behaviors
scores, eg, Quality of Life in Childhood Epilepsy (QOLCE) and
composite Vineland-II scores, were low, limiting the interpret-
ability of results.18,20 A recent review highlighted that the
Vineland Adaptive Behavior Scales may be insensitive to func-
tional changes among children with Lennox-Gastaut syndrome
due to the high degree of impairment among most children.27
The QOLCE was developed for use in patients with epilepsy
and includes items that are not applicable to patients with
severe epilepsy and associated learning difficulties, such as
those seen in Dravet syndrome and Lennox-Gastaut syndrome.
The absence of appropriate instruments limits the ability to gen-
erate quantitative evidence of health-related quality of life out-
comes in a clinical trial setting.
Qualitative research is an established field that enables
in-depth exploration of the impact of a condition and its treatment
on patients or caregivers by allowing them to speak freely about
their experiences outside the constraints of closed question
surveys or questionnaires.28,29 This allows caregivers and
patients to identify and prioritize aspects of the patient’s condition
that are important to them and generates rich contextual data on
the meaning and experience of health, illness, and treatment for
patients or caregivers, as well as the wider impact on their
lives.28 This is particularly useful for rare diseases where quanti-
tative research is lacking. To date, no qualitative studies have
examined the impact of CBD on individuals with Dravet syn-
drome or Lennox-Gastaut syndrome, or specifically explored
the impact of CBD on outcomes beyond seizure control.
The study aim was to understand the impact of ≥6 months of
treatment with CBD on outcomes beyond seizure control (eg,
cognition, behavior, and health-related quality of life) among
individuals with Dravet syndrome or Lennox-Gastaut syn-
drome, their caregivers, and their wider family.
Methods
Study Design and Recruitment
A qualitative interview study with caregivers of individuals with
Dravet syndrome or Lennox-Gastaut syndrome treated with plant-
derived highly purified CBD medicine (Epidiolex [USA], Epidyolex
[UK and Germany]; 100 mg/mL oral solution) in the United States,
the United Kingdom, and Germany was conducted. Recruitment
occurred between February and June 2021 via local patient advocacy
groups and a market research agency (US participants only).
Interested caregivers were provided with a study information sheet
and were asked to complete a screening form.
The study aimed to recruit 20 caregivers per syndrome (n = 40 in
total), based on qualitative research guidelines, which recommend
sample sizes of between 20 and 30 per cohort to achieve data saturation
395
(ie, a point where no new themes or topics emerge).30 A purposive
sampling framework was used, whereby a broad patient age range
and variation in patient intellectual ability were targeted to enable sub-
group comparisons and a wide range of caregiver perceptions and
experiences to be captured.
To minimize bias, it was planned for participants to be blinded to the
study’s focus on CBD during screening prior to interview. The screening
process comprised a 5-minute questionnaire that included 9 questions on
participant and patient characteristics (eg, age, residence, patient diagnosis,
relationship to the patient, etc) and previous patient treatment. During the
initial blinded screening process, a large proportion of participants were
found to be ineligible because the patient had not received CBD for at
least 6 months. At this time, CBD had been relatively recently approved
in the United Kingdom, so only a small proportion of patients were
taking CBD. Ineligible caregivers and patient advocacy groups reported
frustration over the substantial time that caregivers had wasted in complet-
ing the screening process and perceived this as avoidable. Taking into
account the substantial burden of caring for someone with complex
needs, as well as respecting the impact that their caring responsibilities
have on their time, it was decided to inform potential participants of the
study’s focus on CBD before screening to lower the number of caregivers
spending time completing the screening form unnecessarily.
Participants
Inclusion criteria for caregiver participants were as follows: aged ≥18
years; the main, unpaid caregiver of an individual with Dravet syn-
drome or Lennox-Gastaut syndrome aged ≥2 years who had received
CBD medicine for a minimum of 6 months; a resident in the United
States, the United Kingdom, or Germany; and willing to participate
in an audio-recorded interview. Participants were excluded from the
study if they did not meet the inclusion criteria.
All participants were required to provide written informed consent
prior to study participation.
Procedures
Consenting participants completed a background questionnaire on
sociodemographic characteristics, time spent caring, and the patient’s
clinical characteristics. Responses were used to ensure interview ques-
tions were appropriate for the patient’s condition and treatment
characteristics.
All semistructured interviews were conducted using an interview
guide, developed based on a targeted literature review of the symptoms
and impacts of Dravet syndrome and Lennox-Gastaut syndrome (see
Supplemental information). The guide was designed to initially
encourage spontaneous reporting of symptoms of Dravet syndrome/
Lennox-Gastaut syndrome and the impacts on the patient and caregiv-
ers’ health-related quality of life. Caregivers’ views about the symp-
toms of Dravet syndrome and Lennox-Gastaut syndrome currently
experienced, as well as the broader health-related quality of life
impacts on patients, caregivers, and other family members (eg, on
daily or social activities), were then explored. Caregivers were subse-
quently asked whether symptoms or broader impacts had changed over
time and whether this occurred following initiation of treatment with
CBD. This structure allowed participants to speak freely about any
seizure- or beyond-seizure-related impacts of CBD before they were
prompted to speak about this topic, with the aim to minimize potential
bias such as recall and social desirability bias. The interview concluded
with general questions on the caregivers’ experiences of CBD.
396 Journal of Child Neurology 38(6-7)

Interviews were conducted by 3 experienced interviewers using
online video conferencing. All interviews were audio recorded to
permit transcription. German language transcripts were translated
into English prior to analysis. The interviews and transcripts were dei-
dentified and assigned participant identification numbers. All research-
ers involved in the analysis had postgraduate degrees in relevant fields
and more than 19 years’ combined qualitative research experience. The
researchers had no personal experience with epilepsy or seizures, or
familiarity with the study participants.
Analysis
Data from the background questionnaires were summarized descrip-
tively. Interview data were analyzed using thematic analysis in
MAXQDA 2020 (generation 20.3.0), a method for identifying, analyz-
ing, and reporting themes in qualitative data.31 The analysis followed
the 6 stages outlined by Braun and Clarke: familiarization, generation
of codes, searching for themes, reviewing themes, defining the themes,
and reporting.
A coding framework was developed based on the topics covered in
the interview guide. A sample of transcripts were independently coded
by 2 researchers who conducted the interviews; findings were com-
pared and discrepancies discussed. The coding framework was
revised following this discussion, and the remaining transcripts were
coded by 3 researchers. Additional data-driven amendments were
made to the coding framework throughout the coding process.
The codes were then grouped into themes relating to the symptoms
and impacts of Dravet syndrome and Lennox-Gastaut syndrome and
experience with CBD. A conceptual model was developed to illustrate
the symptoms and impacts experienced by individuals with Dravet
syndrome/Lennox-Gastaut syndrome, and the moderating impact of
CBD on these symptoms and impacts.
Data saturation was monitored during the analysis using saturation
matrices to ensure all relevant concepts were fully represented, follow-
ing the methodology suggested by Leidy and Vernon.32
Results
Sample Characteristics
A sample of 21 caregivers (Dravet syndrome = 14; Lennox-Gastaut
syndrome = 7) was achieved. Three caregivers were recruited
through blind screening and 18 through unblinded screening. All,
except 1 caregiver, cared for an individual currently being treated
with CBD (n = 20). Caregiver and patient characteristics are detailed
in Tables 1 and 2. Despite difficulties with recruitment, data satura-
tion matrices provided some evidence that saturation had been
reached, with all but 2 concepts emerging in the first 5 interviews.
Frequencies of spontaneous and prompted reporting of con-
cepts relating to symptoms and functions, and impacts on indi-
viduals with Dravet syndrome or Lennox-Gastaut syndrome,
caregivers, and families are shown in Figures 1 and 2.
Current Symptoms and Functions of Dravet Syndrome
and Lennox-Gastaut Syndrome
Figure 3 shows the conceptual model, illustrating current symp-
toms and impacts of Dravet syndrome and Lennox-Gastaut syn-
drome among individuals living with these conditions.
Seizures. All individuals experienced epileptic seizures.
Seizures were commonly reported to be unpredictable, and

Table 1. Caregiver Characteristics (n = 21).a

DS (n = 14; 67%) LGS (n = 7; 33%)

Mean (SD; range) age (y) 42.29 (7.75; 29-55) 44.86 (11.04; 25-57)
Mean (SD; range) hours spent providing practical and emotional care per week 96.79 (50; 25-168) 120.29 (45.14; 50-168)
Occupation, n (%)
Employed full time 3 (21) 1 (14)
Employed part time 4 (29) 2 (29)
Self-employed 2 (14) 1 (14)
Full-time homemaker/caregiver 7 (50) 3 (43)
Country of residence, n (%)
United States 12 (86) 6 (86)
Germany 1 (7) 1 (14)
United Kingdom 1 (7) 0 (0)
Relationship to individual, n (%)
Mother 13 (93) 7 (100)
Father 1 (7) 0 (0)
Current living situation, n (%)
Living with partner 13 (93) 4 (57)
Living alone 0 (0) 2 (29)
Other 1 (7) 1 (14)
Impact of caring responsibility on work, n (%)
Stopped working 11 (79) 5 (71)
Reduced working hours 9 (64) 3 (43)
Changed job 6 (43) 4 (57)
Abbreviations: DS, Dravet syndrome; LGS, Lennox-Gastaut syndrome; SD, standard deviation.
a
Sum of percentages does not equal 100 in every instance, as some caregivers selected more than one option for certain questions.
Marshall et al 397

Table 2. Characteristics of Individuals With DS or LGS (n = 21).

Characteristic DS (n = 14; 67%) LGS (n = 7; 33%)

Mean (SD; range) age (y)
At diagnosis 1.23 (1.03; 0.50-3) 6.20 (5.89; 1-16)
Current 9.29 (4.66; 4-20) 14.86 (6.18; 6-22)
Mean (SD; range) duration of CBD treatment (n = 17; y) 3.03 (1.98; 0.67-7.33) 1.5 (0.88; 0.58-2.33)
Current antiseizure medication, n (%)
CBD 14 (100) 6 (86)
Cenobamate 1 (7) 2 (29)
Clobazam 11 (79) 5 (71)
Clonazepam 0 (0) 2 (29)
Felbamate 1 (7) 2 (29)
Fenfluramine 2 (14) 0 (0)
Lamotrigine 0 (0) 1 (14)
Levetiracetam 2 (14) 3 (43)
Rufinamide 0 (0) 2 (29)
Sodium valproate 4 (29) 1 (14)
Stiripentol 3 (21) 1 (14)
Topiramate 3 (21) 0 (0)
Zonisamide 2 (14) 2 (29)
Abbreviations: CBD, cannabidiol; DS, Dravet syndrome; LGS, Lennox-Gastaut syndrome; SD, standard deviation.

seizure type, length, and frequency varied on a monthly,
weekly, or daily basis:
There is no rhyme or reason to his [seizures]… they will just
happen… he’s very unpredictable and everything, so we have
to make sure that we are always on guard.—Caregiver of
patient with Dravet syndrome aged 6 years
Seizure types included tonic-clonic (Dravet syndrome = 11;
Lennox-Gastaut syndrome = 6), clonic (Dravet syndrome = 2;
Lennox-Gastaut syndrome = 1), tonic (Dravet syndrome = 1;
Lennox-Gastaut syndrome = 2), atonic (Dravet syndrome = 5;
Lennox-Gastaut syndrome = 4), absence (Dravet syndrome =
6; Lennox-Gastaut syndrome = 4), focal with impaired aware-
ness (Dravet syndrome = 5; Lennox-Gastaut syndrome = 1),
and myoclonic (Dravet syndrome = 7; Lennox-Gastaut syn-
drome = 2). Seizure frequency ranged between 0 and 50 per
day. Tonic-clonic seizures were typically reported to occur 2
to 4 times a week.
Cognitive function and communication. All caregivers stated
that their child had limited cognitive function and delayed devel-
opment. Some also reported impaired short-term memory (Dravet
syndrome = 4; Lennox-Gastaut syndrome = 1):
If you ask her something on a typical day “What did you do at
school?” her automatic response is “Lunch.” And she likes her
lunch, but if you try to ask her about an art project that she
brought home, or an activity that you know went on, maybe
one out of three times she’ll be able to recall that even with a
specific question being asked.—Caregiver of patient with
Dravet syndrome aged 14 years
Conversely, 3 caregivers noted their child had comparatively
functional long-term memory (Dravet syndrome = 2;
Lennox-Gastaut syndrome = 1).
Some caregivers reported their child struggled with plan-
ning, problem solving, and understanding abstract concepts,
such as time, safety, and danger (Dravet syndrome = 3;
Lennox-Gastaut syndrome = 2):
There’s a lot of concepts that are still very difficult to him, espe-
cially with safety, that’s a huge problem. It’s difficult. He
doesn’t understand his actions a lot of the time.—Caregiver
of patient with Dravet syndrome aged 11 years
All caregivers described their child having difficulty in commu-
nicating verbally. This ranged from ability to use full sentences
(albeit at a lower communication level to their peers, Dravet
syndrome = 3; Lennox-Gastaut syndrome = 1), to using short
phrases or words (Dravet syndrome = 6), to having no speech
(Dravet syndrome = 4; Lennox-Gastaut syndrome = 6).
Mobility. The mobility of children was varied. Children were
described as completely mobile (Dravet syndrome = 4; Lennox-
Gastaut syndrome = 1), needing support to walk (Dravet syn-
drome = 4; Lennox-Gastaut syndrome = 3) and/or requiring a
wheelchair for long distances (Dravet syndrome = 5; Lennox-
Gastaut syndrome = 2), or unable to walk (Dravet syndrome = 1;
Lennox-Gastaut syndrome = 3). Of those unable to walk, 2 chil-
dren could not make any purposeful movements (Lennox-
Gastaut syndrome = 2), but 2 were able to crawl and move on
the floor (Dravet syndrome = 1; Lennox-Gastaut syndrome = 1).
Regardless of ability to walk, many individuals had diffi-
culty balancing (Dravet syndrome = 7; Lennox-Gastaut syn-
drome = 2), with patients at risk of falling, or difficulty with
hand-eye coordination (Dravet syndrome = 2; Lennox-Gastaut
syndrome = 1). Children were reported to experience muscle
weakness and low muscle tone (Dravet syndrome = 5;
Lennox-Gastaut syndrome = 2). In some cases, muscle weak-
ness caused tiredness or fatigue (Dravet syndrome = 5).
398
Figure 1. Frequency of spontaneous and prompted reporting of concepts relating to current symptoms and functions, and impacts on
individuals with DS or LGS, caregivers, and families. Abbreviations: DS, Dravet syndrome; LGS, Lennox-Gastaut syndrome.
Behavior. Several caregivers reported their child experi-
enced behavioral difficulties (Dravet syndrome = 14;
Lennox-Gastaut syndrome = 4), some of which were described
as related to a diagnosis of autism spectrum disorder (Dravet
syndrome = 4; Lennox-Gastaut syndrome = 1) or attention-
deficit hyperactivity disorder (Lennox-Gastaut syndrome = 1).
These included episodes of tantrums, crying, and aggressive
behaviors, such as self-injury and hitting/pushing others.
Some caregivers of individuals with Dravet syndrome men-
tioned their child had periods of hyperactivity, repetitive behav-
ior, and limited attention span (Dravet syndrome = 4).
Conversely, other caregivers reported no behavioral issues or
their child being normally “calm” or “chilled” (Dravet syn-
drome = 3; Lennox-Gastaut syndrome = 3).
Pain and discomfort. Some caregivers thought their child
experienced pain and discomfort (Dravet syndrome = 5;
Lennox-Gastaut syndrome = 4); headaches and pain before,
during, or after seizures were most often reported (Dravet syn-
drome = 2; Lennox-Gastaut syndrome = 3). Some caregivers
Journal of Child Neurology 38(6-7)
believed their child had a high pain threshold (Dravet syn-
drome = 6), which they perceived as common for individuals
with Dravet syndrome and could result in injury.
Sleep disturbance. Several caregivers reported their child’s
sleep was disrupted. Insomnia (Dravet syndrome = 4; Lennox-
Gastaut syndrome = 2) and night-time seizures (Dravet syndrome
= 3; Lennox-Gastaut syndrome = 1) were both stated as causes.
Appetite and feeding. Feeding independence varied among
the cohort. Some children could feed themselves (Dravet syn-
drome = 3), and 1 was spoon-fed (Lennox-Gastaut syndrome
= 1). Several caregivers reported their child was fed through a
feeding tube (Dravet syndrome = 3; Lennox-Gastaut syn-
drome = 4) for reasons including poor appetite (Dravet syn-
drome = 2; Lennox-Gastaut syndrome = 1) or limited motor
function (Lennox-Gastaut syndrome = 1). Three children
received all their food this way (Dravet syndrome = 1;
Lennox-Gastaut syndrome = 2).
Other symptoms. Other symptoms reported by caregivers
included gastrointestinal symptoms, for example, vomiting
Marshall et al
Figure 2. Frequency of spontaneous and prompted reporting of concepts relating to changes to symptoms and functions, and impacts on
individuals with DS or LGS, caregivers, and families, since treatment with CBD commenced. Abbreviations: CBD, cannabidiol; DS, Dravet
syndrome; LGS, Lennox-Gastaut syndrome.
(Lennox-Gastaut syndrome = 1) and constipation (Lennox-Gastaut
syndrome = 2); and susceptibility to infections (Dravet syn-
drome = 2; Lennox-Gastaut syndrome = 3), for example, viral
gastrointestinal infections (Lennox-Gastaut syndrome = 2), ear
infections (Dravet syndrome = 1, Lennox-Gastaut syndrome =
1), pneumonia (Lennox-Gastaut syndrome = 1), glandular fever
(Lennox-Gastaut syndrome = 1), and other unspecified infections
(Dravet syndrome = 1).
Current Impacts of Condition on Individuals With Dravet
Syndrome or Lennox-Gastaut Syndrome
Self-care. Some individuals with Lennox-Gastaut syndrome were
fully dependent on caregivers for their self-care, including
washing, dressing, and mobility because of limited motor function
(Lennox-Gastaut syndrome = 3 [age range 6-22 years]) or cogni-
tive function (Lennox-Gastaut syndrome = 1 [aged 21 years]).
399
However, most caregivers reported their child could conduct
certain self-care tasks with supervision (Dravet syndrome = 12
[age range 4–20 years]; Lennox-Gastaut syndrome = 3 [age
range 16-21 years]). For example, a 16-year-old individual with
Lennox-Gastaut syndrome had general basic life skills and was
able to shower and prepare simple meals, with supervision.
Leisure activities. All caregivers stated that their child’s par-
ticipation in leisure activities was affected by seizures, with
most individuals requiring caregiver supervision in case a
seizure occurred (Dravet syndrome = 8; Lennox-Gastaut syn-
drome = 3). Some individuals were also limited by their
seizure triggers.
Leisure activities were affected by motor and cognitive func-
tion. Children with milder physical and cognitive limitation were
less restricted in their activities (Dravet syndrome = 7;
Lennox-Gastaut syndrome = 1); some were able to play basket-
ball, ride a bicycle, or go swimming. Those with more severe
400 Journal of Child Neurology 38(6-7)

Figure 3. Conceptual model illustrating the relationships between symptoms and impacts of DS and LGS, and those mediated by CBD.
a
Symptom/impact not caused by DS or LGS. Symptoms/impacts that are italicized represent mediated changes that were mentioned by ≥5
caregivers. The symptoms/impacts that were positively mediated by CBD are shown in green, those that were negatively mediated are shown in
red, and those that were both positively and negatively mediated are shown in orange. Abbreviations: ADHD, attention-deficit hyperactivity
disorder; DS, Dravet syndrome; LGS, Lennox-Gastaut syndrome.

physical or cognitive limitations could only carry out seated
activities (Dravet syndrome = 2; Lennox-Gastaut syndrome = 3)
or activities not requiring active participation, such as watching
others and being read to (Lennox-Gastaut syndrome = 2).
School. Over half of school-aged children attended school or
nursery, including specialist schools and mainstream schools
with specialist support (Dravet syndrome = 11; Lennox-Gastaut
syndrome = 3). Because of limited motor function, learning
difficulties, and concentration problems, many individuals strug-
gled with schoolwork and required one-to-one classroom support
(Dravet syndrome = 5; Lennox-Gastaut syndrome = 3).
Some caregivers reported their child’s behavior at school could
be disruptive and difficult to manage (Dravet syndrome = 4;
Lennox-Gastaut syndrome = 1). Many individuals regularly
missed school or attended shorter hours because of seizure recovery
or tiredness (Dravet syndrome = 4; Lennox-Gastaut syndrome = 2).
Marshall et al
Social activities and relationships. Although some individuals
were able to form relationships and enjoyed company (Dravet syn-
drome = 6; Lennox-Gastaut syndrome = 2), several caregivers
reported their child had difficulty interacting with peers and
making friends. Reasons cited included the individual’s limited
motor function or inability to speak (Dravet syndrome = 2;
Lennox-Gastaut syndrome = 1), or difficulty understanding bound-
aries or how to interact with their peers (Dravet syndrome = 4).
Concerns about aggressive behavior toward other children
resulted in caregivers avoiding taking their child to parks or
playgrounds when other children were around (Dravet syn-
drome = 2) or other children avoiding interacting with the indi-
vidual (Dravet syndrome = 4).
Emotional well-being. Many caregivers reported their child’s
emotional well-being was impacted because of their condition.
The most reported emotion was frustration, which was sometimes
linked to emotional outbursts (Dravet syndrome = 4;
Lennox-Gastaut syndrome = 1) and was mostly attributed to age
or learning difficulties. However, several individuals were
described as typically happy and rarely exhibiting negative emo-
tions (Dravet syndrome = 9; Lennox-Gastaut syndrome = 3).
Caregiver impacts and responsibilities. Caregivers com-
monly reported their day was focused on providing constant
care for their child, including washing, dressing, and feeding
(Dravet syndrome = 6; Lennox-Gastaut syndrome = 5). In addi-
tion to direct care, many caregivers conducted administrative
tasks, for example, managing and administering medication
(Dravet syndrome = 8; Lennox-Gastaut syndrome = 4).
Several caregivers described the importance of being alert
and continuously monitoring the individual, because of their
inability to recognize danger and/or the unpredictability of sei-
zures (Dravet syndrome = 7; Lennox-Gastaut syndrome = 4).
Some caregivers said they never left their child alone, and
always needed another caregiver present when carrying out
daily activities (Dravet syndrome = 2; Lennox-Gastaut syn-
drome = 2):
You couldn’t leave him just to nip to the toilet… somebody
would have to be with him, or you’d have to take him with
you. He can never be left alone.—Caregiver of patient with
Dravet syndrome aged 6 years
Additionally, 2 caregivers described their need to manage their
child’s behavioral difficulties, especially when outside of the
house (Dravet syndrome = 1; Lennox-Gastaut syndrome = 1).
Daily, leisure, and social activities. Daily, leisure, and social
activities were limited because of caring responsibilities (Dravet
syndrome = 7; Lennox-Gastaut syndrome = 5), including lack of
time to exercise (Dravet syndrome = 3; Lennox-Gastaut syndrome
= 2), travel or go out (Dravet syndrome = 3; Lennox-Gastaut syn-
drome = 1), socialize (Dravet syndrome = 4; Lennox-Gastaut syn-
drome = 2), and engage with hobbies (Dravet syndrome = 2;
Lennox-Gastaut syndrome = 1). This was often attributed to the
continuous supervision of their child, lack of trust in other care-
givers due to complex needs, and the requirement to constantly
change plans.
401
Work and professional life. Almost all caregivers had to
adjust working hours (Dravet syndrome = 5; Lennox-Gastaut
syndrome = 2) or quit their job (Dravet syndrome = 7;
Lennox-Gastaut syndrome = 3) to focus on their caring responsi-
bilities. This was commonly due to the urgent intervention
required during seizures and the frequent hospitalizations. Four
caregivers mentioned being financially impacted due to loss of
income (Dravet syndrome = 3; Lennox-Gastaut syndrome = 1).
Impact on relationships. Caregivers commonly described
how friendships had been impacted by their caring responsibil-
ities; many had a small social circle, consisting only of close
family and friends (Dravet syndrome = 5; Lennox-Gastaut syn-
drome = 3).
Family. Most caregivers described how living with Dravet
syndrome or Lennox-Gastaut syndrome impacted the whole
family and how their daily lives were centered around the individ-
ual with the condition. Difficulty with day trips or holidays as a
family was reported (Dravet syndrome = 5; Lennox-Gastaut syn-
drome = 3).
Many caregivers reported that their other children were
impacted by their sibling’s condition (Dravet syndrome = 7;
Lennox-Gastaut syndrome = 3). This included restrictions to
leisure activities and receiving less attention because of the focus
on the child with Dravet syndrome/Lennox-Gastaut syndrome.
Caregivers described how their other children were often at
the receiving end of their sibling’s aggressive behavior (Dravet
syndrome = 3). Nonetheless, several caregivers still tried to
allow their family to live normal lives and make plans despite
difficulties in caring for their child (Dravet syndrome = 5;
Lennox-Gastaut syndrome = 3).
Changes to Symptoms and Functions Since Taking CBD
In the conceptual model (Figure 3), it is outlined where CBD was
reported as having a mediating influence on seizure and
beyond-seizure-related impacts, based on the qualitative data
obtained. Changes in symptoms were noted for both patients with
Dravet syndrome and Lennox-Gastaut syndrome. Changes in care-
giver and family impacts were mostly reported for individuals with
Dravet syndrome, who represented most of the patient cohort.
Seizures. Several caregivers believed their child’s seizures
had improved since taking CBD (Dravet syndrome = 12;
Lennox-Gastaut syndrome = 4); however, 3 reported that this
improvement lasted for only 2-6 months (Dravet syndrome = 2;
Lennox-Gastaut syndrome = 1). The majority reported a reduced
seizure frequency (Dravet syndrome = 9; Lennox-Gastaut syn-
drome = 3), although reduced seizure severity (Dravet syn-
drome = 1) and length (Dravet syndrome = 5; Lennox-Gastaut
syndrome = 1) were also noted; others witnessed fewer occasions
of seizure clustering (Dravet syndrome = 3). These impacts
improved the caregiver’s ability to manage seizures at home as
status epilepticus and the need for emergency medication or hos-
pitalization were less likely.
CBD was also reported by caregivers to affect their child’s
seizure triggers (Dravet syndrome = 2), including reduced like-
lihood of triggering by temperature changes.
402
The remaining caregivers reported that CBD had no effect on
their child’s seizures (Dravet syndrome = 1; Lennox-Gastaut syn-
drome = 2).
Cognitive function and communication. Most caregivers
reported improvements in their child’s cognitive function
since they started taking CBD (Dravet syndrome = 10;
Lennox-Gastaut syndrome = 2), including 2 caregivers who
reported no effect of CBD on their child’s seizures (Dravet syn-
drome = 1; Lennox-Gastaut syndrome = 1). Cognitive improve-
ments included increased attention span (Dravet syndrome = 4),
awareness, and ability to focus and concentrate (Dravet syn-
drome = 5; Lennox-Gastaut syndrome = 2):
In the past, if he was going to do a puzzle, he may only do two or
three pieces; now, he will complete the whole thing, so he def-
initely can focus on a task for more of an extended period of
time.—Caregiver of patient with Dravet syndrome aged 9 years
Some caregivers mentioned their child’s memory (Dravet syn-
drome = 2) and ability to learn new skills and retain information
(Dravet syndrome = 3; Lennox-Gastaut syndrome = 1) had
improved since taking CBD. Some individuals were reported
to participate in longer conversations because of having
greater ability to focus or having a wider vocabulary.
Many caregivers reported improvements in their child’s ability
to interact (Dravet syndrome = 2; Lennox-Gastaut syndrome = 1)
and communicate (Dravet syndrome = 8; Lennox-Gastaut syn-
drome = 1):
I think a year after taking [CBD], we were fishing one day, and I
turned around and I said, “Buddy, I love you,” he goes, “I love
you.” Hadn’t heard that in 3 years. So amazing.—Caregiver of
patient with Dravet syndrome aged 9 years
Motor function. Three caregivers stated their child’s motor
function had improved since taking CBD (Dravet syndrome =
2; Lennox-Gastaut syndrome = 1 [all aged 11 or under]). This
included 2 individuals with Dravet syndrome reported to have
improved coordination, ability to balance, or strength/stability.
One individual with Lennox-Gastaut syndrome was reported to
have greater upper limb function and ability to crawl and roll on
the floor, perceived to be related to improved awareness of their
surroundings:
He’s just stronger and more stable. The fact that again he learnt
how to swim, that was so huge, that was such a big deal. His
coordination just got a little better.—Caregiver of patient with
Dravet syndrome aged 11 years
She just seems to be aware of what’s going on around her a lot
more, and is able to reach for things, and lift her arms up to ask
to be picked up and is just more cognitively aware of what she
wants.—Caregiver of patient with Lennox-Gastaut syndrome
aged 8 years
In addition, the 3 caregivers who described a reduction in sei-
zures for a limited period also reported that motor function had
Journal of Child Neurology 38(6-7)
improved for this period (Dravet syndrome = 2; Lennox-Gastaut
syndrome = 1). This included 1 Lennox-Gastaut syndrome care-
giver who mentioned their child had “more drive” and improved
fine motor skills, which enabled them to play with toys more easily.
Behavioral difficulties. A change in behavior since taking
CBD was reported for some individuals (Dravet syndrome = 5;
Lennox-Gastaut syndrome = 2); most commonly they became
more calm or relaxed (Dravet syndrome = 3; Lennox-Gastaut
syndrome = 2). Two caregivers described how CBD may have
negatively impacted their child’s behavior (Dravet syndrome =
2), reporting an increased number of “meltdowns” or difficulty
with calming down; it was not clear in either case whether this
was solely due to CBD.
Other symptoms. Some caregivers mentioned changes to
their child’s appetite since taking CBD, with 2 individuals
reported to have greater interest in a wider range of food
types (Dravet syndrome = 1; Lennox-Gastaut syndrome = 1)
and 2 individuals reported to have a reduced appetite (Dravet
syndrome = 1; Lennox-Gastaut syndrome = 1).
Two caregivers of patients with Dravet syndrome stated that
their child had more regular sleep since taking CBD. A further
individual with Dravet syndrome was reported to have experi-
enced less drowsiness and brain “fog.” Conversely, 1 individual
with Dravet syndrome had a higher level of drowsiness since
taking CBD.
One of the most commonly reported negative changes fol-
lowing CBD initiation was worsening gastrointestinal symp-
toms, such as loose stools (Dravet syndrome = 2), diarrhea
(Dravet syndrome = 2; Lennox-Gastaut syndrome = 1), and
constipation (Dravet syndrome = 1).
Changes to Impacts on Individuals With Dravet
Syndrome or Lennox-Gastaut Syndrome Since Taking
CBD
Daily activities. Reported impacts on children’s daily activities
since taking CBD included changes to their ability to take care
of themselves (Dravet syndrome = 1; Lennox-Gastaut syndrome
= 1), with 1 individual reported to now be “potty trained”
(Dravet syndrome = 1) and another now able to lift a cup to
drink independently (Lennox-Gastaut syndrome = 1). Greater
freedom to go outside and increased activeness was also reported;
this related to reduced seizure frequency and seizure triggers, and
reduced time recovering from seizures (Dravet syndrome = 4).
Additionally, 1 individual with Lennox-Gastaut syndrome
was reported to have shown more interest in participating in
outdoor activities, attributed to their improved awareness and
cognitive function:
The fact that she is more cognitively aware definitely has
impacted… the fact that she wants to be picked up, or go
outside, or do things.—Caregiver of patient with
Lennox-Gastaut syndrome aged 8 years
Some caregivers reported improvements in their child’s ability
to actively participate in school since they started taking CBD
Marshall et al
(Dravet syndrome = 2; Lennox-Gastaut syndrome = 2), includ-
ing 1 Lennox-Gastaut syndrome caregiver who had described
their child’s seizure reduction as lasting for a limited period:
She was starting to act more herself. She was getting more active,
she was more interested in like playing with things, and watching
her tablet. She was really enjoying school.—Caregiver of patient
with Lennox-Gastaut syndrome aged 6 years
Emotional well-being. Some caregivers of individuals with
Dravet syndrome reported improvements in their child’s emo-
tional well-being since starting CBD. This included 3 caregiv-
ers who felt the impact of CBD on their child’s seizures and
cognitive function in turn influenced their overall quality of life:
Because we’re seeing improvements, so many improvements,
[…] I would definitely say it’s improved his quality of life, def-
initely… it’s allowing him to develop and grow.—Caregiver of
patient with Dravet syndrome aged 6 years
In addition, 1 individual was reported to have increased
affection since taking CBD (Dravet syndrome = 1) and
another to have increased confidence (Dravet syndrome = 1):
I think he just was able to become more coordinated. […] you
could see things just connecting that we didn’t have before.
Then also just having more seizure stability we were able to try
more things. It opened a whole world of not being afraid to try
something. I think he also felt more confident in himself.—
Caregiver of patient with Dravet syndrome aged 11 years
Social activities and relationships. Some caregivers spoke
about how their child’s social activities had changed since start-
ing CBD (Dravet syndrome = 3; Lennox-Gastaut syndrome = 1),
including a greater interest in friendships and social interaction,
which was attributed to their improved awareness and cognitive
function (Dravet syndrome = 2; Lennox-Gastaut syndrome = 1):
She’s becoming for the first time a little bit interested in friends.
Where there was a lot of parallel play that never went anywhere,
it was nice to have other bodies around but there wasn’t reaching
out or asking about the other[s]. She’s starting now to ask about
other people and wanting to be with other people.—Caregiver of
patient with Dravet syndrome aged 14 years
Additionally, 1 caregiver described that their child could
now communicate with, and relate to, others more easily
(Dravet syndrome = 1). This caregiver also described a stronger
sibling relationship due to improvements in cognitive function
and verbal communication:
I mean they have a really strong relationship with his brothers
and sisters. I do think it helps. The cognitive and speech effects
along with the reduction in seizure length all are very helpful for
the family.—Caregiver of patient with Dravet syndrome aged
8 years
403
Changes to caregiver and family impacts since taking CBD.
Caregivers noted that reduced seizure frequency allowed more
time to focus on other aspects of the individual’s care (Dravet
syndrome = 1), and family life was less disrupted due to
reduced hospital visits (Dravet syndrome = 1).
Some caregivers reported a greater ability to have family life
experiences (Dravet syndrome = 3; Lennox-Gastaut syndrome
= 2) due to reduced anxiety outside of the home owing to
reduced seizure frequency and behavioral improvements:
Being able to travel some, know that she’s enjoying stuff, gives us
those experiences, also allows us to get out and have those expe-
riences. And with her being somewhat stable, it gives us the con-
fidence to be able to branch out a little bit more.—Caregiver of
patient with Lennox-Gastaut syndrome aged 8 years
Caregivers also reported improved emotional well-being, particu-
larly in relation to stress/anxiety about their child’s seizures (Dravet
syndrome = 4; Lennox-Gastaut syndrome = 1). Many caregivers
also mentioned how their child’s improvement in motor and cogni-
tive function increased their happiness and hopes for the future
(Dravet syndrome = 7; Lennox-Gastaut syndrome = 1):
Just watching him every day say a new word, or every couple of
days say a new word. I think it’s helped us a lot, from what he
was a couple of years ago.—Caregiver of patient with Dravet
syndrome aged 9 years
One caregiver described less disruption to their family’s
sleep as the individual had fewer nocturnal seizures since
taking CBD:
We’re sleeping better as a family, because we put her down, we
know that if we stay up another hour then our sleep cycle isn’t
interrupted by an evening seizure.—Caregiver of patient with
Dravet syndrome aged 14 years
Discussion
This was the first qualitative study to explore the effects of CBD
beyond seizure control among individuals with Dravet syn-
drome or Lennox-Gastaut syndrome, their caregivers, and
wider family members, as reported by the caregiver.
Caregivers reported a wide range of symptoms and functions
of Dravet syndrome and Lennox-Gastaut syndrome in addition to
frequent seizures. These included cognitive impairment, commu-
nication, mobility and behavioral difficulties, sleep disruption,
reduced appetite, pain and discomfort, and gastrointestinal
issues. A combination of these symptoms and functions, particu-
larly the risk of seizures, cognitive impairment, mobility, and
behavioral difficulties, meant all individuals with Dravet syn-
drome or Lennox-Gastaut syndrome needed round-the-clock
supervision, and many required assistance with self-care. The
ability of some individuals to carry out leisure and social activi-
ties and attend and participate in school was also affected. The
symptoms and impacts of Dravet syndrome or Lennox-Gastaut
404
syndrome on the individuals discussed in this study largely cor-
respond with those reported previously.1,9,14,33
The impacts of Dravet syndrome and Lennox-Gastaut syn-
drome on caregivers and their wider family found in this
study also largely align with those reported previously.1,12,14,34
Caregivers described how their overall health-related quality of
life was affected, with most reporting lack of personal time and
difficulty making spontaneous or future plans. This affected the
ability of some to sustain a job, maintain friendships, and find
time to exercise, travel, or engage with hobbies.
Many caregivers reported positive changes to the individual’s
cognitive function following treatment with CBD, including
improvements in their awareness of surroundings, attention
span, and ability to learn new skills and retain information.
These improvements were also reported for 1 individual with
Dravet syndrome and another with Lennox-Gastaut syndrome
who did not experience a reduction in severity and frequency
of seizures. This builds on previous findings from open-label
studies of CBD in individuals with treatment-resistant epilepsy,
where improvements in health-related quality of life, considered
independent from reduction in seizure frequency, were seen after
up to 12 months of CBD.21,22
Individuals’ improvements in cognitive function were reported to
have a positive impact on communication. For instance, some care-
givers reported that their child showed greater interest in and ability
to interact with others because of improved awareness, attention
span, and ability to learn words. This supports previous findings of
improvements in cognitive abilities, particularly regarding language,
up to 6 months following CBD initiation.26
Negative changes were also reported by 10 caregivers fol-
lowing their child’s CBD treatment, including loose stools,
diarrhea, somnolence, worsening behavioral difficulties, and
reduced appetite. These are broadly similar to the common
adverse events reported in the largest pivotal trials of CBD in
Dravet syndrome and Lennox-Gastaut syndrome.17–20
Importantly, this study additionally provided novel in-depth
understanding of caregivers’ views about the effects of CBD
on seizure control and other aspects of health-related quality of
life. Following treatment with CBD, some caregivers mentioned
a greater ability to have family life experiences and travel because
of reduced anxiety about seizures or behavioral difficulties when
away from home. Caregivers also reported lower levels of
anxiety/stress and increased hope for the future after witnessing
cognitive and motor function improvements in their child.
Qualitative research is a valuable tool for providing insights into
the experience of patients and their families with rare conditions,
which can be used as a basis for future research. This has been dem-
onstrated for treatments in other rare diseases, such as the medical
management of seizures in tuberous sclerosis complex35 and atalu-
ren in Duchenne muscular dystrophy.36 The benefits of qualitative
research were also highlighted in the US Food and Drug
Administration’s (FDA’s) patient-focused drug development guid-
ance.37 This suggests the inclusion of patient exit interviews in clin-
ical trials for rare diseases as a way of better understanding patient
experience, adding greater depth to data and obtaining input on
meaningful outcomes or changes for patients.
Journal of Child Neurology 38(6-7)
In this study, a patient-centered conceptual model was devel-
oped that was directly based on the important concepts reported
by caregivers. As well as highlighting the symptoms and impacts
of Dravet syndrome/Lennox-Gastaut syndrome and potential
impacts of treatment, the conceptual model can provide a
useful tool for informing a patient-centered measurement strategy
for clinical trials of new treatments. In fact, the researchers are
currently using findings from this study to inform the selection
of appropriate patient-reported outcome (PRO) measures for
use in future observational studies for CBD. This will involve
mapping variables assessed by PRO measures deemed relevant
to the Dravet syndrome/Lennox-Gastaut syndrome patient popu-
lation with the concept identified by this study and assessing
likely sensitivity to treatment effects.
Although this study provides novel insights, it also had some
limitations. Participants were recruited from the United States,
the United Kingdom, and Germany, but a large majority were
from the USA. There was also a larger number of caregivers
of individuals with Dravet syndrome compared with individuals
with Lennox-Gastaut syndrome; all participants cared for indi-
viduals aged ≥4 years. This meant that it was difficult to estab-
lish the impact of CBD across the different countries and
conditions examined and among younger infants. The recruit-
ment target of 40 caregivers was not reached, with 21 caregivers
recruited in total. Several factors likely contributed to the diffi-
culty with caregiver recruitment, including the rarity of Dravet
syndrome and Lennox-Gastaut syndrome, the limited number
of patient groups in some countries, and caregiver unavailabil-
ity because of the need to care for their child. Difficulty in
recruitment during the COVID-19 pandemic and the require-
ment for prior CBD treatment of at least 6 months are also
believed to explain the low number of participants; there were
20 potential participants excluded at screening because of
their child not taking CBD. Lastly, CBD gained marketing
authorization for the treatment of seizures associated with
Lennox-Gastaut syndrome and Dravet syndrome in 2018 in
the USA38 and 2019 in the EU, in conjunction with clobazam,39
so there was limited time between marketing authorization and
study recruitment. Nevertheless, in qualitative research, the
sample size is not necessarily a key indicator of high-quality
research; rather, the depth, richness, and appropriateness of
data and the extent to which sufficient evidence is generated
to address the research question are more critical.40 It is impor-
tant to note that while there was some evidence of data satura-
tion being reached in this study, the heterogeneous nature of the
caregiver and patient experience in our study mean that a larger
sample size may have highlighted additional themes or topics.
It is also possible that the sample may have been biased
towards those with more favorable opinions and experiences
of CBD, as participants were aware that their child had to
have taken the treatment for at least 6 months to be eligible
for the study. Although we were not able to remove this poten-
tial bias, the intention of the study was to review all potential
impacts of ≥6 months of treatment with CBD on patients and
caregivers and summarize these qualitatively. Including
patients with a shorter duration of CBD use may not have
Marshall et al
yielded the longer-term or beyond-seizure impacts of CBD that
were highlighted by some caregivers; however, it may have
captured a greater proportion reporting negative impacts result-
ing from treatment-related adverse events. Nevertheless, the
positive and negative impacts of CBD reported suggest that rep-
resentative views of all aspects of CBD treatment were not
excluded in this qualitative study.
Conclusion
This is the first qualitative study to provide an in-depth explora-
tion of the effects of CBD beyond seizure control among children
and young adults with Dravet syndrome or Lennox-Gastaut syn-
drome, and their caregivers and wider family members. The
results suggest that, in addition to reduced seizure frequency
and/or severity, CBD may have a wide range of beneficial
effects beyond seizure control, which warrants further investiga-
tion. Quantitative studies with larger sample sizes are required to
determine the generalizability of findings, as well as to explore
potential differences by condition and age.
Acknowledgments
The authors would like to thank the study participants for their partic-
ipation in this study. Editorial and medical writing support was pro-
vided to authors by Rosanna Jackson, PhD, of Helios Medical
Communications, Macclesfield, UK, and Clare Stretton, PhD, of
Selene Medical Communications, Macclesfield, UK, and funded by
Jazz Pharmaceuticals, Inc., and approved by all authors.
The authors would like to acknowledge Kelly Hollenack, formerly
of Greenwich Biosciences, Inc (now part of Jazz Pharmaceuticals, Inc),
for her substantial contribution to the conduct of the study, and impor-
tant intellectual content, but who was not involved in the development
of this manuscript
Author Contributions
JM, HS, and PS contributed to conception and design, and LMR and
SB contributed to design, of this study. HS, KK, and PS contributed
to the acquisition, analysis, and interpretation of data, and JM, LMR,
and SB contributed to the analysis and interpretation of data. HS,
KK, and PS drafted the manuscript, and all authors were involved in
critical revision of the manuscript for important intellectual content.
All authors gave their final approval of the version to be published
and agree to be accountable for all aspects of the work.
Ethical Approval
The study protocol was reviewed and approved by the WIRB
Copernicus Group Independent Review Board (IRB tracking
number: 20204291).
Data Sharing Statement
All relevant data are provided with the manuscript and supporting files.
Declaration of Conflicting Interests
All authors met the ICMJE authorship criteria and had full access to
relevant data. Neither honoraria nor payments were made for author-
ship. JM, LMR, and SB are employees of Jazz Pharmaceuticals, Inc.
HS is an employee of Acaster Lloyd Consulting Ltd; PS and KK
405
were employees of Acaster Lloyd Consulting Ltd when the study
was conducted. HS, KK, and PS have consulted for, conducted
studies funded by, or received honoraria for services provided to
GW Pharmaceuticals companies, now a part of Jazz
Pharmaceuticals, Inc.
Funding
The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported by GW Pharmaceuticals, now a part of Jazz
Pharmaceuticals, Inc.
ORCID iD
Sally Bowditch https://orcid.org/0000-0003-1885-1113
Supplemental Material
Supplemental material for this article is available online.
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