Revista de Neurología,
Journal Year:
2024,
Volume and Issue:
79(06), P. 161 - 161
Published: Jan. 1, 2024
This
review,
conducted
by
the
Andalusian
Epilepsy
Society,
provides
an
update
on
recent
advances
in
treatment
of
drug-resistant
epilepsy,
focusing
three
new
anti-seizure
drugs:
cenobamate,
fenfluramine
and
cannabidiol.
These
emerging
drugs
offer
therapeutic
alternatives
for
patients
with
focal
Dravet
syndrome,
Lennox-Gastaut
syndrome.
The
primary
objective
this
review
is
to
provide
healthcare
professionals
up-to-date
overview
efficacy,
safety
potential
clinical
applications
these
treatments,
backed
latest
evidence.
In
addition
reviewing
available
evidence,
document
addresses
essential
practical
considerations
implementation
routine
practice,
including
aspects
such
as
their
dosage,
drug
interactions,
management
side-effects.
With
Society
aims
contribute
improving
care
quality
life
epilepsy
families.
Pharmacology & Therapeutics,
Journal Year:
2025,
Volume and Issue:
unknown, P. 108808 - 108808
Published: Feb. 1, 2025
Out
of
37
antiseizure
medications
(ASMs)
currently
in
the
market,
17
are
chiral
molecules
and
an
additional
one
(oxcarbazepine)
is
a
prodrug
compound
licarbazepine.
Of
ASMs,
six
(ethosuximide,
fenfluramine,
methsuximide,
mephobarbital,
stiripentol
vigabatrin)
marketed
as
racemates,
remainder
licensed
enantiomerically
pure
medicines.
note,
all
ASMs
introduced
prior
to
1990
were
racemates.
Stiripentol,
fenfluramine
vigabatrin
only
racemic
approved
by
FDA
>10
years
after
release
regulatory
guidelines
on
development
Despite
fact
that
pharmacokinetic
pharmacodynamic
differences
between
enantiomers
have
been
recognized
for
decades,
importance
chirality
understanding
biological
actions
not
widely
appreciated,
many
recent
publications
refer
these
if
they
single
molecular
entity.
In
present
article,
we
provide
critical
review
developed
1920s,
when
mephobarbital
was
introduced,
2022,
last
ASM
(ganaxolone)
approved.
We
summarize
available
data
stereoselective
pharmacokinetics
pharmacodynamics
also
discuss
aspects
related
introduction
medicines
within
current
scenario
Europe
U.S.,
focusing
stiripentol,
examples
different
approaches.
identified
number
knowledge
gaps
relevant
use
drugs
epilepsy,
including
remarkable
lack
published
information
comparative
pharmacokinetics,
toxicity
activity
most
ASMs.
The
clinical
discussed,
together
with
rationale
follow-up
compounds
potentially
improved
efficacy,
safety
commercial
viability.
Epilepsia Open,
Journal Year:
2024,
Volume and Issue:
9(5), P. 1643 - 1657
Published: July 4, 2024
Abstract
Fenfluramine
(FFA),
an
antiseizure
medication
(ASM)
with
serotonergic
and
sigma‐1
receptor
activity,
is
used
to
manage
patients
developmental
epileptic
encephalopathies
(DEEs).
It
approved
in
the
US
for
treating
seizures
associated
Dravet
syndrome
(DS)
Lennox–Gastaut
(LGS)
≥2
years
old
as
add‐on
therapy
DS
LGS
EU,
UK,
Japan
similarly
aged
patients.
Consensus
guidelines
treatment
of
have
recommended
FFA
be
early‐line
ASM,
it
has
also
shown
efficacy
managing
LGS.
are
DEEs
a
range
seizure
types,
impairments,
multiple
comorbidities.
Here
we
provide
case
vignettes
describing
4
(3
1
LGS)
4–29
whom
up
14
ASMs
had
previously
failed,
illustrate
real‐world
practice
issues
encountered
by
neurologists.
This
review
provides
guidance
on
use
context
ASM
polytherapy
drug–drug
interactions
(DDIs),
behavioral
issues,
dose
titration,
adverse
events.
Along
data
from
clinical
trial
program,
these
emphasize
low
risk
DDIs,
generally
well‐tolerated
safety
profile,
other
nonseizure
benefits
(eg,
improved
cognition
sleep)
or
Plain
Language
Summary
treat
individuals
syndrome,
but
there
that
clinicians
may
face
when
highlights
four
authors’
everyday
work
offers
practical
considerations
neurologists
expertise
complex
conditions
related
drug
interactions,
dosing,
side
effects
fenfluramine.
Neurological Research and Practice,
Journal Year:
2024,
Volume and Issue:
6(1)
Published: Feb. 22, 2024
Novel
treatments
are
needed
to
control
refractory
status
epilepticus
(SE).
This
study
aimed
assess
the
potential
effectiveness
of
fenfluramine
(FFA)
as
an
acute
treatment
option
for
SE.
We
present
a
summary
clinical
cases
where
oral
FFA
was
used
in
Epilepsia,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 12, 2025
Abstract
Objective
We
analyzed
the
long‐term
safety
and
effectiveness
of
fenfluramine
(FFA)
in
patients
with
Dravet
syndrome
(DS)
an
open‐label
extension
(OLE)
study
after
participating
randomized
controlled
trials
(RCTs)
or
commencing
FFA
de
novo
as
adults.
Methods
Patients
DS
who
participated
one
three
RCTs
were
19
to
35
years
age
started
included.
Key
endpoints
were:
incidence
treatment‐emergent
adverse
events
(TEAEs)
population,
median
percentage
change
monthly
convulsive
seizure
frequency
(MCSF)
from
RCT
baseline
end
(EOS)
modified
intent‐to‐treat
(mITT)
population.
Post
hoc
analyses
compared
on
concomitant
stiripentol
(STP)
vs
those
not
taking
STP,
assessed
(Clinical
Global
Impression‐Improvement
[CGI‐I]
scale
ratings)
enrolled
Results
A
total
374
patients,
including
45
adults,
received
≥1
dose.
Median
exposure
was
824
days
(range,
7–1280).
TEAEs
occurring
≥10%
pyrexia,
nasopharyngitis,
decreased
appetite,
seizure,
blood
glucose,
diarrhea,
abnormal
echocardiography
(only
physiologic
regurgitation),
upper
respiratory
tract
infection,
influenza,
vomiting,
ear
infection;
no
valvular
heart
disease
pulmonary
arterial
hypertension
observed
over
OLE.
In
mITT
population
(
n
=
324),
MCSF
EOS
−66.8%
p
<
.001).
The
post
STP
75)
−36.2%
−71.6%
234)
.0001).
adult
29
41
(70.7%)
42
(69.1%)
demonstrated
clinically
meaningful
improvement
CGI‐I
at
last
visit
rated
by
caregivers
investigators,
respectively.
Significance
Our
OLE
confirmed
previous
positive
findings
extended
up
3.5
years.
No
new
unexpected
signals
sustained
reduction
MCSF.
Deleted Journal,
Journal Year:
2024,
Volume and Issue:
37(1), P. 68 - 78
Published: Jan. 3, 2024
Abstract
Fenfluramine
is
an
antiseizure
medication
for
the
treatment
of
Dravet
and
Lennox–Gastaut
syndromes.
This
review
summarizes
literature
on
efficacy
tolerability
fenfluramine
presents
recommendations
practical
therapeutic
management.
With
regular
monitoring,
this
generally
well
tolerated
to
date
has
shown
no
cardiac
side
effects
such
as
valve
insufficiency
or
pulmonary
hypertension
in
clinical
development
program.
However,
children
may
experience
a
loss
appetite
should
be
closely
monitored
weight
loss,
sedation
was
observed
several
overweight
patients
due
rapid
dosage
titration;
therefore,
slower
increase
than
recommended
might
needed
adults.
Drug
interactions
considered
before
during
therapy,
reductions
are
necessary
when
used
combination
with
stiripentol.
Furthermore,
bromide
levels
could
medication.
Contact
patient
their
relatives
important
determine
general
state
health,
potential
movement
disturbances,
seizure
frequency
so
allow
timely
adjustments
titration
phase.
Expert Opinion on Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
25(9), P. 1121 - 1130
Published: June 12, 2024
Developmental
epileptic
encephalopathies
(DEEs)
pose
significant
challenges
due
to
their
refractory
nature
and
limited
treatment
options.
Despite
advancements
in
genetic
understanding,
effective
therapies
targeting
underlying
pathophysiology
are
lacking.
Serotoninergic
dysfunction
has
been
implicated
epilepsy,
sparking
interest
serotonin
as
a
therapeutic
target.
Behavioural Brain Research,
Journal Year:
2025,
Volume and Issue:
488, P. 115611 - 115611
Published: April 28, 2025
Whereas
preclinical
and
clinical
studies
suggest
serotonin
to
play
an
important
role
in
the
regulation
of
anxiety,
it
remains
unclear
if
its
dominating
impact
is
anxiety-dampening
or
anxiety-provoking.
In
male
rats
exposed
a
well-established
animal
model
i.e.,
context-conditioned
freezing,
we
previously
found
depletion
prior
acquisition
and/or
expression
conditioned
fear
result
reduction
freezing.
We
now
explored
effect
increasing
synaptic
levels
same
paradigm.
Two
compounds
eliciting
robust
increase
extracellular
-
precursor
5-hydroxytryptophan
(5-HTP)
releaser
d-fenfluramine
were
administered
i)
acquisition,
ii)
immediately
after
iii)
fear;
for
comparison,
reuptake
inhibitor
(SSRI)
escitalopram
was
also
tested.
Both
5-HTP
(≥
25
mg/kg)
fenfluramine
0.5
mg/kg),
but
not
(3,
10
30
decreased
dose-dependent
manner.
At
higher
dosage,
both
250
(5
(30
impaired
conditioning
as
well
freezing
displayed
during
presentation
electric
foot
shocks.
contrast,
neither
nor
impacted
when
exposure
The
results
underline
importance
intact
physiologically
regulated
serotonergic
transmission
rats.
