Volume 9, Issue 4, April – 2024 International Journal of Innovative Science and Research Technology

ISSN No:-2456-2165 https://doi.org/10.38124/ijisrt/IJISRT24APR503

Anxiety and Epilepsy: Current Understanding and

Future Perspectives
N.V.L. Suvarchala Reddy1; M. Ganga Raju2; D. Pushyami Sudha3; P. Shrivani4; P. Anusha5
Department of Pharmacology, Gokaraju Rangaraju College of Pharmacy, Hyderabad (500090) India

Abstract:- Anxiety is characterized as an overwhelming anxiety due to inherited or acquired factors, such as stress.
sense of worry or fear for the future, while epilepsy is a These disorders include five main types of generalized
chronic neurological condition. Both anxiety and anxiety disorder, obsessive-compulsive disorder, panic
epilepsy are prevalent conditions that impact individuals disorder, posttraumatic stress disorder (PTSD), social
globally and are associated with diminished function and phobia, and social anxiety disorders [1]. For at least six
life quality. This review article explains about the months, at least three of the following symptoms have been
treatment, etiology, pathophysiology, current advances linked to anxiety: restlessness, which includes irritability,
and neurological relationship between anxiety and tense or agitated sensations, weariness fast, problems
epilepsy. Previous research suggests that anxiety concentrating or losing your mind, impatience, tense
disorders are widespread and clinically relevant muscles, and disturbed sleep [4].
comorbid diseases in epilepsy patients because anxiety
can cause seizures or seizures may cause anxiety. To treat II. TREATMENT
anxiety and epilepsy, a thorough, multidisciplinary
clinical assessment is required. Medication, lifestyle Monoamine reuptake inhibition is currently the most
modifications, and psychotherapy are also required. effective treatment for moderate to mild chronic anxiety [5].
Selective serotonin reuptake inhibitors (SSRIs), the most
Keywords:- Anxiety, Current Advances, Epilepsy, GABA commonly prescribed family of antidepressants, are the
(Gamma Amino Butyric Acid), Treatment, Pathophysiology. first-line therapies for anxiety disorders; tricyclic
antidepressants, buspirone, and pregabalin are also helpful
I. INTRODUCTION [6]. Benzodiazepines are also frequently used to treat acute
anxiety, even though they are useful for the majority of
Anxiety is a state that leads to a heightened sense of patients. Benzodiazepines do, however, appear to be linked
threat and a response to it that might include a variety of to chemical, physical, and mental dependence. The degree
defensive behaviors [1]. When uncertain danger is of anxiety disorders determines how effective a treatment
imminent, anxiety is a physiological state of distress and plan will be; therefore, it is critical to develop novel
restlessness [2]. Anxiety is thought to affect 4.05% of global therapeutic strategies to lessen the negative effects of
population [3]. These are the mental health issues that are anxiety on society and the economic market [7][8][9][10]
most common. Pathological anxiety disorders are caused by
abnormalities in neural circuits involved in mood and  Recent Advances

Table 1 Recently Marketed Drugs for Anxiety

S.no Drug Treatment Refs.
1 Agomelatine Generalized anxiety disorder 11,12
2 Escitalopram Generalized anxiety disorder 11,12
3 Vilazodone Generalized anxiety disorder and social anxiety disorder 13
4 Gepirone Anxiety 14, 15
5 Tandospirone Generalized anxiety disorder 16
6 Psilocybin Anxiolytic better in combination with psychotherapy 17, 18

Table 2 Novel Drugs in Clinical Phase [19]

S.no Drug Phase Indication
1 MM – 120 2 General Anxiety Disorder
2 AVN – 101 2 General Anxiety Disorder
3 ACH 000029 1 General Anxiety Disorder
4 Darigabat 1 Panic Disorder
5 Aloradine 3 Social Anxiety Disorder
6 Cannabidiol 3 General Anxiety Disorder
7 RLS103 1b/2a Social Anxiety Disorder
8 BNC210 2 Social Anxiety Disorder
9 VQW-765 2 Performance anxiety

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Volume 9, Issue 4, April – 2024 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165 https://doi.org/10.38124/ijisrt/IJISRT24APR503

 Etiology
Many biopsychosocial factors seem to contribute to
anxiety disorders. Clinically important illnesses arise from
the interaction of genetic vulnerability and stressful or
traumatic circumstances. Few of the reason anxiety might be
caused are as follows

 Prescription medications
 Substance abuse
 Alcoholism
 Trauma
 Early life events
 Stress
 Illnesses like diabetes and epilepsy
 Other comorbidities like depression can all make anxiety
worse [20]

III. PATHOPHYSIOLOGY

In the central nervous system, dopamine, serotonin,

Fig 2 Pathophysiology of Anxiety [23]
norepinephrine, and gamma-aminobutyric acid (GABA) are
the primary neurotransmitters that cause anxiety. Most
 Introduction
symptoms are mediated by the autonomic nervous system,
Epilepsy, a chronic neurological illness, are seizures,
particularly the sympathetic nervous system. The amygdala
which are recurrent paroxysmal clinical events. These
plays a crucial role in managing anxiety and fright. It has
seizures are brought on by an abnormal and
been discovered that the amygdala responds more strongly
hypersynchronous discharge of a group of brain neurons
to alarming stimuli in patients with anxiety disorders.
[24]. According to a World Health Organization research,
Pharmaceutical or psychological interventions can be used
epilepsy contributes almost seven million years of disability-
to correct anomalies in prefrontal-limbic activation since the
adjusted life years to the worldwide sickness burden,
prefrontal cortex is related to the limbic system and the
making it a major cause of impairment [25]. Among the
amygdala (20).
most common symptoms of epilepsy patients are staring,
jerking, uncontrollably jerky movements, sudden falls,
Because the amygdala projects to the hypothalamus,
perplexity, aura, strange feelings and sensations, loss of
which in turn controls the autonomic nerve system, it affects
consciousness, and concern [26].
blood pressure, heart rate, and changes connected to stress.
 Treatment
The brain's medial temporal lobe contains the
Topiramate, lamotrigine, and valproic acid are the first-
hippocampus, which regulates emotional actions, especially
line medications for atonic, atypical myoclonic, and primary
those related to anxiety, in addition to cognitive processes
generalized tonic clonic seizures. These include valproic
[6]. The diverse ways in which the hippocampus's dorso-
acid, oxcarbazepine, carbamazepine, and phenytoin for
ventral axis regulates anxiety and cognitive functions help to
partial seizures. These include ethosuximide and valproic
explain these unique roles [21]. There is mounting evidence
acid for absence seizures [27].
that the ventral hippocampus plays a major role in the
processing of anxiety. Higher levels of anxiety and higher
Numerous studies and research findings indicate that
levels of hippocampus activity have been linked in previous
the combination of medications aids in the management of
research [6].
the illness. It has been observed that patients respond to the
same medications at various dosages in different ways. This
may indeed be the case, since several pathophysiological
pathways can present in an individual at any given time. To
have better results in this situation, varying therapy
modalities would need to be used to varying degrees. The
combination of lamotrigine and sodium valproate has been
shown in numerous animal models to be effective in treating
both partial-onset and generalized seizures. To treat a variety
of seizures, lamotrigine and topiramate are another
combination that is typically advised, as is valproate and
ethosuximide to manage absence seizures[28].

Fig 1 Pictorial Representation of the Parts of Brain that

Influences the Anxiety [22]

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Volume 9, Issue 4, April – 2024 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165 https://doi.org/10.38124/ijisrt/IJISRT24APR503

 Recent Advances

Table 3 Recently Marketed Drugs for Epilepsy

S.no Drug Treatment Refs.
1 Vigabatrin Infantile spasms and refractory complex partial seizures 29
2 Fenfluramine Dravet syndrome and LGS 30
3 Cenobamate Adult partial onset epilepsy 30
4 Cannabidiol Dravet syndrome 31
5 Valium and nasal midazolam Rescue therapy 30

Table 4 Novel Drugs in Clinical Trials [32]

S.no Drug Phase Population
1 XEN1101 3 Focal and generalized epilepsy
2 BHV-7000 1 Drug-refractory focal and generalized epilepsy
3 ETX-123 Preclinical Drug-refractory focal and generalized epilepsy
4 NBI-921352 2 Focal-onset seizures
5 Lacosamide 2/3 Neonates
6 OV329 1 Rare adult and pediatric epilepsies
7 Alprazolam 3 Long or clustering seizures
8 Ganaxolone 4 CDKL5 deficiency disorder (approved), TSC, LGS, refractory Status epilectus
9 NRTX-1001 ½ Unilateral drug-refractory mesial temporal lobe epilepsy
10 Brivaracetam 2/3 Absence epilepsy
11 Radiprodil 2b Pediatric patients with gain-of-function GRIN variants: seizure cohort, behavioral cohort
12 LP352 1b/2ia DEEs
13 SPN-817 1ia Adult patients with refractory focal impaired awareness epilepsy

 Abbrevations:
TSC- tuberous sclerosis complex, LGS- Lennox–Gastaut syndrome, DEE- developmental and epileptic encephalopathy

Table 5 Novel Devices for Epilepsy [32]

S.no Device Phase Population
1 EASEE 2 Drug-refractory epilepsy
2 Tdcs 3 Drug-refractory epilepsy
3 EmbarcePlus FDA approved Seizure detection
4 EpiCare@Home CE mark approved Seizure detection
5 REMI Ongoing Seizure detection
6 Epihunter CE mark approved Absence seizures

 Abbrevations:  Disturbances in electrolytes (hypo/hyper calcemia,

EASEE- Epicranial Application of Stimulation hypo/hyper natremia)
Electrodes for Epilepsy; REMI, Remote EEG Ambulatory  Adverse reactions to medications
Monitoring; tDCS, transcranial direct current stimulation.  CNS infections
 Traumatic head injury
 Etiology  Hypoxic brain injury
There is a chance for both prompted an unprovoked  Ischemic or hemorrhagic stroke
seizures. Acute symptomatic seizures, also referred to as  Sleep deprivation
provoked seizures, can be caused by a variety of diseases.  Genetics [33]
These ailments include tumors or other mass lesions, brain
trauma, viral infections, poisonings, and vascular anomalies.
Seizures can be brought on by a variety of factors, including
problems with nearly any medical condition. The following
is a list of some typical causes:

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Volume 9, Issue 4, April – 2024 International Journal of Innovative Science and Research Technology
ISSN No:-2456-2165 https://doi.org/10.38124/ijisrt/IJISRT24APR503

 Pathophysiology

Fig 3 Flowchart of the Pathophysiology of Epilepsy [34]

Fig 3 Pathophysiology of Epilepsy [35]

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Volume 9, Issue 4, April – 2024 International Journal of Innovative Science and Research Technology
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ISSN No:-2456-2165 https://doi.org/10.38124/ijisrt/IJISRT24APR503

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