Psychiatric comorbidities and treatment patterns in epilepsy: A retrospective review from a tertiary neuropsychiatric clinic

ABSTRACT

Background:

Psychiatric conditions, including neurodevelopmental disorders are common among people with epilepsy (PwEs). However, data comparing their distribution across different epilepsy types are limited, particularly in Indian context.

Aim:

To explore and compare the psychiatric comorbidities and treatment adherence among focal and generalized epilepsy (FE/GE).

Methods:

This retrospective chart review included 2,258 PwEs attending a tertiary neuropsychiatry clinic in India between 2013 and 2023. Their sociodemographic and clinical data were compared between FE and GE groups.

Results:

Nearly 30% had psychiatric comorbidities, most frequently depression (20.6%). Mood and anxiety disorders were more common in FE, while non-affective psychosis was more common in GE. Neurodevelopmental disorders, particularly intellectual disability (ID), were more prevalent in GE (41.9% vs. 16.3%). Medication compliance was suboptimal (60%) and follow-up rates declined over time, reaching 40% at 1-year.

Conclusion:

PwEs have a high prevalence of psychiatric comorbidities, with differential occurrences across epilepsy types. Inadequate compliance and follow-up rates remain major challenges.

INTRODUCTION

Epilepsy is a chronic neurological condition characterized by recurrent episodes of unprovoked seizures, resulting in increased morbidity and mortality.[1] Approximately 50 million people globally are estimated to have epilepsy.[2] In India, the prevalence is around 1%, comprising of one-sixth of the global burden.[3] Notably, about 30%–40% of people with epilepsy (PwEs) present with comorbid psychiatric conditions, including neurodevelopmental disorders.[4,5,6]

Comorbid conditions significantly reduce the quality of life, that exceeds beyond the effects caused by seizures alone. Additionally, psychiatric conditions can complicate seizure control and antiepileptic drug (AED) adherence. Besides, AEDs have shown to worsen psychiatric symptoms and interact adversely with psychiatry medications.[7] PwEs with psychiatric comorbidities also show an increased risk of suicide.[8,9]

Again, many factors influence the occurrence and pattern of psychiatric manifestations in epilepsy that include seizure type, duration of illness, and treatment response. However, there is a paucity of studies in this area, particularly in the Indian context. This study aimed to explore and compare the psychiatry comorbidities and treatment patterns across major epilepsy types. The findings could inform clinical practice, and help improve the overall well-being of the PwEs.

METHODOLOGY

Study design and setting

This was across-sectional retrospective analysis of patient records spanning over 11 years (2013–2024), conducted at the department of psychiatry, All India Institute of Medical Sciences, Bhubaneswar, a tertiary care center in South-Eastern India.

Study procedure

The study commenced after obtaining approval from the Institute Ethics Committee and followed the guidelines by the Indian Council of Medical Research (2017) and Good Clinical Practices.

It included every patient with confirmed epilepsy (international league against epilepsy [ILAE], 2025 criteria),[10] who sought treatment at the weekly neuropsychiatry clinic of the Department during the entire study period. Any psychiatric disorders were classified using the International Classification of Diseases, 10^th Revision.[11] The patient data was collected from online health records, clinical notes and prescriptions, matched using clinical registry numbers. The data was used to fill pre-formed spreadsheet and those with greater than 20% of unknown (or unfilled) variables were excluded from final analysis.

As per ILAE, patients were classified into two diagnoses: focal epilepsy (FE) and generalized epilepsy (GE).[10] Patterns of psychiatric comorbidities and treatments were then compared between the epilepsy types.

Statistical analysis

The categorical variables (expressed in frequency and percentages) were compared using a Chi-square/Fisher exact test, whereas the continuous variables were copared using unpaired t-test. A two-tailed P value of < 0.05 was considered significant for all statistical analyses. All statistical calculations were done using R (version 4.2.0; R Core Team, R Foundation for Statistical Computing, Vienna, Austria).

RESULTS

A total of 3,542 patient records were initially retrieved, out of which 853 did not have epilepsy and 128 lacked a confirmed diagnosis. Another 303 entries had more than 20% of their records incomplete, who were excluded. Finally, 2,258 persons with epilepsy (PwEs) were included in the retrospective analysis [Table 1]. The patients were predominantly male (68.6%), unmarried (57.0%), and students (38.0%). The sociodemographic and clinical characteristics of the patients are summarized in Tabe 1. The majority of the PwEs had FE (n = 1762; 78.0%) as compared to GE (n = 496, 22.0%). Among those with FE, focal to bilateral tonic-clonic epilepsy was the most frequent type (n = 1713, 97.2%), while generalized tonic-clonic seizures were the most common GE observed (n = 358, 72.2%). Patients with GE had an earlier age of onset compared to FE (16.6 ± 20.3 vs. 22.6 ± 19.4 years; P < 0.001). Overall, cases with GE showed longer seizure duration and a higher frequency of seizure episodes (P < 0.001). In most cases (78.1%), no definite seizure precipitant could be identified. Those with GE had a higher prevalence of birth asphyxia (50.2% vs. 9.6%, P < 0.001) and a history of encephalopathy (38.7% vs. 10.4%, P < 0.001). Conversely, stroke (9.4% vs. 5.0%, P = 0.001) and head injury (4.9% vs. 0.4%, P < 0.001) were more common in the FE group. Patients with FE commonly reported of aura (70%) and automatisms (26%). Also, inter-ictal behavioral manifestations, like intermittent explosive disorder (IED), psychosis and personality changes were predominantly observed in FE as compared to GE (P < 0.001).

Table 1.

Sociodemographic and clinical characteristics of the study population

	n (%)			P*
	Total sample (n=2258)	FE (n=1762)	GE (n=496)
Age	29.1±19.2	30.4±19.0	24.3±19.4	<0.001
Male	1549 (68.6)	1226 (69.6)	323 (65.1)	0.058
Unmarried	1288 (57.0)	1001 (56.8)	287 (57.9)	0.676
Occupation
Student	859 (38.0)	605 (34.3)	254 (51.2)	<0.001
Employed	648 (28.7)	558 (31.7)	62 (12.5)
Unemployed	751 (33.3)	599 (34.0)	180 (36.2)
Age at onset1 (years)	21.3±19.8	22.6±19.4	16.6±20.3	<0.001
TDI1 (years)	7.6±9.0	7.7±8.8	7.4±9.6	0.662
Status epilepticus	201 (8.9)	72 (4.1)	129 (26.0)	<0.001
Febrile convulsions	96 (4.3)	18 (1.0)	78 (15.7)	<0.001
Seizure frequency
≤5 episodes/month	1622 (71.8)	1325 (75.2)	297 (59.9)
6 to ≤10 episodes/month	238 (10.5)	133 (7.5)	105 (21.2)	<0.001
>10 episodes/month	398 (17.6)	304 (17.3)	94 (19.0)
Seizure duration (mins)	3.1±1.8	2.9±1.8	3.8±1.6	<0.001
Pre-ictal phase
Prodrome	39 (1.7)	33 (1.9)	4 (0.8)	<0.001
Ictal phase
Aura	1230 (54.5)	1215 (69.0)	15 (3.0)	<0.001
Automatisms	472 (20.9)	457 (25.9)	15 (3.0)	<0.001
Adversive movements	148 (6.6)	140 (7.9)	8 (1.6)	<0.001
Incontinence	433 (19.2)	340 (19.3)	93 (18.8)	0.846
Injury	583 (25.8)	406 (23.0)	177 (35.7)	<0.001
Inter-ictal phase
IED	116 (5.1)	103 (5.8)	13 (2.6)
Psychosis	100 (4.4)	84 (4.8)	16 (3.2)	<0.001
Personality change	85 (3.8)	80 (4.5)	5 (1.0)
Post-ictal phenomena (yes)	1921 (85.1)	1606 (91.1)	315 (63.5)	<0.001
History of birth asphyxia (yes)	418 (18.5)	169 (9.6)	249 (50.2)	<0.001
History of encephalopathy (yes)	376 (16.7)	184 (10.4)	192 (38.7)	<0.001
Medical comorbidity
Stroke	191 (8.5)	166 (9.4)	25 (5.0)	0.001
History of head injury	86 (3.8)	84 (4.8)	2 (0.4)	<0.001
Migraine	59 (2.6)	32 (1.8)	27 (5.4)	<0.001
CT abnormality
Present	405 (17.9)	318 (18.0)	87 (17.5)	<0.001
Not conducted	1365 (60.5)	1019 (57.8)	346 (69.8)	<0.001
MRI abnormality
Present	513 (22.7)	358 (20.3)	155 (31.3)	<0.001
Not conducted	1423 (63.0)	1091 (61.9)	332 (66.9)	0.129
EEG findings
Focal abnormalities1	627 (27.8)	514 (29.2)	113 (22.8)
Generalized abnormalities	125 (5.5)	71 (4.0)	54 (10.9)	<0.001
Others	110 (4.9)	65 (3.7)	45 (10.9)
Normal	510 (22.6)	410 (23.3)	100 (20.2)
Not conducted	886 (39.2)	702 (39.8)	184 (37.1)	0.269

¹Includes focal, multifocal, and focal with generalized epileptiform discharges. Categorical variables are expressed as frequency (with percentages) and continuous variables are expressed as mean (with standard deviation). *P-value of 0.005 is taken as statistically significant. Chi-square/Fisher exact test was used for categorical variables, Independent Student t-test was used for continuous variables. FE=Focal epilepsy; GE=Generalized epilepsy; IED=Intermittent explosive disorder; EEG=Electroencephalography; MRI=Magnetic resonance imaging; CT=Computed tomography

The neuropsychiatric comorbidities, treatment and compliance patterns of the cohort are summarized in Table 2. Neurodevelopmental comorbidities were found in about a quarter of the cohort. Intellectual disability (ID) was the most prevalent neurodevelopmental disorder (22.0%), followed by attention deficit hyperactivity disorder (ADHD) (2.2%) and autistic disorder (0.5%). ID was significantly more common with GE than FE (41.9% vs. 16.3%, P < 0.001). Psychiatric comorbidities were present in nearly one-third of the sample, with depression being the most frequent (20.6%), followed by anxiety disorder (03.8%). Overall, mood disorders, including depression and bipolar affective disorder, along with anxiety disorders, were more common in FE (P < 0.001). However, non-affective psychoses were exclusively present in GE. Substance use was reported in over 10% of patients, with no significant difference between seizure types (P = 0.273).

Table 2.

Neuropsychiatric comorbidities, antiepileptic use, adherence and follow up patterns of the study population

	n (%)			P*
	Total sample (n=2258)	FE (n=1762)	GE (n=496)
Neurodevelopmental disorder
ID	496 (22.0)	288 (16.3)	208 (41.9)
AD	12 (00.5)	7 (0.4)	5 (1.0)	<0.001
ADHD	49 (2.2)	28 (1.6)	21 (4.2)
Combination	93 (4.1)	55 (3.1)	38 (7.7)
Psychiatric comorbidity
Depression	465 (20.6)	400 (22.7)	65 (13.1)
BPAD	17 (0.8)	15 (0.9)	2 (0.4)
Anxiety/OCD	85 (3.8)	75 (4.3)	10 (2.1)	<0.001
Non-affective psychosis	16 (0.7)	11 (0.6)	5 (1.0)
Dissociation	42 (1.9)	39 (2.2)	3 (0.6)
Substance use	302 (13.4)	243 (13.8)	59 (11.9)	0.273
Initial Monotherapy
Carbamazepine/oxcarbazepine	1620 (71.7)	1489 (84.5)	131 (26.4)
Valproate/divalproex	349 (15.5)	123 (7.0)	226 (45.6)	<0.001
Levetiracetam	183 (8.1)	112 (6.4)	71 (14.3)
Required 2 AEDs	728 (32.2)	573 (32.5)	155 (31.2)	0.593
Required ≥3 AEDs	220 (9.7)	159 (9.0)	61 (12.3)	0.030
Compliance1	1422 (63.0)	1188 (67.4)	234 (47.2)	<0.001
Follow-up
1 month	1773 (78.5)	1476 (83.8)	297 (59.9)	<0.001
3 months	1557 (69.0)	1283 (72.8)	274 (55.2)	<0.001
6 months	1214 (53.8)	979 (55.6)	235 (47.4)	<0.001
12 months	970 (43.0)	785 (44.6)	185 (37.3)	<0.001

¹Measured by adherence charts, pill count, and recall methods. Categorical variables are expressed as frequency (with percentages) and continuous variables are expressed as mean (with standard deviation). *P-value of 0.005 is taken as statistically significant. Chi-square/Fisher exact test was used for categorical variables, Independent Student t-test was used for continuous variables. FE=Focal epilepsy; GE=Generalized epilepsy; AEDs=Antiepileptic drugs; ADHD=Attention deficit hyperactivity disorder; AD=Autistic disorder; BPAD=bipolar affective disorder; ID=Intellectual disability

Neuroimaging investigations revealed that about 20% of patients from each seizure group had abnormalities on computed tomography scans. However, GE group showed significantly more abnormalities in magnetic resonance imaging (MRI)-Brain (31.3% vs. 20.3%, P < 0.001). Only 60.8% of patients performed electroencephalography, out of which 38.2% (n = 862) showed abnormal findings with significant differences in patterns between the two groups.

Prescription patterns showed that the preferred first-line AEDs for FE were carbamazepine/oxcarbazepine (84.5%), while valproate/divalproex (45.6%) and levetiracetam (14.3%) were more commonly used in GE. Approximately 30% of patients required a second AED, and 10% required a third agent. Levetiracetam (10%) and clobazam (9%) were the most common add-on medications in both groups. Medication adherence (as measured by the adherence chart, pill-count, and recall methods) was observed in over 60% of the cohort. Follow-up rates declined over time: 80% of patients attended the first follow-up at one month, 70% at 3 months, 50% at 6 months, and only 40% at 1 year. Consultation-liaison services were availed from the departments of neurology (n = 502, 22.2%), neurosurgery (n = 130, 05.8%), medicine (n = 115, 05.1%), and pediatric (n = 88, 03.9%).

DISCUSSION

This study retrospectively analyzed the health records of a cohort of PwEs spanning over 11 years at the neuropsychiatry clinic of a tertiary care center in India. A significant proportion (nearly 30%) of the cohort had comorbid psychiatric conditions. This is like global estimates.[4,5] Overall, depression was the commonest comorbidity. Previous studies have also highlighted depression as the primary psychiatric challenge in epilepsy.[8,9] Notably, mood and anxiety disorders were more common in FE, while non-affective psychosis was more common in GE. Again, in the inter-ictal phase, IED, personality changes, and psychosis was reported predominantly in FE.

The above findings have two important clinical implications. First, the high comorbidity burden warrants systemic screening for psychiatric symptoms among PwEs,[12] and a better understanding of the bidirectional link between seizures and psychiatric manifestations. Likewise, a high prevalence of comorbid substance uses highlights possible impact on seizure management. Second, the different occurrences of psychiatric conditions across the epilepsy types suggests a potential relationship between seizure localization and behavioral disturbances, consistent with previous literature.[13]

The study also observed a high co-existence of neurodevelopmental disorders, with a predominant presentation of ID among those with GE. Patients with GE showed a younger onset of epilepsy and higher rates of birth asphyxia and encephalopathy. These factors can significantly compromise early brain development, contributing to ID.[6,14] Therefore, it is important to assess for neurodevelopmental disorders in patients presenting with epilepsy early in life.[6] Neuroimaging abnormalities are usually more common in FE as it frequently arises from localized brain insults such as stroke or head injury.[15] However, MRI abnormalities were more frequent in GE in our study. This could be due to referral bias in the tertiary-care setting, where only severe and atypical cases underwent MRI. Furthermore, the study did not analyses the specific types of neuroimaging abnormalities, and GE is often associated with nonspecific findings.[15]

The prescription pattern observed in FE and GE was found to be in accordance with the treatment guidelines for epilepsy and previous evidences.[16] The study findings also reflect the global concerns of treatment compliance among PwEs.[17,18] The contributory factors may include cognitive impairment, psychiatric comorbidities, socioeconomic challenges, and treatment side effects.[17,18] Additionally, the follow-up rates started declining over time implicating the need for strategies such as patient education, family support and community-based interventions.[19]

The study had a few limitations. The retrospective design and dependency on hospital records may cause underreporting of the comorbid disorders. Also, the generalizability of the findings is limited as this was a singe center study conducted at a tertiary care center. However, the major strengths of the study were a large sample size and a long study period. This allowed quantitative analysis of the patterns of psychiatric disorders in a large cohort of PwEs.

CONCLUSION

The study found a high prevalence of psychiatric disorders, neurodevelopmental disorders and substance use among the PwEs. Neurodevelopmental disorders, particularly ID, were more common in GE, whereas mood and anxiety disorders were more frequent in FE. Compliance and long-term follow-up emerged as important treatment challenges among the patients. Future prospective multicentric studies may help generalize the findings.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.