Depression in patients with epilepsy in Northwestern Nigeria: Prevalence and clinical correlates.

BACKGROUND: The impact of seizure disorder on people living with epilepsy (PWE) is worsened by the occurrence of comorbid psychiatric disorders, such as depression, which have been found commonly in PWE. Despite the dire consequences comorbid depression has on PWE, it still remains underdiagnosed and undertreated.
OBJECTIVE: To determine the prevalence of depression and associated clinical factors in PWE in Northwestern Nigeria.
MATERIALS AND METHODS: A total of 255 consecutive patients with epilepsy aged 18 years and above, from two health facilities, were recruited in this cross-sectional study. Following completion of a structured proforma detailing sociodemographic and seizure characteristics, Mini International Neuropsychiatric Interview was administered to diagnose depression in the patients.
RESULTS: A total of 255 patients, with a mean age of 32 years (standard deviation = 1.31), comprising 147 (57.6%) males and 108 (42.4%) females were studied. Majority (79.2%) of the patients had primarily generalized seizure type. Overall, depressive disorder was present in 52 (20.4%) patients. A significant association was found between previous hospitalization for epilepsy (P = 0.009), increased frequency of seizures, (P = 0.004), and prolonged duration of epilepsy, (P = 0.006). The independent predictors of depression included duration of epilepsy (P = 0.0001), previous hospitalization for epilepsy (P = 0.011), and frequency of seizures (P = 0.028).
CONCLUSION: Depression was common in PWE. Female gender, previous hospitalization for epilepsy, increased frequency of seizures and prolonged duration of epilepsy were associated with depression in PWE. Previous hospitalization for epilepsy, increased frequency of seizures, and prolonged duration of epilepsy were independent predictors of depression.

Introduction

Epilepsy is a chronic disorder with devastating sequelae such as stigma, rejection, and social isolation because of misconception about its etiology leading to people with epilepsy (PWE) having difficulty continuing education or maintaining employment with subsequent less accomplishment in these areas amidst other spheres of life.[1] This social consequence of the disorder is further heightened by the presence of comorbid psychiatric disorders which have been found to be common among PWE.[2]

Depressive disorders seem to be the second most common psychiatric disorder among PWE[34] occurring in about 20–50% of people,[5] and up to 85% in certain series.[6] Studies have shown a higher incidence among PWE than the general population[7] and others with chronic conditions such as asthma.[8] The comorbidity with depression further worsens the outcome of epilepsy and is associated with an increased negative impact on quality of life, even more than seizure frequency and severity.[9]

Despite this common occurrence, depression in epilepsy remains underdiagnosed and undertreated.[10] This is because such emotional reaction is assumed to be a normal response to a chronic disease like epilepsy.[11] This may however not be true, as a bidirectional relationship between epilepsy and depression has been postulated.[12] Epidemiological studies have shown that having a prior mood disorder can be associated with an increased risk of epilepsy. In a population-based, case–control study of patients in Sweden with newly diagnosed adult-onset epilepsy, Forsgren, and Nyström found that a history of depression preceding the onset of epilepsy was six times more frequent among patients than in controls.[13] Probable reasons for the bidirectional relationship include the use of proconvulsive antidepressants and common pathogenic mechanisms involved in both conditions such as abnormal central nervous system activity of several neurotransmitters, particularly serotonin, norepinephrine, dopamine, gamma-aminobutyric acid, glutamate, and abnormal function of the hypothalamic–pituitary–adrenal axis.[14]

It was against this background that this study was designed to determine the prevalence of depression and associated clinical factors in a group of patients with epilepsy.

Materials and Methods

This study was a cross-sectional study. The sample was drawn from consecutive patients with epilepsy, aged 18 years and above, who had been seizure-free for 2 weeks. They were recruited from Kumbotso Health Centre and Aminu Kano Teaching Hospital (AKTH), over a period of 4 months. Patients with severe cognitive or neurologic deficit were excluded from the study. Participants with severe cognitive deficits were excluded using scores of ≤15 on modified mini-mental state examination. Data obtained included sociodemographic and seizure characteristics using a structured proforma.

Diagnosis of depression was made using the Mini International Neuropsychiatric Interview (M.I.N.I.) version 5 (M.I.N.I. 5.0.0) which was developed as a short and efficient diagnostic interview to be used in clinical as well as research settings.[15] It follows Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition and the International Classification of Diseases-Tenth Edition criteria for psychiatric disorders, screening for 17 Axis I disorders. The major depressive and dysthymia modules were used in this study.

Major depression was diagnosed if five or more answers from a list of symptoms A1–A3 (total of nine symptoms) were coded yes from major depressive module, and a diagnosis of dysthymia made if two or more B3 (made up of six symptoms) answers were coded yes from dysthymia module. The M.I.N.I. has been validated in the United States and Europe and is available in twenty languages. Administration time ranges from approximately 15–20 min for individuals with few positively endorsed symptoms to 20–30 min for individuals who meet criteria for current diagnoses.[16]

Informed consent was obtained from all participants, and ethical clearance was gotten from the ethical board of AKTH.

All the data generated were collated, checked, and analyzed using a computer-based Statistical Package for the Social Sciences (SPSS) version 16.0 (SPSS Inc. Chicago, IL, USA). Quantitative variables are described using mean, and standard deviation (SD), and the independent sample t-test was used to compare means. Qualitative variables are presented as percentages, and bar charts. The nonparametric test χ2 was used to compare proportions where appropriate. A confidence interval of 95% was used, and a P ≤ 0.05 is considered significant. Binary logistic regression was done on all significant variables to eliminate confounders.

Results

Two hundred and fifty-five patients comprising 147 (57.6%) males and 108 (42.4%) females were studied. Their age ranged between 18 and 76 years with a mean of 32 years (SD = 1.31). Their age at onset of epilepsy was between 1 and 69 years with a mean of 21 years (SD = 1.46). Detailed sociodemographic characteristics of the patients are as shown in Table 1.

Table 1

Sociodemographic characteristics of participants

Demographic characteristics	Frequency (n)**	Percentage
Age (mean±SD)	32±1.31
Sex
Male	147	57.6
Female	108	42.4
Marital status
Married	139	54.5
Single	110	43.1
Divorcee/widow	6	2.4
Religion
Islam	251	98.4
Christianity	4	1.6
Tribe
Hausa/Fulani	246	96.5
Others	9	3.5
Occupation
Student	70	27.5
Full-time homemaker	52	20.4
Trading/business	49	19.2
Civil servant	35	13.7
Artisan	20	7.8
Unemployed	15	5.9
Farming	14	5.5
Level of formal education
Nil	105	41.2
Secondary	72	28.2
Tertiary	52	20.4
Primary	26	10.2

**Number of patients for categorical variables or mean for continuous variables. SD=Standard deviation

All the patients had clinically classifiable seizure types. Seizure characteristics of the patients are showed in Table 2. Majority (79.2%) of the patients had primarily generalized seizure type and most (36.5%) of them presented during the third decade of life [Table 3].

Table 2

Clinical characteristics of seizures among the participants

Seizure factors	n**	Percentage
Duration of epilepsy (mean±SD), years	10±9.3
Frequency of seizures
Once to several/day	12	4.7
Once-thrice/week	31	12.2
Once-twice/month	70	27.5
Once in 3-6 months	111	43.5
<1/year	31	12.2
Family history of epilepsy
Present	41	16.1
Absent	214	83.9
Family history of psychiatric illness
Present	22	8.6
Absent	233	91.4
Previous hospitalization for epilepsy
Present	39	15.3
Absent	216	84.7
EEG
Present	28	11.0
Absent	227	89.0
Seizure type
GTCS	202	79.2
Complex partial	26	10.2
Partial with secondary gen	20	7.8
Simple partial	4	1.6
Generalized clonic	2	0.8
Generalized tonic	1	0.4

**This is purely a descriptive table, no comparison was drawn hence the non inclusion of p-value or significant. SD=Standard deviation, EEG=Electroencephalogram, GTCS=Generalized tonic clonic seizures

Table 3

Distribution of age group at presentation by seizure type

Current age group	GTCS*	Generalized tonic	Generalized clonic	Simple partial	Complex partial	Partial with secondary generalization	Total
11-20	44	0	2	0	5	6	57
21-30	72	0	0	4	10	7	93
31-40	47	1	0	0	3	3	54
41-50	22	0	0	0	3	2	27
51-60	9	0	0	0	2	0	11
61-70	7	0	0	0	3	2	12
71-80	1	0	0	0	0	0	1
Total	202	1	2	4	26	20	255

*Generalized tonic-clonic seizures

Overall, depressive disorder was present in 52 (20.4%) patients; the distribution of the participants by subtypes of depressive disorder is as shown in Table 4.

Table 4

Distribution of the participants by subtypes of depressive disorder

Depression	n	Percentage
Dysthymia only	29	11.4
MDE + dysthmia	13	5.1
MDE only	10	3.9
Total	52	20.4

MDE=Major depressive episode

Patients with generalized seizure type had a higher frequency (21.5%) of depression than those with partial seizure type (16%), however, the difference was not statistically significant (P = 0.390).

A significant association was found between the previous hospitalization for epilepsy and depressive disorder, (P = 0.009). There was a higher frequency (91.7%) of depression among patients with increased frequency of seizures when compared with those with a lower seizure frequency (54.8%), P = 0.004 [Table 5]. The mean duration of epilepsy for those with depression was significantly higher (19 years) in comparison with that of nondepressed patients (8 years), P = 0.006 [Table 5].

Table 5

Seizure factors associated with depression in epilepsy

Associated factors (total number)	Number of patients (%)**		P-value
	Depressive	Disorder
	Yes	No
Seizure type
Generalized (205)	44 (21.5)	161 (78.5)	0.390
Partial (50)	8 (16)	42 (84)
Previous hospitalization for epilepsy
Present (39)	14 (35.9)	25 (64.1)	0.009*
Absent (216)	38 (17.6)	178 (82.4)
Frequency of seizures
Once to several/day (12)	11 (91.7)	1 (8.3)	0.004*
Once-thrice/week (31)	28 (90.3)	3 (9.7)
Once-twice/month (70)	57 (81.4)	13 (18.6)
Once in 3-6 months (111)	90 (81)	21 (18.9)
<1/year (31)	17 (54.8)	14 (45.2)
Family history of epilepsy
Present (41)	8 (19.5)	33 (80.5)	0.879
Absent (214)	44 (20.6)	170 (79.4)
Family history of psychiatric illness
Present (22)	4 (18.2)	18 (81.8)	0.788
Absent (233)	48 (20.6)	185 (79.4)
Age (mean±SD) (years)	31.7±12.3	31.9±13.4	0.930
Duration (mean±SD) (years)	19.3±11.3	7.9±7.2	<0.001*

*P is statistically significant. SD=Standard deviation

After adjusting for confounders such as gender using binary logistic regression, the independent predictors of depression among PWE were the duration of epilepsy, previous hospitalization for epilepsy and frequency of seizures [Table 6].

Table 6

Predictors of depression in epilepsy

Factors	OR	95% CI		P
		Lower	Upper
Sex	0.547	0.253	1.180	0.124
Duration of epilepsy	0.990	0.986	0.993	<0.001*
Previous hospitalization for epilepsy	3.203	1.308	7.843	0.011*
Frequency of seizures	0.650	0.442	0.955	0.028*

*P is statistically significant. OR=Odds ratio, CI=Confidence interval

Discussion

The prevalence of depressive disorders in this study was 20.4%. This figure is comparable to reports from both local and international studies; Kazeem and Dauda in a study among PWE in Nigeria using M.I.N.I. obtained a prevalence of 21.6% for major depressive disorders,[17] Adewuya and Ola found a prevalence of 28% in Nigerian adolescents with epilepsy, using Diagnostic Interview Schedule for Children-IV[3] while Jones et al., in a study assessing Axis I psychiatric morbidity in chronic epilepsy found the prevalence of depressive disorders to be 21.2%.[4] However, other local studies have obtained higher prevalence rates. For instance, Ogunrin and Odiabo in a case–controlled study analyzing self-rating and physician's assessment of depressive symptoms in patients with epilepsy using Hamilton Rating Scale for Depression and Becks Depression Inventory found prevalence rates of 42% and 45%, respectively.[18] Similarly, Onwuekwe et al. using becks depression inventory found a prevalence of depressive symptoms to be 85.5% among PWE in South-East Nigeria.[6] The high prevalence rates obtained in these latter studies could be attributed to the fact that screening tools were used, with the tendency to overestimate symptoms as opposed to diagnostic instruments.[19]

In the current study, there was no significant association between seizure type and development of depression, though depression occurred more in patients with generalized than partial seizures. This finding is contrary to the reports of Grabowska-Grzyb et al. in which patients with epilepsy and depression were more diagnosed as having complex partial seizures than those not depressed.[1] In the same study, nondepressed patients with epilepsy more commonly had secondarily generalized tonic-clonic seizures in contrast to those with epilepsy and depression.[1] This difference could be attributed to the preponderance of patients with generalized seizure type in the current study.

Our study showed a significant association between the previous hospitalization for epilepsy and depression. This finding is in agreement with reports of Grabowska-Grzyb et al. in which a significant association existed between frequent hospitalization due to epilepsy and depression. However, epilepsy-related problems such as drug-resistant seizures and status epilepticus were not more frequent in the depressed group compared with the nondepressed group.[1]

In conformity with the report of Adewuya and Ola[3] a significant association was found between increased frequency of seizures and depression. However, it is worthy of note that the observed association was independent of other factors such as prolonged duration and previous hospitalization for epilepsy. Furthermore, in a study by Ogunrin and Odiabo, the degree of seizure control, which could translate to seizure frequency was the most important predictor of depressive disorders among PWE, though in their study, the impact of seizure control was closely related to drug compliance as PWE with poor drug compliance were likely to have poor seizure control.[18] The index study, however, did not study drug compliance. The relationship between seizure frequency, depressive symptoms, and impaired quality of life seem to be a cyclical phenomenon as studies have also shown that frequent seizures is associated with impaired quality of life in PWE,[20] which further worsens the depressive symptoms.

Our study also showed that prolonged duration of epilepsy was significantly associated with depression and was one of the predictors of depression in PWE. This is similar to report of Fatoye et al. In their study, having epilepsy for more than 10 years significantly increases the chances of having clinically significant depression symptoms.[21] Similarly, Ogunrin and Odiabo found that depressive symptoms were more prevalent among PWE with longer duration of epilepsy.[18] This may be related to the several challenges of living with a chronic unpredictable disorder that has an influence on every aspect of the life of PWE. However, it has been found that occurrence of emotional problems is an interplay of various factors, both biological and psychological.[21]

Overall, this study is in conformity with earlier reports that long duration of epilepsy[21] and previous hospitalization for epilepsy[1] are independent predictors of depression in PWE. It was also able to establish increased frequency of seizures as a predictor of depression in PWE. Nonetheless, these seizure-related factors have been implicated in the development of psychopathology in PWE,[222324] hence, prompt and effective management of epilepsy may prevent or limit their occurrence.

In spite of these findings, the current study was not without limitation; it is a hospital-based study, thus, bias toward the more severe cases might not have been absolutely ruled out; therefore caution should be exercised in the interpretation and generalization of the findings in this study. Unlike many other local studies,[621] the use of diagnostic instrument, M.I.N.I., rather than screening instruments gives the current study an edge. The strength of this study further lies in its detection of predictors of depressive disorders in PWE, as this will serve as a guide for caregivers in the primary prevention and early detection of depression in PWE.

Conclusion

This study showed that depressive disorders are common in PWE. Long duration of epilepsy, previous hospitalization for epilepsy and increased frequency of seizures are independent predictors of depression in PWE.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.