Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 58, Num. 4, 2010, pp. 565-570

Neurology India, Vol. 58, No. 4, July-August, 2010, pp. 565-570

Original Article

Depressive symptoms in patients with epilepsy: Analysis of self-rating and physician's assessment

Ogunrin OlubunmiA, Obiabo YahayaO

Department of Medicine, Neurology Unit, University of Benin Teaching Hospital, Benin City
Correspondence Address:Department of Medicine, PMB 1154, University of Benin, Benin City, bunmifunmi@hotmail.com

Date of Acceptance: 11-Jun-2010

Code Number: ni10149

PMID: 20739793

DOI: 10.4103/0028-3886.68679

Abstract

Keywords: Beck depression inventory, depression, epilepsy, Hamilton′s rating scale, Nigerians, prevalence

Introduction

Depression is the most frequent psychiatric comorbidity in patients with epilepsy (PWE), ^[1] and the prevalence is higher in PWE when compared to patients with other chronic disorders and general population. ^[2],[3],[4] The reported frequency is quite variable, 30%-70%. ^[5],[6],[7] The etiology of depression is multifactorial and results from complex interaction between endogenous, genetic, therapeutic, and environmental factors. ^[1] Sociocultural aspects of epilepsy have effect on the depression. ^{[8],[9],[10],[11]} Nondisclosure or concealment and non-adherence to drug treatment may result in marital disharmony and disrupted family life ^{[9],[12],[13]} and depression may be the consequence of these factors or these factors may contribute to the onset of depression. ^[2],[8] In addition, societal stigma and the myth that epilepsy is contagious are contributing factors for depression, especially following retrenchment at work or disruption of academic work. ^[9],[14] Some of the antiepileptic drugs (AEDs) may cause depression and mood disorders. ^[15] Certain of the variables associated with epilepsy, seizure frequency, degree of seizure freedom, duration of epilepsy and cognitive disturbances have been shown to significantly contribute to the prevalence of depression among PWE. ^[5],[16] There is increasing evidence to suggest that depression has a significant impact on quality of life in PWE. ^{[2],[17],[18]} Unfortunately, most patients with epilepsy are not routinely screened for depression and and are not treated. ^[2] The Hamilton Rating Scale for Depression (HRSD) ^[19] and Beck Depression Inventory (BDI), ^[20] the two instruments designed to measure depressive symptoms.

In most sub-Saharan countries epilepsy is highly stigmatized and the knowledge of the cause of epilepsy among PWE is lacking, ^{[21],[22],[23]} It will not be surprising that the affected persons are often unwilling to share their problems and experiences with someone, including physicians or other health care providers, who have not gained their trust. In sub-Saharan Africa, the prevalence of epilepsy vary between 10 and 55 per 1000 population with an estimated mean prevalence of 15 per 1000. ^[24] This huge burden of the disease demands appropriate management including the management of comorbidities, such as depression. This cross-sectional case-control study assessed the prevalence of depression among PWE in a sub-Saharan African developing country and also the impact of some of the seizure variables on the depression scores.

Materials and Methods

Seventy-six patients with epilepsy aged above 18 years were selected from the Neurology Clinic of the University Teaching Hospital, Benin City, Nigeria, using a random table numbers from a pool of recently diagnosed PWE in the neurology clinic. Patients were on AED therapy for a period of at least 6 months, and have attended the clinic at least once prior to recruitment for the study. Seventy-six age- and sex-matched subjects were recruited as controls. The controls were selected from among the students in the university community and patients receiving treatment for minor ailments in the general outpatient clinic of the hospital. They had no personal or family history of epilepsy and/or depression. The PWE were matched "one-to-one" with the controls. Both the PWE and the controls were litrate, at least nine years of education. Informed consents were obtained from the study participants. Approval to conduct study was given by the Hospital Ethics Committee. Exclusion criteria included: patients younger than 18 years, not on AED medication, with no cognitive dysfunction or mental retardation, with no chronic medical illness, with no previous psychiatric illness, alcohol or substance abuse, and refusal to give informed consent. The presence of cognitive dysfunction was assessed with the modified mini-mental state examination (MMSE). ^[25]

A questionnaire was used to obtain information: demographic data (age, sex, occupation, domicile, and level of education) [Table - 1], AED treatment, drug adherence, degree of seizure control, and duration of epilepsy prior to presentation to the clinic. Seizure control was rated, after 6 months of AED therapy: good: no seizure since the start of AEDs; fair: 1 to 5 seizures since the start of AEDs, and poor: more than five seizures since the start of AEDs. ^[27] The history of seizure recurrence was corroborated by close family members. Drug compliance was rated, after 6 months of AED therapy: satisfactory: not missed any dose since the start of AEDs and unsatisfactory: missed some doses. ^[28] The assessment of drug compliance was based on the patients′ self reports and therapeutic AED monitoring was not done as there is no such facility in our center. The duration of epilepsy was calculated as the interval between the first attack ever (corroborated by a close family member) and the first contact with the patient in our neurology clinic.

The mean age of the PWE and controls was 33.47 ± 16.47 years (range, 18-65 years) with a median age of 29 years. There was a slight female preponderance among both the groups, 1.1:1. Seizures were classified according the seizure classification of International League Against Epilepsy. ^[26] Majority of the patients were single (68.4%) and most were either workers in the civil service or students (the study site serves as a major referral center for the University Health Centre and other school clinics in the environs). The mean duration of epilepsy before presentation to the hospital was 6.33 ± 1.58 years (range, 2 months to 27 years). Majority of the PWE were placed on carbamazepine (73.7%), and the rest were either on phenytoin (15.8%) or sodium valproate (10.5%). Fifty-six of the patients achieved satisfactory drug compliance (73.7%) as they were all motivated to comply with their medications at the initial presentation in the neurology clinic. Despite this high percentage of drug compliance, seizure control at six months was: good in 57.9%; fair in 36.8%; and poor in 5.3% [Table - 2].

The HRSD was used for the assessment of depressive symptoms and the BDI as instrument for patient′s self-evaluation. The HRSD consists of 21 items with a possible maximum score of 66 and a minimum score of 0. Higher scores indicate severe depression. The BDI consists of 21 stem questions and the subject has to choose one statement from the 4 options in each stem question that best describes how he/she has been feeling during the past 2 weeks. It has a minimum score of 0 and a maximum score of 63. These instruments were presented in comprehensible English language because all the study participants were literate. The severity of depression was graded for both measures using the acceptable standard scoring system: (I) for the HRSD: normal - 1-10 score; mild mood disturbance - 11-16 score; borderline clinical depression 17-20 score; moderate depression - 21-30 score; severe depression - 31-40 score; and extreme depression - above 40; ^[19] and (II) for the BDI: normal/insignificant depressive symptoms - 0-9; mild depression - 10-16; moderate depression - 17-29; and severe depression - 30-63. ^[29]

Statistical analysis

Statistical analysis of data was done using the SPSS version 11 software (SPSS Inc., Chicago, IL). Descriptive analysis of the demographic data was expressed as means (± standard deviation; standard error of the mean [SEM]) and percentages. The differences in the BDI and HRSD scores of the controls and the PWE were tested for statistical significance with the Student t test. The scores of the PWE on the BDI and HSRD were correlated with Pearson′s correlation coefficient. The impact of seizure variables on the HRSD and BDI scores was determined for significance using logistic regression analysis and Chi-square test for trend. The level of significance was taken as P < 0.05.

Results

The mean scores of the PWE and controls on the HRSD were 11.37 ± 4.64 (SEM, 1.98) and 3.47 ± 2.13 (SEM, 0.67), respectively. The mean scores for the PWE and controls on the BDI were 8.24 ± 3.78 (SEM, 1.56) and 2.63 ± 1.21 (SEM, 0.38), respectively. There were significant differences in the mean scores of the PWE and controls using both scales (P < 0.001). Significant percent of the PWE had scores within the normal range on both the scales (57.89% on the HRSD and 55.26% on the BDI). Using the HRSD, borderline clinical depression and moderately severe depression were detected in 18.42% and 3.95% of PWE, respectively, whereas 19.74% had mild mood disturbance, but the BDI demonstrated only the presence of borderline clinical depression in 15.79% and mild mood disturbance in 28.95%, whereas no PWE had moderate or severe depression. The prevalence of depressive symptoms using the HRSD was 42.11%, whereas it was 44.74% using the BDI [Table - 3]. The correlation of the PWE scores on the HSRD with their corresponding scores on the BDI yielded a correlation coefficient of 0.78.

There were significant differences in the scores of the male and female PWE on both HRSD and BDI (P < 0.001) [Table - 4]; the female PWE had a mean score of 13.10 ± 2.88 (range, 3-27; 95% confidence interval [CI], 7.27-18.92), whereas the male PWE had a mean score of 9.44 ± 2.72 (range, 0-22; 95% CI, 3.16-15.73) on the HRSD, whereas on the BDI the females′ mean was 7.70 ± 2.10 (range, 0-16; 95% CI, 3.45-11.95) and the males′ 5.78 ± 2.40 (range, 0-18; 95% CI, 0.90-10.66). Furthermore, there were statistically significant differences in the scores of PWE with fair or poor seizure control and those with long duration of epilepsy when compared with PWE with good seizure control and shorter duration of epilepsy (P < 0.05). Higher depression scores were found in women presenting after a period of 1-5 years of recurrent seizures. The PWE with satisfactory drug compliance had lower scores on both the scales implying low prevalence of depressive symptoms among them [Table - 4]. There was no significant difference observed with the type of AED used (P > 0.05). Using logistic regression analysis, the seizure control and the drug compliance were the most important predictors of mood disturbance and clinical depression on the HRSD (F = 3.263; P = 0.04), whereas on the BDI the seizure control, drug compliance, and the age of the patients were predictors of mood disturbance and clinical depression (F = 4.67; P = 0.013). For both the scales, the seizure control is the most potent variable (HRSD: P = 0.004; BDI: P = 0.001).

Discussion

This is the first study to assess the prevalence of depressive symptoms among Nigerian Africans with epilepsy using both BDI and HRSD. This study revealed that depressive symptoms are prevalent in PWE attending our tertiary health facility. Our observations were similar to the observations in the earlier studies. ^{[2],[3],[4],[5],[6],[7],[15]} Interictal depression as a co-morbid disorder has been reported in more than 40% of PWE. ^{[1],[4],[5],[6]} Cole ^[30] reported a prevalence of 20%-55% in patients with chronic epilepsy thus corroborating the prevalence of 42.11% and 44.74% observed with the HRSD and BDI, respectively, in this study. The parity and strong correlation observed in the scores obtained for depression using the HRSD and BDI indicate a significant degree of recognition of depressive symptoms among the PWE and probably suggests that a significant number of PWE are likely to present with or complain of depressive symptoms.

Previous reports have shown that depression is more likely in the untreated PWE and those with poor seizure control. ^{[24],[31],[32],[33]} In our study on logistic regression analysis, the degree of seizure control was the most important predictor of depressive disorder among our PWE. Also, frequent seizures has been associated with impaired quality of life in PWE, ^[34] conversely it is possible that good seizure control may confer a positive psychologic impact on these patients improving their self-esteem. Satisfactory drug compliance was associated with lower depression scores on both the scales. The impact of seizure control was closely related to drug compliance as PWE with poor drug compliance were likely to have poor seizure control. Higher scores observed among female PWE on the BDI and HRSD have been observed in a study using similar scales. ^[5] This may be explained by the fact that depression is more common among females than males in the general population. ^[35] This study also showed that longer duration of seizures was associated with higher depression scores. Similar were the observations in the earlier studies. ^{[5],[15],[16]} There are conflicting reports on the contributory role of age as a risk factor for the development of depression. The age of the patient significantly predisposed to depressive symptoms using the BDI in this study. This may not be unrelated to the duration of epilepsy as depressive symptoms were more prevalent among PWE with longer duration of epilepsy and are more likely to be older.

Although the type of AED the patients were taking did not affect their depression scores significantly, those on carbamazepine had lower scores when compared with others on valproic acid or phenytoin. It is, however, difficult to conclude that carbamazepine prevents depression in PWE since our study did not assess PWE who were not on medication and the effect of long-term treatment with these drugs was not tested. This study, in addition, is limited by the fact that it is a cross-sectional case-control study, and hence the possibility of inadvertently omitting patients with more or less severe attacks of epilepsy, and the lack of facility to monitor the serum levels of AEDs.

Although depression is often treatable, it is underdiagnosed by neurologists and primary-care physicians in the setting of chronic neurologic disease. ^[30] It has significant consequences including increased medical utilization, poor quality of life, social disability, and mortality. ^[4],[8],[18] It has greater negative impact on the quality of life than seizure frequency. ^[3],[5],[17] It is also associated with poorer seizure control and the risk of suicide in patients with epilepsy is greatly increased. ^[17],[18] More attention has, however, been focused on seizure control and AED medication compliance among the PWE than the overall improvement in their quality of life which has been shown to be more adversely affected by psychosocial issues, such as anxiety, depression, societal stigmatization, and cognitive impairments. ^[1],[4],[6] In sub-Saharan Africa, most of the PWE do not have access to basic epilepsy care (which includes health education and supply of AEDs) consequently the provision of and access to comprehensive care (which includes social support, mental health evaluation, neuropsychologic evaluation, vocational/academic/occupational counseling, and psychotherapy in addition to the components of the basic care) appears unrealizable.

Recent studies have suggested the existence of a bi-directional relationship between depression and epilepsy. PWE have a higher risk than the general population of suffering from depression, not just after but also before the onset of epilepsy, ^[10],[36] suggesting the possibility that these two disorders have common pathogenic mechanism. This was substantiated by the demonstration of changes in serotonergic 5-hydroxytryptophan (5HT) 1A receptor density in the brain and brainstem of patients with major depressive disorder as well as in patients with temporal lobe epilepsy using positron emission tomography, and the selective antagonist radiotracers ([11]C) WAY-100835 or ([18]F) FC-WAY. These changes reflect lower extracellular serotonin concentrations in both groups of patients and have some implications for treatment. ^[37],[38]

PWE with depression should receive both psychotherapy and pharmacologic interventions. Antidepressants remain the mainstay of pharmacologic intervention with the selective serotonin re-uptake inhibitors considered as first line treatment notwithstanding the fact that these drugs reduce seizure threshold. ^[15] The goal of therapy in the management of depression in PWE is to achieve complete resolution as depression is a recurring disease. So effective regimen should be ascertained and adequate continuation of treatment is a necessity to prevent a smoldering low-level dysthymia, which may severely restrict the patients′ quality of life. ^[15],[39] Most antidepressants would not cause seizure aggravation when given within the therapeutic range. The doses of antidepressants should be adjusted according to the individual′s clinical needs. ^[40] In addition to the use of antidepressants, there is need for public enlightenment programs to destigmatize and correct the myths and superstitions about epilepsy, thus improving the public attitude toward persons with epilepsy. The provision of specialized facilities and affordable AEDs to care for PWE would reduce the treatment gap and prevent depression.

This study has shown that interictal depression is a common comorbidity in patients with epilepsy and its presence is facilitated by poor seizure control, poor drug compliance, longer duration of epilepsy, and the female gender. Early detection and prompt management of depressive symptoms and good seizure control with appropriate AED by family physicians, neurologists, epileptologists, and psychiatrists caring for these patients may contribute to preventing depression in epilepsy.

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