Search

Objective. Zolpidem is a non-benzodiazepine agonist of GABA-A receptor indicated for the short-term insomnia treatment. Over the years, there have been reports in literature on zolpidem abuse complications and neuropsychiatric side effects involving headache, dizziness, nightmares, confusion, depression, sleepiness, memory deficits as well as hallucinations, sensory distortions, delirium and sleep-related complex behaviours with anterograde amnesia. The aim of this work is to review and highlight the most serious adverse reactions to zolpidem with emphasis on sleep-related amnestic behaviours. We also focus our attention on common traits, patterns and predisposing factors. This paper refers to zolpidem side effects or complex amnestic behaviours, or sleep related amnestic behaviours presented in literature. Literature review. A comprehensive search of PubMed and Google Scholar was conducted to find relevant studies, case reports and literature reviews addressing the zolpidem use in insomniac patients. Conclusions. Zolpidem may pose a risk for serious adverse reactions most common dose-dependent and associated with age, gender, concurrent use of medications and concomitant comorbidities. If severe adverse reactions occur, the drug should be immediately discontinued or switched to another hypnotic. This review indicates an association between psychotic reactions and complex sleep related behavioural abnormalities in patients using zolpidem alone or in combination with other psychotropic medications. Clinicians should adopt a cautious approach prescribing zolpidem and be alert to possible unusual adverse effects of the drug.

Background Post-myocardial depression is a highly prevalent condition worsening the course and prognosis of coronary artery disease. One of the possible pathogenetic factors is dysregulation of the autonomous nervous system, resulting in heart rate variability reduction. Methods Twenty two patients hospitalised due to a first myocardial infarction were included. The Beck Depression Inventory (BDI) was used to rate the severity of their depressive symptoms. Results Depressive symptomatology, defined as BDI ≥10, was present in 36.3% of the patients. Increase in heart rate variability (HRV) was observed in both groups during the first 6 months after the myocardial infarction. The HRV was significantly lower in the depressed group compared to patients without depression. Conclusion Presence of depression after the myocardial infarction (MI) is associated with a significant decrease of the time domain HRV measure SDNN (standard deviation of all normal RR intervals) and with its slower increase during at least a three months period.

Objective Anxiety disorders are frequent comorbid disorder in patients with epilepsy (PWEs). The availability of validated screening instruments to detect anxiety disorders in PWEs is limited. The aim of the present study was to validate State–Trait Anxiety Inventory (STAI) in adult PWEs for the detection of anxiety disorders. Methods A total of 96 outpatients with epilepsy completed the self-report symptom scale and were diagnosed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition Text Revision (DSM-IV-TR) Axis I disorders (SCID-I). The sensitivity, specificity, positive and negative predictive values, and receiver operating characteristic (ROC) curves were assessed to determine the optimal threshold scores for the State-Trait Anxiety Inventory State (STAI-S) and State-Trait Anxiety Inventory Trait (STAI-T) anxiety subscales. Results Receiver operating characteristic analyses for STAI-T showed area under the curve at 84.7%. For diagnoses of anxiety disorders, the STAI-T demonstrated the best psychometric properties for a cutoff score ≥ 52 with sensitivity of 81.3%, specificity of 77.5%, positive predictive value (PPV) of 41.9%, and negative predictive value (NPV) of 95.4%. Conclusions The STAI-T proved to be a valid and reliable psychometric instrument in terms of screening for anxiety disorders in PWEs. In the epilepsy setting, STAI-T maintains adequate sensitivity, acceptable specificity, and high NPV but low PPV for diagnosing anxiety disorders with an optimum cutoff score ≥ 52.

Objective Anxiety disorders are frequent comorbid disorders in patients with epilepsy (PWEs). The availability of validated screening instruments to detect anxiety disorders in PWEs is limited. The aim of the present study was to validate the Polish version of the Hospital Anxiety and Depression Scale (HADS) in adult PWEs for the detection of anxiety disorders. Methods A total of 96 outpatients with epilepsy completed the self-reported symptom scale, the HADS, and were diagnosed using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) axis I disorders (SCID-I). The sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and receiver operating characteristic (ROC) curves were assessed to determine the optimal threshold scores for the HADS anxiety subscale (HADS-A). Results Receiver operating characteristic analyses showed areas under the curve at 80.8%. For diagnoses of anxiety disorder, the HADS-A demonstrated the best psychometric properties for a cutoff score ≥ 10 with sensitivity of 81.3%, specificity of 70.0%, PPV of 31.5%, and NPV of 94.9%. Conclusions The HADS-A proved to be a valid and reliable psychometric instrument in terms of screening for anxiety disorders in our sample of PWEs. In the epilepsy setting, the HADS-A maintains adequate sensitivity, acceptable specificity, and high NPV but low PPV for diagnosing anxiety disorders with an optimum cutoff score ≥ 10.

Background and objectives Despite seemingly simple relationships between the quality of life and depression, the relevant issues are still not fully understood. The aim was to study the role of social support in the quality of life. Methods The study included 104 patients with unipolar or bipolar affective disorder. Beck Depression Inventory and Hamilton Depression Rating Scale were used to determine the level of intensity of depressive symptoms. Quality of life (Quality of Life in Depression Scale) and levels of social support (parts of Berlin Social Support Scales, Social Support Scale) were measured on admission, at discharge from the hospital, and 3 months after discharge. Results Results showed an increase in quality of life during hospitalization. The amount of social support remained constant between three measurements and positively correlated with quality of life. The strongest associations (controlled by depression severity) were found for perceived support at discharge (controlling HRS Rho = −0.44; p Conclusions During hospitalization, the quality of patient's life significantly improves with time. Social support is a significant correlate of quality of life in affective disorders.

Background Despite the fact that depressive disorders are the most common comorbidities among patients with epilepsy (PWE), such disorders often go unrecognized and untreated. In addition, the availability of validated screening instruments to detect depression in PWE is limited. The aim of the present study was thus to validate the Polish version of the Beck Depression Inventory (BDI) in adult PWE. Methods A group of 118 outpatient PWE were invited to participate in the study. Ninety-six patients meeting the inclusion criteria completed the Polish Version of Beck Depression Inventory-I (BDI-I) and were examined by a trained psychiatrist using the Structured Clinical Interview (SICD-I) for Diagnostic and statistical manual of mental disorders - fourth edition (Text revision) (DSM-IV-TR). Receiver operating characteristic (ROC) curves were used to determine the optimal threshold scores for BDI. Results Receiver operating characteristic analysis showed the area under the curve to be approximately 84%. For major depressive disorder (MDD) diagnosis, the BDI demonstrated the best psychometric properties for a cut-off score to be 18, with a sensitivity of 90.5%, specificity of 70.7%, positive predictive value (PPV) of 46.3%, and negative predictive value (NPV) of 96.4%. For the ‘any depressive disorder’ group, the BDI optimum cut-off score was 11, with a sensitivity of 82.5%, specificity of 73.2%, PPV of 68.8%, and NPV of 85.4%. Conclusions The BDI score is a valid psychometric indicator for depressive disorders in PWE maintaining adequate sensitivity and specificity, high NPV, and acceptable PPV with an optimum cut-off score of 18 for MDD diagnosis.

The co-occurrence of psychiatric disorders in people with epilepsy (PWE) is not well documented or studied. Anxiety and depressive disorders are the most frequent comorbid disorders in PWE. In this paper, we characterized the rates of multiple psychiatric disorder comorbidity by reanalyzing data from a study sample of PWE. A total of 96 outpatient PWE completed the self-report symptom scale, and were diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) Axis I disorders (SCID-I). For analyses, patients were assigned to a comprehensive diagnostic group of anxiety and depressive disorders. In order to determine comorbidity across psychiatric diagnoses for the DSM-IV categories, Pearson’s chi-squared test (χ2) was used. In the study sample, eight patients (8.3% of the study sample, n = 96) had comorbid major depressive disorder and anxiety disorder. When looking at comorbidity of each diagnosis separately, it was determined that 50% of individuals with an anxiety disorder had comorbid Major Depressive Disorder (MDD) and 38% patients with MDD had comorbid anxiety disorder. This finding encourages a more systematic reporting of psychiatric prevalence data in epilepsy, especially taking into account the high ratio of multiple comorbid anxiety and depressive disorders in PWE.

Background Impulsivity is a key feature of numerous psychiatric disorders. However, the relationship between impulsivity and anxiety disorders is arguable and not well explored. Several methodological considerations related to data interpretation arise when patients previously exposed to psychotropic medication are included in the study population. To address those issues we designed a study in a well defined cohort of treatment-naive panic disorder patients. Material and methods This case-control study was designed to evaluate impulsivity and its dimensions in the group of 21 psychotropic drug-naive outpatients with panic disorder and 20 healthy controls. The severity of Panic Disorder was assessed with Panic and Agoraphobia Scale (PAS). Impulsiveness was evaluated with the Barratt Impulsiveness Scale, 11th version (BIS-11). Results According to our study patients with panic disorders had higher level of both total impulsivity and all impulsivity dimensions comparing to healthy controls. Limitations The number of participating subjects was relatively small. The study results apply to drug-naive panic disorder patients without agoraphobia. Conclusion Opposing to the traditional conceptualizations suggesting that impulsivity displays a negative relationship with anxiety this study provides evidence for higher level of impulsivity in drug-naive patients with panic disorder comparing to healthy controls.

Objective Anxiety disorders (ADs) are common in patients with epilepsy (PWE). The aim of this study was to estimate the prevalence of specific ADs in outpatients with epilepsy. Methods A group of 118 consecutive outpatients with epilepsy were screened, and 96 patients meeting inclusion criteria were examined by a trained psychiatrist using Structured Clinical Interview (SICD-I) for Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (Text Revision) (DSM-IV-TR). Results A diagnosis of any current AD was established in 16 (16.7%) out of 96 participants. Furthermore, panic disorder (PD) was the most frequent AD; it was observed in 13.5% of PWE and constituted 81.2% of the identified ADs in the study group. Older age and later age of seizure onset were associated with increased odds of AD diagnosis. Study limitations The cross-sectional study design, a consecutive sample of patients presenting to a tertiary referral center, and small sample size of the population could have affected the results. Conclusions Panic disorder and other forms of AD are common among PWE. Age and age of seizure onset are important factors associated with AD among PWE.

Background: Post-myocardial depression is a highly prevalent condition which worsens the course and prognosis of coronary artery disease. One possible pathogenetic factor is dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in cortisol profile disturbances. Methods: Thirty seven patients hospitalized due to a first myocardial infarction (MI) were enrolled in this study. The Beck Depression Inventory (BDI) was used to rate the severity of their depressive symptoms. Morning and afternoon serum cortisol samples were taken on the fifth day of the MI. Results: Depression, defined as BDI ≥ 10, was present in 34.4% of the patients. A statistically significant difference was observed between the mean morning and the evening plasma concentrations in patients with depression compared to the no-depression group: F (1.29) = 5.0405, p = 0.0328. Conclusions: Patients with depressive symptoms directly after MI have a flattened diurnal serum cortisol profile. This is particularly expressed in patients with longer lasting symptoms.

Background Post-myocardial depression is a highly prevalent condition worsening the course and prognosis of coronary artery disease. One of the possible pathogenetic factors is dysregulation of the autonomous nervous system, resulting in heart rate variability reduction. Methods Twenty two patients hospitalised due to a first myocardial infarction were included. The Beck Depression Inventory (BDI) was used to rate the severity of their depressive symptoms. Results Depressive symptomatology, defined as BDI ≥10, was present in 36.3% of the patients. Increase in heart rate variability (HRV) was observed in both groups during the first 6 months after the myocardial infarction. The HRV was significantly lower in the depressed group compared to patients without depression. Conclusion Presence of depression after the myocardial infarction (MI) is associated with a significant decrease of the time domain HRV measure SDNN (standard deviation of all normal RR intervals) and with its slower increase during at least a three months period.

Objective The interictal dysphoric disorder (IDD) is a proposed epilepsy-specific mood disorder characterized by a cluster of symptoms such as depressed mood, irritability, euphoria, and anxiety. Since its introduction, the concept of IDD has been a matter of debate. This study aimed to evaluate the frequency of the IDD and the association between psychiatric disorders and IDD. We also analyzed potential associations between IDD symptoms and epilepsy-related variables. Methods A consecutive group of 118 outpatients with epilepsy were screened. Ninety-six patients met inclusion criteria and examined by a trained psychiatrist using Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders fourth edition Text Revision (DSM-IV-TR) (SCID-I). In order to diagnose IDD, all participants completed the self-rating questionnaire consisting of a set of questions aimed to assess the eight key symptoms of IDD. On completion of the questionnaire, the psychiatrist reviewed all the data for completeness and accuracy with the patient. Results In our group with epilepsy, we observed IDD in 49.0% (47 of 96) of people with epilepsy (PWE) with substantial overlap (85%) of IDD with depressive and anxiety disorders. The frequency of depressive mood, anergia, and irritability was significantly higher in patients with IDD diagnosis. Older age at epilepsy onset was associated with IDD. Study limitations The cross-sectional study design, a consecutive sample of patients presenting to a tertiary referral center, a small sample size of the population, and applied methodology could have affected the results. Conclusions The present study indicates that IDD occurs in high frequency in PWE with a substantial overlap of IDD with depressive and anxiety disorders. The study highlights the importance of the observer-based systematic approach for diagnosing IDD and the usage of operationalized diagnostic criteria for psychiatric comorbidities in PWE. Future research should be directed at validating whether IDD is nosologically independent of other psychiatric conditions.

Objective Anxiety disorders (ADs) are frequent comorbid disorder in patients with epilepsy (PWE). The availability of validated screening instruments to detect AD in PWE is limited. The aim of the present study was to validate the Polish version of the Hamilton Anxiety Rating Scale (HARS) in adult PWE for the detection of AD. Methods A total of 96 outpatient PWE completed the self-report symptom scale, the HARS, and were diagnosed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) Axis I disorders (SCID-I). The sensitivity, specificity, positive and negative predictive value, and receiver operating characteristic (ROC) curves were assessed to determine the optimal threshold scores for the HARS. Results Receiver operating characteristic analyses showed areas under the curve at 81.2%. For diagnoses of AD, the HARS demonstrated the best psychometric properties for a cutoff score ≥ 17 with sensitivity of 68.8%, specificity of 87.5%, positive predictive value of 52.4%, and negative predictive value of 93.3%. Conclusions The Polish version of the HARS performed moderately well as a screening instrument for ADs in PWE. In the epilepsy setting, the HARS maintains moderate sensitivity, high specificity, and excellent Negative perdictive value (NPV) but low Positive perdictive value (PPV) for diagnosing ADs with an optimum cutoff score ≥ 17. These results suggest that the HARS performed better to rule out anxiety, however, because of moderate sensitivity, some cases of anxiety might be missed.

Plasma magnesium concentration alterations, hypercortisolaemia, and systemic inflammation are observed in major depressive disorder (MDD). This exploratory study examined whether, and to what extent, plasma magnesium is related to C-reactive protein (CRP) levels and cortisolaemia in MDD. The concentrations of plasma magnesium, salivary CRP, and baseline plasma cortisol were studied in 20, treatment-naive MDD patients with short-illness-duration, first affective episodes and 20 matched controls. Depressed patients showed a basal score higher than 20 on the Hamilton Rating Scale for Depression (HAMD-17). Significantly higher magnesium (p = 0.016) and baseline cortisol (p = 0.01) concentrations were observed in MDD as compared to controls. No significant difference in CRP concentrations between the MDD and control groups was observed. A significant negative correlation was seen between magnesium and CRP in MDD (p

Objective Depressive disorders are common among patients with epilepsy (PWE). The aim of this study was to estimate the prevalence of different forms of depressive disorders among PWE treated in the outpatient setting. Methods A group of consecutive PWE that visited the epilepsy outpatient clinic was invited to participate in the study. Ninety-six patients met inclusion criteria and were examined by a trained psychiatrist using standardized measures. Results A diagnosis of a current major depression was established in 21 (22.3%) out of 96 participants. Furthermore, almost 20% of the study group fulfilled criteria for mood disorder categories other than MDD, adding up to over 40% of PWE suffering from any mood disorder category. Older age and later age at seizure onset, as well as unemployment, were associated with an increase in the odds of MDD diagnosis. Study limitations A number of limitations are to be considered: the sample size is relatively small, and the findings may not be representative of PWE in general because our population represents a sample coming from a single outpatient clinic with a higher ratio of drug-resistant epilepsy. Conclusions Major depression as well as other forms of depressive disorders are common among PWE. Unemployment, age, and age at seizure onset are important factors associated with major depression among PWE.

We investigated the phenotype of peripheral blood lymphocytes of patients with bipolar disorder type II in different phases of the disease in order to check whether there are specific changes in the immune parameters. Lymphocytes subpopulations were analyzed ex vivo with flow cytometry in patients in euthymic, depression or hypomanic phase of the disease and compared with healthy controls. All BD patients were characterized by lower percentage of CD3+CD4+ and CD3+CD8+ cells compared with healthy people. But only patients in depression and remission had higher percentage of B cells (CD19+ cells) compared with healthy people. The percentage of CD4+CD25+ and CD8+CD25+ cells was decreased in patients in hypomanic phase compared with healthy control. Patients in remission were characterized by increased concentrations of IL-6 and IL-10 and decreased level of TNF in blood serum. Significant correlations between immunologic parameters and the results of Hamilton or Young scale have also been found. Our results demonstrate that there are significant differences in lymphocyte subpopulations which depend on the phase of the disease the patient is currently in.

The aim of the study was to evaluate proliferation capacity and susceptibility to apoptosis of T lymphocytes of patients with bipolar disorder (BD) and to investigate in vitro influence of two standard mood stabilizers: lithium and valproic acid on these parameters using flow cytometry. Our results show that T lymphocytes of BD patients, especially those treated with lithium, have reduced proliferation capacity compared to healthy people. In vitro studies showed that valproic acid reduces the number of cell divisions and percentages of proliferating cells regardless of health status but mainly in very high dose, while lithium has no significant influence on proliferation capacity of patients’ T lymphocytes. Lymphocytes of BD patients are also more prone to apoptosis compared with healthy individuals which is related to high expression of Bax, a pro-apoptotic protein. In vitro lithium protected patients’ lymphocytes from apoptosis proportionally to dose used. Valproic acid protected lymphocytes of patients from apoptosis mainly in therapeutic concentration. Our results show that mood stabilizers used to prevent relapses of the disease have anti-apoptotic effect on T lymphocytes of BD patients but they are not able to improve their proliferation capacity.

The impaired decision-making with high risk-aversive behavior and elevated impulsivity are reported as a trait feature in anxiety disorders including panic disorder (PD). It is hypothesised that PD patients exhibit difficulties in executive functions which can influence patients behavioural strategies e.g. problem solving, decision making, planning, impulse control. The aim of this study was to asses decision making process, risk-taking and impulsivity in PD patients as compared to healthy controls.Twenty-one psychotropic drug-naive PD outpatients and 20 healthy subjects matched by age and sex were examined. Cognitive decision-making and risk-taking behaviour was measured with CGT (Cambridge Gambling Task) from CANTAB battery. The PD severity was assessed with Panic and Agoraphobia Scale (PAS). The level of anxiety and depression was assessed with HADS (Hospital Anxiety and Depression Scale). Impulsivity was evaluated with the Barratt Impulsiveness Scale, 11There were no statistically significant differences on CGT in PD patients as compared to healthy control. However, having observed more closely, there are some differences between patients and healthy control. PD patients with higher anxiety level in HADS exhibited lower percentages of risky decisions comparing to PD with lower anxiety in HADS. PD patients with higher depression level in HADS demonstrated slowed decision-making when compared to PD patients with low level of depression in HADS. Total impulsivity and its attentional and motor dimensions were significantly higher in panic disorder patients versus healthy controls.There were no statistically significant differences with regard to CGT assessed decision-making between drug-naive PD patients and healthy controls. The PD patients with higher HADS-D depression level demonstrated slowed decision-making as compared to PD patients with low level of depression.

Background Central noradrenergic dysfunction with autonomic nervous system dysregulation are reported in major depressive disorder (MDD). Salivary 3-methoxy-4-hydroxyphenylglycol (sMHPG) is indicative of central noradrenergic activity. Studies on MHPG in bodily fluids are inconsistent and scarce data is available regarding baseline sMHPG concentration in MDD. Methods The basal, non-stimulated sMHPG concentration was studied in this cross-sectional case-control study on 20 non-late-life adult, short-illness-duration first-episode, treatment-naive MDD patients and in 20 age- and sex-matched healthy controls. Depressed patients showed a score in the Hamilton rating scale for depression (HAMD-17) higher than 20. Results The baseline sMHPG concentration was significantly lower in depressed individuals as compared to controls ( p =0.025). In post hoc analysis significantly lower sMHPG was present in melancholic MDD ( p =0.009) as related to controls whereas no difference was seen between non-melancholic MDD patients and controls. The concentration of sMHPG was not significantly correlated neither with duration nor the severity of depressive symptoms as measured by the total HAMD-17 score. Limitations The current study is limited by its cross-sectional design and small sample size. Conclusion Low baseline sMHPG concentration was found in MDD. The study provides no support for elevated sMHPG in drug-naive patients with short-illness-duration first episode MDD. Taken into account the physiology of sMHPG secretion the study results corroborate with the evidence for decreased central noradrenergic activity in MDD when sMHPG is considered indicative of central noradrenergic function.

Background Altered monoamine neurotransmission accompanied by hypothalamic–pituitary–adrenal axis dysfunction and autonomic nervous system hyperactivity have been associated with major depressive disorder (MDD). Salivary α-amylase (sAA) is indicative of autonomic activation and reflects central noradrenergic activity. Scarce studies on sAA in MDD produce confounded results and no data is available regarding baseline sAA activity. Methods The basal, non-stimulated sAA activity was studied in this cross-sectional case-control study on 20 non-late-life adult, short-illness-duration first-episode, treatment-naive MDD patients and in 20 age- and sex-matched healthy controls. Depressed patients showed a basal score in the Hamilton Rating Scale for Depression (HAMD-17) higher than 20. Results The sAA was significantly lower in depressed individuals as compared to controls ( p =0.011). In post hoc analysis significantly lower sAA was present in melancholic MDD ( p =0.016) as related to controls whereas no difference was seen between non-melancholic MDD patients and controls. The sAA activity was not significantly correlated neither with duration nor the severity of depressive symptoms as measured by the total HAMD-17 score. Limitations The current study is limited by its cross-sectional design, small sample size, and factors related to saliva sampling methodology. Conclusion Low baseline sAA levels were found in MDD in basal, non-stimulated conditions. The study provides no support for elevated sAA in drug-naive patients with short-illness-duration first episode MDD. The results support the evidence for decreased central noradrenergic transmission in MDD when sAA activity is considered indicative of central noradrenergic function.

Plasma magnesium concentration changes are seen in major depressive disorder (MDD). Dysregulation of magnesium homeostasis is associated with the severity of depression and specific psychopathological features including apathy, anxiety, irritability, fatigue and weakness. Results from studies on magnesium concentrations in MDD patients are inconsistent, and the evidence for magnesium ions being associated with specific features of depression and anxiolytic effects is unclear. This study was designed to examine whether and to what extent plasma magnesium is related to the psychopathological features of depression including severity of symptoms and specific psychopathological aspects. Plasma magnesium levels were studied in this cross-sectional, case-control study and involved 20, non-late-life adults who were treatment-naïve, short- duration, first episode, MDD patients, and 20 age- and sex-matched, healthy controls. Psychometric evaluations were performed using the Hamilton Rating Scale for Depression (HAMD-17) and the Spielberger State-Trait Anxiety Inventory (STAI). A significantly higher magnesium (p = 0.016) concentration was observed in MDD patients compared to controls. No significant correlations were observed between magnesium concentrations and the total HAMD-17 score or with regard to the specific core depression, insomnia, anxiety or somatic HAM-D psychopathological features. In addition, no significant correlations were found between magnesium concentrations and STAIX-1 and STAIX-2 scores. The present study provides evidence of hypermagnesaemia in drug-naïve patients with a short-duration, first episode of MDD. A cross-sectional analysis adds to the evidence linking plasma magnesium concentrations with psychopathology of MDD during early stages of the disease although with no correlations between plasma magnesium concentrations and psychopathology including severity of symptoms and specific psychopathological features.

BACKGROUND Salivary α-amylase (sAA) activity alternations are observed in major depressive disorder (MDD) being associated with depression severity and its specific psychopathological dimensions with anxiety being attributed to distress. No data is available on sAA in MDD according to Hamilton Rating Scale for Depression (HAMD-17) and State-Trait Anxiety Inventory (STAI). The exploratory study examines whether and to what extent baseline sAA level is interrelated to the psychopathological features including severity of symptoms and specific psychopathological dimensions. MATERIAL AND METHODS The basal, non-stimulated sAA activity was studied in 20 non-late-life adult, treatment-naive MDD patients with short-illness-duration and in 20 age- and sex-matched healthy controls along with psychometric assessments with Hamilton Rating Scale for Depression (HAMD-17) and Spielberger State-Trait Anxiety Inventory (STAI). RESULTS Significantly lower (p=0.011) sAA activity was observed in MDD as compared to controls. No significant correlations were observed between sAA activity and the total HAMD-17 score as well as with regard to the specific core depression, insomnia, anxiety and somatic HAM-D psychopathological dimensions. No significant correlations were also found between sAA and STAIX-1 and STAIX-2 scores. CONCLUSIONS Low baseline sAA levels in MDD with no correlations between sAA and psychopathological features including severity of symptoms and specific psychopathological dimensions was found. Key words:Salivary alpha-amylase, major depressive disorder, Spielberger State-Trait Anxiety Inventory, Hamilton Rating Scale for Depression.

Katarzyna Jakuszkowiak-Wojten, Jerzy Landowski, Mariusz S Wiglusz, Wiesław Jerzy Cubała Department of Psychiatry, Medical University of Gdansk, Gdansk, Poland Background: It is unclear whether hypothalamic–pituitary–adrenal axis is involved in the pathophysiology of panic disorder (PD). The findings remain inconsistent. Cortisol awakening response (CAR) is a noninvasive biomarker of stress system activity. We designed the study to assess CAR in drug-naïve PD patients. Materials and methods: We assessed CAR in 14 psychotropic drug-naïve outpatients with PDand 14 healthy controls. The severity of PD was assessed with Panic and Agoraphobia Scale. The severity of anxiety and depression was screened with Hospital Anxiety and DepressionScale. Results: No significant difference in CAR between PD patients and control group was found. No correlations were observed between CAR and anxiety severity measures in PD patients and controls. Limitations: The number of participating subjects was relatively small, and the study results apply to nonsuicidal drug-naïve PD patients without agoraphobia and with short-illness duration. There was a lack of control on subjects’ compliance with the sampling instructions. Conclusion: The study provides no support for elevated CAR levels in drug-naïve PD patients without agoraphobia. Keywords: panic disorder, PD, CAR, cortisol awakening response, HPA axis, hypothalamic–pituitary–adrenal axis

Objective Depressive disorders are the most common comorbidities among patients with epilepsy (PWE). The availability of standardized clinical instruments for PWE is limited with scarce validation studies available so far. The aim of the study was to validate the Polish Version of the Hamilton Rating Scale for Depression (HRSD) in adult PWE. Methods A group of 96 outpatient PWE were examined by a trained psychiatrist using the Structured Clinical Interview (SCID-I) for DSM-IV-TR and the 17-item Polish Version of HRSD (HRSD-17). Receiver operating characteristic (ROC) curves were used to determine the optimal threshold scores. Results The ROC analyses showed areas under the curve approximately 0.9. For diagnoses of MDD, HRSD-17 demonstrated the best psychometric properties for a cutoff score of 11 with sensitivity of 100%, specificity of 89.3%, positive predictive value of 72.4%, and negative predictive value of 100%. Conclusions The 17-item Polish Version of HRSD proved to be reliable and valid in the epilepsy setting with a cutoff score of 11 points.

bez streszczenia

According to American College of Rheumatology fibromyalgia syndrome (FMS) is a common health problem characterized by widespread pain and tenderness. The pain and tenderness, although chronic, present a tendency to fluctuate both in intensity and location around the body. Patients with FMS experience fatigue and often have sleep disorders. It is estimated that FMS affects two to four percent of the general population. It is most common in women, though it can also occur in men. FMS most often first occur in the middle adulthood, but it can start as early as in the teen years or in the old age. The causes of FMS are unclear. Various infectious agents have recently been linked with the development of FMS. Some genes are potentially linked with an increased risk of developing FMS and some other health problems, which are common comorbidities to FMS. It is the genes that determine individual sensitivity and reaction to pain, quality of the antinociceptive system and complex biochemistry of pain sensation. Diagnosis and therapy may be complex and require cooperation of many specialists. Rheumatologists often make the diagnosis and differentiate FMS with other disorders from the rheumatoid group. FMS patients may also require help from the Psychiatric Clinic (Out-Patients Clinic) due to accompanying mental problems. As the pharmacological treatment options are limited and only complex therapy gives relatively good results, the treatment plan should include elements of physical therapy.

CelCelem pracy była ocena ewentualnej zależności pomiędzy wystąpieniem depresji poudarowej (DPU) a wybranymi parametrami klinicznymi oraz demograficznymi.MetodaZbadano pacjentów hospitalizowanych w Klinice Neurologii AMG (kwiecień 2003 - grudzień 2005) z powodu pierwszego, niedokrwiennego udaru mózgu. Wstępnie zakwalifikowano 116 osób (61,4±12,6 lat, kobiety N=42). Analizie podlegały dane demograficzne, strona udaru i miejsce uszkodzenia w oparciu o badania neuroobrazowe, oraz globalny deficyt neurologiczny oceniany w pierwszej dobie po udarze i w dniu wypisu, wg NIHSS (National Institutes of Health Stroke Scale) i Wskaźnika Barthel (BI – Barthel Index of Activity of Daily Living). Badania psychiatrycznie wykonano: 6 (42 dni±3 dni) i 12 tygodni (84 dni±7 dni) oraz 6 (± 14 dni) i 12 miesięcy (± 14 dni) po udarze z oceną w oparciu o kryteria ICD-10 wraz z oceną stopnia sprawności funkcjonalnej (skalą Rankina).WynikiDepresja wystąpiła u 29 pacjentów (27,6%). Nie potwierdzono związku jej wystąpienia z płcią ani wiekiem. W dniu udaru i wypisu osoby bez DPU były nieco sprawniejsze, jednak w stopniu nieznaczącym statystycznie. Potwierdzono zależność pomiędzy obecnością DPU a wynikami skali Rankina, poza stopniem poprawy w czasie obserwacji. W grupie osób z depresją udary lewopółkulowe były nieco częstsze, jednak różnica ta nie osiągnęła istotności statystycznej. Obecności zmian w obrębie płatów czołowych i jąder podstawy towarzyszyło częstsze występowanie depresji.WnioskiStwierdzono związek pomiędzy obecnością DPU i lokalizacją zmian udarowych (w płatach czołowych lub jądrach podstawy) oraz stopniem sprawności funkcjonalnej ocenianej w okresie 12 m-cy po udarze.

Studies and data on prevalence, recognition and clinical features of bipolar disorder (BD) in epilepsy remain limited. Still, there is a growing evidence of BD and epilepsy being frequent co-morbid conditions with some features suggesting shared pathophysiological mechanisms that include the episodic course of both conditions, the possible kindling mechanism and the efficacy of some antiepileptic drugs (AEDs) in BD.The aim of this paper is to review concepts of overlapping phenomena of bipolar disorder and epilepsy. A literature review of the theoretical bases of the relationship between BD and epilepsy is presented.The comorbidity of epilepsy and mood disorders was a subject of interest of many studies for decades. Bipolar disorder and epilepsy have a number of clinical, biochemical and pathophysiological features in common. Bipolar disorder in epilepsy, excluding the ictal or periictal symptoms, can be categorized using standardized measures. Standardized psychiatric interview procedures based on DSM criteria like SCID-I or MINI provide comprehensive way to diagnose mood disorders in patients with epilepsy.

Clozapine is the treatment of choice in drug-resistant schizophrenia. Lamotrigine is a mood stabiliser recommended as combined treatment strategy in clozapine-resistant patients. There are cases of late-onset agranulocytosis reported in literature. Some are associated with clozapine or lamotrigine, others with the combination of both.The article presents a case of rapid-onset agranulocytosis in a 60-year old clozapine-resistant patient, in whom lamotrigine was introduced as potentiation strategy. Discontinuation of both substances and GCSF treatment resulted in normalization of the absolute neutrophil count.The case suggests a possibility of developing rapid-onset agranulocytosis in clozapine-resistant patients who require lamotrigine as augmentation strategy. This emphasises the significance of monitoring a patient's blood count and early management of any dyscrasias noticed.

Depressive disorders are common among patients with epilepsy (PWE). The aim of this study was to explore symptom frequencies of 17-item Hamilton Depression Rating Scale (HDRS-17) and recognize the clinical characteristics of Major Depressive Disorder in PWE.A sample of 40 adults outpatients with epilepsy and depression was diagnosed using SCID-I for DSM-IV-TR and HDRS-17. The total HDRS-17 score was analysed followed by the exploratory analysis based on the hierarchical model.The frequencies of HDRS-17 items varied widely in this study. Insomnia related items and general somatic symptoms items as well as insomnia and somatic factors exhibited constant and higher frequency. Feeling guilty, suicide, psychomotor retardation and depressed mood showed relatively lower frequencies. Other symptoms had variable frequencies across the study population.Depressive disorders are common among PWE. In the study group insomnia and somatic symptoms displayed highest values which could represent atypical clinical features of mood disorders in PWE. There is a need for more studies with a use of standardized approach to the problem.

Dysregulation of hypothalamic-pituitary-adrenal axis (HPA) is seen in numerous mental disorders. Data of HPA axis disturbance in panic disorder are inconsistent. In panic disorder HPA axis hyperactivity has been observed with elevated cortisol levels. However, hypocortisolism has also been noted. Salivary cortisol as a biomarker of HPA-axis activity has received special attention. The aim of this paper is to review the findings on cortisol levels in panic disorder.

Anxiety symptoms and disorders are common. High comorbidity between anxiety and other psychiatric disorders has been observed in community. Still, the relationship between impulsivity and anxiety disorders is controversial and not well explored.The aim of this paper is to review measures of trait impulsivity in anxiety disorders. A literature review of the theoretical bases of the relationship between anxiety disorders and impulsivity is presented.Impulsivity is a key feature of numerous psychiatric disorders. Traditional conceptualizations suggest that impulsivity might display a negative relationship with anxiety. However, an association of impulsivity in patients with anxiety disorders is present. Some studies support proposition that anxiety may influence impulsivity in individuals with predisposition toward behavioural disinhibition.There is a link between anxiety and impulsivity in psychiatric patients characterized by problems with impulse control (e.g. pathological gambling, self-harming behaviour, eating disorders), mood disorders and anxiety disorders. Behavioural and pharmacological interventions for decreasing impulsivity may effectively be used in the treatment.

Impulsivity is associated with a wide variety of psychiatric disorders. However, the relationship between anxiety and impulsivity is not well explored. The objective of this study was to examine whether anxiety symptoms correlate with impulsivity in patients with panic disorder.We examined 21 psychotropic drug-naove patients with panic disorder recruited from the outpatient setting. The severity of Panic Disorder was assessed with Panic and Agoraphobia Scale (PAS)-clinical rating version. Impulsivity was evaluated with Barratt Impulsiveness Scale, 11th version (BIS-11).Our findings indicate the correlation between specific dimensions of impulsivity and selected subscales of Panic and Agoraphobia Scale. The positive correlation between attentional and non-planning dimensions of impulsivity, 'disability' and 'worries about health' in drug-naove patients with PD was observed.The findings corroborate with the prior reports of higher impulsivity trait among patients with anxiety disorders.

Some investigations strongly support a role of glial abnormalities in the pathophysiology of bipolar disorder. The degree of white matter axonal and myelination disruption is measured through the rate of water molecule diffusion. High ADC measures correspond to relatively unimpeded water diffusion, while low ADC measures reflect preserved myelinated axons.Parietal and occipital areas may be involved in the pathophysiology of bipolar disorder, particularly in cognition and perception, along with the prefrontal and temporal cortices for the disruption of emotional processing. In the literature the widespread alterations of the cortical white matter microstructure is documented.This case reports demonstrates the features of the increased mean ADC values in the left occipital lobe. Future DWI studies are expected to investigate the correlation of white matter changes with the functional impairment, which often persists during euthymia in bipolar disorder.

CelCelem badania było oznaczenie stężenia czterech cytokin prozapalnych (IL17a, IL6, TNFα i IL12p70 ) w osoczu pacjentów z zawałem mięśnia sercowego i ocena ich związku z wystąpieniem depresji w ciągu 6 miesięcy od zawału serca.MetodaU 40 pacjentów z pierwszym zawałem mięśnia sercowego z uniesieniem odcinka ST dokonano pomiaru stężeń IL17a, IL6, TNFα i IL12p70 w osoczu w trzecim i piątym dniu zawału, następnie dokonano analizy wyników w zależności od obecności depresji w okresie 6 miesięcy obserwacji.WynikiNie stwierdzono istotnych różnic pomiędzy badanymi grupami pacjentów po zawale m. sercowego pod względem stężenia badanych cytokin. Porównując badane grupy z osobami zdrowymi zaobserwowano miedzy nimi pewne różnice. W porównaniu z grupą osób zdrowych grupa z depresją cechowała się podwyższonymi stężeniami wszystkich badanych cytokin w 3 dni po zawale, w dniu piątym – dwóch z nich: IL17a i IL6, w grupie bez depresji w 3 dniu podwyższone były tylko dwie z czterech badanych cytokin, w dniu 5 jedynie IL6.WnioskiNie stwierdzono istotnych różnic pomiędzy badanymi grupami osób po zawale m. sercowego pod względem stężenia badanych cytokin. Przeprowadzona analiza porównawcza tych grup z osobami zdrowymi może sugerować obecność nieco większej aktywacji badanych cytokin, szczególnie IL17a w grupie pacjentów z obecnością depresji.

A number of preclinical and clinical studies are focused on mechanisms of SSRI discontinuation syndrome as well as the patient populations and agents that are most affected by this phenomenon. Characteristics of onset, duration, and severity of any discontinuation symptoms and spontaneous reports of taper/poststudy-emergent adverse events should be compared with those of the active comparator in these studies. Besides, common clinical practice supplies a number of problems associated with SSRI discontinuation syndrome as related to treatment planning and management. The recommended instrument for evaluating SSRI discontinuation syndrome symptoms is the Discontinuation-Emergent Signs and Symptoms (DESS) inventory. DESS is a 43-item checklist that can be administered in a clinician-rated form, a self-rated form, or an interactive voice-response form. The paper presents the Polish version of DESS inventory along with its application and interpretation instructions. DESS inventory is of substantial advance in common psychiatric practice as it enables effective SSRI discontinuation management on drug tapering and in case of the non-compliance with the treatment. Its use in the systematic studies facilitates conclusive outcome results and is of prime importance as being comparable with literature outcomes.

The aim of this study was to adapt the Quality of Life in Depression Scale to Polish conditions. The scale determines the quality of life, defined in terms of the concept of needs, and focuses on patients with depressive disorders. Since its basic version has been developed, the tool was adapted in many countries, also outside Europe.The adaptation procedure included the translation of the original version into Polish, followed by the English retranslation, and was performed by four independent, qualified translators. The final Polish version was verified during a pilot study.This pilot study confirmed high reliability of the Polish version of Quality of Life in Depression Scale.The Quality of Life in Depression Scale (QLDS) can be considered an interesting tool in view of its broad theoretical background, and a simple procedure to complete during a clinical evaluation. The use of a specialist translation procedure, and the results of our pilot study suggest that the QLDS can be used in further research, both when evaluating a clinical population and when dealing with individual patients.

Central serotonergic dysfunction is reported in major depressive disorder (MDD). Serotonin is primarily metabolized to 5-hydroxyindole acetic acid (5-HIAA) and its plasma, urinary or cerebrospinal fluid concentrations were extensively studied in depression. No data is available on salivary 5-HIAA (s5-HIAA) in MDD to date.The basal, non-stimulated s5-HIAA concentration was studied in this cross-sectional case-control study on 20 non-late-life adult, short-illness-duration first-episode, treatment-naïve MDD patients and in 20 age- and sex-matched healthy controls. Depressed patients showed a score in the Hamilton Rating Scale for Depression (HAMD-17) higher than 20.No significant difference in s5-HIAA concentration between patients with MDD and controls was observed. In post hoc analysis significantly lower s5-HIAA was seen in non-melancholic MDD (p=0.026) as related to controls whereas no difference was seen between melancholic MDD patients and controls. The concentration of s5-HIAA was not significantly correlated neither with duration nor the severity of depressive symptoms as measured by the total HAMD-17 score.No difference was observed in baseline s5-HIAA concentration between MDD patients and healthy controls. That observation corroborates with previous MDD studies on 5-HIAA concentrations in bodily fluids where unaltered 5-HIAA concentration is seen in the absence of serotonin-related behaviours including impulsivity, suicidality, and anxiety. Salivary 5-HIAA use remains to be determined.

In major depressive disorder (MDD) hypozincaemia associated with symptoms severity, melancholia, anxiety and treatment-resistance is reported. Data linking zinc with specific psychopathological dimensions is limited.Plasma zinc was analyzed in this cross-sectional case-control study on 20 non-late-life adult, treatment-naïve MDD patients with short-illness-duration first affective episode and 20 matched healthy controls together with psychometric evaluations including Hamilton Rating Scale for Depression (HAMD-17) and Spielberger State-Trait Anxiety Inventory (STAI).No significant difference in zinc levels was found between MDD subjects and controls. No significant correlations were observed between zinc concentration and the total HAMD-17 score as well as with the specific core depression, insomnia, anxiety and somatic psychopathological dimensions or STAIX-1 and STAIX-2 scores.The study provides evidence for unchanged plasma zinc concentration at early stage of MDD and failed to demonstrate any correlation between plasma zinc and psychopathological features including severity of symptoms and specific psychopathological dimensions in MDD.

Syphilis is a sexually transmitted disease caused by Treponema pallium. The invasion of the central nervous system is observed in 5-10% of untreated patients and may occur at any stage of the disease. The diagnosis of the early stage of syphilitic infection is complex as many patients present either nonspecific symptoms or are asymptomatic. The identification of the most common radiologic characteristics of neurosyphilis is important in the proper diagnosis of the infection.The paper reviews the MR findings in neurosyphilis presented in the literature with the emphasis on common traits, patterns and factors in MR neuroimaging in neurosyphilis.Twelve papers were selected as suitable for analysis. Psychiatric symptomatology was the most common clinical manifestations of neurosyphilis. As MRI findings in neurosyphilis were not highly specific it proved being the most sensitive technique in detecting the changes in cerebral vasculitis commonly presenting with focal areas of high signal intensity in any distribution with areas of infarction and hemorrhage observed at times. In neurosyphilis medium and small vessels are usually involved. Parenchymal and meningeal enhancement was usually demonstrated. The most frequently involved arteries are middle cerebral artery and branches of the basilar artery. However, normal findings were also common.The most common MR diagnostic features are medium contrast enhancement, atrophy, white matter lesions, cerebral infarction, oedema. Radiologists, neurologists, and psychiatrists should take neurosyphilis into consideration when facing the differential diagnosis in central vascuclar disorders.

In Panic Disorder (PD) both somatic and cognitive symptoms occur. Cognitive functions which may be involved with anxiety and maladaptive cognition such as e.g. attention, memory and perception might be decreased.Within the preliminary studies eleven patients diagnosed with panic disorder (DSM-IV-TR), and nine healthy controls were studied. The severity of disorder was measured by the Panic and Agoraphobia Scale. To assess working memory Delayed Match to Sample (DMS) with CANTAB (Cambridge Neuropsychological Test Automated Battery) was used.Percent of correct answers was significantly different in both groups in delayed visual memory and recognition test. In the control group results were higher (M=92.22) than in the experimental group (86.06).PD is associated with impaired performance on a DMS task that requires the stable maintenance of representations in working memory.

Background Hypercortisolemia and low grade systemic inflammation are observed in major depressive disorder (MDD). Studies on markers of systematic inflammation and Hypothalamic–Pituitary–Adrenal (HPA) axis dysregulation in MDD produce confounded results due to heterogeneity of MDD patients related to illness stages and severity with a large proportion suffering from remitted-recurrent and treatment-resistant/chronic depression with first-episode major depression being underrepresented. This study was designed to examine whether and to what extent CRP is related to baseline cortisol concentrations in a well defined cohort of short-illness-duration first-episode, treatment-naive MDD patients. Methods The levels of salivary C-reactive protein (CRP) and baseline plasma cortisol concentrations were studied in this cross-sectional case-control study on 20 non-late-life adult, treatment- naive MDD patients with short-illness-duration first affective episode and in 20 age- and sex-matched healthy controls. Depressed patients showed a basal score in the Hamilton Rating Scale for Depression (HAMD-17) higher than 20. Results No significant difference in CRP concentration between MDD and control groups was found. Significantly higher baseline cortisol ( p =0.01) concentration was observed in MDD as compared to controls. Significant positive correlation was found between cortisol and CRP levels both in MDD subjects ( r =0.57; p =0.008) and controls ( r =0.61; p =0.004). Limitations The current study is limited by its cross-sectional design and small sample size. Conclusion The study supports data on elevated cortisol concentration in MDD providing no evidence for elevated CRP levels at the early stage of the disease.

Background An altered postsynaptic 5-HT 1A receptor function along with hypercortisolemia has been associated with major depressive disorder (MDD). However, several methodological considerations related to data interpretation arise when subjects previously exposed to psychotropic medication are included in the study population. To address those issues we designed a study in a well defined cohort of first-episode, treatment-naive MDD patients. Methods This cross-sectional case–control pharmacologic challenge study was designed to investigate the prolactin (PRL) response to buspirone in 21 non-late-life adult, treatment-naive MDD patients with the first affective episode and in 20 age- and sex-matched healthy controls. Depressed patients showed a basal score in the Hamilton Rating Scale for Depression (HAMD-17) higher than 20. Results No significant difference in PRL response to buspirone between first-episode, treatment-naive patients with MDD and controls, was observed. The correlation between basal cortisol levels and PRL response was not observed in MDD group while significant negative correlation was found in healthy controls. The significantly higher PRL response to buspirone was observed in melancholic patients as compared to non-melancholic subjects. Limitations The current study is limited by its cross-sectional design, small sample size, factors related to neuroendocrine challenge methodology, and no placebo control. Conclusion These results indicate no consistent changes in the hormonal response to the 5-HT 1A agonist buspirone in major depression. Taken into account the interpretation of the buspirone test the present study does not support the hypothesis of an altered functional activity with down-regulation of the postsynaptic 5-HT 1A receptor and/or in the postsynaptic receptor signal transduction in the hypothalamus in the pathogenesis of MDD.

Mood disorders are common in people with epilepsy (PWE) with prevalence rates ranging from 11% to 62%. The variation in epidemiological data results probably from the diversity of methodologies employed and selection of the populations across the studies. Moreover, the symptomathology of mood disorders in epilepsy is often atypical, intermittent and pleomorphic and fails to meet DSM-IV-TR categories. Several studies suggested the existence of distinct interictal dysphoric disorder (IDD) in patients with epilepsy. The majority of research studies in mood disorders in epilepsy were based on screening instruments in the diagnosis of mood disorders in PWE. However, the results in validity and reliability in detecting major depression in epilepsy using self-report inventories of mood symptoms is vague. The aim of this study was to review studies on mood disorders in epilepsy with particular focus on diagnostic methods.The focus of this Review was on patient studies on mood disorders in epilepsy (2000-2012). We searched PubMed using the following search terms (effective date: 20th May 2012): (epilepsy (Title/Abstract) OR seizure (Title/Abstract)) AND depression (Title/Abstract) OR Dysthymia OR mania OR bipolar disorder OR affective disorder OR Interictal Dysphoric Disorder OR AND (humans (MeSH Terms) AND English (lang) AND (2000/01/01(PDAT): 2012/04/31(PDAT)).Depression is the most frequent comorbid psychiatric disorder in epilepsy. Recent studies pointed out that bipolar disorders are not rare in epilepsy. Most of the research in PWE did not rely on standardized psychiatric measures and only about 18% of studies were based on diagnostic psychiatric interviews (mainly MINI and SCID-I). Mood disorders in epilepsy excluding the ictal or periictal symptoms can be categorized using standardized measures.Common self-report depression measures may be used to screen for depression in clinical settings. The use of screening instruments in epilepsy must be followed by structured psychiatric interviews designed to establish a DSM-IV-TR diagnoses. Standardized psychiatric interview procedures based on DSM criteria like SCID-I or MINI provide a comprehensive way to diagnose mood disorders in patients with epilepsy.