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STUDY OF LAMOTRIGINE AND ESCITALOPRAM TREATMENT IN, PATIENTS OF EPILEPSY WITH DEPRESSION

1Yadav J S, 2Kaur S,   3Singh K

Assistant Professor, AIIMS, New Delhi1, Psychologist SRLNM Hospital Varanasi,2 Associate professor, IMS,BHU, Varanasi.3

 

Abstract

Background- Depressions are more common problem in epilepsy with depression; studies reported 38% -63% prevalence in adult patients. SSRIs are main antidepressants proved to be safe in these patients; however there are some controversial studies reported that seizure might increase after some SSRIs.

Aim- To study the antidepressant effects and seizure control on escitalopram and lamotrigine therapy in patients of epilepsy with depression

Methodology 200 patients of epilepsy with depression randomized from neurology OPD,IMS, BHU, Varanasi, out of 200 patients, 160 patients fulfilled the selection criteria. Those patients divided in two groups, group A received escitalopram and group B lamotrigine, patients of both groups rated on HDRS and EEG were recorded.

Results- the mean percentage of improvement on HDRS scores in mild, moderate, severe, very severe categories after escitalopram therapy were 45.50, 38.55, 23.61 and 25 respectively. In lamotrigine group categories of mild, moderate, severe and very severe patients, the mean percentage of improvement on HDRS scale were find less than first group and the improvement in HDRS scores find that the level of severities change at mild and moderate level after 8 week of therapy. In both the groups mild category of depressions changes into no depression. The abnormal records in group A were find to be more while in group B it decreases at subsequent recordings after 4week, 8week. The abnormal wave increases up to 20%in group A in compare to initial recording.

Conclusion-Treatment of depression in epilepsy with Escitalopram decreases more percentage of HDRS score than lamotrigine group and on, EEG recordings it shown 20% more slow wave frequencies than initial recording.

Key Words: Lamotrigine and Escitalopram, Epilepsy with Depression

 

Introduction

Depressions are more common problem in epilepsy, and many antiepileptic also causes depression in attempt to control the seizures. The studies reported 38% -63% depressions in adult with epilepsy, and 80% patients with epilepsy do not routinely screen for depression1. Another retrospective study   reported in patients those were seizure free for 6 months, 10% had intractable epilepsy and were depressed, and 11% did not have intractable epilepsy and were depressed 2. Anti depressant helps to seizure control by alleviating emotional distress and depression for improving compliance. The effects of lamotrigine versus placebo on depressive symptoms in patients with epilepsy were prospectively assessed at the end of the maintenance phase; mean (SD) improvement from baseline was greater with lamotrigine than placebo.  Lamotrigene is only AEDs approved as antidepressant and almost minimal cognitive impairment 3. There was contradiction findings reported in a study with sertraline that antidepressant increases seizure frequency in stabilized depressed patients 4. In our study we have measured the seizure activities in brain after giving escitalopram along with four commonly prescribed antiepileptics and Lamotrigene alone, depressions were rated on HDRS scale and brain activity recorded through EEG at defined intervals. Study with EEG recording to measure Seizure activities after antidepressant therapy in patients of epilepsy with depression not done in study. Therefor in this study we have tried to explore new area of research.

Aim: To study antidepressant effects and seizure control of escitalopram with AEDS and lamotrigine.

Methodology200 patients screened from neurology OPD institute medical sciences, Banaras Hindu University Varanasi, The diagnosis of epilepsy in selected patients were done by consultant neurologists, and then those patients were referred to department of psychiatry, the patients were further diagnosed by consultant incharge for their comorbid depressions and then they were rated on HDRS scale 5 by trained psychologist. The plan of study deign discussed with both consultants, the selection criteria was 1) Age between 18- 45 years. 2) No other physical or psychiatric illness/ disorder. 3) Seizure controlled for more than 6 months. 4) Able to give consent for participation in study. Finally 160 patients fulfilled the selection criteria, these patients were divided into two groups of 80 patients. a) The patients were given antiepileptic and Escitalopram. b) Lamotrigine group, these patients titrated on lamotrigine within 2 weeks. The written consent for treatment was taken from each patient, the socio-demographic data were recorded and base line investigations, CT scan, EEG done. The dose range of Escitalopram prescribed at 10-20 mg/day in single dose, along with three separate  AEDs that is carbamazepine, valproate, phenytoin,  the doses of range were 400+_200 mg/day, 1000 +_250mg/day, 400+__ 200mg/day respectively,  and doses range of lamotrigine  was 150+_50 mg/day in two divided doses. Each patient were given seizure recording diary and phone number and advised that if he has seizure, immediately inform to consultant. The patients those have seizure  during the titration they were given inject able  lorazepam, during the titration four patients developed seizure in lamotrigine group and they were excluded from study, finally 76 patient continued on lamotrigine and 80 patients in Escitalopram group. All the patients were rated on HDRS and EEG done at 0,4, 8  week intervals.

Result:Depression with epilepsy is 26 % in younger age between 18-23 year followed 21% in age between 40-45.  45% single/widows patients have depression with epilepsy during first contact in OPD.  60% patients were less educated, unemployed and have poor socio-economic status. However the separate sociodemographic data on gender based not analysed due to small sample size. Both the groups of patients were analysed on two ways after given therapies 1) analysed on the basis of categories of depressions that is mild, moderate, severe, very severe. 2) Analysed on basis types of antiepileptic received. In Escitalopram with antiepileptic group, the mean percentage of improvement on HDRS scores were 45.50, 38.55, 23.61 and 25 respectively, these improvement felt into no depression category. In lamotrigine group categories of mild, moderate, severe and very severe patients, the mean percentage of improvement on HDRS scale were found less than first group and the improvement in HDRS scores results that severities change at   mild and moderate level of categories on 8 week of therapy (Table-1).

Table -1 Distribution of patients on basis of types of depression, changes in HDRS scores and percentage of improvements after taken treatment of each group of medicines from 0 to 8weeks intervals.

  Categorical

No. of patients

    Mean HDRS score

Percentage of changes in HDRS score after 8 week in each group

        0 day

   after  8 week

E

L

E

   L

E

   L

E

L

Mild

42

39

11.56

11.20

6.30

7.20

45.50

35.71

Moderate

31

28

16.47

17.10

10.12

14.25

38.55

16.67

Severe

6

  7

21.60

22.10

16.50

18.60

23.61

15.84

v. severe

1

   2

24   

25.00

18

21.00

25.00

16.00

 

HDRS- Hamilton Depression Rating Scale, E- ( Escitalopram +AEDs group)                         L-Lamotrigine group.

 

 

 

 

 

 

 

 

 

The analysis on basis of antiepileptics drugs received, 25, 25 and 30 patients, in escitalopram group treated with cabamezepine, valproate, phenytoin respectively while in lamotrigine group 76 patients received single medicine. HDRS scores of all groups of patients separately analysed, the scores decreases in each group. The maximum reduction was found with carbamezipine and minimum with phenytoin in group A, the overall reduction of scores in group A was higher than group B (Table 2).     

 

 

Table- 2 Distribution of HDRS scores in ( AEDs + escitalopram) and lamotrigine groups at 0, 4, and 8 weeks intervals.

Groups

No. Of patients

AEDs

   HDRS score (total mean of all types depressions)

Percentage of improvement after 8week

 

0 day

4 week

8 week

A

25

C+E

14.90

11.53

7.47

49.86

25

V+E

14.01

13.02

7.69

45.11

30

P+E

14.85

13.25

9.20

38.05

B

76

Lam.

14.17

14.13

10.66

24.77

 

 

 

 

 

 

 

 

 

 

 

AEDs- Antiepileptic Drugs, C- Carbamezipine, V- valproate, E- Escitalopram, Lam. –Lamotrigine

The reduction of HDRS scores and improvement with carbmezipine, valproate, phentoin with escitalpram and lamotrigine alone were found to be all stages of treatment but maximum at 8 week. These percentages of improvements were higher among AEDs with escitalopram than lamotrigine group (figure 1).

Figure 1-Pictogram show relative change in mean HDRS Scores and percentage of improvement (between AEDs + escitalopram and Lamotrigine groups) at different time interval.

 

Though the patients in both groups were stabilized and were seizure free, during that phage findings of EEG records were generalized slow, sharp waves and high voltage slow waves in both groups we have taken both in combined. In group A records of separate antiepileptic that is  carbamezipine, valproate,phenytoin were found tobe  2,2, 3 abnormal respectively and in group  B it was 5 on day 0. The abnormal records in group A were found to be more while in group B it decreases at subsequent recordings  after 4wee, 8week. The abnormal wave increases upto 20%in group A in compare to initial recording, in phenytoin group this finding was slightly higher. In contrast to group B in which it decreased 50%.

Figure 2 Relationships between durations and abnormal wave after antiepileptic therapy with or without escitalopram.

 

 

Discussion:  Depressions are more common problem associated epilepsy because there are many factors like psychosocial cognitive, long term antiepileptic therapy and uncertainty in recovery of diseases causes further burden in management of disease. Therefore multidisciplinary comprehensive approaches for management are requires. SSRI s are the common medicines prescribed in depressions with epilepsy however there  are certain issues with antidepressant therapies  like long term management, poor response, adverse effect of multidrug therapy and their rationales  in epilepsy requires further exploration of facts. In this study we have taken commonly prescribed antiepileptics and SSRI in epilepsy with depression. The results were more favourable with escitalopram, but other associated parameters those require for general wellbeing not measured. In this study we find that 38.05 to 49.86 % improvement depressions find, depending upon types of antiepileptic. Similar findings also reported in two studies 6, 7 in those, they included all types of depressions and all types of epilepsies, in both studies patients received antidepressant citalopram and rated on MARDS, after 4moth improvement were 18% and 65.1 % subsequently.  In another study 8 in which 95 % patients have partial epilepsy with depressions, in that study sertraline was given and after 4 months they reported 54% improvement that corresponds to complete remission of depression.  Many studies.9, 10 recently reported that the addition of antidepressants in patient with epilepsy give favourable result after resolution of stresses from epilepsy. In all these studies they not commented on role of these antidepressants on seizures.

 In our study  EEG  recording done in both groups of patient those were on AEDs with escitalopram and lamotrigine alone, on comparing of both groups lamotrigine decreases seizure frequency than other group  at one  month  intervals, we find that  slow wave increases from 10% to20 %,this study similar to Kanner et al8. one with sertraline in which  out of 97 patient sertraline Increase seizure threshold  in one patient and transient increase in five.

Thome-Souza et al11. Studied in 36 (children & adolescents) taken sertraline, fluoxetine they find frequency of seizure increase in two patients.  Vermoesen et, al12 investigated the effects of 4 days of citalopram treatment, in animal find that citalopram reduced seizure frequency and cumulative seizure duration, without affecting seizure severity. Recent experimental studies13 of AEDs used to treat depression lead to the conclusion that it is unlikely that alterations in serotonin and norepinephrine levels are related to an increased risk of seizures.

Our study differs from those studies by recording action potential change in neurons during therapy,  although slow waves are not directly proportional to numbers of seizures frequencies but explores probabilities of causative factors those  not favourable of treatment  with SSRI. Though the antidepressant response with lamotrigine was poor in comparisons to SSRI group but the outcome of treatment in seizure was better than combination of AEDs and SSRI. 

Conclusion- AEDs in combination with Escitalopram are more prone to developed slow wave frequencies while single lamotrigine act as antidepressant and decreases slow wave in patient of depression with epilepsy.

Limitations: Sample selection was hospital based, therefore that did not represent the uniformity of population. In this sample duration, chronicity of illness, past treatment not adjusted, though the sample size was small therefore many other factors not explained. 

References

1.        Kanner AM, Nieto JC. Depressive disorders in epilepsy. Neurology. 1999; 53(5 Suppl 2):S26–32.

2.        Attarian H, Vahle V, Carter J, Hykes E, Gilliam F. Relation between Depression and Intractability of Seizures. Epilepsy Behav 2003; 4:298–301.

3.        Ettinger AB, Kustra RP, Hammer AE. Effect of lamotrigine on depressive symptoms in adult patients with epilepsy. Epilepsy 2007 Feb; 10 (1):148-54. Epub 2006 Oct 27.

4.        Kanner AM, Kozak AM, Frey M. The use of sertraline in patients with epilepsy: is it safe? Epilepsy & Behaviour; 2000; 1:100-5.

5.         Hamilton, M (1960) A rating scale for depression. Journal of Neurology, Neurosurgery and Psychiatry. 23: 56-62.

6.        Specchio LM, Iudice A, Specchio N, La Neve A, Spinelli A,Galli R, Rocchi R, Ulivelli M, De Tommaso M, Pizzanelli C,Murri L. Citalopram as treatment of depression in patientswith epilepsy. Clinical Neuropharmacology.2004; 27(3):133.

7.        Specchio LM, Iudice A, Specchio N, et al. Citalopram as treatment of depression in patients with epilepsy. Clin Neuropharmacol. 2004; 27(3):133–6.

8.        Kanner AM, Kozak AM, Frey M. The use of sertraline in patients with epilepsy: is it safe? Epilepsy & Behaviour; 2000;1:100-5

9.        Hovorka J., Herman E., Nemcova I. Treatment of postictaland interictal depression in patients with epilepsy. Ceska a Slovenska Psychiatrie. 2000; 96(3):147-9.

10.     Specchio LM, Iudice A, Specchio N, La Neve A, Spinelli A, Galli R, Rocchi R, Ulivelli M, De Tommaso M, Pizzanelli C, Murri L. Citalopram as treatment of depression in patients with epilepsy. Clinical Neuropharmacology.2004; 27(3):133-6.

11.     Thome-Souza MS. Kaczynski E. Valente KD. Sertraline and fluoxetine: safe treatments for children and adolescents with epilepsy and depression. Epilepsy & Behavior.2007; 10:417-25.

12.     Vermoesen K, Massie A, Smolders I, Clinckers R (2012). The antidepressants citalopram and reboxetine reduce seizure frequency in rats with chronic epilepsy. Epilepsia 53: 870878.

13.   Montgomery SA. Antidepressants and seizures: emphasis on newer agents and clinical implications. Int J Clin Pract. 2005; 59:1435-1440.