Vijay Sardana              MD; DM(Neurology)        Professor & Head      Deptt. Of Neurology,Govt Medical college, Kota
•   Highest occurrence•   Atypical presentations•   Rec falls from GTCS- Head injury, fractures•   Medical non compliance•...
•   >65 yrs-   elderly population- 13%               Drug consumption- 32%•   Average elderly- 3 medicines in addition to ...
Increase in the proportion of the elderly in Germany                                    (>65 years), 1910–2030 (projected)...
•   Annual incidence (30-50/1,00,000- all ages)       65-69 yrs-    87/1,00,000       >70 yrs-      147/1,00,000       >80...
Age-specific incidence of epilepsy in Rochester,                               Minnesota, 1935–1984                       ...
•   Decline in functional independence•   Fear of falls & loss of self confidence•   Stigma•   Reactions of family & frien...
•    gastric acid secretion•   Slowing of gastric emptying time•    intestinal transit time•    mesentric flow•   Intestin...
Plasma concentration and clearance                     Ageing: effect on PK parameters by                      decreasing...
•   liver blood flow & mass- 25% lower above 65•   Cytochrome p450 system- decline with age        AEDs metabolized-PHT, P...
•   Decreased Renal mass, glomeruli•   GFR decline 50% by 8th decade•   AEDs primarily metabolized by kidney- Gabapentine,...
•   CBZ             25-40%•   PHT             about 25%•   VPA             about 40%•   PB              about 20%•   LTG  ...
•   S Albumin slightly with age    aggravation – ac systemic & Neurological illnesses    free/unbound drug remains unchang...
Corrected Pht level (micro g/ ml) –        measured PHT level      0.2 × Albumin( G/dl) + 0.1
•   Cytochome p450 inhibitors-          H2 blockers, Erythromycin, Clrithromycin,    Fluconazole, Ketoconazole, INH
•   concentration of HMG- coA reductase inhibitors-    Statins•   Low concetration of Warfarin- increased PT?INR•   Low co...
    Osteoporosis is a common problem in elderly                        Changes in bone density in elderly could result f...
•   CVA- 40-50%•   Metabolic disturbance- 10-15%•   Head injury- 5-10%•   Tumors- 5-10%•   Brain infections- 5-10%
•   CVA-   30-40%•   Post traumatic- 2-3%•   Old CNS infections-    2-3%•   Alzheimers & other Neurodegenerative- 8-10%•  ...
•   Stroke – cause in 30-50%. Ac stage-6%                              5 years-15%•   Occult/obvious•   15% elderly ‘idiop...
•   chlorpromazine•   Quitipine•   clozepine•   Cephalosporins•   Penicillin•   TCAs•   Venelafaxin•   Metoclopramide•   I...
   Epilepsy is often incorrectly diagnosed in the                     elderly                    Causes of misdiagnosis ...
Types of seizure                     Majority of newly-diagnosed cases = partial onset                      epilepsy     ...
•   Classical aura less common•   Post ictal phase can be prolonged•   Todd’s paresis more common, often mistaken for    S...
Status Epilepticus (SE)                    Incidence of SE ~5–10-fold higher in older individuals                     (mo...
•   Syncope•   TIA•   Hypoglycemia•   Confusional episode due to overmedication•   Dyselectrolytemia•   Psychogenic
•   Brief runs of temporal slow activity after 50 yrs•   small sharp spikes during sleep & drowsiness
•   Acute symptomatic seizure due to reversible    condition- don’t treat•   Unprovoked seizure- advisable to treat even i...
   Selection of AED therapy should be directed by:                       tolerability                       side effect...
   The ideal AED for the elderly should have the                     following properties:                       Complet...
   In elderly, AEDs are the fifth highest cause of                      AEs among all drug categories                   ...
   In general, newer AEDs – fewer drug interactions                       Older AEDs, particularly CBZ, PHT and PB,     ...
•   Membrane stabilizing drugs(DPH,CBZ, LTG)- risk of    promoting arrythmias•   DPH, CBZ- used with caution in Autonomic ...
•   Initiate with lower dosage than adults•    slow titration with modest maintenance dose•   renal, hepatic & plasma prot...
•   Most prescribed AED•   Non linear kinetics•   Age related decrease in metabolism•   SE-ataxia, imbalance,•   More comm...
•   Dose & frequency adjustment needed•   Use slow release preparations•   Hyponatremia•   Small risk of osteoporosis•   A...
•   Sedation & depression•   Cognitive dysfunction•   Hepatic enzyme inducer-drug interactions•   Low dose- 30-60 mg      ...
•   Age related decrease in clearance- prolonged half life•   No hepatic induction- best PK profile among older    AEDs fo...
•   Equally effective, often at lowes dosages than    younger adults•   Better tolerability•   Lower risk of drug interact...
•   Safe in elderly if renal function is normal•   Not metabolized, minimal protein binding so age    doesn’t alter its me...
•   Ca & Na channel blocker•   Modest protein binding•   Also has mood stabilizing & mood enhancing properties•   Effectiv...
•   Structural analogue of CBZ•   Better tolerability•   Lower incidence of rash•   SE- Hyponatremia ,    metabolism of Es...
•   Rapid absorption, high bio-availability•   No known drug interaction•   Effective in low dosage•   IV & syrup availabl...
Levetiracetam dosage recommendations –           patients with renal impairment             Dose adjustment recommended i...
Other safety studies  Comparison of LTG and CBZ in elderly patients  with newly-diagnosed seizures                        ...
Monotherapy studies  LTG, GBP and CBZ in elderly patients  with newly-diagnosed, partial-onset seizures         Conclusion...
Other safety studiesRetrospective evaluation of safety and tolerabilityof OXC therapy in elderly patients                 ...
Monotherapy studies (in progress)Comparison of LEV, LTG, and CBZ-CR as monotherapyin elderly patients with epilepsy       ...
   Surgical intervention (lesionectomy or lobectomy)                     is an alternative to AED therapies, and may be  ...
Overall conclusion                     Incidence of epilepsy – higher in elderly                     AED use in elderly ...
•   Have a higher degree of suspicion for diagnosis•   use newer AEDs. Consider co-morbidity in    selecting•   Start with...
Treatment of Epilepsy in Eldery Population
Treatment of Epilepsy in Eldery Population
Treatment of Epilepsy in Eldery Population
Upcoming SlideShare
Loading in …5
×

Treatment of Epilepsy in Eldery Population

1,013 views

Published on

Lecture delivered at Indian academy of Geriatrics and Association of Physician of India, Kota, Rajasthan

Published in: Health & Medicine
0 Comments
0 Likes
Statistics
Notes
  • Be the first to comment

  • Be the first to like this

No Downloads
Views
Total views
1,013
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
69
Comments
0
Likes
0
Embeds 0
No embeds

No notes for slide

Treatment of Epilepsy in Eldery Population

  1. 1. Vijay Sardana MD; DM(Neurology) Professor & Head Deptt. Of Neurology,Govt Medical college, Kota
  2. 2. • Highest occurrence• Atypical presentations• Rec falls from GTCS- Head injury, fractures• Medical non compliance• Increased adverse drug effects• Co- morbidity & drug interaction• Few AED drug trials in adults
  3. 3. • >65 yrs- elderly population- 13% Drug consumption- 32%• Average elderly- 3 medicines in addition to AEDs
  4. 4. Increase in the proportion of the elderly in Germany (>65 years), 1910–2030 (projected) 50 Proportion of population (%) 40 30 27% 20 17% 15% 10 5% 0 1910 1950 1990 2030Huying et al., Seizure 2006; 15: 194–197 Year
  5. 5. • Annual incidence (30-50/1,00,000- all ages) 65-69 yrs- 87/1,00,000 >70 yrs- 147/1,00,000 >80 yrs- 159/1,00,000• Prevalence- 1.5% above 65 yrs• 0.7% elderly people treated for Epilepsy• Epilepsy 3rd most common Neurological condition after Stroke & Dementia
  6. 6. Age-specific incidence of epilepsy in Rochester, Minnesota, 1935–1984 200 150 Incidence (per 100,000) 100 50 0 0 20 40 60 80 AgeHauser et al., Epilepsia 1993; 34 (3): 453–468
  7. 7. • Decline in functional independence• Fear of falls & loss of self confidence• Stigma• Reactions of family & friends• Exclusion from activities, marginalization• Assumption of impending death• Loss of driving privileges• Disempowerment & perception of shrinkage of life space
  8. 8. • gastric acid secretion• Slowing of gastric emptying time• intestinal transit time• mesentric flow• Intestinal absorption surface Bio-availability
  9. 9. Plasma concentration and clearance  Ageing: effect on PK parameters by decreasing:  plasma protein content  liver metabolic capability  renal clearance  and increasing:  the volume of distribution (for lipophilic drugs)  elimination half-lifeLeppik. Epilepsia 2006; 47 (Suppl 1): 65–70; Leppik. Geriatrics 2005; 60: 42–47; Perucca et al., Epilepsy Res 2006; 68S: S49–S63
  10. 10. • liver blood flow & mass- 25% lower above 65• Cytochrome p450 system- decline with age AEDs metabolized-PHT, PB, CBZ, OX- CBZ, Ethosuximide, VPA ,Topiramate• Hepatic glucoronidation conjucation- less affected AEDs metabolized- LTG, VPA, Zonisamide
  11. 11. • Decreased Renal mass, glomeruli• GFR decline 50% by 8th decade• AEDs primarily metabolized by kidney- Gabapentine, Levetiracetam, Prega)balin (also Topiramate, Zonisamide)
  12. 12. • CBZ 25-40%• PHT about 25%• VPA about 40%• PB about 20%• LTG about 35%• Gabapentine 30-50%• Levetiracetam 20-40%
  13. 13. • S Albumin slightly with age aggravation – ac systemic & Neurological illnesses free/unbound drug remains unchanged in spite of total low s. conc.• Highly protein bound- PHT, VPA ,, Clonazepam, Clobazam, Diazepam (also CBZ) – free fraction can rise to toxic levels
  14. 14. Corrected Pht level (micro g/ ml) – measured PHT level 0.2 × Albumin( G/dl) + 0.1
  15. 15. • Cytochome p450 inhibitors- H2 blockers, Erythromycin, Clrithromycin, Fluconazole, Ketoconazole, INH
  16. 16. • concentration of HMG- coA reductase inhibitors- Statins• Low concetration of Warfarin- increased PT?INR• Low concentration of Varapamil
  17. 17.  Osteoporosis is a common problem in elderly  Changes in bone density in elderly could result from:  reduced exercise  poor calcium intake  impaired vitamin D metabolism  AED use increases risk of osteoporosis  decrease in bone mineral density  induction of CYP450 – alterations in sex steroid or vitamin D metabolism  enzyme-inducing AEDs (e.g., PHT, PB) and VPA have greatest effect  Polytherapy has higher risk  Newer AEDs safe  potential 2-fold increase in hip fracturesBergey et al., Adv Stud Med 2006; 6 (3C): S195–S209; Cloyd et al., Epilepsy Res 2006; 68 (Suppl 1): S39–S48; Mintzer et al., Epilepsia 2006;47: 510–515; Sato et al., Neurology 2001; 57: 445–449; Martindale. In: Sweetman, 2002.
  18. 18. • CVA- 40-50%• Metabolic disturbance- 10-15%• Head injury- 5-10%• Tumors- 5-10%• Brain infections- 5-10%
  19. 19. • CVA- 30-40%• Post traumatic- 2-3%• Old CNS infections- 2-3%• Alzheimers & other Neurodegenerative- 8-10%• Cryptogenic- 40-50%
  20. 20. • Stroke – cause in 30-50%. Ac stage-6% 5 years-15%• Occult/obvious• 15% elderly ‘idiopathic looking seizures show imaging evidence of CVA• Seizure a risk factor for subsequent stroke, even greater than cholesterol & HT• Stroke patients 20 times more likely to develop Epilepsy as compared to gen population
  21. 21. • chlorpromazine• Quitipine• clozepine• Cephalosporins• Penicillin• TCAs• Venelafaxin• Metoclopramide• INH• Ginko biloba• Ginseng
  22. 22.  Epilepsy is often incorrectly diagnosed in the elderly  Causes of misdiagnosis include:  difficulty obtaining patient histories  absence of classic symptoms  attribution of symptoms to comorbid diseases  Elderly patients are often referred with a diagnosis of altered mental status, confusion, and memory lapsesCloyd et al., Epilepsy Res 2006; 68 (Suppl 1): S39–S48; Treiman & Walker. Epilepsy Res 2006; 68 (Suppl 1): S77–S82
  23. 23. Types of seizure  Majority of newly-diagnosed cases = partial onset epilepsy  incidence of partial onset seizures is 98% in epilepsy patients aged >75 years  Complex partial seizures most common seizure type –accounting for nearly 40% of seizures  After a stroke, initial seizure is often a secondary generalised partial seizureCloyd et al., Epilepsy Res 2006; 68 (Suppl 1): S39–S48; Leppik. Geriatrics 2005; 60: 42–47; Ramsay et al., Neurology 2004; 62(Suppl 2): S24–S29
  24. 24. • Classical aura less common• Post ictal phase can be prolonged• Todd’s paresis more common, often mistaken for Stroke• Atypical presentations of partial seizures- Dizziness, vague feeling related to head, memory loss & confusion
  25. 25. Status Epilepticus (SE)  Incidence of SE ~5–10-fold higher in older individuals (most often partial SE)  Symptoms of non-convulsive SE are common with other elderly disorders – may lead to diagnostic difficulties  Mortality significantly greater in the elderly (36-50%) versus in younger adults (26%)  No specific treatment protocol for elderlyCloyd et al., Epilepsy Res 2006; 68 (Suppl 1): S39–S48; Treiman & Walker. Epilepsy Res 2006; 68 (Suppl 1): S77–S82
  26. 26. • Syncope• TIA• Hypoglycemia• Confusional episode due to overmedication• Dyselectrolytemia• Psychogenic
  27. 27. • Brief runs of temporal slow activity after 50 yrs• small sharp spikes during sleep & drowsiness
  28. 28. • Acute symptomatic seizure due to reversible condition- don’t treat• Unprovoked seizure- advisable to treat even if work up normal
  29. 29.  Selection of AED therapy should be directed by:  tolerability  side effect profile  potential drug–drug interactions  Co-morbidityBergey et al., Adv Stud Med 2006; 6 (3C): S195–S209; Leppik. Geriatrics 2005; 60: 42–47; Leppik. Epilepsia 2006; 47 (Suppl1): 65–70
  30. 30.  The ideal AED for the elderly should have the following properties:  Complete absorption  Linear pharmacokinetics  No active metabolites  Clearance unaffected by renal impairment  No induction/inhibition of hepatic enzymes  Broad-spectrum efficacy  No adverse cognitive effects  No effects on bone loss  Rapid titration  Range of formulations  Reasonable priceBergey et al., Adv Stud Med 2006; 6 (3C): S195–S209; Leppik. Geriatrics 2005; 60: 42–47; Leppik. Epilepsy Res 2006;68 (Suppl 1): S71–S76
  31. 31.  In elderly, AEDs are the fifth highest cause of AEs among all drug categories  Dose-dependent and drug-specific AEs can occur at lower drug blood levels than in younger patients  AEs such as somnolence, dizziness and gait disturbances increase the risk of falls  Many AEs associated with AED use in elderly may be preventableBergey et al., Adv Stud Med 2006; 6 (3C): S195–S209; Leppik. Epilepsia 2006; 47 (Suppl 1): 65–70; Leppik. Geriatrics 2005;60: 42–47; Perucca et al., Epilepsy Res 2006; 68S: S49–S63; Ramsay et al., Neurology 2004; 62 (Suppl 2): S24–S29
  32. 32.  In general, newer AEDs – fewer drug interactions  Older AEDs, particularly CBZ, PHT and PB, significant drug interactions  Side effect profile needs considering  VPA – not best choice in patients with tremor  CBZ – caution in patients with sodium balance issues  Newer AEDs – much more expensive  However, avoiding complications may balance extra costBergey et al., Adv Stud Med 2006; 6 (3C): S195–S209; Leppik. Epilepsia 2006; 47 (Suppl 1): 65–70; Perucca et al., Epilepsy Res2006; 68 (Suppl 1): S49–S63
  33. 33. • Membrane stabilizing drugs(DPH,CBZ, LTG)- risk of promoting arrythmias• DPH, CBZ- used with caution in Autonomic dysfunction• CBZ- can precipitate urinary retention (anticholinergic effect)
  34. 34. • Initiate with lower dosage than adults• slow titration with modest maintenance dose• renal, hepatic & plasma protein assessment before starting• Monotherapy better than polytherapy• Substitute first drug if not controlled• Drug combinations should be avoided/sparingly used• Blood levels whenever indicated
  35. 35. • Most prescribed AED• Non linear kinetics• Age related decrease in metabolism• SE-ataxia, imbalance,• More common in elderly• Dose- 200mg/day 50 mg step increment• Relative contraindication in cardiac conduction defects
  36. 36. • Dose & frequency adjustment needed• Use slow release preparations• Hyponatremia• Small risk of osteoporosis• Ataxia, dizziness more common• Dose- 100mg/day– increase 100 mg/ 2 weeks— 400mg/day maintenance
  37. 37. • Sedation & depression• Cognitive dysfunction• Hepatic enzyme inducer-drug interactions• Low dose- 30-60 mg increase gradually
  38. 38. • Age related decrease in clearance- prolonged half life• No hepatic induction- best PK profile among older AEDs for elderly• Don’t use if Hepatic disease• Dose- start 200mg/day 200 mg increment 600mg/day initial maintenance dose
  39. 39. • Equally effective, often at lowes dosages than younger adults• Better tolerability• Lower risk of drug interaction• Reduced need for therapeutic drug monitoring Newer drugs approved for monotherapy- Oxcarbazepine,Lamotrigine,Levetiracetam
  40. 40. • Safe in elderly if renal function is normal• Not metabolized, minimal protein binding so age doesn’t alter its metabolism/ distribution• Dosage- 900-1800 mg/day• SE- dizziness, somnolence, weight gain & pedal oedeme
  41. 41. • Ca & Na channel blocker• Modest protein binding• Also has mood stabilizing & mood enhancing properties• Effective in both partial & gen seizures• Dose- 25 mg 100 mg maintenance 50-100 (VPA & LTG) 200 (Other C p450 inducer)
  42. 42. • Structural analogue of CBZ• Better tolerability• Lower incidence of rash• SE- Hyponatremia , metabolism of Estrogen• Dose- 150 mg BD increase gradually
  43. 43. • Rapid absorption, high bio-availability• No known drug interaction• Effective in low dosage• IV & syrup available• SE- somnolence, asthenia, in coordination, irritability, personality change• Dose- 125 mg increase 125-250 mg maintenance 750-1000 mg
  44. 44. Levetiracetam dosage recommendations – patients with renal impairment  Dose adjustment recommended in elderly with compromised renal function Creatinine Group clearance Dosage and frequency (ml/min) Normal >80 500–1500 mg twice daily Mild 50–79 500–1000 mg twice daily Moderate 30–49 250–750 mg twice daily Severe <30 250–500 mg twice daily End-stage renal disease – 500–1000 mg once daily2 patients/undergoing dialysis1 1750 mg loading dose is recommended on first day of treatment with LEV 2Following dialysis, a 250 to 500 mg supplemental dose is recommendedE
  45. 45. Other safety studies Comparison of LTG and CBZ in elderly patients with newly-diagnosed seizures Randomised, double-blind monotherapy study Conclusions  LTG – more completers (LTG 71%, CBZ* 42%; p<0.001)  LTG – lower drop-outs due to AEs (LTG 18%, CBZ* 42%)  Rash – AE most frequently associated with withdrawal (LTG 3%, CBZ* 19%)  LTG – higher SF in last 16 weeks of treatment (LTG 39%, CBZ* 21%; p=0.027)Brodie et al., Epilepsy Res 1999; 37: 81–87 *Not CBZ-CR
  46. 46. Monotherapy studies LTG, GBP and CBZ in elderly patients with newly-diagnosed, partial-onset seizures Conclusions  Primary outcome measure: higher 12-month retention rates for GBP and LTG compared with CBZ*  Seizure freedom rates at 12 months: LTG 51.4%, GBP 47.4%, CBZ* 64.3%; p=ns  Terminations due to AEs: LTG 12.1%, GBP 21.6%, CBZ* 31%; p=0.001Rowan et al., Neurology 2005; 64: 1868–1873 *Not CBZ-CR
  47. 47. Other safety studiesRetrospective evaluation of safety and tolerabilityof OXC therapy in elderly patients Retrospective evaluation Conclusions  No significant differences in premature discontinuations due to AEs (>65 vs. 18–64 years)  No significant changes in hepatic, renal, or haematological profiles  OXC tolerability in the elderly – similar to younger patientsKutluay et al., Epilepsy & Behav 2003; 4: 175–180
  48. 48. Monotherapy studies (in progress)Comparison of LEV, LTG, and CBZ-CR as monotherapyin elderly patients with epilepsy Randomised, double-blind, Phase IV monotherapy trial (in progress) Objective  To compare safety, tolerability and efficacy of LEV versus LTG and CBZ-CR as monotherapy in newly- diagnosed patients, ≥60 years, with focal epilepsy Study design  360 patients expected to be enrolled  58-week treatment period Primary outcome  58-week retention rateWerhahn & Schroeder. ClinicalTrials.gov identifier: NCT00438451
  49. 49.  Surgical intervention (lesionectomy or lobectomy) is an alternative to AED therapies, and may be suitable for:  those with comorbid conditions  medically intractable candidates  Palliative procedures (DBS, VNS) may also be options for elderly patientsGallo. Epilepsy Res 2006; 68 (Suppl 1): S83–S86
  50. 50. Overall conclusion  Incidence of epilepsy – higher in elderly  AED use in elderly complicated by:  age-related changes in pharmacokinetics and pharmacodynamics  adverse drug reactions – increased risk due to comorbid conditions  Only two available randomised, double-blind trials  superior tolerability of newer AEDs (LTG, GBP)  further studies needed  Publications so far suggest LTG, LEV and GBP are preferred AEDs for elderly patientsBergey et al., Adv Stud Med 2006; 6 (3C): S195–S209; Karceski et al., Epilepsy & Behav 2005; 7 (Suppl 1): S1–S64; Leppik.Epilepsia 2006; 47 (Suppl 1): 65–70; Perucca et al., Epilepsy Res 2006; 68 (Suppl 1): S49–S63; Rowan et al., Neurology2005; 64: 1868–1873; Stephen et al., Epilepsy & Behav 2006; 8: 434–437
  51. 51. • Have a higher degree of suspicion for diagnosis• use newer AEDs. Consider co-morbidity in selecting• Start with low dose & titrate slowly to a target dose of one half to two third of younger population• Boost the morale

×