1. P: 86 y/o male, diagnosis nocturnal seizures (last seizure 1994)  carbamazepine I: antiepileptic withdrawal? And if so how? C: to not withdrawal/discontinue O: seizure recurrence (risks) Patient related problem not DRP! Cc: referred progressive weakness, instability cognitive impairment. “I don’t like meds…I want less” Tristan Melton Bsc. Pharm

2. Methodology Keywords/terms: Antiepileptic Withdrawal Discontinuation Meta-analysis Carbamazepine Grand mal Search Engines Cochrane (Central & CDSR) Pubmed Embase IPA Medline Search Results 1) Relapse following discontinuation of antiepileptic drugs: a meta-analysis (Berg & Shinnar) 2) Rapid versus slow withdrawal of antiepileptic drugs (Review); (Ranganathan & Ramaratnam) 3) Consequences of antiepileptic drug withdrawal: A randomized, double blind study (Lossius etal)

3. Results (probably/likely) Berg & Shinnar (meta-analysis) 25 studies included Risk of relapse at 2 years after initiating AED 0.29 (95% CI, 0.24-0.34) p<0.0001 4 Lossius et al. (RCT) Seizure relapse 12 months 15 vs 7% withdrawal group/non withdrawal resp. RR 2.46 (95% CI, 0.85-7.08) p=0.095 After withdrawal relapse rates were 27% after 41 months Bottom Line: 1 out of every 4/5 will relapse per 24 months… probably!

4. Results (probably/likely) 3 Risk or relapse is only one component 1 Individualize: must take into account the risks and benefits 1

5. Conclusion & Recommendation Discontinue carbamazepine Recommended titration protocol Follow-up Seizure recurrence Carbamazepine withdrawal Is my recommendation/conclusion relevant to my patient needs/goals

6. Strengths Berg & Shinnar inclusion(25)/exclusion(17) Heterogeneity tested (some explanation) Lossius et al RCT, double blind, controlled, prospective Primary outcome and sub group analysis explanations Weakness Sample sizes Patient population (age) Antiepileptic selectivity Berg & Shinnar Oldie but goldie Trial quality and data analysis No weighting Lossius et al Randomization/allocation/blinding Primary outcome: cognitive impairment and relapse Intention to treat

7. Template Provided By References: 1. Berg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs: A meta- analysis. Neurology 1994; 44: 601-7. 2. Lossius MI, Hessen E, Mowinckel P, Stavem K, Erikssen J, Gulbrandsen P, et al. Consequences of antiepileptic drug withdrawal: a randomized, double-blind study (Akershus Study). Epilepsia [Internet]. 2008 Mar [cited 2011 Jun 30];49(3):455-63. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17888074 3. Ranganathan LN, Ramaratnam S. Rapid versus slow withdrawal of antiepileptic drugs. Cochrane database of systematic reviews (Online) [Internet]. 2006 Jan;(2):CD005003. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16625621 http://www.ncbi.nlm.nih.gov/pubmed/16625621 4. Specchio LM, Beghi E. Should antiepileptic drugs be withdrawn in seizure-free patients? CNS Drugs 2004; 18(4): 201-212