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

Methodology

Keywords/terms: • Antiepileptic

• Withdrawal

• Discontinuation

• Meta-analysis

• Carbamazepine

• Grand mal

Search Engines • Cochrane (Central & CDSR)

• Pubmed

• Embase

• IPA

• Medline

Search Results1) 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)

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 Bottom Line: 1 out of every 4/5 will relapse per 24 months… months… probably!probably!

Results (probably/likely)

3

Risk or relapse is only one component1

Individualize: must take into account the risks and benefits1

Conclusion & Recommendation

Discontinue carbamazepine

Recommended titration protocol

Follow-up•Seizure recurrence •Carbamazepine withdrawal

Is my recommendation/conclusion relevant to my patient needs/goals

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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/178880743. 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/166256214. Specchio LM, Beghi E. Should antiepileptic drugs be withdrawn in seizure-free patients? CNS Drugs 2004; 18(4): 201-212