rigine or topiramate (Marson AJ, et al., Lancet 2007). Another major trial reported that ethosuximide was more effective for absence seizures than lamotrigine and better tolerated than valproate (Glauser TA, et al., N Engl J Med 2010). Further studies demonstrate that rufinamide and soon-to-be-released clobazam are two very effective options for the multiple refractory seizure types in the Lennox Gastuat syndrome while most other antiseizure medications donâ€™t help (Glauser TA, et al., Neurology 2008; Sperling MR, et al., Epilepsia 2004). The bottom line is that correct epilepsy syndrome diagnosis increasingly points to specific medications that are most likely to be effective. The old approach of starting a familiar medication and hoping for the best is no longer the best way to treat our patients. Treating comorbidities
Persistent epilepsy is associated with significant comorbidities that often affect quality of life more than the seizures. Diagnosing and treating these is just as important as treating the seizures. Significant medical conditions strongly associated with ongoing epilepsy include depression and suicide, sudden unexplained death, poor bone health, and impaired fertility. The story of the association between epilepsy and depression is particularly interesting. For many years practitioners knew that major depression occurred in approximately one-third of people with severe epilepsy, three to four times more frequently than in the general population. This was not considered particularly surprising; after all, this group had struggled unsuccessfully with a stigmatizing medical condition and usually sustained many social losses. However, in the last decade it became clearer that both depression and suicide were more common in people at the time of their first seizure than in control groups. Several years ago, Hesdorffer and colleagues demonstrated that people with depression alone are more likely to experience a new onset seizure over time than people
who are not depressed (Hesdorffer DC, et al., Epilepsia 2011). The notion that the depression-prone brain is also seizure-prone has led to the idea that anomalies in serotonin receptors and serotonin trafficking may be responsible for both conditions, and this idea is being actively pursued. However this plays out, it is increasingly clear that the relationship between epilepsy and depression is real and goes both ways. Uncontrolled seizures usually do not occur every day, but untreated depression affects a person more or less continuously. Multiple studies have shown that quality of life in epilepsy is affected more by a personâ€™s mood than by the effect of the seizures. People with epilepsy should therefore be screened for depression and treated if appropriate. A few medications such as levetiracetam and the barbiturates can trigger depression, and this should be considered as a possible cause. Practitioners are often wary of initiating antidepressant medications in people with epilepsy because of concerns that psychotropic drugs will lower seizure threshold. In fact, this is quite rare. There is reasonable evidence that clozapine, chlomipramine, and buproprion at doses higher than 300 mg per day may increase seizure tendency. Other psychotropic medications are very unlikely to trigger seizures. Several antidepressants (fluoxetine, citalopram, imipramine) have actually shown some antiseizure efficacy. Aggressive treatment
Aggressive treatment reduces seizures and may also reverse or prevent the development of comorbidities. After diagnosis, seizures should be treated with an antiseizure medication appropriate for the patientâ€™s seizure type, and medication doses should be increased until seizures are controlled or unacceptable side effects occur. If two appropriate antiseizure medications do not control seizures, referral to confirm diagnosis and consider more aggressive treatment such as resective epilepsy surgery is appropriate. This approach is now standard of care and us-
ually will result in reasonable seizure control. The good news is that recent studies report that aggressive treatment also appears to reverse or prevent epilepsy comorbidities. Long-term follow-up of the large, multicenter epilepsy surgery trial cohort demonstrates that both depression and anxiety improve following successful epilepsy surgery and that this benefit is maintained through five years after the operation. Analysis of the same cohort reveals that successful surgery decreases mortality. A very recent meta-analysis of more than 20,000 patients with medically intractable epilepsy found that risk of sudden death decreases substantially after addition of a new medication even if multiple previous medications have not completely controlled seizures (Ryvlin P, et al., Lancet Neurology 2011). There are many medications and treatment options for epilepsy and the scientific evidence increasingly supports the traditional idea that neither the physician nor the patient should give up.
Our mentors were right
Comprehensive care addressing both seizures and comorbidities will be challenging in the current health care environment. Physicians are pressed daily by increased patient demands, too much information, too little time, and too few resources. It may seem too much to approach a potentially dangerous condition like epilepsy in a new way. Nonetheless, the hard scientific data increasingly show that the intuitions of our older, mentor clinicians were on target: Defining the epilepsy as precisely as possible upfront and treating it as a process is the best way to get our patients better. Collaborative relationships with epilepsy centers (there are four level-4 centers in Minnesota) and leveraging potential benefits of electronic medical records will be important. We are hopeful that we can harness the current emphasis on systems, organization, and pathways to truly make our patients better. Thaddeus Walczak MD, is a neurologist/epileptologist with MINCEP Epilepsy Care in Minneapolis.
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Health care infomation for Minnesota doctors Cover: Clinical reasoning models by David Chapman, PT, PhD Aiming high by Paul Yongquist, MD S...