Literature Monitor

Status epilepticus (SE) significantly increases the all-cause mortality according to a review of more than 82,000 hospitalizations and emergency-department visits. Within this large group were 1,296 patients who presented with only SE, 2,136 patients who had post-epilepsy SE, and nearly 79,000 cases of epilepsy only, which served as controls. Angela M. Malek and associates found a mortality rate of 24.9% among SE only cases, compared with 20% in controls (hazard ratio 1.61) after adjustment for demographic and clinical confounding variables. Patients who presented with post-epilepsy SE had a mortality rate of 29.2% but a hazard ratio of only 1.16.

Malek AM, Wilson DA, Martz GU, et al. Mortality following status epilepticus in persons with and without epilepsy. Seizure. 2016;42:7-13.

Status epilepticus (SE) significantly increases the all-cause mortality according to a review of more than 82,000 hospitalizations and emergency-department visits. Within this large group were 1,296 patients who presented with only SE, 2,136 patients who had post-epilepsy SE, and nearly 79,000 cases of epilepsy only, which served as controls. Angela M. Malek and associates found a mortality rate of 24.9% among SE only cases, compared with 20% in controls (hazard ratio 1.61) after adjustment for demographic and clinical confounding variables. Patients who presented with post-epilepsy SE had a mortality rate of 29.2% but a hazard ratio of only 1.16.

Malek AM, Wilson DA, Martz GU, et al. Mortality following status epilepticus in persons with and without epilepsy. Seizure. 2016;42:7-13.

Status epilepticus (SE) significantly increases the all-cause mortality according to a review of more than 82,000 hospitalizations and emergency-department visits. Within this large group were 1,296 patients who presented with only SE, 2,136 patients who had post-epilepsy SE, and nearly 79,000 cases of epilepsy only, which served as controls. Angela M. Malek and associates found a mortality rate of 24.9% among SE only cases, compared with 20% in controls (hazard ratio 1.61) after adjustment for demographic and clinical confounding variables. Patients who presented with post-epilepsy SE had a mortality rate of 29.2% but a hazard ratio of only 1.16.

Malek AM, Wilson DA, Martz GU, et al. Mortality following status epilepticus in persons with and without epilepsy. Seizure. 2016;42:7-13.

Patients who continue to have seizures after epilepsy surgery should be evaluated for psychogenic nonepileptic seizures (PNES), based on a recent retrospective analysis of 1,105 patients. Among this cohort, 697 patients experienced postoperative seizures, and 27 of the 697 had documented PNES, according to Ali A. Asadi-Pooya and associates. Risk factors associated with post–epilepsy surgery PNES included an intelligence quotient (IQ) below 80 and a history of a psychiatric diagnosis.

Asadi-Pooya AA, Asadollahi M, Tinker J, et al. Post–epilepsy surgery psychogenic nonepileptic seizures. Epilepsia. 2016;57(10):1691-1696.

Patients who continue to have seizures after epilepsy surgery should be evaluated for psychogenic nonepileptic seizures (PNES), based on a recent retrospective analysis of 1,105 patients. Among this cohort, 697 patients experienced postoperative seizures, and 27 of the 697 had documented PNES, according to Ali A. Asadi-Pooya and associates. Risk factors associated with post–epilepsy surgery PNES included an intelligence quotient (IQ) below 80 and a history of a psychiatric diagnosis.

Asadi-Pooya AA, Asadollahi M, Tinker J, et al. Post–epilepsy surgery psychogenic nonepileptic seizures. Epilepsia. 2016;57(10):1691-1696.

Patients who continue to have seizures after epilepsy surgery should be evaluated for psychogenic nonepileptic seizures (PNES), based on a recent retrospective analysis of 1,105 patients. Among this cohort, 697 patients experienced postoperative seizures, and 27 of the 697 had documented PNES, according to Ali A. Asadi-Pooya and associates. Risk factors associated with post–epilepsy surgery PNES included an intelligence quotient (IQ) below 80 and a history of a psychiatric diagnosis.

Asadi-Pooya AA, Asadollahi M, Tinker J, et al. Post–epilepsy surgery psychogenic nonepileptic seizures. Epilepsia. 2016;57(10):1691-1696.

Among relatives of patients with epilepsy, the prevalence of depression is greater among those who believe they have an increased risk of epilepsy because they may have inherited an epilepsy-related mutation. Shawn T. Sorge and his colleagues reached that conclusion after surveying 417 individuals in 104 families in which 4 persons per family had the disease on average. On the other hand, individuals with epilepsy seemed less troubled by the diagnosis: The likelihood of having depression was not related to any potential epilepsy-related mutation among persons who already have epilepsy.

Sorge ST, Hesdorffer DC, Phelan JC, et al. Depression and genetic causal attribution of epilepsy in multiplex epilepsy families. Epilepsia. 2016;57(10):1643-1650.

Among relatives of patients with epilepsy, the prevalence of depression is greater among those who believe they have an increased risk of epilepsy because they may have inherited an epilepsy-related mutation. Shawn T. Sorge and his colleagues reached that conclusion after surveying 417 individuals in 104 families in which 4 persons per family had the disease on average. On the other hand, individuals with epilepsy seemed less troubled by the diagnosis: The likelihood of having depression was not related to any potential epilepsy-related mutation among persons who already have epilepsy.

Sorge ST, Hesdorffer DC, Phelan JC, et al. Depression and genetic causal attribution of epilepsy in multiplex epilepsy families. Epilepsia. 2016;57(10):1643-1650.

Among relatives of patients with epilepsy, the prevalence of depression is greater among those who believe they have an increased risk of epilepsy because they may have inherited an epilepsy-related mutation. Shawn T. Sorge and his colleagues reached that conclusion after surveying 417 individuals in 104 families in which 4 persons per family had the disease on average. On the other hand, individuals with epilepsy seemed less troubled by the diagnosis: The likelihood of having depression was not related to any potential epilepsy-related mutation among persons who already have epilepsy.

Sorge ST, Hesdorffer DC, Phelan JC, et al. Depression and genetic causal attribution of epilepsy in multiplex epilepsy families. Epilepsia. 2016;57(10):1643-1650.

The American Academy of Neurology and the American Epilepsy Society have released their guidelines on how to manage an adult patient who has had their first unprovoked seizure. Based on their review of the evidence, they recommend that clinicians base their decision about immediately initiating an antiepileptic drug after a first seizure on an individualized assessment. That evaluation should weigh the risk of a second seizure occurring against the adverse effects of the medication, as well as patient preferences. The risk of a second seizure increases if the patient has already suffered a symptomatic brain insult such as a stroke or head trauma, among other risk factors. The guidelines also point out that immediate treatment with an antiepileptic agent reduces the likelihood of additional seizures for 2 years but does not have an impact on long-term prognosis for seizure remission.

Tao JX, Davis AM. Management of an Unprovoked First Seizure in Adults. JAMA. 2016;316(15):1590-1591.

The American Academy of Neurology and the American Epilepsy Society have released their guidelines on how to manage an adult patient who has had their first unprovoked seizure. Based on their review of the evidence, they recommend that clinicians base their decision about immediately initiating an antiepileptic drug after a first seizure on an individualized assessment. That evaluation should weigh the risk of a second seizure occurring against the adverse effects of the medication, as well as patient preferences. The risk of a second seizure increases if the patient has already suffered a symptomatic brain insult such as a stroke or head trauma, among other risk factors. The guidelines also point out that immediate treatment with an antiepileptic agent reduces the likelihood of additional seizures for 2 years but does not have an impact on long-term prognosis for seizure remission.

Tao JX, Davis AM. Management of an Unprovoked First Seizure in Adults. JAMA. 2016;316(15):1590-1591.

The American Academy of Neurology and the American Epilepsy Society have released their guidelines on how to manage an adult patient who has had their first unprovoked seizure. Based on their review of the evidence, they recommend that clinicians base their decision about immediately initiating an antiepileptic drug after a first seizure on an individualized assessment. That evaluation should weigh the risk of a second seizure occurring against the adverse effects of the medication, as well as patient preferences. The risk of a second seizure increases if the patient has already suffered a symptomatic brain insult such as a stroke or head trauma, among other risk factors. The guidelines also point out that immediate treatment with an antiepileptic agent reduces the likelihood of additional seizures for 2 years but does not have an impact on long-term prognosis for seizure remission.

Tao JX, Davis AM. Management of an Unprovoked First Seizure in Adults. JAMA. 2016;316(15):1590-1591.

Temporal lobe epilepsy (TLE) is believed to disrupt resting state functional connectivity in the brain. To explore this association in more depth, investigators used group independent component analysis (ICA) to identify the brain’s default mode network (DMN). The DMN has been linked to episodic memory, which does not function normally in patients with TLE. The researchers found functional connectivity instability over time among patients with left and right sided TLE, when compared with healthy controls. The instability within the DMN was most consistently detected within the precuneus region of the brain.

Robinson LF, He X, Barnett P et al. The temporal instability of resting state network connectivity in intractable epilepsy. Hum Brain Mapp. 2016; Sept 15 [Epub ahead of print]

Temporal lobe epilepsy (TLE) is believed to disrupt resting state functional connectivity in the brain. To explore this association in more depth, investigators used group independent component analysis (ICA) to identify the brain’s default mode network (DMN). The DMN has been linked to episodic memory, which does not function normally in patients with TLE. The researchers found functional connectivity instability over time among patients with left and right sided TLE, when compared with healthy controls. The instability within the DMN was most consistently detected within the precuneus region of the brain.

Robinson LF, He X, Barnett P et al. The temporal instability of resting state network connectivity in intractable epilepsy. Hum Brain Mapp. 2016; Sept 15 [Epub ahead of print]

Temporal lobe epilepsy (TLE) is believed to disrupt resting state functional connectivity in the brain. To explore this association in more depth, investigators used group independent component analysis (ICA) to identify the brain’s default mode network (DMN). The DMN has been linked to episodic memory, which does not function normally in patients with TLE. The researchers found functional connectivity instability over time among patients with left and right sided TLE, when compared with healthy controls. The instability within the DMN was most consistently detected within the precuneus region of the brain.

Robinson LF, He X, Barnett P et al. The temporal instability of resting state network connectivity in intractable epilepsy. Hum Brain Mapp. 2016; Sept 15 [Epub ahead of print]

Volumetric correlation analysis of the brain can help detect subtle structural changes in patients with temporal lobe epilepsy (TLE). With that in mind, Conrad and associates performed T1 weighted 3T magnetic resonance imaging in 44 drug-resistant patients with unilateral TLE and in 44 healthy controls. They detected increased correlation in the contralateral areas to seizure foci and networks in several areas of the brains of patients with both left-sided and right-sided TLE. The areas, which included limbic, subcortical, and temporal regions, confirmed that there are coordinated volume changes in this population that are not confined to ipsilateral regions.

Conrad BN, Rogers BP, Abou-Khalil B et al. Increased MRI volumetric correlation contralateral to seizure focus in temporal lobe epilepsy. Epilepsy Res. 2016; 126:53-61.

Volumetric correlation analysis of the brain can help detect subtle structural changes in patients with temporal lobe epilepsy (TLE). With that in mind, Conrad and associates performed T1 weighted 3T magnetic resonance imaging in 44 drug-resistant patients with unilateral TLE and in 44 healthy controls. They detected increased correlation in the contralateral areas to seizure foci and networks in several areas of the brains of patients with both left-sided and right-sided TLE. The areas, which included limbic, subcortical, and temporal regions, confirmed that there are coordinated volume changes in this population that are not confined to ipsilateral regions.

Conrad BN, Rogers BP, Abou-Khalil B et al. Increased MRI volumetric correlation contralateral to seizure focus in temporal lobe epilepsy. Epilepsy Res. 2016; 126:53-61.

Volumetric correlation analysis of the brain can help detect subtle structural changes in patients with temporal lobe epilepsy (TLE). With that in mind, Conrad and associates performed T1 weighted 3T magnetic resonance imaging in 44 drug-resistant patients with unilateral TLE and in 44 healthy controls. They detected increased correlation in the contralateral areas to seizure foci and networks in several areas of the brains of patients with both left-sided and right-sided TLE. The areas, which included limbic, subcortical, and temporal regions, confirmed that there are coordinated volume changes in this population that are not confined to ipsilateral regions.

Conrad BN, Rogers BP, Abou-Khalil B et al. Increased MRI volumetric correlation contralateral to seizure focus in temporal lobe epilepsy. Epilepsy Res. 2016; 126:53-61.

Patients with epilepsy who also have intellectual disabilities seem to fare better when they adhere to a self-management program suggests this pilot study. Since individuals with intellectual disabilities are 20 times more likely to have epilepsy, researchers wanted to determine if a self-management program could make a difference. Their review of pilot and randomized controlled feasibility studies suggests that patients find this type of intervention acceptable and that the programs improve seizure frequency and may improve their quality of life.  Although their analysis highlights the potential for self-management programs, the investigators are currently conducting a randomized controlled trial to obtain more definitive results.

Dannenberg M, Mengoni SE, Gates B, Durand M. Self-management interventions for epilepsy in people with intellectual disabilities: A scoping review.  Seizure. 2016;41:16-25.

Patients with epilepsy who also have intellectual disabilities seem to fare better when they adhere to a self-management program suggests this pilot study. Since individuals with intellectual disabilities are 20 times more likely to have epilepsy, researchers wanted to determine if a self-management program could make a difference. Their review of pilot and randomized controlled feasibility studies suggests that patients find this type of intervention acceptable and that the programs improve seizure frequency and may improve their quality of life.  Although their analysis highlights the potential for self-management programs, the investigators are currently conducting a randomized controlled trial to obtain more definitive results.

Dannenberg M, Mengoni SE, Gates B, Durand M. Self-management interventions for epilepsy in people with intellectual disabilities: A scoping review.  Seizure. 2016;41:16-25.

Patients with epilepsy who also have intellectual disabilities seem to fare better when they adhere to a self-management program suggests this pilot study. Since individuals with intellectual disabilities are 20 times more likely to have epilepsy, researchers wanted to determine if a self-management program could make a difference. Their review of pilot and randomized controlled feasibility studies suggests that patients find this type of intervention acceptable and that the programs improve seizure frequency and may improve their quality of life.  Although their analysis highlights the potential for self-management programs, the investigators are currently conducting a randomized controlled trial to obtain more definitive results.

Dannenberg M, Mengoni SE, Gates B, Durand M. Self-management interventions for epilepsy in people with intellectual disabilities: A scoping review.  Seizure. 2016;41:16-25.

Although ectopic tissue in certain regions of the brain has been linked to epilepsy, a recent review of the literature concluded that periventricular nodular heterotopia rarely causes clinical seizures. The review evaluated chronic invasive EEG recordings and found that nodules alone are rarely responsible for seizures. Their onset is more likely to be connected with overlying neocortex or mesial temporal structures. However, the analysis did find that substantial or complete ablation of nodules usually results in more favorable surgical outcomes.

Thompson SA, Kalamangalam GP, Tandon N. Intracranial evaluation and laser ablation for epilepsy with periventricular nodular heterotopia. Seizure. 2016;41:211-216.

Although ectopic tissue in certain regions of the brain has been linked to epilepsy, a recent review of the literature concluded that periventricular nodular heterotopia rarely causes clinical seizures. The review evaluated chronic invasive EEG recordings and found that nodules alone are rarely responsible for seizures. Their onset is more likely to be connected with overlying neocortex or mesial temporal structures. However, the analysis did find that substantial or complete ablation of nodules usually results in more favorable surgical outcomes.

Thompson SA, Kalamangalam GP, Tandon N. Intracranial evaluation and laser ablation for epilepsy with periventricular nodular heterotopia. Seizure. 2016;41:211-216.

Although ectopic tissue in certain regions of the brain has been linked to epilepsy, a recent review of the literature concluded that periventricular nodular heterotopia rarely causes clinical seizures. The review evaluated chronic invasive EEG recordings and found that nodules alone are rarely responsible for seizures. Their onset is more likely to be connected with overlying neocortex or mesial temporal structures. However, the analysis did find that substantial or complete ablation of nodules usually results in more favorable surgical outcomes.

Thompson SA, Kalamangalam GP, Tandon N. Intracranial evaluation and laser ablation for epilepsy with periventricular nodular heterotopia. Seizure. 2016;41:211-216.

Patients experiencing different types of seizures tend to present with distinct hand gestures during the attacks, according to a recent retrospective analysis published in Neurology. To reach that conclusion, researchers analyzed videotaped hand postures in patients with genetic generalized epilepsy, localization-related epilepsy, and non-epileptic attacks. They found that 96% of patients with localized epilepsy presented with index-finger pointing while 91.3% of patients with genetic generalized epilepsy presented with hand fanning, which only occurred at the onset of the seizures. The investigators also discovered that making a fist, fanning and index-finger pointing was more common among patients who were having epileptic seizures, when compared to those who were having non-epileptic attacks (74% vs 32%).  

Siegel J, Tatum, WO. Hand postures in primary and secondary generalized tonic-clonic seizures. Neurology. 2016; Published online Sept 24.

Patients experiencing different types of seizures tend to present with distinct hand gestures during the attacks, according to a recent retrospective analysis published in Neurology. To reach that conclusion, researchers analyzed videotaped hand postures in patients with genetic generalized epilepsy, localization-related epilepsy, and non-epileptic attacks. They found that 96% of patients with localized epilepsy presented with index-finger pointing while 91.3% of patients with genetic generalized epilepsy presented with hand fanning, which only occurred at the onset of the seizures. The investigators also discovered that making a fist, fanning and index-finger pointing was more common among patients who were having epileptic seizures, when compared to those who were having non-epileptic attacks (74% vs 32%).  

Siegel J, Tatum, WO. Hand postures in primary and secondary generalized tonic-clonic seizures. Neurology. 2016; Published online Sept 24.

Patients experiencing different types of seizures tend to present with distinct hand gestures during the attacks, according to a recent retrospective analysis published in Neurology. To reach that conclusion, researchers analyzed videotaped hand postures in patients with genetic generalized epilepsy, localization-related epilepsy, and non-epileptic attacks. They found that 96% of patients with localized epilepsy presented with index-finger pointing while 91.3% of patients with genetic generalized epilepsy presented with hand fanning, which only occurred at the onset of the seizures. The investigators also discovered that making a fist, fanning and index-finger pointing was more common among patients who were having epileptic seizures, when compared to those who were having non-epileptic attacks (74% vs 32%).  

Siegel J, Tatum, WO. Hand postures in primary and secondary generalized tonic-clonic seizures. Neurology. 2016; Published online Sept 24.

Switching between generic versions of the same antiepileptic drug made by different manufacturers does not appear to change the risk of seizure-related events in patients with epilepsy, according to a population-based, case–crossover study of generic antiepileptic drug users published online ahead of print September 28 in Neurology. Delays and complications of the medication refilling process might increase a patient’s risk for a seizure, said Aaron Kesselheim, MD, JD, MPH, Associate Professor of Medicine at Harvard Medical School in Boston, and colleagues.

“These results add to the growing literature supporting the routine use of interchangeable generic [antiepileptic drugs] among patients with seizure disorders,” he added.

Although previous observational studies have demonstrated increased seizure activity following a switch from brand name to generic antiepileptic drugs, several recent randomized trials have found no
link between generic drug switching and seizure risk, said Dr. Kesselheim.

Investigators identified 59,344 patients with at least one refill of a prescription from the same manufacturer and 5,200 patients who switched from one generic to another from 2000 to 2010 in the Medicaid Analytic eXtract database and from 2005 to 2013 in a commercial health insurance database. Participants acted as their own controls in the study’s comparison of the effects of a refill or a refill with a switch in manufacturer on seizure-related events (ie, a seizure requiring an emergency department visit or hospitalization) during a hazard period, defined as days 2–36 preceding a seizure-related event, and a control period, defined as days 51–85 preceding the seizure-related event.

Overall, generic antiepileptic refilling of the same medication from the same manufacturer was associated with an 8% increase in the odds of having a seizure-related event. When the refill involved a switch to the same generic drug made by a different manufacturer, the odds of a seizure-related event rose by 9%. When the refill involved a change in the shape or color of the pill, the odds increased by 11% but did not increase when the switch was made to a pill with the same color and shape. The increased odds of seizure-related events became nonsignificant when the researchers adjusted these comparisons for the process of refilling, which “is often not straightforward,” said Dr. Kesselheim. “Patients have expressed frustration with delays and other complicating factors relating to refilling.… Greater work to enhance the refilling process, and to determine whether mail order pharmacies successfully improve outcomes on this point, is necessary.”

The study was not supported by any specific targeted funding. The investigators received support from various foundations and from programs within Harvard University and grants from the Agency for Healthcare Research and Quality and the FDA.The investigators also disclosed acting in a research support role for or receiving financial compensation from several pharmaceutical companies and other organizations.

—Jessica Craig

Suggested Reading

Kesselheim AS, Bykov K, Gagne JJ, et al. Switching generic antiepileptic drug manufacturer not linked to seizures: a case-crossover study. Neurology. 2016 Sep 28 [Epub ahead of print].

Krauss GL, Privitera M. More data on the safety of generic substitution: yes, the blue tablet is OK? Neurology. 2016 Sep 28 [Epub ahead of print].

Switching between generic versions of the same antiepileptic drug made by different manufacturers does not appear to change the risk of seizure-related events in patients with epilepsy, according to a population-based, case–crossover study of generic antiepileptic drug users published online ahead of print September 28 in Neurology. Delays and complications of the medication refilling process might increase a patient’s risk for a seizure, said Aaron Kesselheim, MD, JD, MPH, Associate Professor of Medicine at Harvard Medical School in Boston, and colleagues.

“These results add to the growing literature supporting the routine use of interchangeable generic [antiepileptic drugs] among patients with seizure disorders,” he added.

Although previous observational studies have demonstrated increased seizure activity following a switch from brand name to generic antiepileptic drugs, several recent randomized trials have found no
link between generic drug switching and seizure risk, said Dr. Kesselheim.

Investigators identified 59,344 patients with at least one refill of a prescription from the same manufacturer and 5,200 patients who switched from one generic to another from 2000 to 2010 in the Medicaid Analytic eXtract database and from 2005 to 2013 in a commercial health insurance database. Participants acted as their own controls in the study’s comparison of the effects of a refill or a refill with a switch in manufacturer on seizure-related events (ie, a seizure requiring an emergency department visit or hospitalization) during a hazard period, defined as days 2–36 preceding a seizure-related event, and a control period, defined as days 51–85 preceding the seizure-related event.

Overall, generic antiepileptic refilling of the same medication from the same manufacturer was associated with an 8% increase in the odds of having a seizure-related event. When the refill involved a switch to the same generic drug made by a different manufacturer, the odds of a seizure-related event rose by 9%. When the refill involved a change in the shape or color of the pill, the odds increased by 11% but did not increase when the switch was made to a pill with the same color and shape. The increased odds of seizure-related events became nonsignificant when the researchers adjusted these comparisons for the process of refilling, which “is often not straightforward,” said Dr. Kesselheim. “Patients have expressed frustration with delays and other complicating factors relating to refilling.… Greater work to enhance the refilling process, and to determine whether mail order pharmacies successfully improve outcomes on this point, is necessary.”

The study was not supported by any specific targeted funding. The investigators received support from various foundations and from programs within Harvard University and grants from the Agency for Healthcare Research and Quality and the FDA.The investigators also disclosed acting in a research support role for or receiving financial compensation from several pharmaceutical companies and other organizations.

—Jessica Craig

Suggested Reading

Kesselheim AS, Bykov K, Gagne JJ, et al. Switching generic antiepileptic drug manufacturer not linked to seizures: a case-crossover study. Neurology. 2016 Sep 28 [Epub ahead of print].

Krauss GL, Privitera M. More data on the safety of generic substitution: yes, the blue tablet is OK? Neurology. 2016 Sep 28 [Epub ahead of print].

Switching between generic versions of the same antiepileptic drug made by different manufacturers does not appear to change the risk of seizure-related events in patients with epilepsy, according to a population-based, case–crossover study of generic antiepileptic drug users published online ahead of print September 28 in Neurology. Delays and complications of the medication refilling process might increase a patient’s risk for a seizure, said Aaron Kesselheim, MD, JD, MPH, Associate Professor of Medicine at Harvard Medical School in Boston, and colleagues.

“These results add to the growing literature supporting the routine use of interchangeable generic [antiepileptic drugs] among patients with seizure disorders,” he added.

Although previous observational studies have demonstrated increased seizure activity following a switch from brand name to generic antiepileptic drugs, several recent randomized trials have found no
link between generic drug switching and seizure risk, said Dr. Kesselheim.

Investigators identified 59,344 patients with at least one refill of a prescription from the same manufacturer and 5,200 patients who switched from one generic to another from 2000 to 2010 in the Medicaid Analytic eXtract database and from 2005 to 2013 in a commercial health insurance database. Participants acted as their own controls in the study’s comparison of the effects of a refill or a refill with a switch in manufacturer on seizure-related events (ie, a seizure requiring an emergency department visit or hospitalization) during a hazard period, defined as days 2–36 preceding a seizure-related event, and a control period, defined as days 51–85 preceding the seizure-related event.

Overall, generic antiepileptic refilling of the same medication from the same manufacturer was associated with an 8% increase in the odds of having a seizure-related event. When the refill involved a switch to the same generic drug made by a different manufacturer, the odds of a seizure-related event rose by 9%. When the refill involved a change in the shape or color of the pill, the odds increased by 11% but did not increase when the switch was made to a pill with the same color and shape. The increased odds of seizure-related events became nonsignificant when the researchers adjusted these comparisons for the process of refilling, which “is often not straightforward,” said Dr. Kesselheim. “Patients have expressed frustration with delays and other complicating factors relating to refilling.… Greater work to enhance the refilling process, and to determine whether mail order pharmacies successfully improve outcomes on this point, is necessary.”

The study was not supported by any specific targeted funding. The investigators received support from various foundations and from programs within Harvard University and grants from the Agency for Healthcare Research and Quality and the FDA.The investigators also disclosed acting in a research support role for or receiving financial compensation from several pharmaceutical companies and other organizations.

—Jessica Craig

Suggested Reading

Kesselheim AS, Bykov K, Gagne JJ, et al. Switching generic antiepileptic drug manufacturer not linked to seizures: a case-crossover study. Neurology. 2016 Sep 28 [Epub ahead of print].

Krauss GL, Privitera M. More data on the safety of generic substitution: yes, the blue tablet is OK? Neurology. 2016 Sep 28 [Epub ahead of print].