Physicians' attitudes toward generic substitutions of antiseizure drugs in epilepsy.

OBJECTIVES: The safety of generic substitution of antiseizure drugs (ASDs) has been questioned for many years. This study aimed to identify physicians' attitudes to the generic substitution of ASDs in epilepsy and which factors were of significance when deciding on compound substitutions. MATERIAL AND METHODS: A cross-sectional web-based survey was sent to neurologists and neurology residents in public health care and at private practices in two Swedish regions between February and March 2020. The 30-item survey covered drug- and patient-related factors, as well as considerations relating to practical, cost-related, and pharmacokinetic issues. RESULTS: The total response rate was 55.8%. Respondents were generally positive to cutting costs through generic ASD utilization (74%) and prescribing generic compounds when starting a new ASD treatment (84.9%). The most substantial concern was a deterioration in seizure control (17.1%). Physicians refrained from switching if the patient wished to remain on the original compound (76.1%), had a cognitive impairment (52.5%), was on a drug with a narrow therapeutic index (47%), or had shown prior susceptibility to adverse effects (45.6%). Opinions on substitution decisions differed significantly between the Stockholm and Skåne regions. Less than one-third of the respondents were aware of supporting guidelines. CONCLUSIONS: Neurologists generally accept the use of generic antiseizure compounds. Patient preference to remain on brand-name drug treatment was the most important factor that led to avoiding a switch. Our results may constitute material for consensus discussions to decide on quality indicators of interest for future research on substitution outcomes.

Unprovoked seizures after traumatic brain injury: A population-based case-control study.

OBJECTIVE: To quantify the risk of unprovoked seizures after traumatic brain injury (TBI) METHODS: We used the Stockholm Incidence Registry on Epilepsy to carry out a population-based case-control study, including 1,885 cases with incident unprovoked seizures from September 1, 2000 through August 31, 2008, together with 15,080 matched controls. Information of prior hospitalizations for TBI was obtained through record linkage with the Swedish National Inpatient Registry for the period 1980-2008. Relative risks (RRs) for unprovoked seizures were estimated after various TBI diagnoses, and influences of TBI severity and time since trauma were studied in detail. RESULTS: After hospitalization for mild TBI, the RR was 2.0 (95% confidence interval [CI] 1.5-2.7). The RR was higher after brain contusion (5.9, 95% CI 2.4-15.0) or intracranial hemorrhage (ICH) (4.5, 95% CI 2.2-9.0), whereas a combination of both diagnoses led to a further sevenfold increase in RR (42.6, 95% CI 12.2-148.5). The risk was greatest during the first 6 months after severe TBI (RR 48.9, 95% CI 10.9-218.9) or mild TBI (RR 8.1, 95% CI 3.1-21.7), but was still elevated >10 years after any TBI. SIGNIFICANCE: Herein we present a large population-based case-control study on TBI as a risk factor for unprovoked epileptic seizures, including cases of all ages with individually validated seizure diagnoses. The risk for epileptic seizures was substantially increased after TBI, especially during the first 6 months after the injury and in patients with a combination of ICH and brain contusion.

Prior hospitalization for stroke, diabetes, myocardial infarction, and subsequent risk of unprovoked seizures.

PURPOSE: To study diabetes, acute myocardial infarction, and stroke as risk factors for unprovoked seizures in a population-based cohort with incident cases of epilepsy. METHODS: In this nested case-control study, the cases were 933 patients with newly diagnosed unprovoked seizures from the Stockholm Incidence Registry of Epilepsy. Controls, in total 6,039--matched for gender, year of diagnosis, and catchment area--were randomly selected from the register of the Stockholm County population. A history of diabetes, myocardial infarction, and stroke preceding the date of onset of seizure was determined by search of the Swedish Hospital Discharge Registry. Odds ratios (ORs) were calculated to assess the risk of developing unprovoked seizures after hospital admission for any of these diagnoses. RESULTS: The age-adjusted OR (95% confidence interval, 95% CI) for unprovoked seizures after a discharge diagnosis of diabetes was 1.9 (95% CI 1.4-2.8) and after acute myocardial infarction 1.7 (95% CI 1.0-2.9). The OR was 9.4 (95% CI 6.7-13.1) after cerebral infarction, 7.2 (95% CI 3.9-13.6) after intracerebral hemorrhage, 7.2 (95% CI 2.9-18.1) after subarachnoid hemorrhage, and 3.2 (95% CI 1.9-5.5) after transient ischemic attack. The population attributable risk percent (PAR%) was <2% for each of the diagnoses except for cerebral infarction, for which the PAR% was 9%. Taken together the studied diagnoses accounted for 15% of the incident cases of unprovoked seizures. DISCUSSION: As previously known, the risk for unprovoked seizures and epilepsy after a cerebral infarction was highest the first year after the infarction. This risk remained substantial >7 years after a diagnosis of cerebral infarction.

Newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden: First report from the Stockholm Incidence Registry of Epilepsy (SIRE).

PURPOSE: To describe and report initial findings of a system for prospective identification and follow-up of patients with newly diagnosed single unprovoked seizures and epilepsy in Stockholm, Sweden, the Stockholm Incidence Registry of Epilepsy (SIRE). METHODS: From September 2001 through August 2004, a surveillance system has been in use to identify incident cases of first unprovoked seizures (neonatal seizures excluded) and epilepsy among residents of Northern Stockholm, an urban area with approximately 998,500 inhabitants. Potential cases are identified through multiple mechanisms: Network of health care professionals, medical record screening in specific hospital units, including outpatient clinics, emergency room services, and review of requests for electroencephalography (EEG) examination. Potential cases are classified 6 months after the index seizure based on review of medical records. RESULTS: After screening approximately 10,500 EEG requests and 3,300 medical records, 1,015 persons met the criteria for newly diagnosed unprovoked seizures (430 single seizures; 585 epilepsy). The crude incidence for first unprovoked seizures and epilepsy was 33.9/100,000 person years, (the same adjusted to the European Standard Million), highest the first year of life (77.1/100,000) and in the elderly. No cause could be identified in 62.4%. CONCLUSIONS: We have established a sustainable system for prospective identification of new onset epilepsy cases in Stockholm. Despite a possible under-ascertainment, the registry provides a useful starting point for follow-up studies.

The incidence of unprovoked seizures and occurrence of neurodevelopmental comorbidities in children at the time of their first epileptic seizure and during the subsequent six months.

PURPOSE: To evaluate the incidence of unprovoked seizures in children and the prevalence of related neurodevelopmental comorbidities at the time of the presumed first seizure and six months thereafter. METHODS: The medical records of all children (0-18 years of age) seeking medical attention as the result of a first unprovoked seizure between September 1, 2001 and December 31, 2006, and registered in the population-based Stockholm Incidence Registry of Epilepsy (SIRE) were reviewed. Neurodevelopmental comorbidities were evaluated on the basis of the medical records from this first visit and from other healthcare during the following six months. RESULTS: The incidence of unprovoked seizures was between 30 and 204/100,000 person years (n=766) in the different age groups. It was highest among the youngest children and lowest among the 18-year-olds with small gender differences. The most common neurodevelopment comorbidities were developmental delay (22%, CI: 19-25%), speech/language and learning difficulties (23%, CI: 20-26%) and intellectual disability (16%, CI: 13-18%). The types of neurodevelopmental comorbidity varied by age at the time of seizure onset, with cerebral palsy being more common among the 0-5-year-olds, attention deficits among the 6-16-year-olds, and autism and psychiatric diagnosis among the older children. An associated neurodevelopmental comorbidity was more common among those experiencing recurrent than single seizures during follow-up six months from the index seizure (42% versus 66%). In 68% (CI: 64-71%) of the children there was no known or suspected neurodevelopmental comorbidity. CONCLUSION: The incidence of unprovoked, non-febrile seizures among 0-18-year-olds included in the SIRE was 67/100,000 person-years. Neurodevelopmental comorbidities were common already at the time of onset of the seizure disorder, indicating that neither seizure treatment nor seizures were the underlying cause of other neurodevelopmental symptoms in these patients during the period studied.

Hospitalization for psychiatric disorders before and after onset of unprovoked seizures/epilepsy.

OBJECTIVE: To study hospitalization for psychiatric disorders before and after onset of unprovoked epileptic seizures/epilepsy. METHOD: In this population-based case-control study, the cases were 1,885 persons from Stockholm with new onset of unprovoked seizures from September 1, 2000, through August 31, 2008, identified in the Stockholm Epilepsy Register. Controls, in total 15,080, were randomly selected from the register of the Stockholm County population. Odds ratios (ORs) were calculated to assess the risk of developing unprovoked epileptic seizures before and after hospitalization for a psychiatric diagnosis defined as a psychiatric hospital discharge diagnosis using International Classification of Disease codes from the Swedish Hospital Discharge Registry. RESULTS: The age-adjusted OR (95% confidence interval) for unprovoked seizures was 2.5 (1.7-3.7) after a hospital discharge diagnosis for depression, 2.7 (1.4-5.3) for bipolar disorder, 2.3 (1.5-3.5) for psychosis, 2.7 (1.6-4.8) for anxiety disorders, and 2.6 (1.7-4.1) for suicide attempts. The risk of developing unprovoked epileptic seizures was highest less than 2 years before and up to 2 years after a first psychiatric diagnosis. CONCLUSION: The increased rate of psychiatric comorbidity predating and succeeding seizure onset indicates a bidirectional relationship and common underlying mechanisms for psychiatric disorders and epilepsy.

Unprovoked seizures in multiple sclerosis and systemic lupus erythematosus: a population-based case-control study.

To study the risk of developing unprovoked seizures among patients with multiple sclerosis (MS) and systemic lupus erythematosus (SLE), we used 1885 new onset seizure cases, 15,080 controls and defined exposure as a hospital discharge diagnosis of MS or SLE. The odds ratio with 95% confidence interval was 3.7 (CI 1.2-11.0) for MS and 8.0 (2.2-30.0) for SLE, suggesting an increased risk of unprovoked seizures in patients with both these diagnoses.