Psychiatric comorbidity in relation to clinical characteristics of epilepsy: A retrospective observational study.

PURPOSE: Prevalence of psychiatric disorders in people with epilepsy is high. However, diagnostic validity and information about the nature of the seizure disorders are often poor in population-based studies. In a well validated and classified patient sample, we investigated psychiatric comorbidity according to clinical characteristics. METHOD: Participants in The Trøndelag Health Study (HUNT) with ≥ 2 diagnostic epilepsy codes during 1987-2019 were identified. Medical records were reviewed, and epilepsy was validated and classified according to ILAE. Psychiatric comorbidity was defined by ICD-codes. RESULTS: In 448 individuals with epilepsy, 35% had at least one psychiatric disorder (anxiety and related disorders 23%, mood disorders 15%, substance abuse and personality disorders 7%, and psychosis 3%). Comorbidity was significantly higher in women than in men (p = 0.007). The prevalence of psychiatric disorders was 37% in both focal and generalized epilepsy. In focal epilepsy, it was significantly lower when etiology was structural (p = 0.011), whereas it was higher when the cause was unknown (p = 0.024). Comorbidity prevalence was 35% both in patients achieving seizure freedom and in those with active epilepsy but 38% among 73 patients with epilepsy resolved. CONCLUSION: Just over one third of people with epilepsy had psychiatric comorbidities. The prevalence was equal in focal and generalized epilepsy but was significantly higher in focal epilepsy of unknown cause compared to lesional epilepsy. Comorbidity was independent of seizure control at last follow-up but was slightly more common in those with resolved epilepsy, often having non-acquired genetic etiologies possibly linked to neuropsychiatric susceptibility.

Bidirectionality of antiseizure and antipsychotic treatment: A population-based study.

PURPOSE: To study the prevalence and directionality of comorbid epilepsy and psychosis in Norway. METHODS: The Norwegian Prescription Database (NorPD) provided individual-based information on all antiseizure medications (ASMs) and antipsychotic drugs (APDs) dispensed during 2004-2017. Subjects were ≥18 years of age at the end of the study period. Diagnosis-specific reimbursement codes from the 10th revision of the International Classification of Diseases/2nd edition of the International Classification of Primary Care (ICD-10/ICPC-2) combined with ATC codes were used as indicators of diagnosis. Subjects had collected ASMs for epilepsy or APDs for psychosis at least four times, at least once issued with an ICD-10 code from the specialist healthcare service. Directionality was analyzed in subjects receiving both treatments. To reduce prevalent comorbidity bias, we employed a four-year comorbidity-free period (2004-2007). The use of specific ASMs and APDs was analyzed. RESULTS: A total of 31,289 subjects had collected an ASM for epilepsy at least four times, 28,889 an APD for psychosis. Both the prevalence of treatment for epilepsy and of treatment for psychosis was 0.8%. Further, 891 subjects had been treated for both conditions; 2.8% with epilepsy had been treated for psychosis, and 3.1% with psychosis had been treated for epilepsy. Among 558 subjects included in the analyses of directionality, 56% had collected the first APD before an ASM, whereas 41% had collected an ASM first. During the last year prior to comorbidity onset, levetiracetam, topiramate, or zonisamide had been used for epilepsy by approximately 40%, whereas olanzapine and quetiapine were most used in patients with psychosis, and clozapine in 13%. CONCLUSION: The proportion of patients with prior antipsychotic treatment at onset of epilepsy is higher than previously acknowledged, as demonstrated in this nation-wide study. Apart from a shared neurobiological susceptibility, the bidirectionality of epilepsy and psychosis may be influenced by various environmental factors, including the interaction of pharmacodynamic effects. APDs may facilitate seizures; ASMs may induce psychiatric symptoms. In patients with combined treatment, these potential drug effects should receive ample attention, along with the psychosocial consequences of the disorders. A prudent multi-professional approach is required.

Pharmacokinetic data on brivaracetam, lacosamide and perampanel during pregnancy and lactation.

We present pharmacokinetic data during pregnancy and lactation for brivaracetam, lacosamide and perampanel based on two case studies. Patient 1 used brivaracetam as monotherapy and gave birth to twins. Patient 2 used a combination of brivaracetam, lacosamide and perampanel. In both patients, serum drug concentrations were monitored throughout the pregnancies. Drug concentrations were also analysed in umbilical cord blood at birth, in serum from the offspring and in breastmilk after five days and 3-11 weeks. There were minor changes in concentration/dose-ratios for brivaracetam and lacosamide. The mean milk/serum ratios for brivaracetam and lacosamide were 0.71 and 0.83, respectively, five days and 3-5 weeks after delivery. The perampanel serum concentration increased by up to 80% in Patient 2 during the last part of gestation. The mean milk/serum-ratio for perampanel was 0.13, unchanged from five days to five weeks after delivery. Whereas serum concentrations of brivaracetam and lacosamide remained fairly stable throughout pregnancy, perampanel concentrations seemed to steadily increase towards the end. The distribution to milk was considerable for brivaracetam and lacosamide and low for perampanel. More studies on mother-infant pairs are warranted to confirm these results in larger groups.

Experiential seizures related to the hippocampal-parahippocampal spatial representation system.

Ictal visual hallucinations may have occipital as well as temporal lobe origin. We report a patient with clustering of focal aware seizures with visual hallucinations. Ictal EEG findings and seizure semiology with alternating contralateral elementary visual phenomena and non-lateralizing experiential hallucinations (visual scenes, memory flashbacks, spatial distortion) corresponded to a lesion in the posterior part of the right parahippocampal gyrus. This area is part of the hippocampal-parahippocampal system for mapping allocentric space. Within this system, the parahippocampal cortex encodes information about visual environmental scenes in concert with functionally defined neurons relevant for episodic memory and spatial cognitive processes (place, grid, border and head direction cells, as well as neurons tracking the passage of time). These functions are tightly linked to visual exploration. We suggest that the hippocampal-parahippocampal spatial navigation system is a crucial part of the networks responsible for the semiology of experiential seizures with complex visual hallucinations and elements of recall.

Substance use disorders and psychotic disorders in epilepsy: a population-based registry study.

BACKGROUND: Epilepsy affects around 70 million people worldwide. Psychiatric comorbidity may add to the burden of the disease. We studied substance use disorders and psychotic disorders among people with epilepsy from a population-based perspective. METHODS: Norwegian specialist health services (hospitals and outpatient clinics) report diagnoses for individual patients to the Norwegian Patient Register. We used information on subjects born in 1930-1994 who were registered with a diagnosis of epilepsy at least once during the five-year period of 2008-2012. We compared the proportion of people with epilepsy registered with substance use disorders (alcohol use disorders or non-alcohol drug use disorders) and psychotic disorders (schizophrenia spectrum disorders or bipolar disorder) with similar figures in the population without epilepsy. We applied chi-square tests and log-binomial regression for analysis. RESULTS: Overall, 0.90% of the Norwegian adult population was registered with epilepsy in somatic hospitals during 2008-2012. The total proportion registered with alcohol use disorder was 5.74% among people with epilepsy and 1.29% in the population without epilepsy (age- and sex-adjusted relative risk [RR]: 4.42, 95% confidence interval [CI]: 4.22-4.62). The corresponding figures were 4.32% and 1.22% (RR 3.86 [95% CI: 3.67-4.06] for drug use disorder, 1.72% and 0.60% (RR 2.94 [95% CI: 2.71-3.19]) for schizophrenia spectrum disorders, and 1.50% and 0.68% (RR 2.29 [95% CI: 2.10-2.49]) for bipolar disorder. CONCLUSION: People with epilepsy were more often registered with substance use disorders and psychotic disorders than people without epilepsy. Psychiatric comorbidity requires particular attention in both diagnostic work-up and management of epilepsy, and creates complex medical challenges that require close cooperation between neurologists and psychiatrists. These findings may have implications for the organization and further development of comprehensive epilepsy care.