Journal Article Annotations
2024, 4th Quarter
Annotations by Nathan Praschan, MD, MPH, Laura Duque, MD and Jacob Weiss, MD
January, 2025
The finding:
This systematic review assessed the effectiveness and safety of antipsychotics for treating psychosis in individuals with epilepsy. The review identified 13 studies that included 1,180 participants. The type of psychosis was divided into interictal psychosis, postictal psychosis, antiepileptic induced psychotic disorder, schizophrenia, paranoid psychosis, “obsessive–compulsive psychosis” and unspecified psychosis. Most studies suggested that antipsychotics were effective in resolving psychotic symptoms without significantly worsening seizure frequency. The antipsychotics studied included both first-generation agents (e.g., haloperidol, chlorpromazine, thioridazine) and second-generation agents (e.g., risperidone, olanzapine, clozapine, quetiapine), with clozapine carrying the highest seizure risk despite its efficacy. However, the evidence remains inconclusive due to the heterogeneity of study designs and outcomes. Haloperidol equivalents ranged from 2.5 mg/day to 10 mg/day, risperidone equivalents from 2.25 mg/day to 8 mg/day, and chlorpromazine equivalents were 662.7 mg/day in one study.
Strength and weaknesses:
The review’s strengths include adherence to PRISMA guidelines and a comprehensive data synthesis from diverse study designs, categorizing results into case series and cohort studies. However, its limitations arise from the heterogeneity of the included studies and the inability to perform a meta-analysis. Many studies lacked standardized measures for psychosis severity and seizure outcomes, and the inconsistent reporting of antipsychotic doses and duration limits the development of clear guidelines.
Relevance:
The management of neuropsychiatric symptoms in patients with epilepsy often falls within the practice of C-L psychiatry, hence the need for nuanced understanding and management strategies of these patients. The review emphasizes the importance of balancing efficacy with safety in this population and the need for more rigorous randomized trials.
The finding:
Post-ictal psychosis (PIP) is a relatively common occurrence, with roughly 2% of epilepsy patients experiencing an episode in their lifetime—particularly among patients with temporal lobe epilepsy (TLE). The pathophysiology of PIP is poorly understood, and so the authors completed a systematic review of EEG and metabolic imaging literature to clarify mechanisms by which clusters of seizures predispose to psychosis. The authors screened 984 imaging articles and 1732 EEG articles, most of which were screened out due to irrelevance to PIP. They ultimately included a total of 22 studies, which found various EEG changes (including sharps and slowing) predominantly in the temporal lobes and to a lesser extent the frontal lobes (including orbitofrontal and anterior cingula), correlating with the findings of other studies showing increased perfusion in the same regions—notably beyond the epileptogenic zone. The authors hypothesize the PIP may result from a prolonged, aberrant post-ictal neuroendocrine mechanisms involved in seizure termination that promote metabolic dysregulation. Their findings argue against several extant hypotheses of PIP, including that PIP results from limbic epileptic activity or that it results from a predisposition to primary psychosis following a biological stressor.
Strength and weaknesses:
This is the first study of its kind to aggregate and synthesize studies of imaging and EEG in the context of PIP, allowing for a holistic view of the localization of affected networks in PIP. Nonetheless, as with most systematic reviews, the quality of the findings in the review depends on those of the included studies. For example, given the absence of non-psychotic comparators or EEG data immediately following seizure termination in the included studies, it is impossible to determine whether the metabolic and EEG changes may instead simply reflect post-ictal changes or are more specific to PIP. Additionally, though the EEG studies demonstrated similar localization to metabolic studies, there was significant heterogeneity in the type of EEG changes. The authors comment on the challenge in obtaining detailed physiologic data in these patients, both due to the intensive nature of EEG monitoring and the time it takes to obtain metabolic imaging.
Relevance:
CL psychiatrists are often called upon to diagnose and manage psychoses in epilepsy, and familiarity with the pathophysiology of PIP is essential to communicating the diagnosis with the rest of the medical team, the patient, and the family. Indeed, PIP may be confused with a primary psychosis or mania, and helping the primary team arrive at the appropriate diagnosis will avoid mislabelling and potentially unnecessary psychotropic exposure and hospitalization.