Journal Article Annotations
2026, 1st Quarter
Neuropsychiatry
Annotations by Laura Duque, MD, Nathan Praschan, MD, MPH, and Jacob Weiss, MD
March, 2026
PUBLICATION #1
Comparative Efficacy and Acceptability of Treatment Strategies for Antipsychotic-Induced Akathisia: A Systematic Review and Network Meta-analysis
Yuki Furukawa, Kota Imai, Yusuke Takahashi, Orestis Efthimiou, Stefan Leucht
Abstract:
Background: Antipsychotics are the treatment of choice for schizophrenia, but they often induce akathisia. However, comparative efficacy of treatment strategies for akathisia remains unclear.
Design: We performed a systematic review and network meta-analyses (PROSPERO CRD42023450720). We searched multiple databases on July 24, 2023. We included randomized clinical trials comparing 1 or more treatment strategies for antipsychotic-induced akathisia against each other or control conditions. We included adults with schizophrenia or other psychiatric disorders treated with antipsychotics. The primary outcome was akathisia severity at posttreatment. Secondary outcomes included akathisia response, all-cause dropout, psychotic symptoms, and long-term akathisia severity. We synthesized data in random effects frequentist network meta-analyses and assessed confidence in the evidence using CINeMA.
Results: We identified 19 trials with 661 randomized participants (mean age 35.9 [standard deviation 12.0]; 36.7% [195 of 532] women). No trials examined dose reduction or switching of antipsychotics. Findings suggested 5-HT2A antagonists (k = 6, n = 108; standardized mean difference [SMD] -1.07 [95% confidence interval, -1.42; -0.71]) and beta-blockers (k = 8, n = 105; SMD -0.46 [-0.85; -0.07]) may improve akathisia severity, but confidence in the evidence was deemed low. We also found that benzodiazepines (k = 2, n = 13; SMD -1.62 [-2.64; -0.59]) and vitamin B6 (k = 3, n = 67; SMD -0.99 [-1.49; -0.50]) might also be beneficial, but confidence in the evidence was very low. Analyses of secondary outcomes did not provide additional insights.
Conclusions: Our findings suggest that 5-HT2A antagonists, beta-blockers, and with a lesser certainty, benzodiazepines, and vitamin B6 might improve akathisia. Given the low to very low confidence in the evidence of add-on agents and the absence of evidence of their long-term efficacy, careful consideration of side effects is warranted. These recommendations are extremely preliminary and further trials are needed.
Keywords: Akathisia; antipsychotic; network meta-analysis; schizophrenia.
Annotation
The finding: This systematic review and network meta-analysis identified 19 randomized trials involving 661 adults to evaluate pharmacological treatments for antipsychotic-induced akathisia. No trials examined dose reduction or antipsychotic switching despite these being first-line guideline recommendations. Among add-on agents, serotonin 2A (5-HT2A) antagonists (including mirtazapine, mianserin, and trazodone) and beta-blockers showed the most consistent signal for reducing akathisia severity, though confidence in the evidence was rated low. Benzodiazepines and vitamin B6 also showed potential benefit but with very low confidence. No agent demonstrated long-term efficacy, as all trials had short follow-up periods averaging under one week.
Strength and weaknesses: Strengths include a comprehensive search strategy, network meta-analytic design allowing indirect comparisons across agents, and rigorous confidence rating. Limitations are substantial: trials were small (median n=26), predominantly older, and largely conducted in the Middle East and Israel, raising questions about generalizability to different populations. The sample skewed heavily male, limiting conclusions about treatment response in women.
Relevance: Akathisia is a common and distressing antipsychotic side effect frequently encountered in C-L settings, where patients on antipsychotics for delirium, agitation, or comorbid psychiatric conditions may develop motor restlessness that is misattributed to anxiety or worsening psychosis. This review offers a practical, evidence-graded framework for selecting adjunctive treatments when antipsychotic adjustment is not immediately feasible. Given the low certainty of the underlying evidence, treatment choices should remain individualized based on clinical judgment and careful attention to side effect profile.
PUBLICATION #2
Biomarkers for Alzheimer's disease and mild cognitive impairment: Recent advances in task-based EEG
Kornkanok Tripanpitak, Alexandra Wolf, Maryna Kapitonova, Satoshi Umeda, Tonio Ball, Mihoko Otake-Matsuura
Abstract:
Background: Alzheimer's disease (AD) accounts for the majority of dementia-related disorders among aging populations. Given the irreversible nature of AD, early detection of cognitive impairment is critical for improving prognosis and facilitating timely interventions before individuals meet the clinical criteria for AD.
Objective: The objective of this review is to provide a comprehensive summary of recent advances in task-based electroencephalography (EEG), such as using attention and inhibitory control tasks, which has recently emerged as a promising non-invasive biomarker for assessing neurophysiological alterations associated with AD and mild cognitive impairment (MCI).
Methods: This systematic review evaluates the efficacy of task-based EEG biomarkers in distinguishing cognitively impaired individuals from those without impairment. A comprehensive literature search was conducted across PubMed, Semantic Scholar, and SpringerLink databases for studies published between 2017 and 2024.ResultsFindings indicate consistent neurophysiological alterations in MCI and AD, particularly reductions in event-related potential amplitudes and prolonged latencies, with P3 abnormalities observed in about half of the studies assessing selective attention and inhibitory control. Similarly, a comparable number of studies using working memory tasks report disrupted functional connectivity patterns, increased low-frequency oscillations (delta and theta activity), and reduced fast oscillations (alpha and beta activity).
Conclusions: These EEG-based indices demonstrate potential as objective biomarkers for detecting neural alterations associated with cognitive decline in both AD and preclinical dementia stages. Further research is needed to standardize EEG protocols and validate their clinical utility for early diagnosis and disease progression monitoring.
Keywords: Alzheimer's disease; biomarkers; cognitive dysfunction; electroencephalography; electroencephalography phase synchronization; evoked potentials; systematic review.
Annotation
The finding: This systematic review of 74 studies examined task-based EEG, recorded during attention, working memory, and inhibitory control paradigms, as a neurophysiological biomarker for cognitive decline across the MCI-to-Alzheimer's continuum. Individuals with MCI and Alzheimer's disease consistently showed dampened and delayed neural responses, particularly in the P3 component, alongside slower oscillatory activity and reduced brain connectivity. Several markers appeared detectable before formal clinical diagnosis and predicted subsequent conversion from MCI to dementia.
Strength and weaknesses: The review follows PRISMA guidelines and synthesizes a broad range of EEG paradigms across a seven-year window. However, significant heterogeneity in task design, preprocessing, and outcome metrics limits cross-study comparability. Most samples came from research settings with limited demographic diversity, limiting generalizability.
Relevance: C-L psychiatrists are increasingly asked to weigh in on the diagnostic workup of hospitalized patients with acute cognitive changes, where access to PET or CSF testing is limited and standard screening tools may be insufficient. Task-based EEG offers a low-cost, bedside-compatible alternative that captures functional brain changes not visible on structural imaging. While not yet clinically standardized, familiarity with this evolving literature positions C-L psychiatrists to engage meaningfully in multidisciplinary discussions about early dementia identification.
PUBLICATION #3
Suicidal Ideation in Spinocerebellar Ataxia
Levi Peppel, Ruo-Yah Lai, Christian Rummey, Puneet Opal, Jeremy D Schmahmann, Christopher M Gomez, Henry Paulson, Theresa A Zesiewicz, Susan Perlman, George Wilmot, Sarah H Ying, Chiadi U Onyike, Khalaf O Bushara, Michael D Geschwind, Karla P Figueroa, Stefan M Pulst, Sub H Subramony, Antoine Duquette, Tetsuo Ashizawa, Ali G Hamedani, Marie Y Davis, Sharan R Srinivasan, Matthew R Burns, Nadia Amokrane, Lauren R Moore, Vikram G Shakkottai, Liana S Rosenthal, Sheng-Han Kuo, Chi-Ying R Lin
Abstract:
Objective: Suicidal ideation has not been extensively studied in spinocerebellar ataxias (SCAs). The authors examined whether individuals with SCAs have increased suicidal ideation and related factors.
Methods: The authors studied patients with genetically confirmed SCAs enrolled in the Clinical Research Consortium for the Study of Cerebellar Ataxia cohort, examining the percentages of patients with SCA subtypes 1, 2, 3, and 6 who reported suicidal ideation and comparing findings with nationally representative data from the National Survey on Drug Use and Health (NSDUH). Clinical characteristics that may contribute to suicidal ideation in SCAs, including age, disease duration, sex, ataxia severity, depression, and SCA subtype, were also studied.
Results: Suicidal ideation was present among 12% of 769 patients with SCAs and 4.3% of individuals in the general population recorded in the NSDUH. Compared with individuals in the general population, SCA patients had higher odds of suicidal ideation (OR=2.72). Compared with patients with SCA without suicidal ideation, patients with SCA and suicidal ideation had a longer disease duration (mean±SD=13.1±8.2 years vs. 11.2±9.4 years), more severe ataxia (Scale for the Assessment and Rating of Ataxia mean score=15.9±8.6 vs. 12.9±7.6), and more severe depression. Having suicidal ideation at baseline significantly increased the odds of suicidality later in the disease course (OR=58.73, 95% CI=36.00-98.40).
Conclusions: Suicidal ideation was more prevalent among patients with SCAs than in the general population. The findings of this study underscore the importance of continuous suicidal risk screening among individuals with SCAs and the need for effective depression management.
Keywords: Cerebellar Disorders; Cerebellum; Nonmotor Function; Spinocerebellar Ataxia; Suicidal Ideation; Suicide.
Annotation
The finding: Spinocerebellar ataxias have long been framed primarily as motor disorders, yet this registry-based study makes a compelling case that suicidal ideation is a clinically significant and underappreciated feature of the disease. One in eight patients across four genetically confirmed subtypes endorsed suicidal ideation, a rate nearly three times that of the general population. Rather than worsening linearly with disease progression, suicidal risk appeared remarkably stable over time, driven more by the burden of depression and motor disability than by how long someone had lived with the disease. The near-60-fold odds of future suicidal ideation among those with baseline ideation reframes this not as an episodic concern but a chronic risk requiring sustained clinical attention.
Strength and weaknesses: The longitudinal multisite design, sample size, and subtype-specific analyses are notable strengths, but the reliance on a single PHQ-9 item rather than a validated suicide instrument is a meaningful limitation. Key confounders including substance use and psychiatric comorbidities were not captured.
Relevance: C-L psychiatrists will likely encounter SCA patients during hospitalizations for falls or aspiration episodes, and this study makes a compelling case that suicidal risk in this population deserves the same systematic attention given to depression in other neurological conditions. The persistence of suicidal ideation over time argues strongly for longitudinal screening protocols rather than opportunistic assessment.