Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD. Objective: To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT. Design, Setting, and Participants: This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians. Exposures: Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks. Main Outcomes and Measures: Association between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses. Results: Among the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment. Conclusions and Relevance: In this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.

Hypertensive Emergency Secondary to Combining Psilocybin Mushrooms, Extended Release Dextroamphetamine-Amphetamine, and Tranylcypromine.

Data on medication interactions with psychedelics are limited. Here we present what may be the first published report of a hypertensive emergency following the combination of psilocybin mushrooms with a monoamine oxidase inhibitor (MAOI). A 42-year-old man with treatment-resistant major depressive disorder took 1 g of Psilocybe cubensis mushrooms, while prescribed tranylcypromine, extended-release dextroamphetamine-amphetamine, and other medications. Approximately half an hour later, he developed severe hypertension with chest pain, palpitations, and headache. Upon hospital presentation, the electrocardiogram demonstrated ST-elevation. The patient was diagnosed with a myocardial infarction and treated with lorazepam, nitroglycerin, and aspirin. He subsequently underwent emergency cardiac catheterization, which revealed no significant cardiac abnormalities. Following overnight hospitalization, he was discharged home with no lasting physical sequelae. Though data are few, past studies suggest that classic serotonergic psychedelics (5HT-2A receptor agonists) such as dimethyltryptamine (DMT), lysergic acid (LSD), and synthetic psilocybin should not produce hypertensive emergency when combined with MAOIs. We suspect phenylethylamine, found in Psilocybe cubensis and other species of psilocybin mushrooms, interacted with tranylcypromine and dextroamphetamine-amphetamine to produce this hypertensive emergency. Patients prescribed MAOIs should be warned of the potential for hypertensive emergency when consuming psilocybin mushrooms, particularly when also prescribed norepinephrine releasers such as dextroamphetamine-amphetamine.

Formulary Coverage of Esketamine and Ketamine for Depression in Ohio Health Insurance Marketplace and Medicaid Plans.

For more than 2 decades, intravenous ketamine has been demonstrated to have rapid antidepressant effects. However, access to this generic drug is limited due to insurers claiming it is "experimental" because ketamine does not have a Food and Drug Administration indication for depression. In contrast, intranasal esketamine, an enantiomer of ketamine, is approved by the Food and Drug Administration for depression and is still under patent. The goal of this column is to provide a clearer understanding of formulary coverage of these similar medications by insurers. Formularies of all 2023 Ohio Health Insurance Marketplace and Medicaid plans were reviewed to determine the inclusion status of intravenous ketamine and intranasal esketamine for depression. This review found that intravenous ketamine was not covered by any Marketplace or Medicaid plan for depression, while intranasal esketamine was on 72.7% and 100% of formularies, respectively. Thus, members of the analyzed insurance plans can more easily access intranasal esketamine than intravenous ketamine for depression, despite the latter being more cost-effective and possibly more efficacious.

Preexisting Psychiatric Conditions as Risk Factors for Diagnosed Long COVID-19 Syndrome Within Aggregated Electronic Health Record Data.

OBJECTIVE: This study aimed to investigate the frequency of long COVID diagnosis among patients infected with severe acute respiratory syndrome coronavirus 2 with preexisting psychiatric conditions versus those without preexisting psychiatric conditions. METHODS: The TriNetX Analytics platform, an aggregated electronic health record research network containing the deidentified electronic health record data of more than 90 million patients, was queried for patients who were diagnosed with COVID-19 infection based on International Classifications of Disease, Tenth Revision codes. Patients were stratified based on their preexisting psychiatric conditions, and new diagnoses of long COVID were recorded and reported as the primary outcome. RESULTS: Among 1,180,948 patients previously diagnosed with COVID-19, 17,990 patients (1.52%) were diagnosed with long COVID based on the newly implemented International Classifications of Disease, Tenth Revision code "U09: post-COVID-19 condition." After propensity score matching, patients with any preexisting psychiatric diagnosis had a 1.52 (95% confidence interval [CI] = 1.47-1.58) times greater prevalence of diagnosed long COVID within 180 days of infection than patients without preexisting psychiatric diagnoses. Patients with diagnosed anxiety disorders (relative risk [RR] = 1.64; 95% CI = 1.57-1.71), mood disorders (RR = 1.65; 95% CI = 1.57-1.72), bipolar disorder (RR = 1.37; 95% CI = 1.21-1.54), major depressive disorder (RR = 1.69; 95% CI = 1.56-1.83), psychotic disorders (RR = 1.23; 95% CI = 1.06-1.44), and substance use disorders (RR = 1.28; 95% CI = 1.22-1.36) had higher risks for long COVID diagnoses when compared with patients without preexisting psychiatric illness at the time of diagnosis. CONCLUSIONS: Multiple preexisting psychiatric diagnoses are associated with an increased risk of being diagnosed with long COVID after COVID-19 infection.

The Zero Suicide Model in Addiction Treatment Settings: Recognizing the Need for Feasibility and Implementation Data.

The Zero Suicide (ZS) model is a promising approach for preventing all suicides across health care settings. ZS provides guidelines for health care systems to implement best practices in suicide prevention. Patients with substance use disorders are at increased risk for suicide, but no known research has investigated how to integrate the ZS model into addiction treatment settings. This Open Forum encourages clinicians and researchers to integrate ZS into such settings and to study its feasibility and effectiveness. ZS integration into addiction treatment may improve both suicide and addiction outcomes, but additional research is needed.

Quantitative diffusion imaging and genotype-by-sex interactions in a rat model of Alexander disease.

PURPOSE: The clinical diagnosis and classification of Alexander disease (AxD) relies in part on qualitative neuroimaging biomarkers; however, these biomarkers fail to distinguish and discriminate different subtypes of AxD, especially in the presence of overlap in clinical symptoms. To address this gap in knowledge, we applied neurite orientation dispersion and density imaging (NODDI) to an innovative CRISPR-Cas9 rat genetic model of AxD to gain quantitative insights into the neural substrates and brain microstructural changes seen in AxD and to potentially identify novel quantitative NODDI biomarkers of AxD. METHODS: Multi-shell DWI of age- and sex-matched AxD and wild-type Sprague Dawley rats (n = 6 per sex per genotype) was performed and DTI and NODDI measures calculated. A 3 × 2 × 2 analysis of variance model was used to determine the effect of genotype, biological sex, and laterality on quantitative measures of DTI and NODDI across regions of interest implicated in AxD. RESULTS: There is a significant effect of genotype in the amygdala, hippocampus, neocortex, and thalamus in measures of both DTI and NODDI brain microstructure. A genotype by biological sex interaction was identified in DTI and NODDI measures in the corpus callosum, hippocampus, and neocortex. CONCLUSION: We present the first application of NODDI to the study of AxD using a rat genetic model of AxD. Our analysis identifies alterations in NODDI and DTI measures to large white matter tracts and subcortical gray nuclei. We further identified genotype by sex interactions, suggesting a possible role for biological sex in the neuropathogenesis of AxD.

Phencyclidine Positivity on Urine Drug Screening in Patients Treated for Alcohol Withdrawal on a Dual-diagnosis Medically Assisted Withdrawal Unit.

OBJECTIVES: Little contemporary research has explored phencyclidine (PCP) use in people with alcohol use disorder. Therefore, we sought to determine the prevalence of PCP positivity on urine toxicology screening among patients admitted for alcohol withdrawal, identify correlates of PCP positivity, and investigate PCP positivity's relationship to length of stay (LOS) and risk of facility readmission. METHODS: This was a retrospective study of patients admitted to a dual-diagnosis medically assisted withdrawal unit for alcohol withdrawal from 2014 to 2019. Univariate tests and logistic regression were used to investigate potential correlates of PCP positivity on admission toxicology screening (primary outcome). Multivariable linear regression models and survival analyses analyzing LOS and risk of readmission (secondary outcomes) were also developed. RESULTS: Ninety of 3731 patients (2.4%) screened positive for PCP. There were significant associations on univariate testing between PCP positivity and age, race, homeless status, and urine toxicology positivity for amphetamines, benzodiazepines, barbiturates, cocaine, tetrahydrocannabinol, and oxycodone. On multivariate logistic regression, only tetrahydrocannabinol, barbiturates, and cocaine positivity were associated with PCP positivity. Multivariate logistic regression and survival analysis found no statistically significant associations between PCP positivity and LOS or risk of readmission. CONCLUSIONS: This study provides rare analysis of contemporary data on PCP use among patients undergoing medically assisted alcohol withdrawal. Phencyclidine positivity was uncommon, but use appears considerably higher among this patient population than the general population. There was no significant association between PCP positivity and LOS or readmission risk.

Race, economic status, and disparities in the receipt of benzodiazepine prescriptions in a large primary care sample.

OBJECTIVE: To evaluate the relationship between race, economic status, and patient characteristics with benzodiazepine prescribing in an urban and suburban primary care context. METHOD: This retrospective study used data from a previously described cohort of patients seen in a large Ohio healthcare system's primary care clinics from 2019 to 2020. Associations and interactions between race, economic status (using median income of patient ZIP code as a proxy), patient characteristics, and prescription of benzodiazepines were assessed using multivariable logistic regression. RESULTS: 455,537 patients had 1,643,473 primary care visits, and 5.8% of patients were prescribed a benzodiazepine. White patients were prescribed benzodiazepines more often than Multiracial/Multicultural, African American and Asian American patients (6.5%, 3.8%, 2.7% and 2.0% respectively). Patients from lower income ZIP codes were less likely to receive a prescription. Interaction effects were observed between race, patient economic status, gender, insurance status, and diagnoses (general anxiety disorder, insomnia, and panic disorder). The largest prescribing disparities by race were among patients with these three diagnoses. The largest disparity in prescription by income was seen in African American patients. CONCLUSION: African American, Multicultural/Multiracial and Asian American patients were less likely than White patients to receive benzodiazepine prescriptions. Middle and lower-income patients are particularly susceptible to this prescribing disparity.

Prescribing of Z-Drugs With and Without Opioid Coprescribing to Primary Care Patients in a Large Health Care System From 2019-2020.

Objective: This study aimed to characterize Z-drug prescribing with and without opioid coprescribing pre- and post-COVID-19 lockdown in the primary care clinics of a large health care system.Methods: A retrospective, cross-sectional study was conducted that measured the prevalence of Z-drug prescribing with and without opioids for adults aged ≥ 18 years that were seen in the primary care clinics of a large health care system in 2019 and 2020. The pre-COVID time period was defined as March 24, 2019-December 31, 2019, and the post-lockdown time period was defined as March 24, 2020-December 31, 2020.Results: Among 455,537 adult patients, 6,743 (1.48%) were prescribed a Z-drug during the study period. In addition, 1,064 (0.2%) were coprescribed a Z-drug and an opioid at least once, constituting 15.78% of patients receiving a Z-drug prescription. There was no change in the rate of Z-drug prescription post-lockdown (odds ratio [OR] = 0.978, 95% confidence interval [CI] = 0.942-1.010, P = .233), though odds of coprescribing decreased (OR = 0.883, 95% CI = 0.789-0.988, P = .031). Important correlates of receiving a Z-drug prescription during the study period were older age, White race, and diagnosis of opioid use disorder. Older age and a diagnosis of opioid use disorder were also associated with coprescribing. Receiving a de novo Z-drug prescription post-lockdown was associated with increased age, White race, and diagnosis of bipolar disorder, generalized anxiety disorder, and insomnia.Conclusions: Rates of Z-drug prescribing were unchanged post-lockdown, while rates of Z-drug with opioid coprescribing decreased. Some patient populations vulnerable to Z-drug adverse effects were at heightened risk of Z-drug prescription, while racial disparities in Z-drug prescribing were observed.

Three Cases of Reported Improvement in Microsmia and Anosmia Following Naturalistic Use of Psilocybin and LSD.

Cultural awareness of anosmia and microsmia has recently increased due to their association with COVID-19, though treatment for these conditions is limited. A growing body of online media claims that individuals have noticed improvement in anosmia and microsmia following classic psychedelic use. We report what we believe to be the first three cases recorded in the academic literature of improvement in olfactory impairment after psychedelic use. In the first case, a man who developed microsmia after a respiratory infection experienced improvement in smell after the use of 6 g of psilocybin containing mushrooms. In the second case, a woman with anosmia since childhood reported olfactory improvement after ingestion of 100 µg of lysergic acid diethylamide (LSD). In the third case, a woman with COVID-19-related anosmia reported olfactory improvement after microdosing 0.1 g of psilocybin mushrooms three times. Following a discussion of these cases, we explore potential mechanisms for psychedelic-facilitated improvement in olfactory impairment, including serotonergic effects, increased neuroplasticity, and anti-inflammatory effects. Given the need for novel treatments for olfactory dysfunction, increasing reports describing improvement in these conditions following psychedelic use and potential biological plausibility, we believe that the possible therapeutic benefits of psychedelics for these conditions deserve further investigation.

Methamphetamine-associated catatonia: Case series and systematic review of the literature from 1943-2020.

BACKGROUND: Catatonia due to a general medical condition may result from a variety of causes, including substance intoxication and withdrawal. Stimulants are occasionally associated with catatonia, though there has been little investigation of methamphetamine's relationship to catatonia. Here we present 5 cases of catatonia associated with methamphetamine use and a systematic review of the associated literature from 1943 to 2020. METHODS: We performed a systematic review of the literature and present 5 cases of catatonia evaluated using the Bush-Francis Catatonia Rating Scale and KANNER catatonia rating scale. RESULTS: Methamphetamine use was associated with catatonia in a small number of cases in the literature. However, some of these reports included other possible etiologies. The patients in our case series met DSM-5 criteria for catatonia due to a general medical condition, with all reporting recent methamphetamine use and testing positive for amphetamines on urine drug screen. CONCLUSIONS: Given the ongoing rise in methamphetamine use in the United States, it is important that clinicians understand that methamphetamine use can be associated with catatonia. Patients with methamphetamine-associated catatonia may respond favorably to lorazepam and require shorter hospital stays than other catatonic patients. Lastly, methamphetamine-associated catatonia highlights how alteration in dopamine function and projections may be a critical neural mechanism underlying catatonia in general.

A masked, placebo-controlled, randomized clinical trial evaluating safety and the effect on cardiac function of low-dose rapamycin in 17 healthy client-owned dogs.

Introduction: Geroscience studies of low-dose rapamycin in laboratory species have identified numerous benefits, including reversing age-related cardiac dysfunction. Cardiovascular benefits have been observed in dogs with 10 weeks of treatment, raising questions about possible benefits and adverse effects of long-term use of low-dose rapamycin. The objectives of this study were to assess the impact of 6 months of low-dose rapamycin on echocardiographic indices of cardiac function in healthy dogs and to document the occurrence of adverse events. Methods: Seventeen client-owned dogs aged 6-10 years, weighing 18-36 kg, and without significant systemic disease were included in a prospective, randomized, placebo-controlled, masked clinical trial. Low-dose rapamycin (0.025 mg/kg) or placebo was administered three times per week for 6 months. Baseline, 6-month, and 12-month evaluation included physical examination, cardiology examination, and clinicopathology. Three-month evaluation included physical examination and clinicopathology. Owners completed online questionnaires every 2 weeks. Results: There were no statistically significant differences in echocardiographic parameters between rapamycin and placebo groups at 6 or 12 months. No clinically significant adverse events occurred. In 26.8% of the bi-weekly surveys owners whose dogs received rapamycin reported perceived positive changes in behavior or health, compared to 8.1% in the placebo group (p = 0.04). Discussion: While no clinically significant change in cardiac function was observed in dogs treated with low-dose rapamycin, the drug was well-tolerated with no significant adverse events.

Ketamine versus ECT for Nonpsychotic Treatment-Resistant Major Depression.

BACKGROUND: Electroconvulsive therapy (ECT) and subanesthetic intravenous ketamine are both currently used for treatment-resistant major depression, but the comparative effectiveness of the two treatments remains uncertain. METHODS: We conducted an open-label, randomized, noninferiority trial involving patients referred to ECT clinics for treatment-resistant major depression. Patients with treatment-resistant major depression without psychosis were recruited and assigned in a 1:1 ratio to receive ketamine or ECT. During an initial 3-week treatment phase, patients received either ECT three times per week or ketamine (0.5 mg per kilogram of body weight over 40 minutes) twice per week. The primary outcome was a response to treatment (i.e., a decrease of ≥50% from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology-Self-Report; scores range from 0 to 27, with higher scores indicating greater depression). The noninferiority margin was -10 percentage points. Secondary outcomes included scores on memory tests and patient-reported quality of life. After the initial treatment phase, the patients who had a response were followed over a 6-month period. RESULTS: A total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group. After 38 patients had withdrawn before initiation of the assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients. A total of 55.4% of the patients in the ketamine group and 41.2% of those in the ECT group had a response (difference, 14.2 percentage points; 95% confidence interval, 3.9 to 24.2; P<0.001 for the noninferiority of ketamine to ECT). ECT appeared to be associated with a decrease in memory recall after 3 weeks of treatment (mean [±SE] decrease in the T-score for delayed recall on the Hopkins Verbal Learning Test-Revised, -0.9±1.1 in the ketamine group vs. -9.7±1.2 in the ECT group; scores range from -300 to 200, with higher scores indicating better function) with gradual recovery during follow-up. Improvement in patient-reported quality-of-life was similar in the two trial groups. ECT was associated with musculoskeletal adverse effects, whereas ketamine was associated with dissociation. CONCLUSIONS: Ketamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis. (Funded by the Patient-Centered Outcomes Research Institute; ELEKT-D ClinicalTrials.gov number, NCT03113968.).

Development and validation of a novel instrument to capture companion dog mortality data: the Dog Aging Project End of Life Survey.

OBJECTIVE: The researchers and clinicians within the Dog Aging Project (DAP), a longitudinal cohort study of aging in companion dogs, created and validated a novel survey instrument titled the End of Life Survey (EOLS) to gather owner-reported mortality data about companion dogs. SAMPLE: Bereaved dog owners who participated in the refinement, face validity assessment, or reliability assessment of the EOLS (n = 42) and/or completed the entire survey between January 20 and March 24, 2021 (646). PROCEDURES: The EOLS was created and modified by veterinary health professionals and human gerontology experts using published literature, clinical veterinary experience, previously created DAP surveys, and feedback from a pilot study conducted with bereaved dog owners. The EOLS was subjected to qualitative validation methods and post hoc free-text analysis to evaluate its ability to thoroughly capture scientifically relevant aspects of companion dogs' deaths. RESULTS: The EOLS was well received with excellent face validity as assessed by dog owners and experts. The EOLS had fair to substantial reliability for the 3 validation themes-cause of death (κ = 0.73; 95% CI, 0.5 to 0.95), perimortem quality of life (κ = 0.49; 95% CI, 0.26 to 0.73), and reason for euthanasia (κ = 0.3; 95% CI, 0.08 to 0.52)-and had no need for any substantial content alterations based on free-text analysis. CLINICAL RELEVANCE: The EOLS has proven to be a well-accepted, comprehensive, and valid instrument for capturing owner-reported companion dog mortality data and has the potential to enhance veterinarians' ability to care for the aging dog population by illuminating their understanding of companion dogs' end-of-life experiences.

Development and Validation of a Novel Instrument to Capture Companion Dog Mortality Data: The Dog Aging Project End of Life Survey.

Objective: The researchers and clinicians within the Dog Aging Project (DAP), a longitudinal cohort study of aging in companion dogs, created and validated a novel survey instrument titled the End of Life Survey (EOLS) to gather owner-reported mortality data about companion dogs. Sample: Bereaved dog owners who participated in the refinement, face validity assessment, or reliability assessment of the EOLS (n=42) and/or completed the entire survey between January 20 and March 24, 2021 (n=646). Procedures: The EOLS was created and modified by veterinary health professionals and human gerontology experts using published literature, clinical veterinary experience, previously created DAP surveys, and feedback from a pilot study conducted with bereaved dog owners. The EOLS was subjected to qualitative validation methods and post-hoc free-text analysis to evaluate its ability to thoroughly capture scientifically relevant aspects of companion dogs' death. Results: The EOLS was well-received with excellent face validity as assessed by dog owners and experts. The EOLS had fair to substantial reliability for the three validation themes: cause of death (kappa = 0.73; 95% CI [0.5-0.95]), perimortem quality of life (kappa = 0.49; 95% CI [0.26-0.73]), and reason for euthanasia (kappa = 0.3; 95% CI [0.08-0.52]) and had no need for any substantial content alterations based on free-text analysis. Clinical Relevance: The EOLS has proven to be a well-accepted, comprehensive, and valid instrument for capturing owner-reported companion dog mortality data and has the potential to enhance veterinarians' ability to care for the aging dog population by illuminating their understanding of companion dogs' end-of-life experiences.

An Analysis of Benzodiazepine Prescribing to Primary Care Patients in a Large Healthcare System from 2019-2020.

We sought to quantify benzodiazepine prescribing by primary care providers from 2019 to 2020 and identify correlates of prescribing. We hypothesized prescribing would increase post-COVID-19 lockdown. We conducted a retrospective cohort study of adult patients with primary care visits in 2019 or 2020 in a large Ohio healthcare system. Demographics, diagnosis codes, and receipt of benzodiazepine prescriptions were collected. Using multivariable logistic regression, we examined factors associated with benzodiazepine prescription receipt during the whole study period and post-lockdown. 455,537 adult patients had 1,643,473 visits. Benzodiazepines were prescribed in 3.2% (53,049/1,643,473) of visits. Effect sizes for positive associations with benzodiazepine prescription were largest for anxiety disorders. For negative associations, they were largest for Black patients and patients with cocaine use disorder. Benzodiazepine prescribing was positively associated with multiple groups having contraindications, though effect sizes were small. Contrary to our hypothesis, odds of receiving a prescription were 8.8% lower post-lockdown. Benzodiazepine prescribing rates in our system compared favorably to national rates. Year over year odds of receiving a prescription were slightly lower post-lockdown. Racial disparities were present and deserve further study. Strategies to reduce benzodiazepine prescribing to patients with anxiety may yield the largest reductions for benzodiazepine prescribing in primary care settings.

The State of the Catatonia Literature: Employing Bibliometric Analysis of Articles From 1965-2020 to Identify Current Research Gaps.

BACKGROUND: Since Kahlbaum's classic 19th-century description of catatonia, our conceptualization of this syndrome, as well treatment options for it, has advanced considerably. However, little is known about the current state of the catatonia literature since a comprehensive bibliometric analysis of it has not yet been undertaken. OBJECTIVE: The purpose of this study was to conduct a bibliometric analysis, along with a content analysis of articles reporting new findings, to better understand the catatonia literature and how catatonia research is changing. METHODS: Using the search term "Title(catatoni∗)" in Web of Science Core Collection for all available years (1965-2020), all available publications (articles, proceeding papers, reviews) pertaining directly to catatonia were identified, and metadata extracted. Semantic and coauthorship network analyses were conducted. A content analysis was also conducted on all available case reports, case series, and research articles written in English. RESULTS: A total of 1015 articles were identified representing 2861 authors, 346 journals, and 15,639 references. The average number of publications per year over the last 20 years (31.3) more than doubled in comparison to that in the 20 years prior (12.8). The top 3 most common journals were Psychosomatics/Journal of the Academy of Consultation-Liaison Psychiatry, Journal of ECT, and Schizophrenia Research, which represented 12.6% of all publications. Content analysis revealed that catatonia articles are increasingly published in nonpsychiatric journals. There was a notable paucity of clinical trials throughout the study period. Since 2003, articles on catatonia secondary to a general medical condition, as well as articles including child/adolescent patients and patients with autism spectrum disorder or intellectual disability, have made up increasing shares of the literature, with a smaller proportion of articles reporting periodic or recurrent catatonia. We noted a decrease in the proportion of articles detailing animal/in vitro studies, genetic/heredity studies, and clinical trials, along with stagnation in the proportion of neuroimaging studies. CONCLUSIONS: The catatonia literature is growing through contributions from authors and institutions across multiple countries. However, recent growth has largely been driven by increased case reports, with significant downturns observed in both clinical and basic science research articles. A dearth of clinical trials evaluating potential treatments remain a critical gap in the catatonia literature.

Catatonia and Neuroleptic Malignant Syndrome in Patients With Cerebral Palsy: Two Case Reports and a Systematic Review of the Literature.

BACKGROUND: Patients with cerebral palsy, a group of movement disorders with motor, and possibly communication and behavioral features that mimic catatonic signs, may benefit from efforts to improve the detection and treatment of comorbid catatonia. Given that cerebral palsy frequently co-occurs with conditions associated with catatonia, such as autism spectrum disorder, epilepsy, intellectual disability, and mood and psychotic disorders, lifetime prevalence of catatonia in this population may be high. OBJECTIVE: This study aimed to systematically review the literature on catatonia and the related condition of neuroleptic malignant syndrome (NMS) in patients with cerebral palsy while presenting 2 additional cases of catatonia. METHODS: We used the terms "cerebral palsy" in combination with "catatoni∗," related terms for catatonia, and "neuroleptic malignant syndrome" to query Ovid MEDLINE (1948 to November 28, 2022), PsycINFO, Cumulative Index to Nursing, and Allied Health Literature, and Embase for applicable case reports. The Neuroleptic Malignant Syndrome Information Service database was also manually searched. RESULTS: In addition to our 2 catatonia reports, we identified 10 reports of catatonia in patients with cerebral palsy, as well as 8 reports of NMS. Patients with both conditions responded well, and sometimes rapidly, to treatment. Notably, of the 5 patients with catatonia and cerebral palsy who received electroconvulsive therapy, 2 developed recurrent self-limited hyperthermia posttreatment. We also identified several cases of baclofen withdrawal, which can be life threatening because of seizure risk, presenting with NMS-like features in patients with cerebral palsy who had malfunctioning intrathecal baclofen pumps for spasticity management. CONCLUSIONS: Given frequent comorbidity of conditions associated with catatonia in patients with cerebral palsy, as well as routine treatment with medications that can induce NMS, such as metoclopramide and anticholinergics, catatonia and NMS may be underreported in the cerebral palsy patient population, despite being highly treatable. Possible underdiagnosis of catatonia in patients with cerebral palsy may be because of misattribution of overlapping features between the 2 conditions to cerebral palsy. Clinicians should be aware of possible recurrent self-limited fever when using electroconvulsive therapy to treat patients with catatonia and cerebral palsy while also being vigilant for intrathecal baclofen withdrawal when encountering NMS-like features in patients with cerebral palsy.