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 After 38 patients had withdrawn before initiation of the assigned treatment, ketamine was administered to 195 patients and ECT to 170 patients.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.).

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 Survey of American Psychiatrists Concerning Medication Prior Authorization Requirements.

This study examined opinions of American psychiatrists regarding prior authorization (PA) requirements for third-party payer coverage of medications and quantified perceived impact of these requirements on clinical practice. One thousand selected psychiatrist members of the American Psychiatric Association were invited to participate in a survey. Response rate was 33.1%. Respondents predominantly believed the obligation to obtain PA reduces job satisfaction and negatively impacts patient care. A total of 59.9% of respondents reported employing either diagnosis modification or falsification of previous medication trials at least occasionally in order to obtain PA. A total of 66.6% refrained at least occasionally from prescribing preferred medications due to PA requirement or expectation of one. On multivariate analysis, risk factors for refraining at higher frequency included seeing 300 or more patients in the previous 3 months, engaging more frequently in diagnosis modification, and reporting increased perception that obtaining PA reduces time for patient care.

Risk factors for readmission among a cohort of psychiatric inpatients in Lilongwe, Malawi.

Objectives: Inpatient psychiatric capacity is limited in Malawi and no published studies have assessed psychiatric readmissions there. Information about factors associated with readmission may help guide strategies to reduce readmission rates and keep patients stabilised in the community. Our goal was to determine factors associated with readmission among a cohort of psychiatric inpatients in Lilongwe, Malawi.Methods: We conducted a retrospective chart review of all patients admitted to an inpatient psychiatric unit in Lilongwe, Malawi from January 1 to December 31, 2011. We used logistic regression to test for associations between readmissions during the study period and patient variables.Results: 419 patients were hospitalised during the study period. Twenty-nine patients (6.9%) were readmitted at least once during the study period. Readmission was associated only with intentional medication non-adherence at home (aOR: 3.33, p = 0.02).Conclusions: Intentional medication non-adherence is a potentially modifiable behaviour associated with psychiatric readmission. Efforts to improve medication adherence among patients following hospital discharge may help decrease the risk of readmission.KEY POINTSThe prevalence of readmission among psychiatric inpatients in Lilongwe, Malawi was 6.9% during the 1-year study period.Readmission was associated with intentional medication non-adherence at home.Future research efforts in Malawi should focus on improving medication adherence among psychiatric patients in the community to help decrease rates of readmission.

Factors associated with long length of stay in an inpatient psychiatric unit in Lilongwe, Malawi.

PURPOSE: Studies of factors affecting length of stay during psychiatric hospitalization in sub-Saharan Africa are sparse. A better understanding of such factors may lead to interventions resulting in quicker patient stabilization and discharge, freeing up needed psychiatric beds and reducing health care system expenditures. Therefore, we sought to identify factors associated with long length of stay in Malawi. METHODS: We reviewed the charts of 417 patients hospitalized at Kamuzu Central Hospital's Bwaila Psychiatric Unit in Lilongwe, Malawi from January 1 to December 31, 2011. Multivariate logistic regression analysis was employed to test for associations between patient factors and long length of stay (defined as more than 28 days). RESULTS: Mean length of stay was 22.08 ± 27.70 days (range 0-243). 21.82% (91/417) of patients stayed longer than 28 days. Long length of stay was associated with living outside of Lilongwe district [aOR: 3.65 (1.66-8.01), p = 0.001] and treatment for antipsychotic extrapyramidal side effects (EPS) during hospitalization [aOR: 3.45 (1.32-9.03), p = 0.012]. Patients who had more interactions with medical providers for this episode of illness prior to presentation at the unit were less likely to have a long length of stay [aOR: 0.35 (0.16-0.76), p = 0.008]. CONCLUSIONS: Our findings demonstrate areas of possible intervention to reduce length of stay, including securing means for patient transport home, rapid identification and treatment of EPS, and reducing the risk of EPS by decreased use of high potency first-generation antipsychotics.

Rapid transition from methadone to buprenorphine using naltrexone-induced withdrawal: A case report.

Background: Patients taking methadone for opioid use disorder may desire transition to buprenorphine for a number of reasons. However, the current recommended approach for this transition generally takes weeks to months as an outpatient, causing considerable discomfort to the patient and a heightened risk of relapse during the transition period. Case: We describe the case of a patient on methadone maintenance who was rapidly transitioned to buprenorphine because of her desire to not return to her methadone clinic. In order to rapidly transition the patient from methadone to buprenorphine, naltrexone was administered to precipitate acute opioid withdrawal, which was followed soon after by buprenorphine induction. Discussion: Rapid transition from methadone maintenance to buprenorphine can be accomplished in inpatients by precipitating acute withdrawal with naltrexone, providing an effective alternative for patients who cannot tolerate the typical protracted methadone taper required prior to buprenorphine induction as an outpatient.

A Survey of American Psychiatrists' Attitudes Toward Classic Hallucinogens.

Recent years have seen renewed interest and research about the use of hallucinogens as possible agents in the treatment of psychiatric disorders. However, we are unaware of studies assessing the current attitudes of American psychiatrists regarding hallucinogens. Therefore, we e-mailed surveys to 1000 members of the American Psychiatric Association-250 resident-fellows and 750 attending psychiatrists. The response rate was 32.4%. Respondents tended to perceive hallucinogens as potentially hazardous and appropriately illegal for recreational purposes. However, a large minority expressed optimism about the potential use of hallucinogens for psychiatric treatment. Male and trainee respondents, as compared with female and attending respondents, reported less concern about the risks of hallucinogens and greater optimism about their therapeutic potential. Younger psychiatrists also seemed more optimistic. Optimism among trainees and younger psychiatrists may possibly reflect greater exposure to recent positive publications about hallucinogens and less awareness of more negative past reports.

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.

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.

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.

Bibliometric Analysis of Academic Journal Articles Reporting Results of Psychedelic Clinical Studies.

Following a decades long period of investigational dormancy, there is renewed interest in employing psychedelics as psychiatric treatments. The academic journals, institutions, and countries that have helped sustain clinical psychedelic research and the evolution of the literature on clinical studies of psychedelics have only recently begun to be investigated. To expand upon this work, we conducted a bibliometric analysis of clinical studies of 5-methoxy-N, N-dimethyltryptamine (5-MeO-DMT), ayahuasca, dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), ibogaine, mescaline, 3,4-methylenedioxymethamphetamine (MDMA), and psilocybin published from 1965-2021. Our search revealed 394 relevant articles. After a lull from the 1970s-1990s, publications in this area have resurged. Studies most frequently focused on MDMA (49%), LSD (19%), psilocybin (18%), and ayahuasca (7%). A subanalysis of studies from 1965 to 2009 ("Older cohort") compared to 2010-2021 ("Recent cohort") revealed that the Recent cohort had a higher proportion of studies investigating psychedelics' therapeutic applications and a lower proportion of studies investigating the effects of psychedelics on people using them in non-research settings. Compared to the Older cohort, psilocybin studies increased proportionally in the Recent cohort, while DMT and mescaline studies decreased. Network analyses of inter-country collaborations suggested that psychedelic researchers in the United Kingdom have the most diverse international collaborations.

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.

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.