Ketamine for major depressive disorder during an inpatient psychiatric admission: Effectiveness, adverse events, and lessons learned.

OBJECTIVE: Most studies examining the efficacy of ketamine for Major Depressive Disorder (MDD) have been conducted in outpatient or mixed inpatient/outpatient settings. Less is known about effectiveness and tolerability of ketamine for psychiatrically hospitalized patients. Efficacy and tolerability data from a naturalistic sample of acute inpatients may help inform institutions considering ketamine therapy for inpatient services. METHODS: We performed a retrospective chart review of inpatients with non-psychotic MDD treated during the initial 3 years of a ketamine infusion program. Treatment effectiveness was defined using change in Montgomery Asberg Depression Rating Scale (MADRS) scores over five infusions. MDD treatment response was defined by a 50 % reduction of MADRS score, and remission was defined as MADRS score ≤ 10 at any point during the treatment. We also report the frequency of adverse events. RESULTS: 41 patients with MDD were treated and had outcome data. 19 patients (46.5 %) met criteria for response and 15 patients (26.5 %) met criteria for remission during treatment. Four patients (10 %) had adverse psychological or behavioral outcomes. LIMITATIONS: MADRS scales were administered by psychiatrists, psychologists, and trainees in each discipline who did not undergo standardized training in scale administration. Consistent data regarding the race/ethnicity of the patients was not available. CONCLUSION: Twice weekly racemic ketamine infusion is an effective treatment option for patients hospitalized with MDD. Unmonitored or at home ketamine therapy may pose substantial risks.

Low COVID-19 Vaccination Rates Among Psychiatric Inpatients: Implications for Institutional Settings and Outreach Efforts.

OBJECTIVE: This study sought to determine COVID-19 vaccination rates for individuals with serious mental illness admitted to a large health system in New York State. METHODS: Vaccination rates among 12,714 patients admitted to psychiatric units and to medical and surgical units were compared between April 6, 2021, and September 30, 2021. RESULTS: Only 40% (N=416 of 1,029) of patients admitted to psychiatric services had at least one COVID-19 vaccination, whereas 64.4% (7,523 of 11,685) of patients admitted to medical and surgical services had at least one vaccination. After adjustment for differences in key demographic and clinical characteristics, patients admitted to psychiatric services had a significantly lower likelihood of vaccination during the study period (risk ratio=0.78, 95% confidence interval=0.73-0.85, p<0.001). Black psychiatric patients had the lowest vaccination rate (28%). CONCLUSIONS: Psychiatric patients with acute illness had low COVID-19 vaccination rates. Targeted outreach for COVID-19 vaccination is necessary to reach this population.

Inpatient psychiatry response to the SARS-CoV-2 Omicron variant surge.

The increased transmissibility of the omicron variant of the SARS-CoV-2 virus resulted in a rapid increase in infection among many psychiatric inpatients in our hospital between December 2021 and February 2022. This required our institution to close affected units to new admissions. In response, we implemented a model utilizing universal SARS-CoV-2 polymerase chain reaction (PCR) testing at the time of admission, the development of "admitting units" where all patients were quarantined for four days followed by repeat PCR testing, and subsequent transition to COVID-19 negative and COVID-19 positive "receiving units" based on the results of the second test. No unit closures occurred following full implementation of the model.

Universal COVID-19 testing and a three-space triage protocol is associated with a nine-fold decrease in possible nosocomial infections in an inpatient psychiatric facility.

In May of 2020, the Substance Abuse and Mental Health Service Administration (SAMSA) issued guidelines for state psychiatric hospitals, recommending that these facilities adopt universal testing for COVID-19 and "three-space" triage protocols for dedicated COVID-19 positive, negative, and quarantine spaces to mitigate the risk of nosocomial infection. The Westchester Behavioral Health Center of New York Presbyterian Hospital (WBHC-NYP) adopted a comprehensive infection control protocol consistent with these recommendations in April, 2020. We reviewed the records of 1,139 patients treated on the inpatient service at WBHC-NYP between March 14th and June 10th, 2020, dates corresponding to the first COVID-19 surge in the New York City metropolitan region. The incidence of detected nosocomial or possible nosocomial infections before and during the implementation of the protocol was 0.096 (16/167), or 0.96 infections per 10 at-risk patients. The incidence of nosocomial or possible nosocomial infections after complete implementation was 0.0110 (2/182), or 1.1 infections per 100 at-risk patients. The difference in incidence between the two time points was statistically significant (p<.0003) and represents a 9-fold decrease.  Our findings support the institutional use of a combined testing and space allocation protocol to mitigate risk of outbreaks in confined settings.

Illness stage and predominant polarity in bipolar disorder: Correlation with burden of illness and moderation of treatment outcome.

Bipolar disorder often follows a set progression best described in stages where advanced stages are associated with poorer outcomes. Bipolar disorder is also often characterized by a predominance of episode polarity, where some individuals experience more depressive episodes (termed predominant depressive polarity) while others experience more hypo/manic episodes (termed predominant hypo/manic polarity). We examined the associations between staging and predominant polarity with measures of illness burden and treatment outcome utilizing data from a six-month comparative effectiveness trial of lithium and quetiapine in bipolar disorder (Bipolar CHOICE). We used number of self-reported lifetime mood (depressive and hypo/manic) episodes as a proxy for staging and ratio of depressive to manic episodes to define predominant polarity. Polarity and staging were correlated with several measures of burden of illness. Childhood abuse was correlated with more lifetime mood episodes, while more depressive episodes and depressive polarity were correlated with more anxiety disorder comorbidity. Depressive polarity was also correlated with more past trials of psychotropics, particularly antidepressants. However, neither staging nor predominant polarity moderated the randomized treatment effect of lithium vs. quetiapine. Number of depressive episodes in the past year was identified as a potential predictor of overall worse treatment outcome, regardless of medication condition. In conclusion, though staging and predominant episode polarity correlated with several measures of illness burden, they were not associated with differential treatment outcomes. This could be because many of our patients presented for treatment at advanced stages of illness and further highlights the need for early intervention in bipolar disorder.

COVID-19 infection rates in patients referred for psychiatric admission during a regional surge: The case for universal testing.

Some psychiatric hospitals have instituted mandatory COVID-19 testing for all patients referred for admission. Others have permitted patients to decline testing. Little is known about the rate of COVID-19 infection in acute psychiatric inpatients. Characterizing the proportion of infected patients who have an asymptomatic presentation will help inform policy regarding universal mandatory versus symptom-based or opt-out testing protocols. We determined the COVID-19 infection rate and frequency of asymptomatic presentation in 683 consecutively admitted patients during the surge in the New York City region between April 3rd, 2020 and June 8th, 2020. Among these psychiatric inpatients, there was a 9.8 % overall rate of COVID-19 infection. Of the COVID-19 infected patients, approximately 76.1 % (51/67) either had no COVID-19 symptoms or could not offer reliable history of symptoms at the time of admission. Had they not been identified by testing and triaged to a COVID-19 positive unit, they could have infected others, leading to institutional outbreak. These findings provide justification for psychiatric facilities to maintain universal mandatory testing policies, at least until community infection rates fall and remain at very low levels.

A COVID-19 testing and triage algorithm for psychiatric units: One hospital's response to the New York region's pandemic.

Psychiatric patients are at high risk for contracting COVID-19, and inpatient psychiatric units face substantial risks of institutional outbreaks. Here, the authors describe an algorithm for testing and triage in a large psychiatric facility designed to prevent local COVID-19 transmission. The algorithm is based on expert opinion and clinical experience between March and April of 2020, during which the institution cared for 47 COVID-19 positive psychiatric inpatients. The implementation of the algorithm is designed to mitigate COVID-19 transmission, preserve the safest and least restrictive treatment environment for psychiatric inpatients, and provide a model adaptable to other institutional settings.

Bipolar depression and suicidal ideation: Moderators and mediators of a complex relationship.

INTRODUCTION: Not all patients with bipolar depression have suicidal ideation (SI). This study examines some factors that link bipolar depression to SI. METHODS: 482 individuals with bipolar I or II were randomized to either lithium or quetiapine plus adjunctive personalized therapy in a 24 week comparative effectiveness trial. Severity of depression and SI were assessed with the Bipolar Inventory of Symptoms Scale (BISS). We examined potential moderators (age, gender, age of illness onset, bipolar type, comorbid anxiety, substance use, past suicide attempts, childhood abuse and treatment arm) and mediators (severity of anxiety, mania, irritability, impairment in functioning (LIFE-RIFT) and satisfaction and enjoyment of life (Q-LES-Q)) of the effect of depression on SI. Statistical analyses were conducted using generalized estimating equations with repeated measures. RESULTS: Bipolar type and past suicide attempts moderated the effect of depression on SI. Life satisfaction mediated the effect of depression and SI. The relationship between anxiety, depression and SI was complex due to the high level of correlation. Treatment with lithium or quetiapine did not moderate the effect of depression on SI. LIMITATIONS: Suicide assessment was only done using an item on BISS. Patient population was not specifically chosen for high suicide risk. DISCUSSION: Individuals with Bipolar II experienced more SI with lower levels of depression severity. A history of suicide predisposed patients to higher levels of SI given the same severity of depression. Reduced life satisfaction mediates the effect of depression on SI and may be a target for therapeutic interventions.

A double-blind pilot dosing study of low field magnetic stimulation (LFMS) for treatment-resistant depression (TRD).

BACKGROUND: Low field magnetic stimulation is a potentially rapid-acting treatment for depression with mood-enhancing effects in as little as one 20-min session. The most convincing data for LFMS has come from treating bipolar depression. We examined whether LFMS also has rapid mood-enhancing effects in treatment-resistant major depressive disorder, and whether these effects are dose-dependent. OBJECTIVE/HYPOTHESIS: We hypothesized that a single 20-min session of LFMS would reduce depressive symptom severity and that the magnitude of this change would be greater after three 20-min sessions than after a single 20-min session. METHODS: In a double-blind randomized controlled trial, 30 participants (age 21-65) with treatment-resistant depression were randomized to three 20-min active or sham LFMS treatments with 48 h between treatments. Response was assessed immediately following LFMS treatment using the 6-item Hamilton Depression Rating Scale (HAMD-6), the Positive and Negative Affect Scale (PANAS) and the Visual Analog Scale. RESULTS: Following the 3rd session of LFMS, the effect of LFMS on VAS and HAMD-6 was superior to sham (F (1, 24) = 7.45, p = 0.03, Bonferroni-Holm corrected; F (1, 22) = 6.92, p = 0.03, Bonferroni-Holm corrected, respectively). There were no differences between sham and LFMS following the initial or second session with the effect not becoming significant until after the third session. CONCLUSIONS: Three 20-min LFMS sessions were required for active LFMS to have a mood-enhancing effect for individuals with treatment-resistant depression. As this effect may be transient, future work should address dosing schedules of longer treatment courses as well as biomarker-based targeting of LFMS to optimize patient selection and treatment outcomes.

Urinary Retention Associated With Cariprazine: A Case Report.

Urinary retention is a well-documented adverse effect of antipsychotic medications and is thought to be mediated by anticholinergic, adrenergic, and other neurotransmitter effects. Whereas urinary retention has been reported with typical and some atypical antipsychotics, there have been no reports of urinary retention with the novel antipsychotic cariprazine. We report on a case of urinary retention associated with cariprazine. Possible mechanisms for this adverse effect are discussed.

Assessing Decision Making Capacity for Do Not Resuscitate Requests in Depressed Patients: How to Apply the "Communication" and "Appreciation" Criteria.

The Patient Self Determination Act (PSDA) of 1991 brought much needed attention to the importance of advance care planning and surrogate decision-making. The purpose of this law is to ensure that a patient's preferences for medical care are recognized and promoted, even if the patient loses decision-making capacity (DMC). In general, patients are presumed to have DMC. A patient's DMC may come under question when distortions in thinking and understanding due to illness, delirium, depression or other psychiatric symptoms are identified or suspected. Physicians and other healthcare professionals working in hospital settings where medical illness is frequently comorbid with depression, adjustment disorders, demoralization and suicidal ideation, can expect to encounter ethical tension when medically sick patients who are also depressed or suicidal request do not resuscitate orders.

Oxcarbazepine-induced liver injury after sensitization by valproic acid: a case report.

OBJECTIVE: The aim of the present case report is to describe a potential interaction between valproic acid and oxcarbazepine that resulted in hepatic injury. METHODS: We report the case of a 46-year-old man with schizoaffective disorder who was cross-titrated from valproic acid to oxcarbazepine because of liver injury. RESULTS: Initiation of oxcarbazepine four days after stopping valproic acid produced a significant elevation in liver enzymes that normalized with oxcarbazepine discontinuation and did not reappear with its reintroduction five days later. CONCLUSIONS: Our findings suggest that a longer washout period or another agent should be considered when transitioning from valproic acid to oxcarbazepine.

Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness): a pragmatic 6-month trial of lithium versus quetiapine for bipolar disorder.

BACKGROUND: Bipolar disorder is among the 10 most disabling medical conditions worldwide. While lithium has been used extensively for bipolar disorder since the 1970s, second-generation antipsychotics (SGAs) have supplanted lithium since 1998. To date, no randomized comparative-effectiveness study has compared lithium and any SGA. METHOD: Within the duration of the study (September 2010-September 2013), participants with bipolar I or II disorder (DSM-IV-TR) were randomized for 6 months to receive lithium (n = 240) or quetiapine (n = 242). Lithium and quetiapine were combined with other medications for bipolar disorder consistent with typical clinical practice (adjunctive personalized treatment [APT], excluding any SGA for the lithium + APT group and excluding lithium or any other SGA for the quetiapine + APT group). Coprimary outcome measures included Clinical Global Impressions-Efficacy Index (CGI-EI) and necessary clinical adjustments, which measured number of changes in adjunctive personalized treatment. Secondary measures included a full range of symptoms, cardiovascular risk, functioning, quality of life, suicidal ideation and behavior, and adverse events. RESULTS: Participants improved across all measures, and over 20% had a sustained response. Primary (CGI-EI, P = .59; necessary clinical adjustments, P = .15) and secondary outcome changes were not statistically significantly different between the 2 groups. For participants with greater manic/hypomanic symptoms, CGI-EI changes were significantly more favorable with quetiapine + APT (P = .02). Among those with anxiety, the lithium + APT group had fewer necessary clinical adjustments per month (P = .02). Lithium was better tolerated than quetiapine in terms of the burden of side effects frequency (P = .05), intensity (P = .01), and impairment (P = .01). CONCLUSIONS: Despite adequate power to detect clinically meaningful differences, we found outcomes with lithium + APT and quetiapine + APT were not significantly different across 6 months of treatment for bipolar disorder. TRIAL REGISTRATION: ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304.

Perspectives on depression--past, present, future(a).

Depression presents a wide canvas for considering some approaches, issues, and problems in the study of major categories of mental illness in the context of current behavioral and molecular neurobiology. The study of depression encompasses multiple interactions among psychiatry, neurology, and neuroscience, as well as interactions with a host of other disciplines. This paper considers issues from an American perspective and discusses topics including historical aspects of the ways humanity has struggled with depression; the growth of approaches, and the "wars" in psychiatry in the middle of the 20th century between different ideologies; the development of psychiatry as a behavioral science inclusive of many disciplines; current diagnostic systems such as the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) of the American Psychiatric Association, and the ICD-10 Classification of Mental and Behavioral Disorders of the World Health Organization; the efforts to delineate subtypes of depression; the search for new neurobiological and behavioral targets in the context of the National Institute of Mental Health's Research Domain Criteria framework; and examples of potential future discoveries and disciplines that may ultimately improve treatment.

Psychotherapy use in bipolar disorder: Association with functioning and illness severity.

OBJECTIVE: This study examines characteristics of individuals with bipolar disorder who sought psychotherapy versus those who did not. METHODS: Bipolar CHOICE was an 11-site comparative effectiveness study of lithium versus quetiapine in symptomatic outpatients (N = 482) with bipolar disorder. At baseline, participants' psychotherapy use within the past 3 months, mood, functioning, and overall health were assessed. Logistic regressions were used to test whether psychotherapy users and non-users differed on various demographic and clinical variables at baseline. Mixed-effects regression was used to determine whether psychotherapy groups differed on response to treatment over the 6-month study. Kaplan-Meier plots and log-rank tests were employed to test whether there were any differences in time to recovery (CGI-BP ≤ 2 for at least 8 weeks) between the groups. RESULTS: Thirty one percent of participants reported using psychotherapy services. Psychotherapy users reported greater medication side effect burden than non-users and were more likely to have moderate to high suicide risk and at least one anxiety disorder. Participants not utilizing medications or psychotherapy had greater mania symptom severity, were younger, and less educated than medication only users. Medication only users were more likely to be married than the other participants. CONCLUSIONS: These data suggest that a minority of individuals with bipolar disorder attend psychotherapy services, and those that do have greater illness burden.

Medical burden in bipolar disorder: findings from the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE).

OBJECTIVES: Individuals with bipolar disorder have high rates of other medical comorbidity, which is associated with higher mortality rates and worse course of illness. The present study examined common predictors of medical comorbidity. METHODS: The Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder study (Bipolar CHOICE) enrolled 482 participants with bipolar I or bipolar II disorder in a six-month, randomized comparative effectiveness trial. Baseline assessments included current and lifetime DSM-IV-TR diagnoses, demographic information, psychiatric and medical history, severity of psychiatric symptoms, level of functioning, and a fasting blood draw. Medical comorbidities were categorized into two groups: cardiometabolic (e.g., diabetes, hyperlipidemia, and metabolic syndrome) and non-cardiovascular (e.g., seizures, asthma, and cancer). Additionally, we looked at comorbid substance use (e.g., smoking and drug dependence). RESULTS: We found that 96.3% of participants had at least one other medical comorbidity. Older age predicted a greater likelihood of having a cardiometabolic condition. Early age of onset of bipolar symptoms was associated with a lower chance of having a cardiometabolic condition, but a greater chance of having other types of medical comorbidity. Additional predictors of other medical comorbidities in bipolar disorder included more time spent depressed, less time spent manic/hypomanic, and longer duration of illness. Medications associated with weight gain were associated with low high-density lipoprotein and abnormal triglycerides. CONCLUSIONS: There appears to be a substantial medical burden associated with bipolar disorder, highlighting the need for collaborative care among psychiatric and general medical providers to address both psychiatric and other medical needs concomitantly in this group of patients.