Vitamin B12 Supplementation in Psychiatric Practice.

PURPOSE OF REVIEW: Vitamin B12 (B12, cobalamin) deficiency has been associated with neuropsychiatric symptoms, suggesting a role for B12 supplementation both as a treatment for psychiatric symptoms due to B12 deficiency and as an augmentation strategy for pharmacological treatments of psychiatric disorders. This critical review discusses the major causes of B12 deficiency, the range of psychiatric and non-psychiatric manifestations of B12 deficiency, the indications for testing B12 levels, and the evidence for B12 supplementation for major psychiatric disorders. RECENT FINDINGS: We find that high-quality evidence shows no benefit to routine B12 supplementation for mild depressive symptoms or to prevent depression. There is very limited evidence on the role of B12 supplementation to augment antidepressants. No high-quality evidence to date suggests a role for routine B12 supplementation in any other major psychiatric disorder. No formal guidelines indicate when clinicians should test B12 levels for common psychiatric symptoms, in the absence of major risk factors for deficiency or cardinal symptoms of deficiency. No robust evidence currently supports routine B12 supplementation for major psychiatric disorders. However, psychiatrists should be aware of the important risk factors for B12 deficiency and should be able to identify symptoms of B12 deficiency, which requires prompt testing, medical workup, and treatment. Testing for B12 deficiency should be considered for atypical or severe psychiatric presentations.

Lifetime prevalence, comorbidities, and Sociodemographic predictors of post-traumatic stress disorder (PTSD): the National Epidemiology of Iranian Children and adolescents Psychiatric disorders (IRCAP).

OBJECTIVE: The aims of this study were to (a) evaluate the lifetime prevalence of post-traumatic stress disorder (PTSD) according to sociodemographic characteristics, (b) determine sociodemographic factors associated with PTSD, (c) estimate the lifetime prevalence rates of comorbidities by age and gender, and (d) assess the proportion of traumatic events in the non-PTSD sample and the PTSD sample, according to gender. METHODS: The data used for the present study were obtained from the IRCAP study which was a cross-sectional, community-based study on 29,250 children and adolescents aged 6-18 years from all provinces of Iran, which was done using multistage cluster sampling. Trained psychologists conducted diagnostic interviews with parents, children, and adolescents using the Persian version of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). RESULTS: In this study, the prevalence of PTSD across the sample population was 0.6% (95% CI, 0.5-0.7%). Higher rates of PTSD were observed among girls (0.7%, CI 0.5-0.8%), adolescents aged 15-18 years (0.8%, CI 0.6-1.0%), and participants who had unemployed (1.5%, CI 0.8-2.8%), or farmer fathers (1.1%, CI 0.5-2.5%). Of the participants with PTSD, 65.1% met the criteria for at least one other psychiatric disorder. PTSD had a high rate of comorbidity with oppositional defiant disorder (22.9%, CI 17.5-29.4%), generalized anxiety disorder (20.8%, CI 15.7-27.1%), separation anxiety disorder (20.3%, CI 15.2-26.6%), and major depressive disorder (19.8%, CI 14.8-26.0%). We found 9.5% of non-PTSD sample experienced at least one traumatic event. Witness to domestic violence was the most common traumatic event experienced by 32.8% of PTSD sample. CONCLUSION: Our results in the prevalence, comorbidities, and sociodemographic factors associated with PTSD supported findings of previous studies that used a structured diagnostic interview. It is recommended to use purposive sampling and to investigate comorbidities of PTSD and type of traumatic events in a large clinical population.

Antipsychotic agents in anxiety disorders: An umbrella review.

BACKGROUND: Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety disorders. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs. OBJECTIVE: The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other nonantipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO (CRD42021237436). METHODS: An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale. RESULTS: The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta-analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared with first-line treatments for anxiety disorder there was insufficient evidence due to flawed study designs (such as problems with randomization) and small sample sizes within studies. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD). CONCLUSIONS: This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety disorders, FGAs and SGAs may have risks and side effects that outweigh their efficacy, although there were limited data. Further long-term and larger-scale studies of antipsychotics in anxiety disorders are needed.

Psychedelics, With a Focus on Psilocybin: Issues for the Clinician.

There has been a burgeoning interest in psychedelics among the public, state legislatures, psychiatrists and other clinical providers, and within the research community. Increasing numbers of studies evaluating psychedelics for depression, anxiety, posttraumatic stress disorder, and substance use disorders have been conducted or are underway. While discussing psychedelics in general, the focus of this paper is on psilocybin and its mechanism, how it exerts a psychedelic effect, dosing, and a review of the treatment studies of psilocybin, which were primarily for treatment-resistant depression and cancer-related anxiety. Future directions and potential limitations of studying and regulating psilocybin and other psychedelics are also discussed.

Commentary: Mania in Medically Ill Patients.

Patients may present with manic symptoms in medical settings such as emergency rooms and on inpatient medical floors, leading to psychiatric consultation to try to determine the etiology of the symptoms. It is crucial to clarify whether the mania is secondary to a medical illness or whether the patient's symptoms are from a primary bipolar disorder. In this issue, we publish 2 case reports of patients presenting with manic symptoms in medical settings. The first case involves polymicrogyria in the frontal lobe of the brain as a cause of secondary mania. The second case involves a patient who was previously diagnosed with bipolar disorder and subsequently developed symptoms of Behçet's disease. In this case, it appears likely that the bipolar disorder was primary, and that the Behçet disease and the bipolar disorder may have exacerbated each other. Given the complexities involved in assessing and treating patients, especially in acute or emergency settings, it is important for primary medical and psychiatric providers to collaborate and communicate well in assuring that they obtain a thorough history of their patients' symptoms and that patients receive a comprehensive medical evaluation before psychiatric treatment is started.

Disparities in program enrollment and employment outcomes for veterans with psychiatric and co-occurring substance use disorders referred or enrolled for VHA vocational rehabilitation.

Introduction: The purpose of the study was to investigate factors that influence vocational rehabilitation program enrollment and employment at discharge of veterans with psychiatric and co-occurring alcohol and other substance use disorders enrolled at a veteran health administration (VHA) medical center. Methods: A sample of 2,550 veteran patients referred for VHA vocational rehabilitation between 2016 and 2021 were examined for the current study. The current study was classified as quality improvement/assurance, thus resulting in exempt research by the U.S. Department of Veteran Affairs Institutional Review Board. Results: Veterans with active alcohol use disorders (AUDs) and co-occurring depression, anxiety, post-traumatic stress disorder, or bipolar disorders were less likely to be enrolled for vocational rehabilitation program services compared to those without these co-occurring diagnoses. Veterans with AUD (active & in-remission status combined into one category) and a diagnosis of anxiety were less likely to be employed at discharge compared to veterans with AUDs and no anxiety diagnosis (anxiety diagnosis - 3.5% vs. no anxiety diagnosis - 5.8%). Discussion: VHA vocational rehabilitation can be an effective intervention to assist veterans in reintegrating back into the community. Yet, there appears to be some disparities in the program enrollment and employment at discharge, depending on the nature of the psychiatric diagnosis. Investigating the factors contributing (mediating or moderating) to these discrepancies are needed. Although it appears access is not the issue in being referred for vocational rehabilitation services, other factors are likely contributing to program entry.

Commentary: Psychiatric Symptoms Related to Somatic Illness.

Although hallucinations, particularly auditory hallucinations, are most commonly associated with psychotic disorders such as schizophrenia, patients experiencing visual and even auditory hallucinations may actually have an underlying somatic illness that is causing the symptoms. This commentary discusses 2 cases of hallucinations due to nonpsychiatric causes, including a case of a semicircular canal dehiscence causing auditory hallucinations and a case of visual hallucinations in Charles Bonnet syndrome caused by hypertensive episodes. When patients with no history of psychosis present with hallucinations, it is crucial that medical providers perform a full evaluation, including an assessment of the patient's psychiatric history. This is especially important when a patient with no history of psychosis presents later in life with hallucinations without other psychotic symptoms such as disorganization or delusions or other signs of a thought disorder, or when a patient presents with visual hallucinations without auditory hallucinations. Psychiatric consultation services can assist patients and their medical teams in arriving at the proper diagnosis.

Commentary: Futility in Psychiatry.

While other medical professions have grappled with end-of-life care, the areas of palliative psychiatry, and more particularly, futility in psychiatry, have not been thoroughly addressed. The 3 cases presented in this issue illustrate how patients can succumb to a medical condition while presenting with primary psychosis (a patient with treatment-resistant schizophrenia who starves himself), secondary psychosis (a patient with small cell cancer of the lung who develops psychotic symptoms in the context of a paraneoplastic neurological syndrome), or a factitious disorder (a patient with self-induced aplastic anemia from ingesting an oral chemotherapy agent). The descriptions of these challenging cases show how collaborative teamwork among psychiatric and medical treatment teams, including the provision of palliative care, can help patients and families, even if a fatal outcome appears certain.

Impact of substance use disorders on employment for veterans.

Approximately 1.1 million veterans meet criteria for substance use disorders (SUDs) with 1 in 4 struggling with illicit drugs, 4 in 5 struggling with alcohol use, and 1 in 13 struggling with both. The purpose of this study was to examine the impact of SUDs on closure status (exiting with employment, did not exit with employment) for veterans served in a Department of Veterans Affairs' Veterans Health Administration (VHA) vocational rehabilitation (VR) program. Data (N = 2,620) from a VHA VR program in the Veterans Integrated Service Network 12 network were obtained for the purpose of the present study and consisted of veterans enrolled from 2012 to 2018. Findings showed that veterans without SUDs were more likely to exit with employment, and veterans enrolled in transitional work and community-based employment were more likely to exit with employment compared to those within supported employment (SE). Given that SE helps to serve veterans with the most severe psychological or medical conditions (e.g., active psychosis, schizophrenia, bipolar disorder, spinal cord injury, traumatic brain injury), findings suggest veterans are more successful with less serious mental health conditions. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

An umbrella review on the use of antipsychotics in anxiety disorders: A registered report protocol.

Anxiety disorders, including panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), agoraphobia, and specific phobia, are among the most common psychiatric disorders. Although the traditional pharmacologic treatments for anxiety included barbiturates and then benzodiazepines, the introduction of tricyclic antidepressants, followed by the selective serotonin reuptake inhibitors (SSRIs), marked a tidal shift in the treatment of anxiety. Although not approved for treatment of anxiety disorders (with the exception of trifluoperazine) there is ongoing off-label, unapproved use of both first-generation "typical" antipsychotics (FGAs) and second-generation or "atypical" antipsychotics (SGAs) for anxiety. Although there have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of these reviews focused on SGAs, primarily the use of quetiapine in GAD. Given that there is little known about the potential benefits and short-and long-term risks of using antipsychotics in anxiety, there is a need for an umbrella review of systematic reviews and meta-analyses of the use of both FGAs and SGAs in anxiety disorders. The specific aims of this study are as follows: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to SSRIs, serotonin norepinephrine reuptake inhibitors (SNRIs) and other non-antipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects; and (3) Evaluate the short- and long-term risks and side effects of prescribing antipsychotics in anxiety disorders. The review is registered on PROSPERO (CRD42021237436). Since data extraction has not begun, there is not preliminary data to share.

Commentary: Diagnostic Challenges.

The 3 cases presented in this issue highlight diagnostic challenges in evaluating and treating patients with complicated presentations. The first case involved a man with mild neurocognitive disorder due to Alzheimer disease accompanied by depressive and anxiety symptoms and what appeared to be previously undiagnosed attention-deficit/hyperactivity disorder. The second case involved an unusual case of shared psychotic disorder involving a woman with a primary diagnosis of bipolar disorder and her husband with posttraumatic stress disorder. The third case involved a patient with a history of multiple diagnoses who presented with catatonic symptoms, obsessive-compulsive disorder characterized by religious scrupulosity, and some features of obsessive-compulsive personality disorder. These reports illustrate the challenges in evaluating and treating patients whose clinical presentations may not fit neatly into a diagnostic category or that have a nontraditional presentation.

An exploratory study of anxiety-motivated gambling in adolescents: Associations with minority status and gambling, health and functioning measures.

Gambling and anxiety are major public health concerns in adolescents and have been linked to emotion dysregulation and mood-modulating behaviors. While previous studies have shown links between positively reinforcing excitement-motivated gambling, health and functioning measures, and gambling perceptions and behavioral correlates in adolescents, few studies have examined such relationships relative to negatively reinforcing anxiety-motivated gambling (AMG). This study systematically examined relationships between adolescents reporting gambling to relieve anxiety (compared to those who gambled but did not report AMG) and measures of health/functioning and gambling-related measures. Participants included 1,856 Connecticut high-school students. Chi-square and logistic regression models were conducted. AMG was reported by 6.41% of the sample and was associated with identifying with a minority group (Black, Asian-American, Hispanic), at-risk/problem gambling, more permissive attitudes towards gambling, and higher odds of heavy alcohol, tobacco and other drug use, and violence-related measures. Adolescents with AMG were more likely to report non-strategic gambling, and gambling to escape/relieve dysphoria and due to feeling pressure. Additional between-group differences were found for gambling types, locations, motivations, and partners. Together, AMG may represent a mood-modulating behavior indicative of multiple problematic concerns, suggesting that emotional dysregulation may be an important factor in understanding the relationship between anxiety, problem gambling, and risky behaviors in youth. Additionally, the negative reinforcing motivations to gamble to relieve anxiety may be relevant particularly to adolescents from underrepresented minority racial/ethnic groups, and the specific factors underlying this relationship warrant further investigation.

Development and validation of a new scale to measure chronic suicidal ideation: The Chronic Suicidal Ideation Inventory-5 (CSI-5).

OBJECTIVE: Little is known about characteristics that differentiate acute from chronic suicidal ideation. Studies have been hampered by the lack of a formal operational definition or measurement tool for chronic suicidal ideation (CSI). We sought to adapt a standardized measure of obsessive-compulsive thinking to rate chronic suicidal ideation in a mood disorder inpatient cohort. METHOD: We devised a novel self-report instrument, based on constructs related to obsessive-compulsive thinking and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), as applied to preoccupations with suicidal thoughts and their persistence over 24 months in a previously described cohort of 97 inpatients with mood disorder. Exploratory factor analysis and principal components analysis were used to establish the factor structure of the instrument, and Cronbach's alpha and McDonald's omega were calculated to determine internal consistency of the scale. RESULTS: Significant Pearson correlations with individual scale items and total CSI-5 scores were evident in relation to the 2-, 6-, 12- and 24-month periods preceding the index hospitalization. A one-factor solution explained 75% of the variance in total CSI-5 scores. Cronbach's alpha was 0.914, and McDonalds's omega was 0.916. CSI-5 scores were not significantly associated with current depression severity scores or actual past suicide attempts. CONCLUSIONS: This 5-item adaptation of Y-BOCS-type questions provides an internally consistent and reliable assessment of chronic suicidal ideation in patients with mood disorder. The integrated assessment of time occupied by suicidal thoughts, activity interference, associated distress, efforts to resist suicidal thoughts, and degree of control over suicidal thinking provides a cohesive framework for understanding chronic suicidal ideation.

Commentary: Treatment-resistant Depression: Considerations Related to ECT and Ketamine.

Treatment-resistant depression (TRD) may be responsive to interventions beyond antidepressants including brain stimulation such as electroconvulsive therapy (ECT) or to ketamine or esketamine, the latter of which is approved for TRD in an intranasal form. The 3 cases presented in this issue deal with an array of clinical considerations in treating patients with TRD, including the use of ECT in a patient with a history of liver transplantation, the use of heated yoga in a patient nonresponsive to ECT, and intranasal ketamine abuse in a patient with comorbid migraines. Gunther and colleagues described the case of a 73-year-old man who presented with a major depressive episode with psychotic features not responsive to medications 26 years after liver transplantation. Despite his past transplant and antirejection medications, the patient was cleared for ECT and received 9 bitemporal treatments with good response. Sakurai and colleagues reported the case of a 28-year-old woman with chronic TRD and multiple previous ECT treatments who had only a partial response to several antidepressants and maintenance ECT. She was evaluated and treated with a course of twice-weekly 90-minute heated yoga and experienced a remission of her depression. Finally, Rivas-Grajales and colleagues described a 52-year-old woman with recurrent TRD and chronic migraines who was receiving 2 antidepressants and migraine medication, who presented emergently with agitation and paranoia in the context of receiving intranasal ketamine from multiple providers, suggesting a pattern of misuse. Her symptoms abated despite her refusal of prescribed antipsychotics. These 3 cases highlight different challenges and complexities in treating patients with TRD. While ECT remains safe and effective, even in cases of organ transplantation, there is potential for the development of nonpharmacologic adjunctive treatments, such as heated yoga (which is under randomized study). And while eskatamine is an approved treatment for TRD, screening and ongoing monitoring is important to prevent misuse or abuse.

Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options.

(Appeared originally in Frontiers in Psychiatry 2020 Dec 23; 11:595584).

Intensive Dialectical Behavior Treatment for Individuals With Borderline Personality Disorder With and Without Substance Use Disorders.

Treatment of borderline personality disorder (BPD) with comorbid substance use disorder can be challenging due to symptom overlap and limited assessment methods. Preliminary evidence has shown promising effectiveness of dialectical behavioral therapy (DBT) for BPD with comorbid substance use disorders. The current study compared the benefits of a 28-day transitional DBT treatment program for individuals with BPD with and without substance use disorders through evaluating the changes in coping skills, generalized anxiety, and depression symptom scales at admission and discharge. A total of 76 patients were split into two groups: Group 1 consisted of individuals with BPD without substance use disorders (n = 41), and Group 2 involved individuals with BPD and a substance use disorder (SUD) (n = 35). A univariate general linear model showed significant differences between the two groups in improvement of coping skills and depressive symptoms. After a 28-day transitional DBT treatment program there were significant decreases from severe to moderate depression scores in both groups. Our findings support the effectiveness of DBT treatment in patients with comorbid BPD and SUD.

Selective Serotonin Reuptake Inhibitors: How Long Is Long Enough?

Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed medications. They are among the first-line medications for several chronic or relapsing-remitting psychiatric conditions, including major depressive disorder and anxiety disorders. The advantages of SSRI use include ease of titration and their tolerability and safety profile. Guidelines for the short-term use of SSRIs are widely available, but there is no well-organized guidance on how and whether to maintain a patient on SSRIs for the long-term. In this article, we discuss the benefits and possible adverse consequences of long-term SSRI use, as well as clinical practice considerations when using SSRIs chronically. The major benefit of long-term SSRI use is relapse prevention. The current literature suggests that the general health risks of long-term SSRI use are low; however, further research, particularly in special populations including youth and the elderly, is needed. Long-term SSRI use increases the risk of tachyphylaxis and discontinuation syndrome. Recognizing that many patients may remain on SSRIs for many years, there are several factors that prescribers should consider if they choose to use an SSRI when initiating treatment and during long-term monitoring. The decision to continue or to discontinue an SSRI should be an active one, involving both the patient and prescriber, and should be revisited periodically. Patients who remain on SSRIs for the long-term should also have periodic monitoring to reassess the risk-benefit ratio of remaining on the SSRI, as well as to assess the safety, tolerability, and efficacy of the medication.

Commentary: Psychiatric Presentations of Nonpsychiatric Illness or Treatment.

Patients presenting with psychiatric symptoms, even in cases where there is no clear psychiatric history, are often labeled as having "psychogenic" symptoms or a psychosomatic reaction, and a tendency does exist to mislabel and/or misdiagnose certain patients in medical settings. The 3 cases presented in this issue of the Journal provide examples of patients presenting with psychotic or manic symptoms in the context of an underlying nonpsychiatric medical disorder. Kim and colleagues describe the case of a 65-year-old man with no psychiatric history who presented with acute visual hallucinations 1 day after starting omeprazole for gastroesophageal reflux. The visual hallucinations resolved immediately after the medication was stopped. Fipps and Rainey describe the case of a 74-year-old man with chronic generalized anxiety who presented with severe panic and suicidal thinking as well as refractory nausea that were unresponsive to benzodiazepine treatment and to a taper of the benzodiazepine. This patient was later found to have a subdural hematoma that was causing what had at first been suspected to be psychogenic nausea. Finally, Das and Brasseux present the case of a 23-year-old man hospitalized from jail who presented with manic symptoms; this patient was found to have had a traumatic brain injury 2 months earlier and, on brain imaging, was also found to have had a perinatal brain injury. The patient responded to mood stabilizers and the off-label use of memantine for his cognitive deficits. These 3 cases highlight the importance of obtaining a comprehensive neurological and medical history and, if indicated, workup, in cases involving patients with atypical presentations or nonresponse to traditional treatments.