The effect of older age on outcomes of rTMS treatment for treatment-resistant depression.

Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16-100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%-57%/25%-33%; <60: 32%-49%/18%-25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.

Foreseeably Early Deaths in Patients With Psychiatric Disorders: Challenges in Caring for Patients Manifesting Likely Fatal Trajectories.

ABSTRACT: Patients with psychiatric disorders often have foreshortened lives, attributed both to "natural" medical and "unnatural" external causes of death such as suicide, homicide, and accident. Many deaths are foreseeable due to circumstances linked to patients' psychiatric disorders. These can include illness-associated disparities, adverse treatment effects, lack of self-care, and behaviors stemming directly from psychopathological processes. Whereas some of these processes contribute indirectly to patients' causes of death, others are more directly consequential, causing patients to "die from" their psychiatric disorders. Some patients manifest likely fatal trajectories that may lead to "end-stage" psychiatric disorders. Palliative approaches may optimize their quality of life and potentially alter these trajectories, but patients with psychiatric disorders are less likely to receive optimal end-of-life care. Although assuring a "good death" can be challenging, systematic efforts can assist in providing patients with psychiatric disorders deaths with dignity rather than indignity.

Bilateral Cerebellar Repetitive Transcranial Magnetic Stimulation for Chronic Ataxia After Hemorrhagic Stroke: a Case Report.

There are insufficient treatment options available for recovery related to cerebellar ataxia. Limited data using repetitive transcranial magnetic stimulation (rTMS) have demonstrated reduction of symptom burden, though associated with nonuniform cerebellar ataxia etiologies and differing rTMS treatment protocols. Additionally, there are limited available data for use of rTMS in individuals suffering from stroke-related symptoms. We present the case of a patient with chronic cerebellar ataxia following a hemorrhagic stroke who underwent inhibitory rTMS to bilateral cerebellar targets with demonstrated improvement in symptoms.

A Medical Incapacity Hold Policy Reduces Inappropriate Use of Involuntary Psychiatric Holds While Protecting Patients From Harm.

BACKGROUND: The use of involuntary psychiatric holds (IPH) to detain patients who lack the capacity to make health care decisions due to nonpsychiatric conditions is common. While this practice prevents patient harm, it also deprives civil liberties, risks liability for false imprisonment, and may hinder disposition. Medical incapacity hold (MIH) policies, which establish institutional criteria and processes for detaining patients who lack capacity but do not meet criteria for an IPH, provide a potential solution. METHODS: A retrospective chart review was conducted on adult medical/surgical inpatients placed on an IPH or MIH over the 1-year periods before and after implementation of a MIH policy at an academic medical center. The primary outcome was frequency of IPH utilization in patients who did not qualify for an IPH as determined by 2 independent physician reviewers. A Cohen's kappa was calculated to determine inter-rater reliability. Differences in patient demographics and outcomes were compared using a Student's t-test, Wilcoxon rank-sum test, and Pearson chi-square test (α = 0.05). RESULTS: The Cohen's kappa was 0.72 indicating substantial agreement. Seventy MIHs were placed after implementation (mean duration 4.3 days). Before MIH implementation, 17.6% of IPHs were placed on non-qualifying patients, which decreased to 3.9% following MIH implementation (p < 0.01). The average length of stay for patients on an IPH or MIH did not change following MIH implementation. No instances of patient elopement, grievances, or litigation were found. CONCLUSION: MIH policies benefit both patients lacking capacity and the health care systems seeking to protect them while avoiding inappropriate use of IPHs.

The Medical Incapacity Hold: A Policy on the Involuntary Medical Hospitalization of Patients Who Lack Decisional Capacity.

BACKGROUND: Medically hospitalized patients who lack decisional capacity may request, demand, or attempt to leave the hospital despite grave risk to themselves. The treating physician in this scenario must determine how to safeguard such patients, including whether to attempt to keep them in the hospital. However, in many jurisdictions, there are no laws that address this matter directly. In this absence, psychiatrists are often called upon to issue an involuntary psychiatric hold (civil commitment) to keep the patient from leaving. Yet, civil commitment statutes were not intended for, and generally do not address, the needs of the medically ill patient without psychiatric illness. Civil commitment is permitted for patients who pose a danger to themselves or others, or who are gravely disabled, specifically as the result of a mental illness, and allows the transport of such individuals to facilities for psychiatric evaluation. It does not permit detention for medical illnesses nor the involuntary administration of medical treatments. Therefore, the establishment of hospital policies and procedures may be the most appropriate means of detaining medically hospitalized patients who lack capacity to understand the risks of leaving the hospital, in addition to mitigating the potential tort risk faced by the physician for acting in a manner that protects the patient. OBJECTIVE: The purpose of this article is to identify the array of clinical and medical-legal concerns in these scenarios, and to describe the development of a "medical incapacity hold" policy as a means of addressing this unresolved issue.

Sick and tired: mood, fatigue, and inflammation in cancer.

Cancer patients commonly experience depression and fatigue before, during, and after treatment. Symptoms can be debilitating, and the risks associated with unrecognized or inadequately treated depression are substantial. Inflammation may be important in the genesis of depression and fatigue in cancer patients; potential neurobiological mechanisms of inflammation-related behavioral symptoms are reviewed. Randomized studies of pharmacologic treatments for depression in cancer populations are limited, but available data are generally encouraging. Studies of pharmacologic treatments for cancer-related fatigue have been more numerous but with mixed results. A practical approach to pharmacologic treatment of depression and fatigue in cancer patients involves weighing the potential risks and benefits of specific agents, including potential for adverse or advantageous side effects. Progress in understanding the neurobiological mechanisms underlying inflammation-related behavioral symptoms will provide opportunities for the development of novel and targeted treatments.

Words Matter: Why Distinguishing Medical Aid in Dying From Suicide Should Matter to a Consultation-Liaison Psychiatrist.

As more and more American states legalize medical aid in dying (MAID), Consultation-Liaison Psychiatrists will increasingly be asked to assist medical and surgical colleagues in differentiating this end-of-life practice from suicide. Where suicide is traditionally understood as an act clouded by depression, desperation, or both, MAID represents a terminally medically ill patient's effort to take control of their dying process when death is imminent, likely to occur within 6 months, and inevitable. Rendering opinions on patient suicidality in the setting of a complex co-occurring medical illness is a Consultation-Liaison Psychiatrist's bread and butter. This paper seeks to elucidate 4 points that distinguish MAID from suicide: (1) Hastening death when the end of natural life is approaching is not synonymous with suicide in the vernacular American usage of the term. (2) Unlike suicide, MAID is a highly collaborative process in which dying, mentally capable adults involve their doctors and loved ones in legally recognized decisions to hasten death. (3) The clinical presentation of patients requesting MAID differs from that of individuals whose suicidality is driven by psychopathology. (4) Certain behavioral traits differentiate such MAID patients from suicidal ones. Understanding and applying these distinctions in the consultation-liaison arena will help remove the stigma of suicide from end-of-life care deliberations where it does not belong while ensuring appropriate end-of-life care for dying individuals for whom MAID is the culmination of a carefully considered process of self-determination rather than suicide.

The role of sex and age in the differential efficacy of 10 Hz and intermittent theta-burst (iTBS) repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD).

BACKGROUND: Sex- and age-dependent outcome differences have been observed in treatment of Major Depressive Disorder (MDD), including 10 Hz repetitive Transcranial Magnetic Stimulation (rTMS). We examined whether there are sex- and age-dependent differences in outcome with intermittent Theta Burst Stimulation (iTBS), another rTMS protocol. METHODS: The relationship between biological sex, age, and treatment outcome was retrospectively examined among 414 patients with MDD treated with 10 Hz or iTBS rTMS. Linear mixed-effects modeling was used to examine the association between treatment and change in the 30-item Inventory of Depressive Symptomatology Self-Report (IDS-SR30) score from baseline to treatments 10 and 30, with biological sex (M/F), protocol (iTBS/10 Hz), age (≥/<50 years old), and time (treatment 1/10/30) included as fixed effects. The three-way sex-protocol-time and age-protocol-time interactions were used to determine any differential relationships between protocol and outcome dependent on sex and age. Post-hoc t-tests were conducted to examine differences in improvement. RESULTS: There was a significant three-way sex-protocol-time interaction at treatments 10 (p = 0.016) and 30 (p = 0.031). Males showed significantly greater improvement with iTBS than females at treatments 10 (p = 0.041) and 30 (p = 0.035), while females showed numerically greater improvement with 10 Hz treatment. While there was not a significant three-way age-protocol-time interaction, there was a significant interaction between age (≥50 years old) and time at treatments 10 (p = 0.007) and 30 (p = 0.042), and among age, sex, and time at treatment 30 (p = 0.028). LIMITATIONS: Retrospective naturalistic treatment protocol. CONCLUSIONS: iTBS appeared less efficacious in females than in males, and rTMS overall was more efficacious in patients over fifty, particularly females.

Pretreatment pupillary reactivity is associated with outcome of Repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder (MDD).

BACKGROUND: Pre-treatment biomarkers for outcome of repetitive Transcranial Magnetic Stimulation (rTMS) treatment of Major Depressive Disorder (MDD) have proven elusive. One promising family of biomarkers involves the autonomic nervous system (ANS), which is dysregulated in individuals with MDD. METHODS: We examined the relationship between the pre-treatment pupillary light reflex (PLR) and rTMS outcome in 51 MDD patients. Outcome was measured as the percent change in the 30-item Inventory of Depressive Symptomatology Self Rated (IDS-SR) score from baseline to treatment 30. RESULTS: Patients showed significant improvement with rTMS treatment. There was a significant correlation between baseline pupillary Constriction Amplitude (CA) and clinical improvement over the treatment course (R = 0.41, p = 0.003). LIMITATIONS: We examined a limited number of subjects who received heterogeneous treatment protocols. Almost all patients in the study received psychotropic medications concomitant with rTMS treatment. CONCLUSION: PLR measured before treatment may be a predictive biomarker for clinical improvement from rTMS in subjects with MDD.

Pretreatment pupillary reactivity is associated with differential early response to 10 Hz and intermittent theta-burst repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD).

BACKGROUND: Repetitive Transcranial Magnetic Stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD). Two common rTMS protocols, 10 Hz and intermittent theta burst stimulation (iTBS), have comparable rates of efficacy in groups of patients. Recent evidence suggests that some individuals may be more likely to benefit from one form of stimulation than the other. The pretreatment pupillary light reflex (PLR) is significantly associated with response to a full course of rTMS using heterogeneous stimulation protocols. OBJECTIVE: To test whether the relationship between pretreatment PLR and early symptom improvement differed between subjects treated with iTBS or 10 Hz stimulation. METHODS: PLR was measured in 52 subjects who received solely 10 Hz (n = 35) or iTBS (n = 17) to left dorsolateral prefrontal cortex (DLPFC) for the first ten sessions of their treatment course. Primary outcome measure was the percent change of Inventory of Depressive Symptomatology - Self Report (IDS-SR) from session 1 to session 10. RESULTS: There was a positive association between normalized maximum constriction velocity (nMCV) and early improvement in subjects receiving 10 Hz stimulation (R = 0.48, p = 0.004) and a negative association in subjects receiving iTBS (R = -0.52, p = 0.03). ANOVA revealed a significant interaction between nMCV and the type of initial stimulation (p = 0.001). Among subjects with low nMCV, those initially treated with iTBS showed 2.6 times greater improvement after 10 sessions (p = 0.01) than subjects initially receiving 10 Hz stimulation. CONCLUSION: nMCV may detect physiologic differences between those likely to benefit from 10 Hz or iTBS treatment. Future studies should examine whether PLR could guide prospective treatment selection.

A comparison of self- and observer-rated scales for detecting clinical improvement during repetitive transcranial stimulation (rTMS) treatment of depression.

Clinical outcomes of repetitive Transcranial Magnetic Stimulation (rTMS) for treatment of Major Depressive Disorder (MDD) vary widely, and no single mood rating scale is standard for assessing rTMS outcomes. This study of 708 subjects undergoing clinical rTMS compared the performance of four scales in measuring symptom change during rTMS treatment. Self-report and observer ratings were examined weekly with the Inventory of Depressive Symptomatology 30-item (IDS), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item (POMS), and Hamilton Depression Rating Scale 17-item (HDRS). While all scales were correlated and detected significant improvement, the degree of improvement over time as well as response (33-50%) and remission (20-24%) rates varied significantly. Higher baseline severity was associated with lower likelihood of remission, and greater improvement by sessions 5 and 10 predicted response across all scales. Use of only a single scale to assess outcome conferred 14-36% risk of failing to detect response/remission indicated by another scale. The PHQ was most likely to indicate improvement and least likely to miss response or remission. These findings indicate that assessment of symptom burden during rTMS treatment may be most accurately assessed through use of multiple instruments.

Co-created Mobile Apps for Palliative Care Using Community-Partnered Participatory Research: Development and Usability Study.

BACKGROUND: Open design formats for mobile apps help clinicians and stakeholders bring their needs to direct, co-creative solutions. Palliative care for patients with advanced cancers requires intensive monitoring and support and remains an area in high need for innovation. OBJECTIVE: This study aims to use community-partnered participatory research to co-design and pretest a mobile app that focuses on palliative care priorities of clinicians and patients with advanced cancer. METHODS: In-person and teleconference workshops were held with patient and family stakeholders, researchers, and clinicians in palliative care and oncology. Question prompts, written feedback, semistructured interviews, and facilitated group discussions identified the core palliative care needs. Using Chorus, a no-code app-building platform, a mobile app was co-designed with the stakeholders. A pretest with 11 patients was conducted, with semistructured interviews of clinician and patient users for feedback. RESULTS: Key themes identified from the focus groups included needs for patient advocacy and encouragement, access to vetted information, patient-clinician communication support, and symptom management. The initial prototype, My Wellness App, contained a weekly wellness journal to track patient-reported symptoms, goals, and medication use; information on self-management of symptoms; community resources; and patient and caregiver testimonial videos. Initial pretesting identified value in app-based communication for clinicians, patients, and caregivers, with suggestions for improving user interface, feedback and presentation of symptom reports, and gamification and staff coordinators to support patient app engagement. CONCLUSIONS: The development of a mobile app using community-partnered participatory research is a low-technology and feasible intervention for palliative care. Iterative redesign and user interface expertise may improve implementation.

Pancreatic Pain-Knowledge Gaps and Research Opportunities in Children and Adults: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

ABSTRACT: A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities in pancreatic pain. The event was held on July 21, 2021, and structured into 4 sessions: (1) pathophysiology; (2) biomarkers, mediators, and pharmacology of pain; (3) pain assessment; and (4) pain treatment challenges and opportunities. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to better understand the underlying mechanisms of pain in pancreatic diseases, the relationship of visceral neural pathways and central pain centers, the role of behavioral factors and disorders on the perception of pain, and differences in pain perception and processes in children when compared with adults. In addition, the role of genetic risk factors for pain and the mechanisms and role of placebos in pain treatment were discussed. Methods of pain assessment including quantitative sensory testing were examined, as well as the process of central sensitization of pain. Finally, newer approaches to pain management including cognitive behavioral therapy, nerve stimulation, experimental (nonopioid) drugs, and cannabinoid compounds were covered.

Requests for PAD and the Assessment of Capacity.

I was asked to evaluate M by her medical oncologist, Dr. T. As a psychiatrist, I was to perform the duties of a mental health specialist in the care of this fifty-eight-year-old woman with metastatic breast cancer who had requested physician aid in dying. Dr. T had no specific concerns, but she was adhering to the letter of the law by referring the patient to me-a "mental health specialist"-because, according to the patient's medical history, there was "evidence of a mental disorder." That evidence was comprised of depression treated in the remote past. Some years before California passed its End of Life Options Act in 2015, M had begun talking with Dr. T about the circumstances under which she might no longer want to be alive and might even choose to take active steps to end her life. She had fairly specific and durable criteria for knowing "when the time had come." In our interview, she asserted very clearly that the time had not come but that, with the law now active, she hoped to have access to a lethal prescription in case it did.

Psychological Treatment.

Psychological approaches to pain management have been demonstrated to be effective for individuals newly diagnosed with cancer, in remission, and/or with progressive or terminal disease. Modalities that have been demonstrated to be most effective are cognitive behavioral approaches that include relaxation skills and/or hypnotherapy.