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.

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.

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.

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.

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.

Cannabinoids in Medical Practice.

Many patients with chronic medical illnesses use cannabinoids. There are two FDA-approved cannabinoid products, whereas medical marijuana purchased at legal dispensaries is not FDA regulated and may contain uncertain concentrations of various compounds. Cannabinoids have shown efficacy in treating chemotherapy-related nausea and vomiting, poor appetite in advanced HIV, some pain states, and multiple sclerosis-associated spasticity. Recreational cannabinoid use has many known potential serious harms. Physicians should be knowledgeable about cannabinoids and should inquire with their patients about cannabinoid use. Practical suggestions for clinical approaches are included.

Cancer-related pain management in clinical oncology.

Uncontrolled pain is one of the most feared and debilitating symptoms among cancer patients, and many suffer unnecessarily from suboptimal pain control. Cancer-related pain is often multidimensional and can affect all aspects of a patient's life. Hence, achieving adequate pain relief among cancer patients involves a proper assessment of psychosocial, spiritual, and physical pain issues, matched with an individualized treatment plan involving pharmacologic, nonpharmacologic, and procedural therapies when appropriate. Providing effective pain relief can help ease the overall burden of disease among oncology patients while helping them tolerate cancer-directed therapies and achieve the most optimal quality of life throughout all phases of the disease continuum. In this review, the authors will discuss the syndromes, assessment of, and treatment for cancer-related pain in the outpatient setting.

Pharmacokinetic drug interactions in palliative care: focus on opioids.

Opioid analgesics are crucial for pain management in most patients receiving palliative care. Contemporary models advocate for the provision of palliative care services as early as possible in a course of illness, suggesting that many patients will receive palliative care services, and opioids, concurrent with complex disease-modifying therapies. This article reviews the metabolic pathways of commonly prescribed opioid analgesics and provides a survey of what is known about how disease-modifying therapies alter the pharmacokinetics and pharmacodynamics of opioids. Existing treatment guidelines are reviewed. Practical suggestions are offered.

The relationship between cytokines and pain/depression: a review and current status.

Cytokines are small protein molecules secreted in response to immune stimuli. Recent research has outlined important roles for proinflammatory cytokines in the cascade of normal physiologic responses to environmental stresses, encompassing so-called sickness behavior that is thought to be an adaptive response to infection and other illnesses. Cytokines are involved in signaling that activates central nervous system glial cells. This activation is part of a poorly understood interaction between immune challenge or injury and host that can lead to the development or facilitation of persistent mood symptoms or pathologic pain. This article reviews evidence that may enhance our understanding of how pathologic symptoms, such as mood disorders and neuropathic pain, may emerge from proinflammatory cytokine activation. Possible conceptualizations of these illnesses and potential treatment implications are explored.