Adam P. Stern

Occupational functioning and impairment in adults with body dysmorphic disorder

OBJECTIVE Body dysmorphic disorder (BDD) is relatively common and appears to be associated with marked impairment in psychosocial functioning. Previous reports, however, did not investigate occupational functioning in detail, assess impairment specifically in occupational functioning using standardized measures in a nontreatment seeking sample, or examine correlates of occupational impairment. METHODS Occupational functioning and other clinical variables were assessed in 141 adults with BDD. Measures included the Range of Impaired Functioning Tool and other reliable and valid self-report and interviewer-administered measures. RESULTS Fewer than half of subjects were working full-time, and 22.7% were receiving disability pay. Thirty-nine percent of the sample reported not working in the past month because of psychopathology. Of those subjects who worked in the past month, 79.7% reported impairment in work functioning because of psychopathology. Adults with BDD who were not working because of psychopathology were comparable to subjects who were working in most demographic variables, delusionality of BDD beliefs, and duration of BDD. However, compared to subjects who worked in the past month, those not currently working because of psychopathology had more severe BDD and more chronic BDD. They also were more likely to be male, had less education, and had more severe depressive symptoms, a higher rate of certain comorbid disorders, poorer current social functioning and quality of life, a higher rate of lifetime suicidality, and were more likely to have been psychiatrically hospitalized. CONCLUSIONS A high proportion of individuals with BDD were unable to work because of psychopathology; most who worked reported impairment in occupational functioning. Certain clinical variables, including more severe and chronic BDD, were associated with not working.

Adding Low-Field Magnetic Stimulation to Noninvasive Electromagnetic Neuromodulatory Therapies

Driven by the limitations of traditional approaches to treating depression, there has recently been a surge of studies examining the utility of various noninvasive neuromodulation technologies in the treatment of depression. In this issue, Rohan et al [1] report substantial improvement in mood immediately following one twenty-minute treatment application of low-field magnetic stimulation (LFMS), performed with a novel portable tabletop device. The stimulation paradigm they utilize consists of a 1 kHz oscillating magnetic field, adapted from the component of the MRI protocol that they previously serendipitously found to have beneficial mood effects [2]. In the current study, LFMS was applied in a double-blind, sham-controlled design to a heterogeneous group of 63 patients with either bipolar depression or major depressive disorder, and effects on mood were assessed primarily using a self-rated visual analog scales (VAS) and observer-rated Hamilton depression rating scale (HDRS-17). The authors found that real LFMS produced an immediate improvement on several scales across the combined population of depressed patients as compared to sham. Although they must be interpreted with caution and much additional work is necessary before the clinical utility of the approach can be determined, these results are highly intriguing. A particularly striking aspect of the LFMS effect is that a mood-elevation was found immediately after one brief treatment. Psychiatric treatments, including the neuromodulatory gold standard of electroconvulsive therapy [3], generally show much slower onset of effect, typically requiring weeks before separating from placebo in sham-controlled clinical trials. While ketamine has been shown to have a rapid antidepressant effect within twenty-four hours [4], durability and clinical utility need further elucidation. Rohan et al. [1] were able to demonstrate improvement in mood ten to fifteen minutes after completion of the intervention, although whether these effects had any durability could not be determined by their study design. Rapidity of onset can be an essential factor in the clinical realm, where there are few effective treatment options available to rapidly assist the high-risk acutely suicidal patient. The LFMS approach features other notable strengths, including a completely non-invasive approach with no known adverse effects. The absence of any physical sensation with stimulation enables fairly robust blinding, of benefit for future trials. The device is also small and portable, thus enabling potential future home use, and utilizes technology and physical properties that are relatively well known. However, there are a number of unanswered questions that cloud an assessment of the clinical significance of the present results. Most importantly, the study was not designed to measure the durability of mood improvement. Mood effects were evaluated immediately (10 to 15 minutes) after the intervention, but there were no subsequent assessments to see if the effects persisted for any meaningful period of time. A related concern is the unclear validity and reliability of the outcome measures over such short periods of time. For example, one of the two primary outcome measures, the HDRS-17, requires the clinician to assess the patient’s symptoms of depression over the past week; it is difficult to know what reported changes in these measures mean when they are assessed less than an hour apart. Another concern is the relatively small size and heterogeneity of the tested population. The authors included patients with bipolar disorder as well as major depressive disorder. Given that the underlying psychopathologies and the pharmacologic treatments in these two populations are distinct, combining these populations into a single sample may confound the data in unclear ways. A related concern is the heterogeneity of the results between the different subpopulations; a significant benefit over sham was seen in the VAS in the MDD but not the BPD subjects, whereas the opposite was observed on the PANAS-PA, and significant effects were not present in either subpopulation (but were present across all subjects) in the HDRS. This variability underscores the need for reliable assessments in larger, more homogenous populations. Neuromodulation based on electromagnetic induction has become broadly accepted in psychiatric therapeutics thanks to the Food and Drug Administration’s approval in 2008 of the Neuronetics device, and more recently in 2013 of the Brainsway device for the treatment of medication-resistant depression. In the meantime, over 500 TMS devices are in operation in the US alone. Alternative approaches are also being explored including EEG-synchronized transcranial magnetic stimulation (sTMS). A pilot study of this intervention showed that subjects with either fixed or random frequency sTMS had significantly greater reductions in depression severity than those receiving sham [5]. Like LFMS, sTMS is delivered with a portable device and the tolerability was outstanding. In addition, TMS is being actively investigated for a growing number of neurologic disorders [6]. How can we think about the LFMS findings in the larger context of the expanding field of noninvasive neuromodulation? LFMS induces electric fields that are of significantly lower strength (<1 V/m) as compared to more established forms of electromagnetic stimulation (≥100 V/M in electroconvulsive therapy (ECT), deep brain stimulation (DBS) and rTMS, in which the electric field at the target site is of sufficient magnitude to directly induce neuronal depolarization [7]. In contrast to LFMS, DBS and TMS have a more focal field of stimulation and are aiming to target specific neural networks. As a result, the mechanism by which LFMS could be exerting a behaviorally relevant effect is highly undefined. The authors suggest that the effect seen from LFMS may stem from changes in membrane potential in the dendritic cortex in layers 5 and 6, which project to limbic and other subcortical regions. What is evident, however, is that the device produces a global electric field that is likely affecting a wide array of cortical brain structures. With this widespread approach, it is also unclear if specific neuroanatomical structures or functional neural networks may be implicated in the observed behavioral effect. In the absence of a putative neural substrate for the observed effect, moving directly to large-scale clinical trials may be risky, and in conflict with recent NIMH directives calling for assessments of engagement of a defined neurobiologic target or mediator. Further investigation into the potential mechanisms of action of this modality could better inform the approach, and also potentially allow for experimental optimization of parameters to maximize any potential behavioral effect. The consideration of low strength magnetic fields for modulation of biological activity is not new. A recent Cochrane review of electromagnetic fields used in the treatment of osteoarthritis showed that electromagnetic field treatment may provide moderate benefit with regard to pain relief [8]. Low frequency electromagnetic fields have also been shown to have anti-inflammatory and neo-angiogenic effects which can contribute to wound healing [9]. The biological effects of magnetic fields are diverse, and the potential applications for this approach are therefore quite broad and largely undefined. Despite all of the uncertainties, the results described by Rohan et al [1] -- in particular the rapidity of the response -- are highly intriguing and add a novel paradigm to the repertoire of neuromodulation techniques that may have therapeutic utility in neuropsychiatric diseases. It is unclear at this time if these approaches achieve their antidepressant effects through a common mechanism, or whether their approaches may in some ways be complementary. The benefit from combining neuromodulation techniques with conventional behavioral and/or pharmacologic therapy is also an area that needs further exploration. Future research should further also be directed towards an evaluation of the neural substrates and functional networks modulated by these different techniques, optimization of the stimulation parameters to maximize the clinical effect, and an assessment of how these various therapeutic modalities can be integrated together. If the results described in this study are replicated in larger studies, and the effects are shown to be durable, LFMS would be a welcome addition to the clinical armamentarium in the treatment of depression, may find application in other psychiatric and neurologic diseases, and may help to inform and guide us toward future directions in neuromodulation.

H-Coil Repetitive Transcranial Magnetic Stimulation Induced Seizure in an Adult with Major Depression: A Case Report.

We report a seizure induced by repetitive transcranial magnetic stimulation (rTMS) using an FDA-approved protocol for treating depression. The patient was a 27 year-old man with long-standing severe recurrent major depressive disorder. He had co-morbid generalized anxiety disorder and four remote head injuries. At age 17 he was punched and fractured his nasal bone and nasal septum. A head CT showed pneumocephalus without intracranial injury. At age 21 he was assaulted and a head CT showed a fractured orbital bone without intracranial injury. He also played college football and was pulled from practice on two occasions for possible concussion. His only medication was vortioxetine 20 mg/day. He had no personal or family history of seizures and had a normal neurological exam. On the day of the event he reported drinking up to 6 beers over 5 hours at a social event the night before with difficulty sleeping. Wewere delivering TMS using the H1-coil (Brainsway Deep TMS) to the left dorsolateral prefrontal cortex according to the FDAapproved protocol [1]: 18-Hz stimulation for 2 s per train with 20 s between trains, with 55 trains (1980 pulses) delivered over 20 minutes. The intensity of the stimulation was 120% of our patient’s motor threshold (53% of machine output). The stimulation was performed in a large academic center that specializes in noninvasive brain stimulation. The patient tolerated the first 2 weeks of daily treatments using this protocol without any adverse events. The event occurred mid-way through the 12th session. The patient recalled experiencing “numbness” and an inability to control the right side of his face, followed by a similar sensation of his right arm before losing consciousness. The TMS technician noted when the patient had facial grimacing and the rTMS was stopped immediately. The facial grimacing rapidly evolved to generalized tonic clonic movements with bladder incontinence. The treating neurologist (A.D.B.) and psychiatrist (A.P.S.) were both on-site and, along with two nurses, were able to assist the technicianwithin oneminute of the onset of convulsions. The patient was put in a lateral decubitus position and closely monitored until the seizure spontaneously resolved 1–2 minutes later. An emergency crash cart was available but not needed. After the seizure, the patient was breathing spontaneously with a regular pulse. He was sweating profusely and vomited in the postictal period. He was sitting up at the time of vomiting and avoided aspiration. He was poorly responsive to verbal stimuli initially and became increasingly coherent over the next 10–20minutes, at which point he was asking appropriate questions. He was transferred to the Emergency Department where he was monitored and labs were drawn, including a complete blood count andmetabolic panel. These were notable for a mild leukocytosis 12.9 (4–10 K/μL), which is often seen after a generalized seizure. After he returned to his cognitive baseline and was medically cleared, he was discharged home. An MRI of the brain with and without contrast was normal. The assessment was that he experienced an rTMS-provoked focal seizure that secondarily generalized.

Antidepressant Effect of Low-Frequency Right-Sided rTMS in Two Patients with Left Frontal Stroke

Repetitive transcranial magnetic stimulation (rTMS) administered at high frequency over left frontal cortex or low frequency over right frontal cortex [1], has been found effective for treating medication-resistant depression. High frequency left frontal rTMS has also been found effective for treating clinically-defined vascular depression [2] and depression following subcortical or right hemispheric stroke [2,3]. However, when the stroke involves left frontal cortex, the standard rTMS target and therapeutic mechanism may be compromised, with little data upon which to guide treatment or prognosis. We describe two patients with left frontal stroke who benefitted from low frequency rTMS over right frontal cortex. “Mr. A” was an 84-year-old, right-handed man with a history of anxiety, left frontal stroke, and depression for the past six years refractory to fluoxetine, citalopram, escitalopram, venlafaxine, mirtazapine, and bupropion. His stroke occurred thirty-two years prior when he awoke with temporary speech problems. He reported full neurological recovery with no onset of depressive symptoms until 26 years post-stroke. Pre-TMS neurological exam showed a slight decrease in right arm swing but no speech or language deficits with intact strength and symmetric reflexes. A head CT obtained just prior to his TMS evaluation showed sequelae of a chronic left frontal stroke (Fig. 1A). “Ms. B” was a 72-year old left-handed woman with a history of anorexia nervosa, left frontal stroke, breast cancer, and episodic depression since her late 30s. Her stroke occurred 8 months prior to presentation with acute onset of transient speech arrest and subsequent worsening of her long-standing depression. Brain MRI obtained one week after symptom onset showed subacute stroke of the left frontal cortex, with a smaller focus in right frontal cortex (Fig. 1B). Since this stroke she reported full neurological recovery, but worsening of her depression which was refractory to fluoxetine, citalopram, venlafaxine, duloxetine, mirtazapine, and nortriptyline. Pre-TMS neurological exam showed subtle weakness of her right face and arm, but normal speech, language, and reflexes. In both patients, rTMSwas administered using aMagStim Rapid2 Device (1600 pulses at 1 Hz, one session per day, five days a week, 30 sessions total) to the right frontal cortex (5.5 cm anterior to the motor hotspot for the first dorsal interosseous muscle of the left hand). This protocol was chosen for several reasons. First, highfrequency rTMS administered in close proximity to a prior stroke could increase the risk of induced seizure [4]. Second, stroke can alter the current induced by rTMS [5] making safety and stimulation effects hard to predict. Finally, stroke near the stimulation site could undermine therapeutic efficacy by altering the local or remote network effects of rTMS [6,7]. Treatment response was measured using the 24-item Hamilton Psychiatric Rating Scale for Depression (HamD) and The Beck Depression Inventory-II (BDI). Standardized cut-offs for response (a 50% reduction in score on the BDI or Ham-D) and remission (a score ≤12 on the BDI or ≤11 on a 24-item HamD) were used [8]. Both patients met criteria for response and remission after 30 sessions of rTMS. In Mr. A, BDI improved from 19 to 8 and HAMD improved from 18 to 10. In Ms. B, BDI score improved from 31 to 1 and HamD improved from 23 to 6. In both patients rTMS was safe, well tolerated, with no complications or adverse side effects. Although limited to two case reports, these data suggest that lowfrequency rTMS over right frontal cortex may be effective in patients with medication-refractory depression and left frontal stroke. Whether the left frontal stroke contributed to depression in these cases is unknown. Our positive clinical results are consistent with data suggesting that low-frequency rTMS to right frontal cortex is effective in primary depression [1,2] and data suggesting that low frequency stimulation contralateral to the lesion can improve stroke symptoms such as hemiparesis [9], visual impairments [10], and neglect [11]. Low frequency stimulation has the added benefit of reducing seizure risk in a patient population at increased risk [5].

Doctoring while Sick — Is Living with Cancer Making Me a Better or Worse Doctor?

Doctoring while Sick For the author, practicing psychiatry has always been about empathy. But when he is diagnosed with stage 3 kidney cancer, he finds himself seeing his patients’ real and devastating problems as somehow less major than before.

Noninvasive Brain Stimulation: Challenges and Opportunities for a New Clinical Specialty

Noninvasive brain stimulation refers to a set of technologies and techniques with which to modulate the excitability of the brain via transcranial stimulation. Two major modalities of noninvasive brain stimulation are transcranial magnetic stimulation (TMS) and transcranial current stimulation. Six TMS devices now have approved uses by the U.S. Food and Drug Administration and are used in clinical practice: five for treating medication refractory depression and the sixth for presurgical mapping of motor and speech areas. Several large, multisite clinical trials are currently underway that aim to expand the number of clinical applications of noninvasive brain stimulation in a way that could affect multiple clinical specialties in the coming years, including psychiatry, neurology, pediatrics, neurosurgery, physical therapy, and physical medicine and rehabilitation. In this article, the authors review some of the anticipated challenges facing the incorporation of noninvasive brain stimulation into clinical practice. Specific topics include establishing efficacy, safety, economics, and education. In discussing these topics, the authors focus on the use of TMS in the treatment of medication refractory depression when possible, because this is the most widely accepted clinical indication for TMS to date. These challenges must be thoughtfully considered to realize the potential of noninvasive brain stimulation as an emerging specialty that aims to enhance the current ability to diagnose and treat disorders of the brain.

Patient- and Technician-Oriented Attitudes Toward Transcranial Magnetic Stimulation Devices

Four transcranial magnetic stimulation (TMS) devices are currently approved for use in treatment-resistant depression. The authors present the first data-driven study examining the patient- and technician-experience using three of these distinct devices. A retrospective survey design with both patient and technician arms was utilized. The study population included patients who received TMS for treatment-resistant depression at the Berenson Allen Center for Noninvasive Brain Stimulation for the first time between 2013 and 2016 and technicians who worked in the program from 2009 to 2017. Statistical analysis included t tests and analyses of variance to assess differences between and across the multiple groups, respectively. Patients treated with the NeuroStar device reported greater confidence that the treatment was being performed correctly compared with those treated with the Magstim device. Conversely, with regard to tolerability, patients treated with the Magstim device reported less pain in the last week and less pain on average compared with those treated with the NeuroStar device. On average, technicians reported feeling that both the Magstim and NeuroStar devices were significantly easier to use than the Brainsway Deep TMS H-Coil device. Additionally, they found the former two devices to be more reliable and better tolerated. Furthermore, the technicians reported greater confidence in the Magstim and NeuroStar devices compared with the Brainsway Deep TMS H-Coil device and indicated that they would be more likely to recommend the two former devices to other treatment centers.

The Giving Body

I’ve learned that the carving doesn’t happen all at once. It takes place over months and years if you live with the type of cancer that allows for this kind of negotiation. When I was first diagnosed with stage III kidney cancer earlier this year at the age of 33, I didn’t know it; I focused entirely on the chance that the doctors would cut the cancer out of me and I’d be done with it. Perhaps in my mind, I had to take this approach just to get through the daunting prospects of surgery and recovery. My first memory after the removal of my left kidney was to look down at my stitched and glued up abdomen and marvel that the contents inside were suddenly incomplete. In my recovery-room haze, I could still recall what it had been like to remove a cadaver’s kidney 12 years earlier. The stench of formaldehyde remains seared into my neurons. What a cute little organ, I thought as I looked at the corpse’s detached kidney, gripping it like a baseball and never once guessing that someday my own would turn on me.

Initial Response to Transcranial Magnetic Stimulation Treatment for Depression Predicts Subsequent Response

This study provides support for the hypothesis that treatment response to an initial course of repetitive transcranial magnetic stimulation (rTMS) for depression predicts the magnitude of response to a subsequent course of rTMS in the setting of symptom relapse.

Psychiatrists’ Attitudes Toward Transcranial Magnetic Stimulation

Figure 2. Respondents’ ratings to the prompt, “I know and understand the FDA [Food and Drug Administration] indications for TMS [transcranial magnetic stimulation] use in treatment-resistant depression.” Figure 1. Respondents’ ratings to the prompt, “I know how to refer someone for TMS [transcranial magnetic stimulation].” BIDMC, Beth Israel Deaconess Medical Center; MGH, Massachusetts General Hospital; SEMC, St. Elizabeth’s Medical Center. Magnetic Stimulation