Neurocognitive effects of transcranial direct current stimulation (tDCS) in unipolar and bipolar depression: Findings from an international randomized controlled trial.

OBJECTIVE: Transcranial direct current stimulation (tDCS) has been found to have antidepressant effects and may have beneficial neurocognitive effects. However, prior research has produced an unclear understanding of the neurocognitive effects of repeated exposure to tDCS. The study's aim was to determine the neurocognitive effects following tDCS treatment in participants with unipolar or bipolar depression. METHOD: The study was a triple-masked, randomized, controlled clinical trial across six international academic medical centers. Participants were randomized to high dose (2.5 mA for 30 min) or low dose (0.034 mA, for 30 min) tDCS for 20 sessions over 4 weeks, followed by an optional 4 weeks of open-label high dose treatment. The tDCS anode was centered over the left dorsolateral prefrontal cortex at F3 (10/20 EEG system) and the cathode over F8. Participants completed clinical and neurocognitive assessments before and after tDCS. Genotype (BDNF Val66Met and catechol-o-methyltransferase [COMT] Val158Met polymorphisms) were explored as potential moderators of neurocognitive effects. RESULTS: The study randomized 130 participants. Across the participants, tDCS treatment (high and low dose) resulted in improvements in verbal learning and recall, selective attention, information processing speed, and working memory, which were independent of mood effects. Similar improvements were observed in the subsample of participants with bipolar disorder. There was no observed significant effect of tDCS dose. However, BDNF Val66Met and COMT Val158Met polymorphisms interacted with tDCS dose and affected verbal memory and verbal fluency outcomes, respectively. CONCLUSIONS: These findings suggest that tDCS could have positive neurocognitive effects in unipolar and bipolar depression. Thus, tDCS stimulation parameters may interact with interindividual differences in BDNF and COMT polymorphisms to affect neurocognitive outcomes, which warrants further investigation.

Transcranial magnetic stimulation maintenance as a substitute for maintenance electroconvulsive therapy: a case series.

BACKGROUND: Transcranial magnetic stimulation (TMS) is an efficacious, well-tolerated, noninvasive brain stimulation treatment for major depressive disorder. Electroconvulsive therapy (ECT) is an effective maintenance treatment for depression but is not tolerated by some patients and declined by others. OBJECTIVE: We evaluated the effectiveness of TMS as a substitution strategy for successful maintenance ECT. METHODS: A consecutive clinical case series (n = 6) of maintenance ECT patients were transitioned to maintenance TMS because of adverse effects from ECT or because of specific patient request and preference. Patients were in either full remission or had clinical response to ECT at the time of transition. Primary outcome was the change in the Beck Depression Inventory (BDI) score from initiation of TMS maintenance sessions to the last observation time point. Relapse of depressive symptoms was also documented. RESULTS: Mean age of patients was 64 years, and most were female (n = 5). The majority (5 of 6) were diagnosed with major depressive disorder. Reasons for transition from ECT to TMS were, in order of frequency, cognitive adverse effects, fear of general anesthesia, time burden, lack of remission with ECT, and stigma associated with ECT. The mean frequency of TMS sessions was 1 every 3.5 weeks. Based on BDI scores, all patients maintained or improved their clinical status achieved with ECT at 3 and 6 months of TMS treatment. At last observation (range, 7-23 months), 4 patients maintained or improved their clinical status (total BDI score remained constant or decreased by 1-8 points). Two patients had a relapse after 8 and 9 months. Stimulation was well tolerated with adverse effects limited to headache and scalp discomfort. CONCLUSIONS: In this case series, TMS was effective and safe when used as a substitution strategy for successful maintenance ECT.

Transcranial magnetic stimulation (TMS) in the treatment of attention-deficit/hyperactivity disorder in adolescents and young adults: a pilot study.

OBJECTIVE: Transcranial magnetic stimulation (TMS) uses a medical device that applies magnetic pulses noninvasively to the cortex of the brain to depolarize neurons. We tested its safety and efficacy in young persons with a diagnosis of attention-deficit/hyperactivity disorder (ADHD). METHODS: Transcranial magnetic stimulation was applied to the right prefrontal cortex at 10 Hz, at 100% of the observed motor threshold, for 2000 pulses per session, in a 10-session course over 2 weeks in a sham-controlled crossover design (n=9). There was 1 week of no TMS between the active and sham phases. Safety of TMS was assessed by means of serial audiometry, neuropsychological testing, and electroencephalogram (EEG) at baseline, midpoint, and end point of the study. Efficacy was assessed as a primary outcome by changes in the Clinical Global Impression-Improvement (CGI-I) scale and secondarily by change in the ADHD-IV scale. RESULTS: Transcranial magnetic stimulation was found to be safe, with no serious adverse events and no discontinuations due to adverse effects. All randomized subjects completed the full course of sessions. There were no significant changes in auditory thresholds or in electroencephalographic assessments. Neuropsychological testing showed no significant differences between active and sham groups. There was an overall significant improvement in the clinical global impression of improvement and the ADHD-IV scales across the study phases (active and sham TMS combined; P<0.01), but the change between active and sham TMS phases did not differ. CONCLUSION: Transcranial magnetic stimulation was found to be safe, with no serious adverse events observed in this pilot study. Improvement in symptoms was observed across the combined phases of the study, although there was no difference between the active and sham forms of TMS. Effects of clinical importance should be further assessed in larger controlled studies.

Acute and maintenance electroconvulsive therapy for treatment of severe major depression during the second and third trimesters of pregnancy with infant follow-up to 18 months: case report and review of the literature.

Electroconvulsive therapy (ECT) is considered to be a safe and effective treatment in the management of severe mood disorders during pregnancy. Nevertheless, for the clinician in practice, decision making regarding ECT administration in this special population is challenging. This is due both to the risks of untreated or inadequately treated mental illness for the mother and the fetus as well as the risks of complications from ECT itself during pregnancy. Special measures and modifications of ECT procedures are required to minimize the risk of complications in pregnant patients undergoing ECT. Here we report the successful and safe administration of acute and continuation ECT in a 39-year-old pregnant patient with severe major depression. A total of 18 bilateral-bifrontal treatments were administered in the second and third trimesters of pregnancy with presession and postsession fetal monitoring. Following an elective cesarean delivery at 37 weeks of a healthy female infant, a total of 13 additional ECT treatments were administered as maintenance treatment in the first 6 months postpartum during which time the patient was successfully transitioned to antidepressant medication. Development of the child has been assessed as fully normal in all follow-up visits with the pediatrician out to 18 months.

Electroconvulsive therapy for treatment of major depression in a 100-year-old patient with severe aortic stenosis: a 5-year follow-up report.

Although there is no specific age cutoff for electroconvulsive therapy (ECT) and no absolute contraindication to its use, very old age and the presence of cardiac conditions such as aortic stenosis are factors that may negatively affect the physician's decision to administer ECT in individual cases. We report our follow-up of a 100-year-old woman with severe aortic stenosis who has received ECT safely for 5 years now. No cardiac complications have emerged during this period. Her prior unipolar depressive episode with catatonic features remains in remission with a single prophylactic ECT session every 3 months. We have observed from our experience with this unique case that periodic multidisciplinary re-evaluation of the evolving risk-benefit profile of ECT is essential along with the inclusion of family members in this dialogue. Our patient's course illustrates that neither advanced age nor severe aortic stenosis is an absolute contraindication to ECT even over an extended period of time. Each case needs to be evaluated on its merits. To our knowledge, this case represents the oldest patient in the literature where ECT has been administered safely for such an extended period in the setting of severe aortic stenosis.

Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression: A Decade of Clinical Follow-Up.

Objective: Deep brain stimulation (DBS) is an emerging therapy for treatment-resistant depression (TRD) that has shown variable efficacy. This report describes long-term outcomes of DBS for TRD.Methods: A consecutive series of 8 patients with TRD were implanted with ventral capsule/ventral striatum (VC/VS) DBS systems as part of the Reclaim clinical trial. Outcomes from 2009 to 2020 were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Demographic information, MADRS scores, and data on adverse events were collected via retrospective chart review. MADRS scores were integrated over time using an area-under-the-curve technique.Results: This cohort of patients had severe TRD-all had failed trials of ECT, and all had failed a minimum of 4 adequate medication trials. Mean ± SD follow-up for patients who continued to receive stimulation was 11.0 ± 0.4 years (7.8 ± 4.3 years for the entire cohort). At last follow-up, mean improvement in MADRS scores was 44.9% ± 42.7%. Response (≥ 50% improvement) and remission (MADRS score ≤ 10) rates at last follow-up were 50% and 25%, respectively. Two patients discontinued stimulation due to lack of efficacy, and another patient committed suicide after stimulation was discontinued due to recurrent mania. The majority of the cohort (63%) continued to receive stimulation through the end of the study.Conclusions: While enthusiasm for DBS treatment of TRD has been tempered by recent randomized trials, this small open-label study demonstrates that some patients achieve meaningful and sustained clinical benefit. Further trials are required to determine the optimal stimulation parameters and patient populations for which DBS would be effective. Particular attention to factors including patient selection, integrative outcome measures, and long-term observation is essential for future trial design.Trial Registration: ClinicalTrials.gov identifier: NCT00837486.

Guidelines for the management of depression during pregnancy.

Guidelines regarding the treatment of depression during pregnancy were recently published by the American Psychiatric Association and the American College of Obstetricians and Gynecologists. We provide a commentary on these guidelines.

Proposed diagnostic criteria for night eating syndrome.

OBJECTIVE: To propose criteria for diagnosis of the night eating syndrome (NES). METHOD: An international research meeting was held in April 2008, and consensus criteria for NES diagnosis were determined. RESULTS: The core criterion is an abnormally increased food intake in the evening and nighttime, manifested by (1) consumption of at least 25% of intake after the evening meal, and/or (2) nocturnal awakenings with ingestions at least twice per week. Awareness of the eating episodes is required, as is distress or impairment in functioning. Three of five modifiers must also be endorsed. These criteria must be met for a minimum duration of 3 months. DISCUSSION: These criteria help standardize the definition of NES. Additional aspects of the nosology of NES yet to be fully elaborated include its relationship to other eating and sleep disorders. Assessment and analytic tools are needed to assess these new criteria more accurately.

A case of delayed onset of threatened premature labor in association with electroconvulsive therapy in the third trimester of pregnancy.

Electroconvulsive therapy (ECT) is recommended by the American Psychiatric Association Task Force on ECT as a safe and effective treatment of depression throughout pregnancy. We report here administration of ECT in the third trimester of pregnancy in a 33-year-old patient with severe bipolar depression. The patient had a good antidepressant response to ECT. She experienced, however, delayed onset premature uterine contractions at home after her sixth session of ECT (10 hours post-ECT administration). After receiving tocolytics, the patient's contractions did not progress to premature labor. In consultation with the obstetrics team, it was decided to terminate the ECT course earlier than planned. The patient is delivered of a healthy female newborn infant spontaneously at 37 weeks' gestational age. Four months after delivery, the baby's development is progressing normally. This case illustrates that premature contractions in association with ECT during the third trimester of pregnancy may be delayed in onset. Patients and treatment team need to be aware of this possibility, particularly when ECT is conducted on an outpatient basis.

Cognitive behavior therapy for night eating syndrome: a pilot study.

Because no studies of psychotherapy treatments for night eating syndrome (NES) have been published, we conducted a pilot study of a 10-session cognitive behavior therapy (CBT) for NES. Twenty-five patients (19 female, 6 male) were screened and comprehensively assessed before being enrolled. At each visit, patients completed the Night Eating Symptom Scale (NESS), were weighed, and number of awakenings and the number of nocturnal ingestions and daily caloric intake were calculated from weekly food and sleep records. Mixed model regression analyses [of the data] showed significant decreases in caloric intake after dinner (35.0% to 24.9%); number of nocturnal ingestions (8.7 to 2.6 per week); weight (82.5 to 79.4 kg); and NESS score (28.7 to 16.3; all p values <0.0001). Number of awakenings per week, depressed mood, and quality of life also improved significantly (p values <.02). This first clinical trial of CBT for NES shows significant improvements in the core aspects of NES and weight reduction, suggesting the need for a controlled treatment trial.

Circadian rhythm profiles in women with night eating syndrome.

Night eating syndrome (NES) is characterized by evening hyperphagia and frequent awakenings accompanied by food intake. Patients with NES display a delayed circadian pattern of food intake but retain a normal sleep-wake cycle. These characteristics initiated the current study, in which the phase and amplitude of behavioral and neuroendocrine circadian rhythms in patients with NES were evaluated. Fifteen women with NES (mean age +/- SD, 40.8 +/- 8.7 y) and 14 control subjects (38.6 +/- 9.5 y) were studied in the laboratory for 3 nights, with food intake measured daily. Blood also was collected for 25 h (every 2 h from 0800 to 2000 h, and then hourly from 2100 to 0900 h) and assayed for glucose and 7 hormones (insulin, ghrelin, leptin, melatonin, cortisol, thyroid-stimulating hormone [TSH] and prolactin). Statistical analyses utilized linear mixed-effects cosinor analysis. Control subjects displayed normal phases and amplitudes for all circadian rhythms. In contrast, patients with NES showed a phase delay in the timing of meals, and delayed circadian rhythms for total caloric, fat, and carbohydrate intake. In addition, phase delays of 1.0 to 2.8 h were found in 2 food-regulatory rhythms-leptin and insulin-and in the circadian melatonin rhythm (with a trend for a delay in the circadian cortisol rhythm). In contrast, circulating levels of ghrelin, the primary hormone that stimulates food intake, were phase advanced by 5.2 h. The glucose rhythm showed an inverted circadian pattern. Patients with NES also showed reduced amplitudes in the circadian rhythms of food intake, cortisol, ghrelin, and insulin, but increased TSH amplitude. Thus, patients with NES demonstrated significant changes in the timing and amplitude of various behavioral and physiological circadian markers involved in appetite and neuroendocrine regulation. As such, NES may result from dissociations between central (suprachiasmatic nucleus) timing mechanisms and putative oscillators elsewhere in the central nervous system or periphery, such as the stomach or liver. Considering these results, chronobiologic treatments for NES such as bright light therapy may be useful. Indeed, bright light therapy has shown efficacy in reducing night eating in case studies and should be evaluated in controlled clinical trials.

Pregnancy and depression: exploring a new potential treatment option.

The treatment of major depressive disorder during pregnancy is an important but complex clinical topic. Medications, electroconvulsive therapy, and psychotherapy are all reasonable choices, but each has its limitations. In this article, we propose that a novel device technology known as repetitive transcranial magnetic stimulation should be systematically studied as a potential treatment option for women with major depressive disorder during pregnancy.

Transcranial magnetic stimulation in the treatment of psychiatric disorders.

Transcranial magnetic stimulation (TMS) is an emerging novel treatment modality for psychiatric disorders, particularly major depression. A device for delivery of TMS was approved by the US Food and Drug Administration for treatment of major depressive disorder in adults. TMS is being studied for a variety of psychiatric disorders, including obsessive-compulsive disorder, post-traumatic stress disorder, and auditory hallucinations in schizophrenia. In this article, we describe TMS and its neurobiologic basis, as well as the efficacy and safety data of TMS with regard to a range of psychiatric disorders.

Development of criteria for a diagnosis: lessons from the night eating syndrome.

Criteria for inclusion of diagnoses of Axis I disorders in the forthcoming Diagnostic and Statistical Manual (DSM-V) of the American Psychiatric Association are being considered. The 5 criteria that were proposed by Blashfield et al as necessary for inclusion in DSM-IV are reviewed and are met by the night eating syndrome (NES). Seventy-seven publications in refereed journals in the last decade indicate growing recognition of NES. Two core diagnostic criteria have been established: evening hyperphagia (consumption of at least 25% of daily food intake after the evening meal) and/or the presence of nocturnal awakenings with ingestions. These criteria have been validated in studies that used self-reports, structured interviews, and symptom scales. Night eating syndrome can be distinguished from binge eating disorder and sleep-related eating disorder. Four additional features attest to the usefulness of the diagnosis of NES: (1) its prevalence, (2) its association with obesity, (3) its extensive comorbidity, and (4) its biological aspects. In conclusion, research on NES supports the validity of the diagnosis and its inclusion in DSM-V.

Randomized controlled trial of transcranial magnetic stimulation in pregnant women with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) affects 10% of pregnancies. Because transcranial magnetic stimulation (TMS) is a nonmedication option, psychiatric patients who do not tolerate or prefer to avoid antidepressants are good candidates for TMS. METHOD: In a randomized controlled trial of twenty-two women with MDD in the second or third trimester of pregnancy, subjects were randomized to active TMS (n=11) or sham TMS (n=11). This study took place at a single academic center. Subjects received 20 sessions of TMS to the right dorsolateral prefrontal cortex at 1 Hz as a single train of 900 pulses per session at 100% motor threshold. Estradiol and progesterone and were measured before session 1 and after session 20. RESULTS: Results demonstrated significantly decreased Hamilton Depression Rating Scale (HDRS-17) scores for the active compared to the sham group (p=0.003). Response rates were 81.82% for the active and 45.45% for the sham coil (p=0.088). Remission rates were 27.27% for the active 18.18% for the sham coil (p=0.613). Late preterm birth (PTB) occurred in three women receiving active TMS. All other maternal and delivery outcomes were normal. CONCLUSIONS: Right-sided, low frequency TMS was effective in reducing depressive symptoms in this sample of pregnant women. There may be a possibility that TMS is associated with late PTB although a larger sample size would be needed for adequate power to detect a true difference between groups. This study demonstrated that TMS is low risk during pregnancy although larger trials would provide more information about the efficacy and safety of TMS in this population. This trial shows that an RCT of a biologic intervention in pregnant women with psychiatric illness can be conducted.

Uncommon but serious complications associated with electroconvulsive therapy: recognition and management for the clinician.

Electroconvulsive therapy (ECT) is a safe and effective treatment for severe mood disorders. Rarely there can be serious complications, such as postictal agitation, cardiovascular compromise, prolonged seizures, and status epilepticus, all of which are important for the clinician to recognize and treat. Postictal agitation can be severe, requiring emergent intervention and subsequent prophylactic measures to avoid premature ECT discontinuation. Cardiovascular responses to ECT include significant hemodynamic changes that may result in complications, even in patients without preexisting cardiovascular conditions. However, preexisting cardiovascular conditions per se are not contraindications to ECT in patients with disabling psychiatric disease. Recognizing and treating prolonged seizures is essential to prevent progression to status epilepticus. Failure to recognize and treat any of these events may result in increased mortality and morbidity. Understanding such complications and their management strategies avoids unnecessary treatment discontinuation due to manageable ECT complications.

Transcranial magnetic stimulation: a device intended for the psychiatrist's office, but what is its future clinical role?

Repetitive transcranial magnetic stimulation (TMS) is a novel, noninvasive, office-based device technology that delivers focused stimulation to the cortex of the brain by means of magnetic pulses. It is a promising therapeutic approach in a variety of neuropsychiatric disorders. A large number of clinical trials have examined repetitive TMS as a novel treatment for major depression, with additional significant work in schizophrenia, anxiety disorders and pain syndromes. In this review, we describe how repetitive TMS is administered clinically and discuss how excitatory and inhibitory forms of stimulation are applied depending on what is known of the underlying pathophysiology of the disorder. Future putative clinical applications of repetitive TMS in psychiatry are discussed, with the authors' perspective on its likely role in clinical practice. TMS is a promising form of neuromodulation therapy that will most likely become a significant part of clinical practice in the future.

A descriptive study of non-obese persons with night eating syndrome and a weight-matched comparison group.

The purpose of this study was to characterize the Night Eating Syndrome (NES) and its correlates among non-obese persons with NES, and to compare them to non-obese healthy controls. Nineteen non-obese persons with NES were compared to 22 non-obese controls on seven-day, 24-hour prospective food and sleep diaries, the Eating Disorder Examination and the Structured Clinical Interview for DSM-IV Diagnoses interviews, and measures of disordered eating attitudes and behavior, mood, sleep, stress, and quality of life. Compared to controls, persons with NES reported significantly different circadian distribution of food intake, greater depressed mood, sleep disturbance, disordered eating and body image concerns, perceived stress, decreased quality of life, and more frequent Axis I comorbidity, specifically anxiety, mood, and substance use disorders. These findings are the first to describe the clinical significance of night eating syndrome among non-obese individuals in comparison to a non-obese control group, and they suggest that NES has negative health implications beyond that associated with obesity.

The Night Eating Questionnaire (NEQ): psychometric properties of a measure of severity of the Night Eating Syndrome.

The purpose of this study was to evaluate the Night Eating Questionnaire (NEQ) as a measure of severity of the Night Eating Syndrome (NES). The 14-item NEQ assesses the behavioral and psychological symptoms of NES. The NEQ was evaluated in three samples: 1980 persons who completed the NEQ on the Internet; 81 persons diagnosed with NES; and 194 bariatric surgery candidates. Study 1, using principal components analysis, generated four factors (nocturnal ingestions, evening hyperphagia, morning anorexia, and mood/sleep) and an acceptable alpha (.70). Confirmatory factor analysis suggested that 99% of covariation among factors is accounted for by a higher-order construct. Study 2 found convergent validity of the NEQ with additional measures of night eating, disordered eating, sleep, mood, and stress. Study 3 compared scores from obese bariatric surgery candidates with and without NES and found appropriate discriminant validity of the NEQ. The NEQ appears to be an efficient, valid measure of severity for NES.