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Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers. The National Network of Depression Centers, a consortium of 26+ US academic medical centers of excellence providing care for patients with mood disorders, formed a task group with the goals of promoting best clinical practices for the delivery of ECT and to facilitate large-scale, multisite quality improvement and research to advance more effective and safe use of this treatment modality. The National Network of Depression Centers Task Group on ECT set out to define best practices for harmonizing the clinical documentation of ECT across treatment centers to promote clinical interoperability and facilitate a nationwide collaboration that would enable multisite quality improvement and longitudinal research in real-world settings. This article reports on the work of this effort. It focuses on the use of ECT for major depressive disorder, which accounts for the majority of ECT referrals in most countries. However, most of the recommendations on clinical documentation proposed herein will be applicable to the use of ECT for any of its indications.

Objective There is limited information regarding the tolerability of electroconvulsive therapy (ECT) combined with pharmacotherapy in elderly adults with major depressive disorder (MDD). Addressing this gap, we report acute neurocognitive outcomes from Phase 1 of the Prolonging Remission in Depressed Elderly (PRIDE) study. Methods Elderly adults (age ≥60) with MDD received an acute course of 6 times seizure threshold right unilateral ultrabrief pulse (RUL-UB) ECT. Venlafaxine was initiated during the first treatment week and continued throughout the study. A comprehensive neurocognitive battery was administered at baseline and 72 hours following the last ECT session. Statistical significance was defined as a two-sided p-value of less than 0.05. Results A total of 240 elderly adults were enrolled. Neurocognitive performance acutely declined post ECT on measures of psychomotor and verbal processing speed, autobiographical memory consistency, short-term verbal recall and recognition of learned words, phonemic fluency, and complex visual scanning/cognitive flexibility. The magnitude of change from baseline to end for most neurocognitive measures was modest. Conclusion This is the first study to characterize the neurocognitive effects of combined RUL-UB ECT and venlafaxine in elderly adults with MDD and provides new evidence for the tolerability of RUL-UB ECT in an elderly sample. Of the cognitive domains assessed, only phonemic fluency, complex visual scanning, and cognitive flexibility qualitatively declined from low average to mildly impaired. While some acute changes in neurocognitive performance were statistically significant, the majority of the indices as based on the effect sizes remained relatively stable.

Objective There is limited information regarding neurocognitive outcomes of right unilateral ultrabrief pulse width electroconvulsive therapy (RUL-UB ECT) combined with pharmacotherapy in older adults with major depressive disorder. We report longitudinal neurocognitive outcomes from Phase 2 of the Prolonging Remission in Depressed Elderly (PRIDE) study. Method After achieving remission with RUL-UB ECT and venlafaxine, older adults (≥60 years old) were randomized to receive symptom-titrated, algorithm-based longitudinal ECT (STABLE) plus pharmacotherapy (venlafaxine and lithium) or pharmacotherapy-only. A comprehensive neuropsychological battery was administered at baseline and throughout the 6-month treatment period. Statistical significance was defined as a p-value of less than 0.05 (two-sided test). Results With the exception of processing speed, there was statistically significant improvement across most neurocognitive measures from baseline to 6-month follow-up. There were no significant differences between the two treatment groups at 6 months on measures of psychomotor processing speed, autobiographical memory consistency, short-term and long-term verbal memory, phonemic fluency, inhibition, and complex visual scanning and cognitive flexibility. Conclusion To our knowledge, this is the first report of neurocognitive outcomes over a 6-month period of an acute course of RUL-UB ECT followed by one of 2 strategies to prolong remission in older adults with major depression. Neurocognitive outcome did not differ between STABLE plus pharmacotherapy versus pharmacotherapy alone over the 6-month continuation treatment phase. These findings support the safety of RUL-UB ECT in combination with pharmacotherapy in the prolonging of remission in late-life depression.

Objective To provide expert recommendations for the safe and effective application of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD). Participants Participants included a group of 17 expert clinicians and researchers with expertise in the clinical application of rTMS, representing both the National Network of Depression Centers (NNDC) rTMS Task Group and the American Psychiatric Association Council on Research (APA CoR) Task Force on Novel Biomarkers and Treatments. Evidence The consensus statement is based on a review of extensive literature from 2 databases (OvidSP MEDLINE and PsycINFO) searched from 1990 through 2016. The search terms included variants of major depressive disorder and transcranial magnetic stimulation. The results were limited to articles written in English that focused on adult populations. Of the approximately 1,500 retrieved studies, a total of 118 publications were included in the consensus statement and were supplemented with expert opinion to achieve consensus recommendations on key issues surrounding the administration of rTMS for MDD in clinical practice settings. Consensus process In cases in which the research evidence was equivocal or unclear, a consensus decision on how rTMS should be administered was reached by the authors of this article and is denoted in the article as "expert opinion." Conclusions Multiple randomized controlled trials and published literature have supported the safety and efficacy of rTMS antidepressant therapy. These consensus recommendations, developed by the NNDC rTMS Task Group and APA CoR Task Force on Novel Biomarkers and Treatments, provide comprehensive information for the safe and effective clinical application of rTMS in the treatment of MDD.

Background Repetitive transcranial magnetic stimulation (rTMS) was approved in 2008 in the United States, and there are relatively few studies describing its use in regular clinical practice since approval. Methods From April 2011 to October 2014, ten sites within the National Network of Depression Centers (NNDC) provided data on 62 evaluable patients with a depressive episode. Treatment was determined naturalistically. Response was assessed by the Quick Inventory of Depressive Symptoms, Self-Report (QIDS-SR) as the primary outcome, and the Patient Health Questionnaire-9 (PHQ-9) and the clinician-rated Clinical Global Impression (CGI) as secondary depression measures. Results Enrolled patients exhibited significant treatment resistance, with 70.2% reporting more than 4 prior depressive episodes. Most patients received treatment with standard parameters (10 Hz over the left dorsolateral prefrontal cortex), although 22.6% of the patients received 1 or 5 Hz stimulation at some point. Over 6 weeks of treatment, response and remission rates were 29.4% and 5.9%, respectively, for the QIDS-SR; 39.2% and 15.7%, respectively, for the PHQ-9; and 50.9% and 17.9%, respectively, for the CGI. Moderator analyses revealed no effect of prior depressive episodes, history of ECT or gender, although early life stress predicted a better response to rTMS therapy. Limitations The study was an open-label, registry trial, with relatively coarse clinical data, reflecting practice only in academic, depression-specialty centers. Because of the relatively small size and heterogeneity of the sample, type 2 errors are possible and positive findings are in need of replication. Conclusion rTMS demonstrates effectiveness in clinical practice within the NNDC, although remission rates appear slightly lower in comparison with other recent naturalistic studies.

Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression.Ten adolescents with treatment-resistant depression were enrolled in an open-label trial of high-frequency rTMS. Participants were offered 30 rTMS sessions (10 Hz, 120% motor threshold, left 3000 pulses applied to the dorsolateral prefrontal cortex) over 6-8 weeks. Coil placement for treatment was MRI guided. The scalp location for treatment was compared with the locations identified with standard 5 cm rule and Beam F3 methods.Seven adolescents completed 30 rTMS sessions. No safety or tolerability concerns were identified. Depression severity as assessed with the Children's Depression Rating Scale Revised improved from baseline to treatment 10, treatment 20, and treatment 30. Gains in depressive symptom improvement were maintained at 6 month follow-up visits. An MRI-guided approach for coil localization was feasible and efficient. Our results suggest that the 5 cm rule, Beam F3, and the MRI-guided localization approaches provided variable scalp targets for rTMS treatment.Open-label, high-frequency rTMS was feasible, tolerable, and effective for adolescents with treatment-resistant depression. Larger, blinded, sham-controlled trials are needed for definitive safety and efficacy data. Further efforts to understand optimal delivery, dosing, and biomarker development for rTMS treatments of adolescent depression are warranted.

Background: The clinical and neurobiological underpinnings of transient nonmotor (TNM) psychiatric symptoms during the optimization of stimulation parameters in the course of subthalamic nucleus deep brain stimulation (STN-DBS) remain under intense investigation. Methods: Forty-nine patients with refractory Parkinson's disease underwent bilateral STN-DBS implants and were enrolled in a 24-week prospective, naturalistic follow-up study. Patients who exhibited TNM psychiatric manifestations during DBS parameter optimization were evaluated for potential associations with clinical outcome measures. Results: Twenty-nine TNM+ episodes were reported by 15 patients. No differences between TNM+ and TNM- groups were found in motor outcome. However, unlike the TNM- group, TNM+ patients did not report improvement in subsyndromal depression or quality of life. TNM+ episodes were more likely to emerge during bilateral monopolar stimulation of the medial STN. Conclusions: The occurrence of TNM psychiatric symptoms during optimization of stimulation parameters was associated with the persistence of subsyndromal depression and with lower quality of life ratings at 6 months. The neurobiological underpinnings of TNM symptoms are investigated yet remain difficult to explain.

Introduction Isotretinoin, previously marketed as Accutane®, is an oral retinoid medication that is used to treat acne and other cutaneous disorders. Although the data is conflicting, previous reports suggest a causal relationship between isotretinoin and depression. When reviewing these previous reports, many patients who were diagnosed as "depressed" did not undergo a thorough psychiatric evaluation and/or were not diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM). These patients reported agitation, irritability, sleep disturbances, and aggression. We hypothesize that some patients previously reported as "depressed" may have been "misdiagnosed" and were actually experiencing symptoms of mania, mixed mood (depression and mania at the same time), or psychosis. Evidence acquisition An Ovid Medline and PubMed literature search of English language articles was performed using the keywords "isotretinoin", "retinoids", "mood", "psychiatric", "depression", "elevation", "bipolar", and "psychosis". Eleven case reports, three case series, three retrospective chart reviews, five drug registries, and two prospective studies were reviewed. Evidence synthesis We found that many of the patients labeled as "depressed", had signs of activation, agitation, elevated mood, and psychosis. We believe that many of these patients were most likely having manic or mixed mood episodes. These symptoms appeared to be more prevalent in patients with a personal or family history of mental illness. Conclusions Isotretinoin may cause mood instability in both directions - depression and mania - especially in a predisposed population. With this in mind, we urge clinicians prescribing isotretinoin to focus on all psychiatric symptoms (not just depression) including mania, mixed mood, and psychosis, paying particular attention to individuals who have a personal or family history of psychiatric disease.

Background Deep brain stimulation for Parkinson disease has been associated with psychiatric adverse effects including anxiety, depression, mania, psychosis, and suicide. Objective The purpose of this study was to evaluate the safety of deep brain stimulation in a large Parkinson disease clinical practice. Methods Patients approved for surgery by the Mayo Clinic deep brain stimulation clinical committee participated in a 6-month prospective naturalistic follow-up study. In addition to the Unified Parkinson's Disease Rating Scale, stability and psychiatric safety were measured using the Beck Depression Inventory, Hamilton Depression Rating Scale, and Young Mania Rating scale. Outcomes were compared in patients with Parkinson disease who had a psychiatric history to those with no co-morbid psychiatric history. Results The study was completed by 49 of 54 patients. Statistically significant 6-month baseline to end-point improvement was found in motor and mood scales. No significant differences were found in psychiatric outcomes based on the presence or absence of psychiatric comorbidity. Conclusions Our study suggests that patients with Parkinson disease who have a history of psychiatric co-morbidity can safely respond to deep brain stimulation with no greater risk of psychiatric adverse effect occurrence. A multidisciplinary team approach, including careful psychiatric screening ensuring mood stabilization and psychiatric follow-up, should be viewed as standard of care to optimize the psychiatric outcome in the course of deep brain stimulation treatment.

The incidence of aggressive behaviors is higher among persons with schizophrenia spectrum disorders (SSDs) than among persons without such disorders. This phenomenon represents a risk to the well-being of patients, their families, and society. The authors undertook a systematic review of the English language literature to determine the efficacy of neuropharmacological agents for the management of hostility and aggression among persons with SSDs. The search combined findings from the Medline, EMBASE, and PsycINFO databases. Ninety-two full text articles were identified that reported relevant findings. The American Academy of Neurology criteria were used to determine levels of evidence. Paliperidone-extended release is probably effective for the management of hostility among inpatients with SSDs who have not been preselected for aggression (Level B). Clozapine is possibly more effective than haloperidol for the management of overt aggression and possibly more effective than chlorpromazine for the management of hostility among inpatients with SSDs who have not been preselected for aggression (Level C). Clozapine is also possibly more effective than olanzapine or haloperidol for reducing aggression among selected physically assaultive inpatients (Level C). Adjunctive propranolol, valproic acid, and famotidine are possibly effective for reducing some aspects of hostility or aggression among inpatients with SSDs (Level C). Paliperidone-extended release currently appears to be the agent for the management of hostility among inpatients with SSDs for which there is the strongest evidence of efficacy.

OBJECTIVE: The Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy of right unilateral ultrabrief pulse electroconvulsive therapy (ECT) combined with venlafaxine for the treatment of geriatric depression. METHOD: PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, combined with open-label venlafaxine at seven academic medical centers. In phase 2 (reported separately), patients who had remitted were randomly assigned to receive pharmacotherapy (venlafaxine plus lithium) or pharmacotherapy plus continuation ECT. In phase 1, depressed patients received high-dose ECT (at six times the seizure threshold) three times per week. Venlafaxine was started during the first week of treatment and continued throughout the study. The primary outcome measure was remission, assessed with the 24-item Hamilton Depression Rating Scale (HAM-D), which was administered three times per week. Secondary outcome measures were post-ECT reorientation and safety. Paired t tests were used to estimate and evaluate the significance of change from baseline in HAM-D scores. RESULTS: Of 240 patients who entered phase 1 of the study, 172 completed it. Overall, 61.7% (148/240) of all patients met remission criteria, 10.0% (24/240) did not remit, and 28.3% (68/240) dropped out; 70% (169/240) met response criteria. Among those who remitted, the mean decrease in HAM-D score was 24.7 points (95% CI=23.4, 25.9), with a mean final score of 6.2 (SD=2.5) and an average change from baseline of 79%. The mean number of ECT treatments to remission was 7.3 (SD=3.1). CONCLUSIONS: Right unilateral ultrabrief pulse ECT, combined with venlafaxine, is a rapidly acting and highly effective treatment option for depressed geriatric patients, with excellent safety and tolerability. These data add to the evidence base supporting the efficacy of ECT to treat severe depression in elderly patients.

Much is known regarding the physical characteristics, comorbid symptoms, psychological makeup, and neuropsychological performance of patients with functional neurological disorders (FNDs)/conversion disorders. Gross neurostructural deficits do not account for the patients' deficits or symptoms. This review describes the literature focusing on potential neurobiological (i.e. functional neuroanatomic/neurophysiological) findings among individuals with FND, examining neuroimaging and neurophysiological studies of patients with the various forms of motor and sensory FND. In summary, neural networks and neurophysiologic mechanisms may mediate "functional" symptoms, reflecting neurobiological and intrapsychic processes.

This case report describes a 60-year-old woman who experienced a posterior vitreous detachment (PVD) and retinal tear after her 11th session of 1 Hz repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depression. Although we cannot conclude that rTMS caused her PVD and retinal tear, the temporal association is strong, and we hypothesize a possible pathophysiology of the event. As part of the routine clinical monitoring of rTMS side effects, we encourage attention toward ophthalmologic symptoms, especially in older patients.

Objectives Patients with heart failure may experience psychiatric disorders for which electroconvulsive therapy (ECT) is indicated. Little is known, however, about the safety of ECT in these patients. We assessed the safety of ECT in patients with a history of heart failure and decreased left ventricular systolic heart function. Methods We conducted a retrospective review of the medical records of 35 patients with a history of heart failure and reduced left ventricular systolic heart function who underwent ECT at Mayo Clinic in Rochester, Minnesota, between January 1995 and December 2009. Results Of the 35 patients, 18 (51%) were women. The median age was 77 years (range, 54-92 years). The median left ventricular ejection fraction was 30% (range, 15%-40%). The 35 patients underwent 513 ECT sessions (median number of sessions per patient, 10; range, 1-44). The 35 patients tolerated ECT well. No patient died or experienced decompensated heart failure, myocardial ischemia, or myocardial infarction during or within 24 hours after an ECT session. Prophylactic intravenous β-blockers were given to patients who, during previous ECT sessions, had marked hypertension (eg, systolic blood pressure >180-200 mm Hg) or a heart rate greater than 100 beats per minute; overall, this prophylaxis was used in 26 patients during 413 ECT sessions (80% of the total number of ECT sessions). Three patients experienced temporary, non-life-threatening cardiac arrhythmias. Conclusions Electroconvulsive therapy was safe in 35 patients with a history of heart failure and decreased left ventricular systolic heart function treated at our institution.

A number of antidepressant medications, as well as electroconvulsive therapy, have been shown to reduce chronic pain. Slow-frequency repetitive transcranial magnetic stimulation (rTMS) applied to the right dorsolateral prefrontal cortex has also been shown to have an antidepressant effect. Given the high degree of suffering experienced by subjects with chronic neuropathic pain and the treatment resistance noted in this population, the use of slow-frequency rTMS as adjuvant therapy may be of significant clinical benefit.Fifteen sessions of 1-Hz rTMS (1600 stimulations/session) were applied to the right dorsolateral prefrontal cortex as adjuvant treatment in 9 subjects with refractory neuropathic pain over 3 weeks. Pain and depression ratings were performed at baseline, weekly during rTMS treatment, and monthly for up to 3 months after treatment.Five males and 4 females participated, and all had longstanding refractory neuropathic pain (range, 1-19 years), with an average baseline pain rating of 7.3 and no depression (Hamilton Rating Scale for Depression average, 3.6; range, 0-8). Three subjects had a greater than 50% decline in pain ratings by the completion of rTMS treatments, and 1 subject responded more slowly with greater than 50% improvement in pain by the end of the 3-month follow-up. An improvement in pain ratings was noted in responders within the first week.Although these are preliminary findings in an open treatment trial, the subjects in this trial are among the least likely to have a placebo response. Given that rTMS is a well-tolerated and noninvasive intervention, any sustained improvement in neuropathic pain with rTMS is encouraging.

Major depressive disorder (MDD) in adolescents is a common illness and significant public health problem. Treatment is challenging due to recurrences and limited modalities. Selective serotonin reuptake inhibitors (SSRIs) and Cognitive Behavioral Therapy (CBT) are considered the standard of care in severe or treatment resistant MDD in this age group. However, responses to these interventions are often suboptimal. A growing body of research supports the efficacy of repetitive transcranial magnetic stimulation for the treatment of MDD in adults. Induced seizures are a primary safety concern, although this is rare with appropriate precautions. There is, however, limited experience with rTMS as a therapeutic intervention for adolescent psychiatric disturbances. This review will summarize the rTMS efficacy and safety data in adults and describe all published experience with adolescent MDD. Applications in other adolescent psychiatric illnesses such as schizophrenia and attention-deficit/hyperactivity disorder (ADHD) are reviewed. Safety and ethical issues are paramount with investigational treatments in adolescent psychiatric illnesses. However, further research with rTMS in adolescent MDD is imperative to establish standards for optimal stimulation site, treatment parameters, and its role in treatment algorithms. These may diverge from adult data. Early intervention with neuromodulation could also hold the promise of addressing the developmental course of dysfunctional neurocircuitry.

Background Although transcranial magnetic stimulation (TMS) can be an effective acute antidepressant treatment, few studies systematically examine persistence of benefit. Objective We assessed the durability of antidepressant effect after acute response to TMS in patients with major depressive disorder (MDD) using protocol-specified maintenance antidepressant monotherapy. Methods Three hundred one patients were randomly assigned to active or sham TMS in a 6-week, controlled trial. Nonresponders could enroll in a second, 6-week, open-label study. Patients who met criteria for partial response (i.e., >25% decrease from the baseline HAMD 17) during either the sham-controlled or open-label study (n = 142) were tapered off TMS over 3 weeks, while simultaneously starting maintenance antidepressant monotherapy. Patients were then followed for 24 weeks in a naturalistic follow-up study examining the long-term durability of TMS. During this durability study, TMS was readministered if patients met prespecified criteria for symptom worsening (i.e., a change of at least one point on the CGI-S scale for 2 consecutive weeks). Relapse was the primary outcome measure. Results Ten of 99 (10%; Kaplan-Meier survival estimate=12.9%) patients relapsed . Thirty-eight (38.4%) patients met criteria for symptom worsening and 32/38 (84.2%) reachieved symptomatic benefit with adjunctive TMS. Safety and tolerability were similar to acute TMS monotherapy. Conclusions These initial data suggest that the therapeutic effects of TMS are durable and that TMS may be successfully used as an intermittent rescue strategy to preclude impending relapse.

Bailine S, Fink M, Knapp R, Petrides G, Husain MM, Rasmussen K, Sampson S, Mueller M, McClintock SM, Tobias KG, Kellner CH. Electroconvulsive therapy is equally effective in unipolar and bipolar depression. Objective: To determine the relative efficacy of electroconvulsive therapy (ECT) in the treatment of bipolar (BP) and unipolar (UP) depressive illness and clarify its role in BP depression. Method: Patients referred for ECT with both UP and BP depressions. [classified by Structured Clinical Interview for DSM (SCID-I) criteria for history of mania] were included in a multi-site collaborative, double-masked, randomized controlled trial of three electrode placements – right unilateral, bifrontal or bitemporal – in a permutated block randomization scheme. Results: Of 220 patients, 170 patients (77.3%) were classified as UP and 50 (22.7%) as BP depression in the intent-to-treat sample. The remission and response rates and numbers of ECT for both groups were equivalent. Conclusion: Both UP and BP depressions remit with ECT. Polarity is not a factor in the response rate. In this sample ECT did not precipitate mania in depressed patients. Treatment algorithms for UP and BP depression warrant re-evaluation.

Effective strategies to prolong remission after electroconvulsive therapy (ECT) are urgently needed. Fixed schedules for continuation ECT (C-ECT) cannot adapt to early signs of impending relapse. Symptom-Titrated, Algorithm-Based Longitudinal ECT (STABLE) is proposed as a novel patient-focused approach to individualize the ECT schedule. In STABLE, the ECT schedule adapts to symptom fluctuations to prevent overtreatment of those who do not need it and to recapture response in those who might have otherwise relapsed with a rigid dosing schedule. Here we back-test STABLE to optimize the algorithm for subsequent testing in a prospective trial.Three variations of the STABLE algorithm, differing in cutoff points to trigger or withhold additional ECT, were back-tested in a data set of 89 patients randomized to the C-ECT arm in the CORE (Consortium for Research on ECT) Study comparing C-ECT with combination pharmacotherapy.The selected algorithm identified 100% of patients who ultimately relapsed as requiring additional ECT at an average of 2.2 weeks before relapse, while exposing 20% of sustained remitters to additional ECT. Other variations either failed to capture impending relapse or exposed an unacceptably large percentage of patients to potentially unnecessary ECT.This patient-focused approach to relapse prevention is an attempt to provide the first operationalized guidance to the field regarding how to conduct C-ECT. The effectiveness of this approach should be tested in a randomized controlled trial.

Objective The authors examine the differences in outcome between black and white patients receiving electroconvulsive therapy (ECT) as a part of the Consortium for Research on Electroconvulsive Therapy multisite study. Methods A total of 624 patients were enrolled in an National Institute of Mental Health (NIMH)-funded, randomized, controlled ECT trial comparing the efficacy of continuation ECT versus continuation pharmacotherapy between 1997 and 2004. This analysis focuses on the 32 black and 483 white patients who participated in phase I of the study. The authors compared baseline demographic and clinical variables and acute outcomes of these 2 groups. Results Compared with whites, far fewer blacks participated in the study. Those who did were less likely to have failed adequate medication trials and were more likely to have psychotic features. Their initial 24-item Hamilton Rating Scale for Depression scores were higher than those of the whites, and they showed a greater reduction in these 24-item Hamilton Rating Scale for Depression scores by the end of the treatment period. Although sample size limited the statistical significance of the findings, black patients also showed a higher rate of remission after an acute phase of ECT. Conclusions This study found that black and white patients with major depressive disorder had comparable outcomes. We also found that fewer black patients received ECT than whites, a difference that has been reported in other samples.

The Committee on Research of the American Neuropsychiatric Association conducted a review of the noncognitive neuropsychiatric manifestations of frontotemporal dementia. The Committee on Research searched reviews and several online databases for all pertinent publications. Single case reports without pathology were excluded, except for psychosis, where single cases made up much of the literature. The strongest evidence supports an association of frontotemporal dementia with the following behaviors: apathy-abulia; disinhibition-impulsivity; loss of insight and self-referential behavior; decreased emotion and empathy; violation of social and moral norms; changes in dietary or eating behavior; and repetitive behaviors. Frontotemporal dementia is less frequently associated with anxiety and mood disorders, which may be a prodrome or risk factor, and rarely presents with delusions or hallucinations. The results of this review highlight the distinct neuropsychiatric manifestations of frontotemporal dementia and the need to reconsider the current diagnostic criteria for this disorder.

There is limited research examining the treatment of atypical depression with electroconvulsive therapy (ECT). Early research1,2 suggested that ECT was ineffective in treating atypical depression. Although ECT resulted in minor improvement in mood,2 many patients with atypical depressive features did not maintain the effect. However, neither study categorically defined atypical depression. They regarded atypical as being different from typical depression on the basis of undefined or varying symptom feature differences. Also, the study of West and Dally2 was confounded by inclusion of patients who had primary anxiety disorders and secondary depression. While this early research has served as the basis for clinical decision making for decades, advances in both the understanding of atypical depression and the techniques involved in ECT recommend a reevaluation of this notion. Recently, the definition of atypical depression has been operationalized to include the presence of mood reactivity plus 13 or 24,5 of the following additional symptom(s): hypersomnia, increased appetite or weight gain, leaden paralysis, and interpersonal rejection sensitivity. More recent studies also suggest that atypical depression may be more prevalent than previously thought. Early rates of atypical depression varied between 1.4% and 2.8%,6,7 and a lifetime prevalence of 0.7% was found in the Epidemiologic Catchment Area study.8 However, a prevalence rate of 6% was found for atypical depression in the National Comorbidity Survey.9 Also, in the Sequenced Treatment Alternatives to Relieve Depression trial,10 18% of the first 1500 patients met criteria for depression with atypical features. Moreover, the practice of ECT has improved11–13 with standardized lead placement (e.g., bilateral, right unilateral) and improved stimulus dosing.14 Thus, it would be appropriate to reevaluate the clinical efficacy of ECT for the treatment of depression with atypical symptom features. This article describes and characterizes patients with atypical major depressive disorder referred for ECT in a multisite trial examining the efficacy of maintenance ECT and examines the outcome of acute-phase ECT for patients with and without atypical depressive symptom features.

Background We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. Methods In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active ( n = 155) or sham TMS ( n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4–6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery–Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. Results Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. Conclusions Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.

Abnormalities in glutamate neurotransmission may have a role in the pathophysiology of adolescent depression. The present pilot study examined changes in cortical glutamine/glutamate ratios in depressed adolescents receiving high-frequency repetitive transcranial magnetic stimulation. Ten adolescents with treatment-refractory major depressive disorder received up to 30 sessions of 10-Hz repetitive transcranial magnetic stimulation at 120% motor threshold with 3000 pulses per session applied to the left dorsolateral prefrontal cortex. Baseline, posttreatment, and 6-month follow-up proton magnetic resonance spectroscopy scans of the anterior cingulate cortex and left dorsolateral prefrontal cortex were collected at 3T with 8-cm(3) voxels. Glutamate metabolites were quantified with 2 distinct proton magnetic resonance spectroscopy sequences in each brain region. After repetitive transcranial magnetic stimulation and at 6 months of follow-up, glutamine/glutamate ratios increased in the anterior cingulate cortex and left dorsolateral prefrontal cortex with both measurements. The increase in the glutamine/glutamate ratio reached statistical significance with the TE-optimized PRESS sequence in the anterior cingulate cortex. Glutamine/glutamate ratios increased in conjunction with depressive symptom improvement. This reached statistical significance with the TE-optimized PRESS sequence in the left dorsolateral prefrontal cortex. High-frequency repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex may modulate glutamate neurochemistry in depressed adolescents.

Most studies of trends in antidepressant pharmacotherapy have focused on relatively mildly ill, nonpyschotic outpatients. In this report, we provide detailed information on psychotropic use among patients with unipolar depression participating in a large, multisite electroconculsive therapy (ECT) study. Adequacy of antidepressant medication trials was assessed with the Antidepressant Treatment History Form. Among patients with nonpsychotic depression, 27% (60/220) had not had an adequate trial of an antidepressant before ECT, and 63% (139/220) had had at least one inadequate trial. Surprisingly, 33% (79/243) of nonpsychotic patients had been prescribed an antipsychotic. Among patients with psychotic depression, 95% (101/106) had not been given an adequate combination of an antidepressant and antipsychotic agent, mostly due to low doses of the latter class. Among all patients in the trial, 61% (213/352) had been prescribed at least one benzodiazepine, and only 7% (24/352) had been given a lithium augmentation trial. Use of hypnotic agents and anticonvulsants was common. In conclusion, patients with severe depression referred for ECT with a unipolar depressive episode have high rates of psychotropic usage, much of which is inadequate.

Compared with men, women are more likely to experience depression, and depression increases risk of morbidity and mortality in individuals with heart disease. Psychosocial interventions have been developed for depressed patients with heart disease; however, women's experience of chronic disease differs from men's and women may benefit from interventions tailored to address their difficulties. Spirituality and social roles have been related to depressive symptoms in other populations. To identify the relationship between depression and spirituality and social role performance (i.e., role concerns, role rewards and confidence in ability to fulfill roles) in women with heart disease, we assessed depressive symptoms, spirituality, social role functioning and medical history in 125 women with heart disease. After controlling for age and severity of medical conditions, spirituality, role confidence and role concerns were significantly associated with depressive symptoms. Consideration of spirituality and aspects of social role performance may be important when developing psychosocial interventions for depressed women with heart disease.

Objective. Evidence suggests that fibromyalgia (FM) is a centrally mediated pain disorder. Antidepressants, including electroconvulsive therapy, provide some symptomatic relief in FM and other pain disorders. Repetitive transcranial magnetic stimulation (rTMS) is a new antidepressant treatment, which may also be useful in treating chronic pain. Design. As part of a larger study, four women with depression, FM, and borderline personality disorder received 1-Hz rTMS applied to the right dorsolateral prefrontal cortex. Subjects rated pain using an 11-point Likert scale. Results. Pretreatment pain averaged 8.2 (7–9.5) and reduced to 1.5 (0–3.5) after treatment ( P < 0.009). All had improvement in pain, and two had complete resolution of pain. Only one of the four subjects had an antidepressant response. Conclusions. These preliminary findings suggest a possible role for rTMS in treating FM.

The authors determined the efficiency of electronic documentation in consultation-liaison psychiatry. An electronic note system was customized for a psychiatric consultation note. Specific attention given to common diagnoses permitted rapid documentation. Residents learned the system quickly. The standardized nature of the system ensured thorough documentation. Notes were immediately available and more legible. A survey indicated that this system was well received and saved time. Among the eight residents who used both handwriting and typing, an estimated average of 17.5 minutes per note was saved by typing. This program had clear benefits in reinforcing more complete documentation.

Patients treated with electroconvulsive therapy (ECT) were divided into those with less severe depression and those with more severe depression. In the less severely depressed group, high somatic anxiety and hypochondriasis predicted a low likelihood of sustained remission with ECT. In the more severely depressed group, these traits were not predictive of ECT outcome.

Deep brain stimulation (DBS) is a novel and effective surgical intervention for refractory Parkinson's disease (PD). The authors review the current literature to identify the clinical correlates associated with subthalamic nucleus (STN) DBS-induced hypomania/mania in PD patients. Ventromedial electrode placement has been most consistently implicated in the induction of STN DBS-induced mania. There is some evidence of symptom amelioration when electrode placement is switched to a more dorsolateral contact. Additional clinical correlates may include unipolar stimulation, higher voltage (gt;3 V), male sex, and/or early-onset PD. STN DBS-induced psychiatric adverse events emphasize the need for comprehensive psychiatric presurgical evaluation and follow-up in PD patients. Animal studies and prospective clinical research, combined with advanced neuroimaging techniques, are needed to identify clinical correlates and underlying neurobiological mechanisms of STN DBS-induced mania. Such working models would serve to further our understanding of the neurobiological underpinnings of mania and contribute valuable new insight toward development of future DBS mood-stabilization therapies.

To examine changes in motor cortical excitability in adolescent subjects receiving 30 sessions of high-frequency prefrontal repetitive transcranial magnetic stimulation (rTMS).Eight adolescents with treatment-resistant major depressive disorder (MDD) enrolled in an open augmentation trial of 10 Hz rTMS. Resting motor thresholds were obtained by the visualization of movement method with a maximum likelihood threshold hunting computer algorithm at baseline and after every five sessions of rTMS. Motor threshold was recorded as the percentage of total machine output at each measurement.Motor threshold data from baseline, weeks 2, 4, and 5 were included in a mixed model repeated measure analysis to examine a change in least square mean effect over time. The omnibus effect did not reach statistical significance (F=1.25, p=0.32). However, multiple comparisons from the overall model demonstrated a decrease in the least square mean motor threshold. The mean contrast from baseline to week 5 approached significance (p=0.07). Moreover, a post-hoc analysis with a Wilcoxon signed ranks test demonstrated a significant decrease at week 5 (p=0.03).This suggests that high-frequency rTMS may increase cortical excitability in adolescents with treatment-resistant MDD.

Introduction: Major depressive disorder (MDD) is thought to negatively impact cognitive function; however, the relationship has not been well explored.Objective: This study examined the association between depression severity and global cognitive function and memory in subjects with severe, treatment-resistant MDD.Methods: We enrolled 66 subjects with Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosed unipolar MDD in a multicenter trial to assess the efficacy and neurocognitive effects of electroconvulsive therapy (ECT). We measured depression severity with the 24 item Hamilton Rating Scale for Depression (HRSD24). Neuropsychologic measures included the Mini Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), and the Complex Figure Test (CFT). Correlational and regression analyses were conducted to explore associations between depression severity and cognitive function.Results: The mean age of the subjects was 53.6 years (SD=15.8), 65% were female, and mean HRSD24 was 33.9 (SD=6.7). Mean demographic-corrected T-scores for each neurocognitive measure were in the average to borderline range, and HRSD24 values were unrelated to performance on the MMSE, RAVLT immediate and delayed recall, and CFT immediate and delayed recall.Conclusion: In this sample of severely depressed subjects referred for ECT, depression severity was unrelated to global cognitive function or memory. Future research should examine the interactions between other depressive characteristics and neurocognitive function.

BackgroundElectroconvulsive therapy (ECT) is an effective treatment for major depression. Optimising efficacy and minimising cognitive impairment are goals of ongoing technical refinements.AimsTo compare the efficacy and cognitive effects of a novel electrode placement, bifrontal, with two standard electrode placements, bitemporal and right unilateral in ECT.MethodThis multicentre randomised, double-blind, controlled trial (NCT00069407) was carried out from 2001 to 2006. A total of 230 individuals with major depression, bipolar and unipolar, were randomly assigned to one of three electrode placements during a course of ECT: bifrontal at one and a half times seizure threshold, bitemporal at one and a half times seizure threshold and right unilateral at six times seizure threshold.ResultsAll three electrode placements resulted in both clinically and statistically significant antidepressant outcomes. Remission rates were 55% (95% CI 43–66%) with right unilateral, 61% with bifrontal (95% CI 50–71%) and 64% (95% CI 53–75%) with bitemporal. Bitemporal resulted in a more rapid decline in symptom ratings over the early course of treatment. Cognitive data revealed few differences between the electrode placements on a variety of neuropsychological instruments.ConclusionsEach electrode placement is a very effective antidepressant treatment when given with appropriate electrical dosing. Bitemporal leads to more rapid symptom reduction and should be considered the preferred placement for urgent clinical situations. The cognitive profile of bifrontal is not substantially different from that of bitemporal.

Background: This report describes the results of an open-label extension study of active transcranial magnetic stimulation (TMS) in medication-resistant patients with major depressive disorder who did not benefit from an initial course of therapy in a previously reported 6-week, randomized controlled study of active versus sham TMS. Method: Patients with DSM-IV‐defined major depressive disorder were actively enrolled in the study from February 2004 through September 2005 and treated with left prefrontal TMS administered 5 times per week at 10 pulses per second, at 120% of motor threshold, for a total of 3000 pulses/session. The primary outcome was the baseline to endpoint change score on the Montgomery-Asberg Depression Rating Scale (MADRS). Results: In those patients who received sham in the preceding randomized controlled trial (N = 85), the mean reduction in MADRS scores after 6 weeks of open-label active TMS was ‐17.0 (95% CI = ‐14.0 to ‐19.9). Further, at 6 weeks, 36 (42.4%) of these patients achieved response on the MADRS, and 17 patients (20.0%) remitted (MADRS score < 10). For those patients who received and did not respond to active TMS in the preceding randomized controlled trial (N = 73), the mean reduction in MADRS scores was ‐12.5 (95% CI = ‐9.7 to ‐15.4), and response and remission rates were 26.0% and 11.0%, respectively, after 6 weeks of additional openlabel TMS treatment. Conclusions: This open-label study provides further evidence that TMS is a safe and effective treatment of major depressive disorder. Furthermore, continued active TMS provided additional benefit to some patients who failed to respond to 4 weeks of treatment, suggesting that longer courses of treatment may confer additional therapeutic benefit. Trial Registration: clinicaltrials.gov Identifier: NCT00104611 (J Clin Psychiatry 2008;69:441‐451) T

Objective To test whether pre-electroconvulsive therapy (ECT) medication resistance is associated with post-ECT relapse rates. Method In a post hoc analysis of data from a large multicenter trial of post-ECT relapse prevention strategies (conducted from May 1997 to July 2004), we assessed whether response to antidepressant medications prior to ECT for a unipolar nonpsychotic depressive episode (DSM-IV) was associated with differential relapse rates after remission with ECT. Baseline (i.e., pre-ECT) medication use was assessed with the Antidepressant Treatment History Form. Following remission with ECT that was stable for 1 week, patients were randomly assigned to receive 6 months of treatment with either combination lithium carbonate/nortriptyline or continuation ECT. Relapse was assessed with the 24-item Hamilton Rating Scale for Depression. There were 146 patients followed in the first week after remission (termed the interim week in this study), and 73 in the randomized phase of the study. For the purposes of this trial, medication resistance is defined as not having responded to at least 1 adequate trial of an antidepressant medication before ECT. Results In the first week after acute remission, 9.8% of patients not having at least 1 antidepressant medication trial met relapse criteria, while 31.4% of medication-resistant patients met relapse criteria, a difference that was statistically significant (p = .026). In the randomized phase of the study, 34.6% of non-medication-resistant patients relapsed, while 50.0% of medication-resistant patients relapsed, a difference that was not significant (p = .434). Conclusion We conclude that nonpsychotic patients who had at least 1 adequate antidepressant medication trial before ECT may be especially prone to early relapse after successful acute remission with ECT.

Major depression is a common medical illness, which is projected to be second only to ischemic heart disease for global disease burden by 2020. Depression is often a recurrent illness and can be difficult to treat. Because an estimated 20% to 40% of patients fail to respond to antidepressant medications and psychotherapy, new treatment options for depression are needed. ABOUT THE AUTHORS Shirlene M. Sampson, MD, MSc, is with the Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN. H. Brent Solvason, MD, PhD, is with the Department of Psychiatry, Stanford University, Palo Alto, CA. Mustafa Husain, MD, is with the Department of Psychiatry, University of Texas Southwestern, Dallas, TX. Address correspondence to: Shirlene M. Sampson, MD, MSc, Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905; fax 507-284-4158; or email sampson.shirlene@mayo.edu. Dr. Sampson is a research grant recipient for Neuronetics Inc. , developer of NeuroStar TMS (transcranial magnetic stimulation) System. Drs. Solvason and Husain disclosed no relevant financial relationships. EDUCATIONAL OBJECTIVES Discuss technical considerations in performing transcranial magnetic stimulation (TMS). Discuss safety issues related to the use of TMS. Assess how to approach screening patients for possible TMS treatment for depression.

This article reviews the existing literature on the use of computer assisted instruction (CAI) in the field of psychiatry to answer the questions, 1) Is CAI an effective tool for teaching psychiatry? and 2) What are the best methods for studying CAI in a real-world training environment? A Medline search was conducted for relevant articles, which were divided into three categories: media comparative (head-to-head trials), demonstration (reports of single CAI interventions) or analytical (commentary/reviews). Twenty articles were identified. Although they tend to show that CAI is as good as or sometimes better than traditional teaching methods, the data are extremely variable and there are significant methodological difficulties that complicate interpretation of the data. These problems are consistent with difficulties experienced in other medical specialties when studying CAI. It is difficult to draw conclusions about the efficacy of CAI in psychiatry from this disparate sample of articles. Efforts to compare CAI interventions with traditional teaching methods have significant inherent limitations and biases and are very difficult to conduct in a naturalistic educational setting. The author offers alternative approaches to studying CAI in psychiatry.

Background Although electroconvulsive therapy (ECT) has been shown to be extremely effective for the acute treatment of major depression, it has never been systematically assessed as a strategy for relapse prevention. Objective To evaluate the comparative efficacy of continuation ECT (C-ECT) and the combination of lithium carbonate plus nortriptyline hydrochloride (C-Pharm) in the prevention of depressive relapse. Design Multisite, randomized, parallel design, 6-month trial performed from 1997 to 2004. Setting Five academic medical centers and their outpatient psychiatry clinics. Patients Two hundred one patients with Structured Clinical Interview for DSM-IV– diagnosed unipolar depression who had remitted with a course of bilateral ECT. Interventions Random assignment to 2 treatment groups receiving either C-ECT (10 treatments) or C-Pharm for 6 months. Main Outcome Measure Relapse of depression, compared between the C-ECT and C-Pharm groups. Results In the C-ECT group, 37.1% experienced disease relapse, 46.1% continued to have disease remission at the study end, and 16.8% dropped out of the study. In the C-Pharm group, 31.6% experienced disease relapse, 46.3% continued to have disease remission, and 22.1% dropped out of the study. Both Kaplan-Meier and Cox proportional hazards regression analyses indicated no statistically significant differences in overall survival curves and time to relapse for the groups. Mean ± SD time to relapse for the C-ECT group was 9.1 ± 7.0 weeks compared with 6.7 ± 4.6 weeks for the C-Pharm group ( P = .13). Both groups had relapse proportions significantly lower than a historical placebo control from a similarly designed study. Conclusions Both C-ECT and C-Pharm were shown to be superior to a historical placebo control, but both had limited efficacy, with more than half of patients either experiencing disease relapse or dropping out of the study. Even more effective strategies for relapse prevention in mood disorders are urgently needed.

Severe mental illnesses often remain chronic and refractory to medication, leading to substantial morbidity and mortality. For more than 60 years, electroconvulsive therapy has been the only nonpharmacological psychiatric procedure available to treat severe or medication-refractory major depressive disorder and other psychiatric conditions. Memory dysfunction remains the most serious adverse effect, and current research focuses on attempts to ameliorate this complication. Transcranial magnetic stimulation and vagus nerve stimulation, 2 new neuropsychiatric technologies, are emerging as possible additions to our therapeutic armamentarium. Besides providing therapeutic benefits, these 3 methods may help elucidate the pathophysiology of psychiatric illness.

Major depression is a common mental health disorder in adolescents that predicts a significant risk for recurrence in adulthood. Suicide is the third most frequent cause of deaths in this age group, and depression is a significant risk factor for suicidal ideation and attempts. Risks for depression and suicidal ideation are reviewed, and subtypes of depression are discussed. Difficulties associated with identification of depression and suicidal ideation in adolescents and biologic therapies for adolescent depression are reviewed.