A Case Series of 11 Patients With Subacute Serotonin Syndrome.

BACKGROUND: Serotonin syndrome is an acute, life-threatening illness characterized by mental status changes, neuromuscular symptoms, and autonomic instability. Some patients taking serotonergic antidepressants have been noted to have unexplained mental status changes and/or neuromuscular changes without autonomic instability raising the possibility of a more chronic or attenuated form of serotonin syndrome. OBJECTIVE: Assessment of antidepressant blood levels to support the diagnosis of a subacute serotonin syndrome. METHODS: At a tertiary psychiatric outpatient clinic, patients with unexplained mental status and/or neuromuscular changes without autonomic instability had antidepressant blood levels assessed. RESULTS: Eleven patients were identified with signs and symptoms partially consistent with serotonin syndrome. Nine patients had cognitive changes, while four patients had motor changes, and three patients had psychosis. All patients had elevated blood levels of a single serotonergic antidepressant. Limited follow-up suggests that symptoms improve with reduction of antidepressant medication. CONCLUSIONS: These cases suggest that a more chronic, attenuated form of serotonin syndrome exists. Diagnostic criteria are proposed for a distinct clinical entity: subacute serotonin syndrome (SSS). Further research is required to validate these criteria. Clinicians should consider drawing antidepressant levels for patients with symptoms and signs suggestive of SSS-especially those at increased vulnerability for excessive serotonergic agonism. Given the high prevalence of antidepressant medication use, the awareness of SSS could lead to improved patient outcomes and public health.

Isotretinoin: the ups are just as troubling as the downs.

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.

Consensus Recommendations for the Clinical Application of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of 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.

Stimulation-Induced Transient Nonmotor Psychiatric Symptoms following Subthalamic Deep Brain Stimulation in Patients with Parkinson's Disease: Association with Clinical Outcomes and Neuroanatomical Correlates.

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.

Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Transcranial magnetic stimulation potentiates glutamatergic neurotransmission in depressed adolescents.

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.

Neurocognitive effects of repetitive transcranial magnetic stimulation in adolescents with major depressive disorder.

OBJECTIVES: It is estimated that 30-40% of adolescents with major depressive disorder (MDD) do not receive full benefit from current antidepressant therapies. Repetitive transcranial magnetic stimulation (rTMS) is a novel therapy approved by the US Food and Drug Administration to treat adults with MDD. Research suggests rTMS is not associated with adverse neurocognitive effects in adult populations; however, there is no documentation of its neurocognitive effects in adolescents. This is a secondary post hoc analysis of neurocognitive outcome in adolescents who were treated with open-label rTMS in two separate studies. METHODS: Eighteen patients (mean age, 16.2 ± 1.1 years; 11 females, 7 males) with MDD who failed to adequately respond to at least one antidepressant agent were enrolled in the study. Fourteen patients completed all 30 rTMS treatments (5 days/week, 120% of motor threshold, 10 Hz, 3,000 stimulations per session) applied to the left dorsolateral prefrontal cortex. Depression was rated using the Children's Depression Rating Scale-Revised. Neurocognitive evaluation was performed at baseline and after completion of 30 rTMS treatments with the Children's Auditory Verbal Learning Test (CAVLT) and Delis-Kaplan Executive Function System Trail Making Test. RESULTS: Over the course of 30 rTMS treatments, adolescents showed a substantial decrease in depression severity. Commensurate with improvement in depressive symptoms was a statistically significant improvement in memory and delayed verbal recall. Other learning and memory indices and executive function remained intact. Neither participants nor their family members reported clinically meaningful changes in neurocognitive function. CONCLUSION: These preliminary findings suggest rTMS does not adversely impact neurocognitive functioning in adolescents and may provide subtle enhancement of verbal memory as measured by the CAVLT. Further controlled investigations with larger sample sizes and rigorous trial designs are warranted to confirm and extend these findings.

Increased cortical excitability with prefrontal high-frequency repetitive transcranial magnetic stimulation in adolescents with treatment-resistant major depressive disorder.

OBJECTIVE: To examine changes in motor cortical excitability in adolescent subjects receiving 30 sessions of high-frequency prefrontal repetitive transcranial magnetic stimulation (rTMS). METHODS: 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. RESULTS: 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). CONCLUSIONS: This suggests that high-frequency rTMS may increase cortical excitability in adolescents with treatment-resistant MDD.

Posterior vitreous detachment and retinal tear after repetitive transcranial magnetic stimulation.

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.

Adjunctive use of repetitive transcranial magnetic stimulation in depressed adolescents: a prospective, open pilot study.

OBJECTIVE: Depression is often a serious and debilitating illness in adolescents. Unfortunately, a significant number of adolescents do not respond to antidepressant medications or psychotherapy. Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment intervention shown to benefit depression in adults. This study considered rTMS as an adjunctive treatment in adolescents with major depressive disorder. METHOD: This prospective, open, multicenter trial of active adjunctive rTMS was conducted with 8 adolescents with DSM-IV-TR major depressive disorder (MDD) that had not responded sufficiently to 2 adequate antidepressant medication trials. All subjects were maintained on a stable dose of a selective serotonin reuptake inhibitor during the trial. Thirty daily rTMS treatments were given 5 days per week over 6 to 8 weeks. rTMS was applied to the left dorsolateral prefrontal cortex (120% of motor threshold; 10 Hz; 4-second trains; 26-second intertrain interval; 75 trains) for a total of 3,000 stimulations per treatment session. RESULTS: Seven of 8 adolescents completed all 30 treatments. rTMS was well tolerated, and no significant safety issues were identified. Suicidal ideation was present at baseline in 3 of the adolescents, and it improved during treatment. The primary outcome measure was the Children's Depression Rating Scale-Revised (CDRS-R); results improved significantly from baseline (mean [SD]) (65.9 [6.6]) to treatment 10 (50.9 [12]), P < .02. The CDRS-R scores continued to improve through the rTMS treatment series at treatment 20 (40.1 [14]), P < .01; treatment 30 (32.6 [7.3]), P < .0001; and at 6-month follow-up (32.7 [3.8]), P < .0001. CONCLUSIONS: This prospective open trial suggests that rTMS is a safe, feasible, and potentially effective adjunctive therapy for treatment-resistant MDD in adolescents. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00587639.

The use of slow-frequency prefrontal repetitive transcranial magnetic stimulation in refractory neuropathic pain.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Durability of clinical benefit with transcranial magnetic stimulation (TMS) in the treatment of pharmacoresistant major depression: assessment of relapse during a 6-month, multisite, open-label study.

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.

The emerging role for repetitive transcranial magnetic stimulation in optimizing the treatment of adolescent depression.

Major depressive disorder (MDD) in adolescents is a common illness and significant public health problem. Treatment is challenging because of recurrences and limited modalities. Selective serotonin reuptake inhibitors and cognitive behavioral therapy 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 (rTMS) 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 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.

Is baseline medication resistance associated with potential for relapse after successful remission of a depressive episode with ECT? Data from the Consortium for Research on Electroconvulsive Therapy (CORE).

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.

An evidence-based review of the psychopathology of frontotemporal dementia: a report of the ANPA Committee on Research.

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.

Transcranial magnetic stimulation in the treatment of major depressive disorder: a comprehensive summary of safety experience from acute exposure, extended exposure, and during reintroduction treatment.

BACKGROUND: Transcranial magnetic stimulation (TMS) has demonstrated efficacy in the treatment of major depressive disorder; however, prior studies have provided only partial safety information. We examined the acute efficacy of TMS in a randomized sham-controlled trial, under open-label conditions, and its durability of benefit. METHOD: Aggregate safety data were obtained from a comprehensive clinical development program examining the use of TMS in the treatment of major depressive disorder. There were 3 separate clinical protocols, including 325 patients from 23 clinical sites in the United States, Australia, and Canada. Active enrollment occurred between January 2004 and August 2005. Adverse events were assessed at each study visit by review of spontaneous reports with separate reporting of serious adverse events. Safety assessments were also completed for cognitive function and auditory threshold. Assessment of disease-specific risk included the potential for worsening of depressive symptoms. Finally, the time course and accommodation to the most commonly appearing adverse events were considered. RESULTS: TMS was administered in over 10,000 cumulative treatment sessions in the study program. There were no deaths or seizures. Most adverse events were mild to moderate in intensity. Transient headaches and scalp discomfort were the most common adverse events. Auditory threshold and cognitive function did not change. There was a low discontinuation rate (4.5%) due to adverse events during acute treatment. CONCLUSIONS: TMS was associated with a low incidence of adverse events that were mild to moderate in intensity and demonstrated a largely predictable time course of resolution. TMS may offer clinicians a novel, well-tolerated alternative for the treatment of major depressive disorder that can be safely administered in an outpatient setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00104611.

Transcranial magnetic stimulation in the acute treatment of major depressive disorder: clinical response in an open-label extension trial.

BACKGROUND: This report describes the results of an open-label extension study of active trans-cranial 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 open-label 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.

Antidepressant medication treatment failure does not predict lower remission with ECT for major depressive disorder: a report from the consortium for research in electroconvulsive therapy.

OBJECTIVE: To test whether antidepressant medication treatment failure predicts differential remission with electroconvulsive therapy (ECT) in nonpsychotic unipolar depression. METHOD: Depressed patients diagnosed with the Structured Clinical Interview for DSM-IV receiving ECT were assessed for medication use with the Antidepressant Treatment History Form (ATHF) (N = 345). Response to ECT was assessed with the 24-item Hamilton Rating Scale for Depression. Baseline medication treatment failure was analyzed as a possible predictor of remission status. Dates of study enrollment were from May 1997 to July 2004. RESULTS: Resistance to antidepressant medication as assessed by the ATHF, either taken as a whole or for any individual class of medication, was not predictive of acute remission status with ECT. CONCLUSION: Treatment failure with anti-depressant medication does not predict acute remission status with ECT for nonpsychotically depressed patients.

Slow-frequency rTMS reduces fibromyalgia pain.

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.