[Show abstract][Hide abstract] ABSTRACT: We reviewed the literature on transcranial magnetic stimulation and its uses and efficacy in schizophrenia. Multiple sources were examined on transcranial magnetic stimulation efficacy in relieving positive and negative symptoms of schizophrenia. Literature review was conducted via Ovid Medline and PubMed databases. We found multiple published studies and metaanalyses that give evidence that repetitive transcranial magnetic stimulation can have benefit in relieving positive and negative symptoms of schizophrenia, particularly auditory hallucinations. These findings should encourage the psychiatric community to expand research into other applications for which transcranial magnetic stimulation may be used to treat patients with psychiatric disability.
[Show abstract][Hide abstract] ABSTRACT: Depression during pregnancy affects 5%-8% of women. While the percentage of women in the US taking serotonin reuptake inhibitors during pregnancy has risen over the last decade, pregnant women continue to report that they prefer non-pharmacologic interventions.
We review the literature regarding neuromodulation techniques for major depressive disorder during pregnancy. The rationale for their use in this population, new developments, and future directions are discussed.
A literature search was conducted in PubMed Plus, Ovid Medline, and Embase to collect all articles on neuromodulation for the treatment of depression during pregnancy. Key search words included electroconvulsive therapy, transcranial magnetic stimulation, deep brain stimulation, transcranial direct current stimulation, neuromodulation, depression, and pregnancy. Given the sparse literature, all articles from 1960 to 2014 that addressed the use of neuromodulation in pregnancy were included.
The data support the use of electroconvulsive therapy in all trimesters of pregnancy for major depressive disorder. New data are emerging for the use of transcranial magnetic stimulation in pregnancy, which is likely safe, but more data are needed before it can be recommended as a primary treatment modality during pregnancy. Other neuromodulation techniques have not been well studied in this population.
[Show abstract][Hide abstract] ABSTRACT: The majority of literature on superficial brain stimulation for the treatment of psychiatric conditions is focused on transcranial magnetic stimulation (TMS) for major depressive disorder. Given its versatility and mode of action, TMS use has been now extended to other psychiatric disorders including anxiety disorders, bipolar disorder, psychotic disorders, and disorders of executive function. In this chapter we review the rationale and available evidence for the use of TMS as a treatment option in conditions other than major depression - post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, attention-deficit/hyperactivity disorder, catatonia, schizophrenia, and bipolar disorder. Although the rationale for its use in the treatment of the above-mentioned conditions is strong, the available evidence is mixed and limited. At this juncture no definitive conclusions or recommendations can be drawn; however, given the existing positive signals and the significant limitations of the presented evidence, further research is warranted to assess the actual role of TMS in the treatment of psychiatric conditions other than unipolar depression.
No preview · Article · Dec 2013 · Handbook of Clinical Neurology
[Show abstract][Hide abstract] ABSTRACT: Deep brain stimulation (DBS) is an efficacious surgical treatment for many conditions, including obsessive-compulsive disorder and treatment-resistant depression. DBS provides a unique opportunity to not only ameliorate disease but also to study mood, cognition, and behavioral effects in the brain. However, there are many ethical questions that must be fully addressed in designing clinical research trials. It is crucial to maintain sound ethical boundaries in this new era so as to permit the proper testing of the potential therapeutic role DBS may play in ameliorating these devastating and frequently treatment-refractory psychiatric disorders. In this review, we focus on the selection of patients for study, informed consent, clinical trial design, DBS in the pediatric population, concerns about intentionally or inadvertently altering an individual's personal identity, potential use of DBS for brain enhancement, direct modification of behavior through neuromodulation, and resource allocation.
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Mar 2013 · The journal of ECT
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Major depressive disorder is a prevalent, disabling, and often chronic or recurrent psychiatric condition. About 35% of patients fail to respond to conventional treatment approaches and are considered to have treatment-resistant depression (TRD). OBJECTIVE: We compared the safety and effectiveness of different stimulation levels of adjunctive vagus nerve stimulation (VNS) therapy for the treatment of TRD. METHODS: In a multicenter, double blind study, 331 patients with TRD were randomized to one of three dose groups: LOW (0.25 mA current, 130 μs pulse width), MEDIUM (0.5-1.0 mA, 250 μs), or HIGH (1.25-1.5 mA, 250 μs). A highly treatment-resistant population (>97% had failed to respond to ≥6 previous treatments) was enrolled. Response and adverse effects were assessed for 22 weeks (end of acute phase), after which output current could be increased, if clinically warranted. Assessments then continued until Week 50 (end of long-term phase). RESULTS: VNS therapy was well tolerated. During the acute phase, all groups showed statistically significant improvement on the primary efficacy endpoint (change in Inventory of Depressive Symptomatology-Clinician Administered Version [IDS-C]), but not for any between-treatment group comparisons. In the long-term phase, mean change in IDS-C scores showed continued improvement. Post-hoc analyses demonstrated a statistically significant correlation between total charge delivered per day and decreasing depressive symptoms; and analysis of acute phase responders demonstrated significantly greater durability of response at MEDIUM and HIGH doses than at the LOW dose. CONCLUSIONS: TRD patients who received adjunctive VNS showed significant improvement at study endpoint compared with baseline, and the effect was durable over 1 year. Higher electrical dose parameters were associated with response durability.
No preview · Article · Oct 2012 · Brain Stimulation
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
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.
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.
No preview · Article · Apr 2012 · The journal of ECT
[Show abstract][Hide abstract] ABSTRACT: Transcranial magnetic stimulation (TMS) is a US Food and Drug Administration-approved treatment for major depressive disorder (MDD) in patients who have not responded to 1 adequate antidepressant trial in the current episode. In a retrospective cohort study, we examined the effectiveness and safety of TMS in the first 100 consecutive patients treated for depression (full DSM-IV criteria for major depressive episode in either major depressive disorder or bipolar disorder) at an academic medical center between July 21, 2008, and March 25, 2011.
TMS was flexibly dosed in a course of up to 30 sessions, adjunctive to current medications, for 85 patients treated for acute depression. The primary outcomes were response and remission rates at treatment end point as measured by the Clinical Global Impressions-Improvement scale (CGI-I) at 6 weeks. Secondary outcomes included change in the Hamilton Depression Rating Scale (HDRS); Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR); Beck Depression Inventory (BDI); Beck Anxiety Inventory (BAI); and the Sheehan Disability Scale (SDS). Enduring benefit was assessed over 6 months in patients receiving maintenance TMS treatment. Data from 12 patients who received TMS as maintenance or continuation treatment after prior electroconvulsive therapy (ECT) or TMS given in a clinical trial setting were also reviewed.
The clinical cohort was treatment resistant, with a mean of 3.4 failed adequate trials in the current episode. Thirty-one individuals had received prior lifetime ECT, and 60% had a history of psychiatric hospitalization. The CGI-I response rate was 50.6% and the remission rate was 24.7% at 6 weeks. The mean change was -7.8 points in HDRS score, -5.4 in QIDS-SR, -11.4 in BDI, -5.8 in BAI, and -6.9 in SDS. The HDRS response and remission rates were 41.2% and 35.3%, respectively. Forty-two patients (49%) entered 6 months of maintenance TMS treatment. Sixty-two percent (26/42 patients) maintained their responder status at the last assessment during the maintenance treatment. TMS treatment was well tolerated, with a discontinuation rate of 3% in the acute treatment phase. No serious adverse events related to TMS were observed during acute or maintenance treatment.
Adjunctive TMS was found to be safe and effective in both acute and maintenance treatment of patients with treatment-resistant depression.
No preview · Article · Apr 2012 · The Journal of Clinical Psychiatry
[Show abstract][Hide abstract] ABSTRACT: To describe the outcomes of a consecutive series of depressed patients treated with vagus nerve stimulation (VNS) following US Food and Drug Administration (FDA) approval of this intervention.
We implanted a VNS device in 15 consecutive outpatients with treatment-resistant major depressive episodes, including 10 with major depressive disorder and 5 with bipolar disorder (DSM-IV criteria), between November 2005 and August 2006. Existing antidepressant treatment remained fixed as far as clinically possible. The primary outcome was change from baseline in the Beck Depression Inventory (BDI) score. Outcomes were assessed at 6 and 12 months postimplant and compared to those of the VNS pivotal efficacy trial that led to FDA approval of VNS.
The BDI score decreased significantly compared to baseline at 6 months (P < .05) and 12 months (P < .01), from a mean of 37.8 (SD = 7.8) before VNS activation to a mean of 24.6 (SD = 11.4) at 12 months. By 1 year, 28.6% (n = 4) of the sample responded to VNS and 7.1% (n = 1) remitted according to the BDI. Secondary outcomes on the Hamilton Depression Rating Scale 24-Item showed similar improvement at 1 year, with a 43% response rate (n = 6) and 14.3% remission rate (n = 2). No obvious predictors of response were detected. Side effects of VNS included hoarseness (73%), dyspnea (47%), nausea (40%), pain (33%), and anxiety (20%); no patient terminated treatment due to intolerable side effects.
We found that a substantial minority of patients with extremely difficult-to-treat depressive disorders benefited from VNS in an ambulatory clinical practice, with outcomes comparable to those observed in previous VNS efficacy studies and with a similar side effect profile.
No preview · Article · Oct 2011 · The Journal of Clinical Psychiatry
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Given the data that depression is common during pregnancy and that pregnant women prefer non-medication treatment options, we hypothesize repetitive transcranial magnetic stimulation (TMS) may be a treatment option. Given the novelty of TMS, we sought to assess whether patient acceptability would be a barrier to enrolling pregnant women in TMS studies.
In Study 1, 500 pregnant women were surveyed in an outpatient, urban obstetrics clinic using the Edinburgh Depression Rating Scale (EPDS) and a treatment acceptability survey. In Study 2, 51 women were surveyed with the EPDS and acceptability survey using an informational video to increase participant knowledge about TMS.
Approximately 25% of participants had an EPDS score of ≥12 in both studies. Psychotherapy was identified as the most acceptable treatment option. TMS was considered an unacceptable treatment option to virtually all women before the informational video. After the video, 15.7% considered TMS an acceptable treatment option.
Psychotherapy is the most acceptable treatment option for depression to pregnant women. Increasing participant knowledge about TMS increased its acceptability significantly. Large-scale multi-center trials are needed for confirmation of these results.
No preview · Article · Mar 2011 · Journal of Affective Disorders
[Show abstract][Hide abstract] ABSTRACT: 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.
No preview · Article · Mar 2011 · The journal of ECT
[Show abstract][Hide abstract] ABSTRACT: Despite the data that major depressive disorder (MDD) is common during pregnancy and that pregnant women prefer nonmedication treatment options, there is a paucity of research examining alternative treatments for this special population. We present the results of an open label pilot study examining treatment with transcranial magnetic stimulation (TMS) in pregnant women with MDD.
Ten women with MDD in the second or third trimester of pregnancy were treated with 20 sessions of 1-Hz TMS at 100% of motor threshold (MT) to the right dorsolateral prefrontal cortex. The total study dose was 6000 pulses. Antenatal monitoring was performed during treatment sessions 1, 10, and 20.
Seven of ten (70%) subjects responded (decrease ≥50% in Hamilton Depression Rating Scale [HDRS-17] scores). No adverse pregnancy or fetal outcomes were observed. All infants were admitted to the well baby nursery and were discharged with the mother. Mild headache was the only common adverse event and was reported by 4 of 10 (40%) subjects.
TMS appears to be a promising treatment option for pregnant women who do not wish to take antidepressant medications.
Full-text · Article · Feb 2011 · Journal of Women's Health
[Show abstract][Hide abstract] ABSTRACT: Arterial spin labeling (ASL) allows noninvasive quantification of cerebral blood flow (CBF), which can be used as a biomarker of drug effects in pharmacological magnetic resonance imaging (phMRI). In a double-blind, placebo-controlled crossover study, we investigated the effects of a single oral dose of citalopram (20 mg) on resting CBF in 12 healthy subjects, using ASL phMRI. Support-vector machine (SVM) analysis detected significant drug-induced reduction in CBF in brain regions including the amygdala, fusiform gyrus, insula, and orbitofrontal cortex. These regions have been shown to have abnormally elevated CBF in patients with major depression, as well as in subjects genetically prone to depression. Mixed-effects analysis on data extracted from selected regions of interest (ROIs) revealed significant drug effect only in serotonergic areas of the brain (z = -4.45, P < 0.005). These results demonstrate the utility of ASL phMRI as a biomarker of pharmacological activity of orally administered drugs in the brain.
[Show abstract][Hide abstract] ABSTRACT: Although transcranial magnetic stimulation (TMS) can be an effective acute antidepressant treatment, few studies systematically examine persistence of benefit.
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.
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.
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.
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.
No preview · Article · Oct 2010 · Brain Stimulation