Mario A. Cristancho

Effectiveness of transcranial magnetic stimulation in clinical practice post-FDA approval in the United States: results observed with the first 100 consecutive cases of depression at an academic medical center.

INTRODUCTION 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. METHOD 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. RESULTS 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. CONCLUSIONS Adjunctive TMS was found to be safe and effective in both acute and maintenance treatment of patients with treatment-resistant depression.

Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year.

OBJECTIVE 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. METHOD 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. RESULTS 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. CONCLUSIONS 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.

Unexpected Reduction in Migraine and Psychogenic Headaches Following rTMS Treatment for Major Depression: A Report of Two Cases

Our objective is to report a coincident reduction in headache pain in patients treated with repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder (MDD). Two patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD, non-responsive to prior antidepressant treatment who were enrolled in a sham-controlled, double-blind study of rTMS for MDD. After the study, it was revealed that both were in the active-treatment arm. Both patients suffered from near daily headaches and kept logs of headache frequency and severity before, during, and after the study. Headache pain was significantly reduced under double-blind conditions with rTMS treatment, but returned to baseline following cessation of rTMS treatment. Ultimately, when receiving rTMS post-study as a maintenance intervention for MDD (approximately 2 rTMS sessions/week), the positive effects on headache amelioration were sustained. Headache pain is frequently comorbid with mood disorders and has been reported as the most common side effect with rTMS. In these subjects, rTMS was, in fact, associated with relief of depressive symptoms and preexisting headache pain. This indicates that rTMS may be beneficial for both disorders in some patients.

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

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

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

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

The role of quetiapine extended release in the treatment of bipolar depression

Bipolar disorder is a common, recurrent, and chronic condition associated with significant morbidity and reduced longevity mainly due to the depressive pole of the illness. Despite the great need for effective therapies, relatively few randomized controlled trials have been conducted and, to date, only two agents have been approved by the United States Food and Drug Administration for treatment of bipolar depression (olanzapine/fluoxetine combination and quetiapine). Quetiapine is the first approved monotherapy for treatment of bipolar depression, and an extended-release (XR) form of quetiapine is now available. This once-daily, bioequivalent formulation represents a useful alternative for patients who cannot tolerate twice-daily, immediate-release (IR) quetiapine. Here, we summarize the evidence supporting the efficacy of quetiapine for treatment of bipolar depression, and also review the similarities and differences between the two formulations. Additional research on longer-term use of quetiapine XR is needed to establish the durability of therapeutic effects and tolerability over months or years of therapy, both alone and in combination with other mood stabilizers. Studies on the potential utility of lower doses of quetiapine XR and head-to-head studies to evaluate relative efficacy and cost-effectiveness also are needed.

Electroconvulsive therapy in a 72-year-old woman with a history of Takotsubo cardiomyopathy: a case report and review of the literature

Electroconvulsive therapy (ECT) remains the gold standard for treatment of major depression with psychosis and catatonia. Although ECT is generally safe and welltolerated, a cardiac complication of ECT that we recently reported is Takotsubo cardiomyopathy (TCM). TCM is a reversible cardiomyopathy that is initially indistinguishable from myocardial infarction and is often precipitated by stressful circumstances. TCM is characterized by chest pain, dyspnea, ST segment changes on electrocardiogram (EKG), and elevated cardiac troponin levels; however, on coronary angiography, no obstructive lesions are found. Most theories regarding the cause of TCM emphasize the role of a catecholamine surge produced by an emotional or physiologically stressful event. We recently reported the first case of TCM precipitated by ECT, which produces a similar catecholamine surge, and thus may increase the risk for TCM. Subsequently, there have been two other reports, of TCM in the context of ECT. However, such patients are likely to reexperience recurrence of depression; reconsideration of ECT for intractable symptoms may be necessary. Here we detail the first report of successful readministration of ECT in a patient with a history of TCM in association with a prior course of ECT.

Electroconvulsive therapy in a 96-year-old patient with severe aortic stenosis: a case report and review of the literature.

We report the safe administration of a course of electroconvulsive therapy (ECT) in a 96-year-old woman with severe aortic stenosis. The patient experienced a relapse of her severe depression when ECT had been withheld because of increased concerns regarding medical risk given her age and degree of aortic stenosis. Reassessment of the case confirmed severe stenosis with a valve area of 0.5 cm2 and a peak pressure gradient across the valve of 110 mm Hg. The ventricular ejection was normal at 70% however, and after a careful weighing of the risk of ECT treatment versus the risk of withholding ECT, it was decided to proceed with ECT in this case. In the event, ECT was very well tolerated by the patient, and she experienced a full remission of symptoms. She continues to receive maintenance ECT successfully at a once-per-month frequency. This case illustrates that neither age nor aortic stenosis by itself precludes ECT in the setting of severe depression. Rather, in each case, a careful weighing of the risks both of proceeding with and withholding ECT is warranted.

Other therapeutic psychiatric uses of superficial brain stimulation

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.

Drug safety evaluation of olanzapine/fluoxetine combination.

Introduction: Bipolar disorder and treatment-resistant depression (TRD) are common and recurrent conditions associated with significant disability, morbidity and mortality. Despite the clear need for effective treatments, only a few medications have been approved in the US for these indications. The combined formulation of olanzapine–fluoxetine (OFC) has been available for a decade now, thus a review on its safety profile and comparative efficacy is timely and can help clinicians to determine the benefit/risk profile of OFC within the context of other treatment alternatives. Areas covered: This paper summarizes the rationale and evidence supporting the use of OFC for both bipolar I depressive episodes and TRD with a focus on safety and tolerability. Product labels and the search engine PubMed was used to obtain relevant information on this subject. Expert opinion: Although further comparative studies are needed, the literature confirms that the OFC is an effective treatment for bipolar I depressive episodes, as well as major depressive episodes that have not responded to several adequate courses of antidepressant therapy. Its use as a first-line treatment for bipolar I depressive episodes and at a higher rung of algorithms for patients with TRD is limited by its propensity to cause weight gain and associated metabolic symptoms.