Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of quality of life outcome measures in clinical practice.

BACKGROUND: Transcranial magnetic stimulation (TMS) is an effective and safe therapy for major depressive disorder (MDD). This study assessed quality of life (QOL) and functional status outcomes for depressed patients after an acute course of TMS. METHODS: Forty-two, U.S.-based, clinical TMS practice sites treated 307 outpatients with a primary diagnosis of MDD and persistent symptoms despite prior adequate antidepressant pharmacotherapy. Treatment parameters were based on individual clinical considerations and followed the labeled procedures for use of the approved TMS device. Patient self-reported QOL outcomes included change in the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the EuroQol 5-Dimensions (EQ-5D) ratings from baseline to end of the acute treatment phase. RESULTS: Statistically significant improvement in functional status on a broad range of mental health and physical health domains was observed on the SF-36 following acute TMS treatment. Similarly, statistically significant improvement in patient-reported QOL was observed on all domains of the EQ-5D and on the General Health Perception and Health Index scores. Improvement on these measures was observed across the entire range of baseline depression symptom severity. CONCLUSION: These data confirm that TMS is effective in the acute treatment of MDD in routine clinical practice settings. This symptom benefit is accompanied by statistically and clinically meaningful improvements in patient-reported QOL and functional status outcomes.

Transcranial magnetic stimulation (TMS) for major depression: a multisite, naturalistic, observational study of acute treatment outcomes in clinical practice.

BACKGROUND: Few studies have examined the effectiveness of transcranial magnetic stimulation (TMS) in real-world clinical practice settings. METHODS: Forty-two US-based clinical TMS practice sites treated 307 outpatients with Major Depressive Disorder (MDD), and persistent symptoms despite antidepressant pharmacotherapy. Treatment was based on the labeled procedures of the approved TMS device. Assessments were performed at baseline, week 2, at the point of maximal acute benefit, and at week 6 when the acute course extended beyond 6 weeks. The primary outcome was change in the Clinician Global Impressions-Severity of Illness from baseline to end of acute phase. Secondary outcomes were change in continuous and categorical outcomes on self-report depression scales (9-Item Patient Health Questionnaire [PHQ-9], and Inventory of Depressive Symptoms-Self Report [IDS-SR]). RESULTS: Patients had a mean ± SD age of 48.6 ± 14.2 years and 66.8% were female. Patients received an average of 2.5 (± 2.4) antidepressant treatments of adequate dose and duration without satisfactory improvement in this episode. There was a significant change in CGI-S from baseline to end of treatment (-1.9 ± 1.4, P < .0001). Clinician-assessed response rate (CGI-S) was 58.0% and remission rate was 37.1%. Patient-reported response rate ranged from 56.4 to 41.5% and remission rate ranged from 28.7 to 26.5%, (PHQ-9 and IDS-SR, respectively). CONCLUSION: Outcomes demonstrated response and adherence rates similar to research populations. These data indicate that TMS is an effective treatment for those unable to benefit from initial antidepressant medication.

Interaction between levodopa and enteral nutrition.

OBJECTIVE: To report and discuss a drug-nutrient interaction involving levodopa and protein in enteral nutrition. CASE SUMMARY: A 77-year-old male with Parkinson's disease was admitted to an intensive care unit for an intracerebral hemorrhage. To provide nutritional support, an oral gastric tube was placed and continuous enteral nutrition was initiated, with 1.4 g/kg of protein administered daily. The following medications were continued during hospitalization: immediate-release carbidopa/levodopa 25 mg/100 mg, with 1.5 tablets administered 4 times daily; pramipexole 1.5 mg 3 times daily; and entacapone 200 mg 4 times daily. Despite this drug therapy, the patient developed severe rigidity. A review of the literature revealed a potential interaction between levodopa and protein intake. To resolve this interaction, the amount of protein in the enteral nutrition was decreased to 0.9 g/kg/day and the nutritional administration was changed from continuous enteral feeding to bolus feeding, with levodopa given between boluses. After these adjustments, the patient showed marked improvement of parkinsonian symptoms. DISCUSSION: The drug-nutrient interaction between protein and levodopa in outpatient settings has been reported widely in the literature; however, this interaction has not been previously reported with continuous enteral nutrition. Decreased parkinsonian symptom control, despite adherence to an established medication regimen, together with dramatic improvement observed after manipulation of enteral nutrition delivery and content, strongly suggest interference with levodopa absorption. Use of the Naranjo probability scale supports a probable interaction between the protein content in tube feeds and levodopa, resulting in decreased levodopa efficacy. CONCLUSIONS: Clinicians should be cognizant of the potential drug-nutrient interaction between levodopa and enteral nutrition.

Beyond intravenous thrombolysis.

The National Institute of Neurological Disorders and Stroke trial of recombinant tissue plasminogen activator has been considered a landmark study in the acute treatment of ischemic stroke. Unfortunately, only a small percentage of all ischemic stroke patients presents to the hospital in time to receive the drug. Moreover, the recannalization rate of a major artery occlusion, such as the proximal middle cerebral artery or top of the internal carotid artery occlusion, after intravenous (IV) thrombolytic therapy has been disappointingly low. Since the Food and Drug Administration's approval of IV plasminogen activator, there have been numerous randomized clinical trials investigating the safety and efficacy of different thrombolytics administered in various time frames. In addition to the IV administration, efforts have been made in order to study the radiographic as well as clinical effects of intra-arterial (IA) thrombolysis. The combination of IV and IA thrombolysis has been studied. For patients who do not qualify for receiving chemical thrombolysis, new devices have been developed for mechanical thrombectomy. Angioplasty and stenting procedures are being performed more frequently than in the past as one of the treatment modalities for acute ischemic stroke patients. Relentless research effort is being made internationally in order to fight the devastating disease which now goes beyond the conventional IV thrombolysis.

Can Medication Free, Treatment-Resistant, Depressed Patients Who Initially Respond to TMS Be Maintained Off Medications? A Prospective, 12-Month Multisite Randomized Pilot Study.

BACKGROUND: Repetitive transcranial magnetic stimulation (TMS) is efficacious for acute treatment of resistant major depressive disorder (MDD), but there is little information on maintenance TMS after acute response. OBJECTIVE/HYPOTHESIS: This pilot feasibility study investigated 12-month outcomes comparing two maintenance TMS approaches--a scheduled, single TMS session delivered monthly (SCH) vs. observation only (OBS). METHODS: Antidepressant-free patients with unipolar, non-psychotic, treatment-resistant MDD participated in a randomized, open-label, multisite trial. Patients meeting protocol-defined criteria for improvement after six weeks of acute TMS were randomized to SCH or OBS regimens. TMS reintroduction was available for symptomatic worsening; all patients remained antidepressant-free during the trial. RESULTS: Sixty-seven patients enrolled in the acute phase, and 49 (73%) met randomization criteria. Groups were matched, although more patients in the SCH group had failed ≥ 2 antidepressants (p = .035). There were no significant group differences on any outcome measure. SCH patients had nonsignificantly longer time to first TMS reintroduction, 91 ± 66 days, vs. OBS, 77 ± 52 days; OBS patients were nonsignificantly more likely to need reintroduction (odds ratio = 1.21, 95% CI .38-3.89). Reintroduction lasted 14.3 ± 17.8 days (SCH) and 16.9 ± 18.9 days (OBS); 14/18 (78%) SCH and 17/27 (63%) OBS responded to reintroduction. Sixteen patients (32.7%) completed all 53 weeks of the study. CONCLUSIONS: Maintaining treatment-resistant depressed patients off medications with periodic TMS appears feasible in some cases. There was no statistical advantage of SCH vs. OBS, although SCH was associated with a nonsignificantly longer time to relapse. Those who initially respond to TMS have a strong chance of re-responding if relapse occurs.

A multisite, naturalistic, observational study of transcranial magnetic stimulation for patients with pharmacoresistant major depressive disorder: durability of benefit over a 1-year follow-up period.

OBJECTIVE: Transcranial magnetic stimulation (TMS) is an effective and safe acute treatment for patients not benefiting from antidepressant pharmacotherapy. Few studies have examined its longer term durability. This study assessed the long-term effectiveness of TMS in naturalistic clinical practice settings following acute treatment. METHOD: Adult patients with a primary diagnosis of unipolar, nonpsychotic major depressive disorder (DSM-IV clinical criteria), who did not benefit from antidepressant medication, received TMS treatment in 42 clinical practices. Two hundred fifty-seven patients completed a course of acute TMS treatment and consented to follow-up over 52 weeks. Assessments were obtained at 3, 6, 9, and 12 months. The study was conducted between March 2010 and August 2012. RESULTS: Compared with pre-TMS baseline, there was a statistically significant reduction in mean total scores on the Clinical Global Impressions-Severity of Illness scale (primary outcome), 9-Item Patient Health Questionnaire, and Inventory of Depressive Symptoms-Self Report (IDS-SR) at the end of acute treatment (all P < .0001), which was sustained throughout follow-up (all P < .0001). The proportion of patients who achieved remission at the conclusion of acute treatment remained similar at conclusion of the long-term follow-up. Among 120 patients who met IDS-SR response or remission criteria at the end of acute treatment, 75 (62.5%) continued to meet response criteria throughout long-term follow-up. After the first month, when the majority of acute TMS tapering was completed, 93 patients (36.2%) received reintroduction of TMS. In this group, the mean (SD) number of TMS treatment days was 16.2 (21.1). CONCLUSIONS: TMS demonstrates a statistically and clinically meaningful durability of acute benefit over 12 months of follow-up. This was observed under a pragmatic regimen of continuation antidepressant medication and access to TMS retreatment for symptom recurrence. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01114477.

Effectiveness of Factor IX complex concentrate in reversing warfarin associated coagulopathy for intracerebral hemorrhage.

INTRODUCTION: The objective of this study is to show the effectiveness of Factor IX complex concentrate (FIXCC) for rapid reversal of an elevated International Normalized Ratio (INR) in patients with anticoagulation-associated intracerebral hemorrhage (AAICH). METHODS: We, retrospectively, analyzed the clinical data of 19 patients with the diagnosis of AAICH from January 2005 to May 2006. A comparison was made among patients treated with FFP and Vit.K [FFP-group (n = 9)] and patients treated with FIXCC in addition to FFP and Vit.K [FIXCC-group (n = 10)]. INR of 1.4 or less was taken as target. RESULTS: Mean INR on admission for FFP and FIXCC group was 1.84 +/- 0.31 and 2.44 +/- 1.48, respectively (P = 0.315). After administration of therapy, the INR was reduced from 1.84 +/- 0.31 to 1.34 +/- 0.08 (P < 0.05) in FFP group and 2.44 +/- 1.48 to 1.34 +/- 0.07 (P < 0.005) in FIXCC group. Three patients in FFP group (33%) and 8 patients in FIXCC group (80%) reached their target INR in 3-4 h after initiation of therapy (P = 0.012). Mean time taken by both FFP and FIXCC groups to reach the target INR was 8.52 +/- 5.60 h and 4.25 +/- 2.12 h, respectively (P < 0.05). The mean rate of INR correction was 0.06 +/- 0.03 and 0.27 +/- 0.25 per hour for the FFP and FIXCC group, respectively (P < 0.005). There was one death in FIX group and two in FFP group and no thrombotic complications. CONCLUSION: Our data suggests that FIXCC in combination with FFP and Vit.K may result in decreased time required when compared to FFP and Vit.K alone for correction of warfarin associated coagulopathy in neurosurgical emergencies.

Reduction of cerebral infarction using the third circulation.

OBJECTIVE: To ascertain whether ventriculosubarachnoid perfusion of the brain with an oxygen-carrying nutrient emulsion affects the volume of infarction in animals with permanent middle cerebral artery occlusion. DESIGN: Prospective, randomized, controlled trial. SETTING: An animal laboratory in a university setting. SUBJECTS: Twenty-eight closed colony adult cats weighing between 3.5 and 4.5 kg. INTERVENTIONS: Cats were assigned randomly into one of three groups: untreated surgical controls, artificial cerebrospinal fluid (ACSF) perfused, or oxygenated fluorochemical (t-bis perfluorobutylethylene; F44E) nutrient emulsion (OFNE) perfused. The formulation used in this study was developed for clinical use and is currently being used in a phase 1 clinical trial in patients with severe ischemic stroke. Focal cerebral ischemia was induced by permanently clipping the middle cerebral artery via the retro-orbital approach. Treatment was initiated 90 mins postocclusion and continued for 18 hrs. Animals were killed 1 hr after the termination of perfusion, the brains were sectioned and stained with 2,3,5-triphenyltetrazolium chloride, and the infarct area was determined with a computer digitizer. MEASUREMENTS AND MAIN RESULTS: There was a significant difference in cerebral infarct volume in the OFNE-perfused animals compared with the other groups ( p