David L. Dunner

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.

OBJECTIVEnTranscranial 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.nnnMETHODnAdult 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.nnnRESULTSnCompared 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).nnnCONCLUSIONSnTMS 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.nnnTRIAL REGISTRATIONnClinicalTrials.gov identifier: NCT01114477.

The Prevention of Recurrent Episodes of Depression with Venlafaxine for Two Years (PREVENT) Study: Outcomes from the Acute and Continuation Phases

Background We evaluated the comparative efficacy and safety of venlafaxine extended release (ER) and fluoxetine in the acute and continuation phases of treatment. Methods In this multicenter, double-blind study, outpatients with recurrent unipolar major depression were randomly assigned to receive venlafaxine ER (75–300 mg/day; n = 821) or fluoxetine (20–60 mg/day; n = 275). After a 10-week acute treatment phase, responders entered a 6-month continuation phase of ongoing therapy with double-blind venlafaxine ER ( n = 530) or fluoxetine ( n = 185). In the acute phase, the primary outcome was response, defined as a 17-item Hamilton Depression Rating Scale (HDRS) score ≤12 or ≥50% decrease from baseline; the secondary outcome was remission, defined as a HDRS score ≤7. In the continuation phase, the primary outcome was the proportion of patients who sustained response or remission. Secondary measures included time to onset of sustained response or remission (i.e., meeting criteria at two or more consecutive visits), relapse rates, and quality-of-life measures. Results At the acute treatment phase end point, response rates were 79% for both venlafaxine ER and fluoxetine; remission rates were 49% and 50% for venlafaxine ER and fluoxetine, respectively. In the continuation phase, response rates were 90% and 92%, and remission rates were 72% and 69% for venlafaxine ER and fluoxetine, respectively. Rates of sustained remission at the end of the continuation phase were 52% and 58% for venlafaxine ER and fluoxetine, respectively. Conclusion Venlafaxine ER and fluoxetine were comparably effective during both acute and continuation phase therapy.

Psychotic symptoms in patients with bipolar mania.

BACKGROUNDnPsychosis has been identified in as many as 68% of patients with bipolar mania. This analysis identified psychotic symptoms in these patients.nnnMETHODSnData were from two placebo-controlled, 3-week studies in patients with an acute episode of bipolar mania. Symptoms were identified by the 30-item Positive and Negative Syndrome Scale (PANSS; item ratings, 1 = absent to 7 = extremely severe), the Young Mania Rating Scale, and the Global Assessment Scale.nnnRESULTSnPsychotic features at study entry were diagnosed in 264 (51.3%) of the 515 patients. At baseline, these patients had significantly more severe scores on the PANSS, Young Mania Rating Scale, and Global Assessment Scale than patients without psychotic features. Patients with psychotic features had mean (+/-SD) scores of mild (3) or greater on six PANSS items: grandiosity (4.5+/-1.4), delusions (4.4+/-1.4), lack of judgment/insight (4.1+/-1.5), excitement (3.9+/-1.3), suspiciousness/persecution (3.1+/-1.6), and hostility (3.1+/-1.5). Grandiosity symptoms of delusional proportions (scores > or = 4) were noted in 205 (78%) of patients with a diagnosis of psychotic features and in 113 (45%) patients without the diagnosis.nnnLIMITATIONSnThe study was not specifically designed to assess patients with psychotic features and the PANSS was developed to evaluate symptoms of schizophrenia.nnnCONCLUSIONSnThese findings support prior reports indicating high rates of psychosis in patients with bipolar mania and identify the most prominent symptoms in these patients.

Psychosocial outcomes in patients with recurrent major depressive disorder during 2 years of maintenance treatment with venlafaxine extended release

BACKGROUNDnPsychosocial outcomes from the Prevention of Recurrent Episodes of Depression with Venlafaxine ER for Two Years (PREVENT) study were evaluated.nnnMETHODSnAdult outpatients with recurrent major depressive disorder (MDD) and response or remission following 6-month continuation treatment with venlafaxine extended release (ER) were randomized to receive venlafaxine ER or placebo for 1 year. Patients without recurrence on venlafaxine ER during year 1 were randomized to venlafaxine ER or placebo for year 2. Psychosocial functioning was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q), Life Enjoyment Scale-Short Version (LES-S), Social Adjustment Scale-Self-Report (SAS-SR) total and individual factors, Short Form Health Survey (SF-36) (vitality, social functioning, and role function-emotional items), and Longitudinal Interval Follow-up Evaluation (LIFE).nnnRESULTSnAt year 1 end, better overall psychosocial functioning was seen among patients randomly assigned to venlafaxine ER (n=129) vs placebo (n=129), with significant differences at end point on SF-36 role function-emotional, Q-LES-Q, and SAS-SR total, and work, house work, social/leisure, and extended-family factor scores (p≤0.05). At year 2 end, significant differences favored venlafaxine ER (n=43) vs placebo (n=40) on SF-36 vitality and role function-emotional, Q-LES-Q, LES-S, LIFE, and SAS-SR total, social/leisure, and extended-family factor scores (p≤0.05).nnnLIMITATIONSnPatients with chronic MDD or treatment resistance were excluded and long-term specialist care was a financial incentive for treatment compliance. Discontinuation-related adverse events may have compromised the integrity of the treatment blind.nnnCONCLUSIONSnFor patients with recurrent MDD, 2 years maintenance therapy with venlafaxine ER may improve psychosocial functioning vs placebo.

Medicare patient experience with vagus nerve stimulation for treatment-resistant depression

Abstract Background: Major depressive disease (MDD) represents a cost burden to the US healthcare system: approximately one-third of MDD patients fail conventional treatment: multiple failures define treatment-resistant depression (TRD). Vagus nerve stimulation (VNS) therapy is an approved adjunctive treatment for TRD. Objective: To study the healthcare utilization experience of Medicare beneficiaries implanted with VNS (VNSBs) during Medicare coverage, compared with beneficiaries with TRD (TRDBs) and managed depression (Mdeps). Methods: A retrospective analysis of 100% standard analytic file (SAF) Medicare claims from 2006–2009 using specific criteria to identify a VNSB dataset, compared to TRDs and Mdeps datasets (extract of 5% sample SAF from 2001–2009) and 2009 general Medicare beneficiaries (GMBs). Comparative analysis included demographics, mortality, healthcare utilization, and costs. Results: Among patients meeting study criteria for VNSBs (nu2009=u2009690), TRDBs (nu2009=u20094639), Mdeps (nu2009=u20097524), and GMBs (nu2009>u200936 million), VNSBs were on average: younger, more likely to be female, and white, with Medicare eligibility due to disability. Of the VNSBs in the 2-year post-implantation period: 5% died; 22% experienced no negative events (defined as hospitalizations for psychoses or poisoning, emergency room use, electroconvulsive therapy, or poisoning, suicidal ideation, or self-harm diagnoses); 29% experienced multiple negative events; and 41% had either a single hospitalization or only all-cause ER visits. VNSBs experiencing negative events had more complex co-occurring psychiatric diagnoses. The annual mortality rate for VNSBs post-implant was 19.9 deaths per 1000 patient years, compared with 46.2 (CI: 41.9–51.6) and 46.8 (CI: 43.4–50.4) deaths for TRDBs and Mdeps, respectively. The medical costs per patient-year post-VNS implantation for VNSBs (

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

8749) was similar to the Mdeps (

Ronald R Fieve

8960; CI

rTMS effects in patients with co-morbid somatic pain and depressive mood disorders

8555–

Regional cerebral cortical thinning in bipolar disorder.

9381) and was substantially lower than TRDBs (

Recognition and treatment of depression in a primary care setting.

13,618; CI