Treatment-resistant Major Depressive Episode Research Articles

Case Report: Complications in ECT due to Fmr1-Premutation?

After a short summary on Fragile-X-Syndrome and fmr1-premutation, we present a case report on a patient pre diagnosed with fmr1-premutation undergoing a series of 14 ECTs because of a treatment resistant major depressive episode. In the course of the series, several unexpected adverse incidents occurred. According to a literature research we did on PubMed, we concluded that these adverse incidents may be related to fmr1-premutation and associated abnormities in cerebral and other physical features.

Replicating predictive serum correlates of greater translocator protein distribution volume in brain

Greater activation of glia, a key component of neuroinflammation, is an important process to target in neuropsychiatric illnesses. However, the magnitude of gliosis varies across cases so low-cost predictors are needed to stratify subjects for clinical trials. Here, several such blood serum measures were assessed in relation to TSPO VT, an index of translocator protein density, measured with positron emission tomography. Blood serum concentration of several products known to be synthesized by activated microglia (and to some extent astroglia) [prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2α), and tumor necrosis factor alpha (TNFα)], controlled by an index of peripheral inflammation [C-reactive protein (CRP)] and TSPO VT were measured in 3 cohorts: prefrontal cortex TSPO VT of 20 subjects with major depressive episodes (MDEs) from major depressive disorder (MDD); and 56 subjects with treatment resistant MDEs from MDD; and dorsal caudate TSPO VT of 20 subjects with obsessive-compulsive disorder. Ln(PGE2/CRP) and ln(TNFα/CRP) consistently correlated with TSPO VT (R2 = 0.36 to 0.11, p = 0.0030 to p = 0.0076). Assessment of threshold serum values to predict highly elevated TSPO VT, demonstrated that a positive predictive value (PPV) of 80% was possible while retaining 40% of participant samples and that receiver operating curves (ROC) ranged from 75 to 81%. Post-hoc selection of ln(CRP) was more predictive (R2 = 0.23 to 0.39, p = 0.0058 to p = 0.00013; ROC > 80%). Systematic assessment of selected peripheral inflammatory markers is promising for developing low cost predictors of TSPO VT. Marker thresholds with high PPV will improve subject stratification for clinical trials of glial targeting therapeutics.

Rapid Anti-Depressant Relief by Ketamine: Exploring A Complex Mechanism of Action

Background: Suicide rates and narcotic overdose have doubled since 2000. At least 30 percent of people with major depression are Treatment-Resistant (TR) and require novel therapeutics. ketamine at low doses has been shown in clinical trials to induce a rapid, short-lived anti-suicide and anti-depressant effect. Objective: To review the potential mechanism of action of ketamines’ alleviation of depressive symptoms from both animal and available human literature. Methods: This is a synthesis of information from papers listed in PUBMED Central. Although not exhaustive, this review highlights the most compelling work in the field related to this remarkable clinical rapid anti-depressant effect. Results: While there have been several theories and with some scientific evidence to date, the conclusion here is that currently, an exact and acceptable mechanism of action (MOA) for ketamines’ rapid anti-depressant effect is not apparent. The MOA of this compound with psychoactive abuse potential at a higher dosage and acute antidepressive effect in the most resistant patients is unknown. Discussion: Possible MOAs reviewed, include dopamine receptor modulation through epigenetic neuroadaptation via specific D1/D2 antagonism, D1 activation using optogenetic stimulation, and the role of D2/D3 availability in the ketamine therapeutic action. Conclusion: Unraveling MOA could guide the development of other unique Psychoplastogens capable of rapidly promoting structural and functional neural plasticity in cases of TR Major Depressive Episodes (MDE) and unipolar Major Depression Disorder (MDD).

Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial

Treatment-resistant major depressive disorder is common; repetitive transcranial magnetic stimulation (rTMS) by use of high-frequency (10 Hz) left-side dorsolateral prefrontal cortex stimulation is an evidence-based treatment for this disorder. Intermittent theta burst stimulation (iTBS) is a newer form of rTMS that can be delivered in 3 min, versus 37·5 min for a standard 10 Hz treatment session. We aimed to establish the clinical effectiveness, safety, and tolerability of iTBS compared with standard 10 Hz rTMS in adults with treatment-resistant depression. In this randomised, multicentre, non-inferiority clinical trial, we recruited patients who were referred to specialty neurostimulation centres based at three Canadian university hospitals (Centre for Addiction and Mental Health and Toronto Western Hospital, Toronto, ON, and University of British Columbia Hospital, Vancouver, BC). Participants were aged 18-65 years, were diagnosed with a current treatment-resistant major depressive episode or could not tolerate at least two antidepressants in the current episode, were receiving stable antidepressant medication doses for at least 4 weeks before baseline, and had an HRSD-17 score of at least 18. Participants were randomly allocated (1:1) to treatment groups (10 Hz rTMS or iTBS) by use of a random permuted block method, with stratification by site and number of adequate trials in which the antidepressants were unsuccessful. Treatment was delivered open-label but investigators and outcome assessors were masked to treatment groups. Participants were treated with 10 Hz rTMS or iTBS to the left dorsolateral prefrontal cortex, administered on 5 days a week for 4-6 weeks. The primary outcome measure was change in 17-item Hamilton Rating Scale for Depression (HRSD-17) score, with a non-inferiority margin of 2·25 points. For the primary outcome measure, we did a per-protocol analysis of all participants who were randomly allocated to groups and who attained the primary completion point of 4 weeks. This trial is registered with ClinicalTrials.gov, number NCT01887782. Between Sept 3, 2013, and Oct 3, 2016, we randomly allocated 205 participants to receive 10 Hz rTMS and 209 participants to receive iTBS. 192 (94%) participants in the 10 Hz rTMS group and 193 (92%) in the iTBS group were assessed for the primary outcome after 4-6 weeks of treatment. HRSD-17 scores improved from 23·5 (SD 4·4) to 13·4 (7·8) in the 10 Hz rTMS group and from 23·6 (4·3) to 13·4 (7·9) in the iTBS group (adjusted difference 0·103 [corrected], lower 95% CI -1·16; p=0·0011), which indicated non-inferiority of iTBS. Self-rated intensity of pain associated with treatment was greater in the iTBS group than in the 10 Hz rTMS group (mean score on verbal analogue scale 3·8 [SD 2·0] vs 3·4 [2·0] out of 10; p=0·011). Dropout rates did not differ between groups (10 Hz rTMS: 13 [6%] of 205 participants; iTBS: 16 [8%] of 209 participants); p=0·6004). The most common treatment-related adverse event was headache in both groups (10 Hz rTMS: 131 [64%] of 204; iTBS: 136 [65%] of 208). In patients with treatment-resistant depression, iTBS was non-inferior to 10 Hz rTMS for the treatment of depression. Both treatments had low numbers of dropouts and similar side-effects, safety, and tolerability profiles. By use of iTBS, the number of patients treated per day with current rTMS devices can be increased several times without compromising clinical effectiveness. Canadian Institutes of Health Research.

Electroconvulsive therapy and age: Age-related clinical features and effectiveness in treatment resistant major depressive episode

ObjectiveThis study was aimed to compare clinical features, treatments outcomes and tolerability between young (18–45 years), middle age (46–64 years) and old (≥ 65 years) patients treated with bilateral ECT for treatment resistant major depressive episode. Method402 patients were evaluated 1 day prior to ECT and a week after the treatment termination using the Clinical Global Impression Scale (CGI), the Hamilton Rating Scale for Depression-17 items (HAM-D-17), the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS) and the Mini Mental State Examination (MMSE). Response was defined as a reduction of at least 50% from baseline on the HAM-D-17 score. Remission was defined as a score ≤ 7 on the HAM-D-17 at the final evaluation. ResultsRates of response were not statistically different in the three groups (69.6% in old versus 63.5% in young and 55.5% in middle age groups). No significant differences were also observed in the proportions of remitters between the age groups (31.4% in young group, 27.7% in middle age group and 29.3% in old group). One week after the end of the ECT course the middle and old age groups showed a statistically significant increase in the MMSE score compared to baseline. We did not find significant differences between the three age groups in rates of premature drops-out due to ECT-related side effects. ConclusionOur data support the use of ECT in elderly patients with treatment-resistant major depressive episode, with rates of response around 70% and effectiveness being independent from age. In the old age group the baseline cognitive impairment improved after ECT and no life-threatening adverse event was detected.

High frequency repetitive transcranial magnetic stimulation treatment for major depression: Dissociated effects on psychopathology and neurocognition

ObjectivesThis open-label pilot study explored the effects of a course of accelerated high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on two neurocognitive domains (decision-making and impulse control) in patients with major depressive disorder (MDD). MethodsParticipants with MDD and a treatment resistant major depressive episode (n=24) underwent twice-daily HF-rTMS targeted at the left dorsolateral prefrontal cortex (lDLPFC) over two weeks. Psychopathology was assessed by clinician-administered and self-reported measures of depression and anxiety; decision-making was assessed by the Iowa Gambling Task, the Balloon Analog Risk Task and the Game of Dice Task; impulse control was assessed by the Stroop Color-Word Task, the Continuous Performance Task and the Stop-Signal Task. ResultsDepression and anxiety scores significantly improved from pre-post HF-rTMS treatment. However, none of the decision-making or impulse control variables of interest changed significantly from pre-post HF-rTMS. Moreover, there was no correlation between changes in psychopathological symptoms and in neurocognition. LimitationsThis is a moderately sized open label trial, and the confounds of ongoing psychotropics and illness chronicity can not be excluded in this treatment resistant sample. ConclusionsThere is dissociation between acute symptomatic benefit after a course of accelerated HF-rTMS applied to the lDLPFC in treatment resistant MDD and performance on tests of decision making and impulse control. Though rTMS appears cognitively safe, additional research is warranted to understand this potential dissociation and its putative clinical implications.

Repetitive Transcranial Magnetic Stimulation (5 and 10 Hz) With Modified Parameters in the Treatment of Resistant Unipolar and Bipolar Depression in a Private Practice Setting.

A limited number of studies have investigated the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) in the treatment of resistant depression in an outpatient private practice setting. We hypothesized that rTMS would be safe and effective in the treatment of resistant depression in a nonresearch population. We treated 22 outpatients with unipolar or bipolar depression who were experiencing a moderate to severe treatment-resistant major depressive episode (MDE). Treatment was based on a flexible dose schedule of either 5 Hz or 10 Hz rTMS applied over the left dorsolateral prefrontal cortex with modified parameters. Assessments were performed at baseline, then on a weekly basis. The patients had received at least 2 trials of antidepressant medication of an adequate dose and duration without satisfactory improvement in the index MDE. There was a significant change in Montgomery-Asberg Depression Rating Scale scores from baseline (29.14±5.85) to the end of week 4 (16.27±11.20); 50.00% (11/22) were responders and 40.9% (9/22) achieved remission. No major side effects were observed aside from mild headache in some patients. rTMS applied to the left dorsolateral prefrontal cortex was safe and effective in an important subset of outpatients with a moderate to severe MDE in a naturalistic setting. Outcomes demonstrated response rates similar to research populations. Further larger studies are needed to confirm the safety and effectiveness of rTMS in naturalistic conditions.

An Open-Label Feasibility Trial of Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Major Depressive Episodes.

Repetitive transcranial magnetic stimulation (rTMS) has been reported to be a new treatment option for treatment-resistant depression. In Japan, there has been limited research into its feasibility, efficacy, and tolerability. We have launched a trial of rTMS for treating medication-resistant major depressive disorder and bipolar depression. We are investigating low-frequency rTMS to the right dorsolateral prefrontal cortex and traditional high-frequency rTMS to the left dorsolateral prefrontal cortex, in 20 patients. The primary outcome of the study is the treatment completion rate. This study will provide new data on the usefulness of rTMS for treatment-resistant depression in Japan.

Transcranial Magnetic Stimulation of Left Dorsolateral Prefrontal Cortex Induces Brain Morphological Changes in Regions Associated with a Treatment Resistant Major Depressive Episode: An Exploratory Analysis.

Repetitive transcranial magnetic stimulation (TMS) is an FDA-approved antidepressant treatment but little is known of its mechanism of action. Specifically, downstream effects of TMS remain to be elucidated. This study aims to identify brain structural changes from TMS treatment of a treatment resistant depressive episode through an exploratory analysis. Twenty-seven subjects in a DSM-IV current major depressive episode and on a stable medication regimen had a 3T magnetic resonance T1 structural scan before and after five weeks of standard TMS treatment to the left dorsolateral prefrontal cortex. Twenty-seven healthy volunteer (HVs) subjects had the same brain MRI acquisition. Voxel-based morphometry was performed using high dimensional non-linear diffusomorphic anatomical registration (DARTEL). Six clusters of gray matter volume (GMV) that were lower in pre-treatment MRIs of depressed subjects than in HVs. GMV in four of these regions increased in MDD after TMS treatment by 3.5-11.2%. The four brain regions that changed with treatment were centered in the left anterior cingulate cortex, the left insula, the left superior temporal gyrus and the right angular gyrus. Increases in the anterior cingulate GMV with TMS correlated with improvement in depression severity. To our knowledge, this is the first study of brain structural changes during TMS treatment of depression. The affected brain areas are involved in cognitive appraisal, decision-making and subjective experience of emotion. These effects may have potential relevance for the antidepressant action of TMS.

Posterior vitreous detachment and electroconvulsive therapy: Insights from a case

A case of bilateral posterior vitreous detachment after electroconvulsive therapy (ECT) has been reported previously in the literature. There is not enough evidence about ocular side effects of this treatment. The literature supports a slight increase in intraocular pressure (IOP), although no ocular complications have been reported in normal, glaucomatous or postsurgical eyes. In this case report, we describe a 73-year-old female patient suffering a recurrent depressive disorder, who was admitted to acute psychiatric unit because a treatment-resistant major depressive episode (after an adequate trial of antidepressant drugs and transcranial magnetic stimulation) and clinical suspicion of visual delusions by her reference psychiatrist. The nonpsychiatric history consisted of hypertension, glaucoma and ulcerative colitis in treatment with azathioprine and mesalazine. After a careful examination in the emergency room, we consulted to ophthalmologist because miodesopsias and glaucoma history. The IOP was normal, but a bilateral posterior vitreous detachment (PVD) was identified. Because this entity is not an absolute contraindication for ECT, and there is scarce evidence, we informed the patient and her family. After that, and through informed consent, we decided to undergo ECT. After fourteen sessions, the patient could be discharged because significant clinical benefit and no ocular complications. Outpatient continuation ECT was indicated.ConclusionsECT can be a safe treatment choice in cases of PVD.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Can quetiapine extended release (ER) induce labial edema in a female patient with treatment-resistant major depressive episode?

Major depressive episode (MDE) is a clinical condition affecting about 350 million people worldwide, and leading a high morbidity and mortality. There are a large proportion of patients who still do not always respond to currently available and conventional pharmacological treatments (antidepressant medication). Rates of treatment-resistant depression (TRD) range from 2–3 to 30 %, vary according to the threshold of unsuccessful trials: it remains, however, a significant clinical challenge [1]. Quetiapine extended release (ER) is classified as an atypical antipsychotic that is commonly prescribed for a broad range of psychiatric conditions, also in off label use (such as sleep disturbances in dementia, anxiety and personality disorders). It has been approved and proven to be effective in the treatment of schizophrenia, bipolar disorder (acute phases and long-term treatment) and, recently, as an adjunctive agent in patients with partial or no response to a conventional treatment [2]. It is mainly metabolized in the liver via cytochrome P450 isoenzyme CYP3A4 and it is characterized by the weakest affinity for dopamine D2 receptors of all the antipsychotics: this drug certainly binds D2 receptors, but rapidly dissociates from them. It exhibits a strong affinity for antagonism at histamine H1-receptors, similar to that of diphenhydramine, amitriptyline, mirtazapine, and has a moderate affinity for serotonin type 2A (5-HT2A) receptors. Other neurotransmitter systems are involved such as serotoninergic (5-HT2C, 5-HT6, 5-HT7), adrenergic (a1, a2), muscarinic (M1, M3) receptors, and a partial agonist to serotonin 5HT1A receptors. Case reports reporting peripheral edema induced by quetiapine are described in literature [3] but no case report exists reporting labial edema.

Effectiveness of Electroconvulsive Therapy in a Patient With a Treatment-Resistant Major Depressive Episode and Comorbid Body Dysmorphic Disorder

A 24-year-old man experiencing comorbid body dysmorphic disorder since age 16 years, complicated in recent months by a major depressive episode with psychotic features, showed resistance to various drug and psychotherapy combinations. We suggested electroconvulsive therapy (ECT) to overcome treatment resistance. After 1 ECT cycle, mood and anxiety symptoms improved significantly, delusional interpretations and ideas of reference subsided, and dysmorphophobic symptoms improved as well. Six months later, the patient was doing well with a mood stabilizer/antipsychotic combination. Electroconvulsive therapy may improve symptoms of comorbid body dysmorphic disorder along with mood improvement in treatment-resistant depressive disorder.

Prevention of Relapse With Maintenance Electroconvulsive Therapy in Elderly Patients With Major Depressive Episode

To evaluate the effectiveness and safety of maintenance electroconvulsive therapy (mECT) in elderly patients with treatment-resistant Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depressive episode. Seven elderly patients with treatment-resistant major depressive episode were treated with a complete ECT cycle. Thereafter, they received one monthly ECT session as maintenance for 1 year. Response to treatment was defined as at least a 50% drop from baseline on the Hamilton Depression Rating Scale (HamD) and remission as not meeting criteria for major depression, a HamD score of 7 or less, and Clinical Global Impressions-Severity of Illness score of 1. We compared their response with the response of 7 elderly patients with treatment-resistant major depression who were treated with a full cycle of ECT but did not receive mECT (non-mECT). We compared the 2 groups for the number of relapses or recurrences of major depressive episodes after remission was achieved; a relapse or a recurrence occurred when HamD scores were 14 or higher, or when Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision major depressive episode criteria were met, or when Clinical Global Impressions-Severity of Illness score was 3 or higher and increased by at least 2 points from response/remission. The mECT group (4 women and 3 men; mean age, 73 years) had significantly less mean relapses/recurrences (0 vs 1.57) and hospitalizations (0 vs 1) and received less drug treatment than the nonMECT group (similar for age and sex composition) during the 12-month follow-up period. All patients with mECT improved during treatment and did not relapse. Maintenance ECT protected elderly patients from recurrent depressive episodes from relapsing/recurring more than standard ECT.

Effectiveness and Safety of Vagus Nerve Stimulation for Severe Treatment-Resistant Major Depression in Clinical Practice After FDA Approval

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.

P.2.a.015 Transcranial direct current stimulation in patients with treatment-resistant major depressive episode

P.2.a.015 Transcranial direct current stimulation in patients with treatment-resistant major depressive episode

Two-Year Outcome of Vagus Nerve Stimulation (VNS) for Treatment of Major Depressive Episodes

Vagus nerve stimulation (VNS) had antidepressant effects in an initial open, acute phase pilot study of 59 participants in a treatment-resistant major depressive episode (MDE). We examined the effects of adjunctive VNS over 24 months in this cohort. Adult outpatients (N = 59) with chronic or recurrent major depressive disorder or bipolar (I or II) disorder and experiencing a treatment-resistant, nonpsychotic MDE (DSM-IV criteria) received 2 years of VNS. Changes in psychotropic medications and VNS stimulus parameters were allowed only after the first 3 months. Response was defined as > or = 50% reduction from the baseline 28-item Hamilton Rating Scale for Depression (HAM-D-28) total score, and remission was defined as a HAM-D-28 score < or = 10. Based on last observation carried forward analyses, HAM-D-28 response rates were 31% (18/59) after 3 months, 44% (26/59) after 1 year, and 42% (25/59) after 2 years of adjunctive VNS. Remission rates were 15% (9/59) at 3 months, 27% (16/59) at 1 year, and 22% (13/59) at 2 years. By 2 years, 2 deaths (unrelated to VNS) had occurred, 4 participants had withdrawn from the study, and 81% (48/59) were still receiving VNS. Longer-term VNS was generally well tolerated. These results suggest that patients with chronic or recurrent, treatment-resistant depression may show long-term benefit when treated with VNS.

Enhanced Attention-dependent Auditory Processing by Electroconvulsive Therapy in Psychotic Depression

There is a lack of knowledge about the effect of electroconvulsive therapy (ECT) on auditory event-related potentials (ERPs) in severe psychotic depression. The aim of this study was to investigate both the effect of ECT on attention-dependent ERP (P300) and the correlation of P300 values with depression level. We recorded the auditory ERPs of 23 patients expressing psychotic symptoms and fulfilling the DSM-III-R criteria for treatment-resistant severe major depressive episode before and a week after successful bitemporal ECT. The clinical status was assessed with Hamilton (Ham-D) and Montgomery and Asberg (MADRS) depression scales. ECT was clinically very effective with these scales. On the level of auditory processing, ECT increased P300 amplitude with no significant effect on latency. Small amplitudes over the left hemisphere before treatment were associated with bigger Ham-D-score decrement. ECT produces a significant increase in brain activity at the level of attention-dependent auditory processing in severe depression. The change in electrical responses seems to represent a largely independent variable from the clinical assessment scales, even if the recovery rate was remarkable, because the change in overall symptom scores did not correlate with the P300 changes.

Pramipexole in treatment-resistant depression: An extended follow-up

We evaluated the long-term antidepressant safety and response of adjunctive pramipexole, a D2-D3 dopamine agonist, in the course of drug-resistant depression. Twenty-three patients with treatment-resistant major depressive episode (MDE) were followed up after a 16-week pramipexole add-on trial. Pramipexole was added to current treatment with TCA or SSRI, at increasing doses from 0.375-1.500 mg/day. The LIFE scale was administered at baseline of the acute trial, at Weeks 16, 32, and 48. Patients were analyzed for sustained remission (score= <2 at LIFE for at least 8 weeks) and recurrence (after remission score > =3 at LIFE for at least 2 weeks) of depression. Of 23 patients, 12 had major depression and 11 had bipolar depression (16 women; mean age=52.8 years). Mean age of onset and median duration of current MDE were 35.1 years and 6 months, respectively; all subjects had at least two prior MDEs. Mean pramipexole dose was 0.990 mg/day. Median duration of follow-up was 28 weeks. Mean baseline MADRS and CGI-S scores were 33.7+/-8.4 (sd) and 4.6+/-0.8, respectively. Median time to sustained remission from baseline was 10 weeks and overall 60.9% (14/23) of subjects recovered within Week 22. Recurrence of depression occurred in 35.7% (5/14) of remitters after Week 24 and within Week 28 from remission. Although there were no sleep attacks, two cases of hypomania and one case of psychotic mania occurred at Weeks 22, 24, and 30, respectively. Pramipexole augmentation of antidepressant treatment was relatively safe and presumably effective in the long-term course of treatment resistant depression.

Vagus nerve stimulation (VNS) for major depressive episodes: one year outcomes

Background: Vagus nerve stimulation has shown promising results in an open, acute phase pilot study of adults in a treatment-resistant major depressive episode. This open, naturalistic follow-up study was conducted to determine whether the initial promising effects were sustained, and whether changes in function would be observed.Methods: Thirty adult outpatients in a treatment-resistant, nonpsychotic major depressive episode received an additional 9 months of vagus nerve stimulation treatment following exit from the 3-month acute study. Changes in psychotropic medications and vagus nerve stimulation stimulus parameters were allowed during this longer-term follow-up study. A priori definitions were used to define response (≥ 50% reduction in baseline Hamilton Rating Scale for Depression total score) and remission (Hamilton Rating Scale for Depression ≤ 10).Results: The response rate was sustained [40% (12/30) to 46% (13/28); p = .317] and the remission rate significantly increased [17% (5/30) to 29% (8/28); p = .045] with an additional 9 months of long-term vagus nerve stimulation treatment after exit from the acute study (1 year total vagus nerve stimulation treatment). Significant improvements in function between acute study exit and the 1-year follow-up assessment as measured by the Medical Outcomes Study Short Form-36 were observed.Conclusions: Longer-term vagus nerve stimulation treatment was associated with sustained symptomatic benefit and sustained or enhanced functional status in this naturalistic follow-up study.

Vagus Nerve Stimulation (VNS™) for Treatment-Resistant Depression: Efficacy, Side Effects, and Predictors of Outcome

This open pilot study of vagus nerve stimulation (VNS™) in 60 patients with treatment-resistant major depressive episodes (MDEs) aimed to: 1) define the response rate; 2) determine the profile of side effects; and, most importantly; 3) establish predictors of clinical outcome. Participants were outpatients with nonatypical, nonpsychotic, major depressive or bipolar disorder who had not responded to at least two medication trials from different antidepressant classes in the current MDE. While on stable medication regimens, the patients completed a baseline period followed by device implantation. A 2-week, single blind, recovery period (no stimulation) was followed by 10 weeks of VNS. Of 59 completers (one patient improved during the recovery period), the response rate was 30.5% for the primary HRSD28 measure, 34.0% for the Montgomery-Äsberg Depression Rating Scale (MADRAS), and 37.3% for the Clinical Global Impression-Improvement Score (CGI-I of 1 or 2). The most common side effect was voice alteration or hoarseness, 55.0% (33/60), which was generally mild and related to output current intensity. History of treatment resistance was predictive of VNS outcome. Patients who had never received ECT (lifetime) were 3.9 times more likely to respond. Of the 13 patients who had not responded to more than seven adequate antidepressant trials in the current MDE, none responded, compared to 39.1% of the remaining 46 patients (p = .0057). Thus, VNS appears to be most effective in patients with low to moderate, but not extreme, antidepressant resistance. Evidence concerning VNS' long-term therapeutic benefits and tolerability will be critical in determining its role in treatment-resistant depression.