Showing papers on "Treatment-resistant depression published in 2010"

[Treatment-resistant depression].

Abstract: Hochdosierung von Antidepressiva Bei Vorliegen einer Therapieresistenz ist der erste Schritt im Behandlungsregime die Optimierung der Dosierung und Behandlungsdauer des aktuell eingenommenen Antidepressivums. Aufgrund der erheblichen interindividuellen Variabilität bezüglich pharmakokinetischer und -dynamischer Prozesse und einer eher selten vorhandenen engen Dosis-Wirkungsbeziehung ist für den Patienten die notwendige Dosierung individuell zu definieren. Wenn trotz zuverlässiger Einnahme der Antidepressiva die Plasmaspiegel unterhalb des therapeutischen Bereichs liegen bzw. wenn bei Antidepressiva weder eine Therapieresponse noch unerwünschte Wirkungen zu beobachten sind, kann eine Hochdosisbehandlung in Erwägung gezogen werden. Hochdosisbehandlung bedeutet dabei eine Dosierung an der oberen Grenze oder oberhalb des empfohlenen Dosierungsbereichs. In einer Übersichtsarbeit von Adli et al. [4] finden sich 11 Studien, welche die Wirksamkeit einer Hochdosisbehandlung bei therapieresistenten Depressionen untersuchten. Von den 11 Studien waren 7 doppelblinde, randomisierte, kontrollierte Studien und 4 kleinere offene Studien. Zu den Trizyklika (TCA) lag keine Studie vor, jedoch fanden sich u.a. 5 Studien zu Fluoxetin, 2 zu Sertralin und 1 zu Paroxetin. Auf der Basis der zur Verfügung stehenden Studien lässt sich die Wirksamkeit einer Antidepressivahochdosisbehandlung nicht eindeutig beantworten. Für Triund Tetrazyklika finden sich keine Studien zur Wirksamkeit der Hochdosisbehandlung, für selektive Serotonin-Wiederaufnahmehemmer (SSRI) scheint die Hochdosisbehandlung eine sinnvolle Strategie zu sein. Für Monoaminoxidase-Hemmer (MAO-Hemmer) lassen sich in einer äußerst dünnen Datenlage Hinweise für eine mögliche Effektivität sehr hoher Dosen Tranycypromin finden. Für Venlafaxin ist die Datenlage ebenfalls eher spärlich, 2 vor Kurzem publizierte Studien [5, 6] belegen jedoch den klinischen Eindruck und weisen auf eine mögliche positive Dosiswirkungsbeziehung hin.

Therapeutic options for treatment-resistant depression.

Abstract: Treatment-resistant depression (TRD) presents major challenges for both patients and clinicians. There is no universally accepted definition of TRD, but results from the US National Institute of Mental Health’s (NIMH) STAR*D (Sequenced Treatment Alternatives to Relieve Depression) programme indicate that after the failure of two treatment trials, the chances of remission decrease significantly.

Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression.

Abstract: Background Repetitive transcranial magnetic stimulation (rTMS) has shown safety and efficacy for treatment-resistant depression (TRD) but requires daily treatment over 4–6 weeks. Accelerated TMS, with all treatments delivered over a few days, would have significant advantages in terms of access and patient acceptance.

Two-Year Outcome of Vagus Nerve Stimulation in Treatment-Resistant Depression

Abstract: One of the major goals of antidepressant treatment is a sustained response and remission of depressive symptoms. Some of the previous studies of vagus nerve stimulation (VNS) have suggested antidepressant effects. Our naturalistic study assessed the efficacy and the safety of VNS in 74 European patients with therapy-resistant major depressive disorder. Psychometric measures were obtained after 3, 12, and 24 months of VNS. Mixed-model repeated-measures analysis of variance revealed a significant reduction (P or =50% reduction in the HRSD28 scores from baseline) and 38.9% (19/49) fulfilled the remission criteria (HRSD28 scores < or = 10). The proportion of patients who fulfilled the remission criteria remained constant as the duration of VNS treatment increased. Voice alteration, cough, and pain were the most frequently reported adverse effects. Two patients committed suicide during the study; no other deaths were reported. No statistically significant differences were seen in the number of concomitant antidepressant medications. The results of this 2-year open-label trial suggest a clinical response and a comparatively benign adverse effect profile among patients with treatment-resistant depression.

Rapid antidepressant effect of ketamine anesthesia during electroconvulsive therapy of treatment-resistant depression: comparing ketamine and propofol anesthesia.

Abstract: BACKGROUND: Reports of the superiority of the antidepressant effect of ketamine during the conduct of electroconvulsive therapy (ECT) have been limited. We conducted an open-label trial of ketamine to determine whether ketamine as the anesthetic during ECT would provide a greater antidepressant effect than the antidepressant effect obtained with propofol. METHODS: Between April 2006 and April 2007, 31 inpatients with treatment-resistant depression gave written consent for ECT and to participate in this study. An anesthesiologist who was unaware of the mental symptoms of the subjects assigned them to receive propofol or ketamine anesthetic according to the preferences of the patients, and the patients underwent 8 ECT sessions for 4 weeks. The Hamilton Depression Rating Scale (HDRS) was valuated before ECT and after the completion of the second, fourth, sixth, and eighth ECT sessions. RESULTS: The HDRS scores improved earlier in the ketamine group, with decreases in HDRS scores that were significantly greater in the ketamine group. CONCLUSIONS: The results suggested that it is possible to improve symptoms of depression earlier by using ketamine anesthesia.

RESEARCH: Validation of the Massachusetts General Hospital Antidepressant Treatment History Questionnaire (ATRQ)

Abstract: The low rate of response to antidepressants in treatment resistant depression (TRD) justifies studies of next-step therapies following a treatment failure. In TRD clinical trials, it is important to verify the accurate diagnosis of treatment resistance for all enrolled subjects using a reliable and valid instrument. Self-rated scales can reduce the impact of investigator bias and reduce the time burden for clinical researchers. The Massachusetts General Hospital (MGH) Antidepressant Treatment Response Questionnaire (ATRQ) is a self-rated scale used to determine treatment resistance in major depressive disorder (MDD). The ADAPT-A study is a multi-center double-blind, placebo-controlled study of low-dose aripiprazole adjunctive to ADT among outpatients with TRD. At the screening assessment, potential subjects completed the MGH ATRQ. The ADAPT-A medical monitors subsequently performed remote patient interviews and obtained detailed medication histories. The data obtained from the MGH ATRQ and by the medical monitors were compared for congruency. Of the 186 patients enrolled by the local sites, no subjects deemed treatment resistant by the MGH ATRQ were found to be nonresistant by the medical monitors. In 76.3% (n = 142) of the subjects, the number of failed adequate antidepressant trials reported by the MGH ATRQ was concordant with the data collected by medical monitors. In 16.1% (n = 30) of all cases, the medical monitors found a greater number of failed trials; in 7.5% (n = 14) of cases, the medical monitors found fewer failed medication trials. The discrepancy was by more than one medication trial in only 4.0% (n = 7) of cases. We found the MGH ATRQ to be relatively concordant in its assessment of treatment resistance in depression compared with independent clinical researchers. Although the MGH ATRQ tended to underreport the number of unsuccessful treatment trials relative to the clinical interviews, its accuracy in cases it detected was confirmed by raters.

Lithium's emerging role in the treatment of refractory major depressive episodes: augmentation of antidepressants.

Abstract: Background: The late onset of therapeutic response and a relatively large proportion of nonresponders to antidepressants remain major concerns in clinical practice. Therefore, there is a critical need for effective medication strategies that augment treatment with antidepressants. Methods: To review the available evidence on the use of lithium as an augmentation strategy to treat depressive episodes. Results: More than 30 open-label studies and 10 placebo-controlled double-blind trials have demonstrated substantial efficacy of lithium augmentation in the acute treatment of depressive episodes. Most of these studies were performed in unipolar depression and included all major classes of antidepressants, however mostly tricyclics. A meta-analysis including 10 randomized placebo-controlled trials has provided evidence that lithium augmentation has a statistically significant effect on the response rate compared to placebo with an odds ratio of 3.11, which corresponds to a number-needed-to-treat of 5. The meta-analysis revealed a mean response rate of 41.2% in the lithium group and 14.4% in the placebo group. One placebo-controlled trial in the continuation treatment phase showed that responders to acute-phase lithium augmentation should be maintained on the lithium-antidepressant combination for at least 12 months to prevent early relapses. Preliminary studies to assess genetic influences on response probability to lithium augmentation have suggested a predictive role of the –50T/C single nucleotide polymorphism of the GSK3β gene. Conclusion: Augmentation of antidepressants with lithium is currently the best-evidenced augmentation therapy in the treatment of depressed patients who do not respond to antidepressants.

Use of deep brain stimulation in treatment-resistant depression.

Abstract: Deep brain stimulation has emerged as an experimental treatment option for the sizeable proportion of patients with major depression that is refractory to multiple medications and psychotherapy. Chronic stimulation of the ventral internal capsule/ventral striatum has been shown to improve function and mood in patients with severe obsessive-compulsive disorder, and has likewise been applied to patients with treatment-resistant depression. Multicenter experience with chronic deep brain stimulation of the ventral capsule/ventral striatum in 17 patients with severe treatment-resistant depression has demonstrated sustained improvements across multiple scales of depression, anxiety, and global function. Further research on deep brain stimulation in larger populations of patients with treatment-refractory depression is under way. While such research should benefit from the recent US Food and Drug Administration approval of deep brain stimulation for severe obsessive-compulsive disorder, it must adhere to strict principles for appropriate patient selection.

Chronic and treatment-resistant depression: a study using arterial spin labeling perfusion MRI at 3Tesla.

Abstract: The aim of the present study was to compare patients displaying chronic and treatment-resistant depression with healthy controls, using the resting-state perfusion with arterial spin labeling (ASL) perfusion magnetic resonance imaging (MRI) technique at 3T. The study focused on the subgenual anterior cingulate cortex (sACC), which is a key component in the pathophysiology of depression. Six patients with chronic and treatment-resistant depression and six healthy control subjects were included. ASL is an innovative imaging technique which sidesteps the limitations of other functional neuroimaging techniques (functional MRI, positron emission tomography). A statistical analysis of perfusion maps was performed using SPM2 software. Statistically significant hyperperfusion regions were found in the depressed patient group compared with the healthy control group in the following: the bilateral sACC, left prefrontal dorsomedian cortex, left ACC and left subcortical areas (putamen, pallidum and amygdala). This study confirmed the involvement of the sACC in depression, particularly chronic and treatment-resistant depression, using ASL at 3T, a safe perfusion technique that seems to be appropriate for investigating functional abnormalities in psychiatric disorders.

High-frequency rTMS treatment increases left prefrontal myo-inositol in young patients with treatment-resistant depression.

Abstract: Background Neuroimaging studies suggest that the prefrontal cortex (PFC) is involved in the pathophysiology of major depression. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. In this study metabolic changes within PFC of severely depressed patients before and after rTMS were evaluated by proton magnetic resonance spectroscopy (1H-MRS). Method Thirty-four young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study〔active ((n = 19) vs. sham(n = 15)), and the PFC was investigated before and after high-frequency (15 Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy. Response was defined as a 50% reduction of the Hamilton depression rating scale. The results were compared with 28 age- and gender-matched healthy controls. Results In depressive patients a significant reduction in myo-inositol (m-Ino) was observed pre-rTMS ( p Conclusions Our results support the notion that major depressive disorder is accompanied by state-dependent metabolic alterations, especially in myo-inositol metabolism, which can be partly reversed by successful rTMS.

Deep Brain Stimulation for Treatment-Resistant Depression

Abstract: Brian did reasonably well for about 3 years, with occasional worsening of depressive symptoms but generally with good functioning, when he developed his current major depressive episode. This was his most severe episode to date, with active suicidal ideation with a plan (but no immediate intent) to shoot himself. Over the next year, he had a number of treatments, among them multiple antidepressant medications, including selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, mirtazapine, tricyclic antidepressants, and tranylcypromine, as well as augmentation with lithium, thyroid hormone, buspirone, atypical antipsychotics, anticonvulsants, stimulants, light therapy, and ongoing psychotherapy. No treatment was able to achieve remission or a persistent clinically signifi cant reduction in symptoms. Given his degree of treatment resistance and continued overall deterioration, including increased suicidal ideation, he was referred for ECT. He achieved a good response (50%‐60% symptom reduction) with eight highdose right unilateral ECT treatments. ECT was delivered concurrently with ongoing medications, and attempts were made to optimize medications during and after ECT. However, Brian relapsed in about 6 weeks, and repeat ECT (including four right unilateral and eight bitemporal treatments delivered concurrently with ongoing medications) was unsuccessful in achieving signifi cant symptom reduction but was associated with notable cognitive impairment.

Deep brain stimulation for obsessive-compulsive disorder and treatment-resistant depression: systematic review

Abstract: In spite of advances in psychotherapy and pharmacotherapy, there are still a significant number of patients with depression and obsessive-compulsive disorder that are not aided by either intervention. Although still in the experimental stage, deep brain stimulation (DBS) offers many advantages over other physically-invasive procedures as a treatment for these psychiatric disorders. The purpose of this study is to systematically review reports on clinical trials of DBS for obsessive-compulsive disorder (OCD) and treatment-resistant depression (TRD). Locations for stimulation, success rates and effects of the stimulation on brain metabolism are noted when available. The first observation of the effects of DBS on OCD and TRD came in the course of using DBS to treat movement disorders. Reports of changes in OCD and depression during such studies are reviewed with particular attention to electrode locations and associated adverse events; although these reports were adventitious observations rather than planned. Subsequent studies have been guided by more precise theories of structures involved in DBS and OICD. This study suggests stimulation sites and prognostic indicators for DBS. We also briefly review tractography, a relatively new procedure that holds great promise for the further development of DBS. Articles were retrieved from MEDLINE via PubMed. Relevant references in retrieved articles were followed up. We included all articles reporting on studies of patients selected for having OCD or TRD. Adequacy of the selected studies was evaluated by the Jadad scale. Evaluation criteria included: number of patients, use of recognized psychiatric rating scales, and use of brain blood flow measurements. Success rates classified as "improved" or "recovered" were recorded. Studies of DBS for movement disorders were included if they reported coincidental relief of depression or reduction in OCD. Most of the studies involved small numbers of subjects so individual studies were reviewed. While the number of cases was small, these were extremely treatment-resistant patients. While not everyone responded, about half the patients did show dramatic improvement. Associated adverse events were generally trivial in younger psychiatric patients but often severe in older movement disorder patients. The procedures differed from study to study, and the numbers of patients was usually too small to do meaningful statistics or make valid inferences as to who will respond to treatment. DBS is considered a promising technique for OCD and TRD. Outstanding questions about patient selection and electrode placement can probably be resolved by (a) larger studies, (b) genetic studies and (c) imaging studies (MRI, fMRI, PET, and tractography).

Pharmacologic Approaches to Treatment Resistant Depression: A Re-examination for the Modern Era

Abstract: Importance of the field: Treatment-resistant depression (TRD) is common and debilitating. Initial treatment is often insufficient to achieve full remission in a given depressive episode, resulting in more frequent episodes, worsened severity, and major disability.Areas covered in this review: This review surveys literature on the diagnosis and pharmacological management of TRD in light of recent developments. Evidence regarding commonly used treatment options is critically examined and key recommendations are offered. The review ends by considering drugs acting on the melatonin, acetylcholine, and glutamate systems that hold promise as future options for TRD.What the reader will gain: Recent trends and research findings have impacted how the evidence supporting different approaches to TRD should be evaluated. For example, many earlier TRD studies employed tricyclics as the primary antidepressant, but tricyclics have now been superseded by selective serotonin reuptake inhibitors (SSRIs) in routine clinical...

Comparisons of the Efficacy and Tolerability of Extended-Release Venlafaxine, Mirtazapine, and Paroxetine in Treatment-Resistant Depression: A Double-Blind, Randomized Pilot Study in a Chinese Population

Abstract: To compare the efficacy and tolerability of antidepressants switch with extended-release venlafaxine (venlafaxine-XR), mirtazapine, and paroxetine in Chinese patients with major depressive disorder who had 2 consecutive unsuccessful antidepressant trials. One hundred fifty adult patients with treatment-resistant depression according to their medical records and/or response to current treatments were randomly assigned to receive fixed-dosage treatment of venlafaxine-XR 225 mg/d (n = 50), mirtazapine 45 mg/d (n = 55), or paroxetine 20 mg/d (n = 45) for 8 weeks. The primary outcome was the remission rates that were defined as a score 7 or lower on the 17-item Hamilton Rating Scale for Depression (HRSD-17). Secondary outcomes included the remission rate defined by the Self-Rating Depression Scale of 50 or lower and the response rate defined by a 50% reduction or greater on the HRSD-17 total score, and the improvement of patients' general health functions. The completion rates were 82% for venlafaxine-XR, 81.8% for mirtazapine, and 82.2% for paroxetine. Only one patient in paroxetine arm discontinued the study owing to an adverse event. The remission rates based on the HRSD-17 were 42.0% for venlafaxine-XR, 36.4% for mirtazapine, and 46.7% for paroxetine. There were no statistical significances between treatment arms in remission rates. Similarly, there were also no significant differences between groups in secondary outcome measure. Venlafaxine-XR, mirtazapine, and paroxetine were equally effective in the treatment of Chinese patients with major depressive disorder who failed at least 2 previous antidepressant treatments. Selecting any of these 3 antidepressants as a third-step antidepressant is a reasonable choice for this group of patients.

The Use of a Series of Ketamine Infusions in Two Patients With Treatment-Resistant Depression

Abstract: Treatment-resistant depression often leads to increased morbidity and disability. The authors report the use of ketamine, a selective N-methyl-D-aspartate (NMDA) receptor antagonist, in two patients with treatment-resistant depression. Multiple ketamine treatments may provide an effective rapid antidepressant effect with prolonged benefit.

Adding a low dose atypical antipsychotic drug to an antidepressant induced a rapid increase of plasma brain-derived neurotrophic factor levels in patients with treatment-resistant depression.

Abstract: Only two-thirds of depressive patients respond to antidepressant treatment. Recently, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we examined the effects of various atypical antipsychotic drugs as adjuvant to antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin noradrenaline reuptake inhibitors, tricyclic antidepressants and mood stabilizers, on plasma BDNF levels in refractory depressed patients. Forty-five patients who met the DSM-IV criteria for major depressive disorder (n=31) or bipolar disorder (10 with bipolar I, 4 with bipolar II) were enrolled in the study. Twenty-one were male and 24 were female, and their ages ranged from 28 to 71 (mean+/-SD=49+/-12) years. Plasma BDNF levels were measured using a sandwich ELISA. The plasma BDNF levels in responders (those showing a decline in HAM-D scores of 50% or more) were significantly increased 4weeks after the administration of each atypical antipsychotic drug, while the levels in non-responders were not changed. Furthermore, there was a significant correlation between the changes in HAM-D scores and the changes in plasma BDNF levels. These results suggest that adding an atypical antipsychotic drug to ongoing treatment with an antidepressant or mood stabilizer is useful and well-tolerated for refractory depressed patients, and the efficacy of atypical antipsychotics as an adjuvant might involve an increase of plasma BDNF levels.

Do the old psychostimulant drugs have a role in managing treatment-resistant depression?

Abstract: Parker G, Brotchie H. Do the old psychostimulant drugs have a role in managing treatment-resistant depression? Objective: As the authors have observed clinical benefit from the psychostimulants methylphenidate and dexamphetamine for treating resistant melancholic and bipolar depression, those drugs were evaluated in a consecutively recruited sample of 50 such patients. Method: Patients (27 bipolar, 23 unipolar) received either methylphenidate (n = 44) or dexamphetamine (n = 6), with 30 having it prescribed as an augmenting drug and 20 as monotherapy. At the final review, ranging from 6 weeks to 62 months (mean 57 weeks), 52% were still receiving their psychostimulant. Results: Thirty-four per cent reported the psychostimulant as distinctly improving their depression, 30% reported some level of improvement and 36% reported no improvement and/or side-effects. For improvers, the modal dose of methylphenidate was 20 mg. Significant side-effects were reported by 18% (including one manic response), switching was rare and limited to the bipolar subjects, and most side-effects were minor. Any positive response occurred rapidly and loss of efficacy was rare. Testing of tricyclic levels in some patients suggested that stimulant drugs may raise tricyclic levels in those who are rapid metabolizers. Conclusion: Although this study was not controlled, the high success rate in a diagnostically refined sample implies that the psychostimulants may be efficacious for patients with melancholic and bipolar depression who have failed to respond to orthodox antidepressant drugs.

Asymmetrical contribution of brain structures to treatment-resistant depression as illustrated by effects of right subgenual cingulum stimulation.

Abstract: Major depressive disorder is one of the most common psychiatric disorders, with a worldwide lifetime prevalence rate of 10%-20% in women and a slightly lower rate in men. While many patients are successfully treated using established therapeutic strategies, a significant percentage of patients fail to respond. This report describes the successful recovery of a previously treatment-resistant patient following right unilateral deep brain stimulation of Brodmann's area 25. Current therapeutic approaches to treatment-resistant patients are reviewed in the context of this case with an emphasis on the role of the right and left hemispheres in mediating disease pathogenesis and clinical recovery.

Olanzapine/fluoxetine combination in patients with treatment-resistant depression: rapid onset of therapeutic response and its predictive value for subsequent overall response in a pooled analysis of 5 studies.

Abstract: OBJECTIVE To characterize response profiles of olanzapine/fluoxetine combination therapy in treatment-resistant depression (TRD) and to investigate predictive relationships of early improvement with olanzapine/fluoxetine combination for subsequent response/remission during the acute phase of treatment. METHOD Results were pooled from 5 outpatient studies comparing oral olanzapine/fluoxetine combination, fluoxetine, or olanzapine for a maximum of 8 weeks in patients with TRD who had at least 1 historical antidepressant treatment failure during the current episode and who failed a prospective antidepressant therapy during the study lead-in period. Mean Montgomery-Asberg Depression Rating Scale (MADRS) total and core mood items scores from the 8-week evaluation period were compared across treatment groups. Positive and negative predictive values (PPVs, NPVs) were computed from olanzapine/fluoxetine combination-treated patients demonstrating response and remission based on whether they demonstrated early improvement. RESULTS Mean olanzapine/fluoxetine combination MADRS score reductions were significantly greater than fluoxetine by week 0.5 and olanzapine by week 1. Significantly more olanzapine/fluoxetine combination patients demonstrated MADRS onset of response compared with fluoxetine and olanzapine patients (P < .001 for both MADRS total and core mood items). In olanzapine/fluoxetine combination patients, 38.1% exhibited MADRS total score response versus 26.9% of fluoxetine patients (P < .001) and 22.2% of olanzapine patients (P < .001). NPVs for MADRS total and core mood items response and remission ranged from 85.7% to 92.1%; PPVs ranged from 29.9% to 45.1%. CONCLUSIONS Olanzapine/fluoxetine combination is superior to fluoxetine and olanzapine in producing early improvement in patients with TRD. The absence of early improvement is highly predictive for overall response failure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00035321.

Psychosocial functioning in patients with treatment-resistant depression after group cognitive behavioral therapy

Abstract: Background Although patients with Treatment Resistant Depression (TRD) often have impaired social functioning, few studies have investigated the effectiveness of psychosocial treatment for these patients. We examined whether adding group cognitive behavioral therapy (group-CBT) to medication would improve both the depressive symptoms and the social functioning of patient with mild TRD, and whether any improvements would be maintained over one year.

Effects of erythropoietin on depressive symptoms and neurocognitive deficits in depression and bipolar disorder

Abstract: Background: Depression and bipolar disorder are associated with reduced neural plasticity and deficits in memory, attention and executive function. Drug treatments for these affective disorders have insufficient clinical effects in a large group and fail to reverse cognitive deficits. There is thus a need for more effective treatments which aid cognitive function. Erythropoietin (Epo) is involved in neuroplasticity and is a candidate for future treatment of affective disorders. The investigators have demonstrated that a single dose of Epo improves cognitive function and reduces neurocognitive processing of negative emotional information in healthy and depressed individuals similar to effects seen with conventional antidepressants. The current study adds to the previous findings by investigating whether repeated Epo administration has antidepressant effects in patients with treatment resistant depression and reverses cognitive impairments in these patients and in patients with bipolar disorder in remission. Methods/design: The trial has a double-blind, placebo-controlled, parallel-group design. 40 patients with treatment-resistant major depression and 40 patients with bipolar disorder in remission are recruited and randomised to receive weekly infusions of Epo (Eprex; 40,000 IU) or saline (NaCl 0.9%) for 8 weeks. Randomisation is stratified for age and gender. The primary outcome parameters for the two studies are: depression severity measured with the Hamilton Depression Rating Scale 17 items (HDRS-17) [1] in study 1 and, in study 2, verbal memory measured with the Rey Auditory Verbal Learning Test (RAVLT) [2,3]. With inclusion of 40 patients in each study we obtain 86% power to detect clinically relevant differences between intervention and placebo groups on these primary outcomes. Trial registration: The trial is approved by the Local Ethics Committee: H-C-2008-092, Danish Medicines Agency: 2612-4020, EudraCT: 2008-04857-14, Danish Data Agency: 2008-41-2711 and ClinicalTrials.gov: NCT 00916552.

Current nosology of treatment resistant depression: a controversy resistant to revision

Abstract: Treatment-Resistant Depression (TRD) represents a source of ongoing clinical and nosological controversy and confusion. While no univocal consensus on its definition and specific correlation with major mood disorders has been reached to date, a progressively greater number of evidences tend to suggest a revision of current clinical nosology. Since a better assessment of TRD should be considered mandatory in order to achieve the most appropriate clinical management, this narrative review aims to briefly present current most accepted definitions of the phenomenon, speculating on its putative bipolar diathesis for some of the cases originally assessed as unipolar depression.