Treatment-refractory Major Depressive Disorder Research Articles

Factor structure of posttraumatic stress disorder (PTSD) in persons with serious mental illness

Background Trauma and posttraumatic stress disorder (PTSD) are common among individuals with serious mental illness (SMI; e.g., schizophrenia, schizoaffective disorder, bipolar disorder, treatment refractory major depressive disorder), with resultant functional impairment. Previous studies have not evaluated the factor structure of the PTSD Checklist (PCL) among persons with SMI. Aims This study evaluated the factor structure of the PCL in two large SMI samples from public mental health treatment sectors screened for PTSD using the PCL. Methods Four different models of PTSD were tested using confirmatory factor analyses. Results Results indicated that the DSM-5 4-factor model (intrusion, avoidance, numbing, and hyperarousal) had the best fit. Further, the DSM-5 4-factor model demonstrated measurement invariance. Conclusions Results supported the suitability of the DSM-5 4-factor model of PTSD among people with SMI.

Metabolic features of treatment-refractory major depressive disorder with suicidal ideation

Peripheral blood metabolomics was used to gain chemical insight into the biology of treatment-refractory Major Depressive Disorder with suicidal ideation, and to identify individualized differences for personalized care. The study cohort consisted of 99 patients with treatment-refractory major depressive disorder and suicidal ideation (trMDD-SI n = 52 females and 47 males) and 94 age- and sex-matched healthy controls (n = 48 females and 46 males). The median age was 29 years (IQR 22–42). Targeted, broad-spectrum metabolomics measured 448 metabolites. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) were measured as biomarkers of mitochondrial dysfunction. The diagnostic accuracy of plasma metabolomics was over 90% (95%CI: 0.80–1.0) by area under the receiver operator characteristic (AUROC) curve analysis. Over 55% of the metabolic impact in males and 75% in females came from abnormalities in lipids. Modified purines and pyrimidines from tRNA, rRNA, and mRNA turnover were increased in the trMDD-SI group. FGF21 was increased in both males and females. Increased lactate, glutamate, and saccharopine, and decreased cystine provided evidence of reductive stress. Seventy-five percent of the metabolomic abnormalities found were individualized. Personalized deficiencies in CoQ10, flavin adenine dinucleotide (FAD), citrulline, lutein, carnitine, or folate were found. Pathways regulated by mitochondrial function dominated the metabolic signature. Peripheral blood metabolomics identified mitochondrial dysfunction and reductive stress as common denominators in suicidal ideation associated with treatment-refractory major depressive disorder. Individualized metabolic differences were found that may help with personalized management.

Closed-Loop Neurostimulation for Biomarker-Driven, Personalized Treatment of Major Depressive Disorder.

Deep brain stimulation involves the administration of electrical stimulation to targeted brain regions for therapeutic benefit. In the context of major depressive disorder (MDD), most studies to date have administered continuous or open-loop stimulation with promising but mixed results. One factor contributing to these mixed results may stem from when the stimulation is applied. Stimulation administration specific to high-symptom states in a personalized and responsive manner may be more effective at reducing symptoms compared to continuous stimulation and may avoid diminished therapeutic effects related to habituation. Additionally, a lower total duration of stimulation per day is advantageous for reducing device energy consumption. This protocol describes an experimental workflow using a chronically implanted neurostimulation device to achieve closed-loop stimulation for individuals with treatment-refractory MDD. This paradigm hinges on determining a patient-specific neural biomarker that is related to states of high symptoms and programming the device detectors, such that stimulation is triggered by this read-out of symptom state. The described procedures include how to obtain neural recordings concurrent with patient symptom reports, how to use these data in a state-space model approach to differentiate low- and high-symptom states and corresponding neural features, and how to subsequently program and tune the device to deliver closed-loop stimulation therapy.

Therapeutic Compatibility of Orally Administered Racemic Ketamine with Modafinil, a CYP3A4 Enzyme Inducer, in Treatment-Refractory Major Depressive Disorder.

Therapeutic Compatibility of Orally Administered Racemic Ketamine with Modafinil, a CYP3A4 Enzyme Inducer, in Treatment-Refractory Major Depressive Disorder.

Association of anhedonia and suicidal ideation in patients with treatment-refractory depression after intravenous ketamine infusions

Objectives Accumulating evidence suggests that the effects of ketamine administered intravenously at subanaesthetic doses on both anhedonic symptoms and suicidal ideation occur independently of depressive symptoms in major depressive disorder (MDD) and bipolar disorder (BD). This study sought to determine the relationship between anhedonia and suicidal ideation after serial ketamine infusions. Methods A total of 79 subjects with either treatment-refractory MDD (n = 60) or BD (n = 19) were included in a clinical ketamine study. The Montgomery–Åsberg Depression Rating Scale (MADRS) anhedonia factor and the first five items of the Scale for Suicidal Ideations (SSI-Part I) were used to assess anhedonia symptoms and suicidal ideation, respectively. Results At baseline, anhedonia, as measured by the MADRS, was not significantly associated with suicidal ideation or specific suicide-related ideation as measured by SSI-Part I (all p’s > 0.05). Only the ‘wish to die’ and ‘desire to make a suicide attempt’ items were positively associated with anhedonia at two weeks after the sixth ketamine infusion, which was independent of the reductions in depressive symptoms (all p’s < 0.05). Conclusion Anhedonia as measured by the MADRS appeared to not be positively related to suicidal ideation after serial ketamine infusions. KEY POINTS Serial ketamine (0.5 mg/kg) infusions have shown quick and dramatic antisuicidal and antianhedonic effects in patients with depression. The association between anhedonia and suicidal ideation after serial ketamine infusions is unclear. Anhedonia appeared to not be positively related to suicidal ideation after serial ketamine infusions.

Feasibility, Acceptability, and Potential Utility of Peer-supported Ecological Momentary Assessment Among People with Serious Mental Illness: a Pilot Study.

To examine the feasibility, acceptability, and initial validity of using smartphone-based peer-supported ecological momentary assessment (EMA) as a tool to assess loneliness and functioning among adults with a serious mental illness diagnosis. Twenty-one adults with a diagnosis of a serious mental illness (i.e., schizophrenia, schizoaffective disorder, bipolar disorder, or treatment-refractory major depressive disorder) and at least one medical comorbidity (i.e., cardiovascular disease, obesity, diabetes, chronic obstructive pulmonary disease, hypertension, and/or high cholesterol) aged 18 years and older completed EMA surveys via smartphones once per day for 12-weeks. Nine peer support specialists prompted patients with SMI to complete the EMA surveys. Data were collected at baseline and 12-weeks. EMA acceptability (15.9%) was reported, and participants rated their experience with EMA methods positively. EMA responses were correlated with higher social support at 3 months. Higher levels of EMA-measured loneliness were significantly correlated with levels of social support, less hope, and less empowerment at 3 months. Lastly, those who contacted their peer specialist reported higher levels of loneliness and lower levels of functioning on that day suggesting that participants were able to use their peers for social support. Peer-supported EMA via smartphones is a feasible and acceptable data collection method among adults with SMI and appears to be a promising mobile tool to assess loneliness and functioning. These preliminary findings indicate EMA-measured loneliness and functioning are significantly predicted by baseline variables and such variables may impact engagement in EMA. EMA may contribute to future research examining the clinical utility of peer support specialists to alleviate feelings of loneliness and improve functioning.

Assessing a digital peer support self-management intervention for adults with serious mental illness: feasibility, acceptability, and preliminary effectiveness

Objective To assess the feasibility, acceptability, and preliminary effectiveness of digital peer support integrated medical and psychiatric self-management intervention (“PeerTECH”) for adults with a serious mental illness. Methods Twenty-one adults with a chart diagnosis of a serious mental illness (i.e., schizophrenia, schizoaffective disorder, bipolar disorder, or treatment-refractory major depressive disorder) and at least one medical comorbidity (i.e., cardiovascular disease, obesity, diabetes, chronic obstructive pulmonary disease, hypertension, and/or high cholesterol) aged 18 years and older received the PeerTECH intervention in the community. Nine peer support specialists were trained to deliver PeerTECH. Data were collected at baseline and 12-weeks. Results This pilot study demonstrated that a 12-week, digital peer support integrated medical and psychiatric self-management intervention for adults with serious mental illness was feasible and acceptable among peer support specialists and patients and was associated with statistically significant improvements in self-efficacy to manage chronic disease and personal empowerment. In addition, pre/post non-statistically significant improvements were observed in psychiatric self-management, medical self-management skills, and feelings of loneliness. Conclusions This single-arm pre/post pilot study demonstrated preliminary evidence peer support specialists could offer a fidelity-adherent digital peer support self-management intervention to adults with serious mental illness. These findings build on the evidence that a digital peer support self-management intervention for adults with serious mental illness designed to improve medical and psychiatric self-management is feasible, acceptable, and shows promising evidence of improvements in clinical outcomes. The use of technology among peer support specialists may be a promising tool to facilitate the delivery of peer support and guided evidence-based self-management support. People with serious mental illness (SMI; defined as individuals diagnosed with schizophrenia spectrum disorder, bipolar disorder, or treatment-refractory major depressive disorder) are increasingly utilizing peer support services to support their health and recovery. Peer support is defined as shared knowledge, experience, emotional, social, and/or practical assistance to support others with similar lived experiences (Solomon, 2004). Most recently the definition also includes the provision of evidence-based peer-supported self-management services (Fortuna et al., 2020). Mental health peer support can augment the traditional mental health treatment system through providing support services to maintain recovery between clinical encounters (Solomon, 2004) and is classified by the World Health Organization as an essential element of recovery (World, Health, and Organization, About social determinants of health, 2017).

Gamma knife radiosurgery versus deep brain stimulation for treatment-refractory depression and obsessive-compulsive disorder: A brief comparative summary.

Both gamma knife surgery (GKS) and deep brain stimulation (DBS) have documented success in management of treatment-refractory major depressive disorder (MDD) and obsessive-compulsive disorder (OCD), but there are no formal randomized controlled trials to compare these treatment modalities in cases of psychiatric illnesses. In this brief review, comparison of GKS and DBS for management of MDD and OCD was done with regard to their efficacy, accompanying risks, reversibility of therapeutic effects, costs, availability, and daily life issues. Currently available evidence does not support the superiority of either evaluated treatment modality over each other in terms of clinical efficacy in cases of MDD and OCD. Nevertheless, with regard to risks, costs, device maintenance, and daily life issues, GKS definitely seems more advantageous. Reversibility of therapeutic effects of DBS is certainly highly attractive, while may be a bit overhyped. In any case, synergy between GKS and DBS for management of mental illnesses lies in the continuing pursuit of improvement and raising the bar of excellence.

Association of VEGF With Antianhedonic Effects of Repeated-Dose Intravenous Ketamine in Treatment-Refractory Depression.

Objectives: To first explore the role of plasma vascular endothelial growth factor (VEGF) concentrations in ketamine's antianhedonic effects, focusing on Chinese patients with treatment-refractory depression (TRD).Methods: Seventy-eight patients with treatment-refractory major depressive disorder (MDD) or bipolar disorder (BD) were treated with six ketamine infusions (0.5 mg/kg). Levels of anhedonia were measured using the Montgomery–Åsberg Depression Rating Scale (MADRS) anhedonia item at baseline, day 13 and 26. Plasma VEGF concentrations were examined at the same time points as the MADRS.Results: Despite a significant reduction in anhedonia symptoms in individuals with treatment-refractory MDD (n = 59) or BD (n = 19) after they received repeated-dose ketamine infusions (p < 0.05), no significant changes in plasma VEGF concentrations were found at day 13 when compared to baseline (p > 0.05). The alteration of plasma VEGF concentrations did not differ between antianhedonic responders and non-responders at days 13 and 26 (all ps > 0.05). Additionally, no significant correlations were observed between the antianhedonic response to ketamine and plasma VEGF concentrations (all ps > 0.05).Conclusion: This preliminary study suggests that the antianhedonic effects of ketamine are not mediated by VEGF.

Gender Differences in Transcranial Magnetic Stimulation Treatment Outcomes for Major Depressive Disorder: A Single Institution Experience

Background: Transcranial Magnetic Stimulation is an FDA-approved treatment option for patients with treatment refractory major depressive disorder and obsessive compulsive disorder. Previous studies have suggested that there are significant differences in treatment outcomes for MDD based on gender1. The objective of this study was to determine if this difference was reproduced in the patient population of a new TMS clinic. Methods: A retrospective analysis of recent cases of patients ages 28 to 72 who underwent treatment with TMS for refractory major depressive disorder in 2019. The Beck's Depression Inventory-II (BDI-II) was used to gauge symptom severity at the initiation and completion of treatment, and the differences between the BDI-II for each patient was used to calculate the change in BDI-II as the primary outcome measure. The BDI-II changes divided by patient sex, and the averages of each group were analyzed using the two-sample T-test. A secondary analysis was performed after separating the female cohort into premenopausal up to age 50 and postmenopausal groups. Results: Of the 22 individuals in the study, 16 were female and 6 were male. The statistical analysis of treatment outcomes revealed no significant differences in BDI-II changes between females versus male patients, even when separating the female cohort into premenopausal (n=3) and postmenopausal groups (n=13); p > 0.05, two-tailed test. Conclusions: Conclusions are limited due to sample size.

Rare variants and biological pathways identified in treatment-refractory depression.

Individuals diagnosed with major depressive disorder not responding to at least two adequate treatments are defined as treatment-refractory major depressive disorder (TR-MDD). Some TR-MDD patients have altered metabolic phenotypes that may be pharmacologically reversed. The characterization of these phenotypes and their underlying etiologies is paramount, particularly their genetic components. In this study, TR-MDD patients (n=124) were recruited and metabolites were quantified in their cerebrospinal fluid (CSF) and peripheral blood. Three sub-categories of deficiencies were examined, namely 5-methyltetrahydrofolte (in CSF; n=13), tetrahydrobiopterin (in CSF; n=11), and abnormal acylcarnitine profiles (in peripheral blood; n=8). Whole exome sequencing was performed on genomic DNA from the entire TR-MDD cohort and exonic variant allele frequencies for cases were compared to a control cohort (1:5 matching on ancestry). Low frequency, damaging alleles were identified and used for in silico pathway analyses. Three association signals for TR-MDD approached genome-wide significance on chromosomes 22, 7, and 3. Three risk-associated variants from a prior depression study were replicated. Relevant biological pathways were identified that contained an enrichment of rare, damaging variants in central nervous system (CNS)-specific pathways, including neurotransmitter receptors, potassium channels, and synapse transmission. Some TR-MDD patients had rare variants in genes that were previously associated with other psychiatric disorders, psychiatric endophenotypes, CNS structural defects, and CNS-related cellular and molecular functions. Exome analysis of metabolically phenotyped TR-MDD patients has identified potentially functional gene pathways and low frequency, deleterious gene variants for further investigation. Further studies in larger cohorts of biochemically phenotyped TR-MDD patients are desirable to extend and confirm these findings.

Chromosome 15q13.3 microduplications are associated with treatment refractory major depressive disorder.

Major depressive disorder (MDD) affects approximately 15 million Americans. Approximately 2 million of these are classified as being refractory to treatment (TR-MDD). Because of the lack of available therapies for TR-MDD, and the high risk of suicide, there is interest in identifying new treatment modalities and diagnostic methods. Understanding of the impact of genomic copy number variation in the etiology of a variety of neuropsychiatric phenotypes is increasing. Low copy repeat elements at 15q13.3 facilitate non-allelic homologous recombination, resulting in recurrent copy number variants (CNVs). Numerous reports have described association between microdeletions in this region and a variety of neuropsychiatric phenotypes, with CHRNA7 implicated as a candidate gene. However, the pathogenicity of 15q13.3 duplications is less clear. As part of an ongoing study, in which we have identified a number of metabolomic anomalies in spinal fluid from TR-MDD patients, we also evaluated genomic copy number variation in patients (n = 125) and controls (n = 26) via array-based copy number genomic hybridization (CGH); the case frequency was compared with frequencies reported in a prior study as well as a larger population-sized cohort. We identified five TR-MDD patients with microduplications involving CHRNA7. CHRNA7 duplications are the most common CNVs identified by clinical CGH in this cohort. Therefore, this study provides insight into the potential involvement of CHRNA7 duplications in the etiology of TR-MDD and informs those involved with care of affected individuals.

Clinical Trial of the Potassium Channel Activator Diazoxide for Major Depressive Disorder Halted Due to Intolerability.

Some glutamatergic modulators have demonstrated rapid and relatively sustained antidepressant properties in patients with major depressive disorder. Because the potassium channel activator diazoxide increases glutamate uptake via potassium channel activation, we hypothesized that it might exert antidepressant effects by increasing the removal of glutamate from the synaptic cleft, thereby reducing excessive glutamate transmission. This randomized, double-blind, placebo-controlled, crossover, single-site inpatient clinical study was conducted at the National Institute of Mental Health to assess the efficacy and safety of a 3-week course of diazoxide (200-400 mg daily, twice a day) versus a 3-week course of placebo in 6 participants with treatment-refractory major depressive disorder. The primary clinical outcome measure was change in Montgomery-Asberg Depression Rating Scale score from baseline to posttreatment. Quantitative insulin sensitivity check index, as well as concomitant imaging measures (electroencephalography, proton magnetic resonance spectroscopy, magnetoencephalography), were used as potential surrogate markers of target (KATP channel) engagement. The study was halted due to severe adverse effects. Given the small sample size, statistical evaluation of the effect of diazoxide on Montgomery-Asberg Depression Rating Scale scores or the imaging measures was not pursued. Visual inspection of the quantitative insulin sensitivity check index test revealed no evidence of target engagement. Although the results are negative, they are an important addition to the literature in this rapidly changing field.

Deep brain stimulation of the medial forebrain bundle elevates striatal dopamine concentration without affecting spontaneous or reward-induced phasic release

Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) induces rapid improvement of depressive symptoms in patients suffering from treatment-refractory major depressive disorder (MDD). It has been hypothesized that activation of the dopamine (DA) system contributes to this effect. To investigate whether DBS in the MFB affects DA release in the striatum, we combined DBS with fast-scan cyclic voltammetry (FSCV) in freely moving rats. Animals were implanted with a stimulating electrode at the border of the MFB and the ventral tegmental area, and a FSCV microelectrode in the ventromedial striatum to monitor extracellular DA during the acute onset of DBS and subsequent continued stimulation. DBS onset induced a significant increase in extracellular DA concentration in the ventromedial striatum that was sustained for at least 40s. However, continued DBS did not affect amplitude or frequency of so-called spontaneous phasic DA transients, nor phasic DA release in response to the delivery of unexpected food pellets. These findings suggest that effects of DBS in the MFB are mediated by an acute change in extracellular DA concentration, but more research is needed to further explore the potentially sustained duration of this effect. Together, our results provide both support and refinement of the hypothesis that MFB DBS activates the DA system: DBS induces an increase in overall ambient concentration of DA, but spontaneous or reward-associated more rapid, phasic DA dynamics are not enhanced. This knowledge improves our understanding of how DBS affects brain function and may help improve future therapies for depressive symptoms.

Metabolomic signatures of drug response phenotypes for ketamine and esketamine in subjects with refractory major depressive disorder: new mechanistic insights for rapid acting antidepressants.

Ketamine, at sub-anesthetic doses, is reported to rapidly decrease depression symptoms in patients with treatment-resistant major depressive disorder (MDD). Many patients do not respond to currently available antidepressants, (for example, serotonin reuptake inhibitors), making ketamine and its enantiomer, esketamine, potentially attractive options for treatment-resistant MDD. Although mechanisms by which ketamine/esketamine may produce antidepressant effects have been hypothesized on the basis of preclinical data, the neurobiological correlates of the rapid therapeutic response observed in patients receiving treatment have not been established. Here we use a pharmacometabolomics approach to map global metabolic effects of these compounds in treatment-refractory MDD patients upon 2 h from infusion with ketamine (n=33) or its S-enantiomer, esketamine (n=20). The effects of esketamine on metabolism were retested in the same subjects following a second exposure administered 4 days later. Two complementary metabolomics platforms were used to provide broad biochemical coverage. In addition, we investigated whether changes in particular metabolites correlated with treatment outcome. Both drugs altered metabolites related to tryptophan metabolism (for example, indole-3-acetate and methionine) and/or the urea cycle (for example, citrulline, arginine and ornithine) at 2 h post infusion (q<0.25). In addition, we observed changes in glutamate and circulating phospholipids that were significantly associated with decreases in depression severity. These data provide new insights into the mechanism underlying the rapid antidepressant effects of ketamine and esketamine, and constitute some of the first detailed metabolomics mapping for these promising therapies.

Transcranial magnetic stimulation potentiates glutamatergic neurotransmission in depressed adolescents

Abnormalities in glutamate neurotransmission may have a role in the pathophysiology of adolescent depression. The present pilot study examined changes in cortical glutamine/glutamate ratios in depressed adolescents receiving high-frequency repetitive transcranial magnetic stimulation. Ten adolescents with treatment-refractory major depressive disorder received up to 30 sessions of 10-Hz repetitive transcranial magnetic stimulation at 120% motor threshold with 3000 pulses per session applied to the left dorsolateral prefrontal cortex. Baseline, posttreatment, and 6-month follow-up proton magnetic resonance spectroscopy scans of the anterior cingulate cortex and left dorsolateral prefrontal cortex were collected at 3T with 8-cm3 voxels. Glutamate metabolites were quantified with 2 distinct proton magnetic resonance spectroscopy sequences in each brain region. After repetitive transcranial magnetic stimulation and at 6 months of follow-up, glutamine/glutamate ratios increased in the anterior cingulate cortex and left dorsolateral prefrontal cortex with both measurements. The increase in the glutamine/glutamate ratio reached statistical significance with the TE-optimized PRESS sequence in the anterior cingulate cortex. Glutamine/glutamate ratios increased in conjunction with depressive symptom improvement. This reached statistical significance with the TE-optimized PRESS sequence in the left dorsolateral prefrontal cortex. High-frequency repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex may modulate glutamate neurochemistry in depressed adolescents.

Resting-State Cortico-Thalamic-Striatal Connectivity Predicts Response to Dorsomedial Prefrontal rTMS in Major Depressive Disorder

Despite its high toll on society, there has been little recent improvement in treatment efficacy for major depressive disorder (MDD). The identification of biological markers of successful treatment response may allow for more personalized and effective treatment. Here we investigate whether resting-state functional connectivity predicted response to treatment with repetitive transcranial magnetic stimulation (rTMS) to dorsomedial prefrontal cortex (dmPFC). Twenty-five individuals with treatment-refractory MDD underwent a 4-week course of dmPFC-rTMS. Before and after treatment, subjects received resting-state functional MRI scans and assessments of depressive symptoms using the Hamilton Depresssion Rating Scale (HAMD17). We found that higher baseline cortico-cortical connectivity (dmPFC-subgenual cingulate and subgenual cingulate to dorsolateral PFC) and lower cortico-thalamic, cortico-striatal, and cortico-limbic connectivity were associated with better treatment outcomes. We also investigated how changes in connectivity over the course of treatment related to improvements in HAMD17 scores. We found that successful treatment was associated with increased dmPFC-thalamic connectivity and decreased subgenual cingulate cortex-caudate connectivity, Our findings provide insight into which individuals might respond to rTMS treatment and the mechanisms through which these treatments work.

P 107. Performance of electroconvulsive therapy in a patient with clipping of the middle intracerebral artery (Yasargil titanium clip) without major complications

Little is known regarding the risks of electroconvulsive therapy (ECT) in patients with clippings of intracerebral aneurysms. Currently, literature merely provides few anecdotal reports ( Najiar and Guttmacher, 1998 ) and manufacturers of such clipping systems (usually made of titanium) refrain from any suggestions concerning the safety during the performance of ECT. Thus, clinicians facing the coincidence of therapy-refractory depression (suggesting performance of ECT) and presence of intracerebral clips have to trade of possible benefits of ECT against theoretical risks in the complete absence of any guidelines or recommendations. Indeed, titanium is principally inert and the application of electric current should therefore not result in significant warming (with the risk of damaging surrounding brain tissue). However, the indication of ECT under these conditions must be confirmed meticulously. A case report is presented in order to to contribute to the available experience concerning this clinical situation. We present the case of a 55-year old female patient who successfully underwent clipping (Yasargil Titanium Clip, Aesculap®) of the left middle cerebral artery (MCA) due to MCA-aneurysm three years prior. The patient suffered from treatment-refractory major depressive disorder (recurrent type). Taking into account that various pharmacologic treatment attempts failed, ECT was considered. The patient was comprehensively informed about possible risks of the procedure related to the titanium clip. Before ECT CT-angiography was performed showing no re-development of the surgically treated aneurysm or development of new aneurysms. 12 cycles of right-unilateral ECT were performed without any complications despite ECT-related tachycardia. During ECT the patient was treated with esmolol. Subsequently, the patient’s clinical situation significantly improved. Though clear guidelines or suggestions of manufacturers of neurosurgical clips regarding safety during ECT are absent we did not observe any major complications during ECT in a patient with an intracerebral Yasargil titanium clip. However, the material behaviour of titanium during application of electric current remains to be studied systematically in order to rule out problematic warming with the risk of tissue damage.

Neuromodulation for treatment-refractory major depressive disorder

Major depressive disorder is among the most prevalent psychiatric disorders and is a leading cause of morbidity and lost productivity.[1][1] The 1-year prevalence of major depressive disorder in the Canadian population is 3.2%–4.6%.[2][2] A large, multisite prospective trial showed that only 28%

The Effectiveness and Safety of Adjunctive Aripiprazole in Taiwanese Patients With Antidepressant-Refractory Major Depressive Disorder

There is currently no published clinical trial on the safety and effectiveness of aripiprazole in Taiwanese patients with treatment-refractory major depressive disorder. We were interested in determining the applicability of current recommended doses of aripiprazole as an adjunct to antidepressant therapy in this population. We conducted a prospective, open-label nonrandomized, 4-week flexibly dosed (2.5-5 mg/d) trial with aripiprazole augmentation in 9 Taiwanese patients who had a history of nonresponse to at least 2 adequate courses of antidepressant therapy with different types of antidepressants. The primary end point for clinical effectiveness was mean change in the 17-item Hamilton Rating Scale for Depression at the end of the 4-week trial. Secondary end points for clinical effectiveness included mean change in Beck Depression Inventory and Beck Anxiety Inventory scores. The Systematic Assessment of Treatment Emergent Events-General Inquiry was used to assess adverse effects. All patients completed the trial and responded to treatment; the remission rate was 77.8%. The mean daily dose of adjunctive aripiprazole was 4.2 mg. Common treatment-emergent adverse events included insomnia and sedation (33.3%) and akathisia (22.2%). We found high effectiveness despite a lower mean daily dose of adjunctive aripiprazole (4.2 mg) when compared with previously reported findings; however, we also observed a higher frequency of treatment-emergent adverse effects. Additional studies are required to ascertain whether there are ethnic differences in the pharmacokinetics and/or pharmacodynamics of aripiprazole in treatment-refractory depression.