
EffectsOfTranscranialPulseStimulationOnDepression-PilotRCT
Major Depressive DisorderThe aim of this study is to evaluate the effects of transranial pulse stimulation (TPS) on young adults with symptoms of depression in Hong Kong. Methods: This is a single-blind randomized controlled trial design with two-armed repeated measures, and participants will be followed up at a 3-months post-stimulation period. Eligbility: 1) aged 18 or over; 2) able to understand/read Chinese; 3) HAM-D-17 score of ≥ 8; 4) provide written informed consent. Exclusion criteria includes: 1) individuals being prescribed a DSM-5 diagnosis other than major depressive disorder (e.g., bipolar affective disorder or schizophrenia); 2) Alcohol or substance dependence; 3) Concomitant unstable major medical conditions or major neurological conditions such as brain tumour, brain aneurysm; 4) Haemophilia or other blood clotting disorders or thrombosis; 5) Significant communicative impairments; 6) Participants with metal implant in brain or treated area of the head; 7) Participants who undertook corticosteroid treatment within the last six weeks before first TPS treatment; 8) Pregnant or breastfeeding women. Recruitment: A total of 30 subjects will be recruited from collaborative NGOs and PolyU and randomly assigned into the Intervention Group (TPS) and the Waitlist Control Group on a 1: 1 ratio. Intervention: All participants (both TPS group and the waitlist control group) will receive six 30 minute-TPS sessions (300 pulse in each session, total: 1800 pulse) in 2 weeks' time. Outcome measurements include depression, anhedonia, instrumental activities of daily living, cognition and neuroimaging.

Prediction of Antidepressant Treatment Response Using Machine Learning Classification Analysis
Major Depressive DisorderDespite significant advances in pharmacological treatment, the global burden of depression is increasing worldwide. The major challenge in antidepressant treatment is the clinicians' inability to predict the variability in individual response to the treatment. The development of biomarkers to predict treatment outcomes would enable clinician to find the right medication for a particular patient at the early stage of the treatment and thus could reduce prolonged suffering and ineffective protracted treatment. Brain imaging studies that examined brain predictors of treatment response based on group comparisons have limited value in classifying individuals as responders or non-responders. Machine learning classification techniques such as the support vector machine (SVM) method have proven useful in the classification of individual brain image observations into distinct groups or classes. However, studies that have applied the SVM method to structural and functional magnetic resonance scans (fMRI) involved small sample sizes and were confounded by placebo responses. Furthermore, a recent meta-analysis of clinical trials and EEG studies have shown that early clinical responses and brain changes at the early phase of antidepressant treatment may predict later clinical outcomes suggesting that neural markers measured in the early phase of antidepressant treatment may improve predictive accuracy. However, there is no fMRI study to date that has examined the predictive accuracy of data obtained in early phase of the treatment. We have preliminary fMRI data relating to early treatment response that form the basis of this proposed study. The main objective of this study is to use machine learning method to examine the predictive value (sensitivity, specificity, accuracy) of resting state and emotional task-related fMRI data collected at pre-treatment baseline (week 0) and in the early phase of antidepressant treatment (week 2) in the classification of remitters (< 10 MADRS scores after 12 weeks of treatment) and non-remitters in patients with major depressive disorder (MDD). A secondary objective is to determine which data set (week 0 or week 2) gives the best predictive value.

A Study of Sustained-Release Desvenlafaxine Hydrochloride for the Treatment of Major Depressive...
Major Depressive DisorderA multicenter, 10-week study to evaluate the efficacy and safety of Sustained-Release Desvenlafaxine Hydrochloride versus Sustained-Release venlafaxine Hydrochloride in adult with major depressive disorder.

Pharmacogenetic Decision Support IT System for Psychiatric Hospitalization: RCT
Major Depressive DisorderThis Randomized Clinical Trial (RCT) compares outcomes in patients with major depressive disorder (MDD) treated according to the patient's CYP2D6 genotype status versus empiric "standard-of-care" psychotropic therapy. The hypothesis is that provision of medication based on the functional status of the patient's CYP2D6 enzyme inferred from genotype results within 48 hours of admission to treating clinicians will, through refined selection of psychotropic medication during hospitalization, decrease length of psychiatric hospitalization stay and decrease the rate of 30 day re-admission. The trial setting is the Hartford Hospital Institute of Living (IOL). The IOL operated the Clinical Evaluation and Monitoring System (CEMS), an innovative electronic messaging system developed by Co-Investigator Dr. J.W. Goethe. The Hartford Hospital Genetics Research Center (GRC) performs the genotype testing. CYP2D6 genotype analysis detects all known polymorphisms that result in an enzyme with sub-normal or supra-normal function. In this study, CEMS transmits clinically actionable guidance based on the patient's genotype to the clinician, advancing the medication alerts in real time. The RCT will test the effects of timely incorporation of medication recommendations based on CYP2D6 genotype into CEMS. The RCT randomizes patients to standard therapy (Group S) for whom CYP2D6 genetic information is determined but not transmitted to the treating clinician, allowing psychotropic therapy to be empirically determined, and to genetically guided therapy (Group G) where genotyping result and treatment recommendations are furnished via CEMS to the clinician within 48 hours of admission. For patients in Group G who are poor or rapid metabolizers, medications primarily metabolized by the CYP2D6 enzyme are proscribed. The primary outcome is hospital length of stay and the secondary outcome, the frequency of 30 day hospital readmission. Additional genetic stratification of both Group S and Group G will allow investigation of specific psychotropic usage. The expected benefits are (1) quantitative understanding of the effect of providing CYP2D6 pharmacogenetic information on length of hospitalization, 30 day readmission rate, and associated costs; and (2) objective benchmarking for the comparative effectiveness of CYP2D6 genotyping for guiding psychotropic therapy.

Ketamine Infusions for Major Depression Disorder
Depressive DisorderMajorKetamine has been safely used for induction and maintenance of anesthesia for decades and more recently has been used for chronic pain. Ketamine is a noncompetitive, high-affinity antagonist of the N-methyl-D-aspartate type glutamate receptor, with additional effects on dopamine and μ-opioid receptors. During the last 9 years several uncontrolled reports have been published, showing a rapid and impressive effect of ketamine in TRD patients (Berman, Cappiello et al. 2000; Zarate, Singh et al. 2006; Mathew, Murrough et al. 2010; Aan Het Rot, Zarate et al. 2012; Mathew, Shah et al. 2012; Murrough, Iosifescu et al. 2013). Recently three placebo-controlled trials showed that a single dose of sub-anesthetic, (0.5 mg/kg) slow intravenous (IV) ketamine improves depressive symptoms dramatically. Across studies, a clinically significant antidepressant response was maintained for up to 72 hours in 12 of 25 patients. Nonetheless, all but two patients relapsed <2 weeks post-ketamine (Zarate, Singh et al. 2006; aan Het Rot, Zarate et al. 2012). Rot et al. showed that repeated IV ketamine infusions prolongs the duration of improvement. The investigators believe that the data presented above allows us to provide ketamine treatment here in the Sheba Medical Center for TRD patients.

Oxytocin and Tibolone Adjuncts in Treatment Resistant Depression - A Pilot Study
DepressionMajor Depressive DisorderThe purpose of this study is to determine whether an oxytocin ad-on, or oxytocin and tibolone ad-on can induce a response to antidepressants in patients with treatment resistant depression.

Mindfulness-based Behavioural Therapy (MIBT) Versus Psychodynamic Therapy for Patients With Major...
Major Depressive DisorderPersonality DisorderBackground: According to the WHO, major depressive disorder is the second largest healthcare problem worldwide in terms of disability caused by illness. It afflicts an estimated 17% of individuals during their lifetimes at tremendous costs. A number of depressive patients are treated with antidepressant medication. The efficacy of antidepressant medication has been studied in a number of systematic reviews, and in recent years some of these reviews have shown that the efficacy is questionable for many patients. So are there other effective treatments for this serious illness? Cognitive- and psychodynamic therapies are probably both significantly more effective for depression than no treatment, but only limited comparisons have been made between the two interventions. A Cochrane review shows that cognitive therapy has a preventive effect against recurrent depression, and that this effect may surpass the preventive effect of antidepressant medication. Mindfulness training may be an effective technique in preventing relapse in patients who have had at least 3 previous depressive episodes. But efficacy in treating currently depressed patients has not been studied. Objective To perform a randomised clinical trial with blinded assessment of efficacy variables in order to study the effects of mindfulness based behavioral therapy (cognitive therapy and mindfulness) versus psychodynamic therapy in depressive patients. Methods A randomised clinical trial of 84 consecutive patients diagnosed with major depressive disorder, referred to the day clinic, Roskilde psychiatric services. The patients will be randomised to one of two interventions: MIBT (mindfulness-based behavioural therapy) PT (psychodynamic therapy)

Escitalopram and Sleep Architecture in Patients With Major Depressive Disorder
Major Depressive DisorderThe purpose of this study is to assess the effect of escitalopram on sleep architecture utilizing a prospective design. Hypothesis: Escitalopram will improve REM latency in patients with MDD that have responded clinically to treatment.

Efficacy Study of Escitalopram for Depression in Patients With Diabetes
Major DepressionDiabetes MellitusPatients with diabetes and major depression treated with Escitalopram might experience significant improvement in depression and anxiety scores; functional ability; diabetes-related self-care; and pain symptoms

Efficacy of 18-Months of Antidepressive Medication Plus CBT or Dynamic or Supportive Psychotherapy...
Major DepressionMajor Depressive Disorder affects approximately 16% of the adult population over the lifetime. Controlled studies indicate that short-term antidepressive medications or psychotherapy produce full remission in only about 46% of patients. Furthermore, about 80% of patients will continue to have subsequent recurrences after remission of the first episode, with each episode increasing the probability of future recurrences. This pilot study will examine whether antidepressive medications plus one of three commonly available types of psychotherapy used in the short-term treatment of depression can protect against the recurrence of depression if active treatment is extended to 18-months duration. Results will aid designing a more complete study. Adults with an acute episode of major depressive disorder with at least one prior episode will be randomized to Antidepressive medications (ADM) plus 18-months of either Cognitive-behavioral therapy (CBT) or Dynamic psychotherapy (DYN), or to a standard control therapy, Supportive Clinical Management (SUP-CM). We will determine whether a higher percentage of those receiving either CBT or DYN remain well after three years of follow-up, compared to those receiving the standard control treatment. We will also examine the reduction in psychological risk factors as well as potential economic benefits of the three approaches.