Lisdexamfetamine Dimesylate Augmentation in Adults With Persistent Executive Dysfunction After Partial or Full Remission of Major Depressive Disorder

Evaluate lisdexamfetamine dimesylate (LDX) augmentation of antidepressant monotherapy for executive dysfunction in partially or fully remitted major depressive disorder (MDD). This randomized, placebo-controlled study ({"type":"clinical-trial","attrs":{"text":"NCT00985725","term_id":"NCT00985725"}}NCT00985725) enrolled 143 adults (18–55 years) with mild MDD (Montgomery-Åsberg Depression Rating Scale (MADRS) score ⩽18) and executive dysfunction (Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Self-Report Global Executive Composite (GEC) T score ⩾60) on stable antidepressant monotherapy for ⩾8 weeks. After 2 weeks of screening, participants were randomized to 9 weeks of double-blind LDX (20–70 mg/day) or placebo augmentation, followed by 2 weeks of single-blind placebo. The primary end point was change from baseline to week 9/end of study (EOS) in BRIEF-A Self-Report GEC T score; secondary assessments included the BRIEF-A Informant Report, MADRS, and treatment-emergent adverse events (TEAEs). Of 143 randomized participants, 119 completed double-blind treatment (placebo, n=59; LDX, n=60). Mean±standard deviation (SD) BRIEF-A GEC T scores decreased from baseline (placebo, 74.2±8.88; LDX, 76.8±9.66) to week 9/EOS (placebo, 61.4±14.61; LDX, 55.2±16.15); the LS mean (95% CI) treatment difference significantly favored LDX (−8.0 (−12.7, −3.3); P=0.0009). The LS mean (95% CI) treatment difference for MADRS total score also significantly favored LDX (−1.9 (−3.7, 0.0); P=0.0465). TEAE rates were 73.6% with placebo and 78.9% with LDX; serious TEAE rates were 4.2 and 2.8%. In this trial, LDX augmentation significantly improved executive dysfunction and depressive symptoms in participants with mild MDD. The safety profile of LDX was consistent with prior studies in adults with attention-deficit/hyperactivity disorder.     

帕罗西汀联合喹硫平治疗抑郁症的疗效观察

目的观察帕罗西汀联合喹硫平治疗抑郁症的疗效和安全性。方法将55例在精神病专科医院接受住院治疗的抑郁症患者随机分配为两组,疗程为4周。用汉密尔顿抑郁量表（HRSD）进行疗效评定,用副反应量表（TESS）评估患者的药品不良反应,采用重复测量的方差分析比较帕罗西汀联合喹硫平与单用帕罗西丁治疗抑郁症的起效快慢及疗效。结果在4周的疗程中,分组与时间之间存在交互作用（F=7．107,P=0．000）,两组药品不良反应之间无统计学差异（r=0．162,P=0．688〉0．05）。两组在第4周末的疗效有统计学差异（t=5．720,P=0．000〈0．05）。结论帕罗西汀合用喹硫平治疗抑郁症起效时间及疗效均优于单用帕罗西汀,联合用药未增加药物的不良反应。     

Selective Orexin Receptor Antagonists as Novel Augmentation Treatments for Major Depressive Disorder: Evidence for Safety and Efficacy From a Phase 2B Study of Seltorexant

There is a large unmet need for effective treatment of major depressive disorder (MDD), an often chronic/recurrent disorder that affects 1 in 5 adults during their lifetime in the United States. Clinicians and individuals with MDD often rely on augmentation approaches given the low rate of remission with the initial antidepressant treatment. Therefore, the report by Savitz and colleagues on the safety and efficacy of seltorexant is of great interest because it provides initial evidence for the antidepressant potential of drugs targeting orexin neurotransmission. Findings of this study suggest that seltorexant 20 mg is more effective than placebo, especially in individuals with moderate or insomnia symptoms at baseline. Given that insomnia is a common feature of depression, orexin 2 receptor antagonists may serve as important new treatment alternatives for people with MDD.     

Increased Matrix Metalloproteinases in Cerebrospinal Fluids of Patients With Major Depressive Disorder and Schizophrenia

BackgroundChronic inflammation of the brain has a pivotal role in the pathophysiology of major depressive disorder (MDD) and schizophrenia (SCZ). Matrix metalloproteinases (MMPs) are extracellular proteases involved in pro-inflammatory processes and interact with interleukin-6, which is increased in the cerebrospinal fluid (CSF) of patients with MDD and SCZ. However, MMPs in the CSF in patients with MDD and SCZ remain unclear. Therefore, we compared MMPs in the CSF of patients with MDD and SCZ with those of healthy controls (HC).MethodsJapanese patients were diagnosed with DSM-IV-TR and clinical symptoms were assessed with the Hamilton Rating Scale for Depression for MDD and the Positive and Negative Syndrome Scale for SCZ. CSF was obtained from MDD (n = 90) and SCZ (n = 86) and from age- and sex-matched HC (n = 106). The levels of MMPs in CSF were measured with multiplex bead-based immunoassay.ResultsThe levels of MMP-2 in CSF were higher in both MDD and SCZ than HC and were positively correlated with clinical symptomatic scores in MDD, but not in SCZ. Regardless of diagnosis, the levels of MMP-2, -7, and -10 were positively correlated with each other, and the levels of MMP-7 and -10 were higher in MDD, but not in SCZ, compared with HC.ConclusionIncreased CSF levels of MMP-2 in MDD and SCZ may be associated with brain inflammation. State-dependent alteration of MMP-2 and activation of cascades involving MMP-2, -7, and -10 appeared to have a role in the pathophysiology of MDD.     

Effects of Duloxetine Treatment on Brain Response to Painful Stimulation in Major Depressive Disorder

Major depressive disorder (MDD) is characterized by a constellation of affective, cognitive, and somatic symptoms associated with functional abnormalities in relevant brain systems. Painful stimuli are primarily stressful and can trigger consistent responses in brain regions highly overlapping with the regions altered in MDD patients. Duloxetine has proven to be effective in treating both core emotional symptoms and somatic complaints in depression. This study aimed to assess the effects of duloxetine treatment on brain response to painful stimulation in MDD patients. A total of 13 patients and a reference group of 20 healthy subjects were assessed on three occasions (baseline, treatment week 1, and week 8) with functional magnetic resonance imaging (fMRI) during local application of painful heat stimulation. Treatment with duloxetine was associated with a significant reduction in brain responses to painful stimulation in MDD patients in regions generally showing abnormally enhanced activation at baseline. Clinical improvement was associated with pain-related activation reductions in the pregenual anterior cingulate cortex, right prefrontal cortex, and pons. Pontine changes were specifically related to clinical remission. Increased baseline activations in the right prefrontal cortex and reduced deactivations in the subgenual anterior cingulate cortex predicted treatment responders at week 8. This is the first fMRI study addressed to assess the effect of duloxetine in MDD. As a novel approach, the application of painful stimulation as a basic neural stressor proved to be effective in mapping brain response changes associated with antidepressant treatment and brain correlates of symptom improvement in regions of special relevance to MDD pathophysiology.     

Reduced Cerebrospinal Fluid Levels of Lysophosphatidic Acid Docosahexaenoic Acid in Patients With Major Depressive Disorder and Schizophrenia

BackgroundLysophosphatidic acid (LPA) is involved in numerous biological processes, including neurodevelopment, chronic inflammation, and immunologic response in the central nervous system. Autotaxin (ATX) is a secreted enzyme that produces LPA from lysophosphatidylcholine (LPC). Previous studies have demonstrated decreased protein levels of ATX in cerebrospinal fluid (CSF) of patients with major depressive disorder (MDD). Based on those studies, the current study investigated the levels of lysophospholipids species including LPA and related metabolic enzymes, in CSF of patients with MDD and schizophrenia (SCZ).MethodsThe levels of lysophospholipids species and related metabolic enzymes were measured with either liquid chromatography-tandem mass spectrometry or enzyme-linked immunosorbent assay. Japanese patients were diagnosed with DSM-IV-TR. CSF was obtained from age- and sex-matched healthy controls (n = 27) and patients with MDD (n = 26) and SCZ (n = 27).ResultsOf all lysophospholipids species, the levels of LPA 22:6 (LPA - docosahexaenoic acid) were significantly lower in patients with MDD and SCZ than in healthy controls. These levels were negatively correlated with several clinical symptomatic scores of MDD, but not those of SCZ. In addition, the levels of LPA 22:6 were significantly correlated with the levels of LPC 22:6 among all 3 groups. On the other hand, the levels of LPA 22:6 were not correlated with ATX activity in patients with MDD and SCZ.ConclusionThe lower levels of LPA 22:6 in patients with MDD and SCZ suggest an abnormality of LPA 22:6 metabolism. In addition, several depressive symptoms in patients with MDD were significantly associated with the lower levels of LPA 22:6, suggesting an involvement of LPA 22:6 in the pathophysiology of MDD.     

Vortioxetine: a New Treatment for Major Depressive Disorder

Introduction: Vortioxetine is a structurally novel medication that has recently been approved for treatment of major depressive disorder (MDD). This medication is a serotonin reuptake inhibitor that also has a number of other potentially relevant effects on serotoninergic receptors, which may differentiate the drug’s effects from those of current first-line antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs).

Areas Covered: This article will review the basic clinical pharmacology of vortioxetine, summarize the major clinical trials that were performed prior to approval by the US Food and Drug Administration (FDA), discuss relevant post-marketing studies of this drug, and offer expert commentary on the significance of this new agent in clinical practice. Pre-approval studies were identified as all randomized, placebo-controlled studies of vortioxetine listed on clinicaltrials.gov. Other referenced studies were identified via a MEDLINE database literature search in August 2015 using the key search terms, vortioxetine and Lu AA21004, combined with additional terms that included pharmacological profile, pharmacokinetics, drug interactions, adverse effects, side effects, safety, major depression, and major depressive disorder. We identified relevant systematic reviews, meta-analyses, randomized trials and preclinical studies of importance.

Expert Opinion: Results of placebo-controlled trials suggest efficacy and an overall safety profile comparable to existing first-line antidepressants. The most common side effects are nausea, vomiting and constipation. Results of several studies indicate that vortioxetine may have therapeutic effects on cognition (e.g., memory and executive functioning) that exceed that of standard antidepressants. Disadvantages include cost and the current paucity of long-term efficacy data from large clinical trials. The authors suggest that vortioxetine is currently a good second-line antidepressant option and shows promise, pending additional long-term data, to become a first-line antidepressant option.     

Brexpiprazole for the Treatment of Schizophrenia and Major Depressive Disorder: A Comprehensive Review of Pharmacological Considerations in Clinical Practice

Mood and psychotic disorders are a group of illnesses that affect behavior and cognition. Schizophrenia is characterized by positive symptoms, such as delusions and hallucinations, as well as negative symptoms. Major depressive disorder (MDD) is a mood disorder that affects the patient’s emotions, energy, and motivation. Brexpiprazole works as a partial agonist at serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at serotonin 5-hydroxytryptamine2A. Schizophrenia and MDD have a wide range of risk factors, both biological and environmental. Third generation antipsychotics, which include brexpiprazole, are the latest group of drugs to reach the market, demonstrating efficacy and tolerability. Patients with acute schizophrenia have responded well to brexpiprazole. In this regard, in patients who have MDD plus anxiety symptoms, brexpiprazole can be effective as an adjunctive therapy and can reduce anxiety symptoms. In summary, brexpiprazole has proved to be an effective alternative to typical or first and second-generation atypical antipsychotics.     

Effect of Vortioxetine on Cognitive Impairment in Patients With Major Depressive Disorder: A Systematic Review and Meta-analysis of Randomized Controlled Trials

BackgroundDementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks. Vortioxetine is a new antidepressant with multipharmacologic actions that elevate the concentration of serotonin and modulate multiple neurotransmitter receptors in the brain. We conducted a meta-analysis to explore whether the cognitive function of patients with major depressive disorder (MDD) treated with vortioxetine would improve.MethodsWe systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to assess the treatment effects of vortioxetine on the cognitive function of patients with MDD. The outcome measures included the Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire (PDQ), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pooled results were calculated using a fixed-effects or random-effects model according to the heterogeneity of the included trials.ResultsSix RCTs with a total of 1782 patients were included in the meta-analysis, which demonstrated that vortioxetine improved DSST, PDQ, and MADRS scores in patients with MDD. The results were consistent at the 10- and 20-mg doses. In the 20-mg group, the decrease in MADRS scores was more significant than that in the placebo group.ConclusionsBoth the 10- and 20-mg doses of vortioxetine can significantly increase DSST scores and decrease PDQ and MADRS scores in patients with MDD and cognitive dysfunction, but further studies with longer follow-up periods to assess mental function are required.     

The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review

Levomilnacipran, the more active enantiomer of the serotonin and norepinephrine reuptake inhibitor (SNRI) milnacipran, was recently approved in the US for the treatment of major depressive disorder (MDD). The drug was developed as an extended release (ER) capsule formulation to allow for once-daily administration, thereby improving patient adherence. This agent differs from other available SNRIs in having a greater potency for inhibition of norepinephrine relative to serotonin reuptake. The efficacy of levomilnacipran ER has been evaluated in seven randomised, double-blind clinical trials (one Phase II and four Phase III trials, and two long-term efficacy studies). These studies documented that levomilnacipran is generally more effective than placebo for the treatment of MDD in the short-term, whereas no firm evidence exists on long-term efficacy for relapse prevention. Preliminary evidence suggests that levomilnacipran ER may be effective in improving not only depressive symptoms but also symptoms related to functioning (social life, work, and family life). Short-and longer-term studies found that the rate of withdrawal from levomilnacipran therapy due to adverse events was rather low. Moreover the drug appeared to be generally well tolerated. The most common adverse effects included nausea, hyperhidrosis, constipation, tachycardia, palpitations, erectile dysfunction and ejaculation disorder. As hypertension or orthostatic hypotension may occur in a few patients, the cardiovascular safety of levomilnacipran needs to be more extensively investigated especially on long-term treatment. Additional active comparator trials evaluating efficacy, tolerability and cost-effectiveness are required to better define the role of levomilnacipran ER in the treatment of MDD in relation to currently available antidepressants including other SNRIs.     

文拉法辛与艾司西酞普兰治疗抑郁症的最小成本分析

目的:比较文拉法辛与艾司西酞普兰治疗抑郁症的经济学效果。方法:采用回顾性调查法,抽取我院2007年9月-2009年9月采用文拉法辛与艾司西酞普兰治疗抑郁症的89例门诊患者病历,记录其疗效并运用药物经济学原理进行最小成本分析。结果:文拉法辛组与艾司西酞普兰组的有效率分别为90.7%、100.0%(P>0.05),平均成本分别为912.53、1510.86元(P<0.05)。结论:文拉法辛组方案较经济。     

Reconciling Variable Findings of White Matter Integrity in Major Depressive Disorder

Diffusion tensor imaging (DTI) has been used to evaluate white matter (WM) integrity in major depressive disorder (MDD), with several studies reporting differences between depressed patients and controls. However, these findings are variable and taken from relatively small studies often using suboptimal analytic approaches. The presented DTI study examined WM integrity in large samples of medication-free MDD patients (n=134) and healthy controls (n=54) using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) approaches, and rigorous statistical thresholds. Compared with health control subjects, MDD patients show no significant differences in fractional anisotropy, radial diffusivity, mean diffusivity, and axonal diffusivity with either the VBM or the TBSS approach. Our findings suggest that disrupted WM integrity does not have a major role in the neurobiology of MDD in this relatively large study using optimal imaging acquisition and analysis; however, this does not eliminate the possibility that certain patient subgroups show WM disruption associated with depression.     

Efficacy and Safety of Seltorexant as Adjunctive Therapy in Major Depressive Disorder: A Phase 2b,Randomized, Placebo-Controlled,Adaptive Dose-Finding Study

BackgroundSeltorexant, a selective antagonist of human orexin-2 receptors, demonstrated antidepressant effects in a previous exploratory study in patients with major depressive disorder (MDD).MethodsTo replicate and extend this observation, a double-blind, adaptive dose-finding study was performed in patients with MDD who had an inadequate response to 1–3 selective serotonin/serotonin-norepinephrine reuptake inhibitors in the current episode. Patients were randomized (2:1:1) to placebo or seltorexant (20 mg or 40 mg) once-daily, administered adjunctively to the antidepressant the patient had been receiving at screening. After an interim analysis (6 weeks post-randomization of 160th patient), newly recruited patients randomly received (3:3:1) placebo or seltorexant 10 mg or 20 mg; the 40-mg dose was no longer assigned. Patients were stratified by baseline Insomnia Severity Index (ISI) scores (ISI ≥ 15 vs < 15). The primary endpoint was change from baseline Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6.ResultsMixed-Model for Repeated Measures analysis showed a greater improvement in MADRS total score in the seltorexant 20-mg group vs placebo at weeks 3 and 6; least-square means difference (90% CI): −4.5 (−6.96; −2.07), P = .003; and −3.1 (−6.13; −0.16), P = .083, respectively. The improvement in MADRS score at week 6 for seltorexant 20 mg was greater in patients with baseline ISI ≥ 15 vs those with ISI < 15; least-square means difference (90% CI) vs placebo: −4.9 (−8.98; −0.80) and −0.7 (−5.16; 3.76), respectively. The most common (≥5%) adverse events with seltorexant were somnolence, headache, and nausea.ConclusionsA clinically meaningful reduction of depressive symptoms was observed for seltorexant 20 mg. In the subset of patients with sleep disturbance (ISI ≥ 15), a larger treatment difference between seltorexant 20 mg and placebo was observed, warranting further investigation. No new safety signal was identified.RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03227224","term_id":"NCT03227224"}}NCT03227224Previous presentationPoster presented at 58th Annual Meeting of American College of Neuropsychopharmacology (ACNP), December 8–11, 2019, Orlando, FL.     

Extended Release Quetiapine Fumarate (Quetiapine XR) as Adjunct Therapy in Patients with Generalized Anxiety Disorder and a History of Inadequate Treatment Response: A Randomized,Double-Blind Study

Objective

To evaluate the efficacy and tolerability of adjunct extended release quetiapine fumarate (quetiapine XR) in patients with generalized anxiety disorder (GAD) and inadequate response to selective serotonin reuptake inhibitors/ serotonin norepinephrine reuptake inhibitors (SSRI/SNRIs).

Methods

11-week (1-week single-blind placebo run-in; 8-week randomized treatment; 2-week post-treatment period), double-blind, placebo-controlled study. Patients were randomized to quetiapine XR or placebo adjunct to SSRI/SNRI. 50 mg initial dose; 150 mg/day, Day 3; 300 mg/day, Weeks × and 4 if indicated (Clinical Global Impressions-Severity of Illness [CGI-S] ≥ 4; 150 mg/day tolerated). Primary endpoint: change from randomization to Week 8 in HAM-A total score. Secondary variables: Hamilton Rating Scale for Anxiety (HAM-A) psychic/somatic clusters, response and remission; and CGI-S.

Results

409 patients were randomized to quetiapine XR (n = 209) or placebo (n = 200); 41% and 55% of patients, respectively, had dose increases (300 mg/day). Week 8 mean change in HAM-A total score was not statistically significant for quetiapine XR (–10.74; p = 0.079) versus placebo (–9.61). Secondary variables were generally consistent with the primary analysis, except a significant reduction in HAM-A total score at Week 1 (–6.45, quetiapine XR versus –4.47, placebo; p < 0.001); significant improvements in HAM-A psychic cluster (p < 0.05) and CGI-S total (p < 0.05) scores at Week 8. Adverse events (.10% either group) were dry mouth, somnolence, sedation, headache, and dizziness.

Conclusions

In patients with GAD and inadequate response to SSRI/SNRI, adjunct quetiapine XR did not show a statistically significant effect for the primary endpoint at Week 8, although some secondary endpoints were statistically significant versus placebo. Quetiapine XR was generally well tolerated.     

柴胡疏肝散辅助治疗重度抑郁症的网络药理学研究

目的:研究柴胡疏肝散辅助治疗重度抑郁症(MDD)的潜在分子机制。方法:采用网络药理学方法。利用基因表达综合数据库(GEO)下载MDD患者基因芯片数据集GSE76826,再利用R语言软件中的limma包筛选出MDD患者样本中的差异基因。利用中药系统药理学数据库和分析平台(TCMSP)筛选柴胡疏肝散的活性成分及其对应的靶标。通过在线软件venny 2.1.0对MDD的差异基因和柴胡疏肝散的靶标取交集,获取柴胡疏肝散治疗MDD的共同靶标基因,然后将共同靶标基因导入Cytoscape3.6.1软件构建"柴胡疏肝散活性成分-MDD靶标基因"关系网络。利用BisoGenet插件构建蛋白互作(PPI)网络,并对其进行拓扑结构分析,筛选核心靶标基因,进行京都基因与基因组百科全书(KEGG)通路分析。结果:柴胡疏肝散治疗MDD的活性成分有139种,包括槲皮素、山柰酚、木犀草素、豆甾醇等;其作用的核心靶点基因共有8个,包括NR3C2、DPP4、ALOX5、GSTM1、CCND1、IGFBP3等;其主要通过调节细胞受体、嘌呤代谢、类固醇生物合成、氨酰生物合成等信号通路发挥治疗MDD的作用。结论:柴胡疏肝散可...     

西酞普兰治疗以头痛为主诉的抑郁性情感障碍31例

［摘要］目的比较西酞普兰与阿米替林治疗以头痛为主诉的抑郁性情感障碍的疗效和安全性。方法将符合入选标准的患者91例随机分为治疗组31例、对照1组30例和对照2组30例，分别口服西酞普兰20 mg·d 1、阿米替林100～150 mg·d 1和镇痛对症药物治疗6周；分别于治疗前和治疗后1,2,4,6 周末采用汉密尔顿（HAMD）量表评分，用TESS量表评定不良反应。结果治疗6周后，治疗组和对照1组临床好转率分别达87.1%和 86.7%，多数患者头痛缓解、睡眠改善、生活和工作能力恢复，对照2组临床好转率仅26.7%。治疗后1,2周，治疗组HAMD评分较治疗前明显下降（P＜0.05），而对照1组评分较治疗前下降不明显(P＞0.05)；治疗组和对照1组治疗后4～6周HAMD评分均较治疗前明显下降(P＜0.01)，但两组差异无显著性(P＞0.05)；治疗组不良反应较对照1组少而轻，与对照2组相当。结论 西酞普兰治疗以头痛为主诉的抑郁性情感障碍疗效与阿米替林相当，但起效较快，安全性高，不良反应轻微。     

黛力新对高血压并发混合性焦虑抑郁障碍患者治疗效果的影响

目的:黛力新与降压药联合应用观察其对高血压并发混合性焦虑抑郁障碍患者的降压效果.方法:查阅高血压患者560例,其中71例并发混合性焦虑抑郁障碍,随机分为两组,治疗组用非洛地平与黛力新,对照组用非洛地平,观察两组降压效果和有效率.结果:非洛地平与黛力新合用组治疗8周后收缩压与舒张压均明显下降,降压有效率也明显提高.结论:高血压并发混合性焦虑抑郁障碍患者在降压药基础上联合黛力新能明显提高降压有效率.     

Disproportionate Reduction of Serotonin Transporter May Predict the Response and Adherence to Antidepressants in Patients with Major Depressive Disorder: A Positron Emission Tomography Study with 4-[18F]-ADAM

Background:

Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants.

Methods:

We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[¹⁸F]fluorophenylthio)benzylamine (4-[¹⁸F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more.

Results:

Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders.

Conclusions:

The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD.