Maurizio Fava

• MD
• Chair at Massachusetts General Hospital

Previous studies have investigated the role of inflammatory markers in suicidality of patients with major depressive disorder (MDD) or panic disorder (PD). However, few studies have investigated associations between serum inflammatory cytokine levels and suicidality. We hypothesized that MDD and PD status might be significantly associated with seru...

NSI-189 is a novel neurogenic compound independent of monoamine reuptake pathways. This trial evaluated oral NSI-189 as monotherapy in major depressive disorder. To improve signal detection, the sequential-parallel comparison design (SPCD) was chosen. Two hundred and twenty subjects were randomized to NSI-189 40 mg daily, 80 mg daily, or placebo fo...

**Selected as Editor's choice article (Vol. 248, JAD) https://www.journals.elsevier.com/journal-of-affective-disorders/editors-choice/editors-choice-articles-journal-of-affective-disorders** - Background: Subthreshold hypomania is defined as a distinct period of elevated, expansive or irritable mood lasting for at least four days, but insufficient...

Previous studies have reported dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis in patients with major depressive disorder (MDD). Outpatients diagnosed with MDD (n = 199) underwent psychological evaluation, and were followed up with a phone interview after 6 months, using the Patient Health Questionnaire (PHQ-9). At 6-month follow-up, 5...

This 19-week, double-blind, placebo-controlled, randomized phase 2 study evaluated the efficacy, safety, and tolerability of adjunctive cariprazine (0.1-0.3 and 1.0-2.0 mg/day) as an antidepressant treatment for adults with treatment-resistant major depressive disorder (MDD) (NCT00854100). The primary endpoint was change in the Montgomery-Åsberg De...

Purpose/background: The objective of this study was to determine whether a novel α7 nicotinic acetylcholine receptor partial agonist improves cognition during nicotine withdrawal and improves abstinence rates. To do so, the effect of the α7 nicotinic acetylcholine receptor partial agonist, encenicline, on cognition and abstinence was evaluated whe...

Introduction: Attention deficit hyperactivity disorder (ADHD) symptoms, even those below diagnostic threshold, enhance the likelihood of nicotine dependence, suggesting a neurobiological link between disorders. Of particular interest is the salience network (SN), which mediates attention to salient internal/external stimuli to guide behavior and i...

Introduction: The ability to direct smoking cessation treatment based on neuroscientific findings holds incredible promise. However, there is a strong need for consistency across studies to confirm neurobiological targets. While our prior work implicated enhanced insula reactivity to smoking cues in tobacco smoking relapse vulnerability, this find...

Objective: Tamoxifen is an estrogen receptor antagonist used to prevent recurrence of breast cancer, which may provoke depression and anxiety and increase follicle-stimulating hormone (FSH) to patients. We compared anxiety and depression symptoms and FSH levels who received conventional tamoxifen alone and combination treatment of goserelin, a gon...

Objective: To examine motoric, cardiovascular, endocrine, and metabolic effects of adjunctive ziprasidone in adults with major depressive disorder (MDD) and prior nonresponse to 8 weeks of open-label escitalopram. Methods: A multicenter, parallel, randomized, double-blind, placebo-controlled trial was conducted at 3 US academic medical centers f...

Background: Approximately 50% of patients with major depressive disorder (MDD) do not respond adequately to their antidepressant treatment (ADT), underscoring the need for more effective treatment options. The objective of this study was to investigate the effect of adjunctive brexpiprazole on depressive symptoms in patients with MDD who were not...

Background: Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy as augmentation for depressive breakthrough on pro-dopaminergic antidepressant regimens. Methods: 12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stim...

Objective: To identify symptoms potentially representative of a noradrenergic symptom cluster as possible predictors of response to the selective norepinephrine reuptake inhibitor (NRI) edivoxetine when used as monotherapy or adjunctive treatment in patients with DSM-IV-TR major depressive disorder (MDD). Methods: Pooled data from 4 adjunctive trea...

Objective: This pilot study evaluated the effects of Tai Chi training on sleep quality (primary outcomes), and depression and social functioning levels (secondary outcomes) among patients with depression. Participants: Sixteen depressed Chinese patients. Methods: Participants received 1-hr Tai Chi training sessions 2 times per week for 10 week...

Major depressive disorder (MDD) is a debilitating disease that is characterized by depressed mood, diminished interests, impaired cognitive function and vegetative symptoms, such as disturbed sleep or appetite. MDD occurs about twice as often in women than it does in men and affects one in six adults in their lifetime. The aetiology of MDD is multi...

Objective: Stigma has been proposed to be a major underlying factor contributing to lower rates of mental health service utilization among racial/ethnic minorities in the United States. Yet, surprisingly little research has specifically explored associations between stigma, race/ethnicity, and psychiatric morbidity. This study aims to assess the im...

Brain bioenergetic abnormalities have been observed frequently in adults with major depressive disorder (MDD); however, results have been inconsistent regarding whether decreased or increased metabolism was observed. Phosphorus-31 magnetic resonance spectroscopy (31P MRS) allows for the quantification of bioenergetic molecules, containing high-ener...

Hypochondriasis is defined as the tendency to worry excessively about having a serious illness. This study aimed to investigate cross-national differences in hypochondriasis symptoms between Korean and American patients with major depressive disorder (MDD). This study examined 1592 Korean and 3744 American MDD outpatients of age ≥18 years using the...

Objective: This study evaluates the effectiveness of a telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT) intervention to improve treatment outcomes for depressed Chinese American immigrants. Methods: Participants were Chinese Americans recruited from primary care settings from February 1, 2009, to July 31, 2012, with DSM...

Objective: To evaluate the effects of adjunctive brexpiprazole on symptoms of irritability in patients with major depressive disorder (MDD). Methods: Patients diagnosed with MDD according to DSM-IV-TR criteria who had inadequate response to antidepressant treatment continued treatment with their current antidepressant for 2 weeks. Patients still...

Introduction: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. Methods: Subjec...

Major depressive disorder (MDD) and suicidal behavior have been associated with structural and functional changes in the brain. However, little is known regarding alterations of brain networks in MDD patients with suicidal ideation. We investigated whether or not MDD patients with suicidal ideation have different topological organizations of white...

Background: Major depressive disorder (MDD) is a well-known risk factor for suicidality, but depressed mood has been used non-specifically to describe the emotional state. We sought to compare influence of MDD versus sustained depressed mood on suicidality. Methods: A total of 12,532 adults, randomly selected through the one-person-per-household...

Previously, we found an anxiolytic effect of ziprasidone augmentation to escitalopram (compared with placebo augmentation) in patients with depression in an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial. Here, we carried out a post-hoc analysis, comparing changes in the Hamilton Depression and Anxiety Rating Scales betw...

Objective: The aim of this work is to compare the efficacy of pharmacologic agents for the treatment of major depressive disorder (MDD) and bipolar depression. Data sources: MEDLINE/PubMed databases were searched for studies published in English between January 1980 and September 2014 by cross-referencing the search term placebo with each of the...

Background: Ketamine rapidly reduces thoughts of suicide in patients with treatment-resistant depression who are at low risk for suicide. However, the extent to which ketamine reduces thoughts of suicide in depressed patients with current suicidal ideation remains unknown. Methods: Between April 2012 and October 2013, 14 outpatients with DSM-IV-...

Objective: Anxious depression has a distinct neurobiology, clinical course and treatment response from non-anxious depression. Role of inflammation in anxious depression has not been examined. As an exploratory study to characterize the role of inflammation on a development of anxious depression, we aimed to determine the relationship between whit...

Results of independent remote patient screening for a LFMS trial in MDD.

Objective: There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants. The adjunctive use of standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. While many studies have been conducted in this ar...

Background: Cariprazine is an atypical antipsychotic currently under investigation as adjunctive therapy in patients with major depressive disorder (MDD) who have inadequate response to standard antidepressant therapy. Method: A randomized, double-blind, placebo-controlled, flexible-dose study was conducted from December 2011 to December 2013 in...

Objective: To evaluate remission and recovery, safety, and tolerability for up to 12 months of open-label adjunctive L-methylfolate calcium 15 mg. Method: Subjects in this analysis were adult outpatients (18-65 years) enrolled from 2 acute, double-blind, placebo-controlled trials comparing adjunctive L-methylfolate and placebo for DSM-IV major d...

Unlabelled: Remission rates for Major Depressive Disorder (MDD) are low and unpredictable for any given antidepressant. No biological or clinical marker has demonstrated sufficient ability to match individuals to efficacious treatment. Biosignatures developed from the systematic exploration of multiple biological markers, which optimize treatment...

Objective: Preliminary evidence supports the safety and efficacy of subanesthetic ketamine as an experimental antidepressant, although its effects are often not sustained beyond one week. Studies are lacking that have examined the sustained effects of escalating ketamine doses as augmentation in outpatients with treatment-resistant depression. The...

Objective: Major depressive disorder has been associated with dysregulation of the endogenous opioid system. The authors sought to determine whether opioid modulation achieved through administration of ALKS 5461, a combination of a μ- and κ-opioid partial agonist, buprenorphine, and a μ-opioid antagonist, samidorphan, would exhibit antidepressant...

Model-based approach is recognized as a tool to make drug development more productive, and to better support regulatory and therapeutic decisions. The objective of this study was to develop a novel model-based methodology based on the response surface analysis and a non-linear optimizer algorithm to maximize the clinical performances of drug treatm...

Purpose: The purpose of this study was to assess the association of obsessive-compulsive symptoms (OCS) with suicide risk among college students. Methods: Subjects were 474 college students who attended mental health screenings at two private universities and completed multiple self-report questionnaires. Results: Presence of one or more OCS w...

The aim of this work is to investigate the impact of placebo response rates on the relative risk of response to drug versus placebo in randomized, double-blind, placebo-controlled clinical trials of pharmacological therapy in Bipolar Depression (BPD). Medline/PubMed publication databases were searched for randomized, double-blind, placebo-controlle...

Table S1. Demographic and clinical variables Table S2. FA in white matter parcellated ROIs Table S3. Outcome measures from probabilistic tractography Table S4. Correlation coefficient for relationship between FA in ROIs (top) and tractography (bottom) and clinical measures by site.

The standard double-blind, placebo-controlled trials in mood disorders frequently yield uninterpretable results, due in part to high placebo responses. Previous studies have shown that the advantage of the mood disorder treatment over placebo decreased as the degree of symptom reduction with placebo increased.This chapter will review the single-bli...

Objective: Obsessive-compulsive symptoms (OCS) may be underrecognized in patients suffering from major depressive disorder. These patients may not receive optimal psychopharmacologic or psychological treatment if their OCS are not attended to. We performed a secondary analysis of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D)...

We wanted to examine tolerability and efficacy of NSI-189, a benzylpiperizine-aminiopyridine neurogenic compound for treating major depressive disorder (MDD). This was a Phase 1B, double blind, randomized, placebo controlled, multiple-dose study with three cohorts. The first cohort received 40 mg q.d. (n=6) or placebo (n=2), the second cohort 40 mg...

Background: Even when patients experience remission with antidepressants, many continue to report anger attacks and excessive irritability despite continued treatment. Iloperidone antagonizes 5-HT-2a, D2, and alpha-1 receptors, which can have anti-aggressive effects. We examined iloperidone's safety and efficacy as an augmentation agent in outpati...

Background: Postpartum depression (PPD) is a type of clinical depression that can affect women after childbirth. Few previous studies have explored the association of depressive and physical symptoms among women with PPD in a nationwide community study. Method: A total of 18,807 adults, randomly selected, completed a face-to-face interview using...

The aim of this study was to evaluate the effects of levomilnacipran extended-release (ER) on depression-related fatigue in adults with major depressive disorder. Post-hoc analyses of five phase III trials were carried out, with evaluation of fatigue symptoms based on score changes in four items: Montgomery-Åsberg Depression Rating Scale (MADRS) it...

Background: Major depressive disorder (MDD) is a debilitating disorder characterized by widespread brain abnormalities. The literature is mixed as to whether or not white matter abnormalities are associated with MDD. This study sought to examine fractional anisotropy (FA) in white matter tracts in individuals with MDD using diffusion tensor imagin...

Many people with major depressive disorder (MDD) show evidence of systemic inflammation, including elevations in inflammatory factors, but the cause is unclear. The purpose of this analysis was to determine if obesity might contribute to the pro-inflammatory state in MDD patients. Blood was obtained from 135 MDD patients and 50 controls. Serum was...

Major depressive disorder is often accompanied by elevated levels of anger, hostility, and irritability, which may contribute to worse outcomes. The present study is a secondary analysis examining the role of anger/hostility in the treatment response to low-dose aripiprazole added to antidepressant therapy in 225 patients with major depressive diso...

Novel interventions have been developed to bridge disparities in accessing mental health care for minority populations. However, challenges arise when trying to implement and study novel interventions in real-world community settings. Our objective is to describe the challenges implementing the Culturally Focused Psychiatric (CFP) Consultation Prog...

Transcranial near-infrared radiation (NIR) is an innovative treatment for major depressive disorder (MDD), but clinical evidence for its efficacy is limited. Our objective was to investigate the tolerability and efficacy of NIR in patients with MDD. We conducted a proof of concept, prospective, double-blind, randomized study of 6 sessions of NIR ve...

Suicide risk evaluation is one of the most challenging assessments of patients with major depressive disorder (MDD). Initial risk evaluation might be insufficient in predicting emergence of suicidal ideation during the maintenance period. We aimed to elucidate factors associated with emergence or persistence of suicidal ideation 6 months after init...

We examined efficacy and safety of one specific cranial electrical stimulator (CES) device at a fixed setting in subjects with treatment-resistant major depressive disorder (MDD). Thirty subjects (57% female, mean age 48.1 ± 12.3 years) with MDD and inadequate response to standard antidepressants were randomized to 3 weeks of treatment with CES (15...

Anhedonia, disrupted reward processing, is a core symptom of major depressive disorder. Recent findings demonstrate altered reward-related ventral striatal reactivity in depressed individuals, but the extent to which this is specific to anhedonia remains poorly understood. The authors examined the effect of anhedonia on reward expectancy (expected...

Suicide is a tragedy that has massive impact on society. In order to prevent suicide, active government intervention is necessary. The suicide rate in Seoul is rapidly increasing and is more than five times higher than that in the state of Massachusetts (MA) during the last decade, especially in the elderly. The suicide prevention program of MA is...

Optimal successive treatment decisions are not well established after an initial medication nonresponse in major depressive disorder or bipolar disorder. While practice guidelines offer consensus-based expert treatment recommendations, little is known about "real world" pharmacology decision making by practicing psychopharmacologists. We surveyed v...

The authors sought to test the efficacy of adjunctive ziprasidone in adults with nonpsychotic unipolar major depression experiencing persistent symptoms after 8 weeks of open-label treatment with escitalopram. This was an 8-week, randomized, double-blind, parallel-group, placebo-controlled trial conducted at three academic medical centers. Particip...

Major Depressive Disorder (MDD) is clinically, and likely pathophysiologically, heterogeneous. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes. Guided by the NIMH Research Domain Criteria (RDoC) initiative, we used source localization of scalp-recorded EEG resting data to examine the neural corr...

The annual suicide rate in South Korea is the highest among the developed countries. Paraquat is a highly lethal herbicide, commonly used in South Korea as a means for suicide. We have studied the effect of the 2011 paraquat prohibition on the national suicide rate and method of suicide in South Korea. We obtained the monthly suicide rate from 2005...

Objective: The aim of this study was to examine whether gender differences may have affected treatment response to S-adenosyl methionine (SAMe) in a recent failed randomized clinical trial (RCT) for adults with major depressive disorder. Methods: Data from a 2-site, 12-week, double-blind RCT (n=189) assessing the efficacy of SAMe vs. placebo and a...

Longitudinal investigation of the neural correlates of reward processing in depression may represent an important step in defining effective biomarkers for antidepressant treatment outcome prediction, but the reliability of reward-related activation is not well understood. Thirty-seven healthy control participants were scanned using fMRI while perf...

Cognitive deficits are often associated with acute depressive episodes and contribute to the functional impairment seen in patients with Major Depressive Disorder (MDD). Many patients sustain residual cognitive deficits after treatment that may be independent of the core MDD disorder. We tracked changes in cognitive deficits relative to antidepress...

We examined whether fatigue was associated with greater symptomatic burden and functional impairment in college students with depressive symptoms. Using data from the self-report Beck Depression Inventory (BDI), we stratified a group of 287 students endorsing significant symptoms of depression (BDI score ≥13) into 3 levels: no fatigue, mild fatigue...

Psychosocial treatments and medications both have been shown to be effective in treating major depressive disorder. We hypothesized that cognitive-behavioral therapy (CBT) would outperform medication on measures of cognitive change. We randomized depressed individuals to 12 weeks of CBT (n = 15) or escitalopram (n = 11). In an intent-to-treat analy...

In the last decade, many studies have used automated processes to analyze magnetic resonance imaging (MRI) data such as cortical thickness, which is one indicator of neuronal health. Due to the convenience of image processing software (e.g., FreeSurfer), standard practice is to rely on automated results without performing visual inspection of inter...

Anhedonia represents a core symptom of major depression and may be a potential marker for melancholia. However, current understanding of this construct in depressive sub-types is limited. Participants were recruited from the Black Dog Institute (Sydney) and Massachusetts General Hospital (Boston). Diagnostic groups were derived on the basis of agre...

One of the main reasons for the inefficiency of multicenter randomized clinical trials (RCTs) in depression is the excessively high level of placebo response. The aim of this work was to propose a novel methodology to analyze RCTs based on the assumption that centers with high placebo response are less informative than the other centers for estimat...

Objective: To examine the effectiveness of genetic testing in a real-world setting and to assess its impact on clinician treatment decisions. Method: This was a naturalistic, unblinded, prospective analysis of psychiatric patients and clinicians who utilized a commercially available genetic test (between April and October of 2013), which incorpo...

Objective. We sought to demonstrate that maca root may be an effective treatment for antidepressant-induced sexual dysfunction (AISD) in women. Method. We conducted a 12-week, double-blind, placebo-controlled trial of maca root (3.0 g/day) in 45 female outpatients (mean age of 41.5 ± 12.5 years) with SSRI/SNRI-induced sexual dysfunction whose depre...

The Sequential Parallel Comparison Design (SPCD) is one of the novel approaches addressing placebo response. The analysis of SPCD data typically classifies subjects as 'placebo responders' or 'placebo non-responders'. Most current methods employed for analysis of SPCD data utilize only a part of the data collected during the trial. A repeated measu...

Although evidence suggests that there is an increase in suicide rates in the general population following celebrity suicide, the rates are heterogeneous across celebrities and countries. It is unclear which is the more vulnerable population according to the effect sizes of celebrity suicides to general population. All suicide victims in the general...

Depression is characterized by poor executive function, but - counterintuitively - in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flan...

Suicide is the third leading cause of death in college students, but there is limited consensual evidence to guide clinicians' assessment and management of suicide. The aim of the current study was to assess the capability of a simple and practical measure, the Beck Depression Inventory (BDI) suicide item, to identify college students at high risk...

Major depressive disorder (MDD) and nicotine dependence are highly co-morbid, with studies showing that ~50% of individuals with MDD smoke. The link between these disorders persists even after the clinical symptoms of depression subside, as indicated by high levels of nicotine dependence among individuals with remitted depression (rMDD). Recent evi...

Unlabelled: Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be difficult to treat with traditional antidepressant monotherapy. The purpose of this study was to assess the efficacy of ziprasidone monotherapy in patients with anxious depression versus non-anxious depression. One hundred...

Background Longitudinal studies of illness progression in Major Depressive Disorder (MDD) indicate that the onset of subsequent depressive episodes becomes increasingly decoupled from external stressors. A possible mechanism underlying this phenomenon is that multiple episodes induce long-lasting neurobiological changes that confer increased risk f...

To examine the comparative antidepressant efficacy of S-adenosyl-l-methionine (SAMe) and escitalopram in a placebo-controlled, randomized, double-blind clinical trial. One hundred eighty-nine outpatients (49.7% female, mean [SD] age = 45 [15] years) with DSM-IV-diagnosed major depressive disorder (MDD) were recruited from April 13, 2005, to Decembe...

Underutilization of mental health services in the U.S. is compounded among racial/ethnic minorities, especially Chinese Americans. Culturally based illness beliefs influence help-seeking behavior and may provide insights into strategies for increasing utilization rates among vulnerable populations. This is the first large descriptive study of depre...

Although opioids have known antidepressant activity, their use in major depressive disorder (MDD) has been greatly limited by risk of abuse and addiction. Our aim was to determine whether opioid modulation achieved through a combination of a μ opioid partial agonist, buprenorphine (BUP), and a potent μ opioid antagonist, samidorphan (SAM), would de...

Background Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF i...

The aim of this work is to investigate placebo response rates in placebo-controlled randomized clinical trials (RCTs) of pharmacological therapy in bipolar depression (BPD) and to identify predictors of placebo response and clinical trial outcome in BPD. Medline/PubMed publication databases were searched for RCTs of oral drugs used as monotherapy f...

This randomized, double-blind, placebo-controlled trial evaluated the efficacy of CP-601,927, an α4β2 nicotinic acetylcholine receptor partial agonist and an augmenting agent of antidepressants in major depressive disorder patients with insufficient response to selective serotonin reuptake inhibitors (SSRIs). After open-label treatment with an SSRI...

Background: Although previous studies have suggested that childhood trauma and parental death are strongly associated with suicidality in adulthood, it is still unclear how these factors interact within the same population. A total of 1396 adults were recruited through nationwide multistage probability sampling in South Korea. Subjects were evaluat...

Background: The Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (CPFQ) was developed to assess clinically relevant cognitive and physical symptoms associated with depression that are not adequately assessed by traditional measures. Although the CPFQ has been shown previously to be a reliable and valid measure, the p...