Jonathan W. Stewart

Jonathan W. Stewart
New York State · Therapeutics

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227
Publications
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Publications

Publications (227)
Article
Full-text available
Previous neuroimaging studies have shown that serotonin-norepinephrine reuptake inhibitor antidepressants alter functional activity in large expanses of brain regions. However, it is not clear how these regions are systemically organized on a connectome level with specific topological properties, which may be crucial to revealing neural mechanisms...
Article
Brain gray matter is organized in a manner with interconnected brain regions, resulting in a notable covariance pattern that recapitulates either the functional coactivation or structural connectivity of brain regions, which is believed to underpin psychiatric disorders such as depression. This study aimed to investigate whether and how antidepress...
Article
Background Triple chronotherapy (wake night [one night without sleep], sleep phase advance, and early morning bright light exposure) demonstrated rapid efficacy primarily in bipolar depression, but has not been as well studied in unipolar depression. Our primary hypothesis is that triple chronotherapy is associated with a significantly greater Week...
Article
Full-text available
Cognitive behavior models present major depressive disorder (MDD) as a failure in emotional processing associated with disrupted metacognitive skills. Self-observation, a metacognitive ability, plays a vital role in emotion regulation. Studies have noted the role of mindfulness in cognitive behavioral therapy (CBT); however, few address psychologic...
Article
Objective: To compare white matter integrity (WMI) in bipolar disorder (BD) relative to healthy volunteers (HV) and major depressive disorder (MDD). To determine the relationship of bipolar specific differences in WMI to cerebral perfusion, body mass index (BMI) and blood pressure as indices of cardiovascular function. Methods: 32 participants w...
Article
Antidepressant medications offer an effective treatment for depression, yet nearly 50% of patients either do not respond or have side-effects rendering them unable to continue the course of treatment. Mechanistic studies might help advance the pharmacology of depression by identifying pathways through which treatments exert their effects. Toward th...
Article
Background Antidepressant medications offer an effective treatment for depression, yet nearly 50% of patients either do not respond or have side-effects rendering them unable to continue the course of treatment. Mechanistic studies might help advance the pharmacology of depression by identifying pathways through which treatments exert their effects...
Article
Introduction: Pharmacotherapy of non-major persistent depressive disorder (PDD) is little studied. We report a study of the serotonin-norepinephrine reuptake inhibitor (SNRI) desvenlafaxine (DVLX) for PDD. Method: Non-psychotic, non-bipolar outpatients aged 20–65 having PDD without concurrent major depression (MDD) were randomized double-blind to d...
Article
Objectives: Patients with bipolar disorder spend the most time in the depressed phase, and that phase is associated with the most morbidity and mortality. Treatment of bipolar depression lacks a test to determine who will respond to treatment. White matter disruptions have been found in bipolar disorder. Previous reports suggest that white matter...
Conference Paper
INTRODUCTION Multiple lines of evidences suggest that the diagnosis of Major Depressive Disorder (MDD) encompass a heterogeneous group of disorders with various genetic patterns, neurobiological mechanisms, symptoms profiles, course-trajectories and ultimately differential treatment responses. We hypothesized that age-related neurobiological differ...
Article
The right and left side of the brain are asymmetric in anatomy and function. We review electrophysiological (EEG and event-related potential), behavioral (dichotic and visual perceptual asymmetry), and neuroimaging (PET, MRI, NIRS) evidence of right-left asymmetry in depressive disorders. Recent electrophysiological and fMRI studies of emotional pr...
Article
Objective: To determine efficacy of continued treatment with the serotonin norepinephrine reuptake inhibitor duloxetine on symptom reduction and functional improvement in outpatients with dysthymia. Method: Fifty outpatients with DSM-IV-TR diagnosed dysthymia who had participated in a 10 week double-blind, placebo-controlled study of duloxetine...
Article
(Reprinted from the American Journal of Psychiatry 2015; 172:450-459, with permission from American Psychiatric Association Publishing).
Article
A prior study (Bruder, G.E., Stewart, J.W., Mercier, M.A., Agosti, V., Leite, P., Donovan, S., Quitkin, F.M., 1997. Outcome of cognitive-behavioral therapy for depression: relation of hemispheric dominance for verbal processing. Journal of Abnormal Psychology 106, 138-144.) found left hemisphere advantage for verbal dichotic listening was predictiv...
Article
Objective: Observational studies show that when a depressed mother's symptoms remit, her children's psychiatric symptoms decrease. Using randomized treatment assignment, the authors sought to determine the differential effects of a depressed mother's treatment on her child. Method: The study was a randomized double-blind 12-week trial of escital...
Article
Chronic depression is associated with significant impairment in work functioning, relationships, and health. Such impairment often persists following medication-induced remission of depressive symptoms. We adapted and tested Behavioral Activation therapy with a goal of return to work (BA-W) in subjects with chronic depression who had responded to m...
Article
Full-text available
Background Executive dysfunction and psychomotor slowing in depressed patients have been associated with poor antidepressant clinical response, but little is known about the value of neurocognitive tests for differential prediction of response. Methods This report presents new findings for 70 depressed patients tested on neurocogntive tests before...
Article
Objective: This work tested the hypothesis that patients with high negative affectivity (NA) would have a better response to a serotonergic agent (escitalopram) than to one not thought to act directly on serotonin (bupropion). Method: Data from a study conducted between August 2007 and July 2011 were reanalyzed retrospectively. Patients (N = 245...
Article
Introduction: Patients who do not remit following one or more attempts at treatment present a clinical challenge, as well as prolonged suffering and disability. Discouragement is common, so knowledge of likelihood of eventual remission as well as which treatments might ultimately be effective would help patient and clinician alike. Method: Thirt...
Article
Although studies have linked childhood trauma to depression resembling the atypical subtype, a majority of these studies did not use DSM-IV criteria for atypical features nor assess trauma both before and after depression onset. This study examined the relationship between atypical depression and lifetime trauma with the hypothesis that atypically...
Article
Full-text available
Importance The default mode network (DMN) is a collection of brain regions that reliably deactivate during goal-directed behaviors and is more active during a baseline, or so-called resting, condition. Coherence of neural activity, or functional connectivity, within the brain's DMN is increased in major depressive disorder relative to healthy contr...
Article
Introduction Only about a third of patients with an episode of major depressive disorder remit with a given treatment and few remissions occur within the first weeks of treatment. This study tested whether combining escitalopram and bupropion as initial treatment would result in quicker remission and a higher remission rate than monotherapy with ei...
Article
To estimate the prevalence of current psychiatric disorders among children and adolescents (collectively called children) of mothers entering treatment for depression; to examine maternal predictors of child psychopathology among children of depressed mothers; and to determine consistency of findings with a similar child study ancillary to Sequence...
Article
Numerous double-blind studies have assessed the efficacy of antidepressants in treating chronic depressive disorder, including dysthymic disorder, low-grade chronic depression. However, there are no double-blind, placebo-controlled studies of serotonin-norepinephrine reuptake inhibitors in chronic depressive disorder. Outpatients with chronic depre...
Article
Objective: Numerous double-blind studies have assessed the efficacy of antidepressants in treating chronic depressive disorder, including dysthymic disorder, low-grade chronic depression. However, there are no double-blind, placebo-controlled studies of serotonin-norepinephrine reuptake inhibitors in chronic depressive disorder. Method: Outpatients...
Conference Paper
Full-text available
Background: Despite the overlap of cortical and limbic structures involved in olfaction, emotion and depression, there has been little study of olfactory function in depression. Methods: 49-channel ERPs were recorded from 25 clinically-depressed and 27 healthy controls during an odor detection task using pleasant (Citronalva; CIT) and unpleasant (h...
Article
Prior studies have found abnormalities of functional brain asymmetry in patients having a major depressive disorder (MDD). This study aimed to replicate findings of reduced right hemisphere advantage for perceiving dichotic complex tones in depressed patients, and to determine whether patients having "pure" dysthymia show the same abnormality of pe...
Article
Several meta- or mega-analyses suggest antidepressant medications should be given only to severely depressed patients. In our experience, mild depression benefits from medication. We reanalyzed 1 clinic's randomized placebo-controlled antidepressant studies, limiting analyses to patients with major depressive disorder (MDD) without severe illness,...
Article
To examine prevalence, correlates, comorbidity and treatment-seeking among individuals with a lifetime major depressive episode (MDE) with and without atypical features. Data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions, a large cross-sectional survey of a representative sample (N = 43,093) of the...
Article
The clinical effects of antidepressant combinations vs. monotherapy as initial treatment for major depression with melancholic features (MDD-MF) are unknown. Outpatients with chronic or recurrent major depression (MDD) were randomized to initial treatment with escitalopram+placebo (the MONO condition), bupropion-sustained release+escitalopram, or v...
Article
Full-text available
Two antidepressant medication combinations were compared with selective serotonin reuptake inhibitor monotherapy to determine whether either combination produced a higher remission rate in first-step acute-phase (12 weeks) and long-term (7 months) treatment. The single-blind, prospective, randomized trial enrolled 665 outpatients at six primary and...
Article
Full-text available
Despite recent success in pharmacologic treatment of depression, the inability to predict individual treatment response remains a liability. This study replicates and extends findings relating pretreatment electroencephalographic (EEG) alpha to treatment outcomes for serotonergic medications. Resting EEG (eyes-open and eyes-closed) was recorded fro...
Article
Little is known about the quantity or quality of residual depressive symptoms in patients with major depressive disorder (MDD) who have responded but not remitted with antidepressant treatment. This report describes the residual symptom domains and individual depressive symptoms in a large representative sample of outpatients with nonpsychotic MDD...
Article
Previous reports have suggested that lamotrigine is effective as an antidepressant augmentation agent in patients with treatment-resistant unipolar depression. This study is the largest double-blind placebo-controlled study conducted to date of lamotrigine in this role. In this multicenter trial, conducted at 19 sites, patients aged 18-65 years wit...
Article
Full-text available
Studies of regional hemispheric asymmetries point to relatively less activity in left frontal and right posterior regions in depression. Anxiety was associated with increased right posterior activity, which may be related to arousal and, in anxious-depressed individuals, offset the posterior asymmetry typically seen in depression. These asymmetries...
Article
Objective/Introduction : We sought to characterize the impact of the 90-item Symptom Checklist (SCL-90) subscales for paranoid ideation (PI) and psychoticism (P) in patients with major depressive disorder (MDD), on acute anti-depressant response and on relapse prevention. Methods : Subjects with Structured Clinical Interview for DSM Disorders-diag...
Article
Sixty alcoholic patients with depressive disorders completed a 12-week, open-label trial of imipramine; 27 (45%) had a favorable response, defined as substantial improvement in both mood and sobriety. The authors examine demographic and clinical predictors of response. Responders were less likely to be minorities, bad lower Hamilton Rating Scale fo...
Article
In an open trial of bromocriptine in seven outpatients with cocaine addiction, most patients experienced reduced dysphoria and craving but none achieved abstinence. These results may suggest limitations of the dopamine agonist approach. Cautious interpretation is required because this may have been a treatment-refractory sample.
Article
The impact of personality disorders (PD) on the course of depression has been gaining interest among clinical researchers over the past decade. Recent observational studies have found that PD was associated with impaired social functioning and reduced likelihood of depression recovery. Elevated rates of PD have been noted in early-onset and chronic...
Article
There have been conflicting findings as to whether the P3 brain potential to targets in oddball tasks is reduced in depressed patients. The P3 to novel distracter stimuli in a three-stimulus oddball task has a more frontocentral topography than P3 to targets and is associated with different cognitive operations and neural generators. The novelty P3...
Article
Full-text available
Atypical features were incorporated into the American Psychiatric Association's Diagnostic and Statistical Manual, Fourth Edition (DSM-IV, 1994) as an illness specifier for major depression and dysthymia. The validity of depression with atypical features was supported by differences relative to depression with melancholic features in syndromal symp...
Article
We previously reported a novelty P3 reduction in depressed patients compared to healthy controls (n=20 per group) in a novelty oddball task using a 31-channel montage. In an independent replication and extension using a 67-channel montage (n=49 per group), reference-free current source density (CSD) waveforms were simplified and quantified by a tem...
Article
Only 30%-40% of depressed patients remit after 8 weeks of treatment with an antidepressant. We hypothesized that beginning treatment with two antidepressants would improve remission rates. Relatively treatment-naive depressed outpatients (with DSM-IV diagnoses of major depressive disorder, dysthymic disorder, or depression not otherwise specified)...
Article
Full-text available
Depressed patients with atypical features have an earlier onset of depression, a more chronic course of illness, several distinctive biological and familial features, and a different treatment response than those without atypical features. The efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) have not been fully evaluated...
Article
Untreated major depressive disorder (MDD) is a major risk factor for suicide, but some data suggest antidepressants may be associated with increased suicidal ideation (SI) in some depressed patients. The purpose of this study was to determine whether, and in whom, treatment of MDD is associated with increased or emergent SI. Patients were treated w...
Article
Depression with atypical features responds preferentially to monoamine oxidase inhibitors relative to tricyclic antidepressants. The efficacies of newer agents have been little studied in this group, although fluoxetine was more effective than placebo. Studies with newer agents seem indicated. Twenty outpatients having major depression with atypica...
Article
Monotherapy with a selective serotonin reuptake inhibitor (SSRI) is the most common initial treatment for major depressive disorder (MDD), but this monotherapy leads to remission in fewer than a third of patients. The combination of the SSRI escitalopram and bupropion-SR is commonly used for treating patients with MDD who have had an inadequate res...
Article
Full-text available
Studies suggest that neuropsychological measures may provide prognostic information regarding SSRI treatment response, yet it is unclear which specific cognitive domains are the most effectual predictors. The aim of this study was to characterize the cognitive profile associated with SSRI nonresponse using a comprehensive set of neuropsychological...
Article
There is growing evidence that individual differences among depressed patients on electrophysiologic (EEG), neuroimaging, and neurocognitive measures are predictive of therapeutic response to antidepressant drugs. This study replicates prior findings of pretreatment differences between selective serotonin reuptake inhibitor (SSRI) responders and no...
Article
To compare rates of comorbidity, treatment utilization, the course of illness, and past year social functioning of Hypomania with and without Dysphoria Hypomania (mixed state). The National Epidemiological Survey on Alcohol and Related Conditions (NESARC) was a nationally representative face-to-face survey of 43,093 respondents, aged 18 years and o...
Article
Event-related potentials (31-channel ERPs) were recorded from 38 depressed, unmedicated outpatients and 26 healthy adults (all right-handed) in tonal and phonetic oddball tasks developed to exploit the perceptual challenge of a dichotic stimulation. Tonal nontargets were pairs of complex tones (corresponding to musical notes G and B above middle C)...
Article
Full-text available
The success of well-developed protocols has been limited in real-world practice, where even effective strategies have not been sufficient to meet patient needs in routine clinical care owing to Axis I and III comorbidities. The Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) trial required that antidepressant medication treatment...
Article
Full-text available
This report assesses whether age at onset defines a specific subgroup of major depressive disorder in 4,041 participants who entered the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. The study enrolled outpatients 18-75 years of age with nonpsychotic major depressive disorder from both primary care and psychiatric care prac...
Article
Studies using neuroimaging, electrophysiologic and cognitive measures have raised hopes for developing predictors of therapeutic response to antidepressants. Pretreatment measures of functional brain asymmetry have been found to be related to response to the selective serotonin reuptake inhibitor fluoxetine. This report examines the extent to which...
Article
Sparse data exist regarding the risks and benefits of treating bipolar-II depression with antidepressants alone. On the basis of studies of bipolar-I patients, treatment guidelines suggest antidepressants should be augmented with mood stabilizers. Whether these recommendations apply to bipolar-II is unclear. A post-hoc analysis of a double-blind st...
Article
Full-text available
Premature attrition from treatment may lead to worse outcomes and compromise the integrity of clinical trials in major depressive disorder. The purpose of this study was to identify the pretreatment predictors of attrition during acute treatment with citalopram in a large, "real world" clinical trial. A total of 4,041 adult outpatients with nonpsyc...
Article
Depression with atypical features is characterized by mood reactivity and 2 or more symptoms of vegetative reversal (including overeating, oversleeping, severe fatigue or leaden paralysis, and a history of rejection sensitivity). Another important feature of atypical depression is its preferential response to monoamine oxidase inhibitor (MAOI) trea...
Article
Depression with atypical features was first recognized in a subset of patients with depression who preferentially responded to the monoamine oxidase inhibitor (MAOI) phenelzine, in contrast to patients with melancholic depression. This article reviews the history of approaches in treating depression with atypical features. Initial studies in the ea...
Article
The Diagnostic and Statistical Manual, Fourth Edition (DSM-IV, 1994) included atypical features as an illness specifier for major depression and dysthymia. We asked whether subsequent literature supported its validity and addressed the relationship between depression with atypical features and melancholia. Literature review focusing on studies addr...
Article
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This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=12...
Article
Full-text available
Loss of response to a previously effective antidepressant is a common clinical problem. Retrospective analyses have shown that the pattern of response during antidepressant treatment (late onset and persistent versus other patterns) can be used to predict relapse during continuation and maintenance treatment and possibly to identify placebo respons...
Article
Full-text available
The purpose of this study was to compare the effectiveness and tolerability of tranylcypromine and combination treatment with extended-release venlafaxine and mirtazapine in patients with treatment-resistant major depression whose current depressive episode had not responded adequately to treatment in three prior prospective medication trials. Adul...
Article
Full-text available
After unsuccessful treatment for depression with a selective serotonin-reuptake inhibitor (SSRI), it is not known whether switching to one antidepressant is more effective than switching to another. We randomly assigned 727 adult outpatients with a nonpsychotic major depressive disorder who had no remission of symptoms or could not tolerate the SSR...
Article
This study examined the utility of baseline psychomotor speed, measured with neuropsychological tests, to predict fluoxetine response in moderately depressed outpatients. The authors hypothesized that since psychomotor slowing in depressed patients has been linked to reduced dopaminergic neurotransmission, patients with slowing would be unresponsiv...