Papers by Michael E Thase
Dialogues in Clinical Neuroscience
Dialogues in Clinical Neuroscience, 2006
This review examines the relationship between sleep and depression. Most depressive disorders are... more This review examines the relationship between sleep and depression. Most depressive disorders are characterized by subjective sleep disturbances, and the regulation of sleep is intricately linked to the same mechanisms that are implicated in the pathophysiology of depression. After briefly reviewing the physiology and topography of normal sleep, the disturbances revealed in studies of sleep in depression using polysomnographic recordings and neuroimaging assessments are discussed. Next, treatment implications of the disturbances are reviewed at both clinical and neurobiologic levels. Most antidepressant medications suppress rapid eye movement (REM) sleep, although this effect is neither necessary nor sufficient for clinical efficacy. Effects on…
The American journal of psychiatry, Mar 3, 2017
The authors evaluated the efficacy and durability of a therapist-supported method for computer-as... more The authors evaluated the efficacy and durability of a therapist-supported method for computer-assisted cognitive-behavioral therapy (CCBT) in comparison to standard cognitive-behavioral therapy (CBT). A total of 154 medication-free patients with major depressive disorder seeking treatment at two university clinics were randomly assigned to either 16 weeks of standard CBT (up to 20 sessions of 50 minutes each) or CCBT using the "Good Days Ahead" program. The amount of therapist time in CCBT was planned to be about one-third that in CBT. Outcomes were assessed by independent raters and self-report at baseline, at weeks 8 and 16, and at posttreatment months 3 and 6. The primary test of efficacy was noninferiority on the Hamilton Depression Rating Scale at week 16. Approximately 80% of the participants completed the 16-week protocol (79% in the CBT group and 82% in the CCBT group). CCBT met a priori criteria for noninferiority to conventional CBT at week 16. The groups did no...
The Journal of Clinical Psychiatry, 2017
Objective: To provide a quantitative meta-analysis of the antidepressant effects of sleep depriva... more Objective: To provide a quantitative meta-analysis of the antidepressant effects of sleep deprivation to complement qualitative reviews addressing response rates. Data Sources: English-language studies from 1974 to 2016 using the keywords sleep deprivation and depression searched through PubMed and PsycINFO databases. Study Selection: A total of 66 independent studies met criteria for inclusion: conducted experimental sleep deprivation, reported the percentage of the sample that responded to sleep deprivation, provided a priori definition of antidepressant response, and did not seamlessly combine sleep deprivation with other therapies (eg, chronotherapeutics, repetitive transcranial magnetic stimulation). Data Extraction: Data extracted included percentage of responders, type of sample (eg, bipolar, unipolar), type of sleep deprivation (eg, total, partial), demographics, medication use, type of outcome measure used, and definition of response (eg, 30% reduction in depression ratings). Data were analyzed with meta-analysis of proportions and a Poisson mixed-effects regression model. The overall response rate to sleep deprivation was 45% among studies that utilized a randomized control group and 50% among studies that did not. The response to sleep deprivation was not affected significantly by the type of sleep deprivation performed, the nature of the clinical sample, medication status, the definition of response used, or age and gender of the sample. Conclusions: These findings support a significant effect of sleep deprivation and suggest the need for future studies on the phenotypic nature of the antidepressant response to sleep deprivation, on the neurobiological mechanisms of action, and on moderators of the sleep deprivation treatment response in depression.
BJPsych Open, 2016
SummaryThe appeal of ketamine – in promptly ameliorating depressive symptoms even in those with n... more SummaryThe appeal of ketamine – in promptly ameliorating depressive symptoms even in those with non-response – has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives – derived from evidence and clinical experience – and to consider strategies for future investigations.
Journal of consulting and clinical psychology, Jan 14, 2015
To determine the extent to which prospectively identified responders to cognitive therapy (CT) fo... more To determine the extent to which prospectively identified responders to cognitive therapy (CT) for recurrent major depressive disorder (MDD) hypothesized to be lower risk show significantly less relapse or recurrence than treated higher risk counterparts across 32 months. Outpatients (N = 523), aged 18-70, with recurrent MDD received 12-14 weeks of CT. The last 7 consecutive scores from the Hamilton Rating Scale for Depression (HRSD-17) were used to stratify or define responders (n = 290) into lower (7 HRSD-17 scores of less than or equal to 6; n = 49; 17%) and higher risk (n = 241; 83%). The lower risk patients entered the 32-month follow-up. Higher risk patients were randomized to 8 months of continuation-phase CT or clinical management plus double-blind fluoxetine or pill placebo, with a 24-month follow-up. Lower risk patients were significantly less likely to relapse over the first 8 months compared to higher risk patients (Kaplan-Meier [KM] estimates; i.e., 4.9% = lower risk; 2...
The Journal of clinical psychiatry, 2003
Historically, clinical researchers have gauged the short-term effectiveness of antidepressants by... more Historically, clinical researchers have gauged the short-term effectiveness of antidepressants by response rates, which have been defined as a "significant" reduction of symptoms or a global impression of at least moderate benefit. However, increased focus over the past decade has led many researchers to suggest that remission, i.e., a virtual elimination of depressive symptoms and restoration of psychosocial functioning, should be the primary goal of the initial phase of therapy. This article examines the relative efficacy of various antidepressant therapies. There is some evidence that medications affecting multiple neurochemical systems, such as the tricyclics amitriptyline and clomipramine (in studies of hospitalized patients) and the more selective "dual reuptake inhibitor" venlafaxine, may result in higher rates of remission relative to other agents. Given the better tolerability of newer antidepressants relative to tricyclics, both logic and an increasing ...
The Journal of clinical psychiatry, 2007
The term atypical depression dates to the first wave of reports describing differential response ... more The term atypical depression dates to the first wave of reports describing differential response to monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). In contrast to more TCA-responsive depressions, patients with so-called atypical symptoms (e.g., hypersomnia, interpersonal sensitivity, leaden paralysis, increased appetite and/or weight, and phobic anxiety) were observed to be more responsive to MAOIs. After several decades of controversy and debate, the phrase "with atypical features" was added as an episode specifier in the DSM-IV in 1994. The 1-year prevalence of the defined atypical depression subtype is approximately 1% to 4%; around 15% to 29% of patients with major depressive disorder have atypical depression. Hardly "atypical" in contemporary contexts, atypical depression also is common in dysthymic bipolar II disorders and is notable for its early age at onset, more chronic course, and high rates of comorbidity with social phobia ...
Journal of Consulting and Clinical Psychology, 2014
Objective-Continuation phase cognitive therapy (C-CT) or fluoxetine (FLX) reduces relapse in adul... more Objective-Continuation phase cognitive therapy (C-CT) or fluoxetine (FLX) reduces relapse in adults with major depressive disorder (MDD; Jarrett, Minhajuddin, Gershenfeld, Friedman, & Thase, 2013). Among patients at higher risk for relapse, we hypothesized that continuation phase treatment reduces residual symptoms and facilitates stable remission and recovery. Method-Outpatients (N=241) with recurrent MDD who responded to acute-phase CT with higher risk for relapse (i.e., had unstable remission defined by any of the last 7 acute-phase Hamilton Rating Scale for Depression scores ≥7) were randomized to 8 months of C-CT, FLX, or pill placebo and followed 24 additional months. Psychiatric Status Ratings of 1 or 2 (absent or minimal depressive symptoms) for 6 and 35 continuous weeks post-randomization defined stable remission and recovery, respectively. Results-Actuarial estimates of stable remission (97%) and recovery (94%) by the end of follow-up were high and did not differ among groups. Observed (unadjusted) proportions of
Sleep Medicine Reviews, 2004
Sleep disturbances are almost always present in patients with depression. Though sleep disturbanc... more Sleep disturbances are almost always present in patients with depression. Though sleep disturbances generally abate with the resolution of depression, some patients continue to report poor sleep. Since a number of studies have demonstrated that insomnia increases the risk of new-onset depression and recurrence of depression, optimal management of insomnia associated with depression becomes an important clinical goal. Antidepressant agents have variable effects on sleep and in fact, some antidepressants seem to worsen sleep in patients with depression. This article reviews various treatment options in the management of patients presenting with insomnia and depression, including single agents, combination strategies and behavioral interventions.
Psychological Science in the Public Interest, 2002
Depression is one of the most common and debilitating psychiatric disorders and is a leading caus... more Depression is one of the most common and debilitating psychiatric disorders and is a leading cause of suicide. Most people who become depressed will have multiple episodes, and some depressions are chronic. Persons with bipolar disorder will also have manic or hypomanic episodes. Given the recurrent nature of the disorder, it is important not just to treat the acute episode, but also to protect against its return and the onset of subsequent episodes.Several types of interventions have been shown to be efficacious in treating depression. The antidepressant medications are relatively safe and work for many patients, but there is no evidence that they reduce risk of recurrence once their use is terminated. The different medication classes are roughly comparable in efficacy, although some are easier to tolerate than are others. About half of all patients will respond to a given medication, and many of those who do not will respond to some other agent or to a combination of medications. ...
Neuropsychopharmacology, 2009
Stewart et al (2009) have outlined the evidence in support of the validity of the DSM-IV definiti... more Stewart et al (2009) have outlined the evidence in support of the validity of the DSM-IV definition of the 'With Atypical Features' episode specifier. Although recognizing the historical significance and clinical utility of the concept of atypical depression, this article takes issue with the DSM-IV criteria. It is concluded that mood reactivity, the A or obligative criterion, is neither significantly associated with the other symptomatic criteria nor useful to diagnose atypical depression, and thus should be eliminated. Problems with operationalization, specification, and reliability of ratings of the diagnostic criteria further limit validity. Despite these limitations in classification, many of the features associated with atypical depression are linked to an early onset of affective illness, including trait-like interpersonal sensitivity, comorbid social anxiety and agoraphobia, a history of childhood physical or sexual trauma, and indicators of the 'soft' side of the bipolar spectrum. Neurophysiologic studies also suggest that chronic, early-onset atypical depressions differ from both melancholia and normality. Re-analyses of the Columbia group's seminal studies suggest that preferential response to phenelzine vs imipramineFarguably the strongest validator of atypical depressionFsimilarly appears to be limited to patients with chronic, early-onset syndromes. The criteria for atypical depression need to be revised in DSM-V, including sharpening the operational definitions for the specific symptoms. The importance of age of onset and comorbid anxiety warrant further study. Research examining the validity of a subform of atypical depression characterized by trait-like interpersonal sensitivity and a chronic, early-onset course may further enhance the clinical utility of the DSM-V classification.
Journal of Consulting and Clinical Psychology, 2008
The main aim of the present novel reanalysis of archival data was to compare the time to remissio... more The main aim of the present novel reanalysis of archival data was to compare the time to remission during 12 weeks of treatment of chronic depression following antidepressant medication (n = 218), psychotherapy (n = 216), and their combination (n = 222). Cox regression survival analyses revealed that the combination of medication and psychotherapy produced full remission from chronic depression more rapidly than either of the single modality treatments, which did not differ from each other. Receiver operating characteristic curve analysis was used to explore predictors (treatment group, demographic, clinical, and psychosocial) of remission. For those receiving the combination treatment, the most likely to succeed were those with low baseline depression (24-item Hamilton Rating Scale for Depression [HRSD; M. Hamilton, 1967] score < 26) and those with high depression scores but low anxiety (HRSD ≥ 26 and Hamilton Anxiety
The Journal of Clinical Psychiatry, 2006
The Journal of Clinical Psychiatry, 2011
Objective-Insomnia and objectively measured sleep disturbances predict poor treatment outcomes in... more Objective-Insomnia and objectively measured sleep disturbances predict poor treatment outcomes in patients with major depressive disorder (MDD). However, prior research has utilized individual clinical trials with relatively small sample sizes and has focused on insomnia symptoms or objective measures, but not both. The present study is a secondary analysis that examines the degree to which insomnia, objective sleep disturbances, or their combination, predicts depression remission following pharmacotherapy and/or psychotherapy treatment. Methods-Participants were 711 depressed patients drawn from six clinical trials. Remission status, defined as a score of ≤ 7 on the Hamilton Rating Scale for Depression (HDRS) over two consecutive months, served as the primary outcome. Insomnia was assessed via the 3 sleep items on the HDRS. Objectively measured short sleep duration (total sleep time < = 6 hours), and prolonged sleep latency (SL >30 minutes) or wakefulness after sleep onset (WASO>30) were derived from in-laboratory polysomnographic (PSG) sleep studies. Logistic regression predicted the odds of non-remission according to insomnia, each of the objective sleep disturbances, or their combination, after adjusting for age, sex, treatment modality, and baseline depressive symptoms. Results-Prolonged sleep latency alone (OR = 1.82; CI: 1.23, 2.70) or in combination with insomnia (OR = 2.03; CI: 1.13, 3.95) predicted increased risk of non-remission. In addition, insomnia and sleep duration individually and in combination were each associated with a significantly increased risk of non-remission (p's < .05). suggest that objectively measured prolonged sleep latency and short sleep duration independently, or in conjunction with insomnia are risk factors for poor depression treatment outcome. Insomnia and objectively measured sleep disturbances are associated with slower treatment response and poorer treatment outcomes in patients with major depression. 1-3 Although complete recovery is the goal of depression treatment, this is often an elusive goal, and sleep disturbances are among the most common residual symptoms. 4-6 A recent study found a residual insomnia rate of 51% among patients who showed remission of other depressive symptoms following 20 weeks of either cognitive behavioral therapy or pharmacotherapy.
Journal of Affective Disorders, 2013
Background: Recent investigations have revealed multiple actions of vascular endothelial growth f... more Background: Recent investigations have revealed multiple actions of vascular endothelial growth factor (VEGF) in the nervous system. The role of VEGF in the molecular background of mood disorders has also been proposed. In this study we were interested in investigating a possible association between VEGF levels and treatment response in patients with a current episode of major depression (MDE). Methods: 34 patients with MDE were enrolled in our study. Depressive symptoms were monitored by the Montgomery-Åsberg Depression Rating Scale at baseline (V 1 ) and after a 4-week treatment period (V 2 ). Patients with less than a 50% improvement in MADRS total scores during this period were regarded as non-responders. Results: Plasma VEGF levels did not change during the treatment period in either the total sample or in the responder and non-responder subsamples. There was a strong trend for higher baseline VEGF levels in the non-responder group than in the responder group (p¼ 0.055) and this difference-as a weak trend-was still detectable at the end of the treatment period (p ¼0.097). Regression analysis revealed that the baseline VEGF level was a significant predictor for the endpoint MADRS score (p¼ 0.02). Limitations: Sample size was relatively small; sample consists of both patients with MDD and bipolar disorder. Conclusions: Our preliminary results raise the possibility that baseline levels of peripheral VEGF may predict treatment response in patients with mood disorders. Considering the limitations of our study, further investigations should resolve whether VEGF is a useful biomarker for treatment response in depression in clinical practice.
Current Pharmaceutical Biotechnology, 2006
British Journal of Psychiatry, 2013
SummaryIt is suggested that a finding that apparently challenges current practice guidelines, nam... more SummaryIt is suggested that a finding that apparently challenges current practice guidelines, namely that patients with a rapid-cycling pattern of bipolar disorder can take antidepressant monotherapy for months without increasing risk of cycling, may be parsimoniously understood by the way that the investigators defined rapid cycling and by their use of acute-phase fluoxetine monotherapy prior to randomisation to continutaion-phase therapy with fluoxetine, lithium or placebo.
Biological Psychiatry, 2000
Although most of the care received by bipolar patients occurs during the maintenance phase, relat... more Although most of the care received by bipolar patients occurs during the maintenance phase, relatively little empirical data is available to guide long-term treatment decisions. We review literature pertaining to key questions related to use of pharmacotherapy in the maintenance phase of bipolar disorder. The few double-blind trials with a reasonable sample size are restricted to bipolar I patients and address a modest range of questions mostly related to use of lithium. One rigorous multicenter trial found valproate to have prophylactic benefit. Other studies with valproate alone and in combination suggest efficacy equivalent to lithium and perhaps greater than carbamazepine. Data available for combination treatment are sparse but moderately encouraging. Maintenance treatment with standard antidepressant medications appears destabilizing for some bipolar patients, particularly following a mixed episode. Although some bipolar patients may benefit from combined treatment with a mood stabilizer and a standard antidepressant medication, current knowledge does not allow confident selection of the bipolar patients who might benefit. Clozapine and perhaps other atypical antipsychotics are promising options for maintenance treatment but have not been evaluated in double-blind trials. The numerous other agents used in maintenance treatment are primarily adjuncts to lithium, valproate, or carbamazepine, and information about them is largely anecdotal and uncontrolled. Study design for maintenance trials remains an imperfect art. Conclusions must be drawn cautiously, given the limited generalizability of study designs that accession samples enriched with presumed treatment responders, randomize patients after brief periods of partial remission, abruptly taper prior treatment, make no attempt to distinguish relapse from recurrence, use no formal outcome assessments, or report hospitalization as the only outcome criterion.
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Papers by Michael E Thase