Abstract Introduction Negativity bias in depression has been repeatedly demonstrated in the judgment and decision-making literature. Research investigating the impact of sleep deprivation on self-evaluation of performance in healthy or depressed populations is limited. We examined 1) whether individuals with Major Depressive Disorder (MDD) exhibit a negativity bias in subjective ratings of performance on the Psychomotor Vigilance Task (PVT) as compared with healthy adults, and 2) the impact of total sleep deprivation (TSD) on these ratings. Methods N=33 individuals with MDD and n=9 healthy adults completed a 5-day study protocol including two baseline nights (B1-B2, 9h TIB), 36 hours of TSD, and one night of recovery sleep opportunity (Rec). The PVT was administered every 2-4 hours. A brief questionnaire was administered immediately prior to (PRE) and following (POST) the PVT, asking participants to estimate their average reaction time (RT) using a 9-point Likert-type scale. Mixed-effects models examined the impact of group (MDD, Control), protocol day (B1, B2, SD, Rec), and their interaction on objective PVT performance (mean RT) and subjective performance estimates (PRE and POST ratings). Results Mean RT was significantly slower during TSD (p<0.001) for all participants. Individuals with MDD and healthy adults did not differ in objective PVT performance (p=0.25) across days. There was no significant interaction between group and protocol day (p=0.96). Both groups predicted slower RTs during TSD as compared with baseline or recovery days (PRE-PVT, p=0.006). Individuals with MDD anticipated slower RTs as compared with healthy adults (p=0.001). On POST-PVT estimates, all participants reported subjective poorer performance during TSD (p<0.008). Individuals with MDD reported slower RTs as compared with healthy adults (p=0.002). Interaction effects between group and protocol day on PRE- and POST- performance ratings were not significant. Conclusion This project is the first to investigate subjective estimates of PVT performance in healthy and depressed individuals. Individuals with MDD subjectively reported slower response times as compared with control participants, despite similar objective performance. Depressive symptoms may be a potential confounder of subjective, but not objective, PVT performance. Support 5R01MH107571

This paper is devoted to stability analysis of continuous-time delay systems with interval time-varying delays having known bounds on the delay derivatives. A parameterized family of Lyapunov–Krasovskii functionals involving multiple integral terms is introduced, and novel multiple integral inequalities are utilized to derive sufficient stability condition for systems with time-varying delays. The efficiency of the proposed method is illustrated by numerical examples.

The main objectives of this multicenter, naturalistic, open-label study is to evaluate the effectiveness, tolerability and safety of venlafaxine extended release (VXR) in a sample of 59 patients older than 60 years of age diagnosed of depressive disorders in the primary care setting. VXR was administered for 24 weeks at daily doses ranging from 75 mg to 225 mg. Effectiveness measurements included the 17 items Hamilton Depression Rating Scale (HAM-D17), the Clinical Global Impression Scales for Severity (CGI-S) and Improvement (CGI-I), the Visual Analogical Scale for Pain (P-VAS), and the Mini-Mental State Examination (MMSE) scale. At the endpoint, VXR achieved response and remission rates of 81.6% and 59.2%, respectively. Treatment was associated with a significant improvement of the patient's condition (89.8% of patients were rated by physicians as “much/very much improved”). Painful physical symptoms (p < 0.0001) and cognitive state (p = 0.0017) scores decreased along the study. A total of 83% of patients completed the study. Seven adverse events were recorded for four patients (6.8% overall). Data of this study suggest that VXR could be an effective and safe therapeutic option in the treatment of geriatric depression, reducing also the associated painful physical symptoms.

Emergency physicians can utilize bedside ultrasound to aid in the diagnosis of abdominal wall hernias and in the reduction of incarcerated hernias.To review the sonographic appearance and diagnostic criteria of abdominal wall hernias and to describe the potential use of ultrasound as an aid in hernia reduction.An emergency physician utilized bedside ultrasound to confirm the diagnosis of an incarcerated ventral abdominal wall hernia and to assist in its successful reduction.A physician trained in bedside ultrasound can diagnose an abdominal wall hernia and facilitate the appropriate treatment of an incarcerated hernia.

Back to table of contents Previous article Next article PerspectivesFull AccessComparative Effectiveness of Psychodynamic Psychotherapy and Cognitive-Behavioral Therapy: It’s About Time, and What’s Next?Michael E. Thase, M.D.Michael E. ThaseSearch for more papers by this author, M.D.Published Online:1 Sep 2013https://doi.org/10.1176/appi.ajp.2013.13060839AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail Since depression is one of the world’s greatest public health problems, conducting research to accurately weigh the benefits and risks of commonly used interventions should be as much a research priority as developing novel treatments or investigating mechanisms of disease pathophysiology. Psychotherapy is one of the most widely used classes of treatment, but unfortunately there is no commercial entity analogous to the pharmaceutical industry to support research and development of the current and next generations of interventions. The impact of this state of affairs is particularly evident with respect to the ability to conduct larger-scale studies of comparative treatment effectiveness, for which there are only a handful of relevant studies. Thus, although psychodynamic psychotherapy has been used to treat depressed outpatients for decades, the utility of this time-honored approach, as measured by the results of randomized controlled trials of treatment efficacy and effectiveness, has not been extensively studied. The study by Driessen et al. (1) in this issue of the Journal is therefore noteworthy because it provides some of the strongest evidence to date that short-term psychodynamic psychotherapy is an effective treatment for major depressive disorder.The study, in which 341 outpatients seeking treatment for major depressive disorder at three different psychiatric centers in Amsterdam were randomly assigned, is the largest randomized controlled trial of psychodynamic psychotherapy ever conducted. It is a relatively inclusive study conducted under real-world conditions. The study had two phases, a 16-session (22 weeks) acute phase contrasting psychodynamic psychotherapy against a standard comparator with established efficacy, cognitive-behavioral therapy (CBT), and a 1-year naturalistic follow-up. Severely depressed patients, who comprised about 40% of the sample, could receive concomitant antidepressant pharmacotherapy. The 93 therapists were practicing psychologists and psychiatrists with an average of ≥7 years posttraining experience. For the purposes of the study, they completed standardized training in one of the two modalities (presumably based on their interest) and subsequently were supervised by members of the respective national associations for psychodynamic psychotherapy and CBT. Outcomes were assessed by independent (albeit unblinded) evaluators using standard measures, including the Hamilton Depression Rating Scale (HAM-D). The primary outcome of interest was the posttreatment remission rate, defined as a final HAM-D score ≤7. Although the investigators included all randomly assigned patients in analyses of symptom change, only 233 of the 341 randomly assigned patients (68%) were counted in the primary analysis.The primary finding of this trial was that psychodynamic psychotherapy was noninferior to CBT; posttreatment score remission rates were 21% (26/122) and 24% (27/111) for the psychodynamic psychotherapy and CBT groups, respectively. No significant differences were seen between treatments on any measure at any time point, and the overall pattern of results generally followed the primary outcome, namely that psychodynamic psychotherapy was not inferior to CBT.The statistical concept of noninferiority is not exactly intuitive, although in a sense it is the converse of using a statistical test to assert that one treatment is superior to another. Importantly, it is a much different result than one that states that the difference between two treatments is “not statistically significantly different.” This is because a noninferiority trial has been planned from the outset to test the hypothesis that, with at least 95% certainty, the effect of one treatment falls within a narrow, predetermined margin of the other, more established treatment’s effect. In the Driessen et al. study, the boundaries, which were determined by expert consensus, were a 10% difference in remission rates and a 2.6-point difference on HAM-D scores. Although one might quibble with the generosity of these boundaries (i.e., noninferiority studies should use the narrowest boundaries practicable), there is no argument that the observed between-group differences at all time points, on all key dependent measures and on most secondary analyses of subsets of patients, were not clinically meaningful. On the basis of these findings, there is no reason to believe that psychodynamic psychotherapy is a less effective treatment of major depressive disorder than CBT.This large study greatly expands the literature on controlled studies of psychodynamic psychotherapy, which heretofore was relatively meager. Of course, conducting randomized controlled trials was not part of the culture of academic psychiatry when psychodynamic psychotherapy was the dominant model of psychotherapy, and, in contrast to the strategy taken by the developers of “second-wave” interventions such as cognitive therapy, behavior therapy, and interpersonal psychotherapy, for which there has been evidence of efficacy from randomized controlled trials since the 1970s (2–4), the traditions of psychodynamic training and practice placed little emphasis on the grouped data generated by randomized controlled trials, instead emphasizing clinical observations from individual cases. It was indeed a curious circumstance that, for several decades, there was far more evidence that the newer forms of psychotherapy were efficacious than there was for the older and more widely practiced one.The absence of evidence (from randomized controlled trials) is not necessarily the evidence of absence (of efficacy for treatment of major depressive disorder); however, the Driessen et al. study adds to a slowly growing body of work that indicates that psychodynamic psychotherapy is indeed an effective treatment option for outpatients with major depressive disorder. The results of this randomized controlled trial complement those of a relatively recent meta-analysis (5), which also was led by Driessen. This meta-analysis, which included both controlled and uncontrolled studies, generally supported the efficacy of psychodynamic psychotherapy (i.e., clinically meaningful differences in comparisons versus minimal or no treatment conditions), although the results of a subanalysis examining 13 randomized controlled trials that used “other psychotherapies” as an active comparison group suggested that psychodynamic psychotherapy may be less effective than other forms of therapy. Because all but three of these comparisons involved various cognitive and behavioral therapies, one might conclude that the results of the Driessen et al. prospective study (1) are at variance with those from the meta-analysis (5). As such, one might wonder which result is stronger and/or more believable: the one based on a single large-scale study or the one derived from a meta-analysis of a number of smaller studies?The likely answer to this question is that findings may accurately describe different aspects of the treatment research landscape. Specifically, in the prospective study, great efforts were taken to ensure that the two therapies were delivered with the same expertise and with comparable expectations of benefit. By contrast, some of the smaller studies included in the meta-analysis used a psychodynamic psychotherapy group as an active comparison group, which at times can be perceived by clinicians and patients alike as sort of a psychological “brand X” (6). The advantage of the other therapies in the meta-analysis was modest (an effect size of 0.3) and in the range of the so-called allegiance effect, in which the expertise (and, in all likelihood, the expectations, enthusiasm, and interpretive biases) of the principal investigator(s) has been shown to predict the outcome of the study (6). Thus, when compared on a level playing field, the two forms of therapy may be comparably useful for treatment of depressed outpatients, both singly and in combination with antidepressants.From another vantage point, whereas Driessen et al. demonstrated that psychodynamic psychotherapy was not inferior to CBT, they also showed that the outcomes of depressed outpatients were far from ideal, even when receiving good treatments from capable therapists. Indeed, the outcomes of both psychotherapy groups are strikingly comparable to those observed in the CBT arms included in the second level of the Sequenced Treatment Alternatives to Relieve Depression study (7), which likewise was an inclusive, multicenter study aimed at evaluating comparative effectiveness under real-world conditions. Since many clinicians may have already believed that the findings of Driessen et al. were true (i.e., the two therapies are comparably effective), perhaps the more important finding of this study is to underscore the harsh reality that we still need more effective treatments for major depressive disorder, and this need is as true for psychotherapy as it is for pharmacotherapy.From the Perelman School of Medicine of the University of Pennsylvania, Philadelphia.Address correspondence to Dr. Thase ([email protected]med.upenn.edu).Dr. Thase has served as a consultant to Alkermes, Allergan, AstraZeneca, Bristol-Myers Squibb, Dey, Eli Lilly, Forest Laboratories (PGx), Janssen Pharmaceutica, Lundbeck, Merck, Neuronetics, Novartis, Otsuka, Pfizer, Pharmaneuroboost, Roche, Shire, Takeda, and Transcept; he has received speaking fees from AstraZeneca, Dey, Lundbeck, and Pfizer; and he has received research funding from AstraZeneca, Eli Lilly, Forest Laboratories, Otsuka, Pfizer, PharmaNeuroboost, and Roche, as well as NIMH and the Agency for Healthcare Research and Quality. Dr. Thase’s spouse is an employee of Peloton Advantage, which does business with Pfizer. Dr. Freedman has reviewed this editorial and found no evidence of influence from these relationships.References1 Driessen E, Van HL, Don FJ, Peen J, Kool S, Westra D, Hendriksen M, Schoevers RA, Cuijpers P, Twisk JWR, Dekker JJM: The efficacy of cognitive-behavioral therapy and psychodynamic therapy in the outpatient treatment of major depression: a randomized clinical trial. Am J Psychiatry 2013; 170:1041–1050Link, Google Scholar2 Rush AJ, Beck AT, Kovacs M, Hollon SD: Comparative efficacy of cognitive therapy and pharmacotherapy in the treatment of depressed outpatients. Cognit Ther Res 1977; 1:17–38Crossref, Google Scholar3 McLean PD, Hakstian AR: Clinical depression: comparative efficacy of outpatient treatments. J Consult Clin Psychol 1979; 47:818–836Crossref, Medline, Google Scholar4 Weissman MM, Prusoff BA, Dimascio A, Neu C, Goklaney M, Klerman GL: The efficacy of drugs and psychotherapy in the treatment of acute depressive episodes. Am J Psychiatry 1979; 136(4B):555–558Abstract, Google Scholar5 Driessen E, Cuijpers P, de Maat SC, Abbass AA, de Jonghe F, Dekker JJ: The efficacy of short-term psychodynamic psychotherapy for depression: a meta-analysis. Clin Psychol Rev 2010; 30:25–36Crossref, Medline, Google Scholar6 Gaffan EA, Tsaousis I, Kemp-Wheeler SM: Researcher allegiance and meta-analysis: the case of cognitive therapy for depression. J Consult Clin Psychol 1995; 63:966–980Crossref, Medline, Google Scholar7 Thase ME, Friedman ES, Biggs MM, Wisniewski SR, Trivedi MH, Luther JF, Fava M, Nierenberg AA, McGrath PJ, Warden D, Niederehe G, Hollon SD, Rush AJ: Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR*D report. Am J Psychiatry 2007; 164:739–752Link, Google Scholar FiguresReferencesCited byDetailsCited byComparison of Clinical Significance of Cognitive-Behavioral Therapy and Psychodynamic Therapy for Major Depressive DisorderJournal of Nervous & Mental Disease, Vol. 206, No. 9Further Evidence for Short-Term Psychodynamic Therapy in Major Depressive Disorder5 January 2017 | The Canadian Journal of Psychiatry, Vol. 62, No. 1Clinical Psychology Review, Vol. 42The Empirical Status of Psychodynamic Psychotherapy - An Update: Bambi's Alive and Kicking28 March 2015 | Psychotherapy and Psychosomatics, Vol. 84, No. 3Depression and Anxiety, Vol. 31, No. 4Psychotherapeut, Vol. 59, No. 3Journal of Affective Disorders, Vol. 168Journal of Affective Disorders, Vol. 169Contemporary Psychoanalysis, Vol. 50, No. 1-2Psychoanalytic Psychotherapy, Vol. 28, No. 1Psychodynamic Psychiatry, Vol. 42, No. 1Psychodynamic Psychiatry, Vol. 42, No. 3The Psychoanalytic Review, Vol. 100, No. 6 Volume 170Issue 9 September 2013Pages 953-956 Metrics PDF download History Accepted 1 June 2013 Published online 1 September 2013 Published in print 1 September 2013

Bipolar Disorder (BD) and Major Depressive Disorder (MDD) have a huge impact on functioning and quality of life; moreover, they are linked to extensive direct and indirect costs. This systematic review with meta-analysis aims to evaluate the utility of pharmacogenetic tests (PGT) in terms of efficacy and tolerability into the routine clinical treatment of mood disorders.The first part of the review is a qualitative overview of the PGTs used in the included studies. The second part aims to compare, in terms of efficacy and tolerability, patients affected by BD and MDD treated as usual (TAU), according to the clinicians’ prescribing attitude, versus patients whose psychopharmacological treatments were set up following the PGT suggestions.6 studies on MDD and 2 studies on BD were included. Regarding MDD, the meta-analysis shows a significantly higher number of patients achieving better outcome in terms of efficacy, through the evaluation of response rate and remission rate at the HDRS (Hamilton Depression Rating Scale) in the group of patients treated under the PGT suggestions; regarding BD the meta-analysis does not show any significant difference in terms of efficacy. In terms of adverse events, the available data suggest promising results about the utility of PGT to set more tolerated therapies.Although the limited number of studies, results confirm the importance of PGT in setting up psychopharmacological therapies as a support to clinicians’ choices.

Bipolar disorder is a chronic illness that requires long-term treatment, the goal of which is to shorten or prevent mood episodes without increasing cycle frequency, thereby increasing the length of well periods. Treatment guidelines recommend mood stabilizers as first-line medications, and several atypical antipsychotics are also approved as monotherapy or as adjuncts to mood stabilizers for maintenance treatment. Combination therapy with 2 mood stabilizers or with a mood stabilizer and an antipsychotic may be necessary to achieve or maintain remission of the patient's symptoms. When treating patients with mood stabilizers and atypical antipsychotics during the maintenance phase, physicians should systematically monitor for adverse effects, particularly weight gain, and tolerability issues, and address those issues in a timely manner in order to enhance treatment adherence and improve patient outcomes.

Introduction Two 6-week, double-blind, placebo-controlled studies evaluated quetiapine XR (QTP-XR) adjunct to ongoing antidepressant therapy in patients with MDD and an inadequate response to prior antidepressant treatment (D14486/D14487). Objective and aim A post hoc pooled analysis examined clinical and demographic characteristics as potential predictors of response to adjunct QTP-XR Methods Pooled MITT population (n = 616 QTP-XR [both doses]; n = 303 placebo) data were analysed from the two adjunct QTP-XR (150 or 300 mg/day) studies. Effects of psychiatric history and baseline demographic and disease characteristics on efficacy were evaluated in subgroups based on Week 6 MADRS total score reduction: ≥50% reduction (responders: n = 345 QTP-XR, n = 140 placebo) versus Impact of baseline CGI-S score and number of episodes (0, 1, 2–3, 4–10, ≥10) over previous year and lifetime on Week 6 MADRS total score change was evaluated. Effect of baseline MADRS individual item (1–10) scores on Week 6 change in CGI-I score was evaluated. Results No major differences between responders and non-responders to QTP-XR were observed for patient characteristics. There was no predictive association between baseline CGI-S score, number of depressive episodes, and baseline MADRS item scores and efficacy outcomes for adjunct QTP-XR. Conclusions This pooled analysis showed no major differences between responders and non-responders, and no suggestion of a predictive association between the parameters assessed and efficacy outcomes for adjunct QTP-XR. Further investigation including logistic regression may be required. AstraZeneca funded.

This paper reviews the evidence on combining antidepressants (ADs) for treatment of major depressive disorder. Although widely used and usually safe, the efficacy of even the most widely prescribed combinations of ADs has not been established by properly controlled, adequately powered, clinical trials. This stands in contrast to several adjunctive strategies for AD nonresponders, including adjunctive lithium, thyroid hormone, or newer-generation antipsychotics. The wide use of AD combinations no doubt reflects the limited efficacy of commonly used ADs and the unmet need for effective strategies for patients with treatment-resistant depression. Although of unproven efficacy, potential merits of combining selected ADs include: 1) avoiding discontinuation-emergent symptoms and cross-titration schedules, 2) at worst, the second AD should be as effective in combination as it would be as a monotherapy following a switch, and 3) the possibility of complementary neuropharmacologic effects that may enhance efficacy or improve tolerability. The dearth of controlled studies of such a commonly used strategy for such a highly prevalent condition is symptomatic of shortcomings in the way clinically relevant research is funded, points to the need for industry–academic–federal collaborations, and underscores the need for large, practice-based, research groups that can efficiently complete publicly funded studies of high public health impact.

Attrition rates are high during treatment for major depressive disorder (MDD), and patients who drop out are less likely to reach remission. This report evaluates the incidence, timing, and predictors of attrition during second-step medication treatment. Outpatients in the multisite Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study receiving a medication augmentation (n=563) or medication switch (n=723) for non-psychotic MDD after an unsatisfactory outcome with citalopram were evaluated to determine attrition rates and pretreatment sociodemographic or clinical predictors of attrition. Twenty percent of participants receiving a medication augmentation and 27% receiving a medication switch dropped out before 12 wk in the second treatment step. Remission rates were lower for dropouts [7% vs. 43% (medication augmentation); 12% vs. 31% (medication switch)]. For medication augmentation, Black and other non-Caucasian races, Hispanic ethnicity, younger age, family history of drug abuse, concurrent drug abuse, sociodemographic disadvantage, less symptom improvement with initial citalopram treatment, and greater symptom severity when beginning augmentation were associated with attrition. For medication switch, Black and other non-Caucasian races, younger age, more melancholic features, and lower exit doses but more severe side-effects with citalopram treatment were associated with attrition. Minority status, younger age, and greater difficulty with the first treatment step are risk factors for attrition in the second treatment step. Focus on patients with attrition risk factors for medication augmentation or switch strategies may enhance retention and improve outcomes.