A Contextual Behavior Science Framework for Understanding How Behavioral Flexibility Relates to Anxiety.

There is a growing literature focusing on the emerging idea that behavioral flexibility, rather than particular emotion regulation strategies per se, provides greater promise in predicting and influencing anxiety-related psychopathology. Yet this line of research and theoretical analysis appear to be plagued by its own challenges. For example, middle-level constructs, such as behavioral flexibility, are difficult to define, difficult to measure, and difficult to interpret in relation to clinical interventions. A key point that some researchers have made is that previous studies examining flexible use of emotion regulation strategies (or, more broadly, coping) have failed due to a lack of focus on context. That is, examining strategies in isolation of the context in which they are used provides limited information on the suitability, rigid adherence, or effectiveness of a given strategy in that situation. Several of these researchers have proposed the development of new models to define and measure various types of behavioral flexibility. We would like to suggest that an explanation of the phenomenon already exists and that we can go back to our behavioral roots to understand this phenomenon rather than focusing on defining and capturing a new process. Indeed, thorough contextual behavioral analyses already yield a useful account of what has been observed. We will articulate a model explaining behavioral flexibility using a functional, contextual framework, with anxiety-related disorders as an example.

The Impact of Experiential Avoidance and Event Centrality in Trauma-Related Rumination and Posttraumatic Stress.

Cognitive control strategies like rumination often increase posttraumatic stress disorder (PTSD) symptoms. However, extant research has provided equivocal results when attempting to explain why this phenomenon occurs. The current study explored several mechanisms that may clarify such findings. For this study, 193 trauma-exposed community members completed measures of PTSD, rumination, experiential avoidance, and event centrality. Elevated reports of rumination were associated with greater PTSD symptomology, experiential avoidance, and event centrality. Results suggest that rumination indirectly influenced PTSD symptom severity through experiential avoidance. This pattern held true regardless of whether a trauma survivor viewed their reported trauma as central or peripheral to their personal identity. These data suggest that the link between ruminating about a traumatic experience and enhanced PTSD symptomology may be partially explained by increasingly restrictive cognitive patterns and enhanced avoidance of aversive internal stimuli. Furthermore, they provide preliminary evidence to suggest that rumination and experiential avoidance are strongly associated with one another (and subsequent PTSD symptomology) among trauma survivors, regardless of how central a traumatic event is to an individual's personal narrative. Such findings support clinical interventions like exposure, which progressively support new learning in response to feared or unwanted experiences in service of expanding an individual's cognitive and behavioral repertoires.

Sexual minority college students' perceptions on dating violence and sexual assault.

While the majority of research on dating violence (DV) and sexual assault (SA) in college students has focused on heterosexual students, victimization rates among sexual minority students are the same or higher than that of their heterosexual counterparts. The current study sought to explore sexual minority college students' perceptions of the prevalence of DV and SA, risk and protective factors, and barriers to seeking help, using focus groups. A total of 14 sexual minority students ranging in age from 18 to 24 participated across 2 focus groups. Findings suggest the majority of the students perceived DV and SA among sexual minority individuals to be less common compared to their heterosexual counterparts and to be less common on their campus compared to other colleges and universities. Students' reflections about risk and protective factors overlapped with those previously established among heterosexuals as well as factors unique to the sexual minority community. Students identified societal, community, and psychological-level barriers related to help-seeking. We provide recommendations for practice based on the current findings (e.g., colleges could expand current educational material about DV and SA to include more recognition of these issues for sexual minority students). (PsycINFO Database Record

A pilot study of acupuncture monotherapy in patients with major depressive disorder.

BACKGROUND: We have previously shown that a standardized acupuncture augmentation was effective for antidepressant partial responders with major depressive disorder (MDD). This pilot study examines the efficacy and safety of this protocol as monotherapy for MDD. METHODS: Thirty outpatients (73% female, mean age 47±12 yrs) with SCID-diagnosed MDD were recruited and received 8 weeks of standardized 30-minute open acupuncture treatment using 5 specific body points on the arms and legs bilaterally, with manual stimulation every 10 min, and concurrent electroacupuncture (2Hz current) at two points along the midline of the head. Subjects were assigned to once-weekly (n=21) or twice-weekly (n=9) treatment, depending on preference. Change in Hamilton-D-17 score was the primary outcome measure, and positive response to treatment (defined as ≥50% improvement in HAM-D-17 scores compared to baseline) was the secondary outcome measure. RESULTS: HAM-D-17 scores decreased from 19.1±4.4 to 9.9±6.3 (p<0.001) in the once-weekly acupuncture group, and from 21.9±5.3 to 14.3±6.1 (p=0.012) in the twice-weekly acupuncture group. Improvement did not differ significantly between treatment arms. Response rates were 62% for the once-weekly acupuncture group and 22% for the twice-weekly acupuncture group (NS). Twenty patients (14 in weekly treatment group and 6 in twice-weekly treatment group) completed the study. The most common side effects included mild soreness/pain (n=13), and mild bleeding (n=16) at the needle site. LIMITATIONS: Open design and small sample. CONCLUSIONS: Standardized acupuncture treatment was safe, well-tolerated and effective, suggesting good feasibility in outpatient settings. Replication in controlled trials is warranted.

Does the frequency of follow-up assessments affect clinical trial outcome? A meta-analysis and meta-regression of placebo-controlled randomized trials.

The number and temporal distribution of follow-up assessments during a clinical trial is a critical factor which may influence the outcome as well as the overall cost of a trial. Therefore, we aimed to examine whether the overall and differential frequency of study observations during the course of a clinical trial affects the risk ratio (RR) of responding to antidepressants vs. placebo, specifically in trials for major depressive disorder (MDD). Medline/Pubmed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants for adults with MDD (1 January 1980-11 May 2010). A total of 142 manuscripts involving 256 drug-placebo comparison were pooled (n=38 860). We found that higher overall frequency (OF, frequency of assessments during the entire trial) and higher late frequency (LF, frequency of assessments after the first 3 wk of the trial), but not higher early frequency (EF, frequency of assessments during the first 3 wk of the trial), of follow-up visits predicted a significantly greater RR of responding to antidepressant vs. placebo (coefficient=0.213, p=0.014; coefficient=0.238, p=0.003; and coefficient=0.021, p=0.755, respectively, for OF, LF and EF). None of the measures of frequency examined (OF, EF, LF) significantly predicted the RR of discontinuing antidepressant vs. placebo. These findings suggest that increasing the number of follow-up visits, specifically after the third week rather than within the first 3 wk of the trial, may be an effective approach to improve the likelihood of success in placebo-controlled clinical trials for MDD.

Do early changes in the HAM-D-17 anxiety/somatization factor items affect the treatment outcome among depressed outpatients? Comparison of two controlled trials of St John's wort (Hypericum perforatum) versus a SSRI.

To assess whether early changes in Hamilton Depression Rating Scale-17 anxiety/somatization items predict remission in two controlled studies of Hypericum perforatum (St John's wort) versus selective serotonin reuptake inhibitors for major depressive disorder. The Hypericum Depression Trial Study Group (National Institute of Mental Health) randomized 340 patients to Hypericum, sertraline, or placebo for 8 weeks, whereas the Massachusetts General Hospital study randomized 135 patients to Hypericum, fluoxetine, or placebo for 12 weeks. The investigators examined whether remission was associated with early changes in anxiety/somatization symptoms. In the National Institute of Mental Health study, significant associations were observed between remission and early improvement in the anxiety (psychic) item (sertraline arm), somatic (gastrointestinal item; Hypericum arm), and somatic (general) symptoms (placebo arm). None of the three treatment arms of the Massachusetts General Hospital study showed significant associations between anxiety/somatization symptoms and remission. When both study samples were pooled, we found associations for anxiety (psychic; selective serotonin reuptake inhibitors arm), somatic (gastrointestinal), and hypochondriasis (Hypericum arm), and anxiety (psychic) and somatic (general) symptoms (placebo arm). In the entire sample, remission was associated with the improvement in the anxiety (psychic), somatic (gastrointestinal), and somatic (general) items. The number and the type of anxiety/somatization items associated with remission varied depending on the intervention. Early scrutiny of the Hamilton Depression Rating Scale-17 anxiety/somatization items may help to predict remission of major depressive disorder.

Antidepressants for major depressive disorder in patients with a co-morbid axis-III disorder: a meta-analysis of patient characteristics and placebo response rates in randomized controlled trials.

The objective of this study is to assess whether the antidepressants are effective in treating major depressive disorder (MDD) in patients with a co-morbid axis-III disorder, and to compare the relative efficacy (vs. placebo) of antidepressants between these patients and those enrolled in general MDD trials. Medline/Pubmed publication databases were searched. We selected for randomized, double-blind, placebo-controlled trials of antidepressants for MDD, whether conducted in a general population, or in populations with an axis-III disorder. Antidepressants were more effective than placebo in patients with axis-III disorders overall [risk ratio for response (RR)=1.42, P<0.0001], as well as specifically for post-stroke (RR=1.43, P=0.04), human-immunodeficiency virus positive or acquired immunodeficiency syndrome (RR=1.66, P=0.005), but not cancer patients (RR=1.26, P=0.19). There was a trend for higher placebo response rates in studies, which did (41.2%) versus those which did not (37.7%) select for axis-III disorders (P=0.06), and significantly higher antidepressant response rates in studies which did (57.4%) versus those which did not (53.5%) select for axis-III disorders (P=0.01). Antidepressants are effective for MDD in patients who present with co-morbid axis-III disorders and as effective (vs. placebo) in this population as they are in the general MDD population. Higher general response rates observed in the co-morbid MDD population are intriguing, and require replication.

A pilot study of acupuncture augmentation therapy in antidepressant partial and non-responders with major depressive disorder.

BACKGROUND: Acupuncture is widely used for treating major depressive disorder (MDD). There is evidence supporting acupuncture as an antidepressant monotherapy, but its efficacy as augmentation in antidepressant partial and non-responders has not been well-investigated. METHODS: Thirty subjects (47% female, mean age 48±11 years) with a history of SCID-diagnosed MDD and partial or non-response after ≥8 weeks of antidepressant therapy were assigned 8 weeks of standardized 30-min open acupuncture augmentation sessions on a weekly (n=24) or twice-weekly (n=6) basis. Change in the Hamilton-D-17 score was the primary outcome measure, and response rates (based on HAM-D-17 score improvement of ≥50%) the secondary outcome. RESULTS: Twenty subjects (40% female; 18 in weekly and 2 in twice-weekly treatment) completed the study. In the intent-to-treat (ITT) sample (N=30), HAM-D-17 scores decreased from 18.5±3.8 to 11.2±5.3 in the weekly group (p<0.001), and from 18.5±3.3 to 11.8±4.8 in the twice-weekly group (p=0.03). Improvement did not differ significantly between treatment arms (p=0.76). Response rates were 47% for all ITT subjects, 50% for the weekly group and 33% for the twice-weekly group (p=0.66). The most common side effects included soreness/pain (n=7), bruising (n=4), and mild bleeding (n=1) at the needle site. One subject discontinued because of side effects (pain). LIMITATIONS: Open design, small sample, polypharmacy with antidepressants. CONCLUSIONS: Once or twice-weekly acupuncture augmentation was safe, well-tolerated and effective in antidepressant partial and non-responders, suggesting good feasibility in outpatient settings. Replication in controlled trials is warranted.

Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials.

OBJECTIVE: Late-life depression is an important public health issue, given the growing proportion of the elderly relative to the general population in the developed world. The purpose of this study was to examine the efficacy of antidepressants for the treatment of major depressive disorder (MDD) in elderly patients. DATA SOURCES: PubMed/MEDLINE was searched for randomized, double-blind, placebo-controlled trials of antidepressants for treatment of both adult (nonelderly) MDD (patients aged < 65 years) and late-life MDD (patients aged ≥ 55 years). The search was limited to articles published between January 1, 1980, and March 3, 2010 (inclusive). The year 1980 was used as a cutoff in our search to decrease diagnostic variability, since the DSM-III was introduced in 1980. Our search cross-referenced the term placebo with each of the following antidepressants: amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, trimipramine, protriptyline, dothiepin, doxepin, lofepramine, amoxapine, maprotiline, amineptine, nomifensine, bupropion, phenelzine, tranylcypromine, isocarboxazid, moclobemide, brofaromine, fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine, zimelidine, tianeptine, trazodone, nefazodone, agomelatine, venlafaxine, desvenlafaxine, duloxetine, milnacipran, reboxetine, mirtazapine, and mianserin. We also reviewed the reference lists of all studies identified through the PubMed/MEDLINE search. STUDY SELECTION: Articles were selected that reported on randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for treatment of MDD and that met numerous a priori criteria pertaining to MDD diagnosis criteria, study duration, study design, drug formulation, original data, age thresholds, primary and secondary outcome measures, and exclusions of other disorders. Final inclusion of articles was determined by consensus between the authors. Seventy-four articles were found eligible for inclusion in our analysis (15 late-life MDD trials and 59 adult MDD trials). RESULTS: Antidepressants were found to be efficacious for late-life MDD (age 55 and older; P < .0001), although there was evidence for heterogeneity across studies (Q22 = 67.302, P < .001). However, antidepressants were not found to be efficacious in the subset of studies using age thresholds of 65 years or older (older late-life MDD) (P = .265). Finally, when we controlled for study design characteristics, antidepressant but not placebo response rates were lower among late-life MDD patients than among adult MDD patients. CONCLUSIONS: The present meta-analysis suggests that antidepressants are efficacious in late-life MDD, but significant study heterogeneity suggests that other factors may contribute to these findings. A secondary analysis raises the possibility that efficacy of these agents may be reduced in trials involving patients aged 65 years or older. Why antidepressants may be less efficacious in elderly versus younger subjects remains unclear.

Fluoxetine-clonazepam cotherapy for anxious depression: an exploratory, post-hoc analysis of a randomized, double blind study.

Anxious depression, defined as major depressive disorder (MDD) accompanied by high levels of anxiety, seems to be both common and difficult to treat, with antidepressant monotherapy often yielding modest results. We sought to examine the relative benefits of antidepressant-anxiolytic cotherapy versus antidepressant monotherapy for patients with anxious depression versus without anxious depression. We conducted a post-hoc analysis of an existing dataset (N=80), from a 3-week, randomized, double-blind trial which demonstrated cotherapy with fluoxetine and clonazepam to result in superior efficacy than fluoxetine monotherapy in MDD. The present analysis involved examining whether anxious depression status served as a predictor and moderator of symptom improvement. Anxious depression status was not found to predict symptom improvement, or serve as a moderator of clinical improvement to cotherapy versus monotherapy. However, the advantage in remission rates in favor of cotherapy versus monotherapy was, numerically, much larger for patients with anxious depression (32.2%) than it was for patients without anxious MDD (9.7%). The respective number needed to treat statistic for these two differences in response rates were, approximately, one in three for patients with anxious depression versus one in 10 for patients without anxious depression. The efficacy of fluoxetine-clonazepam cotherapy compared with fluoxetine monotherapy was numerically but not statistically enhanced for patients with anxious depression than those without anxious depression.