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A double-blind randomized controlled trial of augmentation and switch strategies for refractory social anxiety disorder

Pollack, Mark H; Van Ameringen, Michael; Simon, Naomi M; Worthington, John W; Hoge, Elizabeth A; Keshaviah, Aparna; Stein, Murray B
OBJECTIVE: Most patients remain symptomatic after an initial intervention with approved treatments for generalized social anxiety disorder. This randomized controlled trial provides systematic, prospectively derived data on the relative benefits of "next-step" pharmacotherapies to improve outcomes for individuals with generalized social anxiety disorder who remain symptomatic after initial treatment. METHOD: This three site, 12-week, double-blind randomized controlled trial compared the relative benefits of three strategies for patients remaining symptomatic (Liebowitz Social Anxiety Scale [LSAS] score >50) after a 10-week trial of sertraline alone: the addition of up to 3.0 mg/day of clonazepam (sertraline plus clonazepam), a switch to up to 225 mg/day of venlafaxine, or prolonged sertraline treatment with placebo (sertraline plus placebo). RESULTS: A total of 397 participants received at least one dose of sertraline; 181 nonresponders (LSAS score >50) at week 10 were randomly assigned to sertraline plus clonazepam, switch to venlafaxine, or sertraline plus placebo. Overall, 21% of patients achieved remission (LSAS score
PMID: 24399428
ISSN: 1535-7228
CID: 2281322

A Cross-sectional Examination of Telomere Length and Telomerase in a Well-Characterized Sample of Individuals with Major Depressive Disorder Compared to Controls [Meeting Abstract]

Simon, Naomi M; Walton, Zandra; Prescott, Jennifer; Hoge, Elizabeth; Keshaviah, Aparna; Bui, THEric; Schwarz, Noah; Dryman, Taylor; Ojserkis, Rebecca A; Mischoulon, David; Worthington, John; DeVivo, Immaculata; Fava, Maurizio; Wong, Kwok-Kin
ISI:000209477100527
ISSN: 1740-634x
CID: 2725622

Complicated grief symptoms in anxiety disorders: prevalence and associated impairment

Marques, Luana; Bui, Eric; LeBlanc, Nicole; Porter, Eliora; Robinaugh, Donald; Dryman, M Taylor; Nadal-Vicens, Mireya; Worthington, John; Simon, Naomi
BACKGROUND: Previous research has identified high rates of comorbid anxiety disorders among individuals presenting with primary CG. In the present study, we examined the prevalence of comorbid CG in bereaved primary anxiety disorder (AD) patients compared to bereaved healthy controls. We also examined the impairment associated with comorbid CG in AD. METHODS: Participants were 242 bereaved adults (mean (SD) age = 41.5 (13.1), 44.2% women) with a primary AD diagnosis, including generalized anxiety disorder (GAD; n = 57), panic disorder (PD; n = 49), posttraumatic stress disorder (PTSD; n = 29), and generalized social anxiety disorder (GSAD; n = 107), as well as 155 bereaved healthy controls with no current DSM-IV Axis I diagnosis (mean (SD) age = 43.0 (13.6), 51.0% women). CG symptoms were measured using the 19-item inventory of complicated grief (ICG), with threshold CG defined as an ICG score of >/=30. Quality of life and functional impairment were assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Range of Impaired Functioning Tool (LIFE-RIFT), respectively. RESULTS: Participants with primary ADs had significantly higher rates of threshold CG symptoms than bereaved controls (12.0% vs. 0.65%; Fisher's Exact P < 0.001). Rates of threshold CG were significantly elevated for each AD when compared to bereaved controls. After adjustment for age, sex, education, and comorbid major depressive disorder, threshold CG was associated with lower quality of life (beta = -0.140, P = 0.023) and greater impairment (beta = 0.141, P = 0.035) among individuals with AD. CONCLUSIONS: Our findings suggest that threshold CG is of clinical relevance in bereaved individuals with a primary anxiety disorder. Screening for CG in patients with ADs may be warranted.
PMCID:4038035
PMID: 23495105
ISSN: 1520-6394
CID: 2725022

D-cycloserine augmentation of cognitive behavioral group therapy of social anxiety disorder: prognostic and prescriptive variables

Smits, Jasper A J; Hofmann, Stefan G; Rosenfield, David; DeBoer, Lindsey B; Costa, Paul T; Simon, Naomi M; O'Cleirigh, Conall; Meuret, Alicia E; Marques, Luana; Otto, Michael W; Pollack, Mark H
OBJECTIVE: The aim of the current study was to identify individual characteristics that (a) predict symptom improvement with group cognitive behavioral therapy (CBT) for social anxiety disorder (SAD; i.e., prognostic variables) or (b) moderate the effects of d-cycloserine (DCS) versus placebo augmentation of CBT for SAD (i.e., prescriptive variables). METHOD: Adults with SAD (N = 169) provided Liebowitz Social Anxiety Scale scores in a trial evaluating DCS augmentation of group CBT. Rate of symptom improvement during therapy and posttreatment symptom severity were evaluated using multilevel modeling. As predictors of these 2 parameters, we selected the range of variables assessed at baseline (demographic characteristics, clinical characteristics, personality traits). Using step-wise analyses, we first identified prognostic and prescriptive variables within each of these domains and then entered these significant predictors simultaneously in 1 final model. RESULTS: African American ethnicity and cohabitation status were associated with greater overall rates of improvement during therapy and lower posttreatment severity. Higher initial severity was associated with a greater improvement during therapy but also higher posttreatment severity (the greater improvement was not enough to overcome the initial higher severity). DCS augmentation was evident only among individuals low in conscientiousness and high in agreeableness. CONCLUSIONS: African American ethnicity, cohabitation status, and initial severity are prognostic of favorable CBT outcomes in SAD. DCS augmentation appears particularly useful for patients low in conscientiousness and high in agreeableness. These findings can guide clinicians in making decisions about treatment strategies and can help direct research on the mechanisms of these treatments.
PMCID:4241751
PMID: 23937345
ISSN: 1939-2117
CID: 2724982

Development of a brief version of the Social Phobia Inventory using item response theory: the Mini-SPIN-R

Aderka, Idan M; Pollack, Mark H; Simon, Naomi M; Smits, Jasper A J; Van Ameringen, Michael; Stein, Murray B; Hofmann, Stefan G
The Social Phobia Inventory (SPIN) is a widely used measure in mental health settings and a 3-item version (mini-SPIN) has been developed as a screening instrument for social anxiety disorder. In the present study, we examined the psychometric properties of the SPIN and developed a brief version (mini-SPIN-R) designed to assess social anxiety severity using item response theory. Our sample included 569 individuals with social anxiety disorder who participated in 2 clinical trials and filled out a battery of self-report measures. Using a nonparametric kernel smoothing method we identified the most sensitive items of the SPIN. These 3 items comprised the mini-SPIN-R, which was found to have greater internal consistency, and to capture a greater range of symptoms compared to the mini-SPIN. The mini-SPIN-R evidenced superior convergent validity compared to the mini-SPIN and both measures had similar divergent validity. Thus, the mini-SPIN-R is a promising brief measure of social anxiety severity.
PMID: 24094790
ISSN: 1878-1888
CID: 2724972

Sleep quality predicts treatment outcome in CBT for social anxiety disorder

Zalta, Alyson K; Dowd, Sheila; Rosenfield, David; Smits, Jasper A J; Otto, Michael W; Simon, Naomi M; Meuret, Alicia E; Marques, Luana; Hofmann, Stefan G; Pollack, Mark H
BACKGROUND: Sleep quality may be an important, yet relatively neglected, predictor of treatment outcome in cognitive-behavioral therapy (CBT) for anxiety disorders. Specifically, poor sleep quality may impair memory consolidation of in-session extinction learning. We therefore examined sleep quality as a predictor of treatment outcome in CBT for social anxiety disorder and the impact of d-cycloserine (DCS) on this relationship. METHODS: One hundred sixty-nine participants with a primary diagnosis of DSM-IV generalized social anxiety disorder were recruited across three sites. Participants were enrolled in 12 weeks of group CBT. Participants randomly received 50 mg of DCS (n = 87) or pill placebo (n = 82) 1 hr prior to sessions 3-7. Participants completed a baseline measure of self-reported sleep quality and daily diaries recording subjective feelings of being rested upon wakening. Outcome measures including social anxiety symptoms and global severity scores were assessed at each session. RESULTS: Poorer baseline sleep quality was associated with slower improvement and higher posttreatment social anxiety symptom and severity scores. Moreover, patients who felt more "rested" after sleeping the night following a treatment session had lower levels of symptoms and global severity at the next session, controlling for their symptoms and severity scores the previous session. Neither of these effects were moderated by DCS condition. CONCLUSIONS: Our findings suggest that poor sleep quality diminishes the effects of CBT for social anxiety disorder and this relation is not attenuated by DCS administration. Therapeutic attention to sleep quality prior to initiation of CBT and during the acute treatment phase may be clinically indicated.
PMCID:4043139
PMID: 24038728
ISSN: 1520-6394
CID: 2281292

D-cycloserine enhancement of exposure therapy for social anxiety disorder depends on the success of exposure sessions

Smits, Jasper A J; Rosenfield, David; Otto, Michael W; Marques, Luana; Davis, Michelle L; Meuret, Alicia E; Simon, Naomi M; Pollack, Mark H; Hofmann, Stefan G
OBJECTIVE: The evidence for the efficacy of D-cycloserine (DCS) for augmenting cognitive behavioral therapy (CBT) for anxiety disorders has been mixed. Guided by preclinical research and initial findings from a small-scale study involving humans, we tested the hypothesis that DCS enhancement of exposure therapy would be specific to successful exposure sessions. METHOD: Medication-free adults with generalized social anxiety disorder (N = 145) received 50 mg of DCS or placebo 1 h before each of 5 exposure sessions that were part of a standardized 12-session group CBT protocol. Participants provided fear ratings at the beginning and just before the end of exposure exercises. Independent raters, blind to group assignment, administered the clinical global impression improvement and severity scales at each session and at posttreatment. RESULTS: Mixed-effects analyses revealed that, among patients who reported low fear at the end of an exposure session, those who had received DCS evidenced significantly greater clinical improvement at the next session, relative to those who had received placebo. In contrast, when exposure end fear was high, patients receiving DCS exhibited less clinical improvement at the following session than patients receiving placebo. Similarly, patients who had received DCS evidenced lower clinical severity at posttreatment, relative to patients who had received placebo, only when their average end fear for medication-augmented sessions had been in the low to moderate range. Finally, these moderating effects of exposure success as indexed by end fear were not better accounted for by within-session extinction. CONCLUSIONS: The efficacy of DCS for augmenting exposure-based CBT depends on the success of exposure sessions. These findings may help guide the development of an algorithm for the effective use of DCS for augmenting exposure-based CBT. TRIAL REGISTRY: http://www.ClinicalTrials.gov, ID# NCT00633984, http://www.clinicaltrials.gov/ct2/show/NCT00633984.
PMCID:3747985
PMID: 23870811
ISSN: 1879-1379
CID: 2281282

Smiles may go unseen in generalized social anxiety disorder: evidence from binocular rivalry for reduced visual consciousness of positive facial expressions

Anderson, Eric C; Dryman, M Taylor; Worthington, John; Hoge, Elizabeth A; Fischer, Laura E; Pollack, Mark H; Barrett, Lisa Feldman; Simon, Naomi M
Research has demonstrated increased attention to negative social cues and reduced attention to positive social cues in generalized social anxiety disorder (GSAD), but little is known about whether GSAD also involves differences in lower levels of visual processing. This study explored visual experience in GSAD compared to participants with generalized anxiety disorder (GAD) and healthy controls using binocular rivalry. Participants were presented with dissimilar images to each eye, and the two images competed for perceptual dominance. Consistent with the hypothesis that GSAD involves a reduced visual salience for positive social cues, we found that smiling faces were dominant for significantly shorter durations in GSAD compared to GAD and controls. Contrasting with our hypothesis of greater visual salience of negative social cues, we found no difference in negative stimuli salience. These findings are consistent with the broader view that a perceiver's affective state directly influences the content of visual consciousness.
PMID: 24064330
ISSN: 1873-7897
CID: 2281302

Two weeks of pretreatment with escitalopram facilitates extinction learning in healthy individuals

Bui, Eric; Orr, Scott P; Jacoby, Ryan J; Keshaviah, Aparna; LeBlanc, Nicole J; Milad, Mohammed R; Pollack, Mark H; Simon, Naomi M
OBJECTIVE: We aimed to examine whether pretreatment with escitalopram would be associated with reduced fear acquisition and enhanced extinction learning in a fear conditioning paradigm, compared with placebo. METHODS: Healthy volunteers were randomized in double-blind fashion, to 14 days of escitalopram 10 mg/day (n = 18) or placebo (n = 20) prior to a classical fear conditioning paradigm. RESULTS: Although escitalopram was associated with a smaller skin conductance (SC) orienting response during habituation, no medication effects on fear acquisition were found. Escitalopram was associated with faster extinction of SC responses, compared with placebo, as revealed by a significant drug x conditioned stimulus x trial interaction for early extinction (F(3, 30) = 3.26, p = 0.035) and late extinction (F(3, 30) = 3.27, p = 0.035) trials. After adjustment for age, orienting response, and acquisition, results from linear contrast remained significant for early extinction (F(1, 29) = 5.43, p = 0.027). CONCLUSIONS: Escitalopram administered for 14 days prior to a fear conditioning paradigm did not influence acquisition of a conditioned fear response but did facilitate extinction learning. Impairments in extinction learning have been identified as a key component of posttraumatic stress disorder; our preliminary findings suggest that additional experimental and clinical studies assessing the efficacy of selective serotonin reuptake inhibitors for posttraumatic stress disorder prevention are warranted.
PMID: 23776033
ISSN: 1099-1077
CID: 2281252

Normal grief and complicated bereavement among traumatized Cambodian refugees: cultural context and the central role of dreams of the dead [Case Report]

Hinton, Devon E; Peou, Sonith; Joshi, Siddharth; Nickerson, Angela; Simon, Naomi M
This article profiles bereavement among traumatized Cambodian refugees and explores the validity of a model of how grief and post-traumatic stress disorder (PTSD) interact in this group to form a unique bereavement ontology, a model in which dreams of the dead play a crucial role. Several studies were conducted at a psychiatric clinic treating Cambodian refugees who survived the Pol Pot genocide. Key findings included that Pol Pot deaths were made even more deeply disturbing owing to cultural ideas about "bad death" and the consequences of not performing mortuary rites; that pained recall of the dead in the last month was common (76 % of patients) and usually caused great emotional and somatic distress; that severity of pained recall of the dead was strongly associated with PTSD severity (r = .62); that pained recall was very often triggered by dreaming about the dead, usually of someone who died in the Pol Pot period; and that Cambodians have a complex system of interpretation of dreams of the deceased that frequently causes those dreams to give rise to great distress. Cases are provided that further illustrate the centrality of dreams of the dead in the Cambodian experiencing of grief and PTSD. The article shows that not assessing dreams and concerns about the spiritual status of the deceased in the evaluation of bereavement results in "category truncation," i.e., a lack of content validity, a form of category fallacy.
PMCID:3759644
PMID: 23868080
ISSN: 1573-076x
CID: 2281272