Predictors of clinical worsening during a discontinuation trial of serotonin reuptake inhibitors for obsessive compulsive disorder.

OBJECTIVE: To explore predictors and moderators of clinical worsening during a double-blind trial in which patients with obsessive-compulsive disorder (OCD) were randomized to either continue or discontinue their Serotonin Reuptake Inhibitor (SRI) medication after achieving wellness from the addition of exposure and response prevention (EX/RP) therapy. METHOD: The data came from a double-blind discontinuation trial that included N = 101 participants, 35 of whom were removed from the study due to clinical worsening. We first used LASSO logistic regression to identify which of the 34 potential baseline variables of interest (including demographics, diagnoses, other relevant clinical constructs, and specific genotypes), might moderate or predict this clinical worsening. Then logistic regression was used to examine which of these identified variables were significantly related to later clinical worsening. We verified the validity of our final prediction model using k-fold cross-validation. RESULTS: There was one significant predictor of clinical worsening: In both groups, those with more past diagnoses had a greater likelihood of clinical worsening (p = .015). There were several moderators. Rates of clinical worsening were higher in the Discontinuation group compared to the Continuation group for participants who were taking a shorter half-life SRI (p = .044), were female (p = .022), had higher baseline levels of maladaptive metacognitions (p < .001), had fewer sleep problems at baseline (p = .001), and/or had more years of education (p < .001). CONCLUSIONS: Our results identified several factors that may predict the development of clinical worsening in OCD patients discontinuing SRI medication following successful EX/RP treatment.

Maintenance of Wellness in Patients With Obsessive-Compulsive Disorder Who Discontinue Medication After Exposure/Response Prevention Augmentation: A Randomized Clinical Trial.

IMPORTANCE: Serotonin reuptake inhibitors (SRIs) are the only medications approved for obsessive-compulsive disorder (OCD), yet most patients taking SRIs exhibit significant symptoms. Adding exposure/response prevention (EX/RP) therapy improves symptoms, but it is unknown whether patients maintain wellness after discontinuing SRIs. OBJECTIVE: To assess whether patients with OCD who are taking SRIs and have attained wellness after EX/RP augmentation can discontinue their SRI with noninferior outcomes compared with those who continue their SRI therapy. DESIGN, SETTING, AND PARTICIPANTS: A 24-week, double-blind, randomized clinical trial was performed from May 3, 2013, to June 25, 2018. The trial took place at US academic medical centers. Participants included 137 adults with a principal diagnosis of OCD (≥1 year) who were taking an SRI (≥12 weeks), had at least moderate symptoms (defined as Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] score ≥18 points), and received as many as 25 sessions of EX/RP therapy. Those who attained wellness (Y-BOCS score ≤14 points; 103 patients [75.2%]) were study eligible. Data were analyzed from June 29, 2019, to October 2, 2021. INTERVENTION: Participants were randomly assigned either to receive taper to placebo (taper group) or to continue their SRI (continuation group) and monitored for 24 weeks. MAIN OUTCOME AND MEASURES: The Y-BOCS score (range, 0-40 points) was the primary outcome; the Hamilton Depression Rating Scale (HDRS; range, 0-52 points) and the Quality-of-Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF; range, 0%-100%) scores were secondary outcomes. Outcomes were assessed at 8 time points by independent evaluators who were blinded to randomization. The taper regimen was hypothesized to be noninferior to continuation at 24 weeks using a 1-sided α value of .05. RESULTS: A total of 101 patients (mean [SD] age, 31.0 [11.2] years; 55 women [54.5%]) participated in the trial: 51 patients (50.5%) in the taper group and 50 patients (49.5%) in the continuation group. At 24 weeks, patients in the taper group had noninferior results compared with patients in the continuation group (mean [SD] Y-BOCS score: taper group, 11.47 [6.56] points; continuation group: 11.51 [5.97] points; difference, -0.04 points; 1-sided 95% CI, -∞ to 2.09 points [below the noninferiority margin of 3.0 points]; mean [SD] HDRS score: taper group, 5.69 [3.84] points; continuation group, 4.61 [3.46] points; difference, 1.08 points; 1-sided 95% CI, -∞ to 2.28 points [below the noninferiority margin of 2.5 points]; mean [SD] Q-LES-Q-SF score: taper group, 68.01% [15.28%]; continuation group, 70.01% [15.59%]; difference, 2.00%; 1-sided 95% CI, -∞ to 6.83 [below the noninferiority margin of 7.75]). However, the taper group had higher rates of clinical worsening (23 of 51 [45%] vs 12 of 50 [24%]; P = .04). CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial show that patients with OCD who achieve wellness after EX/RP therapy could, on average, discontinue their SRI with noninferior outcomes compared with those who continued their SRI. Those who tapered the SRI had higher clinical worsening rates. Future research should evaluate if SRI half-life alters these rates. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01686087.

The Association of Obsessive-Compulsive Disorder, Anxiety Disorders, and Posttraumatic Stress Disorder with Impairment Related to Eating Pathology.

Prior work has shown a number of similarities between obsessive-compulsive disorder (OCD) and eating disorders such as perfectionism and depressive symptoms. However, distress and impairment due to eating pathology are also highly comorbid with other disorders, which brings into question whether the relationship with eating pathology is unique to OCD. The aims of the current study were 1) to test perfectionism and depression as mediators of the relationship between OCD and eating pathology, and 2) to determine whether OCD is related to greater distress/impairment regarding eating habits, exercising, or feelings about eating, shape, or weight above and beyond other disorders. Symptoms were assessed in 329 treatment-seeking patients in a secondary analysis of a clinical battery. The results showed that depressive symptoms and perfectionism were found to mediate the relationship between OCD and eating pathology. Additionally, a regression analysis showed that OCD, social anxiety disorder, and panic disorder symptoms were associated with eating pathology to a greater extent than other disorders. These results suggest that distress and impairment related to eating habits, exercising, or feelings about eating, shape, or weight are not unique to OCD and that depression and perfectionism may, in part, explain the association between OCD and eating pathology.

Maximizing remission from cognitive-behavioral therapy in medicated adults with obsessive-compulsive disorder.

Practice guidelines for adults with obsessive-compulsive disorder (OCD) recommend augmenting serotonin reuptake inhibitors (SRIs) with exposure and ritual prevention (EX/RP). However, fewer than half of patients remit after a standard 17-session EX/RP course. We studied whether extending the course increased overall remission rates and which patient factors predicted remission. Participants were 137 adults with clinically significant OCD (Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score ≥18) despite an adequate SRI trial (≥12 weeks). Continuing their SRI, patients received 17 sessions of twice-weekly EX/RP (standard course). Patients who did not remit (Y-BOCS ≤12) received up to 8 additional sessions (extended course). Of 137 entrants, 123 completed treatment: 49 (35.8%) remitted with the standard course and another 46 (33.6%) with the extended course. Poorer patient homework adherence, more Obsessive-Compulsive Personality Disorder (OCPD) traits, and the Brain-Derived Neurotrophic Factor (BDNF) Val66MET genotype were associated with lower odds of standard course remission. Only homework adherence differentiated non-remitters from extended course remitters. Extending the EX/RP course from 17 to 25 sessions enabled many (69.3%) OCD patients on SRIs to achieve remission. Although behavioral (patient homework adherence), psychological (OCPD traits), and biological (BDNF genotype) factors influenced odds of EX/RP remission, homework adherence was the most potent patient factor overall.

Trauma-Related Cognitions and Cognitive Emotion Regulation as Mediators of PTSD Change Among Treatment-Seeking Active-Duty Military Personnel With PTSD.

Trauma-related cognitions about the self and the world have been identified as a mediator of posttraumatic stress disorder (PTSD) change during prolonged exposure (PE) therapy. However, the extent to which negative cognitions mediate PTSD change in other PTSD treatments is unclear. In addition, previous studies have not tested alternate mediators of PTSD change during PE. In a sample of 216 treatment-seeking active-duty military personnel with PTSD, the present study examined the specificity of the negative cognition mediation effect in both PE and present-centered therapy (PCT). In addition, we examined another possible mediator, cognitive emotion regulation. Lagged mediational analyses indicated that negative cognitions about the self and world and the unhelpful cognitive emotion regulation strategy of catastrophizing each significantly mediated change in PTSD from baseline to 6-month follow-up. In a combined model, the mediating effect of catastrophizing was greater than negative cognitions about the world, and similar to negative cognitions about the self. Moderated mediation analyses revealed that the effect of catastrophizing was greater in PE than in PCT. Findings show that trauma-related cognitions and, to a greater degree, the emotion regulation strategy catastrophizing, both mediate PTSD change. Further research is needed to determine whether these mediating variables represent mechanisms of therapeutic change.

Does CBT for anxiety-related disorders alter suicidal ideation? Findings from a naturalistic sample.

BACKGROUND: Anxiety disorders commonly co-occur with suicidal ideation (SI). To our knowledge, no studies have reported on the baseline prevalence of SI and the reduction in SI in a naturalistic sample receiving cognitive behavior therapy (CBT) for anxiety-related disorders. METHODS: Participants (n = 355) recruited from an anxiety specialty clinic reported SI at pre-, mid-, and post-CBT. Multilevel mixed effects logistic regression models compared differences in SI endorsement over Time. RESULTS: Posttraumatic stress disorder (PTSD) and social anxiety disorder (SAD) were associated with significantly elevated baseline SI relative to specific phobia. PTSD and unspecified anxiety-related disorders were associated with significant reductions in SI, whereas reductions in SAD, GAD, OCD, and panic disorder did not reach significance. Rates of new onset and exacerbation of SI were low. DISCUSSION: CBT for anxiety disorders was associated with significant reductions in SI over time, with no evidence for exacerbation of suicide risk. Clinical implications are discussed, as well as future research directions to further understand the effect of anxiety disorder treatments on SI.

Behavioral avoidance predicts treatment outcome with exposure and response prevention for obsessive-compulsive disorder.

BACKGROUND: Many individuals with obsessive-compulsive disorder (OCD) display behavioral avoidance related to their obsessional thoughts and compulsive behaviors. However, how these avoidance behaviors impact treatment outcomes with exposure and response prevention (EX/RP) remains unclear. We examined pretreatment avoidance behaviors as predictors of EX/RP outcomes. METHODS: Data came from a randomized controlled trial of augmentation strategies for inadequate response to serotonin reuptake inhibitors comparing EX/RP (N = 40), risperidone (N = 40), and placebo (N = 20). Baseline avoidance was rated with the avoidance item from the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Primary analyses examined avoidance behaviors as predictors of EX/RP outcomes. To test specificity, we explored whether avoidance also related to outcomes among patients receiving risperidone and placebo. RESULTS: More than half (69%) of the full sample had moderate or severe avoidance behaviors at baseline. In EX/RP, controlling for baseline severity, pretreatment avoidance predicted posttreatment YBOCS symptoms (ß = 0.45, P < .01). Avoidant individuals were less likely to achieve remission with EX/RP (odds ratio = 0.04, 95% confidence interval [CI] range 0.01-0.28, P = .001). Baseline avoidance was also associated with degree of patient adherence to between-session EX/RP assignments, which mediated the relationship between baseline avoidance and EX/RP outcomes (P < .05). Baseline avoidance did not predict outcomes or wellness among patients receiving risperidone or placebo. CONCLUSIONS: These results suggest that avoidance behaviors are an important clinical factor in EX/RP outcomes and indicate that assessing avoidance may provide an efficient method for predicting EX/RP outcomes. Avoidance may be particularly relevant in EX/RP as compared to medication treatment, though future replication of these initial results is required.

The impact of social support, unit cohesion, and trait resilience on PTSD in treatment-seeking military personnel with PTSD: The role of posttraumatic cognitions.

BACKGROUND: The personal resources of social support, unit cohesion, and trait resilience have been found to be associated with posttraumatic stress disorder (PTSD) severity among military personnel. However, the underlying mechanisms of these relationships are unclear. We hypothesized that negative posttraumatic cognitions, which are associated with PTSD, mediate the relationships between these personal resources and PTSD. METHODS: The relationship between PTSD symptom severity and a latent factor comprised of social support, unit cohesion, and trait resilience was evaluated using cross-sectional data from 366 treatment-seeking active duty military personnel with PTSD following deployments to or near Iraq or Afghanistan. Structural equation modeling (SEM) was used to test whether posttraumatic cognitions mediated this relationship. RESULTS: The SEM model indicated that (1) a robust latent variable named personal resources (indicated by social support, unit cohesion, and trait resilience) was negatively associated with PTSD severity; (2) personal resources were negatively associated with negative posttraumatic cognitions; (3) negative posttraumatic cognitions fully mediated the association between personal resources and PTSD severity. The final SEM mediation model showed a highly satisfactory fit [χ2 (22) = 16.344, p = 0.798; χ2/df = 0.743; CFI = 1; RMSEA = 0.000]. CONCLUSIONS: These findings suggest that among active duty military personnel seeking treatment for PTSD, personal resources (social support, unit cohesion, and trait resilience) may mitigate PTSD severity by reducing negative posttraumatic cognitions.