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.

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.

Acceptability, Feasibility, and Effectiveness of Internet-Based Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder in New York.

Cognitive-behavioral therapy (CBT), consisting of exposure and response prevention (EX/RP), is both efficacious and preferred by patients with obsessive-compulsive disorder (OCD), yet few receive this treatment in practice. This study describes the implementation of an Internet-based CBT program (ICBT) developed in Sweden in individuals seeking OCD treatment in New York. After translating and adapting the Swedish ICBT for OCD, we conducted an open trial with 40 adults with OCD. Using the RE-AIM implementation science framework, we assessed the acceptability, feasibility, and effectiveness of ICBT. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was the primary outcome measure. Of 40 enrolled, 28 participants completed the 10-week ICBT. In the intent-to-treat sample (N = 40), Y-BOCS scores decreased significantly over time (F = 28.12, df = 2, 49, p < . 001). Depressive severity (F = 5.87, df = 2, 48, p < . 001), and quality of life (F = 12.34, df = 2, 48, p < . 001) also improved. Sensitivity analyses among treatment completers (N = 28) confirmed the intent-to-treat results, with a large effect size for Y-BOCS change (Cohen's d = 1.38). ICBT took less time to implement than face-to face EX/RP and participants were very to mostly satisfied with ICBT. On a par with results in Sweden, the adapted ICBT program reduced OCD and depressive symptoms and improved quality of life among individuals with moderate to severe OCD. Given its acceptability and feasibility, ICBT deserves further study as a way to increase access to CBT for OCD in the United States.

Six-month follow-up of a randomized controlled trial augmenting serotonin reuptake inhibitor treatment with exposure and ritual prevention for obsessive-compulsive disorder.

OBJECTIVE: This article describes the long-term effects of augmenting serotonin reuptake inhibitors (SRIs) with exposure and ritual prevention or stress management training in patients with DSM-IV obsessive-compulsive disorder (OCD). METHOD: Between November 2000 and November 2006, 111 OCD patients from 2 academic outpatient centers with partial SRI response were randomized to the addition of exposure and ritual prevention or stress management training, delivered twice weekly for 8 weeks (acute phase); 108 began treatment. Responders (38 of 52 in the exposure and ritual prevention condition, 11 of 52 in the stress management training condition) entered a 24-week maintenance phase. The Yale-Brown Obsessive Compulsive Scale (YBOCS) was the primary outcome measure. RESULTS: After 24 weeks, patients randomized to and receiving exposure and ritual prevention versus stress management training had significantly better outcomes (mean YBOCS scores of 14.69 and 21.37, respectively; t = 2.88, P = .005), higher response rates (decrease in YBOCS scores ≥ 25%: 40.7% vs 9.3%, Fisher exact test P < .001), and higher rates of excellent response (YBOCS score ≤ 12: 24.1% vs 5.6%, Fisher exact test P = .01). During the maintenance phase, the slope of change in YBOCS scores was not significant in either condition (all P values ≥ .55), with no difference between exposure and ritual prevention and stress management training (P > .74). Better outcome was associated with baseline variables: lower YBOCS scores, higher quality of life, fewer comorbid Axis I diagnoses, and male sex. CONCLUSIONS: Augmenting SRIs with exposure and ritual prevention versus stress management training leads to better outcome after acute treatment and 24 weeks later. Maintenance outcome, however, was primarily a function of OCD severity at entrance. Greater improvement during the acute phase influences how well patients maintain their gains, regardless of treatment condition.

Challenges using motivational interviewing as an adjunct to exposure therapy for obsessive-compulsive disorder.

Exposure and response prevention (EX/RP) is an efficacious treatment for obsessive-compulsive disorder (OCD). However, patients often do not adhere fully to EX/RP procedures. Motivational interviewing (MI) has been shown to improve treatment adherence in other disorders. This pilot study used a randomized controlled design to examine whether MI can be successfully added to EX/RP and whether this intervention (EX/RP+MI) could improve patient adherence to between-session EX/RP procedures relative to EX/RP alone. Thirty adults with OCD were randomized to 18 sessions of EX/RP or EX/RP+MI. Therapists rated patient adherence at each exposure session. Independent evaluators assessed change in OCD and depressive symptoms, and patients completed self-report measures of readiness for change and quality of life. The two treatment conditions differed in degree of congruence with MI but not in conduct of EX/RP procedures. Both groups experienced clinically significant improvement in OCD symptoms, without significant group differences in patient adherence. There are several possible reasons why EX/RP+MI had no effect on patient adherence compared to standard EX/RP, each of which has important implications for the design of future MI studies in OCD. We recommend that MI be further evaluated in OCD by exploring alternative modes of delivery and by focusing on patients less ready for change than the current sample.

A placebo-controlled trial of phenelzine, cognitive behavioral group therapy, and their combination for social anxiety disorder.

CONTEXT: Medication and cognitive behavioral treatment are the best-established treatments for social anxiety disorder, yet many individuals remain symptomatic after treatment. OBJECTIVE: To determine whether combined medication and cognitive behavioral treatment is superior to either monotherapy or pill placebo. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Research clinics at Columbia University and Temple University. PARTICIPANTS: One hundred twenty-eight individuals with a primary DSM-IV diagnosis of social anxiety disorder. INTERVENTIONS: Cognitive behavioral group therapy (CBGT), phenelzine sulfate, pill placebo, and combined CBGT plus phenelzine. MAIN OUTCOME MEASURES: Liebowitz Social Anxiety Scale and Clinical Global Impression (CGI) scale scores at weeks 12 and 24. RESULTS: Linear mixed-effects models showed a specific order of effects, with steepest reductions in Liebowitz Social Anxiety Scale scores for the combined group, followed by the monotherapies, and the least reduction in the placebo group (Williams test = 4.97, P < .01). The CGI response rates in the intention-to-treat sample at week 12 were 9 of 27 (33.3%) (placebo), 16 of 34 (47.1%) (CBGT), 19 of 35 (54.3%) (phenelzine), and 23 of 32 (71.9%) (combined treatment) (chi(2)(1) = 8.76, P < .01). Corresponding remission rates (CGI = 1) were 2 of 27 (7.4%), 3 of 34 (8.8%), 8 of 35 (22.9%), and 15 of 32 (46.9%) (chi(2)(1) = 15.92, P < .01). At week 24, response rates were 9 of 27 (33.3%), 18 of 34 (52.9%), 17 of 35 (48.6%), and 25 of 32 (78.1%) (chi(2)(1) = 12.02, P = .001). Remission rates were 4 of 27 (14.8%), 8 of 34 (23.5%), 9 of 35 (25.7%), and 17 of 32 (53.1%) (chi(2)(1) = 10.72, P = .001). CONCLUSION: Combined phenelzine and CBGT treatment is superior to either treatment alone and to placebo on dimensional measures and on rates of response and remission.

A randomized, controlled trial of cognitive-behavioral therapy for augmenting pharmacotherapy in obsessive-compulsive disorder.

OBJECTIVE: Although serotonin reuptake inhibitors (SRIs) are approved for the treatment of obsessive-compulsive disorder (OCD), most OCD patients who have received an adequate SRI trial continue to have clinically significant OCD symptoms. The purpose of this study was to examine the effects of augmenting SRIs with exposure and ritual prevention, an established cognitive-behavioral therapy (CBT) for OCD. METHOD: A randomized, controlled trial was conducted at two academic outpatient clinics to compare the effects of augmenting SRIs with exposure and ritual prevention versus stress management training, another form of CBT. Participants were adult outpatients (N=108) with primary OCD and a Yale-Brown Obsessive Compulsive Scale total score > or = 16 despite a therapeutic SRI dose for at least 12 weeks prior to entry. Participants received 17 sessions of CBT (either exposure and ritual prevention or stress management training) twice a week while continuing SRI pharmacotherapy. RESULTS: Exposure and ritual prevention was superior to stress management training in reducing OCD symptoms. At week 8, significantly more patients receiving exposure and ritual prevention than patients receiving stress management training had a decrease in symptom severity of at least 25% (based on Yale-Brown Obsessive Compulsive Scale scores) and achieved minimal symptoms (defined as a Yale-Brown Obsessive Compulsive Scale score < or = 12). CONCLUSIONS: Augmentation of SRI pharmacotherapy with exposure and ritual prevention is an effective strategy for reducing OCD symptoms. However, 17 sessions were not sufficient to help most of these patients achieve minimal symptoms.

National trends in ethnic disparities in mental health care.

OBJECTIVE: To compare trends in office-based treatment of mental disorders between Hispanics and non-Hispanics. DESIGN, SETTING, AND PARTICIPANTS: Analysis of a nationally representative sample of visits to office-based physicians conducted between 1993 and 2002 (N = 251,905). Visits were grouped into 3 discrete time periods, 1993-1996, 1997-1999 and 2000-2002. MAIN OUTCOME MEASURES: Rate of diagnosis, type of mental health visit, type of treatment received (medication or psychotherapy), rate of psychotropic medications prescription, and specialty of the treating physician. RESULTS: From 1993-1996 to 2000-2002, the proportion of office visits in which mental health care was provided decreased for Hispanics from 12.2% to 11.7% while it increased from 13.1% to 15.7% for non-Hispanics (P < 0.05). Visits with a diagnosis of mental disorder decreased from 5.2% to 5.1% in Hispanics but increased from 6.0% to 8.8% in non-Hispanics (P < 0.05). Visits resulting in prescription of a psychotropic medication decreased from 10.2% to 9.3% in Hispanics, while they increased from 10.2% to 12.5% in non-Hispanics (P < 0.05). Psychotherapy visits decreased from 2.4% to 1.3% in Hispanics (P < 0.05), whereas they remained constant (2.5%) in non-Hispanics. Visits to a psychiatrist decreased from 2.5% to 1.3% in Hispanics (P < 0.05), while they increased (nonsignificantly) from 3.1% to 3.5% for non-Hispanics. Most differences persisted after adjusting for age and insurance status. CONCLUSIONS: From 1993 to 2002, there was an increase in mental health care disparities between Hispanics and non-Hispanics treated by office-based physicians. Improvement of the mental health care for Hispanics continues to be an important public health priority, with clear opportunities and challenges for health care policy-makers and practitioners.

National trends in the outpatient diagnosis and treatment of bipolar disorder in youth.

CONTEXT: Although bipolar disorder may have its onset during childhood, little is known about national trends in the diagnosis and management of bipolar disorder in young people. OBJECTIVES: To present national trends in outpatient visits with a diagnosis of bipolar disorder and to compare the treatment provided to youth and adults during those visits. DESIGN: We compare rates of growth between 1994-1995 and 2002-2003 in visits with a bipolar disorder diagnosis by individuals aged 0 to 19 years vs those aged 20 years or older. For the period of 1999 to 2003, we also compare demographic, clinical, and treatment characteristics of youth and adult bipolar disorder visits. SETTING: Outpatient visits to physicians in office-based practice. PARTICIPANTS: Patient visits from the National Ambulatory Medical Care Survey (1999-2003) with a bipolar disorder diagnosis (n = 962). MAIN OUTCOME MEASURES: Visits with a diagnosis of bipolar disorder by youth (aged 0-19 years) and by adults (aged > or = 20 years). RESULTS: The estimated annual number of youth office-based visits with a diagnosis of bipolar disorder increased from 25 (1994-1995) to 1003 (2002-2003) visits per 100,000 population, and adult visits with a diagnosis of bipolar disorder increased from 905 to 1679 visits per 100,000 population during this period. In 1999 to 2003, most youth bipolar disorder visits were by males (66.5%), whereas most adult bipolar disorder visits were by females (67.6%); youth were more likely than adults to receive a comorbid diagnosis of attention-deficit/hyperactivity disorder (32.2% vs 3.0%, respectively; P < .001); and most youth (90.6%) and adults (86.4%) received a psychotropic medication during bipolar disorder visits, with comparable rates of mood stabilizers, antipsychotics, and antidepressants prescribed for both age groups. CONCLUSIONS: There has been a recent rapid increase in the diagnosis of youth bipolar disorder in office-based medical settings. This increase highlights a need for clinical epidemiological reliability studies to determine the accuracy of clinical diagnoses of child and adolescent bipolar disorder in community practice.

Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder.

OBJECTIVE: The purpose of the study was to test the relative and combined efficacy of clomipramine and exposure and ritual prevention in the treatment of obsessive-compulsive disorder (OCD) in adults. Serotonin reuptake inhibitors (SRIs) and cognitive behavior therapy by exposure and ritual prevention are both established treatments for OCD, yet their relative and combined efficacy have not been demonstrated conclusively. METHOD: A double-blind, randomized, placebo-controlled trial comparing exposure and ritual prevention, clomipramine, their combination (exposure and ritual prevention plus clomipramine), and pill placebo was conducted at one center expert in pharmacotherapy, another with expertise in exposure and ritual prevention, and a third with expertise in both modalities. Participants were adult outpatients (N=122 entrants) with OCD. Interventions included intensive exposure and ritual prevention for 4 weeks, followed by eight weekly maintenance sessions, and/or clomipramine administered for 12 weeks, with a maximum dose of 250 mg/day. The main outcome measures were the Yale-Brown Obsessive Compulsive Scale total score and response rates determined by the Clinical Global Impression improvement scale. RESULTS: At week 12, the effects of all active treatments were superior to placebo. The effect of exposure and ritual prevention did not differ from that of exposure and ritual prevention plus clomipramine, and both were superior to clomipramine only. Treated and completer response rates were, respectively, 62% and 86% for exposure and ritual prevention, 42% and 48% for clomipramine, 70% and 79% for exposure and ritual prevention plus clomipramine, and 8% and 10% for placebo. CONCLUSIONS: Clomipramine, exposure and ritual prevention, and their combination are all efficacious treatments for OCD. Intensive exposure and ritual prevention may be superior to clomipramine and, by implication, to monotherapy with the other SRIs.

Use of psychotropic medications for patients with office visits who receive a diagnosis of panic disorder.

OBJECTIVE: We sought to examine trends in the medication management of panic disorder from a nationally representative sample of visits to psychiatrists and primary care physicians in office-based practice. METHOD: We analyzed physician-reported data from the 1992-1995 and 1996-1999 National Ambulatory Medical Care Survey, focusing on medication management of panic disorder by primary care physicians and psychiatrists. Rates for which doctors prescribed medication for patients with a diagnosis of panic disorder were compared over the course of time to identify changes in medication management between physician groups. We used logistic regression models to identify predictors of medication prescription, adjusting for the presence of other covariates. RESULTS: Both physician groups prescribed a psychotropic medication to a majority of patients for panic disorder in each time period. In 1992-1995, primary care physicians were less likely than psychiatrists to prescribe psychotropic medications. This difference was not evident in 1996-1999. The prescribing of benzodiazepines was common in both physician groups and time periods. Overall rates of psychotropic prescriptions by physician groups converged over time, although no single drug class accounted individually for the convergence. CONCLUSION: In recent years, changes in the medication management of patients with panic disorder by primary care physicians have resulted in greater similarity with the pharmacologic treatment of panic disorder provided in psychiatric practice.

Post-treatment effects of exposure therapy and clomipramine in obsessive-compulsive disorder.

We sought to determine whether adults with obsessive-compulsive disorder (OCD) who respond to intensive exposure and response (ritual) prevention (EX/RP) with or without clomipramine (CMI) fare better 12 weeks after treatment discontinuation than responders receiving CMI alone. After receiving 12 weeks of treatment (EX/RP, CMI, EX/RP+CMI, or pill placebo [PBO] in a randomized clinical trial conducted at three outpatient research centers), 46 adults with OCD who responded to treatment (18 EX/RP, 11 CMI, 15 EX/RP+CMI, 2 PBO) were followed after treatment discontinuation for 12 weeks. Patients were assessed every 4 weeks with the Yale-Brown Obsessive-Compulsive Scale, the National Institutes of Health Global Obsessive-Compulsive Scale, and the Clinical Global Impressions scale by an evaluator who was blind to original treatment assignment. The primary hypothesis was that EX/RP and EX/RP+CMI responders would be less likely to relapse 12 weeks after treatment discontinuation than responders to CMI alone. Twelve weeks after treatment discontinuation, EX/RP and EX/RP+CMI responders, compared to CMI responders, had a significantly lower relapse rate (4/33 = 12% versus 5/11 = 45%) and a significantly longer time to relapse. The CMI relapse rate was lower than previously reported. Nonetheless, responders receiving intensive EX/RP with or without CMI fared significantly better 12 weeks after treatment discontinuation than responders receiving CMI alone.

Citalopram treatment of social anxiety disorder with comorbid major depression.

Treatment of patients with both social anxiety disorder and major depression has been little studied although social anxiety disorder and depression frequently co-occur. Each disorder has been shown to respond to serotonin reuptake inhibitor treatment. Objectives of this study were to characterize a sample of these comorbid patients and to assess response to treatment with citalopram. Patients with primary DSM-IV generalized subtype of social anxiety disorder and comorbid major depression (N = 21) were assessed for symptoms of each disorder, including atypical depressive features, and functional impairment. Patients were treated with a flexible dose of open label citalopram for 12 weeks. Response rates for the intention-to-treat sample at week 12 were 14/21 (66.7%) for social anxiety disorder and 16/21 (76.2%) for depression. All continuous measures of social anxiety, depression, and functional impairment improved significantly with treatment, but depression symptoms responded more rapidly and more completely than social anxiety symptoms. Mean dose of citalopram at study endpoint was 37.6 mg/day. Only three patients (14.3%) fulfilled DSM-IV criteria for atypical features of depression, although 18 (85.7%) fulfilled the criterion for interpersonal rejection sensitivity. Citalopram treatment may benefit patients with primary social anxiety disorder and comorbid major depression, and it should be further studied in controlled trials. Improvement in social anxiety disorder symptoms lagged behind improvement in depression, and greater than 12 weeks of treatment may be required to assess full social anxiety response in patients with comorbid depression. The overlap of social anxiety disorder with atypical features of depression may primarily be due to the shared feature of rejection sensitivity.

Fluoxetine in children and adolescents with OCD: a placebo-controlled trial.

OBJECTIVE: To examine the safety and efficacy of fluoxetine in child and adolescent obsessive-compulsive disorder (OCD). METHOD: Between 1991 and 1998, 43 patients were randomly assigned to fluoxetine or placebo for 8 weeks. Dosing was fixed for the first 6 weeks (up to 60 mg/day) and then could be increased to 80 mg/day. Responders entered an 8-week maintenance phase. The primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impression-Improvement (CGI-I) scale. Analyses were done on the intent-to-treat sample. RESULTS: Fluoxetine patients (n = 21) had significantly lower CY-BOCS scores than placebo patients (n = 22) after 16 (but not 8) weeks. Fluoxetine responders (n = 11) had significantly lower CY-BOCS scores than placebo responders (n = 7) after an additional 8 weeks of treatment. After 16 weeks, 57% of fluoxetine (versus 27% of placebo) patients were much or very much improved on the CGI-I scale (p <.05). No patient terminated the study because of adverse medication effects. CONCLUSION: Fluoxetine was well tolerated and effective for the treatment of child and adolescent OCD, but fluoxetine's full effect took more than 8 weeks to develop.