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1.  Do Comorbid Anxiety Disorders Moderate the Effects of Psychotherapy for Bipolar Disorder? Results From STEP-BD 
The American journal of psychiatry  2014;171(2):178-186.
At least 50% of individuals with bipolar disorder have a lifetime anxiety disorder. Individuals with both bipolar disorder and a co-occurring anxiety disorder experience longer illness duration, greater illness severity, and poorer treatment response. The study explored whether comorbid lifetime anxiety in bipolar patients moderates psychotherapy treatment outcome.
In the Systematic Treatment Enhancement Program randomized controlled trial of psychotherapy for bipolar depression, participants received up to 30 sessions of intensive psychotherapy (family-focused therapy, interpersonal and social rhythm therapy, or cognitive-behavioral therapy) or collaborative care, a three-session comparison treatment, plus pharmacotherapy. Using the number needed to treat, we computed effect sizes to analyze the relationship between lifetime anxiety disorders and rates of recovery across treatment groups after 1 year.
A total of 269 patients (113 women) with a comorbid lifetime anxiety disorder (N=177) or without a comorbid lifetime anxiety disorder (N=92) were included in the analysis. Participants with a lifetime anxiety disorder were more likely to recover with psychotherapy than with collaborative care (66% compared with 49% recovered over 1 year; number needed to treat=5.88, small to medium effect). For patients without a lifetime anxiety disorder, there was no difference between rates of recovery in psychotherapy compared with collaborative care (64% compared with 62% recovered; number needed to treat=50, small effect). Participants with one lifetime anxiety disorder were likely to benefit from intensive psychotherapy compared with collaborative care (84% compared with 53% recovered; number needed to treat=3.22, medium to large effect), whereas patients with multiple anxiety disorders exhibited no difference in response to the two treatments (54% compared with 46% recovered; number needed to treat=12.5, small effect).
Depressed patients with bipolar disorder and comorbid anxiety may be in particular need of additional psychotherapy for treating acute depression. These results need to be replicated in studies that stratify bipolar patients to treatments based on their anxiety comorbidity status.
PMCID: PMC3946300  PMID: 24077657
2.  Impulsivity as a moderator of the intention-behavior relationship for illicit drug use in patients undergoing treatment 
Addictive behaviors  2012;38(3):1651-1655.
Evident across clinical practice and clinical trials is a divergence between stated intentions and subsequent drug-related behaviors in substance abuse treatment settings. Impulsivity, itself related to drug abuse, may be one variable which may moderate the degree of disconnect in the intention-behavior relationship. The present study examines the relationship between self-stated desire to quit, impulsivity, and drug use in a group of outpatients receiving methadone maintenance treatment. In particular, we examined the direct and moderating influence of different facets of impulsivity (urgency, lack of premeditation, sensation seeking, and lack of perseverance) on drug use in the context of a stated desire to abstain from drugs.
84 opioid-dependent individuals undergoing counseling and methadone maintenance treatment completed a battery of self-report questionnaires including measures of impulsivity (UPPS Impulsivity Scale), stated desire to quit, and past 30-day drug use. We hypothesized that two facets of impulsivity, urgency and (lack of) premeditation, would moderate the relationship between desire to quit and past 30-day drug use, such that the relationship between intention and behavior would be weaker in those with high levels of these facets of impulsivity.
Consistent with the disconnect between intentions and drug-use behaviors typical of treatment settings, desire to quit was not directly associated with self-reported past month drug use. However, in separate regression analyses, 2 facets of impulsivity, premeditation and sensation seeking, moderated the relationship between desire to quit and past month use. Whereas there was not a significant relationship between desire to quit and drug use in individuals high in sensation-seeking or lack of premeditation, the relationship between intention and drug use behaviors was preserved in those low in these facets of impulsivity.
These findings indicate that the relationship between desire to quit and self-reported past-month drug use is weak for those high in sensation seeking or low in premeditation. These results are discussed in the context of current interventions for substance dependence.
PMCID: PMC3558639  PMID: 23254213
3.  Augmentation of exposure therapy with post-session administration of d-cycloserine 
Journal of psychiatric research  2012;47(2):168-174.
Pre-session administration of d-cycloserine (DCS) has been found to augment exposure therapy outcomes in a variety of anxiety disorders. To be able to enhance learning only for successful exposure sessions, it would be beneficial to have the option of administering DCS after rather than before the session, a strategy encouraged by pre-clinical work. We believe the present study is the first published report on the efficacy of post-session administration of DCS in humans.
Adults (N = 29) with a DSM-IV diagnosis of acrophobia were randomized to receive two sessions of virtual reality exposure therapy (VRE) in combination with placebo or 50 mg of DCS. Instead of administering the pill prior to each of the sessions, as has been done in extant work, we administered the pill immediately following each session. Measures of acrophobia severity were collected at baseline, at each treatment session, 1-week post-treatment, and at 1-month follow-up.
Mixed-effects repeated-measures ANOVAs and GLMMs revealed significant improvement in all outcome measures over time, but no between-group differences were observed. At post-treatment, 63.5% of patients in the placebo condition vs. 60.0% of those in the DCS condition were in remission. At 1-month follow up, 63.4% of those in the placebo condition vs. 66.6% of those in the DCS condition were in remission.
These findings do not support the application of post-session DCS administration for augmenting the efficacy of exposure-based treatments. Possible reasons for these findings are discussed. Trial Registry: The Trial is registered at (NCT01102803).
PMCID: PMC3732105  PMID: 23098672
Augmentation; CBT; Cognitive behavioral therapy; d-cycloserine; Exposure treatment; Randomized controlled trial; Acrophobia
4.  Predictors of Dropout from Psychosocial Treatment in Opioid-Dependent Outpatients 
Background and Objectives
Early dropout is common in substance abuse treatment settings and may lead to poorer outcomes relative to those completing a full course of treatment. Attempts to identify predictors of dropout have yielded mixed results, highlighting the need for additional research in this area to clarify risk and protective factors to guide intervention and retention efforts. This study evaluated predictors of dropout from psychosocial treatment among opioid-dependent patients on methadone maintenance therapy.
Participants included 78 patients who had failed to respond to at least 4 months of methadone maintenance plus group counseling with clinic substance abuse counselors, and were enrolled in a study of randomized psychosocial treatment in addition to treatment-as-usual. Several factors that have been implicated in previous studies as well as two affective variables (distress intolerance and coping motives for drug use) were examined.
Results indicated that when controlling for various risk factors, age was the only significant predictor of dropout, with younger patients more likely to discontinue treatment early.
This study replicates previous findings in opioid-dependent samples that younger patients are at an increased risk of early treatment dropout.
Conclusions and Significance
Targeted intervention may be needed to retain young patients in drug abuse treatment.
PMCID: PMC3651588  PMID: 23398222
5.  Cognitive Therapy Alone and in Combination with Antidepressants for Anxious Depression: A STAR*D Report 
Journal of affective disorders  2012;142(1-3):213-218.
Anxious depression, defined as MDD with high levels of anxiety, has been associated with lower rates of antidepressant response and remission as well as greater chronicity, suicidality and antidepressant side-effect burden. The primary aim of this study was to assess the effectiveness of cognitive therapy (CT) alone or in combination with medications for anxious versus non-anxious depression.
We assessed the STAR*D study participants who were partial or non-responders to citalopram. Subjects were then either switched (n = 696) to a new antidepressant or to CT alone, or they were kept on citalopram and augmented (n = 577) with another antidepressant or CT. We compared response and remission rates of those who met criteria for anxious depression to those who did not across treatment conditions.
Those with anxious depression had significantly lower remission rates based on the QIDS, whether assigned to switch or augmentation, compared to those with non-anxious depression. Those with anxious depression, compared to those without, had significantly lower response rates based on the QIDS only in the switch group. There was no significant interaction between anxious depression and treatment assignment.
Limitations include the use of citalopram as the only Level 1 pharmacotherapy and medication augmentation option, depression-focused CT rather than anxiety-focused CT, and focus on acute treatment outcomes.
Individuals with anxious depression appear to experience higher risk of poorer outcome following pharmacotherapy and/or CT after an initial course of SSRI, and continued efforts to target this challenging form of depression are needed.
PMCID: PMC3483355  PMID: 22877961
anxious depression; MDD; CT; psychosocial interventions; STAR*D
6.  Rates of mood and anxiety disorders and contributors to continued heroin use in methadone maintenance patients: A comparison by HIV status 
Neurobehavioral HIV medicine  2010;2010(2):49-57.
The frequency of mood and anxiety disorders is elevated among individuals with a history of intravenous drug abuse and among those with human immunodeficiency virus (HIV), and these disorders are associated with continued substance use despite treatment. The present study examined rates of mood and anxiety disorders, and recent heroin use, among HIV-infected and HIV-noninfected patients receiving methadone maintenance therapy. Participants were 160 (80 HIV-infected, 80 HIV-noninfected) methadone patients. Clinician-administered, semistructured interviews were used to identify unipolar and bipolar depression, and four major anxiety disorders (panic disorder with agoraphobia [PDA], generalized anxiety disorder [GAD], post-traumatic stress disorder [PTSD], and social anxiety disorder [SAD]). Toxicology screens and self-reporting were used to assess heroin, cocaine, marijuana, and alcohol use over the past month. The entire sample met criteria for at least one psychiatric disorder other than substance dependence. Substantial proportions of participants met criteria for major depressive disorder (55.6%), bipolar I, bipolar II, or cyclothymia (6.4%), PDA (34.4%), GAD (22.5%), SAD (16.9%), and PTSD (34.4%). A greater proportion of HIV-infected participants met criteria for SAD (χ2 = 5.03), and a greater proportion of HIV-noninfected participants met criteria for GAD (χ2 = 5.39, P < 0.01). About 14% of participants continued to use heroin over the past month, a significantly greater proportion of whom were HIV-infected. In adjusted analyses, none of the mood or anxiety disorders emerged as significant predictors of recent heroin use, but being HIV-infected did. This study highlights the high rate of psychopathology and continued heroin use despite substance abuse treatment, and underscores the need for interventions that help mitigate these problems among methadone patients.
PMCID: PMC3779458  PMID: 24062619
psychopathology; substance dependence; human immunodeficiency virus; methadone
7.  Refining the Measurement of Distress Intolerance 
Behavior therapy  2011;43(3):641-651.
Distress intolerance is an important transdiagnostic variable that has long been implicated in the development and maintenance of psychological disorders. Self-report measurement strategies for distress intolerance have emerged from several different models of psychopathology and these measures have been applied inconsistently in the literature in the absence of a clear gold standard. The absence of a consistent assessment strategy has limited the ability to compare across studies and samples, thus hampering the advancement of this research agenda. This study evaluated the latent factor structure of existing measures of DI to examine the degree to which they are capturing the same construct. Results of confirmatory factor analysis in 3 samples totaling 400 participants provided support for a single factor latent structure. Individual items of these four scales were then correlated with this factor to identify those that best capture the core construct. Results provided consistent supported for 10 items that demonstrated the strongest concordance with this factor. The use of these 10 items as a unifying measure in the study of DI and future directions for the evaluation of its utility are discussed.
PMCID: PMC3483633  PMID: 22697451
distress tolerance; distress intolerance; anxiety sensitivity; discomfort intolerance; assessment
8.  Extreme Attributions Predict the Course of Bipolar Depression: Results from the STEP-BD Randomized Controlled Trial of Psychosocial Treatment 
Little is known about predictors of recovery from bipolar depression or moderators of treatment response. In the present study we investigated attributional style (a cognitive pattern of explaining the causes of life events) as a predictor of recovery from episodes of bipolar depression and as a moderator of response to psychotherapy for bipolar depression.
106 depressed outpatients with DSM-IV bipolar I or II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were randomized to intensive psychotherapy for depression (n=62), or collaborative care (n=44), a minimal psychoeducational intervention. The primary outcome was recovery status at each study visit as measured by the Clinical Monitoring Form. Attributional style was measured at baseline using the Attributional Style Questionnaire. Data were collected between 1998 and 2005.
All analyses were by intention to treat. Extreme attributions predicted a lower likelihood of recovery (p=.01, OR=0.93, 95% CI=.88-.98) and longer time until recovery (p<.01, OR=0.96, 95% CI=.93-.99), independent of the effects of initial depression severity. Among individuals with more pessimistic attributional styles, initial depression severity predicted a lower likelihood of recovery (p=.01, OR=0.64, 95% CI=.45-.91) and longer time until recovery (p<.001, OR=0.76, 95% CI=.66-.88). There was no difference in recovery rates between intensive psychotherapy and collaborative care (OR=0.90, 95% CI=0.40-2.01) in the full sample.
These results suggest that extreme, rigid attributions may be associated with a more severe course of depression, and that evaluating attributional style may help clinicians to identify patients who are at risk for experiencing a more severe course of depression.
PMCID: PMC3646511  PMID: 23561230
9.  Sexual HIV Risk Behaviors in a Treatment-Refractory Opioid-Dependent Sample 
Journal of psychoactive drugs  2012;44(3):237-242.
The propensity to engage in risk behaviors confers an elevated risk of HIV and other infectious disease transmission in opioid-dependent populations. Although drug abuse treatment may decrease drug-related risk behaviors such as needle-sharing, additional intervention may be needed to reduce HIV risk behavior. In this investigation, we assessed sexual HIV risk behaviors in opioid-dependent patients who were engaging in regular drug use despite ongoing counseling and methadone maintenance therapy. Potential risk and protective factors for engaging in sexual HIV risk behavior were examined. Taking into account demographic, psychiatric, substance use, and psychological variables, the only significant predictor of risk behavior was age. Specifically, younger patients were more likely to engage in sexual HIV risk behavior. The implications of these results for reducing sexual HIV risk behavior and for HIV prevention in methadone-maintained, treatment-refractory opioid-dependent patients are discussed.
PMCID: PMC3755954  PMID: 23061323
age; HIV; methadone; opioids; risk behaviors; substance dependence
10.  Shared Variance among Self-Report and Behavioral Measures of Distress Intolerance 
Cognitive therapy and research  2011;35(3):266-275.
Distress intolerance may be an important individual difference variable in understanding maladaptive coping responses across diagnostic categories. However, the measurement of distress intolerance remains inconsistent across studies and little evidence for convergent validity among existing measures is available. This study evaluated the overlap among self-report and behavioral measures of distress intolerance in four samples, including an unselected sample, a sample of patients with drug dependence, and two samples of cigarette smokers. Results suggested that the self-report measures were highly correlated, as were the behavioral measures; however, behavioral and self-report measures did not exhibit significant associations with each other. There was some evidence of domain specificity, with anxiety sensitivity demonstrating strong associations with somatic distress intolerance, and a lack of association between behavioral measures that elicit affective distress and those that elicit somatic distress. These findings highlight a potential divergence in the literature relative to the conceptualization of distress intolerance as either sensitivity to distress or as the inability to persist at a task when distressed. Further research is needed to elucidate the conceptualization and measurement of distress intolerance to facilitate future clinical and research applications of this construct.
PMCID: PMC3721199  PMID: 23894216
Distress Intolerance; Measurement; Task Persistence; Anxiety Sensitivity
11.  Cognitive Behavioral Therapy for Adherence and Depression (CBT-AD) in HIV-infected Injection Drug Users: A Randomized Controlled Trial 
Depression and substance use, the most common comorbidities with HIV, are both associated with poor treatment adherence. Injection drug users comprise a substantial portion of individuals with HIV in the U.S. and globally. The present study tested cognitive-behavioral therapy for adherence and depression (CBT-AD) in patients with HIV and depression in active substance abuse treatment for injection drug use.
This is a two-arm, randomized controlled trial (N = 89) comparing CBT-AD to enhanced treatment as usual (ETAU). Analyses were conducted for two time-frames: 1) baseline to post-treatment 2) post-treatment to follow-up at 3- and 6-months after intervention discontinuation.
At post-treatment, the CBT-AD condition showed significantly greater improvement than ETAU in MEMS (electronic pill cap) based adherence (γslope = 0.8873, t (86) = 2.38, p = .02; dGMA-raw = .64), and depression, assessed by blinded assessor [Mongomery-Asberg Depression Rating Scale (F(1,79) = 6.52, p<.01); d = .55)] and clinical global impression [(F(1,79) = 14.77, p<.001; d = .85)]. After treatment discontinuation, depression gains were maintained, though adherence gains were not. Viral load did not differ across condition, however, the CBT-AD condition had significant improvements in CD4 cell counts over time compared to ETAU (γslope= 2.09, t (76) = 2.20, p = .03; dGMA-raw = .60).
In patients managing multiple challenges including HIV, depression, substance dependence, and adherence, CBT-AD is a useful way to integrate treatment of depression with an adherence intervention. Continued adherence counseling is likely needed, however, to maintain or augment adherence gains in this population.
PMCID: PMC3365619  PMID: 22545737
HIV; AIDS; Antiretroviral therapy; ART; depression; randomized controlled trial; adherence; substance abuse
12.  Exploring exercise as an avenue for the treatment of anxiety disorders 
Expert review of neurotherapeutics  2012;12(8):1011-1022.
Anxiety disorders constitute a significant public health problem. Current gold standard treatments are limited in their effectiveness, prompting the consideration of alternative approaches. In this review, we examine the evidence for exercise as an intervention for anxiety disorders. This evidence comes from population studies, studies of nonclinical anxiety reduction, as well as a limited number of studies of clinically anxious individuals. All of these studies provide converging evidence for consistent beneficial effects of exercise on anxiety, and are consistent with a variety of accounts of the mechanism of anxiety reduction with exercise. Further study of clinical populations is encouraged, as are studies of the mechanism of change of exercise interventions, which have the potential to help refine exercise intervention strategies. Likewise, studies that identify moderators of treatment efficacy will assist clinicians in deciding how and for whom to prescribe exercise.
PMCID: PMC3501262  PMID: 23002943
anxiety; anxiety disorders; exercise; intervention; physical activity; treatment
13.  Intensive Psychosocial Intervention Enhances Functioning in Patients With Bipolar Depression: Results From a 9-Month Randomized Controlled Trial 
The American journal of psychiatry  2007;164(9):1340-1347.
Psychosocial interventions are effective adjuncts to pharmacotherapy in delaying recurrences of bipolar disorder; however, to date their effects on life functioning have been given little attention. In a randomized trial, the authors examined the impact of intensive psychosocial treatment plus pharmacotherapy on the functional outcomes of patients with bipolar disorder over the 9 months following a depressive episode.
Participants were 152 depressed outpatients with bipolar I or bipolar II disorder in the multisite Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. All patients received pharmacotherapy. Eighty-four patients were randomly assigned to intensive psychosocial intervention (30 sessions over 9 months of interpersonal and social rhythm therapy, cognitive behavior therapy [CBT], or family-focused therapy), and 68 patients were randomly assigned to collaborative care (a 3-session psychoeducational treatment). Independent evaluators rated the four subscales of the Longitudinal Interval Follow-Up Evaluation–Range of Impaired Functioning Tool (LIFE-RIFT) (relationships, satisfaction with activities, work/role functioning, and recreational activities) through structured interviews given at baseline and every 3 months over a 9-month period.
Patients in intensive psychotherapy had better total functioning, relationship functioning, and life satisfaction scores over 9 months than patients in collaborative care, even after pretreatment functioning and concurrent depression scores were covaried. No effects of psychosocial intervention were observed on work/role functioning or recreation scores during this 9-month period.
Intensive psychosocial treatment enhances relationship functioning and life satisfaction among patients with bipolar disorder. Alternate interventions focused on the specific cognitive deficits of individuals with bipolar disorder may be necessary to enhance vocational functioning after a depressive episode.
PMCID: PMC3579578  PMID: 17728418
14.  Psychosocial Treatments for Bipolar Depression: A 1-Year Randomized Trial From the Systematic Treatment Enhancement Program 
Archives of general psychiatry  2007;64(4):419-426.
Psychosocial interventions have been shown to enhance pharmacotherapy outcomes in bipolar disorder.
To examine the benefits of 4 disorder-specific psychotherapies in conjunction with pharmacotherapy on time to recovery and the likelihood of remaining well after an episode of bipolar depression.
Randomized controlled trial.
Fifteen clinics affiliated with the Systematic Treatment Enhancement Program for Bipolar Disorder.
A total of 293 referred outpatients with bipolar I or II disorder and depression treated with protocol pharmacotherapy were randomly assigned to intensive psychotherapy (n=163) or collaborative care (n=130), a brief psychoeducational intervention.
Intensive psychotherapy was given weekly and biweekly for up to 30 sessions in 9 months according to protocols for family-focused therapy, interpersonal and social rhythm therapy, and cognitive behavior therapy. Collaborative care consisted of 3 sessions in 6 weeks.
Main Outcome Measures
Outcome assessments were performed by psychiatrists at each pharmacotherapy visit. Primary outcomes included time to recovery and the proportion of patients classified as well during each of 12 study months.
All analyses were by intention to treat. Rates of attrition did not differ across the intensive psychotherapy (35.6%) and collaborative care (30.8%) conditions. Patients receiving intensive psychotherapy had significantly higher year-end recovery rates (64.4% vs 51.5%) and shorter times to recovery than patients in collaborative care (hazard ratio, 1.47; 95% confidence interval, 1.08–2.00; P=.01). Patients in intensive psychotherapy were 1.58 times (95% confidence interval, 1.17–2.13) more likely to be clinically well during any study month than those in collaborative care (P=.003). No statistically significant differences were observed in the outcomes of the 3 intensive psychotherapies.
Intensive psychosocial treatment as an adjunct to pharmacotherapy was more beneficial than brief treatment in enhancing stabilization from bipolar depression. Future studies should compare the cost-effectiveness of models of psychotherapy for bipolar disorder.
Trial Registration Identifier: NCT00012558
PMCID: PMC3579612  PMID: 17404119
15.  Domain-General and Domain-Specific Strategies for the Assessment of Distress Intolerance 
Recent research has provided evidence that distress intolerance—the perceived inability to tolerate distressing states—varies based on the domain of distress (e.g., pain, anxiety). Although domain-specific assessment strategies may provide information targeted to specific disorders or maladaptive behaviors, domain-general measures have the potential to facilitate comparisons across studies, disorders, and populations. The current study evaluated the utilization of self-report measures of distress intolerance as domain-general measures by examining their association with indices of behavioral avoidance and substance craving. Two groups of participants (N = 55) were recruited including a substance-dependent group and a comparison group equated based on the presence of an affective disorder. Results provided support for the validity of domain-general measures for assessing distress intolerance across varied domains. The importance of both domain-general and domain-specific measurement of distress intolerance is discussed.
PMCID: PMC3232280  PMID: 21823763
distress intolerance; assessment; substance dependence; affective disorders
16.  Modifying Exposure-Based CBT for Cambodian Refugees with Posttraumatic Stress Disorder 
Cognitive and behavioral practice  2006;13(4):261-270.
Cambodian refugees represent a severely traumatized population living in the United States. In this paper, we describe the modification of a cognitive-behavior therapy program to facilitate delivery of an exposure-based treatment for posttraumatic stress disorder while addressing some of the challenges brought by differences in language and culture between providers and patients. Our treatment modifications include the use of metaphors and culturally relevant examples to aid the communication of core concepts by interpreters, an emphasis on teaching the “process” of exposure therapy rather than relying on specific exposure practice in the group setting, a focus on interoceptive exposure to allow more effective group practice and to address culturally specific symptom interpretations, attention to the way in which treatment procedures interacted with culturally specific beliefs, and efforts to integrate treatment services within the community. Although data are limited, results to date suggest that this modified treatment was acceptable to patients and offered benefits on the order of large effect sizes.
PMCID: PMC2804994  PMID: 20072706
17.  The efficacy of vigorous-intensity exercise as an aid to smoking cessation in adults with elevated anxiety sensitivity: study protocol for a randomized controlled trial 
Trials  2012;13:207.
Although cigarette smoking is a leading cause of death and disability in the United States (US), over 40 million adults in the US currently smoke. Quitting smoking is particularly difficult for smokers with certain types of psychological vulnerability. Researchers have frequently called attention to the relation between smoking and anxiety-related states and disorders, and evidence suggests that panic and related anxiety vulnerability factors, specifically anxiety sensitivity (AS or fear of somatic arousal), negatively impact cessation. Accordingly, there is merit to targeting AS among smokers to improve cessation outcome. Aerobic exercise has emerged as a promising aid for smoking cessation for this high-risk (for relapse) group because exercise can effectively reduce AS and other factors predicting smoking relapse (for example, withdrawal, depressed mood, anxiety), and it has shown initial efficacy for smoking cessation. The current manuscript presents the rationale, study design and procedures, and design considerations of the Smoking Termination Enhancement Project (STEP).
STEP is a randomized clinical trial that compares a vigorous-intensity exercise intervention to a health and wellness education intervention as an aid for smoking cessation in adults with elevated AS. One hundred and fifty eligible participants will receive standard treatment (ST) for smoking cessation that includes cognitive behavioral therapy (CBT) and nicotine replacement therapy (NRT). In addition, participants will be randomly assigned to either an exercise intervention (ST+EX) or a health and wellness education intervention (ST+CTRL). Participants in both arms will meet 3 times a week for 15 weeks, receiving CBT once a week for the first 7 weeks, and 3 supervised exercise or health and wellness education sessions (depending on randomization) per week for the full 15-week intervention. Participants will be asked to set a quit date for 6 weeks after the baseline visit, and smoking cessation outcomes as well as putative mediator variables will be measured up to 6 months following the quit date.
The primary objective of STEP is to evaluate whether vigorous-intensity exercise can aid smoking cessation in anxiety vulnerable adults. If effective, the use of vigorous-intensity exercise as a component of smoking cessation interventions would have a significant public health impact. Specifically, in addition to improving smoking cessation treatment outcome, exercise is expected to offer benefits to overall health, which may be particularly important for smokers. The study is also designed to test putative mediators of the intervention effects and therefore has the potential to advance the understanding of exercise-anxiety-smoking relations and guide future research on this topic.
Clinical trials registry, NCT01065506,
PMCID: PMC3522063  PMID: 23148822
Smoking; Smoking cessation; Intervention; Randomized controlled trial; Exercise; Aerobic exercise; Anxiety; Anxiety sensitivity
18.  Cognitive Enhancers for Anxiety Disorders 
Cognitive behavioral therapy is an effective intervention for anxiety disorders. However, a significant number of people do not respond or only show partial response even after an adequate course of the treatment. Recent research has shown that the efficacy of the intervention can be improved by the use of cognitive enhancers that augment the core learning processes of cognitive-behavior therapy. This manuscript provides a review of the current state of cognitive enhancers for the treatment of anxiety disorders.
PMCID: PMC3114287  PMID: 21134394
cognitive enhancer; anxiety; fear; cognitive behavioral therapy
19.  Attending to Emotional Cues for Drug Abuse: Bridging the Gap Between Clinic and Home Behaviors 
Classical conditioning models of addiction provide keys to understanding the vexing discrepancy between substance abuse patients’ desire to abstain when they are in therapy sessions and their tendency to relapse. Experiments using these models demonstrate the power of environmental relapse cues and support clinical approaches, including active exposure, aimed at helping patients recognize and withstand them. Internal cues, including emotions and somatic states such as withdrawal, can trigger urges as powerfully as external cues such as people, places, and things associated with prior abuse. The authors describe a cognitive-behavioral therapy approach that focuses on identifying and actively inducing each patient’s high-risk emotions, then helping him or her develop and practice healthy responses. Clinical trials support the approach for patients with panic disorder who have trouble discontinuing benzodiazepines, and early trials suggest it may be useful for patients addicted to other drugs as well.
PMCID: PMC2851069  PMID: 17514074
20.  Influence of Psychiatric Comorbidity on Recovery and Recurrence in Generalized Anxiety Disorder, Social Phobia, and Panic Disorder: A 12-Year Prospective Study 
The American Journal of Psychiatry  2005;162(6):1179-1187.
The authors sought to observe the long-term clinical course of anxiety disorders over 12 years and to examine the influence of comorbid psychiatric disorders on recovery from or recurrence of panic disorder, generalized anxiety disorder, and social phobia.
Data were drawn from the Harvard/Brown Anxiety Disorders Research Program, a prospective, naturalistic, longitudinal, multicenter study of adults with a current or past history of anxiety disorders. Probabilities of recovery and recurrence were calculated by using standard survival analysis methods. Proportional hazards regression analyses with time-varying covariates were conducted to determine risk ratios for possible comorbid psychiatric predictors of recovery and recurrence.
Survival analyses revealed an overall chronic course for the majority of the anxiety disorders. Social phobia had the smallest probability of recovery after 12 years of follow-up. Moreover, patients who had prospectively observed recovery from their intake anxiety disorder had a high probability of recurrence over the follow-up period. The overall clinical course was worsened by several comorbid psychiatric conditions, including major depression and alcohol and other substance use disorders, and by comorbidity of generalized anxiety disorder and panic disorder with agoraphobia.
These data depict the anxiety disorders as insidious, with a chronic clinical course, low rates of recovery, and relatively high probabilities of recurrence. The presence of particular comorbid psychiatric disorders significantly lowered the likelihood of recovery from anxiety disorders and increased the likelihood of their recurrence. The findings add to the understanding of the nosology and treatment of these disorders.
PMCID: PMC3272761  PMID: 15930067
21.  Anxiety Sensitivity: A Unique Predictor of Dropout Among Inner-city Heroin and Crack/Cocaine Users in Residential Substance Use Treatment 
Behaviour research and therapy  2008;46(7):811-818.
The present study examined the extent to which anxiety sensitivity (AS) at treatment entry was related to prospective treatment dropout among 182 crack/cocaine and/or heroin dependent patients in a substance use residential treatment facility in Northeast Washington DC. Results indicated that AS incrementally and prospectively predicted treatment dropout after controlling for the variance accounted for by demographics and other drug use variables, legal obligation to treatment (i.e., court ordered vs. self-referred), alcohol use frequency, and depressive symptoms. Findings are discussed in relation to the role of AS in treatment dropout and substance use problems more generally.
PMCID: PMC3175736  PMID: 18466878
anxiety sensitivity; heroin; crack/cocaine; drug treatment; treatment completion
22.  Cognitive-Behavioral Therapy for Substance Use Disorders 
Cognitive behavioral therapy (CBT) for substance use disorders has demonstrated efficacy as both a monotherapy and as part of combination treatment strategies. This article provides a review of the evidence supporting the use of CBT, clinical elements of its application, novel treatment strategies for improving treatment response, and dissemination efforts. Although CBT for substance abuse is characterized by heterogeneous treatment elements—such as operant learning strategies, cognitive and motivational elements, and skills building interventions—across protocols several core elements emerge that focus on overcoming the powerfully reinforcing effects of psychoactive substances. These elements, and support for their efficacy, are discussed.
PMCID: PMC2897895  PMID: 20599130
Substance Use Disorders; Cognitive Behavioral Therapy; Contingency Management; Relapse Prevention; Motivational Interviewing
23.  The Serotonin Transporter Gene and Risk for Alcohol Dependence: A Meta-Analytic Review 
Drug and alcohol dependence  2010;108(1-2):1-6.
Previous studies have implicated a relationship between particular allelic variations of the serotonin transporter gene (5HTTLPR) and alcohol dependence. To provide a current estimate of the strength of this association, particularly in light of inconsistent results for 5HTTLPR, we conducted a meta-analytic review of the association between 5HTTLPR and a clinical diagnosis of alcohol dependence. Of 145 studies initially identified, 22 (including 8,050 participants) met inclusion criteria. Results indicated that there was a significant albeit modest association between alcohol dependence diagnosis and the presence of at least 1 short allele (OR = 1.15, 95% CI = 1.01, 1.30, p < .05). Slightly more robust results were observed for participants who were homogeneous for the short allele (OR = 1.21, 95% CI = 1.02, 1.44, p < .05). These results were unrelated to sex and race/ethnicity of participants; however, the effect size was moderated by study sample size and publication year. Additionally, the fail-safe N analysis indicated potential publication bias. Therefore, although our review indicates that there is a significant association between 5HTTLPR and alcohol dependence diagnosis, this result should be interpreted with caution.
PMCID: PMC2835838  PMID: 20060655
Serotonin transporter gene; 5HTTLPR; Alcohol Dependence
24.  D-cycloserine Deters Reacquisition of Cocaine Self-administration by Augmenting Extinction Learning 
Augmentation of cue exposure (extinction) therapy with cognitive-enhancing pharmacotherapy may offer an effective strategy to combat cocaine relapse. To investigate this possibility at the preclinical level, rats and squirrel monkeys were trained to self-administer cocaine paired with a brief visual cue. Lever pressing was subsequently extinguished by withholding cocaine injections while maintaining response-contingent presentations of the cue. The glycine partial agonist D-cycloserine (DCS; 15 and 30 mg/kg in rats, 3 and 10 mg/kg in monkeys) was evaluated for its effects on the rate of extinction and subsequent reacquisition of cocaine self-administration. Compared to vehicle, pretreatment with 30 mg/kg DCS 0.5 hr before extinction training reduced the number of responses and latency to reach the extinction criterion in rats, but neither dose of DCS altered these measures in monkeys. In both species pretreatment with the higher dose of DCS before extinction training significantly attenuated reacquisition of cocaine self-administration compared to either extinction training in the absence of DCS or DCS in the absence of explicit extinction. Furthermore, treatment with 30 mg/kg DCS accompanied by brief handling (a stress induction) immediately after but not 6 hr after extinction training attenuated reacquisition of cocaine self-administration in rats. No adverse effects of 10 mg/kg DCS were evident in quantitative observational studies in monkeys. The results suggest that DCS augmented consolidation of extinction learning to deter reacquisition of cocaine self-administration in rats and monkeys. The results suggest that DCS combined with exposure therapy may constitute a rational strategy for the clinical management of cocaine relapse.
PMCID: PMC2928163  PMID: 19741593
Cocaine; Cognitive enhancer; D-cycloserine; Extinction training; Relapse; Self-administration
25.  D-cycloserine Deters Reacquisition of Cocaine Self-Administration by Augmenting Extinction Learning 
Neuropsychopharmacology  2009;35(2):357-367.
Augmentation of cue exposure (extinction) therapy with cognitive-enhancing pharmacotherapy may offer an effective strategy to combat cocaine relapse. To investigate this possibility at the preclinical level, rats and squirrel monkeys were trained to self-administer cocaine paired with a brief visual cue. Lever pressing was subsequently extinguished by withholding cocaine injections while maintaining response-contingent presentations of the cue. The glycine partial agonist D-cycloserine (DCS; 15 and 30 mg/kg in rats, 3 and 10 mg/kg in monkeys) was evaluated for its effects on the rate of extinction and subsequent reacquisition of cocaine self-administration. Compared with vehicle, pretreatment with 30 mg/kg DCS 0.5 h before extinction training reduced the number of responses and latency to reach the extinction criterion in rats, but neither dose of DCS altered these measures in monkeys. In both species, pretreatment with the higher dose of DCS before extinction training significantly attenuated reacquisition of cocaine self-administration compared with either extinction training in the absence of DCS or DCS in the absence of explicit extinction. Furthermore, treatment with 30 mg/kg DCS accompanied by brief handling (a stress induction) immediately after but not 6 h after extinction training attenuated reacquisition of cocaine self-administration in rats. No adverse effects of 10 mg/kg DCS were evident in quantitative observational studies in monkeys. The results suggest that DCS augmented consolidation of extinction learning to deter reacquisition of cocaine self-administration in rats and monkeys. The results suggest that DCS combined with exposure therapy may constitute a rational strategy for the clinical management of cocaine relapse.
PMCID: PMC2928163  PMID: 19741593
cocaine; cognitive enhancer; D-cycloserine; extinction training; relapse; self-administration

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