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.
anxious depression; MDD; CT; psychosocial interventions; STAR*D
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.
psychopathology; substance dependence; human immunodeficiency virus; methadone
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.
distress tolerance; distress intolerance; anxiety sensitivity; discomfort intolerance; assessment
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.
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.
age; HIV; methadone; opioids; risk behaviors; substance dependence
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.
Distress Intolerance; Measurement; Task Persistence; Anxiety Sensitivity
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.
HIV; AIDS; Antiretroviral therapy; ART; depression; randomized controlled trial; adherence; substance abuse
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.
anxiety; anxiety disorders; exercise; intervention; physical activity; treatment
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.
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.
clinicaltrials.gov Identifier: NCT00012558
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.
distress intolerance; assessment; substance dependence; affective disorders
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
ClinicalTrials.gov, NCT01065506, http://clinicaltrials.gov/ct2/show/NCT01065506
Smoking; Smoking cessation; Intervention; Randomized controlled trial; Exercise; Aerobic exercise; Anxiety; Anxiety sensitivity
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.
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.
cognitive enhancer; anxiety; fear; cognitive behavioral therapy
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.
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.
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.
anxiety sensitivity; heroin; crack/cocaine; drug treatment; treatment completion
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.
Substance Use Disorders; Cognitive Behavioral Therapy; Contingency Management; Relapse Prevention; Motivational Interviewing
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.
Serotonin transporter gene; 5HTTLPR; Alcohol Dependence
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.
Cocaine; Cognitive enhancer; D-cycloserine; Extinction training; Relapse; Self-administration
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.
cocaine; cognitive enhancer; D-cycloserine; extinction training; relapse; self-administration
In a prospective, longitudinal, population-based study of 643 women participating in the Harvard Study of Moods and Cycles we examined whether psychosocial variables predicted a new or recurrent onset of an anxiety disorder. Presence of anxiety disorders was assessed every six months over three years via structured clinical interviews. Among individuals who had a new episode of anxiety, we confirmed previous findings that history of anxiety, increased anxiety sensitivity (the fear of anxiety related sensations), and increased neuroticism were significant predictors. We also found trend level support for assertiveness as a predictor of anxiety onset. However, of these variables, only history of anxiety and anxiety sensitivity provided unique prediction. We did not find evidence for negative life events as a predictor of onset of anxiety either alone or in interaction with other variables in a diathesis-stress model. These findings from a prospective longitudinal study are discussed in relation to the potential role of such predictors in primary or relapse prevention efforts.
To evaluate cognitive behavioral therapy to enhance medication adherence and reduce depression (CBT-AD) in individuals with HIV.
A two arm, randomized, controlled, cross-over trial comparing CBT-AD, to enhanced treatment as usual only (ETAU). ETAU, which both groups received, included a single-session intervention for adherence and a letter to the patient’s provider documenting her or his continued depression. The intervention group also received 10 to 12 sessions of CBT-AD.
Main Outcome Measures
Adherence to antiretroviral therapy as assessed by Medication Event Monitoring Systems (MEMs) and depression as assessed by blinded structured evaluation.
At the acute outcome assessment (3-months), those who received CBT-AD evidenced significantly greater improvements in medication adherence and depression relative to the comparison group. Those who were originally assigned to the comparison group who chose to cross over to CBT-AD showed similar improvements in both depression and adherence outcomes. Treatment gains for those in the intervention group were generally maintained at 6 and 12-month follow-up assessments. By the end of the follow-up period, those originally assigned CBT-AD demonstrated improvements in plasma HIV RNA concentrations, though these differences did not emerge before the cross-over, and hence there were not between-group differences.
CBT-AD is a potentially efficacious approach for individuals with HIV struggling with depression and adherence. Replication and extension in larger efficacy trials are needed.
HIV; adherence; Cognitive behavioral therapy
Daily dosing with D-cycloserine has inconsistently improved negative symptoms in schizophrenia patients, whereas intermittent dosing significantly facilitated exposure-based therapy in two studies of patients with phobic anxiety. In animal models, single dose administration enhances memory consolidation, but tachyphylaxis develops with repeated dosing. The objective of this exploratory study was to assess whether once-weekly dosing with D-cycloserine will produce persistent improvements in negative symptoms and cognition.
Fifty stable adult schizophrenia outpatients treated with any antipsychotic except clozapine were enrolled and 38 were randomized, double-blind, in a parallel-group, 8-week add-on trial of D-cycloserine 50 mg or placebo administered once-weekly. Symptom rating scales and a cognitive battery were administered at baseline and week 8 before the dose of study drug. As an exploratory analysis of memory consolidation, the Logical Memory Test, modified to measure recall after 7 days, was administered at baseline and after the first weekly dose of D-cycloserine. The primary outcome measures were change from baseline to week 8 on the SANS total score and on a composite cognitive score.
Thirty-three subjects (87%) completed the trial. D-cycloserine significantly improved SANS total scores compared to placebo at week 8. Cognitive performance did not improve with D-cycloserine at 8 weeks. Delayed thematic recall on the Logical Memory Test was significantly improved with the first dose of D-cycloserine compared to placebo. Performance on immediate thematic recall and item recall on the Logical Memory Test did not differ between treatments.
Once-weekly dosing with D-cycloserine for 8 weeks produced persistent improvement of negative symptoms compared to placebo, although statistical significance was, in part, the result of worsening of negative symptoms with placebo. Consistent with animal models, a single dose of D-cycloserine facilitated memory consolidation tested after 7 days on a test of thematic recall. These results must be considered preliminary since a number of outcomes were examined without correction for multiple tests. These findings suggest that once-weekly dosing with D-cycloserine for the treatment of negative symptoms merits further study, as do D-cycloserine effects on memory consolidation.
Among psychologically distressed Cambodian refugees, somatic complaints are particularly prominent. Cambodians interpret anxiety-related somatic sensations in terms of “Wind” (khyâl), an ethnophysiology that gives rise to multiple catastrophic interpretations; and they have prominent trauma-memory associations to anxiety-related somatic symptoms. In this article, we detail some of the common sensation-related dysphoric networks of Cambodian refugees, focusing on catastrophic cognitions and trauma associations. We argue that delineating symptom-related dysphoric networks is crucial to successfully adapt cognitive-behavioral interventions to treat panic disorder and posttraumatic stress disorder among Cambodian refugees, and that such an approach may be useful for the culturally sensitive adaptation of cognitive-behavior therapy for other traumatized non-Western groups.