Lia K. Rosenstein

Have treatment studies of depression become even less generalizable?: a review of the inclusion and exclusion criteria used in placebo-controlled antidepressant efficacy trials published during the past 20 years

OBJECTIVE To compare the inclusion and exclusion criteria used in antidepressant efficacy trials (AETs) published during the past 5 years with those used in studies published during the previous 15 years. PATIENTS AND METHODS We conducted a comprehensive literature review of placebo-controlled AETs published from January 1995 through December 2014. We included trials whether or not the medication has received regulatory approval for the treatment of depression. We compared the inclusion and exclusion criteria of studies published during the past 5 years (2010-2014) with those of studies published during the previous 15 years (1995-2009). RESULTS We identified 170 placebo-controlled AETs published during the past 20 years, 56 of which were published during the past 5 years. The more recent studies were significantly more likely to exclude patients with comorbid Axis I disorders and personality disorders, patients with the episode duration either too long or too short, and patients who had made a suicide attempt in the past. The severity threshold on depression rating scales required for inclusion was higher in the more recent studies. CONCLUSION The inclusion and exclusion criteria of AETs have become more stringent over the past 5 years, thereby suggesting that AETs may be even less generalizable than they were previously (when concerns about their generalizability had already been raised).

A clinically useful self-report measure of the DSM-5 anxious distress specifier for major depressive disorder.

OBJECTIVE To acknowledge the clinical significance of anxiety in depressed patients, DSM-5 included criteria for an anxious distress specifier for major depressive disorder. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we modified our previously published depression scale to include a subscale assessing the DSM-5 anxious distress specifier. METHOD From December 1995 to August 2013, 773 psychiatric outpatients with major depressive disorder completed the Clinically Useful Depression Outcome Scale (CUDOS) supplemented with questions for the DSM-5 anxious distress specifier (CUDOS-A). To examine discriminant and convergent validity, the patients were rated on clinician severity indices of depression, anxiety, and irritability. Discriminant and convergent validity was further examined in a subset of patients who completed other self-report symptom severity scales. Test-retest reliability was examined in a subset who completed the CUDOS-A twice. We compared patients who did and did not meet the DSM-5 anxious distress specifier on indices of psychosocial functioning and quality of life. RESULTS The CUDOS-A subscale had high internal consistency and test-retest reliability; was more highly correlated with other self-report measures of anxiety than with measures of depression, substance use problems, eating disorders, and anger; and was more highly correlated with clinician severity ratings of anxiety than depression and irritability. CUDOS-A scores were significantly higher in depressed outpatients with a current anxiety disorder than in depressed patients without a comorbid anxiety disorder (P < .001). Finally, patients who met the DSM-5 anxious distress specifier reported poorer psychosocial functioning and quality of life than patients who did not meet the anxious distress specifier. CONCLUSIONS In the present study of a large sample of psychiatric outpatients, the CUDOS-A was a reliable and valid measure of the DSM-5 anxious distress specifier for major depressive disorder.

Comorbid bipolar disorder and borderline personality disorder and substance use disorder

Abstract Bipolar disorder (BD) and borderline personality disorder (BPD) are disabling and life-threatening conditions. Both disorders share relevant comorbidities, particularly the risk of having a lifetime substance use disorder (SUD). We tested the hypothesis that patients with both BD type I (BDI) or II (BDII) and BPD would have a higher rate of SUD than would patients with either disorder alone. A total of 3651 psychiatric patients were evaluated with semistructured diagnostic interviews for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, axis I and II disorders. A total of 63 patients were diagnosed with both BD and BPD, and these patients were significantly more likely to have a SUD compared with BDII patients without BPD (76% vs. 50%, &khgr;2 = 9.69, p < 0.01). There were no differences when comparing the comorbid group with BPD patients without BD (76% vs. 71%, &khgr;2 = 0.519, p = 0.4). The present study shows the importance of taking both BPD and BD into consideration insofar as the co-occurrence of the disorders increased the risk of having a SUD especially when compared with BDII alone.

The Clinical Significance of Single Features of Borderline Personality Disorder: Anger, Affective Instability, Impulsivity, and Chronic Emptiness in Psychiatric Outpatients.

Although dimensional models of borderline personality disorder (BPD) are consistent with findings showing that minimal levels of pathology are associated with substantial increases in psychosocial impairment, it is still unclear whether different individual BPD criteria are each clinically significant on their own. The current study uses semistructured interview data from 1,870 adults presenting for outpatient psychiatric treatment to investigate whether the BPD criteria of impulsivity, affective instability, emptiness, and anger are each related to psychosocial morbidity when met in the absence of the other eight criteria. Analyses showed that each of these criteria was associated with dysfunction in comparison with a control group meeting zero BPD criteria, but only the emptiness criterion was a marker of impairment on all indices of psychosocial morbidity: suicidality, history of suicide attempts and psychiatric hospitalizations, social and work dysfunction, Axis I comorbidity, and global functioning. Implications for the study of borderline pathology are discussed.

Body mass index, depression, and suicidality: The role of self-esteem in bariatric surgery candidates

BACKGROUND Previous research suggests a relationship between weight and depression/suicidality, although few studies have examined the mechanisms underlying this association. This study examined the mediating role of self-esteem in the relationship between BMI and depression/suicidality, as well as the moderating role of gender in the mediated pathways. METHODS As part of a screening process in consideration for bariatric surgery, 3,101 adults (81.4% female, 18.6% male) were assessed one time. Five univariate mediation and five univariate moderated-mediation models were hypothesized and analyzed. For the mediation models, we entered five outcome variables separately: 1) severity of depressed mood, 2) diagnosis of Major Depressive Disorder, 3) lifetime history of suicide attempts, 4) suicidal ideation at the time of evaluation, and 5) severity of suicidality, BMI as the independent variable, and self-esteem as the mediator. For the moderated-mediated models, gender was examined as a moderator to examine whether self-esteem was a stronger mediator for one gender, compared to the other. RESULTS Findings supported the mediating role of self-esteem across all five outcomes. Further, the mediated effect was moderated by gender, such that the mediation effect was stronger for males, compared to females. LIMITATIONS The majority of the sample consisted of White females, limiting broad applicability of findings. All variables were assessed simultaneously, at baseline, limiting the ability to make causal attributions. CONCLUSIONS Study findings suggest that self-esteem may help explain the relationship between BMI and depression/suicidality, particularly for men. Thus, interventions targeting self-esteem may be useful for improving psychological outcomes among those presenting for bariatric surgery.

Problems in the Descriptions of the Psychiatric Inclusion and Exclusion Criteria in Publications of Antidepressant Efficacy Trials: A Qualitative Review and Recommendations for Improved Clarity

We recently conducted a comprehensive review of the psychiatric inclusion and exclusion criteria used in 170 placebo-controlled antidepressant efficacy trials (AETs) that were published between 1995 and 2014. In conducting this literature review, we identified a number of instances in which the descriptions of the inclusion/exclusion criteria were vague, redundant, or difficult to interpret. In the present article, we describe nine problems we encountered in our literature review. We recommend that future publications follow the examples found in a few studies in which the inclusion/exclusion criteria are clearly defined and listed in a table.

Modification of the medical exclusion criterion in DSM-5 social anxiety disorder: Comorbid obesity as an example

BACKGROUND The DSM 5 modified the medical exclusion criterion from DSM-IV, which now allows for a diagnosis of social anxiety disorder (SAD) to be given if the fears are related only to the medical condition (e.g., obesity) yet cause significant impairment or distress. METHODS To examine this modification, the current study compared bariatric surgery candidates with DSM-IV SAD (n=135), modified SAD (clinically significant social fears related to obesity only; n=40), and no history of Axis I disorders (n=616) on variables related to pre-surgical problematic eating behaviors, body image dissatisfaction, functional impairment, and other characteristics related to bariatric surgery. Participants were referred by their surgeon for a psychiatric evaluation as part of the clearance process, and completed a comprehensive, semi-structured diagnostic interview and self-report measures. RESULTS There were several differences between those with DSM-IV SAD and modified SAD compared to those with no disorder (e.g., on binge and emotional eating), but the two SAD groups did not differ from each other on any of the comparisons. LIMITATIONS Results may not generalize to individuals suffering from obesity in the general population or those seeking other types of weight loss treatment. Because they were seeking psychiatric clearance, they also may have underreported symptoms/problems for fear that they would not get cleared. CONCLUSIONS Overall, the modified SAD group more closely resembled the DSM-IV SAD group rather than the no disorder group, providing further support for diagnosing SAD even when the social fears are related to obesity only.

Community and Clinical Epidemiology of Borderline Personality Disorder

Several studies of the prevalence of borderline personality disorder in community and clinical settings have been carried out to date. Although results vary according to sampling method and assessment method, median point prevalence is roughly 1%, with higher or lower rates in certain community subpopulations. In clinical settings, the prevalence is around 10% to 12% in outpatient psychiatric clinics and 20% to 22% among inpatient clinics. Further research is needed to identify the prevalence and correlates of borderline personality disorder in other clinical settings (eg, primary care) and to investigate the impact of demographic variables on borderline personality disorder prevalence.

The Role of Emotion Regulation Difficulties in the Connection Between Childhood Emotional Abuse and Borderline Personality Features

In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we examined the role of emotion dysregulation as a mediator between childhood abuse and borderline personality disorder (BPD) feature severity among a sample of 964 adults presenting for treatment at an outpatient clinic. A structural equation model suggested that emotional abuse relates to BPD features both directly and through difficulties with emotion regulation, whereas physical abuse showed only a weak indirect relation with BPD features. There was no link between sexual abuse and BPD feature severity in the model. Results add specificity to etiological theories of BPD and suggest that future research in treatment should focus on developing and strengthening emotion regulation strategies in clinical populations with a history of emotional abuse. Clinicians should be sure to assess the presence of childhood emotional abuse in addition to sexual and physical abuse.

Inclusion/exclusion criteria in late life depression antidepressant efficacy trials.

The generalizability of antidepressant efficacy trials (AETs) has been questioned. No studies have examined the inclusion/exclusion criteria used in placebo‐controlled studies of late life depression and compared them to the criteria used in non‐late life AETs.