The Effects of the Angiotensin II Receptor Antagonist Losartan on Appetitive Versus Aversive Learning: A Randomized Controlled Trial.

BACKGROUND: Exposure therapy is a first-line treatment for anxiety disorders but remains ineffective in a large proportion of patients. A proposed mechanism of exposure involves inhibitory learning whereby the association between a stimulus and an aversive outcome is suppressed by a new association with an appetitive or neutral outcome. The blood pressure medication losartan augments fear extinction in rodents and may have similar synergistic effects on human exposure therapy, but the exact cognitive mechanisms underlying these effects remain unknown. METHODS: We used a reinforcement learning paradigm with compound rewards and punishments to test the prediction that losartan augments learning from appetitive relative to aversive outcomes. In a double-blind parallel design, healthy volunteers were randomly assigned to single-dose losartan (50 mg) (n = 28) versus placebo (n = 25). Participants then performed a reinforcement learning task, which simultaneously probes appetitive and aversive learning. Participant choice behavior was analyzed using both a standard reinforcement learning model and analysis of choice switching behavior. RESULTS: Losartan significantly reduced learning rates from aversive events (losses) when participants were first exposed to the novel task environment, while preserving learning from positive outcomes. The same effect was seen in choice switching behavior. CONCLUSIONS: This study shows that losartan enhances learning from positive relative to negative events. This effect may represent a computationally defined neurocognitive mechanism by which the drug could enhance the effect of exposure in clinical populations.

Measuring psychiatric patients satisfaction with the initial evaluation: A comparison of 2 measures.

As part of Maintenance of Certification (MOC) for physicians, the American Board of Psychiatry and Neurology (APBN) developed a patient satisfaction form. We are not aware of any studies of the ABPN satisfaction survey. The goal of the present study was to examine the psychometric characteristics of the ABPN survey, and to compare it to a satisfaction measure that was designed to assess satisfaction with the initial evaluation. Two hundred seven patients completed the APBN measure and the Clinically Useful Patient Satisfaction Scale (CUPSS) after their initial meeting with the psychiatrist. The patients also completed a questionnaire asking which of the two scales were better measures of satisfaction with the initial evaluation. The items on both scales were negatively skewed, and approximately 90% of the ratings on the APBN scale received the highest rating. Both scales had high internal consistency. All items were significantly correlated with indicators of global satisfaction. There was sufficient variability in satisfaction ratings to detect differences amongst clinicians. Significantly more patients indicated that the CUPSS was a better indicator of their satisfaction with the evaluation. The results of the present study raise some concerns about the ABPN measure. There was evidence of a ceiling effect, and this ceiling effect raises questions about the usefulness of the scale for the purposes of self-improvement. The psychometrics of the CUPSS were stronger, and it was preferred by patients as a measure of satisfaction with the initial evaluation.

Screening for psychiatric disorders with self-administered questionnaires.

Given the time demands of clinical practice it is not surprising that diagnoses are sometimes missed. To improve diagnostic recognition, self-administered screening scales have been recommended. A problem with much of the research effort on screening scales is the confusion between diagnostic testing and screening. It is important for a screening test to have high sensitivity because the more time intensive/expensive follow-up diagnostic inquiry will presumably only occur in patients who are positive on the initial screen. Investigators vary in how they analyze their data in determining the recommended cutoff score on a self-administered screening questionnaire. To illustrate this, in the present report we examined how often each of the different approaches towards determining a cutoff score on bipolar disorder screening scales were used. We reviewed 68 reports of the performance of the 3 most commonly researched bipolar disorder screening scales to determine how the recommended cutoff on the scale was derived. Most studies recommended a cutoff point on the screening scale that optimized the level of agreement with the diagnostic gold standard. Only 11 (16.2%) studies recommended a cutoff that prioritized the scale's sensitivity. It is important for clinicians to understand the difference between screening and diagnostic tests. The results of the present study indicate that most studies of the performance of the 3 most commonly studied bipolar disorder screening measures have taken the wrong approach in deriving the cutoff score on the scale for the purpose of screening.

The impact of anonymity on psychiatric patients' ratings of satisfaction with the initial evaluation.

BACKGROUND: Preserving anonymity is believed to yield more honest appraisals of patient satisfaction, although the data addressing this issue are sparse. The goal of this study from the Rhode Island Methods to Improve Diagnostic Assessment and Services project was to determine the impact of anonymity on patient satisfaction ratings after the initial evaluation. METHODS: The Clinically Useful Patient Satisfaction Scale (CUPSS) is a brief, self-administered questionnaire assessing patients' satisfaction with the initial evaluation. Every 2 to 3 months, we switched from anonymous to non-anonymous completion of the CUPSS. More than 1,300 patients completed the scale (729 anonymous, 603 non-anonymous). RESULTS: Anonymity was not associated with scores on the scale. In both the anonymous and non-anonymous conditions, the CUPSS had high internal consistency, all item-scale correlations were significant, and all items were significantly correlated with global satisfaction ratings. There was sufficient variability in satisfaction ratings to detect differences among clinicians. CONCLUSIONS: Anonymity was not associated with patient satisfaction ratings, did not affect the psychometric properties of the scale, and did not compromise the scale's ability to discriminate among clinicians. That is, anonymity did not affect the reliability or validity of satisfaction ratings.

Measuring anxiety in depressed patients: A comparison of the Hamilton anxiety rating scale and the DSM-5 Anxious Distress Specifier Interview.

DSM-5 included criteria for an anxious distress specifier for major depressive disorder (MDD). In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we examined whether a measure of the specifier, the DSM-5 Anxious Distress Specifier Interview (DADSI), was as valid as the Hamilton Anxiety Scale (HAMA) as a measure of the severity of anxiety in depressed patients. Two hundred three psychiatric patients with MDD were interviewed by trained diagnostic raters who administered the Structured Clinical Interview for DSM-IV (SCID) supplemented with questions to rate the DADSI, HAMA, and Hamilton Depression Rating Scale (HAMD). The patients completed self-report measures of depression, anxiety, and irritability. Sensitivity to change was examined in 30 patients. The DADSI and HAMA were significantly correlated (r = 0.60, p < 0.001). Both the DADSI and HAMA were more highly correlated with measures of anxiety than with measures of the other symptom domains. The HAMD was significantly more highly correlated with the HAMA than with the DADSI. For each anxiety disorder, patients with the disorder scored significantly higher on both the DADSI and HAMA than did patients with no current anxiety disorder. A large effect size of treatment was found for both measures (DADSI: d = 1.48; HAMA: d = 1.37). Both the DADSI and HAMA were valid measures of anxiety severity in depressed patients, though the HAMA was more highly confounded with measures of depression than the DADSI. The DADSI is briefer than the HAMA, and may be more feasible to use in clinical practice.

Reliability and validity of the DSM-5 Anxious Distress Specifier Interview.

BACKGROUND: To acknowledge the clinical significance of anxiety in depressed patients, DSM-5 included an anxious distress specifier for major depressive disorder (MDD). In the present report we describe the reliability and validity of a semi-structured interview assessing the features of the anxious distress specifier. Our goal was to develop an instrument that could be used for both diagnostic and outcome measurement purposes. METHODS: One hundred seventy-three psychiatric patients with MDD were interviewed by a trained diagnostic rater who administered the Structured Clinical Interview for DSM-IV (SCID) supplemented with questions from the DSM-5 Anxious Distress Specifier Interview (DADSI). Inter-rater (n=25) and test-retest (n=25) reliability of the DADSI was examined in separate groups of patients. The patients were rated on clinician rating scales of depression, anxiety and irritability, and patients completed self-report measures of these constructs. Sensitivity to change was examined in 16 patients. RESULTS: Approximately three-quarters of the depressed patients met the criteria for the anxious distress specifier (78.0%, n=135). The DADSI had excellent joint-interview reliability and good test-retest reliability. DADSI total scores were more highly correlated with other clinician-rated and self-report measures of anxiety than with measures of depression and anger. DADSI scores were significantly higher in depressed outpatients with a current anxiety disorder than depressed patients without a comorbid anxiety disorder. The DADSI was sensitive to improvement. CONCLUSION: The DADSI is a reliable and valid measure of the presence of the DSM-5 anxious distress specifier for MDD as well as the severity of the features of the specifier.

A clinically useful self-report measure of psychiatric patients' satisfaction with the initial evaluation.

Patient satisfaction is one component of the quality of care. Studies of satisfaction in samples of established patients are biased because dissatisfied patients are more likely to have dropped out of treatment. We, therefore, sought to develop a new instrument assessing patients' satisfaction with the initial psychiatric evaluation. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we describe the development, reliability, and validity of the Clinically Useful Patient Satisfaction Scale (CUPSS). The CUPSS is a brief, self-administered questionnaire covering 3 areas: clinician's attitude and behavior, office environment and staff, and overall satisfaction. A sample of psychiatric outpatients (n=412) and partial hospital patients (n=500) completed the measure immediately after their initial meeting with the psychiatrist. The scale had high internal consistency, and all item-scale correlations were significant. All items were significantly correlated with each of the indicators of global satisfaction. There was sufficient variability in satisfaction ratings to detect differences amongst clinicians. The results of the present study of psychiatric outpatients and partial hospital patients indicate that the CUPSS was minimally to not at all burdensome to complete, it had good psychometric properties, and it can discriminate amongst clinicians.

The Psychiatric Inclusion and Exclusion Criteria in Placebo-Controlled Monotherapy Trials of Bipolar Depression: An Analysis of Studies of the Past 20 Years.

BACKGROUND: Concerns about the generalizability of pharmacotherapy efficacy trials to "real-world" patients have been raised for more than 40 years. Almost all of this literature has focused on treatment studies of major depressive disorder (MDD). OBJECTIVE: The aim of the study was to review the psychiatric inclusion and exclusion criteria used in placebo-controlled trials that assessed the efficacy of medications for bipolar depression (bipolar disorder efficacy trials [BDETs]) and compare the criteria used in BDETs with those used in efficacy trials of antidepressants to treat MDD (antidepressant efficacy trials [AETs]). METHODS: We searched the MEDLINE, Embase, and PsycINFO databases for articles published from January 1995 through December 2014. We identified 170 placebo-controlled AETs and 22 BDETs published during these 20 years. Two of the authors independently reviewed each article and completed a pre-specified information extraction form listing the psychiatric inclusion and exclusion criteria used in the study. RESULTS: Six inclusion/exclusion criteria were used in at least half of the BDETs: minimum severity on a depression symptom severity scale, significant suicidal ideation, diagnosis of alcohol or drug use disorder, presence of a comorbid nondepressive, nonsubstance use Axis I disorder, current episode of depression being too long, and absence of current manic symptoms. BDETs were significantly less likely than AETs to exclude patients with a history of psychotic features/disorders, borderline personality disorder, and post-traumatic stress disorder and more likely to exclude individuals who scored too low on the first item of the Hamilton Depression Rating Scale. Nearly two-thirds of the BDETs placed an upper limit on the duration of the current depressive episode, three times higher than the rate in the AETs. There was no difference on other variables between the AETs and BDETs. CONCLUSIONS: Similar to treatment studies of nonbipolar MDD, the treatment studies of bipolar depression frequently excluded patients with comorbid psychiatric and substance use disorders and insufficient severity of depressive symptoms as rated on standardized scales. These findings indicate that concerns about the generalizability of data from trials of recently approved medications for the treatment of bipolar depression are as relevant as the concerns that have been raised about studies of antidepressants for nonbipolar depression.