Use of a Fully Automated Internet-Based Cognitive Behavior Therapy Intervention in a Community Population of Adults With Depression Symptoms: Randomized Controlled Trial.

BACKGROUND: Although internet-based cognitive behavior therapy (iCBT) interventions can reduce depression symptoms, large differences in their effectiveness exist. OBJECTIVE: The aim of this study was to evaluate the effectiveness of an iCBT intervention called Thrive, which was designed to enhance engagement when delivered as a fully automated, stand-alone intervention to a rural community population of adults with depression symptoms. METHODS: Using no diagnostic or treatment exclusions, 343 adults with depression symptoms were recruited from communities using an open-access website and randomized 1:1 to the Thrive intervention group or the control group. Using self-reports, participants were evaluated at baseline and 4 and 8 weeks for the primary outcome of depression symptom severity and secondary outcome measures of anxiety symptoms, work and social adjustment, psychological resilience, and suicidal ideation. RESULTS: Over the 8-week follow-up period, the intervention group (n=181) had significantly lower depression symptom severity than the control group (n=162; P<.001), with a moderate treatment effect size (d=0.63). Moderate to near-moderate effect sizes favoring the intervention group were observed for anxiety symptoms (P<.001; d=0.47), work/social functioning (P<.001; d=0.39), and resilience (P<.001; d=0.55). Although not significant, the intervention group was 45% less likely than the control group to experience increased suicidal ideation (odds ratio 0.55). CONCLUSIONS: These findings suggest that the Thrive intervention was effective in reducing depression and anxiety symptom severity and improving functioning and resilience among a mostly rural community population of US adults. The effect sizes associated with Thrive were generally larger than those of other iCBT interventions delivered as a fully automated, stand-alone intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT03244878; https://clinicaltrials.gov/ct2/show/NCT03244878.

Subjective quality of life and sexual dysfunction in outpatients with schizophrenia or schizoaffective disorder.

The objective of this research was to examine the association between sexual dysfunction and subjective quality of life in outpatients with schizophrenia and schizoaffective disorder. The authors evaluated a sample of 238 adult outpatients with diagnoses of schizophrenia or schizoaffective disorder who took quetiapine, olanzapine, or risperidone at study entry with a 1-time rating of the Arizona Sexual Experience Scale and the general life satisfaction scale item of the quality of life index. The authors used multiple linear robust regression and Spearman partial correlation coefficient to examine the relation between subjective quality of life (measured by the general life satisfaction scale item) and sexual functioning (measured by the Arizona sexual experience scale). The authors found a significant negative linear relation between the Arizona Sexual Experience Scale total score and the general life satisfaction scale item for the overall sample (r(s) = -0.16, p = .01), but not separately for men or women. Sexual dysfunction in men and women with schizophrenia and schizoaffective disorder is associated with decreased subjective quality of life, although the magnitude of the effect size was relatively small. Improving clinicians' awareness of the importance of sexual dysfunction in patients may improve tolerability and subsequent treatment outcomes.

A single assessment with the Brief Adherence Rating Scale (BARS) discriminates responders to long-acting injectable antipsychotic treatment in patients with schizophrenia.

OBJECTIVE: To determine if a single baseline adherence assessment (Brief Adherence Rating Scale [BARS]) could identify patients who are likely to respond to long-acting injectable (LAI) antipsychotic treatment. METHOD: The current secondary analysis included a sub-sample of adult outpatients (N = 176) with schizophrenia or schizoaffective disorder who participated in the "A Comparison of Long-Acting Injectable Medications for Schizophrenia (ACLAIMS)" trial and had a baseline BARS assessment and a baseline and month 3 Positive and Negative Syndrome Scale (PANSS) rating. The main outcome was LAI treatment response, defined as a ≥ 20% decrease (baseline to month 3) on the PANSS total score. Receiver Operating Characteristic (ROC) and Area Under the Curve (AUC) analysis was conducted to determine the optimal cutpoint of baseline BARS adherence in discriminating LAI treatment response at month 3. A logistic mixed model estimated the odds of response to LAI treatment at month 3 from the optimal baseline BARS cutpoint. RESULTS: The ROC analysis determined that the single baseline BARS rating (cutoff ≤66%), indicating low adherence, best discriminated patients likely to respond to LAI treatment (AUC = 0.603, SE = 0.046, 95% binomial exact CI = 0.527 to 0.676, p = 0.025), with 38% sensitivity and 85% specificity. The logistic mixed model analysis revealed that patients with ≤66% BARS adherence had 3.464 times the predicted odds (95% CI = 1.604 to 7.480, p = 0.001) of responding to LAI treatment than those who were >66% BARS adherent. CONCLUSION: A single baseline BARS assessment discriminated response to LAI treatment suggesting it is a reasonable tool to identify candidates for LAI antipsychotic treatment.

The Youth Aware of Mental Health Intervention: Impact on Help Seeking, Mental Health Knowledge, and Stigma in U.S. Adolescents.

PURPOSE: Suicide is a leading cause of death among U.S. youth aged 12-18 years. Youth Aware of Mental Health (YAM), a promising, universal, school-based mental health promotion/suicide primary prevention intervention for adolescents, has been evaluated in Europe but not in the U.S. The present study used an uncontrolled, pretest/post-test design to document the potential for YAM to reduce suicidal ideation, attempt, and suicide. A demonstration that help seeking behaviors, mental health literacy, and mental health stigmatizing attitudes improve after the intervention would suggest that the program is promising in the U.S., as well as in Europe, and that further investigation is merited. METHODS: YAM was delivered to 1,878 students in 11 schools as part of regular school curricula. A subset of these students (n = 436) completed surveys before and 3 months postdelivery. Surveys included five questions about help seeking behaviors, a measure of intent to seek help (General Help Seeking Questionnaire), two mental health literacy scales, and two mental illness stigma scales (Reported and Intended Behavior Scale and Personal Stigma and Social Distance Scale). Both McNemar's test and repeated measures linear models were used to determine whether the survey outcomes changed after YAM delivery. RESULTS: Among the 436 adolescents (286 and 150 in Montana and Texas, respectively), significant increases were found pre- to post-intervention in three of five help seeking behaviors, along with improved mental health literacy and decreased mental health-related stigma. Intent to seek help was unchanged. CONCLUSIONS: Several help seeking behavioral factors, mental health knowledge, and stigma improved post-YAM intervention. All three domains are likely protective against suicide. A randomized controlled trial testing the efficacy of YAM in preventing suicidal behaviors is warranted.

Feasibility and Acceptability of the Youth Aware of Mental Health (YAM) Intervention in US Adolescents.

Suicide is the second leading cause of death among US adolescents, and rates of suicide among youth have been increasing for the past decade. This study assessed the feasibility and acceptability of the universal, school-based Youth Aware of Mental Health (YAM) program, a promising mental health promotion and suicide primary prevention intervention, in US youth. Using an uncontrolled design, the feasibility and acceptability of delivering and studying YAM were assessed in Montana and Texas schools. Thirteen of 16 (81.3%) schools agreed to support YAM delivery, and five Montana and 6 Texas schools were included in analyses. Facilitators delivered YAM in 78 classes (1,878 students) as regular high school curriculum. Of the total number of students who received YAM, 519 (27.6%) provided parental consent and assent. 436 (84.0%) consented students participated in pre- and post-surveys. Students, parents, and school staff found YAM highly acceptable based on satisfaction surveys. In summary, this study found YAM feasible to implement in US schools. Results also suggest students, parents, and school staff supported school-based programs and were highly satisfied with the YAM program. A randomized controlled trial is warranted to test the efficacy of YAM in promoting mental health and preventing suicidal thoughts and behaviors in US adolescents.

Effects of aripiprazole on prolactin levels in subjects with schizophrenia during cross-titration with risperidone or olanzapine: analysis of a randomized, open-label study.

Hyperprolactinemia, an adverse effect associated with the use of typical antipsychotics and the atypical antipsychotic risperidone, has both acute and chronic clinical consequences. One option for clinical management is switching to an agent with a lower liability for inducing hyperprolactinemia. This post-hoc sub-analysis of an 8-week, open-label study in outpatients with schizophrenia (CN138-215) examined short-term effects on prolactin levels during a switch from risperidone or olanzapine to aripiprazole 30 mg/day. Three switch strategies were used: (I) immediate aripiprazole initiation with simultaneous immediate discontinuation of olanzapine/risperidone; (II) immediate aripiprazole initiation while tapering off olanzapine/risperidone over 14 days; (III) titrating aripiprazole upwards while tapering off olanzapine/risperidone over 14 days. Changes in prolactin levels from baseline to each last observation carried forward time point were compared with t-tests using Bonferroni correction for multiple comparisons. This sub-analysis included 269 subjects: 105 previously treated with risperidone; 164 previously treated with olanzapine. Mean baseline prolactin levels (ng/mL) were within normal range for the three olanzapine groups (Group-I, 11.7; Group-II, 13.2; Group-III, 11.2), but above normal for the risperidone groups (Group-I, 39.7; Group-II, 48.5; Group-III, 33.5). Following aripiprazole initiation, mean prolactin levels decreased significantly (p<0.001) at week-1 and were maintained to week-8 in all groups irrespective of prior treatment. Previously elevated prolactin levels in the risperidone groups were reduced to within normal range within 1 week, irrespective of switching strategy. Tolerability was good regardless of prior medication or switching strategy. Overall, rapid decreases of prolactin levels were achieved safely with all three aripiprazole switching strategies. Reversal of hyperprolactinemia during the crossover period indicates the safety and potential utility of aripiprazole addition in patients with elevated prolactin.

The Brief Adherence Rating Scale (BARS) validated against electronic monitoring in assessing the antipsychotic medication adherence of outpatients with schizophrenia and schizoaffective disorder.

Among outpatients with schizophrenia, antipsychotic non-adherence is common, grossly under-detected by patients and their prescribers, and is associated with poor clinical outcomes. Using electronic monitoring (EM) as the reference standard we evaluated the reliability and validity as well as the sensitivity and specificity of a recently developed, brief, pencil-paper, clinician-administered adherence instrument [the Brief Adherence Rating Scale (BARS)] to assess the oral antipsychotic medication adherence of outpatients with schizophrenia and schizoaffective disorder. EM and BARS adherence and symptom severity ratings were gathered at baseline and prospectively at 6 monthly visits in 61 participants (n=35 with schizophrenia; n=26 with schizoaffective disorder). A significant positive relationship was found between mean BARS and EM adherence (beta=0.98; rs=0.59, p<0.0001). Cronbach's coefficient alpha revealed very high internal reliability for the BARS (alpha=0.92). A moderate-to-strong degree of test-retest reliability was also found for the BARS (beta ranged from 0.53 to 0.92 and rs ranged from 0.46 to 0.86). Regarding concurrent validity of the BARS, greater mean BARS adherence was significantly related to lower mean PANSS total scores (beta=-0.40; rs=-0.39, p=0.002) and to lower mean Positive symptom sub-scale scores (beta=-0.08, p=.007; rs=-0.28, p=.02). An initial 3-month monitoring period with the BARS also demonstrated good sensitivity (73%) and specificity (74%) in identifying non-adherent outpatients (defined as <70% mean EM adherence). Relative to EM, the BARS appears to provide valid, reliable, sensitive, and specific estimates of antipsychotic medication adherence of outpatients with schizophrenia and schizoaffective disorder. The BARS appears to be a promising candidate as a brief adherence assessment instrument for feasible use in community-based settings.

Electronic monitoring of antipsychotic medication adherence in outpatients with schizophrenia or schizoaffective disorder: an empirical evaluation of its reliability and predictive validity.

This study examined the reliability and predictive validity of electronic monitoring (EM) in assessing the oral antipsychotic medication adherence of outpatients with schizophrenia or schizoaffective disorder. Sixty-one adult outpatients with schizophrenia or schizoaffective disorder who took a single oral antipsychotic medication were assessed monthly over a 6-month study period with EM of medication bottle opening. Symptom severity, as measured by the Positive and Negative Syndrome Scale (PANSS) total score, was assessed monthly over the 6-month study period. Cronbach's coefficient alpha revealed very high internal reliability (alpha=0.94). A high degree of test-retest reliability was found (beta ranged from 0.75 to 1.19 and r ranged from 0.63 to 0.90). As for predictive validity, greater mean EM adherence was significantly related to lower mean symptom severity.

Sexual functioning associated with quetiapine switch vs. risperidone continuation in outpatients with schizophrenia or schizoaffective disorder: a randomized double-blind pilot trial.

This study evaluated the effect of switching to quetiapine vs. risperidone continuation on sexual functioning in outpatients with risperidone-associated sexual dysfunction. Outpatients (n=42, age>or=18 years) with schizophrenia or schizoaffective disorder who experienced risperidone-associated sexual dysfunction were randomized to 6 weeks of double-blind risperidone continuation (mean dose=4.1 mg/day, S.D.=1.2) or quetiapine switch (mean dose=290.0 mg/day, S.D.=55.2) treatment. The five-item Arizona Sexual Experience Scale (ASEX) assessed sexual functioning at baseline and subsequently at weeks 2, 4 and 6. A mixed-model analysis of repeated measures included gender and baseline ASEX and PANSS scores as covariates. There was no significant Treatment Group effect for ASEX total scores and ASEX sub-items, and no significant Treatment GroupxPeriod interaction for ASEX total scores and ASEX sub-items. Treatment Group effects were not significantly different in any of the prospective weeks for ASEX total scores and ASEX sub-items. Adjusted mean ASEX total scores were slightly lower in the quetiapine switch group than in the risperidone continuation group at weeks 2 and 6 (21.27 vs. 22.18 and 18.51 vs. 20.53, respectively), but were nearly identical at week 4 (20.01 vs. 20.15). In this pilot trial, sexual functioning did not differ significantly between outpatients receiving quetiapine switch vs. risperidone continuation, although the quetiapine switch group had slightly lower adjusted mean ASEX total scores at weeks 2 and 6.

Validity of electronically monitored medication adherence and conventional adherence measures in schizophrenia.

OBJECTIVE: This study evaluated the validity of prescriber, patient, and research assistant ratings of adherence to prescribed oral antipsychotic medication among outpatients with schizophrenia or schizoaffective disorder in comparison with electronic monitoring. METHODS: Adult outpatients with schizophrenia (N=35) or schizoaffective disorder (N=26) received adherence assessments via electronically monitored medication vial caps as well as by monthly prescriber, patient, and research assistant report for up to six months. RESULTS: Electronic monitoring detected greater nonadherence rates (57%) than either prescribers (7%) or patients (5%), though the research assistant ratings were 54%. No directional bias was found between electronic monitoring and assignment of adherence by research assistants, although disagreement occurred in 36% of cases. CONCLUSIONS: Both patients and prescribers grossly overestimated medication adherence, which may interfere with or reduce the effectiveness of diligent medication management.

A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome.

BACKGROUND: Cortical hyperexcitability due to abnormal fast-spiking inhibitory interneuron function has been documented in fmr1 KO mice, a mouse model of the fragile X syndrome which is the most common single gene cause of autism and intellectual disability. METHODS: We collected resting state dense-array electroencephalography data from 21 fragile X syndrome (FXS) patients and 21 age-matched healthy participants. RESULTS: FXS patients exhibited greater gamma frequency band power, which was correlated with social and sensory processing difficulties. Second, FXS patients showed increased spatial spreading of phase-synchronized high frequency neural activity in the gamma band. Third, we observed increased negative theta-to-gamma but decreased alpha-to-gamma band amplitude coupling, and the level of increased theta power was inversely related to the level of resting gamma power in FXS. CONCLUSIONS: Increased theta band power and coupling from frontal sources may represent a mechanism providing compensatory inhibition of high-frequency gamma band activity, potentially contributing to the widely varying level of neurophysiological and behavioral abnormalities and treatment response seen in full-mutation FXS patients. These findings extend preclinical observations and provide new mechanistic insights into brain alterations and their variability across FXS patients. Electrophysiological measures may provide useful translational biomarkers for advancing drug development and individualizing treatments for neurodevelopmental disorders with associated neuronal hyperexcitability.

Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome.

BACKGROUND: Studies in the fmr1 KO mouse demonstrate hyper-excitability and increased high-frequency neuronal activity in sensory cortex. These abnormalities may contribute to prominent and distressing sensory hypersensitivities in patients with fragile X syndrome (FXS). The current study investigated functional properties of auditory cortex using a sensory entrainment task in FXS. METHODS: EEG recordings were obtained from 17 adolescents and adults with FXS and 17 age- and sex-matched healthy controls. Participants heard an auditory chirp stimulus generated using a 1000-Hz tone that was amplitude modulated by a sinusoid linearly increasing in frequency from 0-100 Hz over 2 s. RESULTS: Single trial time-frequency analyses revealed decreased gamma band phase-locking to the chirp stimulus in FXS, which was strongly coupled with broadband increases in gamma power. Abnormalities in gamma phase-locking and power were also associated with theta-gamma amplitude-amplitude coupling during the pre-stimulus period and with parent reports of heightened sensory sensitivities and social communication deficits. CONCLUSIONS: This represents the first demonstration of neural entrainment alterations in FXS patients and suggests that fast-spiking interneurons regulating synchronous high-frequency neural activity have reduced functionality. This reduced ability to synchronize high-frequency neural activity was related to the total power of background gamma band activity. These observations extend findings from fmr1 KO models of FXS, characterize a core pathophysiological aspect of FXS, and may provide a translational biomarker strategy for evaluating promising therapeutics.

Erratum to: Neural synchronization deficits linked to cortical hyper-excitability and auditory hypersensitivity in fragile X syndrome.

[This corrects the article DOI: 10.1186/s13229-017-0140-1.].

Electronically monitored adherence in outpatients with schizophrenia or schizoaffective disorder: a comparison of first- vs. second-generation antipsychotics.

OBJECTIVE: To examine the effect of first- vs. second-generation antipsychotics on electronically monitored adherence in outpatients with schizophrenia or schizoaffective disorder. METHOD: The sample consisted of 61 outpatients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who took either a first-generation (N=25) or second-generation (N=36) oral antipsychotic during study participation. Treatment group designation (first-vs. second-generation antipsychotic) was based on the particular antipsychotic medication the patient was receiving as part of routine care at study entry (i.e., non-random assignment). Adherence to prescribed antipsychotic medication was assessed monthly over a 6-month study period using electronic monitoring (EM) of medication bottle opening. Various participant characteristics were collected at baseline to test for group differences and for potential associations with prospectively measured adherence. The primary data analysis was a mixed-model analysis of repeated measures. RESULTS: The analysis of EM adherence revealed no significant difference between those taking first-generation (6-month adjusted mean adherence=64.35%) and second-generation antipsychotics (6-month adjusted mean adherence=69.17%; Group effect, p=.29) and no significant Group X Period interaction (p=.13). CONCLUSION: There was no statistical difference in EM adherence, over a 6-month period, between patients taking first- and second-generation antipsychotics. However, since the patients were not randomized, conclusions must be interpreted within the context of the quasi-experimental design used in the current study.

Sexual dysfunction associated with second-generation antipsychotics in outpatients with schizophrenia or schizoaffective disorder: an empirical evaluation of olanzapine, risperidone, and quetiapine.

OBJECTIVE: Evaluate sexual dysfunction, as measured by the Arizona Sexual Experience Scale (ASEX), in olanzapine-, quetiapine-, and risperidone-treated outpatients with schizophrenia or schizoaffective disorder. METHOD: The sexual functioning of 238 outpatients (age> or =18 years) with diagnoses of schizophrenia or schizoaffective disorder who took quetiapine (n=57), olanzapine (n=94), or risperidone (n=87) was evaluated with a one-time rating of the ASEX. The dose range for each treatment group was 5 to 40 mg/day (M=16.6 mg/day, SD=7.4) for olanzapine; 1 to 8 mg/day (M=3.9 mg/day, SD=1.6) for risperidone; and 50 to 900 mg/day (M=376.8 mg/day, SD=213.4) for quetiapine. Antipsychotic group designation was based on medication treatment at study entry (i.e., non-random assignment). Participant characteristics were collected to test for treatment group differences and for potential associations with severity of sexual dysfunction. The primary data analysis was a mixed linear model analysis of covariance with age, gender, and presence/absence of antidepressant known to cause sexual dysfunction included as covariates. RESULTS: There was a significant treatment effect on severity of sexual dysfunction, as measured by ASEX total scores (p=.04). The adjusted average ASEX total scores were lower in the quetiapine (M=17.80) than in the risperidone (M=19.69) or olanzapine (M=20.34) groups. Individual comparisons of the treatments on adjusted average ASEX total scores indicated a significant difference between olanzapine and quetiapine (p=.04), but no difference between risperidone and quetiapine (p=.17) or olanzapine and risperidone (p=.76). CONCLUSIONS: Quetiapine was associated with less severe sexual dysfunction than olanzapine and risperidone (albeit the effect between risperidone and quetiapine was not statistically significant). Olanzapine and risperidone were associated with a comparable degree of sexual dysfunction. Patients in all three treatment groups, nonetheless, experienced a moderately high degree of sexual dysfunction. Because the patients were not randomized, conclusions must be interpreted within the context of the quasi-experimental design.

An empirical evaluation of the Arizona sexual experience scale and a simple one-item screening test for assessing antipsychotic-related sexual dysfunction in outpatients with schizophrenia and schizoaffective disorder.

We examined the reliability and construct validity of the 5-Item Arizona Sexual Experience Scale (ASEX) in patients with schizophrenia or schizoaffective disorder. In addition, we assessed the performance of two 1-item screening questions to detect sexual dysfunction as defined by a cut-off scoring criteria of sexual dysfunction for the ASEX. One question was a general question about any side effects. The second question asked specifically about sexual dysfunction. Altogether 247 participants with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder provided data at a single interview. Results indicated that the ASEX has good internal consistency and construct validity for the patients with schizophrenia and schizoaffective disorder. The point-biserial correlations and logistic regression found a high degree of agreement between the one-item specific screening question for sexual dysfunction and the ASEX. Overall, sensitivity (85%), specificity (63.7%), and positive (83%) and negative (67.1%) predictive values for the specific one-item screening question were satisfactory. The single general side effect question performed poorly (sensitivity=11.3%; specificity=92.5%; positive predictive value=76%; negative predictive value=33%). The current findings demonstrate the highly acceptable psychometric properties of the ASEX in patients with schizophrenia or schizoaffective disorder. In addition, a specific one-item screening question is of clinical utility in patients with schizophrenia or schizoaffective disorder.

Cost-Effectiveness of Long-Acting Injectable Paliperidone Palmitate Versus Haloperidol Decanoate in Maintenance Treatment of Schizophrenia.

OBJECTIVE: This study assessed the relative cost-effectiveness of haloperidol decanoate (HD), a first-generation long-acting injectable (LAI) antipsychotic, and paliperidone palmitate (PP), a second-generation LAI antipsychotic. METHODS: A double-blind, randomized 18-month clinical trial conducted at 22 clinical research sites in the United States compared the cost-effectiveness of HD and PP among 311 adults with schizophrenia or schizoaffective disorder who had been clinically assessed as likely to benefit from an LAI antipsychotic. Patients were randomly assigned to monthly intramuscular injections of HD (25-200 mg) or PP (39-234 mg) for up to 24 months. Quality-adjusted life years (QALYs) were measured by a schizophrenia-specific algorithm based on the Positive and Negative Syndrome Scale and side-effect assessments; total health care costs were assessed from the perspective of the health system. RESULTS: Mixed-model analysis showed that PP was associated with .0297 greater QALYs over 18 months (p=.03) and with $2,100 more in average costs per quarter for inpatient and outpatient services and medication compared with HD (p<.001). Bootstrap analysis with 5,000 replications showed an incremental cost-effectiveness ratio for PP of $508,241 per QALY (95% confidence interval=$122,390-$1,582,711). Net health benefits analysis showed a .98 probability of greater cost-effectiveness for HD compared with PP at an estimated value of $150,000 per QALY and a .50 probability of greater cost-effectiveness at $500,000 per QALY. CONCLUSIONS: HD was more cost-effective than PP, suggesting that PP's slightly greater benefits did not justify its markedly higher costs, which are likely to fall once the medication's patent expires.

A trial of compliance therapy in outpatients with schizophrenia or schizoaffective disorder.

OBJECTIVE: To evaluate the efficacy of compliance therapy when delivered to outpatients with schizophrenia or schizoaffective disorder. METHOD: Thirty patients with schizophrenia or schizoaffective disorder (DSM-IV criteria) were recruited from urban psychiatric outpatient clinics in an open trial of compliance therapy. Compliance therapy is a cognitive/psychoeducational approach consisting of 4 to 6 sessions lasting 30 to 60 minutes each. The primary outcome was electronically measured antipsychotic medication adherence. Adherence data were analyzed for effects during an initial treatment period (month -1 to month +1) and a subsequent 5-month follow-up period. Secondary outcome measures included clinician and patient ratings of adherence, symptoms, insight, and attitudes to medication treatment. Data were collected from August 2001 to January 2004. RESULTS: Compliance therapy was not associated with improvements in antipsychotic medication adherence. Patient ratings of adherence improved during the month -1 to month +1 period, but not in the subsequent 5-month follow-up. A diagnosis of schizoaffective disorder was associated with poorer adherence than was a diagnosis of schizophrenia during the month -1 to month +1 period. A higher degree of insight at baseline (end of month -1) was associated with greater adherence in the 5-month follow-up period. Symptoms, insight, and attitudes to medication treatment did not change significantly during the study. CONCLUSION: In this uncontrolled trial, outpatients with schizophrenia or schizoaffective disorder did not benefit from compliance therapy.

Predicting placebo response in adolescents with major depressive disorder: The Adolescent Placebo Impact Composite Score (APICS).

OBJECTIVE: The aim of this study was to construct a composite scoring system to predict the probability of placebo response in adolescents with Major Depressive Disorder (MDD). METHOD: Participants of the current study were 151 adolescents (aged 12-17 years) who were randomized to the placebo arm (placebo transdermal patches) of a randomized controlled trial (RCT) comparing the selegiline transdermal patch with placebo (DelBello et al., 2014). The primary outcome of response was defined as a CGI-I score of 1 or 2 (very much or much improved) at week 12 (study-end) or exit. As a first step, a multiple logistic mixed model was used to estimate the odds of placebo response from each predictor in the model, including age, CDRS-R total at baseline (depressive symptom severity), history of recurrent depression (yes vs. no), sex (female vs. male), and race (non-Caucasian vs. Caucasian). On the basis of the initial logistic mixed model analysis, we then constructed an Adolescent Placebo Impact Composite Score (APICS) that became the sole predictor in a re-specified Bayesian logistic regression model to estimate the probability of placebo response. Finally, the AUC for the APICS was tested against a nominal area of 0.50 to evaluate how well the APICS discriminated placebo response status. RESULTS: Among the 151 adolescents, with a mean age of 14.6 years (SD = 1.6) and a mean baseline CDRS-R total of 60.6 (SD = 12.1), 68.2% were females, 50.3% was Caucasian, and 39.7% had a history of recurrent depression. Placebo response rate was 58.3%. Based on the logistic mixed model, the re-specified equation with the highest discriminatory ability to estimate the probability of placebo response was APICS = age + (0.32 × CDRS-R Total at baseline) + (-2.85 × if female) + (-5.50 × if history of recurrent depression) + (-5.85 × if non-Caucasian). The AUC for this model was 0.59 (p = .049). Within a Bayesian decision-theoretic framework, in 95.5% of the time, the 10,000 posterior Monte Carlo samples suggested that as APICS decreased the probability of placebo response increased. The observed APICS and related probability of responding to placebo in this adolescent sample ranged from 14.1 = 74.1% (in placebo responders) to 39.1 = 41.8% (in placebo non-responders). CONCLUSION: The APICS model estimates the probability of placebo response in adolescents with MDD with a modest degree of accuracy (AUC = 0.59) and with a reasonable degree of positive predictive value (74.5%), and is based on five previously identified patient characteristics of placebo response from prior meta-analytic studies (Bridge et al., 2009; Cohen et al., 2010) of randomized placebo-controlled trials of antidepressants in youth with MDD. Calculation of the APICS should be restricted to the range of the adolescent ages (12-17 years) and CDRS-R total scores (17-113); thus, the APICS can assume possible calculated values and related probability of responding to placebo ranging from about 3 (84%) to 53 (25%). The APICS Bayesian logistic model, based on a given aggregate patient profile, has a range of predicted probabilities of placebo response that is fairly wide, albeit truncated, but potentially meaningful for predicting the probability of placebo response among adolescent youth with MDD. The ability of the APICS to objectify the probability of placebo response in adolescents with MDD could be accounted for in the clinical research design of the trial itself and perhaps aid clinicians in treatment strategy for youth who are more likely to experience placebo response.

Evaluation of anhedonia with the Snaith-Hamilton Pleasure Scale (SHAPS) in adult outpatients with major depressive disorder.

Anhedonia or inability to experience pleasure not only is a core symptom of major depressive disorder (MDD), but also is identified as an important component of the positive valence system in the NIMH Research Domain Criteria. The Snaith-Hamilton Pleasure Scale (SHAPS) has been developed for the assessment of hedonic experience or positive valence, but has not been well-studied in depressed outpatient populations. The current study examined the reliability and validity of the SHAPS using a sample of adult outpatients with treatment resistant MDD. Data for the current study were obtained from 122 adult outpatients with a diagnosis of MDD and non-response to adequate treatment with an SSRI and who participated in Project TReatment with Exercise Augmentation for Depression (TREAD). A Principal Components Analysis was used to define the dimensionality of the SHAPS. Convergent and discriminant validity were evaluated via correlations of the SHAPS total score with "gold standard" measures of depression severity and quality of life. The SHAPS was found to have high internal consistency (Cronbach's coefficient α = .82). A Principal Components Analysis suggests that the SHAPS is mainly "unidimensional" and limited to hedonic experience among adult outpatients with MDD. Convergent and discriminant validity were assessed by examining the Spearman rank-order correlation coefficient between the SHAPS total score and the HRSD17 (rs = 0.22, p < .03), IDS-C30 (rs = 0.26, p < .01), IDS-SR30 (rs = 0.23, p < .02), QIDS-C16 (rs = 0.22, p < .03), QIDS-SR16 (rs = 0.17, p < .10), QLES-Q (rs = -0.32, p < .002), and the pleasure/enjoyment item (sub-item 21) of the IDS-C (rs = 0.44, p < .0001) and IDS-SR (rs = 0.38, p < .0002). The self-administered SHAPS showed modest sensitivity (76%) and specificity (54%) with the self-administered pleasure/enjoyment single item (sub-item 21) of IDS-SR30. The current study shows that the SHAPS is a reliable and valid instrument to assess hedonic experience or positive valence in adult outpatients with MDD and provides a broader assessment of this important domain.