Design of a real-world, prospective, longitudinal, observational study to compare vortioxetine with other standard of care antidepressant treatments in patients with major depressive disorder: a PatientsLikeMe survey.

BACKGROUND: Major depressive disorder (MDD) is a recurrent psychiatric condition that presents challenges in responding to treatment and achieving long-term remission. To improve outcomes, a shared decision-making treatment approach with patient and healthcare practitioner (HCP) engagement is vital. PatientsLikeMe (PLM), a peer community of patients, provides information on MDD, symptoms, and treatment through forums and resources, helping patients stay engaged in their treatment journey. Data on PLM can be harnessed to gain insights into patient perspectives on MDD symptom management, medication switches, and treatment goals and measures. METHODS: This ongoing, decentralized, longitudinal, observational, prospective study is being conducted using the PLM platform in two parts, enrolling up to 500 patients with MDD in the United States aged ≥ 18 years to compare vortioxetine with other monotherapy antidepressants. The first qualitative component consists of a webinar and discussion forum with PLM community members with MDD, followed by a pilot for functionality testing to improve the study flow and questions in the quantitative survey. The quantitative component follows on the PLM platform, utilizing patient-reported assessments, over a 24-week period. Three surveys will be conducted at baseline and weeks 12 and 24 to collect data on patient global impression of improvement, depression severity, cognitive function, quality of life (QoL) and well-being, medication satisfaction, emotional blunting, symptoms of anhedonia and resilience, as well as goal attainment. Quantitative results will be compared between groups. The qualitative component is complete; patient recruitment is underway for the quantitative component, with results expected in late 2023. DISCUSSION: These results will help HCPs understand patient perspectives on the effectiveness of vortioxetine versus other monotherapy antidepressants in alleviating symptoms of MDD and improvements in QoL. Data from the PLM platform will support a patient goal-based treatment approach, as results can be shared by patients with their HCPs, providing them with insights on patient-centric goals, treatment management and adherence, as well as allowing them to observe changes in patient-related outcomes scores. Findings from the study will also help to optimize the PLM platform to build scalable solutions and connectivity within the community to better serve patients with MDD.

Clinical validation of the Symptom Self-rating Scale for Schizophrenia (4S) among inpatients.

PURPOSE: Self-reports of psychosis-related symptoms may be a valuable supplement to clinician-ratings, but more validation studies are required. The aim of this study was to conduct clinical validation for the Symptom Self-rating Scale for Schizophrenia (4S) in an inpatient setting. MATERIALS AND METHODS: Inpatients diagnosed with schizophrenia were invited to participate in the study. The participants completed the 4S, the 5-item World Health Organization Wellbeing Index (WHO-5) and the Sheehan Disability Scale (SDS) at two time points. Trained raters assessed participants using the 6-item Positive And Negative Syndrome Scale (PANSS-6). The relationship between the 4S and PANSS-6, self-reported side effects, functioning and wellbeing was assessed using Spearman's correlation coefficient (rho). RESULTS: Sixty-one participants completed the 4S at least once (yielding a total of 91 completed 4S questionnaires). The 4S total score was weakly correlated with the PANSS-6 total score (rho = 0.37, p < 0.001). The rho's for individual 4S and PANSS-6 subscales and item comparisons ranged from -0.24 (thought disorder) to 0.69 (hallucinations). Finally, the 4S hallucination subscale was also sensitive to change. The 4S was strongly inversely correlated with wellbeing (WHO-5) and moderately inversely correlated with functioning (SDS total score). CONCLUSION: The 4S holds promise as a valid self-report of core schizophrenia symptoms among inpatients. While the hallucination subscale seems superior to existing scales, the thought disorder subscale needs to be re-developed.

Inter-rater reliability of ratings on the six-item Positive and Negative Syndrome Scale (PANSS-6) obtained using the Simplified Negative and Positive Symptoms Interview (SNAPSI).

PURPOSE: The six-item version of the Positive And Negative Syndrome Scale (PANSS-6) is a brief rating scale focusing on core symptoms of schizophrenia. In order to facilitate rating of PANSS-6 and selected items from other common psychiatric rating scales, we recently developed the Simplified Negative and Positive Symptoms Interview (SNAPSI). The objective of the present study was to test the inter-rater reliability of PANSS-6 ratings obtained using the SNAPSI. MATERIALS AND METHODS: Using the SNAPSI, seven raters (psychiatrists, first-year psychiatry residents and psychologists) performed a total of 56 PANSS-6 ratings of 12 in- or outpatients with schizophrenia. As a measure of inter-rater reliability, we calculated the intra-class correlation coefficient (ICC, ≥0.75 = excellent, 0.40-0.74 = fair to good, <0.40 = poor) for the PANSS-6 total score and individual item scores. Furthermore, for the PANSS-6 total scores obtained by the six noncertified PANSS raters, we calculated the median deviation from the PANSS-6 total scores obtained by the only certified PANSS rater. RESULTS: The ICC for the PANSS-6 total score was 0.74 (F = 2.84, p = .03). The ICCs for the six individual PANSS-6 items ranged from 0.45 (N6 - Lack of spontaneity & flow of conversation) to 0.76 (P3 - Hallucinatory behavior). The PANSS-6 total scores obtained by the six noncertified PANSS raters deviated by a median of 12.7% (interquartile range: 6.2-20.0) from the PANSS-6 total scores obtained by the certified PANSS rater. CONCLUSIONS: We found a good level of inter-rater reliability of PANSS-6 ratings obtained using the SNAPSI for seven raters with varying levels of clinical and research experience.

Validation of the Five-Factor Model of the Arabic Version of the Positive and Negative Syndrome Scale in Schizophrenia.

BACKGROUND: The Positive and Negative Syndrome Scale (PANSS) is a widely used assessment for patients with schizophrenia across clinical and research settings. This scale allows the classification of the psychotic symptoms to better understand the psychopathology in patients with schizophrenia. There are no available data on the different components of psychopathology in Arab patients with schizophrenia. OBJECTIVES: This study examined the factor structure of the validated Arabic version of the PANSS in a sample of Arab patients with schizophrenia. METHODS: The Arabic version of the PANSS was administered to 101 patients with schizophrenia, and principal component analysis (PCA) was carried out after the cross-cultural adaptation and validation of this version. RESULTS: This sample had more males (66.3%) than females (33.7%) with a mean age of 35.03 years (SD = 9.99). PCA showed that 28 items loaded on 5 components: cognitive, negative, excited, depressed and positive. These factors explained 63.19% of variance. The 2 remaining items, grandiosity and somatic concerns, did not load well on any of these components. CONCLUSION: Our results support the common 5-dimension PANSS model shown in other cultures with different languages. Nevertheless, there were minor differences, which could reflect cultural or semantic differences.

Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.

Reliability, validity and factorial structure of the Arabic version of the international suicide prevention trial (InterSePT) scale for suicidal thinking in schizophrenia patients in Doha, Qatar.

BACKGROUND: Patients with schizophrenia are known to have higher rates of mortality and morbidity when compared to the general population. Suicidality is a major contributor to increased mortality. The International Suicide Prevention Trial (InterSePT) Scale for Suicidal Thinking (ISST) is a validated tool to assess current suicidal ideation in patients with schizophrenia. The aims of the study were to culturally adapt the Arabic translation of ISST and to examine the psychometric characteristics of the Arabic version of the ISST among patients with schizophrenia in Qatar. METHODS: ISST was translated and adapted into formal Arabic using the back translation method. Patients diagnosed with schizophrenia were randomly recruited from the department of Psychiatry, Rumailah Hospital, Doha, Qatar. Healthy controls were randomly recruited from two primary health care centers in Doha, Qatar. The Arabic version of Module B for suicidality in Mini International Neuropsychiatric Interview was used as the gold standard to which the Arabic ISST was compared. RESULTS: The study sample (n = 199) was composed of 100 patients diagnosed with schizophrenia (age 35.30 ± 10.04 years; M/F is 2/1) and 99 controls (age 33.98 ± 8.33 years; M/F is 2/3). The mean score on the ISST was 3.03 ± 4.75 vs. 0.47 ± 1.44 for the schizophrenia and control groups, respectively. Inter-rater reliability coefficient was 0.95, p > 0.001. The overall Cronbach's alpha was 0.92. Principal Component Analysis produced 3 factors explaining a total of 73.8% of variance. CONCLUSIONS: This is the first study in the Arab countries to validate the Arabic version of the ISST. The psychometric properties indicate that the Arabic ISST is a valid tool to assess the severity of suicidal ideation in Arabic patients with schizophrenia.

Validity and Reliability of the Arabic Version of the Positive and Negative Syndrome Scale.

BACKGROUND: The Positive and Negative Syndrome Scale (PANSS) is widely used for patients with schizophrenia. This scale is reliable and valid. The PANSS was translated and validated in several languages. OBJECTIVE: The aim of this study was to translate and validate the PANSS in the Arab population. SUBJECTS AND METHODS: The PANSS was translated into formal Arabic language using the back-translation method. 101 Arab patients with schizophrenia and 98 Arabs with no diagnosis of any mental disorder were recruited. The Arabic version of the Mini International Neuropsychiatric Interview (MINI-6) was used as a diagnostic tool to confirm the diagnosis of schizophrenia or rule out any diagnosis for the healthy control group. Reliability of the scale was assessed by calculating internal consistency, interrater reliability and test-retest reliability. Construct validity was assessed using the Arabic version of the MINI-6. PANSS total scores were correlated with the Clinical Global Impression-Severity scale. RESULTS: Our findings showed that the internal consistency was good (0.92). Scores on the PANSS of the patients were much higher than those of the healthy controls. The PANSS showed good interrater reliability and test-retest reliability (0.92 and 0.75, respectively). In comparison with the MINI-6, the PANSS showed good sensitivity and specificity, which implies good construct validity of this version. CONCLUSION: In conclusion, the Arabic version of the PANSS is a reliable and valid instrument for the assessment of patients with schizophrenia in the Arab population.

Pharmacotherapy of cognitive deficits in schizophrenia.

While second-generation antipsychotics treat negative as well as positive symptoms, recovery for persons with schizophrenia remains elusive, in part because there are no FDA-approved medications that treat the cognitive deficits of schizophrenia (CDS). Recent work has identified agents that, when added to antipsychotics, improve cognition in schizophrenia. This work and hypothesized mechanisms of action will be reviewed.

A qualitative investigation of the Montgomery-Åsberg depression rating scale: discrepancies in rater perceptions and data trends in remote assessments of rapid-acting antidepressants in treatment resistant depression.

Introduction: Despite the development of many successful pharmaceutical interventions, a significant subset of patients experience treatment-resistant depression (TRD). Ketamine and its derivatives constitute a novel therapeutic approach to treat TRD; however, standard tools, such as the Montgomery-Åsberg Depression Rating Scale (MADRS) are still being used to measure symptoms and track changes. Methods: The aim of this study was to review item-level differences between rate of data change (MADRS score) and rater-weighted perception of the most useful items for assessing change in symptoms while remotely conducting the 10-item version of the MADRS in TRD in a clinical trial of rapid-acting antidepressants. Two studies of rapid-acting antidepressants in the treatment of TRD were used to identify item-scoring trends when MADRS is administered remotely and repeatedly (733 subjects across 10 visits). Scoring trends were evaluated in tandem to a rater survey completed by 75 raters. This was completed to gain insight on MADRS items' perceived level of helpfulness when assessing change of symptoms in rapid-acting antidepressant trials. Results: MADRS items 'Reduced sleep', 'Apparent sadness', and 'Pessimistic thoughts' were found to have the greatest average data change by visit, while raters ranked 'Reported sadness', 'Lassitude' and 'Apparent sadness' as the most helpful items when assessing symptom change. Discussion: The diversion between rate of data-change ranking and rater perception of helpfulness could be related to difficulty in assessing specific items, to the novel treatment itself, and/or to the sensitivity to symptom change to which raters are accustomed in traditional antidepressant treatments.

Enrichment using speech latencies improves treatment effect size in a clinical trial of bipolar depression.

Clinical trials in depression lack objective measures. Speech latencies are an objective measure of psychomotor slowing with face validity and empirical support. 'Turn latency' is the response time between speakers. Retrospective analysis was carried-out on the utility of turn latencies as an enrichment tool in a clinical trial of bipolar I depression. Speech data was obtained from 274 participants during 1,352 Montgomery-Åsberg Depression Rating Scale (MADRS) recordings in a randomized, placebo controlled, 6-week clinical trial of SEP-4199 (200 mg or 400 mg). Post-randomization turn latencies were compared between patients with moderate to severe depression and patients whose depression had remitted. A cutoff was determined and applied to turn latencies pre-randomization to classify individuals into two groups: Speech Latencies Slow (SL-Slow) and Speech Latencies Normal (SL-Normal). At week 6, SL-Slow (N = 172) showed significant separation in MADRS scores between placebo and treatment arms. SL-Normal (N = 102) showed larger MADRS improvements and no significant separation between placebo and treatment arms. Excluding SL-Normal increased primary outcome effect size by 52 % and 100 % for the treatment arms. Turn latencies are an objective measure available from standard clinical assessments and may assess the severity of symptoms more accurately and screen out placebo responders.

Functioning and Cognition in Patients with Schizophrenia After Initiating Treatment with Aripiprazole Lauroxil: Secondary Outcomes and Post Hoc Analysis.

Background: Clinical practice guidelines support efforts to improve functioning in patients with schizophrenia. Discrepancies in the perception of cognitive status between clinicians, patients with schizophrenia, and their caregivers have been associated with impaired functional abilities in patients; medication side effects might worsen both cognition and daily functioning. We assessed daily/social functioning and cognition in stable patients with schizophrenia who switched to the long-acting injectable (LAI) antipsychotic aripiprazole lauroxil (AL). Methods: Clinically stable adults with residual symptoms of schizophrenia or intolerance following three or more doses of paliperidone palmitate or risperidone LAI were switched to flexibly dosed open-label AL treatment (441mg, 662mg, or 882mg every 4 weeks or 882mg every 6 weeks) for six months (ClinicalTrials.gov identifier: NCT02634320). Daily/social functioning was assessed using the Personal and Social Performance Scale (PSP); total and subscale scores were summarized using descriptive statistics. The cognitive status of patients was assessed using the New York Assessment of Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) at baseline and Month 6 or early termination, providing patient, caregiver, and clinician perspectives. A post hoc analysis assessed level of agreement in ratings of cognitive status among respondents, evaluated at baseline and last assessment, using weighted kappa coefficients (0.01-0.20, slight agreement; 0.21-0.40, fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, substantial agreement.). Results: All 51 enrolled patients received one or more AL doses; 35 completed the study, and 45 contributed data at last assessment. Mean age was 40.6 years; 72.5 percent of patients were male. Based on PSP total score, functioning was maintained from baseline (mean [standard deviation (SD)]: 55.1 [10.5]) through six months of AL treatment (mean [SD]: 57.7 [13.2]). Proportions of patients rating personal and social functioning issues as "not present" or "mild" remained stable between baseline and Month 6 for each PSP subscale. At baseline (n=50), cognitive difficulties were most commonly rated "not present" or "mild" in all NY-AACENT domains by patients (58-86% across domains), clinicians (62-94%), and caregivers (50-92%), and these rates were maintained or increased at last assessment for all reporters. Weighted kappa coefficients indicated fair-to-substantial agreement between patients and clinicians across domains at last assessment (0.32-0.64; baseline: 0.14-0.55); patient-caregiver agreement ranged from 0.07 to 0.50 at last assessment (baseline: 0.25-0.60). Conclusion: In clinically stable patients with schizophrenia who initiated AL, self-reported functioning was maintained over six months of treatment. Clinician-, caregiver-, and patient-reported cognitive function was stable at baseline and maintained in all NY-AACENT domains; patient-clinician agreement on level of cognitive impairment increased over six months of treatment with AL.

Evaluating speech latencies during structured psychiatric interviews as an automated objective measure of psychomotor slowing.

We sought to derive an objective measure of psychomotor slowing from speech analytics during a psychiatric interview to avoid potential burden of dedicated neurophysiological testing. Speech latency, which reflects response time between speakers, shows promise from the literature. Speech data was obtained from 274 subjects with a diagnosis of bipolar I depression enrolled in a randomized, doubleblind, 6-week phase 2 clinical trial. Audio recordings of structured Montgomery-Åsberg Depression Rating Scale (MADRS) interviews at 6 time points were examined (k = 1,352). We evaluated speech latencies, and other aspects of speech, for temporal stability, convergent validity, sensitivity/responsivity to clinical change, and generalization across seven socio-linguistically diverse countries. Speech latency was minimally associated with demographic features, and explained nearly a third of the variance in depression (categorically defined). Speech latency significantly decreased as depression symptoms improved over time, explaining nearly 20 % of variance in depression remission. Classification for differentiating people with versus without concurrent depression was high (AUCs > 0.85) both cross-sectionally and longitudinally. Results replicated across countries. Other speech features offered modest incremental contribution. Neurophysiological speech parameters with face validity can be derived from psychiatric interviews without the added patient burden of additional testing.

Assessing the sources of unreliability (rater, subject, time-point) in a failed clinical trial using items of the Positive and Negative Syndrome Scale (PANSS).

BACKGROUND: Considering the increasing attention to the study of failed clinical trials, the goal of this study was to identify the sources of unreliability in a failed clinical trial by assessing scores on the Positive and Negative Syndrome Scale (PANSS). METHODS: This study is a substudy from a failed phase 2 double-blind, placebo-controlled trial of schizophrenia. Using the generalizability theory, this substudy assesses reliability on 3 conditions: raters, time points (PANSS evaluations, 1 week apart), subjects for 3 groups (placebo responders, placebo nonresponders, and treatment group). RESULTS: The placebo response rate was 40.07% (32/71). For all PANSS positive symptom items, the most variability was for raters (range, 33%-72%) for the placebo responders, 31% to 68% for the placebo nonresponders, and 29% to 60% for the treatment group. The variability of the interaction of rater and time point was the second source of unreliability, with an average of 12.28% compared to 12.00% for the placebo nonresponders and 10.00% for the treatment group. All items of the negative symptom subscale showed the most percent variability for raters, for all groups. For general psychopathology items (except preoccupation), raters accounted for the most variability in the scores for placebo responders with an average of 51.00% across items. A similar pattern was observed for the placebo nonresponders and for the treatment group; for the treatment group, the interaction between rater and time point accounted for the most variability for somatic concern and anxiety. CONCLUSIONS: Results confirm the efficacy of applying the generalizability theory to the estimation of reliability to identify a source of unreliability and provide evidence for the relationship between low reliability and failed trials. Findings can be used to guide data monitoring, rater training, and identification of PANSS items, which may require supplementary training.

Prenatal stress and affective disorders in a population birth cohort.

OBJECTIVES: Pregnant women exposed to an acute traumatic event are thought to produce offspring with an increased incidence of affective disorders. It is not known whether there are specific times in pregnancy which confer increased vulnerability, or if psychosocial stress alone can increase the incidence of affective disorders in offspring. We examined the relationship of the timing of an acute psychosocial threat during pregnancy to the incidence of affective disorders in offspring using data from a large birth cohort. METHODS: Using data on 90079 offspring born in Jerusalem in 1964-1976 and linked to Israel's psychiatric registry, we constructed proportional hazards models to evaluate the link between gestational age during the Arab-Israeli war of June 1967 and incidence of mood disorders. RESULTS: Those in their first trimester of fetal development during the war were more likely to be admitted to hospitals for any mood disorders [relative risk (RR) = 3.01, 95% confidence interval (CI): 1.68-5.39, p = 0.0002]; for bipolar disorder the risk was doubled (RR = 2.44, 95% CI: 0.996-5.99, p = 0.054) and for all 'other' mood disorders the risk was tripled (RR = 3.61, 95% CI: 1.68-7.80, p = 0.001). Mood disorders were also increased in offspring whose mothers had been in the third month of pregnancy in June of 1967 (RR = 5.54, 95% CI: 2.73-11.24, p < 0.0001). CONCLUSIONS: A time-limited exposure to a severe threat during early gestation may be associated with an increased incidence of affective disorders in offspring. The third month of fetal development was a moment of special vulnerability.

Recommendations for selection and adaptation of rating scales for clinical studies of rapid-acting antidepressants.

The novel mechanisms of action (MOA) derived from some recently introduced molecular targets have led to regulatory approvals for rapid acting antidepressants (RAADs) that can generate responses within hours or days, rather than weeks or months. These novel targets include the N-methyl-D-glutamate receptor antagonist ketamine, along with its enantiomers and various derivatives, and the allosteric modulators of gamma-aminobutyric acid (GABA) receptors. There has also been a strong resurgence in interest in psychedelic compounds that impact a range of receptor sites including D1, 5-HT7, KOR, 5-HT5A, Sigma-1, NMDA, and BDNF. The RAADs developed from these novel targets have enabled successful treatment for difficult to treat depressed individuals and has generated a new wave of innovation in research and treatment. Despite the advances in the neurobiology and clinical treatment of mood disorders, we are still using rating instruments that were created decades ago for drugs from a different era (e.g., The Hamilton and Montgomery-Åsberg depression rating scales, HDRS, and MADRS) continue to be used. These rating instruments were designed to assess mood symptoms over a 7-day time frame. Consequently, the use of these rating instruments often requires modifications to address items that cannot be assessed in short time frames, such as the sleep and appetite items. This review describes the adaptative approaches that have been made with the existing scales to meet this need and examines additional domains such as daily activities, side effects, suicidal ideation and behavior, and role functioning. Recommendations for future studies are described, including the challenges related to implementation of these adapted measures and approaches to mitigation.

Clinical Outcome Assessment Instruments in Schizophrenia: A Scoping Literature Review with a Focus on the Potential of Patient-reported Outcomes.

Objective: The complexity inherent in the treatment of schizophrenia results in a multitude of outcome assessments being employed when conducting clinical trials. Subjective outcome assessments and minimal clinically important differences (MCIDs) to evaluate clinical meaningfulness have gained traction; however, the extent of application in evaluation of treatments for schizophrenia is unknown. A scoping review was conducted to assess the availability of published psychometric evaluations, including MCIDs, for clinical outcome assessments used to evaluate treatments for schizophrenia. Method of Research: Key databases (PubMed®, Embase®, APA PsycINFO®, International Society for Pharmacoeconomics and Outcomes Research) were searched for studies on schizophrenia published from 2010 to 2020. Secondary sources (ClinicalTrials.gov, PROLABELS™, FDA.gov) were also reviewed. Clinical outcome assessments were organized by type (patient-reported outcomes [PROs], clinician-reported outcomes [ClinROs], observer-reported outcomes [ObsROs]) and further classified by intended use (generic, mental health, schizophrenia). Reliability and internal consistency were evaluated using Cronbach's α. External validity was evaluated by intraclass correlation coefficient (ICC). Results: Across 140 studies, 66 clinical outcome assessments were identified. MCIDs were reported for eight of the 66 studies. Of these, two were PROs (generic) and six were ClinROs/ObsROs (three mental health-specific, three schizophrenia-specific). Reliability was good across generic, mental health-specific, and schizophrenia-specific categories, whereas external validity was strong mainly for schizophrenia-specific PROs. Overall, ClinROs/ObsROs that focused on mental health had good reliability and strong external validity. Conclusion: This review provides a comprehensive overview of the clinical outcome assessments used in schizophrenia research during the past ten years. Results highlight the heterogeneity of existing outcomes and a growing interest in PROs for schizophrenia.

Are informants required to obtain valid ratings on the Positive and Negative Syndrome Scale (PANSS)?

Ratings on the Positive and Negative Syndrome Scale (PANSS) are ideally based on both a patient interview and an informant questionnaire. In research and clinical settings, however, the informant questionnaire is often omitted. This study investigated the consequences of omitting informant information by comparing PANSS ratings of patients with schizophrenia (n = 49 patients, 77 ratings) conducted with and without informant information, respectively. Additionally, changes in symptom severity over time based on ratings with and without informant information were also compared for the full PANSS and the six-item version of the PANSS (PANSS-6). PANSS ratings including informant information were higher than those without, both at the total score and individual item level. Additionally, the full PANSS appeared less "responsive" to baseline-to-endpoint changes for ratings without informant information compared to ratings including informant information, while no differences were found for the PANSS-6.

Validation of ratings on the six-item Positive and Negative Syndrome Scale obtained via the Simplified Negative and Positive Symptoms Interview among outpatients with schizophrenia.

BACKGROUND: The six-item Positive and Negative Syndrome Scale (PANSS-6) is a measure of the severity of core symptoms of schizophrenia, which can be administered via the brief Simplified Negative and Positive Symptoms Interview (SNAPSI). A recent study has confirmed the validity of PANSS-6 ratings as derived by SNAPSI (PANSS-6SNAPSI) among inpatients with schizophrenia. AIMS: We aimed to test the validity of PANSS-6SNAPSI among outpatients with schizophrenia using PANSS-6 ratings extracted from the 30-item PANSS-30 as derived by the Structured Clinical Interview for the Positive and Negative Syndrome Scale (PANSS-6SCI-PANSS) as a gold standard reference. METHODS: PANSS-6SNAPSI and PANSS-6SCI-PANSS ratings were obtained at two time points by independent raters with established inter-rater reliability. Agreement between PANSS-6SNAPSI and PANSS-6SCI-PANSS ratings was estimated via intra-class coefficients (ICCs) and responsiveness over time was quantified using Spearman's rank correlation coefficients. Post hoc "leave-one-out" analyses were carried out, in which each rater in turn was excluded from the ICC calculations. RESULTS: Seventy-three outpatients with schizophrenia participated in the study (mean age: 38.3 years; 56% males). The ICC for PANSS-6SNAPSI versus PANSS-6SCI-PANSS was 0.67 [95%CI = 0.56-0.76] and the Spearman's rank correlation coefficient for responsiveness was 0.40 (p = 0.004). When data from a specific outlying rater were excluded, the ICC for PANSS-6SNAPSI versus PANSS-6SCI-PANSS was 0.75 [95% CI = 0.63-0.83] and the Spearman's rank correlation coefficient for responsiveness was 0.55 (p = 0.018). CONCLUSIONS: We found PANSS-6SNAPSI ratings to have acceptable clinical validity, suggesting that PANSS-6SNAPSI can be used for both inpatients and outpatients with schizophrenia.

Emotional and neurobehavioural status in chronic pain patients.

OBJECTIVE: To investigate the emotional and neurobehavioural status of patients suffering from chronic pain. METHODS: Fifteen male patients with chronic lower back pain and 15 healthy control subjects were studied for approximately six months. Pain was measured using a visual analogue scale. The WHO Neurobehavioral Core Test Battery (NCTB) was used to assess neurobehavioural effects of environmental and occupational exposures. RESULTS: Visual analogue scale results demonstrated a modest range of reported pain (mean [± SD] 62.0 ± 10.8) in chronic pain patients, whereas control subjects reported no measurable pain. With the NCTB, it was found that scores of negative mood state, including anger-hostility, depression-dejection, fatigue-inertia and tension-anxiety in pain patients were significantly higher than scores in the control subjects. By contrast, scores of positive mood state (vigour-activity) in chronic pain patients were lower than those in the control group. The NCTB scores of the Santa Ana Dexterity and Pursuit Aiming II tests in chronic lower back pain patients were lower than those of the control group. Scores for other NCTB subtests, including the Digit Span, Benton Visual Retention and Digit Symbol tests, were not significantly different compared with controls. Asunto(s) Emociones , Trastornos de la Destreza Motora/etiología , Dolor/complicaciones , Dolor/psicología , Tiempo de Reacción/fisiología , Adulto , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Dolor/diagnóstico , Dimensión del Dolor , Estimulación Luminosa , Retención en Psicología/fisiología , Encuestas y Cuestionarios

Standardized training in the rating of the six-item Positive And Negative Syndrome Scale (PANSS-6).

The six-item Positive And Negative Syndrome Scale (PANSS-6) allows for a brief assessment of the severity of core symptoms of schizophrenia. However, implementing the PANSS-6 in clinical practice requires that staff members' ratings are accurate and reliable. We aimed to investigate whether such accuracy and reliability can be obtained via a brief video-based training program. One-hundred-and-four staff members from a psychiatric hospital in Denmark participated in the training. Participants performed a baseline PANSS-6 rating based on a video of a patient being interviewed using the Simplified positive And Negative Symptoms interview (SNAPSI). Subsequently, a theoretical introduction video was displayed followed by five successive videotaped SNAPSI patient interviews. After each SNAPSI video, individual ratings were conducted before a video providing the gold standard rating was displayed. The accuracy of ratings was estimated by calculating the proportion of participants not deviating from the gold standard rating with >2 points on individual items or >6 points on the PANSS-6 total score. Reliability was tested after each step in the training by means of Gwet's Agreement Coefficient (Gwet). By the end of the training, 72% of the participants rated within the acceptable deviations of the gold standard, ranging from 60% (nurses) to 91% (medical doctors & psychologists). The reliability improved (Gwet baseline vs. endpoint) for all PANSS-6 items, except for Blunted affect. In conclusion, the majority of the staff members conducted accurate PANSS-6 ratings after a brief standardized training program, supporting the implementation of PANSS-6 in clinical settings to facilitate measurement-based care.