PRECISE trial (Pain RElief Combination Intervention StratEgies): protocol for the clinical trial of a pregabalin-melatonin combination for fibromyalgia.

INTRODUCTION: Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia. METHODS AND ANALYSIS: This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT-PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT-PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0-10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels). ETHICS AND DISSEMINATION: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen's University Health Sciences Research Ethics Board (Queen's HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings. TRIAL REGISTRATION NUMBER: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.

An analysis of the Painful and Provocative Events Scale: Some painful and provocative findings.

This research investigated the latent structure and correlates of the 26-item Painful and Provocative Events Scale (PPES). For a sample of 290 community respondents, results from parallel analysis indicated a 5-factor structure. Based on principal axis factoring with varimax rotation, scales of Intense physicality, Physical and mental trauma, Physical risk taking, Psychopathy, and Body enhancement were constructed, and these demonstrated a pattern of convergent and discriminant correlations with suicide-associated and demographic variables that supported the delineation of these scales as being distinct. In general, results challenge the current scoring of the PPES and, with developed scales being differentially related to demographic variables, indicate that both respondent age and sex require consideration for scale score interpretation.

Randomized, double-blind, controlled trial of a combination of alpha-lipoic acid and pregabalin for neuropathic pain: the PAIN-CARE trial.

ABSTRACT: We compared a combination of the nonsedating antioxidant, alpha-lipoic acid (ALA), with the sedating anticonvulsant, pregabalin, vs each monotherapy to treat neuropathic pain due to peripheral neuropathies. In this randomized, double-blind, 3-period crossover trial, participants received oral ALA, pregabalin, and their combination-each for 6 weeks. The primary outcome was mean daily pain intensity at maximal tolerated doses (MTD); secondary outcomes included quality of life (SF-36), sleep (Medical Outcomes Study-Sleep Scale), adverse effects, drug doses, and other measures. Of 55 participants randomized (20-diabetic neuropathy, 19-small fiber neuropathy, and 16-other neuropathies), 46 completed 2 periods, and 44 completed 3. At MTD, the primary outcome of mean pain intensity (0-10) was 5.32 (standard error, SE = 0.18), 3.96 (0.25), 3.25 (0.25), and 3.16 (0.25) at baseline, ALA, pregabalin, and combination, respectively ( P < 0.01 for ALA vs combination and pregabalin). Treatment differences were similar in subgroups with diabetic neuropathy and with other neuropathies. SF-36 total scores (higher number indicates better quality of life) were 66.6 (1.88), 70.1 (1.88), and 69.4 (1.87) with ALA, pregabalin, and combination ( P < 0.05 for ALA vs combination and pregabalin). At MTD, there were no statistically significant treatment differences in adverse effects or drug doses. This trial demonstrates superiority of pregabalin vs ALA but provides no evidence to suggest added benefit of combining ALA with pregabalin to treat neuropathic pain.

The Mediating Role of Tolerance for Psychological Pain in the Relationship Between Different Types of Childhood Traumatic Experiences and Suicidal Ideation.

The aim of the present research was to evaluate the mediating effects of facets of the tolerance for psychological pain on the relationship between childhood trauma and suicidal ideation. A sample of 437 community individuals and a sample of 316 college students participated. For the community sample, managing the pain mediated the relationship between childhood trauma, the different types of traumatic experiences and suicidal ideation. In the college sample, managing the pain and enduring the pain mediated the relationship between childhood trauma, the different types of traumatic experiences and suicidal ideation, except for the case of sexual abuse. The present results have potential clinical implications. Mental health professionals should be aware of the long-term consequences of exposure to childhood trauma and need to assess the ability to tolerate psychological pain so as to implement appropriate psychological interventions that help individuals cope with their pain.

Combination analgesic development for enhanced clinical efficacy (the CADENCE trial): a double-blind, controlled trial of an alpha-lipoic acid-pregabalin combination for fibromyalgia pain.

ABSTRACT: Drug therapy for fibromyalgia is limited by incomplete efficacy and dose-limiting adverse effects (AEs). Combining agents with complementary analgesic mechanisms-and differing AE profiles-could provide added benefits. We assessed an alpha-lipoic acid (ALA)-pregabalin combination with a randomized, double-blind, 3-period crossover design. Participants received maximally tolerated doses of ALA, pregabalin, and ALA-pregabalin combination for 6 weeks. The primary outcome was daily pain (0-10); secondary outcomes included Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events, and other measures. The primary outcome of daily pain (0-10) during ALA (4.9), pregabalin (4.6), and combination (4.5) was not significantly different ( P = 0.54). There were no significant differences between combination and each monotherapy for any secondary outcomes, although combination and pregabalin were both superior to ALA for measures of mood and sleep. Alpha-lipoic acid and pregabalin maximal tolerated doses were similar during combination and monotherapy, and AEs were not frequent with combination therapy. These results do not support any additive benefit of combining ALA with pregabalin for fibromyalgia. The observation of similarly reached maximal tolerated drug doses of these 2 agents (which have differing side-effect profiles) during combination and monotherapy-without increased side effects-provides support for future development of potentially more beneficial combinations with complementary mechanisms and nonoverlapping side effects.

IAT faking indices revisited: Aspects of replicability and differential validity.

Research demonstrates that IATs are fakeable. Several indices [either slowing down or speeding up, and increasing errors or reducing errors in congruent and incongruent blocks; Combined Task Slowing (CTS); Ratio 150-10000] have been developed to detect faking. Findings on these are inconclusive, but previous studies have used small samples, suggesting they were statistically underpowered. Further, the stability of the results, the unique predictivity of the indices, the advantage of combining indices, and the dependency on how faking success is computed have yet to be examined. Therefore, we reanalyzed a large data set (N = 750) of fakers and non-fakers who completed an extraversion IAT. Results showed that faking strategies depend on the direction of faking. It was possible to detect faking of low scores due to slowing down on the congruent block, and somewhat less with CTS-both strategies led to faking success. In contrast, the strategy of increasing errors on the congruent block was observed but was not successful in altering the IAT effect in the desired direction. Fakers of high scores could be detected due to slowing down on the incongruent block, increasing errors on the incongruent block, and with CTS-all three strategies led to faking success. The results proved stable in subsamples and generally across different computations of faking success. Using regression analyses and machine learning, increasing errors had the strongest impact on the classification. Apparently, fakers use various goal-dependent strategies and not all are successful. To detect faking, we recommend combining indices depending on the context (and examining convergence).

Melatonin for Neuropathic Pain: Protocol for a Double-blind, Randomized Controlled Trial.

BACKGROUND: Neuropathic pain (NP), a complication of several conditions (eg, diabetic neuropathy and varicella zoster), is a common challenging problem, and there is a growing need to develop safe and effective nonopioid treatments. Sleep disturbance is commonly associated with NP because pain intensity in NP conditions is often worse at night. The pineal hormone melatonin has been shown to reduce pain in both preclinical and clinical settings, in addition to multiple trials demonstrating efficacy for primary insomnia and delayed sleep phase syndrome. OBJECTIVE: We propose to conduct a clinical trial to evaluate the efficacy and safety of melatonin for NP. METHODS: Using a double-blind, placebo-controlled, crossover design, 30 adults with NP will be randomly allocated to one of two sequences of treatment with melatonin and placebo. During each of the two treatment periods, participants will take capsules containing melatonin or placebo for 4 weeks, followed by a 7-day washout period. The primary outcome will be mean daily pain intensity (scored 0-10) at maximally tolerated doses (MTDs) during each period. Secondary outcomes, assessed at MTDs, will include global improvement, adverse events, mood, and quality of life. RESULTS: This trial was registered in the International Standard Randomized Controlled Trial registry May 4, 2022 (ISRCTN #16215617), attained conditional ethics approval May 9, 2022 (Queen's University Health Sciences & Affiliated Teaching Hospitals Research Ethics Board protocol number ANAE-387-22), and recruitment is set to start August 2022. CONCLUSIONS: This trial will provide rigorous evidence comparing the efficacy of melatonin to that of placebo in the treatment of NP. TRIAL REGISTRATION: ISRCTN Registry 16215617; https://www.isrctn.com/ISRCTN16215617. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/40025.

Results from Two Countries on How Thwarted Interpersonal Needs Contribute to Understanding Self-Harm.

Self-harming behavior (SHB) represents an important public health issue and is one of the most critical predictors of completed death by suicide. The current study evaluated the incremental contribution of the Interpersonal Theory of Suicide constructs of thwarted belongingness and perceived burdensomeness for the prediction of SHB beyond that associated with having a psychiatric diagnosis. Community adults from two different countries included a Portuguese sample of 414 adults, aged between 18 and 65 years (M = 45.09, SD = 13.11), and predominantly female (79%), and an American sample of 290 adults (198 men, 91 women, 1 unreported) with a mean age of 37.76 years (SD = 10.84) ranging from 20 to 71, who participated online. Results demonstrated mediation effects for perceived burdensomeness in the association of thwarted belongingness with SHB, partial mediation in the Portuguese sample and full mediation in the American sample. Findings also indicated that the interaction between thwarted belongingness and perceived burdensomeness failed to make a statistically significant contribution to the prediction of SHB. The results are discussed within the Interpersonal Theory of Suicide and its relevance for clinical practice.

Challenging response latencies in faking detection: The case of few items and no warnings.

AbstractFaking detection is an ongoing challenge in psychological assessment. A notable approach for detecting fakers involves the inspection of response latencies and is based on the congruence model of faking. According to this model, respondents who fake good will provide favorable responses (i.e., congruent answers) faster than they provide unfavorable (i.e., incongruent) responses. Although the model has been validated in various experimental faking studies, to date, research supporting the congruence model has focused on scales with large numbers of items. Furthermore, in this previous research, fakers have usually been warned that faking could be detected. In view of the trend to use increasingly shorter scales in assessment, it becomes important to investigate whether the congruence model also applies to self-report measures with small numbers of items. In addition, it is unclear whether warning participants about faking detection is necessary for a successful application of the congruence model. To address these issues, we reanalyzed data sets of two studies that investigated faking good and faking bad on extraversion (n = 255) and need for cognition (n = 146) scales. Reanalyses demonstrated that having only a few items per scale and not warning participants represent a challenge for the congruence model. The congruence model of faking was only partly confirmed under such conditions. Although faking good on extraversion was associated with the expected longer latencies for incongruent answers, all other conditions remained nonsignificant. Thus, properties of the measurement and properties of the procedure affect the successful application of the congruence model.

Psychache, unmet interpersonal needs, childhood trauma and suicide ideation in young adults.

This 5-month, 2-wave study evaluated the mediating effects of psychache and unmet interpersonal needs on the relationship between childhood trauma and suicide ideation in 208 young adults, controlling for depression. Path analysis demonstrated that changes in depression, perceived burdensomeness, and thwarted belongingness mediated the relationship between childhood trauma and changes in positive suicide ideation, and that changes in depression and perceived burdensomeness mediated the relationship between childhood trauma and changes in negative suicide ideation. Results indicated the importance of assessing interpersonal needs, in addition to depression, for understanding the mechanism linking childhood trauma to suicide ideation in young adults.

Biopsychosocial predictors of suicide risk in patients with interstitial cystitis/bladder pain syndrome.

INTRODUCTION: The impact of interstitial cystitis/bladder pain syndrome (IC/BPS) is prevalent and severe. Studies examining the IC/BPS prevalence and predictors of suicide risk are limited by their lack of theoretically relevant suicide research variables. This research reports suicide risk prevalence and its biopsychosocial predictors for a community IC/BPS sample. METHODS: Self-identified female patients suffering from IC/BPS (n=813; 18-80 years, mean 46.60, standard deviation [SD] 14.10) recruited from online IC/BPS support groups completed measures of demographic, pain, symptoms, and psychosocial variables. Descriptive statistics, correlations, and multivariable logistic regressions examined prevalence, variable associations, and suicide risk prediction. RESULTS: Suicide risk prevalence was 38.1%. Suicide risk was associated with greater odds for exposure to suicide, psychache, hopelessness, and perceived burdensomeness to others. Further, examining suicide risk by levels of pain showed that exposure to suicide and hopelessness were consistent suicide risk predictors across pain levels; psychache for lower levels of pain, depression in moderate levels of pain, and perceived burdensomeness in moderate and severe pain levels. CONCLUSIONS: The high prevalence of suicide risk is alarming and signifies an imperative for recognizing this risk within the IC/BPS population. The identified psychosocial risk factors may be used in refining screening and treatment, and in directing future IC/BPS research.

Dimensionality of Suicide Behaviors: Results within Two Samples from Two Different Countries.

Across two countries and two languages, this research examined the multidimensional associations of suicide behaviors (i.e., life-time attempts, life-time communication of intent to others, life-time self-harming, life-time suicide notes, and current suicide ideation) and empirically relevant psychological risk factors (i.e., different facets of mental pain, perceived burdensomeness, thwarted belongingness, and acquired capability), controlling for depressive symptoms. For the Portuguese sample, two underlying dimensions emerged: an ideation dimension and a behavioral dimension, and for the Canadian sample, three dimensions emerged: an ideation dimension and two behavioral dimensions that can be viewed as a splitting of the Portuguese second dimension. Results highlight possible cultural differences between the two countries and that suicide behaviors should be viewed as a multidimensional phenomenon not as a one-dimensional continuum.

Stability and Change in Trait Emotional Intelligence in Emerging Adulthood: A Four-Year Population-Based Study.

Trait Emotional Intelligence (EI)-related competencies are in growing demand in educational and vocational settings. The present study assesses the developmental dynamics of trait EI in emerging adulthood by capitalizing on the inclusion of a measure of trait EI in the National Longitudinal Survey of Children and Youth (NLSCY) called the Emotional Quotient Inventory: Mini (EQ-i: Mini). A sample of 1064 young adults (50% female) from ages 20-21 to 24-25 years was used to assess 4-year rank-order stability and mean-level change of trait EI, as well as whether the EQ-i: Mini functions equivalently over time (longitudinal measurement invariance). Results revealed full configural, partial metric, and scalar invariance of the construct for this time period. The Stress Management subscale achieved invariance at the residual level. After controlling for partial non-invariance, moderate levels of rank-order stability coefficients were found, suggesting malleability of the construct during emerging adulthood. Consistent with the maturity principle, there was a moderate increase in trait EI (specifically in the Interpersonal and Adaptability subscales). The malleability of trait EI suggests opportunities for enhancing socioemotional competencies in emerging adults, such as through formal and continuing education programing, on-the-job training, and targeted employment interventions.

Invalidating childhood environments and nonsuicidal self-injury in university students: Depression and mental pain as potential mediators.

OBJECTIVES: The aim of this study was to evaluate the potential mediating effects of depression and psychache (i.e., extreme mental pain) on the relationship between parental invalidation and nonsuicidal self-injury (NSSI) in young adults. METHOD: A sample of 2474 university students responded to previously validated measures of current NSSI, childhood parental invalidation, depression, and psychache. RESULTS: Using a parallel mediation model, path analysis using structural equation modeling demonstrated full mediation by depression and psychache of the link between parental invalidation and NSSI. CONCLUSIONS: Findings suggest that the association between invalidating childhood environments and NSSI has the potential to be mitigated by addressing issues of depression and psychache.

Psychological pain and previous suicide attempts in young adults: Results with the Portuguese version of the Psychache Scale.

OBJECTIVES: In this study, we tested whether the unbearable pain scale of the Psychache Scale provides value for the statistical prediction of a previous suicide attempt; we evaluated whether psychological pain has incremental value in the statistical prediction of a previous suicide attempt relative to the reporting of having had a psychiatric diagnosis, and we established a cut-score for the Psychache Scale. METHOD: Two samples participated: a sample consisting of 1,460 young adults and a sample of 628 Portuguese community adults. RESULTS AND CONCLUSIONS: Results demonstrated that unbearable pain is not a stronger predictor of a previous suicide attempt than is the bearable pain score of the Psychache Scale; that the total score of the Psychache scale provides an additional statistically significant contribution to the statistical prediction of a previous suicide attempt relative to the reporting of having had a psychiatric diagnosis.

The multidimensionality of suicide risk factors and criteria in a nonclinical population: Replication across two countries and two languages.

Across two countries and two languages, this research examined the multidimensional associations between suicidality (e.g., past ideation/attempts, communication of intent) and empirically important psychological risk factors (e.g., mental pain, perceived burdensomeness, thwarted belongingness). For samples of 228 Canadian and 331 Portuguese university undergraduates, four dimensions emerged in each sample with two of these, intrapersonal and interpersonal, demonstrating strong replicability across countries and languages. It was concluded that suicidality is a phenomenon that demonstrates some multidimensional similarities across cultures.

Psychache Predicts Suicide Attempter Status Change in Students Starting University.

OBJECTIVES: Unlike many investigations that focus on suicide ideation rather than suicidal behavior, the present research evaluates the merit and relative efficacy of psychache (i.e., unbearable mental pain) for predicting self-reported suicide attempts among university students who are starting university. METHOD: A sample of 516 elevated-risk undergraduates was assessed during the first three weeks of starting university and, again, 10 weeks later. RESULTS: Psychache and depression, but not hopelessness, could predict change in suicide attempter status. When measures of psychache, depression, and hopelessness were considered simultaneously, only psychache provided significant, unique predictive power. CONCLUSIONS: Findings are interpreted as supporting Shneidman's model whereby psychache is seen as the cause of suicide.

Exposure to Suicide in the Family: Suicidal Ideation and Unmet Interpersonal Needs in Young Adults Who Have Lost a Family Member by Suicide.

The aims of the present study were to compare a sample of individuals exposed to suicide in their families with a control group, on suicidal ideation, and to test possible potentiating effects for unmet interpersonal needs. Three hundred eighty-six young Portuguese adults participated. Two groups were defined: a group exposed to suicide in the family (n = 38) and a control group (n = 335). Groups differed significantly on suicidal ideation, on depressive symptoms, and on perceived burdensomeness and tended to differ on thwarted belongingness. Results from a hierarchical multiple regression analysis demonstrated that having lost a family member by suicide and perceived burdensomeness each provided a significant unique contribution to explaining variance in suicidal ideation when controlling for levels of depressive symptoms and having had a psychiatric diagnosis. The interaction between group membership and perceived burdensomeness provided a further enhancement to the statistical prediction of suicidal ideation.

Psychological pain and suicidal ideation in undergraduates: The role of pain avoidance.

In the present study, the first with a Western sample, we tested the relationship between three dimensions of psychological pain and suicidal ideation in a sample of 331 Portuguese college students. When controlling for the effect of depressive symptoms, the avoidance dimension, but not the cognitive and affective dimensions of psychological pain, made a significant contribution in predicting the three indicators of suicidal ideation. According to these results, psychotherapeutic action may focus either on enabling clients to tolerate mental pain or on providing more effective and adaptive strategies to cope with this pain.

Avoidance of psychological pain and suicidal ideation in community samples: Replication across two countries and two languages.

OBJECTIVES: A multidimensional psychological pain model of suicide has been developed that includes three dimensions: affective, cognitive, and avoidance. In the present research, we evaluated the relationships between the three dimensions of psychological pain and suicidal ideation. METHOD: Two community samples from Portugal and the U.S. participated in the research. RESULTS: Hierarchical multiple regression analysis demonstrated that when controlling for the effects of depressive symptoms and psychache, the avoidance dimension, but not the cognitive or affective dimension of psychological pain, explained significant, and unique variance in suicidal ideation in each sample. CONCLUSION: Even when individuals perceive psychological pain, there may not be an elevated risk of suicide, provided that they do not consider suicide as a form of coping to decrease that pain.