Web-Based Cognitive Behavior Therapy for Chronic Pain Patients with Aberrant Drug-Related Behavior: Outcomes from a Randomized Controlled Trial.

Objective: There is high unmet need for effective behavioral treatments for chronic pain patients at risk for or with demonstrated histories of opioid misuse. Despite growing evidence supporting technology-based delivery of self-management interventions for chronic pain, very few such programs target co-occurring chronic pain and aberrant drug-related behavior. This randomized controlled trial evaluated the effectiveness of a novel, web-based self-management intervention, grounded in cognitive behavior therapy, for chronic pain patients with aberrant drug-related behavior. Methods: Opioid-treated chronic pain patients at a specialty pain practice who screened positive for aberrant drug-related behavior (N = 110) were randomized to receive treatment as usual plus the web-based program or treatment as usual alone. The primary outcomes of pain severity, pain interference, and aberrant drug-related behavior, and the secondary outcomes of pain catastrophizing and pain-related emergency department visits, were assessed during the 12-week intervention and at one and three months postintervention. Results: Patients assigned to use the web-based program reported significantly greater reductions in aberrant drug-related behavior, pain catastrophizing, and pain-related emergency department visits-but not pain severity or pain interference-relative to those assigned to treatment as usual. The positive outcomes were observed during the 12-week intervention and for three months postintervention. Conclusions: A web-based self-management program, when delivered in conjunction with standard specialty pain treatment, was effective in reducing chronic pain patients' aberrant drug-related behavior, pain catastrophizing, and emergency department visits for pain. Technology-based self-management tools may be a promising therapeutic approach for the vulnerable group of chronic pain patients who have problems managing their opioid medication.

Developing patient-centered treatment protocols in brain stimulation: a rationale for combining quantitative and qualitative approaches in persons with HIV.

This article reports and discusses how quantitative (physiological and behavioral) and qualitative methods are being combined in an open-label pilot feasibility study. The study evaluates safety, tolerability, and acceptability of a protocol to treat depression in HIV-infected individuals, using a 2-week block of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex. Major depressive disorder (MDD) is the second most prevalent psychiatric disorder after substance abuse among HIV-positive adults, and novel antidepressant treatments are needed for this vulnerable population. The authors describe the challenges and contributions derived from different research perspectives and methodological approaches and provide a philosophical framework for combining quantitative and qualitative measurements for a fuller examination of the disorder. Four methodological points are presented: (1) the value of combining quantitative and qualitative approaches; (2) the need for context-specific measures when studying patients with medical and psychiatric comorbidities; (3) the importance of research designs that integrate physiological, behavioral, and qualitative approaches when evaluating novel treatments; and (4) the need to explore the relationships between biomarkers, clinical symptom assessments, patient self-evaluations, and patient experiences when developing new, patient-centered protocols. The authors conclude that the complexity of studying novel treatments in complex and new patient populations requires complex research designs to capture the richness of data that inform translational research.

Pancreatic pain: a mini review.

Pain management is one of the corner stones in the treatment of pancreatitis. There are a variety of pharmacological and non-pharmacological strategies to manage the symptoms. Recognizing the type of pain, nociceptive or neuropathic, is essential for appropriate treatment. The pharmacological armamentarium currently available is substantial and includes adjuvant analgesics, non-steroidal anti-inflammatories, and opioids that are customized to the etiology of the pain. When pain relief is suboptimal with pharmacological interventions, celiac block and other interventions should be considered. In acute pancreatitis the use of opioids is widely accepted while its use in chronic states is more controversial. When opioids are utilized, special care has to be taken for the assessment of indicators of misuse or abuse. A multidisciplinary approach to manage these complex patients will result in a high yield of success in controlling this and other symptoms. and IAP.

Abnormal heat and pain perception in remitted heroin dependence months after detoxification from methadone-maintenance.

Patients receiving methadone maintenance therapy (MMT) for opiate dependence have altered nociception, complicating analgesic treatment. Increasing numbers of patients are choosing opiate-free treatment programs, yet data on the course of this abnormality months after detoxification from methadone is contradictory and based exclusively on cold pressor experiments. Heat and pain thresholds were measured by quantitative sensory testing (QST) in 23 subjects with heroin dependence in full, sustained remission months after detoxification from methadone and 27 healthy non-drug using controls. Self reports of pain intensity and unpleasantness were also collected. Test scores were compared across groups and correlated with measures of drug use history. There were significant differences between remitted opiate-dependent subjects and controls on the measures of heat threshold (38.83 vs. 35.96; Mann-Whitney U=177.5, p=0.006), and the measure of pain threshold (48.73 vs. 47.62; Mann-Whitney U=217.5, p=0.043). There was no correlation of any measure of drug use history with the heat or pain experience. Abstinent, formerly opioid-dependent patients continue to demonstrate abnormal noxious perception months after detoxification from methadone.

MMTP patients with chronic pain switching to pain management clinics. A problem or an acceptable practice?

Among the many patients served by methadone maintenance treatment programs (MMTPs) is a small population with severe, refractory pain that may be effectively managed using long-term opioid therapy. Pain specialists have begun to treat these patients, and in some cases, methadone has been selected as the opioid analgesic administered for pain management. The use of methadone for pain in patients treated by MMTPs may lead to complex management issues. We present four patients who illustrate different outcomes associated with one challenging scenario, specifically the expressed desire on the part of the patient to withdraw from the MMTP because the opioid has become available for pain. Research is needed to evaluate the phenomenology of pain and addiction in this population and the outcomes associated with varied therapeutic strategies.

Association of fatigue and depression with circulating levels of proinflammatory cytokines and epidermal growth factor receptor ligands: a correlative study of a placebo-controlled fatigue trial.

CONTEXT: The biology of fatigue and depression in cancer patients is poorly understood. Hypotheses regarding cytokines and growth factors related to sickness behavior and disruption of circadian signaling have been proposed. OBJECTIVES: We prospectively examined proinflammatory cytokines (e.g., sickness behavior model) and epidermal growth factor receptor (EGFR) ligands (e.g., circadian disruption model) in the serum of cancer patients enrolled in a clinical trial testing levocarnitine for fatigue. METHODS: Serum samples were collected at baseline and week 4. Cytokine/growth factor analyses were performed with a Luminex analyzer. The Brief Fatigue Index and the Center for Epidemiologic Studies Depression Index were used to measure fatigue and depression severity. The association between cytokine and symptoms was examined using logistic models. RESULTS: Among 101 analyzable patients, all ten cytokines/growth factors examined were highly elevated at baseline and all significantly decreased at week 4 (p<0.001) regardless of treatment intervention. At baseline, the odds of severe fatigue significantly increased for patients with higher level of interleukin-1 receptor antagonist (IL-1Ra), whereas patients with higher levels of IL-1Ra, tumor necrosis factor-α, interleukin (IL)-6, IL-8, interferon-γ, transforming growth factor α, and vascular endothelial growth factor had higher odds of severe depression. At week 4, fatigue (p=0.023) and depression (p=0.007) responders had less decrease in IL-1 level than the corresponding non-responders. CONCLUSION: In this correlative analysis of a fatigue clinical trial, levels of fatigue were significantly associated with levels of IL-1 and IL-1Ra. Circadian-signaling pathways related to EGFR signaling were correlated with depression as were other cytokines. A major placebo effect was associated with a global decrease in cytokine and growth factors. These data provide further basis for testing hypotheses regarding the mechanisms of fatigue and depression in cancer patients.

Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study.

Carnitine deficiency is among the many metabolic disturbances that may contribute to fatigue in patients with cancer. Administration of exogenous L-carnitine may hold promise as a treatment for this common symptom. Little is known about L-carnitine safety, tolerability, and dose-response in patients with cancer. We conducted a Phase I/II open-label trial to assess the safety and tolerability of exogenous L-carnitine and clarify the safe dose range associated with symptom effects for future controlled trials. Adult patients with advanced cancer, carnitine deficiency (free carnitine <35 for males or <25 microM/L for females, or acyl/free carnitine ratio >0.4), moderate to severe fatigue, and a Karnofsky Performance Status (KPS) score > or =50 were entered by groups of at least three into a standard maximum tolerated dose design. Each successive group received a higher dose of L-carnitine (250, 750, 1250, 1750, 2250, 2750, 3000 mg/day, respectively), administered in two daily doses for 7 days. To compare symptom outcomes before and after supplementation, patients completed validated measures of fatigue (Brief Fatigue Inventory [BFI]), depressed mood (Center for Epidemiologic Studies Depression Scale [CES-D]), quality of sleep (Epworth Sleeplessness Scale [ESS]), and KPS at baseline and 1 week later. Of the 38 patients screened for carnitine levels, 29 were deficient (76%). Twenty-seven patients participated ("intention to treat, ITT") (17 males, 10 females), and 21 completed the study ("completers"); 17 of these patients ("responders," mean+/-[SD] age=57.9+/-15) had increased carnitine levels at the end of the supplementation period. The highest dose achieved was 3000 mg/day. No patient experienced significant side effects and no toxicities were noted. Analysis of all the patients accrued (ITT, n=27) showed a total carnitine increase from 32.8+/-10 to 54.3+/-23 microM/L (P<0.001) and free carnitine increase from 26.8+/-8 to 44.1+/-17 microM/L (P<0.001). BFI decreased significantly, from 66+/-12 to 39.7+/-26 (P<0.001); ESS decreased from 12.9+/-12 to 9+/-6 (P=0.001); and CES-D decreased from 29.2+/-12 to 19+/-12 (P<0.001). A separate analysis of the 17 "responders" showed a dose-response relationship for total- (r=0.54, P=0.03), free-carnitine (r=0.56, P=0.02) levels, and fatigue (BFI) scores (r=-0.61, P=0.01). These findings suggest that l-carnitine may be safely administered at doses up to 3000 mg/day and that positive effects may be more likely at relatively higher doses in this range. This study provides the basis for the design of future placebo-controlled studies of l-carnitine supplementation for cancer-related fatigue.

Patient vs provider reports of aberrant medication-taking behavior among opioid-treated patients with chronic pain who report misusing opioid medication.

During long-term opioid therapy for chronic noncancer pain, monitoring medication adherence of patients with a history of aberrant opioid medication-taking behaviors (AMTB) is an essential practice. There is limited research, however, into the concordance among existing monitoring tools of self-report, physician report, and biofluid screening. This study examined associations among patient and provider assessments of AMTB and urine drug screening using data from a randomized trial of a cognitive-behavioral intervention designed to improve medication adherence and pain-related outcomes among 110 opioid-treated patients with chronic pain who screened positive for AMTB and were enrolled in a pain program. Providers completed the Aberrant Behavior Checklist (ABC) and patients completed the Current Opioid Misuse Measure (COMM) and the Chemical Coping Inventory (CCI). In multivariate analyses, ABC scores were compared with COMM and CCI scores, while controlling for demographics and established risk factors for AMTB, such as pain severity. Based on clinical cutoffs, 84% of patients reported clinically significant levels of AMTB and providers rated 36% of patients at elevated levels. Provider reports of AMTB were not correlated with COMM or CCI scores. However, the ABC ratings of experienced providers (nurse practitioners/attending physicians) were higher than those of less experienced providers (fellows) and were correlated with CCI scores and risk factors for AMTB. Associations between patient- and provider-reported AMTB and urine drug screening results were low and largely nonsignificant. In conclusion, concordance between patient and provider reports of AMTB among patients with chronic pain prescribed opioid medication varied by provider level of training.

Measurement of QTc in patients receiving chronic methadone therapy.

Recent reports suggest that methadone may prolong the QTc interval and cause torsades de pointes. This study was conducted to evaluate the prevalence of QTc prolongation during oral methadone therapy and identify factors associated with prolongation. Patients receiving oral methadone as treatment for chronic pain or addiction were eligible for the study. One hundred four patients who were receiving > or = 20 mg methadone per day for > or = 2 weeks underwent electrocardiograms to measure QTc interval duration. Sixty-three (61%) patients were male and 63 (61%) were receiving methadone maintenance for opioid addiction. The mean (+/- SD) age was 45.3 +/- 9.4 years. The median (range) methadone dose was 110 mg/day (20-1200 mg/day); median (range) number of months on methadone was 12.5 months (1-444 months). The median (range) QTc interval was 428 msec (396-494 msec). Thirty-three percent had QTc prolongation (males 40%, females 20%; P=0.03). No patient had a QTc longer than 500 msec. Significant dose response was observed in males on methadone <12 months (rho=0.60, P=0.02). Our study suggests that methadone may prolong the QTc interval in specific subpopulations but poses little risk of serious prolongation.

L-carnitine supplementation in patients with HIV/AIDS and fatigue: a double-blind, placebo-controlled pilot study.

BACKGROUND: The purpose of this study was to determine the effect of L-carnitine supplementation on fatigue in patients with terminal human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, patients who had end-stage HIV/AIDS with carnitine deficiency and fatigue received 3 g of oral L-carnitine or placebo for 2 weeks, followed by a 2-week, open-label phase with the same amount of L-carnitine for all patients. The primary outcome was the degree of fatigue according to the Brief Fatigue Inventory. Secondary outcomes included serum carnitine and lactate levels, physical, emotional, social, and functional well-being, performance status, mood, and CD4 count. RESULTS: Eighteen patients in the treatment arm and 17 in the placebo arm completed the trial. At the end of the double-blind phase, total and free carnitine levels in the treatment arm rose from 28±9 to 48±17 nM/L (P<0.001) and from 24±8 to 40±13 nM/L (P<0.001) respectively, with no changes in the placebo arm. The primary outcome, ie, fatigue measured at the end of the blinded phase, did not improve. Secondary outcomes of function, quality of life, and mood did not show improvement either. The secondary outcome of serum lactate decreased from baseline in the treatment group (1.45±0.76 to 1.28±0.52 mmol/L) and increased in the placebo group (1.38±0.62 to 1.84±0.74 mmol/L; P<0.005). CONCLUSION: Our study suggests that 3 g of oral L-carnitine supplementation for 2 weeks in terminally ill HIV/AIDS patients does not improve fatigue. This study might help to determine the dose and duration of treatment used in future clinical trials, as higher doses and/or longer periods of supplementation might be needed in order to detect an improvement. The reduction in serum lactate levels suggests a potential role for L-carnitine supplementation in patients undergoing certain types of antiretroviral therapy. This study contributes evidence-based data to the field of alternative and complementary medicine, a multibillion dollar industry in which controlled studies are not the norm.

Potential impact of abrupt opioid therapy discontinuation in the management of chronic pain: a pilot study on patient perspective.

OBJECTIVES: This survey highlights the perspective of patients with chronic pain when confronted with the possibility of abrupt opioid discontinuation. DESIGN: Anonymous and self-administered survey. SETTING: Pain Clinic in an urban academic hospital setting. PARTICIPANTS: Patients with chronic pain of at least 6 months, and age 18 years or older. MAIN OUTCOME MEASURES: The perceived impact of abrupt opioid discontinuation on mood, daily functioning, and potential for opioid misuse. RESULTS: When patients were asked how they would feel if told their opioids would be discontinued, the responses were neglected (scale mean, 7.1), angry (6.3), helpless (6.7), and upset (7.0) on a scale of 0-10. The majority predicted loss of independence in activities of daily living (scale mean, 7.5), inability to enjoy their lives (7.4), and inability to work (7.8). A group of 19 patients (11.6 percent) reported that they would obtain opioids from friends or family, and 7 (4.4 percent) would obtain them illegally. These patients reported higher scores of neglect, anger, suspicion, helplessness, and upset (p = 0.000-0.019) and were more likely to have previously obtained opioids illegally (p = 0.008-0.023). The most common nonopioid strategies tried by patients were lumbar epidural (71.5 percent), physical therapy (78.9 percent), and exercise (83.5 percent). The strategies considered to be effective as opioid replacement therapy were lumbar epidural (42.3 percent), exercise (43.2 percent), and massage (42.0 percent). CONCLUSIONS: These data suggest that opioid therapy discontinuation is an emotionally distressing experience for most patients, and the transition to nonopioid treatments is a complex process that will require patient participation to achieve optimal care.

Methadone safety: a clinical practice guideline from the American Pain Society and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society.

UNLABELLED: Methadone is used for the treatment of opioid addiction and for treatment of chronic pain. The safety of methadone has been called into question by data indicating a large increase in the number of methadone-associated overdose deaths in recent years that has occurred in parallel with a dramatic rise in the use of methadone for chronic pain. The American Pain Society and the College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society, commissioned an interdisciplinary expert panel to develop a clinical practice guideline on safer prescribing of methadone for treatment of opioid addiction and chronic pain. As part of the guideline development process, the American Pain Society commissioned a systematic review of various aspects related to safety of methadone. After a review of the available evidence, the expert panel concluded that measures can be taken to promote safer use of methadone. Specific recommendations include the need to educate and counsel patients on methadone safety, use of electrocardiography to identify persons at greater risk for methadone-associated arrhythmia, use of alternative opioids in patients at high risk of complications related to corrected electrocardiographic QTc interval prolongation, careful dose initiation and titration of methadone, and diligent monitoring and follow-up. Although these guidelines are based on a systematic review, the panel identified numerous research gaps, most recommendations were based on low-quality evidence, and no recommendations were based on high-quality evidence. PERSPECTIVE: This guideline, based on a systematic review of the evidence on methadone safety, provides recommendations developed by a multidisciplinary expert panel. Safe use of methadone requires clinical skills and knowledge in use of methadone to mitigate potential risks, including serious risks related to risk of overdose and cardiac arrhythmias.

Putative physiological mechanisms underlying tDCS analgesic effects.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that induces changes in excitability, and activation of brain neurons and neuronal circuits. It has been observed that beyond regional effects under the electrodes, tDCS also alters activity of remote interconnected cortical and subcortical areas. This makes the tDCS stimulation technique potentially promising for modulation of pain syndromes. Indeed, utilizing specific montages, tDCS resulted in analgesic effects in experimental settings, as well as in post-operative acute pain and chronic pain syndromes. The promising evidence of tDCS-induced analgesic effects raises the challenging and complex question of potential physiologic mechanisms that underlie/mediate the accomplished pain relief. Here we present hypotheses on how the specific montages and targets for stimulation may affect the pain processing network.

False sense of safety by daily QTc interval monitoring during methadone IVPCA titration in a patient with chronic pain.

It has been proposed that some deaths attributed to methadone are related to prolongation of the QTc interval; however, there are no clear recommendations on electrocardiogram (ECG) monitoring in patients undergoing intravenous methadone infusion. This is a report on a patient receiving methadone intravenous patient-controlled analgesia titration for the treatment of chronic pain. Initially, her daily ECGs showed QTc intervals within normal limits; however, she experienced a rapid increase in QTc interval from 317 ms to 784 ms within a 24-hour period after methadone had been discontinued for excessive sedation. QTc interval greater than 500 ms is considered to be high risk for the fatal arrhythmia Torsades de Pointes. Daily ECGs did not detect a gradual increase in the QTc interval that would have alerted the medical staff of the need to decrease or stop the methadone before reaching a prolonged QTc interval associated with cardiotoxicity. In selected cases where aggressive methadone titration is required, more intensive monitoring, such as telemetry or ECG determinations every 12 hours, might help detect changes in QTc interval duration that might otherwise be missed by daily ECG determinations.

Transcranial direct current stimulation (tDCS) relieved itching in a patient with chronic neuropathic pain.

UNLABELLED: Itching is often called the second modality of nociception besides pain, and affects many chronic pain patients. OBJECTIVES: This case report presents a first note on beneficial effects of transcranial direct current stimulation (tDCS) on itching associated with chronic neuropathic pain in a patient diagnosed with syringomyelia. METHODS: tDCS is a novel noninvasive neuromodulatory method with promising therapeutic potential in pain and symptom management. The primary mechanism of tDCS is subthreshold modulation of the neuronal resting membrane potential that induces a polarity-dependent modification of N-Methyl-D-aspartate receptor function that plays a role in neuroplasticity. The patient, a 46-year-old white male diagnosed with syringomyelia 2 decades ago, continuously reported weakness in the arms and dyesthesias including pain and itch that fluctuated in severity. Pharmacological treatment with baclofen, duloxetine, and bupropion was partially helpful; however, did not prevent flares of pain and other dysesthesias, including itch. The patient underwent 3 tDCS treatment courses consisting of 20 minutes of tDCS on 5 consecutive days at each course over 13 months. RESULTS: Although there was no change in pain intensity or quality during or after tDCS, the treatment resulted in a reduction in itch to a mild, tolerable intensity that persisted for 3 to 4 months after each course, before returning to the pretreatment level. The patient has agreed to a plan of care that will incorporate neurostimulation every 4 to 6 months, as long as its effectiveness continues. DISCUSSION: This case provides a rationale for future studies of neuromodulatory treatments for itch, and indicates a potential clinical use of neuromodulation in patients with unrelieved itching.

Epigenetics: a promising paradigm for better understanding and managing pain.

UNLABELLED: Epigenetic regulation of gene expression is a rapidly growing area of research. Considering the longevity and plasticity of neurons, the studies on epigenetic pathways in the nervous system should be of special interest for both epigeneticists and neuroscientists. Activation or inactivation of different epigenetic pathways becomes more pronounced when the cells experience rapid changes in their environment, and such changes can be easily caused by injury and inflammation, resulting in pain perception or distortion of pain perception (eg, hyperalgesia). Therefore, in this regard, the field of pain is at an advantage to study the epigenetic pathways. More importantly, understanding pain from an epigenetics point of view would provide a new paradigm for developing drugs or strategies for pain management. In this review, we introduce basic concepts of epigenetics, including chromatin dynamics, histone modifications, DNA methylation, and RNA-induced gene silencing. In addition, we provide evidence from published studies suggesting wide implication of different epigenetic pathways within pain pathways. PERSPECTIVE: This article provides a brief overview of epigenetic pathways for gene regulation and highlights their involvement in pain. Our goal is to expose the readers to these concepts so that pain-related phenotypes can be investigated from the epigenetic point of view.

Current and future options for the management of phantom-limb pain.

Phantom-limb pain (PLP) belongs among difficult-to-treat chronic pain syndromes. Treatment options for PLP are to a large degree implicated by the level of understanding the mechanisms and nature of PLP. Research and clinical findings acknowledge the neuropathic nature of PLP and also suggest that both peripheral as well as central mechanisms, including neuroplastic changes in central nervous system, can contribute to PLP. Neuroimaging studies in PLP have indicated a relation between PLP and the neuroplastic changes. Further, it has been shown that the pathological neuroplastic changes could be reverted, and there is a parallel between an improvement (reversal) of the neuroplastic changes in PLP and pain relief. These findings facilitated explorations of novel neuromodulatory treatment strategies, adding to the variety of treatment approaches in PLP. Overall, available treatment options in PLP include pharmacological treatment, supportive non-pharmacological non-invasive strategies (eg, neuromodulation using transcranial magnetic stimulation, visual feedback therapy, or motor imagery; peripheral transcutaneous electrical nerve stimulation, physical therapy, reflexology, or various psychotherapeutic approaches), and invasive treatment strategies (eg, surgical destructive procedures, nerve blocks, or invasive neuromodulation using deep brain stimulation, motor cortex stimulation, or spinal cord stimulation). Venues of further development in PLP management include a technological and methodological improvement of existing treatment methods, an implementation of new techniques and products, and a development of new treatment approaches.

Dose equivalence of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone: a randomized, double-blind trial incorporating a measure of assay sensitivity.

UNLABELLED: Dose selection of a once-daily, osmotic-controlled extended-release (ER) hydromorphone assumes that this drug and immediate-release (IR) hydromorphone are dose equivalent. This trial evaluated dose equivalence using a measure of assay sensitivity. Patients were converted to open-label IR hydromorphone, underwent dose titration, and those on a satisfactory dose entered a randomized, double-blind phase receiving 7 days of: 1) hydromorphone IR 5 times/day at approximately this dose; 2) once-daily hydromorphone ER at this dose; or 3) once-daily hydromorphone ER at one-half this dose. Efficacy was measured using breakthrough medication use, pain, sleep, and global assessments. Of 148 patients, 113 (76%) were randomized. IR and full-dose ER groups produced comparable effects on all measures. Although the prespecified primary analysis of the difference in total daily dose of breakthrough medication between the full-dose ER and half-dose ER groups was not significant, more patients in the half-dose ER group required an increase in breakthrough medication (P = .026) and the half-dose ER group both increased the number of breakthrough doses (P = .026) and had greater percent change in the total daily dose of breakthrough medication (P = .037) than the full-dose group, suggesting that switching from IR to ER hydromorphone at the same daily dose provides equivalent analgesia. PERSPECTIVE: In a randomized, double-blind trial, the same total daily dose of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone had comparable effects. Detection of different effects between blinded dose levels was used as a measure of assay sensitivity. The measure of assay sensitivity can enhance the interpretation of dose equivalence or noninferiority trials.

Using Transcranial Direct Current Stimulation to Treat Depression in HIV-Infected Persons: The Outcomes of a Feasibility Study.

UNLABELLED: Transcranial direct current stimulation (tDCS) is a novel non-invasive neuromodulatory method that influences neuronal firing rates and excitability of neuronal circuits in the brain. tDCS has been shown to relieve Major Depressive Disorder (MDD) in the general population, suggesting its potential for other vulnerable populations with high MDD prevalence. AIMS: This study evaluated the feasibility, safety, acceptability, and clinical outcomes of a 2-week tDCS antidepressant treatment in HIV-MDD co-diagnosed patients, and the feasibility of collecting serum and saliva for analysis of immunity biomarkers. METHODS: Ten enrolled patients underwent baseline evaluation and started the tDCS treatment (Monday-Friday for 2 weeks) delivered with Phoresor II 850 PM for 20 min at 2 mA at each visit, using two saline-soaked sponge electrodes placed over the F3 position of EEG 10-20 system and the contralateral supraorbital region. Outcome measures were collected at baseline, after the last tDCS and 2 weeks later. A quantitative microarray (Ray Bio Tech Inc.) for TH1/TH2 cytokines was used for saliva and plasma analysis. RESULTS: Analyzable outcome-data were obtained from eight subjects. Depression scores significantly decreased (p < 0.0005) after the treatment. No serious adverse events occurred. Several transient minor AEs and occasional changes of blood pressure and heart rate were noted. Mini-mental state examination scores remained unchanged or increased after the treatment. All subjects were highly satisfied with the protocol and treatment results and described the desire to find new treatments for HIV-MDD as motivating participation. CONCLUSION: Findings support feasibility and clinical potential of tDCS for HIV-MDD patients, and justify larger-sample, sham-controlled trials.