Erin E. Krebs

Association of Mental Health Disorders With Prescription Opioids and High-Risk Opioid Use in US Veterans of Iraq and Afghanistan

CONTEXT Record numbers of Iraq and Afghanistan veterans survive their war injuries and yet continue to experience pain and mental health problems, particularly posttraumatic stress disorder (PTSD). Little is known about the association of mental health disorders and prescription opioid use. OBJECTIVE To investigate the effect of mental health disorders, particularly PTSD, on risks and adverse clinical outcomes associated with prescription opioid use. DESIGN Retrospective cohort study involving 141,029 Iraq and Afghanistan veterans who received at least 1 non-cancer-related pain diagnosis within 1 year of entering the Department of Veterans Affairs (VA) health care system from October 1, 2005, through December 31, 2010. MAIN OUTCOME MEASURES Independent association of mental health disorders and the prescription of opioids, higher risk opioid use, and adverse clinical outcomes (eg, accidents and overdose) within 1 year of receiving a pain-related diagnosis. RESULTS A total of 15,676 veterans were prescribed opioids within 1 year of their initial pain diagnosis. Compared with 6.5% of veterans without mental health disorders, 17.8% (adjusted relative risk [RR], 2.58; 95% CI, 2.49-2.67) of veterans with PTSD and 11.7% (adjusted RR, 1.74; 95% CI, 1.67-1.82) with other mental health diagnoses but without PTSD were significantly more likely to receive opioids for pain diagnoses. Of those who were prescribed pain medication, veterans with PTSD were more likely than those without mental health disorders to receive higher-dose opioids (22.7% vs 15.9%, adjusted RR, 1.42; 95% CI, 1.31-1.54), receive 2 or more opioids concurrently (19.8% vs 10.7%, adjusted RR, 1.87; 95% CI, 1.70-2.06), receive sedative hypnotics concurrently (40.7% vs 7.6%, adjusted RR, 5.46; 95% CI, 4.91-6.07), or obtain early opioid refills (33.8% vs 20.4%; adjusted RR, 1.64; 95% CI, 1.53-1.75). Receiving prescription opioids (vs not) was associated with an increased risk of adverse clinical outcomes for all veterans (9.5% vs 4.1%; RR, 2.33; 95% CI, 2.20-2.46), which was most pronounced in veterans with PTSD. CONCLUSION Among US veterans of Iraq and Afghanistan, mental health diagnoses, especially PTSD, were associated with an increased risk of receiving opioids for pain, high-risk opioid use, and adverse clinical outcomes.

Pharmacotherapy of chronic pain: a synthesis of recommendations from systematic reviews

OBJECTIVES Chronic pain is one of the most prevalent, costly and disabling conditions in both clinical practice and the workplace, yet often remains inadequately treated. Moreover, chronic pain commonly co-occurs with depression, anxiety and somatoform disorders, and adversely affects response of these conditions to psychiatric treatments. This article provides an evidence-based approach to the pharmacotherapy of chronic pain. METHODS This narrative review is derived largely from meta-analyses and systematic reviews published since 2005. For a few medications, findings from multiple recent trials are synthesized if a systematic review had not yet been published. Classes of medications are first reviewed, followed by an overview of four common pain disorders: neuropathic pain, low back pain, fibromyalgia and osteoarthritis. RESULTS A stepped care approach based upon existing evidence includes (1) simple analgesics (acetaminophen or nonsteroidal anti-inflammatory drugs); (2) tricyclic antidepressants (if neuropathic, back or fibromyalgia pain) or tramadol; (3) gabapentin, duloxetine or pregabalin if neuropathic pain; (4) cyclobenzaprine, pregabalin, duloxetine, or milnacipran for fibromyalgia; (5) topical analgesics (capsaicin, lidocaine, salicylates) if localized neuropathic or arthritic pain; and (6) opioids. Disease-specific recommendations for neuropathic, low back, fibromyalgia and osteoarthritis pain are reviewed. CONCLUSIONS A number of medications have proven effective in chronic pain disorders and their use individually or in combination should improve the management of chronic pain.

Reciprocal Relationship Between Pain and Depression: A 12-Month Longitudinal Analysis in Primary Care

UNLABELLED Pain and depression are the most prevalent physical and psychological symptom-based disorders, respectively, and co-occur 30 to 50% of the time. However, their reciprocal relationship and potentially causative effects on one another have been inadequately studied. Longitudinal data analysis involving 500 primary care patients with persistent back, hip, or knee pain were enrolled in the Stepped Care for Affective Disorders and Musculoskeletal Pain (SCAMP) study. Half of the participants had comorbid depression and were randomized to a stepped care intervention (n = 123) or treatment as usual (n = 127). Another 250 nondepressed patients with similar pain were followed in a parallel cohort. Outcomes were assessed at baseline, 3, 6, and 12 months. Mixed effects model repeated measures (MMRM) multivariable analyses were conducted to determine if change in pain severity predicted subsequent depression severity, and vice versa. Change in pain was a strong predictor of subsequent depression severity (t-value = 6.63, P < .0001). Likewise, change in depression severity was an equally strong predictor of subsequent pain severity (t-value = 7.28, P < .0001). Results from the full cohort were similar in the clinical trial subgroup. In summary, pain and depression have strong and similar effects on one another when assessed longitudinally over 12 months. PERSPECTIVE This study strengthens the evidence for a bidirectional and potentially causative influence of pain and depression on one another. A change in severity of either symptom predicts subsequent severity of the other symptom. Thus, recognition and management of both conditions may be warranted, particularly when treatment focused on 1 condition is not leading to an optimal response.

Phytoestrogens for treatment of menopausal symptoms: a systematic review

OBJECTIVE: To assess the efficacy and tolerability of phytoestrogens for treatment of menopausal symptoms. DATA SOURCES: We searched the Cochrane Library and MEDLINE from 1966 to March 2004, using a detailed list of terms related to phytoestrogens and menopausal symptoms and also hand-searched abstracts from relevant meetings. METHODS OF STUDY SELECTION: Randomized trials were eligible if they involved symptomatic perimenopausal or postmenopausal women, compared phytoestrogen with placebo or control, reported hot flush frequency or menopausal symptom scores, and were at least 4 weeks in duration. TABULATION, INTEGRATION, AND RESULTS: Data were extracted onto standardized forms using a prospectively developed protocol. Twenty-five trials involving 2,348 participants met criteria. At baseline, the mean age was 53.1 years, mean duration of menopause was 4.3 years, and mean daily hot flush frequency was 7.1. Mean study duration was 17 weeks. Trials were grouped into categories according to type of phytoestrogen: soy foods, beverages, or powders (n = 11); soy extracts (n = 9); and red clover extracts (n = 5). Of the 8 soy food trials reporting hot flush frequency outcomes, 7 were negative. Five trials of soy foods provided information to calculate effect sizes; these were in the small-to-medium range, favoring placebo in 3 trials and soy in 2. Of the 5 soy extract trials reporting hot flush frequency, 3 (including the 2 largest trials) were negative. Effect sizes were calculated for 2 soy extract trials: one favored placebo with small effect size and the other favored soy with moderate effect size. Red clover trials showed no improvement in hot flush frequency (weighted mean difference −0.60, 95% confidence interval −1.71 to 0.51). Adverse effects were primarily gastrointestinal and taste intolerance in the soy food and beverage trials. CONCLUSION: The available evidence suggests that phytoestrogens available as soy foods, soy extracts, and red clover extracts do not improve hot flushes or other menopausal symptoms.

Accuracy of the Pain Numeric Rating Scale as a Screening Test in Primary Care

BACKGROUNDUniversal pain screening with a 0–10 pain intensity numeric rating scale (NRS) has been widely implemented in primary care.OBJECTIVETo evaluate the accuracy of the NRS as a screening test to identify primary care patients with clinically important pain.DESIGNProspective diagnostic accuracy studyPARTICIPANTS275 adult clinic patients were enrolled from September 2005 to March 2006.MEASUREMENTSWe operationalized clinically important pain using two alternate definitions: (1) pain that interferes with functioning (Brief Pain Inventory interference scale ≥ 5) and (2) pain that motivates a physician visit (patient-reported reason for the visit).RESULTS22% of patients reported a pain symptom as the main reason for the visit. The most common pain locations were lower extremity (21%) and back/neck (18%). The area under the receiver operator characteristic curve for the NRS as a test for pain that interferes with functioning was 0.76, indicating fair accuracy. A pain screening NRS score of 1 was 69% sensitive (95% CI 60–78) for pain that interferes with functioning. Multilevel likelihood ratios for scores of 0, 1–3, 4–6, and 7–10 were 0.39 (0.29–0.53), 0.99 (0.38–2.60), 2.67 (1.56–4.57), and 5.60 (3.06–10.26), respectively. Results were similar when NRS scores were evaluated against the alternate definition of clinically important pain (pain that motivates a physician visit).CONCLUSIONSThe most commonly used measure for pain screening may have only modest accuracy for identifying patients with clinically important pain in primary care. Further research is needed to evaluate whether pain screening improves patient outcomes in primary care.

Women at war: understanding how women veterans cope with combat and military sexual trauma.

The wars in Iraq (Operation Iraqi Freedom, OIF) and Afghanistan (Operation Enduring Freedom, OEF) have engendered a growing population of US female veterans, with women now comprising 15% of active US duty military personnel. Women serving in the military come under direct fire and experience combat-related injuries and trauma, and are also often subject to in-service sexual assaults and sexual harassment. However, little is known regarding how women veterans cope with these combat and military sexual trauma experiences once they return from deployment. To better understand their experiences, we conducted semi-structured interviews with nineteen OEF/OIF women veterans between January-November 2009. Women veterans identified stressful military experiences and post-deployment reintegration problems as major stressors. Stressful military experiences included combat experiences, military sexual trauma, and separation from family. Women had varying abilities to address and manage stressors, and employed various cognitive and behavioral coping resources and processes to manage their stress.

Comparative risk for harms of second-generation antidepressants : a systematic review and meta-analysis.

Background: Evidence indicates that only minor differences in efficacy exist among second-generation antidepressants for the treatment of major depressive disorder (MDD). However, a comprehensive assessment of both benefits and harms is crucial to evaluate the net benefit.Objective: To review systematically the comparative harms of second-generation antidepressants for the treatment of MDD in adults by including both experimental and observational evidence.Data sources: We searched MEDLINE®, EMBASE, PsychLit, The Cochrane Library and the International Pharmaceutical Abstracts from 1980 to April 2007. We manually searched reference lists of pertinent review articles and explored the Center for Drug Evaluation and Research database to identify unpublished research.Study selection: Eligible study designs were trials and observational studies comparing one drug of interest with another.Data extraction: Two persons independently reviewed abstracts and full-text articles. One investigator extracted relevant data. A senior reviewer checked data for completeness and accuracy.Data synthesis: We included 104 experimental and observational studies. If data were sufficient, we conducted meta-analyses of randomized controlled trials on the relative risk of specific adverse events. Findings indicate that the spectrum of adverse events is similar. The frequency of specific adverse events, however, differed across drugs. Venlafaxine was associated with a significantly higher rate of nausea and vomiting than selective serotonin reuptake inhibitors. Compared with other drugs, paroxetine frequently led to more sexual adverse effects and bupropion to fewer such effects; mirtazapine and paroxetine was associated with more weight gain and sertraline with a higher rate of diarrhoea. Overall, however, these differences did not lead to different discontinuation rates. The evidence is insufficient to draw conclusions about rare but severe adverse events.Conclusions: Adverse event profiles are similar among second-generation antidepressants. However, different frequencies of specific adverse events might be clinically relevant and influence the choice of a treatment.

Prevalence of painful musculoskeletal conditions in female and male veterans in 7 years after return from deployment in Operation Enduring Freedom/Operation Iraqi Freedom

BackgroundWe sought to describe sex differences in the prevalence of painful musculoskeletal conditions in men and women Veterans after deployment in Operation Enduring Freedom (Afghanistan) and Operation Iraqi Freedom (Iraq) (OEF-OIF). MethodsThis is an observational study using Veterans Affairs (VA) administrative and clinical databases of OEF-OIF Veterans who had enrolled in and used VA care. The prevalence of back problems, musculoskeletal conditions, and joint disorders was determined at years 1 through 7 after deployment for female and male Veterans using ICD-9 code groupings for these conditions. ResultsFemale Veterans were younger (mean age 29 vs. 30, P<0.0001), more likely to be African American (26% vs. 13%, P<0.0001), and less likely to be married (34% vs. 47%, P<0.0001). For both female and male Veterans, the prevalence of painful musculoskeletal conditions increased each year after deployment. After adjustment for significant demographic differences, women were more likely than men to have back problems [year 1 odds ratio (OR) 1.06 (1.01, 1.11)], musculoskeletal problems [year 1 OR 1.32 (1.24, 1.40)], and joint problems [year 1 OR 1.36 (1.21, 1.53)] and the odds of having these conditions increased each year for women compared with men in years 1 to 7 after deployment. DiscussionTo provide quality care to female Veterans, the VA must understand the impact of deployment on womens health. Our findings provide an important picture of the increasing prevalence of musculoskeletal conditions in the female Veteran population and highlight the importance of the VA targeting treatment programs that focus on issues of particular importance to women with musculoskeletal pain.

The Burden of Illness in the First Year Home: Do Male and Female VA Users Differ in Health Conditions and Healthcare Utilization

BACKGROUND we sought to describe gender differences in medical and mental health conditions and health care utilization among veterans who used Veterans Health Administration (VA) services in the first year after combat in Iraq and Afghanistan. METHODS this is an observational study, using VA administrative and clinical data bases, of 163,812 Operation Enduring Freedom/Operation Iraqi Freedom veterans who had enrolled in VA and who had at least one visit within 1 year of last deployment. RESULTS female veterans were slightly younger (mean age, 30 years vs. 32 for men; p <.0001), twice as likely to be African American (30% vs. 15%; p <.0001), and less likely to be married (32% vs. 49%; p < .0001). Women had more visits to primary care (2.6 vs. 2.0; p < .001) and mental health (4.0 vs. 3.6; p < .001) clinics and higher use of community care outside the VA (14% vs. 10%; p < .001). After adjustment for significant demographic differences, women were more likely to have musculoskeletal and skin disorders, mild depression, major depression, and adjustment disorders, whereas men were more likely to have ear disorders and posttraumatic stress disorder. Thirteen percent of women sought care for gynecologic examination, 10% for contraceptive counseling, and 7% for menstrual disorders. CONCLUSION female veterans had similar rates of physical conditions, but higher rates of some mental health disorders and additionally, used the VA for reproductive health needs. They also had slightly greater rates of health care service use. These findings highlight the complexity of female Veteran health care and support the development of enhanced comprehensive womens health services within the VA.

Meta-analysis of Major Depressive Disorder Relapse and Recurrence With Second-Generation Antidepressants

OBJECTIVE This meta-analysis reviewed data on the efficacy and effectiveness of second-generation antidepressants for preventing major depression relapse and recurrence during continuation and maintenance phases of treatment, respectively. METHODS MEDLINE, EMBASE, and PsycINFO, the Cochrane Library, and International Pharmaceutical Abstracts were searched for the period of January 1980 through April 2007 for reviews, randomized controlled trials, meta-analyses, and observational studies on the topic. Two persons independently reviewed abstracts and full-text articles using a structured data abstraction form to ensure consistency in appraisal and data extraction. RESULTS Four comparative trials and 23 placebo-controlled trials that addressed relapse or recurrence prevention were included. Results of comparative trials have not demonstrated statistically significant differences between duloxetine and paroxetine, fluoxetine and sertraline, fluvoxamine and sertraline, and trazodone and venlafaxine. Pooled data for the class of second-generation antidepressants compared with placebo suggested a relatively large effect size that persists over time. For preventing both relapse and recurrence, the number of patients needed to treat is five (95% confidence interval of 4 to 6). Differences in the length of open-label treatment before randomization, drug type, and trial duration did not affect pooled estimates of relapse rates. Across all trials, 7% of patients randomly assigned to receive active treatment and 5% of patients randomly assigned to receive a placebo discontinued treatment because of adverse events. CONCLUSIONS This review demonstrates the overall benefits of continuation- and maintenance-phase treatment of major depression with second-generation antidepressants and emphasizes the need for additional studies of comparative differences among drugs.