Brief Pain Inventory Average Pain Score Research Articles

Abstract PO1-11-06: Evaluating Symptom Clusters in Patients with Breast Cancer Experiencing Aromatase Inhibitor-Associated Musculoskeletal Symptoms

Abstract Background: Although treatment with an aromatase inhibitor (AI) for 5-10 years decreases 10-year breast cancer mortality by about 40%, up to 25% of patients will stop treatment early because of treatment-related, intolerable joint and muscular pain and stiffness, called aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). We previously identified that nociplastic pain, or chronic pain in the absence of tissue damage or inflammation, is associated with increased likelihood of developing AIMSS. Other studies have found that symptom clusters, such as the SPPADE symptoms (sleep disturbance, pain, physical function impairment, anxiety, depression, and low energy/fatigue) are prevalent and co-occur in patients with cancer. Here we examine the prevalence of SPPADE symptoms for patients experiencing AIMSS and willing to enroll on a clinical trial examining use of cannabidiol (CBD) to treat their symptoms. Methods: Patients with stage 0-3 hormone receptor-positive breast cancer experiencing AIMSS (defined as worst joint pain ≥4/10 during prior 7 days that developed or worsened since starting AI therapy) were eligible for enrollment in this single arm, single center phase 2 open label clinical trial (NCT04754399). Enrolled patients completed validated questionnaires at baseline and then received CBD (Epidiolex) for 15 weeks. Patient-reported outcomes (PRO) data was collected serially, including the following questionnaires which addressed SPPADE symptoms: Brief Pain Inventory (BPI) to assess pain, PROMIS Profile 29+2 v2.1 to assess multiple symptoms, and Fibromyalgia Survey (FMS) to assess nociplastic pain. Results: 39 patients enrolled on this clinical trial. The median age at enrollment was 57 (range 37-59) and 21% of patients were over age 70. The majority of patients were white (92%) and average BMI was 31 (SD 6.6). Anastrozole was the most used aromatase inhibitor (74%), followed by exemestane (18%), and letrozole (8%). 5 patients (13%) required concomitant GnRHa therapy. Baseline PRO data was obtained from 37 patients. BPI average pain score over the week prior to enrollment was 5.1 (SD 1.5) and worst pain score was 7.2 (SD 1.3). Pain interference reported on the BPI was 4.1 (SD 2.1). Compared to the general population, enrolled patients reported better physical function (T-score 60.2, SE 3.7), less depression (T-score 45.5, SE 4.7) and fatigue (T-score 46.7, SE 5.1), and similar levels of anxiety (T-score 51, SE 7.1) and sleep disturbance (T-score 49.5, SE 5.9) on the PROMIS Profile. On the FMS, 62% of patients had evidence of nociplastic pain, with average score 13.3 (SD 5.7). The median number of sites of pain in the body reported by patients was 8 (range 1-16). Conclusions: While patients enrolling on an AIMSS clinical trial reported a high degree of daily pain that regularly interferes with their activities, for most patients these symptoms did not appear to have a negative impact on mood, affect, or other symptoms that typically cluster with pain. Though it is difficult to extrapolate results from a small population, the unexpected absence of co-occurring symptoms in this population raises additional questions about the interplay of AIMSS and other symptoms commonly reported in interventional AIMSS studies. Follow-up PRO data will be obtained in this clinical trial, allowing us to examine the impact of CBD use on pain, pain interference, and other patient-reported symptoms, as well as to explore which patients are more likely to obtain benefit from CBD treatment. Funding support provided by Conquer Cancer, the ASCO Foundation and the Rising Tide Foundation for Clinical Cancer Research. Citation Format: Fleege Nicole, N. Lynn Henry. Evaluating Symptom Clusters in Patients with Breast Cancer Experiencing Aromatase Inhibitor-Associated Musculoskeletal Symptoms [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-11-06.

The Pain Clinic for Older People.

Multidisciplinary pain clinics have an established role in the management of persistent pain, but there is little evidence to support this approach in an older population. This study describes the characteristics and pain outcomes of patients attending a pain clinic designed exclusively for older people. A retrospective audit was performed of outcomes of the Pain Clinic for Older People (PCOP) in 2015-2019. Response to treatment was determined by change in Brief Pain Inventory (BPI) scores at initial attendance and after a treatment program. Clinically meaningful improvement was defined by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus criteria of ≥30% improvement in average pain and one-point improvement in pain interference. Results were compared with the national benchmark collated by the electronic Persistent Pain Outcomes Collaboration (ePPOC), which reports the combined results from 67 participating Australian and New Zealand pain services. Patients attending the PCOP had a mean age of 80.5 years and had high rates of frailty (84%), cognitive impairment (30%), and multimorbidity. Significant reductions in BPI average pain and BPI pain interference scores were achieved. Clinically meaningful improvement in BPI average pain was achieved in 63% of patients attending the PCOP who were 65-74 years of age and in 46% of patients who were ≥75 years of age, which met the national benchmark set by ePPOC of 40% for both age groups. Clinically meaningful improvement in BPI pain interference was achieved in 69% of those attending the PCOP who were 65-74years of age and in 66% of those who were ≥75 years of age, comparable to the ePPOC benchmark of 71% and 65% for the respective age groups. PCOP clients achieved significant and meaningful improvements in their pain outcomes that satisfied the national benchmark. Advanced age, cognitive impairment, frailty and multimorbidity should not be regarded as barriers to benefit from a pain clinic specifically designed for older people.

Abstract PD12-03: Predictors of pain reduction in trials of interventions for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS)

Abstract Background: Up to half of AI-treated breast cancer patients experience AIMSS, and 20-30% have severe symptoms that lead to treatment discontinuation. Multiple interventions have been examined in randomized clinical trials, including in SWOG S0927 (omega-3 fatty acids vs placebo), S1202 (duloxetine vs placebo), and S1200 (true acupuncture vs sham acupuncture vs wait list control). We hypothesized that we could identify predictors of pain reduction in AIMSS intervention trials by combining data from these trials. Methods: The S0927, S1200, and S1202 clinical trials had similar eligibility criteria, and all used the same patient-reported outcomes measures to assess arthralgias and endocrine symptoms. The Brief Pain Inventory (BPI) examines average pain, worst pain, and pain interference; higher numbers reflect more symptoms. Endocrine symptoms were assessed with the Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), which includes subscales for functional and physical well-being; higher scores reflect better function. We also used validated measures to assess joint symptoms in the knees/hips (WOMAC) and hands (M-SACRAH), where higher scores indicate greater symptom severity. We analyzed the subset of patients enrolled on these three trials who had a baseline BPI average pain score of at least 4/10 (S0927, n=185; S1200, n=158; S1202, n=240). The primary outcome was 50% reduction in BPI average pain from baseline to week 12. Variable cut-point selection was performed on each continuous variable to identify a binary cut-point that optimally distinguished high versus low levels of pain reduction. Logistic regression was performed for each variable. A risk model was built by summing the number of statistically significant baseline predictors and categorizing patients by low vs. medium vs. high likelihood of pain reduction. All analyses were stratified by study and adjusted for treatment arm. Results: Of the 583 analyzed patients, median age was 60 years (range 27-84), median body mass index was 30 kg/m2 (range 18-84), and 208 patients (35.7%) had at least a 50% reduction in BPI average pain. Factors significantly associated with at least a 50% reduction in pain included lower pain and pain interference and better physical and functional status at study enrollment (Table). Patients with 2-4 of the 7 statistically significant factors were twice as likely to experience pain reduction compared to those with fewer than 2 factors (37.8% vs. 22.5%; odds ratio [OR] 2.08, 95% CI 1.38-3.13, p<.001). Those with 5-7 factors were more than 5 times more likely to experience pain reduction (61.2% vs. 22.5%; OR 5.66, 95% CI 3.21-9.98, p<.001). Conclusions: Patients with AIMSS who have lower pain and better functional status are more likely to experience meaningful pain reduction in intervention trials for AIMSS. These findings suggest early intervention for treating AIMSS may be important. Baseline pain and functional status should be considered as stratification factors in future interventional trials. Funding: NIH/NCI Grant Award CA189974; and in part by the Hope Foundation for Cancer Research. Association of baseline characteristics with 50% reduction in average pain from baseline to 12 weeksFactorRates of pain reductionOdds Ratio (95% CI)P valueAge: <70 vs ≥70 years37.1% vs. 26.3%1.66 (0.96-2.86)0.07BMI: <30 vs. ≥30 kg/m237.9% vs. 33.6%1.27 (0.90-1.79)0.17BPI average pain: 4 vs. ≥548.6% vs. 31.7%1.93 (1.30-2.86)0.001BPI worst pain: <6 vs. ≥649.0% vs. 32.8%1.95 (1.26-3.02)0.003BPI pain interference: <3 vs. ≥347.8% vs. 31.9%2.21 (1.47-3.32)0.0001FACT-ES Functional Well-Being: ≥24 vs. <2449.3% vs. 33.9%1.97 (1.18-3.30)0.01FACT-ES Physical Well-Being: ≥12 vs. <1238.6% vs. 21.1%2.45 (1.44-4.18)0.001FACT-ES Endocrine Subscale: ≥42 vs. <4236.7% vs. 29.7%1.44 (0.84-2.47)0.19WOMAC: <50 vs. ≥5049.0% vs. 26.0%2.63 (1.85-3.74)<.001M-SACRAH: <33 vs. ≥3345.6% vs. 27.4%2.18 (1.54-3.10)<.001 Citation Format: N. Lynn Henry, Joseph M Unger, Cathee Till, Katherine D Crew, Michael J Fisch, Dawn L Hershman. Predictors of pain reduction in trials of interventions for aromatase inhibitor (AI)-associated musculoskeletal symptoms (AIMSS) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-03.

Clinical pain management by a multidisciplinary palliative care team: Experience from a tertiary cancer center in China.

To investigate the effect of multidisciplinary interventions on pain management in cancer inpatients.Four hundred thirty eight patients with cancer pain, who performed the multidisciplinary intervention were recruited. Before and after intervention, the Brief Pain Inventory (BPI) and the MD Anderson Symptom Inventory (MDASI) score as the primary endpoints and QOL scores as the secondary endpoint were all evaluated. To investigate the factors that led to different responses to multidisciplinary interventions, patients were classified as non-responders or responders.Finally, 92 patients (63 male and 29 female) scheduled for cancer pain management by inter-professional team were studied. After individualized multidisciplinary therapy, both pain and symptom severity was improved, as demonstrated by lowered BPI worst and average pain scores, as well as symptom severity score measured by MDASI (P = .017, P = .003, and P = .011, respectively). The proportion of patients with mild pain increased regarding the BPI worst and average pain at baseline and after treatment (P < .05). The QOL analyses showed multidisciplinary interventions could significantly improve the function and symptom scores (P < .001). More patients in responder group received chemotherapy (58, 70.7%, P = .003), while fewer received mini-invasive therapy (6, 7.32%, P = .011).Multidisciplinary interventions had certain beneficial effect on cancer pain management, especially in patients with moderate or severe pain.

Preoperative ultrasound-guided multilevel paravertebral blocks reduce the incidence of postmastectomy chronic pain: a double-blind, placebo-controlled randomized trial.

PurposeChronic postsurgical pain is a challenging problem after breast cancer surgery. This prospective, randomized, double-blinded, parallel-group, placebo-controlled trial was conducted to evaluate the influence of preoperative ultrasound-guided multilevel paravertebral blocks (PVBs) on chronic pain following mastectomy.Patients and methodsOne hundred eighty-four women were randomized to receive ultrasound-guided multilevel (T1–T5) PVBs with 5 mL of ropivacaine 0.5% or normal saline per level. The primary end point was the incidence of chronic pain at 3 months following mastectomy assessed by the brief pain inventory (BPI), while the secondary end points were the acute postoperative pain, the number of patients requiring rescue analgesia, postoperative nausea and vomiting (PONV), side effects, and chronic pain at 6 months after surgery assessed by the BPI.ResultsA total of 172 patients completed the study. Ultrasound-guided multilevel PVBs significantly decreased immediate postoperative pain for the first 12 hours (P<0.001). Additionally, fewer patients in the PVB group required rescue analgesia in the first 48 hours post-operatively compared to the control group (5/86 vs 28/86, OR =0.128, 95% CI: 0.047–0.351, P<0.001). No statistically significant difference was tested between the two groups (9.3% vs 17.4%, OR =0.419, 95% CI: 0.162–1.087, P=0.068) in the incidence of PONV. At 3 months, the incidence of chronic pain (BPI average pain score ≥3) was 34.5% and 51.2% (OR =0.511, 95% CI: 0.277–0.944, P=0.031) in the PVB and control groups, respectively, and at 6 months, the incidence was 22.1% and 37.2% (OR =0.479, 95% CI: 0.245–0.936, P=0.03), respectively. No complications occurred during the study.ConclusionThis study indicated that perioperative ultrasound-guided multilevel PVBs with ropivacaine improved acute postoperative pain and decreased postmastectomy chronic pain at 3 and 6 months postoperatively.

Omega-3 fatty acid use for obese breast cancer patients with aromatase inhibitor-related arthralgia (SWOG S0927).

Although aromatase inhibitors (AIs) prolong survival in post-menopausal breast cancer (BC) patients, AI-associated arthralgia can lead to discontinuation. Obese patients have higher rates of AI arthralgia than non-obese patients, but treatment options are limited. Omega-3 fatty acid (O3-FA) treatment for AI arthralgia has produced mixed results. We performed an exploratory analysis of SWOG S0927, a multicenter randomized placebo-controlled trial of O3-FA use for AI arthralgia. Post-menopausal women with stage I-III BC taking an AI were randomized to 24 weeks of O3-FAs or placebo. Brief Pain Inventory (BPI) questionnaires and fasting serum were collected at baseline, 12, and 24 weeks. The BPI assessment included worst pain, average pain, and pain interference scores (range 0-10). Among the 249 participants, 139 had BMI < 30kg/m2 (56%) and 110 had BMI ≥ 30kg/m2 (44%). Among obese patients, O3-FA use was associated with significantly lower BPI worst pain scores at 24 weeks compared with placebo (4.36 vs. 5.70, p = 0.02), whereas among non-obese patients, there was no significant difference in scores between treatment arms (5.27 vs. 4.58, p = 0.28; interaction p = 0.05). Similarly, O3-FA use was associated with lower BPI average pain and pain interference scores at 24 weeks compared with placebo among obese patients, but no significant difference between treatment arms in non-obese patients (interaction p = 0.005 and p = 0.01, respectively). In obese BC patients, O3-FA use was associated with significantly reduced AI arthralgia compared to placebo.

Duloxetine 60 mg for chronic low back pain: post hoc responder analysis of double-blind, placebo-controlled trials.

IntroductionDuloxetine has demonstrated efficacy in chronic low back pain (CLBP). We examined the predictors of response to duloxetine for CLBP.Patients and methodsThis was a post hoc analysis of pooled data from 4 double-blind, ran-domized, placebo-controlled trials of duloxetine (60 mg/day for 12–14 weeks) in adult patients with CLBP. Primary outcome was proportion of patients with ≥30% reduction in Brief Pain Inventory (BPI) average pain (“pain reduction”) at 12–14 weeks. The proportion of patients with ≥30% and ≥50% (secondary outcome) pain reduction in duloxetine and placebo groups was compared. Variables for responder analyses were early improvement (≥15% pain reduction at Week 2), sex, age, baseline BPI average pain score, duration of CLBP, and number of painful body sites according to the Michigan Body Map (≥2 vs 1 [isolated CLBP]; 1 trial); relative risk (RR) and 95% confidence interval (CI) were calculated.ResultsCompared with placebo (n = 653), a greater proportion of duloxetine-treated patients (n = 642) achieved ≥30% (59.7% vs 47.8%; P < 0.001) and ≥50% pain reduction (48.6% vs 35.1%; P < 0.001). Among duloxetine-treated patients, early improvement was associated with greater likelihood of ≥30% (RR [95% CI], 2.91 [2.30–3.67]) or ≥50% (3.24 [2.44–4.31]) pain reduction. Women were slightly more likely than men to achieve ≥30% (RR [95% CI], 1.14 [1.00–1.30]) or ≥50% (1.17 [0.99–1.38]) pain reduction. Response rates were similar between age, CLBP duration, and baseline BPI average pain score subgroups. Patients with ≥2 painful sites were more likely to respond to duloxetine 60 mg relative to placebo than patients with isolated CLBP (RR, duloxetine vs placebo [95% CI]: ≥30% reduction, ≥2 painful sites 1.40 [1.18–1.66], isolated CLBP 1.07 [0.78–1.48]; ≥50% reduction, ≥2 painful sites 1.51 [1.20–1.89], isolated CLBP 1.23 [0.81–1.88]).ConclusionEarly pain reduction was indicative of overall response. Patients with multiple painful sites had more benefit from duloxetine than patients with isolated CLBP.

Patient Expectations in the Treatment of Painful Diabetic Polyneuropathy: Results from a Non-Interventional Study

Pain control is the main objective when treating patients with painful diabetic peripheral neuropathic pain (DPNP). However, DPNP is associated with further substantial patient burden that often is not appropriately addressed. Our study identified patients' needs and asked patients what they expected from DPNP treatment. Baseline data were collected in a German prospective, non-interventional study in patients with DPNP starting or switching pain medication at the discretion of the investigator. DPNP severity was evaluated using Brief Pain Inventory (BPI) and Clinician/Patient Global Impression-Severity (CGI-S/PGI-S). Primary objective of this study was to evaluate for which interference item of the BPI DPNP patients expected most to improve due to DPNP therapy. We enrolled 2,576 patients with DPNP from 307 outpatient centers (mean [standard deviation {SD}] age: 65.8 years [11.5], 51.2% female). Mean (SD) CGI-S and PGI-S at baseline were 4.4 (0.91) and 4.5 (1.05), respectively. BPI average pain score was 5.1 (2.04). The BPI interference score was 4.8 (2.18); items most impaired at baseline were walking ability 5.5 (2.60) and general activity 5.4 (2.37). The most frequently chosen BPI interference items expected to improve as a result of the pain treatment were: General activity (29.3%; 95% confidence interval [CI] 27.5-31.0%) and walking ability (24.4%; 95% CI 22.8-26.1%), followed by sleep (14.7%), enjoyment of life (13.6%), mood (8.3%), normal work (7.7%), and relations with other people (1.9%). The majority of patients identified "general activity" and "walking ability" as most relevant BPI interference items for which they expect improvement from DPNP treatment.

Morphine/Naltrexone

Oral morphine/naltrexone extended release capsules comprise the selective mu-opioid receptor agonist morphine in a sustained-release formulation combined with a sequestered core of the mu-opioid receptor antagonist naltrexone for use in the management of moderate to severe pain. When morphine/naltrexone is taken as intended, naltrexone exerts no clinically significant effect. However, when the capsule contents are taken after being tampered with by crushing, chewing or dissolution, naltrexone is rapidly released and absorbed, thereby mitigating the effects of morphine. Morphine/naltrexone was effective in the treatment and management of moderate to severe chronic pain in patients with pain due to osteoarthritis of the hip or knee participating in a randomized, double-blind, placebo-controlled, phase III study (n = 344). Changes in mean Brief Pain Inventory (BPI) average scores from baseline of the double-blind maintenance phase to 12 weeks were significantly better with morphine/naltrexone (20 mg/0.8 mg to 80 mg/3.2 mg twice daily) than with placebo. In a 12-month, open-label safety study, morphine/naltrexone also provided effective pain relief and sustained pain control in patients with chronic, moderate to severe, nonmalignant pain (n = 465 at baseline; 162 at study end). Furthermore, significant mean changes from baseline in BPI worst, least, average and current pain scores were seen from week 1 onwards. Morphine/naltrexone treatment was generally well tolerated in adult patients with chronic moderate to severe nonmalignant pain in clinical trials of up to 1-year duration.

Duloxetine

Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor available in delayed-release capsules for oral use. Duloxetine 60 mg/day, compared with placebo, was associated with a greater reduction from baseline in the Brief Pain Inventory (BPI) average pain severity score, a greater improvement in the patient-rated global impression of improvement (PGI-I) scale in patients with fibromyalgia, with or without major depressive disorder, in two 12- and 15-week phase III studies. In a 27-week, phase III trial, there was no significant difference between duloxetine (60 or 120 mg/day) and placebo for the least squares mean change from baseline to endpoint in BPI average pain scores and the PGI-I score. The significant improvements in efficacy that occurred in patients with fibromyalgia during 8 weeks of open-label treatment with duloxetine 60 mg/day were generally maintained during 52 weeks of subsequent blinded treatment at the same dosage in a phase III trial. Nonresponders during treatment with open-label duloxetine 60 mg/day, demonstrated no increased ability to respond if the duloxetine dosage was up-titrated to 120 mg/day than those who remained on the same dosage during the subsequent 52-week, double-blind phase. Duloxetine was generally well tolerated in studies of up to 1 year in duration, with nausea being the most frequent adverse event and main cause for discontinuing therapy.

Cutpoints for mild, moderate and severe pain in patients with osteoarthritis of the hip or knee ready for joint replacement surgery

BackgroundCutpoints (CPs) for mild, moderate and severe pain are established and used primarily in cancer pain. In this study, we wanted to determine the optimal CPs for mild, moderate, and severe pain in joint replacement surgery candidates with osteoarthritis (OA) of the hip or knee, and to validate the different CPs.MethodsPatients (n = 353) completed the Brief Pain Inventory (BPI), the WOMAC Arthritis Index, and the SF-36 health status measure. Optimal CPs for categorizing average pain with three severity levels were derived using multivariate analysis of variance, using different CP sets for average pain as the independent variable and seven interference items from the BPI as the dependent variable. To validate the CPs, we assessed if patients in the three pain severity groups differed in pain as assessed with WOMAC and SF-36, and if BPI average pain with the optimal CPs resulted in higher correlation with pain dimensions of the WOMAC and SF-36 than other CPs.ResultsThe optimal CPs on the 0–10 point BPI scale were CP (4,6) among hip patients and CP (4,7) among knee patients. The resulting pain severity groups differed in pain, as assessed with other scales than those used to derive the CPs. The optimal CPs had the highest association of average pain with WOMAC pain scores.ConclusionCPs for pain severity differed somewhat for patients with OA of the hip and knee. The association of BPI average pain scores categorized according to the optimal CPs with WOMAC pain scores supports the validity of the derived optimal CPs.

Duloxetine for the Treatment of Fibromyalgia in Women: Pooled Results from Two Randomized, Placebo-Controlled Clinical Trials

To assess the efficacy (in particular, in pain, functional impairment, and quality of life) and safety and tolerability (incidence of adverse events, discontinuation rates, changes in laboratory findings, and vital signs) of duloxetine in female patients with fibromyalgia. Data were pooled from two placebo-controlled clinical trials of similar design (randomized, 12-week, and double-blind), comparing duloxetine 60 mg a day (q.d.) or 60 mg twice daily (b.i.d.) (n = 326) with placebo (n = 212), in women who met the American College of Rheumatology criteria for primary fibromyalgia. Compared with the patients receiving placebo, duloxetine-treated female patients demonstrated a significantly greater improvement in the Brief Pain Inventory (BPI) average pain severity score and in the Fibromyalgia Impact Questionnaire (FIQ) total score, beginning at week 1 and continuing through week 12 (p < 0.001). Duloxetine was superior to placebo on all efficacy measures, including mean tender point threshold, Clinical Global Impression of Severity, Patient Global Impression of Improvement, and average interference from pain scores. The duloxetine-treated group was superior to placebo on all quality of life and functional measures, including each domain of the Medical Outcomes Study Short Form-36 (SF-36). A direct treatment effect of duloxetine on pain reduction was demonstrated and shown to be independent of secondary improvement in mood (based on BPI average pain score). Significantly more duloxetine-treated patients reported treatment-emergent adverse events (296 [90.8%] duloxetine-treated and 165 [77.8%] placebo-treated, p < 0.001). Rates of serious adverse events were similar between duloxetine-treated and placebo-treated patients. The pooled results of these studies demonstrate that duloxetine is a safe and efficacious treatment for both the pain and functional impairment associated with fibromyalgia in female patients, while significantly improving quality of life.

Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder

Background: While emotional symptoms such as depressed mood and loss of interest have traditionally been considered to constitute the core symptoms of major depressive disorder (MDD), the prevalence and importance of painful physical symptoms such as back pain, abdominal pain, and musculoskeletal pain is becoming increasingly appreciated. Antidepressants possessing dual serotonin/norepinephrine (5-HT/NE) reuptake inhibition may demonstrate greater efficacy in the alleviation of pain. The efficacy of duloxetine, a balanced and potent dual reuptake inhibitor of 5-HT and NE, was evaluated within a cohort of depressed patients with associated painful physical symptoms. Methods: In this multicenter, double-blind, placebo-controlled study, patients meeting DSM-IV criteria for MDD were randomized to receive placebo ( N=141) or duloxetine 60 mg QD ( N=141). Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD 17) total score ⩾15, a Clinical Global Impression of Severity (CGI-S) score ⩾4, and a Brief Pain Inventory (BPI) Average Pain score ⩾2 at baseline. The primary efficacy measure was the BPI Average Pain score, while secondary measures included other BPI items, the HAMD 17 total score, CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQSS). Safety was evaluated by recording treatment-emergent adverse events (spontaneously reported), vital signs, and laboratory analytes. Results: Mean changes in BPI Average Pain for duloxetine- and placebo-treated patients differed significantly at most visits, but only approached significance at endpoint ( p=0.066). For the main effect of treatment (pooling all visits), significant advantages for duloxetine-treated patients were found in 10 of 11 assessed BPI pain severity and pain interference items, in addition to VAS overall pain and back pain. Mean changes in pain measures for duloxetine-treated patients corresponded to improvements of 25–50%, compared with 19–39% for placebo. Mean changes at endpoint in depression rating scales (HAMD 17, CGI-S, PGI-I) did not differ significantly between duloxetine and placebo treatment groups due to unusually high placebo response. The magnitude of placebo treatment effects (as measured by HAMD 17 total score and Maier subscale) was significantly smaller in patients with ⩾1 previous depressive episode, compared to those patients with no previous episodes. In patients with ⩾1 previous depressive episode the advantage of duloxetine over placebo was similar to previous studies. Rates of discontinuation due to adverse events were 14.2% vs. 2.1% for duloxetine and placebo, respectively ( p<0.001). Treatment-emergent adverse events reported at a significantly higher rate by duloxetine-treated patients included nausea, dry mouth, fatigue, and decreased appetite. Conclusions: In this study, duloxetine (60 mg QD) was shown to be an effective treatment for the painful physical symptoms which are frequently associated with depression. Improvements in pain severity occurred independently of changes in depressive symptom severity.