ObjectiveThe objective of this study was to assess the effectiveness of duloxetine monotherapy, in comparison with selective serotonin reuptake inhibitor (SSRI) monotherapy, in the treatment of painful physical symptoms (PPS) in Japanese patients with major depressive disorder (MDD) in real-world clinical settings.MethodsThis was a multicenter, 12-week prospective, observational study. This study enrolled MDD patients with at least moderate PPS, defined as a Brief Pain Inventory-Short Form (BPI-SF) average pain score (item 5) ≥3. Patients were treated with duloxetine or SSRIs (escitalopram, sertraline, paroxetine, or fluvoxamine) for 12 weeks, and PPS were assessed by BPI-SF average pain score. The primary outcome was early improvement in the BPI-SF average pain score at 4 weeks post-baseline.ResultsA total of 523 patients were evaluated for treatment effectiveness (duloxetine N=273, SSRIs N=250). The difference in BPI-SF average pain score between the two groups was not statistically significant at 4 weeks post-baseline, the primary endpoint (least-squares mean change from baseline [95% confidence interval]: duloxetine, −2.8 [−3.1, −2.6]; SSRIs, −2.5 [−2.8, −2.3]; P=0.166). There was a numerical advantage for duloxetine in improvement from 4 to 12 weeks post-baseline, and the difference was statistically significant at 8 weeks post-baseline (least-squares mean change from baseline [95% confidence interval]: duloxetine, −3.6 [−3.9, −3.3]; SSRIs, −3.1 [−3.4, −2.8]; P=0.023). The 30% and 50% responder rates were significantly higher in patients treated with duloxetine at 4 and 8 weeks post-baseline. There were no serious adverse events experienced by duloxetine-treated patients. The rate of discontinuations due to adverse events was similar for duloxetine and the SSRIs (1.0% and 0.8% of patients, respectively).ConclusionIn this observational study, BPI-SF improvement was not significantly different at 4 weeks, the primary endpoint; however, patients treated with duloxetine tended to show better improvement in PPS compared to those treated with SSRIs.

ObjectiveTo examine how clinical and demographic patient baseline characteristics influence effectiveness of duloxetine versus selective serotonin reuptake inhibitor (SSRI) treatment, in real-world Japanese clinical settings of patients with major depressive disorder (MDD) and associated painful physical symptoms (PPS).MethodsThis was a multicenter, 12-week, prospective, observational study in patients with MDD (Quick Inventory of Depressive Symptomatology ≥16) and at least moderate PPS (Brief Pain Inventory-Short Form [BPI-SF] average pain ≥3). Patients received duloxetine or SSRIs (escitalopram, sertraline, paroxetine, or fluvoxamine). Assessments were made by using BPI-SF average pain, 17-item Hamilton Rating Scale for Depression (HAM-D17), EuroQol 5-dimension questionnaire, Social Adaptation Self-Evaluation Scale, Global Assessment of Functioning, and ability to work. Predefined subgroups included the number of previous episodes of depression (0 vs ≥1), baseline BPI-SF average pain score (≤6 vs >6), baseline HAM-D17 total score (≤18 vs >18), baseline HAM-D17 retardation (≤7 vs >7) and anxiety somatic subscale scores (≤6 vs >6), and age (<65 vs ≥65 years).ResultsTreatment effectiveness was evaluated in 523 patients (duloxetine N=273, SSRIs N=250). Treatment with duloxetine was superior to SSRIs on most outcome measures in patients experiencing their first depressive episode, those with higher baseline PPS levels, and in patients with more severe baseline depression. This was also the case for older patients. In patients with less severe depression, SSRI treatment tended to show more improvements in depression and quality of life measures versus duloxetine treatment.ConclusionThese preplanned subgroup analyses of data from a prospective observational study suggest that, for Japanese MDD patients with PPS, duloxetine is more effective than SSRIs in patients with a first episode of MDD, with more severe depression, or more severe PPS.

Aims/Introduction To assess the prevalence of diabetic polyneuropathy (DPN)‐related sensory symptoms/signs and associated factors in patients with polyneuropathy, considering non‐linear effects for numerical variables. Materials and Methods A cross‐sectional survey of patients with type 2 diabetes mellitus from 17 primary care clinics across Japan was carried out. DPN and DPN‐related sensory symptoms/signs were diagnosed according to the Diabetic Neuropathy Study Group in Japan criteria. Results Of the 9,914 patients with type 2 diabetes mellitus in this study, 2,745 had DPN and 1,689 had DPN‐related sensory symptoms/signs (61.5% of patients with DPN). There were significant correlations between DPN‐related sensory symptoms/signs and smoking status (odds ratio 2.04 for current and 1.64 for former; P < 0.001 and P = 0.002, respectively), sex (odds ratio 0.56 for male/female; P < 0.001) and alcohol consumption (odds ratio 2.02 for former/never; P = 0.004). Based on the non‐linear logistic regression model, significant correlations were observed between the presence of DPN‐related sensory symptoms/signs and higher systolic blood pressure (SBP), longer diabetes duration, and decreasing age. The logarithm of odds for SBP increased until reaching approximately 130 mmHg, then it plateaued. Conclusions Some modifiable factors assessed in the large survey database might be associated with DPN‐related sensory symptoms/signs, namely smoking, alcohol consumption and SBP. Maintaining SBP <130 mmHg was associated with lower odds of DPN‐related sensory symptoms/signs in patients with DPN.

Objective To investigate the relationship between Hamilton Depression Rating Scale (HAM-D) score and psychiatrists’ judgment of working ability in patients with major depressive disorder (MDD) and painful physical symptoms. Methods This was a prospective, observational, 12-week study in patients who received duloxetine or a selective serotonin reuptake inhibitor. Patients were ≥20 years old, resided in Japan, and had at least moderate depression (Quick Inventory of Depressive Symptomatology ≥16) and at least moderate painful physical symptoms (Brief Pain Inventory-Short Form average pain ≥3). The main outcome in this post-hoc analysis was the HAM-D17 cutoff best corresponding with patients’ working ability according to the investigator’s judgment. Area under the receiver-operator curve was used to determine the time point with the strongest relationship between HAM-D17 and working ability. The optimal HAM-D17 cutoff was determined based on the maximum of sensitivity (true positive rate) minus ([1 minus specificity] [true negative rate]). For the evaluation of binary data, a mixed effects model with repeated measures analysis was used. Results For the estimation of the HAM-D17 cutoff, the area under the receiver-operator curve was maximal at 12 weeks, when a HAM-D17 score of 6 resulted in the best correspondence with working ability in the combined study population. At 12 weeks, a HAM-D17 score of 6 also resulted in the maximum predictive ability in each of the two treatment groups separately. For predicted working ability at 12 weeks, 52.7% of duloxetine-treated patients achieved the HAM-D17 cutoff of ≤6, whereas 48.5% of SSRIs-treated patients achieved HAM-D17 ≤6 ( P =0.477). Conclusion In this study of patients with major depressive disorder and painful physical symptoms, a HAM-D17 score ≤6 corresponded best with patients’ working ability. This finding is consistent with previous studies showing that a HAM-D17 cutoff of ≤7 may overestimate functional recovery from MDD.

Introduction Opioid use disorder is a global problem. Although opioid analgesics are prescribed less frequently in Japan than in many other countries, the rate of aberrant prescription opioid-taking behaviors in Japan is unknown. Methods An internet survey was conducted to estimate the prevalence of and risk factors for prescription opioid misuse, abuse, diversion and doctor shopping in Japanese subjects with chronic pain who had been prescribed opioid analgesics. Results The proportion of respondents ( n = 387) who reported opioid misuse was 45.5% (95% confidence interval [CI]: 40.4–50.6); rates were: 24.6% (95% CI: 20.3–29.2) for abuse; 15.0% (95% CI: 11.6–19.0) for diversion; and 10.6% (95% CI: 7.7–14.1) for doctor shopping. Aberrant prescription opioid-taking behaviors were higher in participants with chronic post-cancer treatment pain (misuse, 64.2%; abuse, 52.2%) or chronic cancer pain (misuse, 57.4%; abuse, 26.2%) than in those with chronic noncancer pain (misuse, 37.8%; abuse, 17.0%). Younger age, male sex, smoking, habitual drinking, diagnosis of psychiatric disease, use of opioids other than tramadol, and use of opioids for chronic post-cancer treatment pain and chronic cancer pain were identified as risk factors for aberrant prescription opioid-taking behaviors. Conclusion Even in Japan, which has not experienced the surge in opioid consumption documented in other countries, aberrant prescription opioid-taking behaviors were observed. When prescribing opioid analgesics, universal precautions should always be taken for both cancer and non-cancer patients. Trial Registration UMIN000041788. Supplementary Information The online version contains supplementary material available at 10.1007/s40122-022-00409-6.