Painful Physical Symptoms Research Articles

Painful physical symptoms and antidepressant treatment outcome in depression: a systematic review and meta-analysis.

Painful physical symptoms (PPS) are highly prevalent in patients with major depressive disorder (MDD). Presence of PPS in depressed patients are potentially associated with poorer antidepressant treatment outcome. We aimed to evaluate the association of baseline pain levels and antidepressant treatment outcomes. We searched PubMed, Embase and Cochrane Library databases from inception through February 2023 based on a pre-registered protocol (PROSPERO: CRD42022381349). We included original studies that reported pretreatment pain measures in antidepressant treatment responder/remitter and non-responder/non-remitter among patients with MDD. Data extraction and quality assessment were performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses by two reviewers independently. The primary outcome was the difference of the pretreatment pain levels between antidepressant treatment responder/remitter and non-responder/non-remitter. Random-effects meta-analysis was used to calculate effect sizes (Hedge's g) and subgroup and meta-regression analyses were used to explore sources of heterogeneity. A total of 20 studies were included. Six studies reported significantly higher baseline pain severity levels in MDD treatment non-responders (Hedge's g = 0.32; 95% CI, 0.13-0.51; P = 0.0008). Six studies reported the presence of PPS (measured using a pain severity scale) was significantly associated with poor treatment response (OR = 1.46; 95% CI, 1.04-2.04; P = 0.028). Five studies reported significant higher baseline pain interference levels in non-responders (Hedge's g = 0.46; 95% CI, 0.32-0.61; P < 0.0001). Four studies found significantly higher baseline pain severity levels in non-remitters (Hedge's g = 0.27; 95% CI, 0.14-0.40; P < 0.0001). Eight studies reported the presence of PPS significantly associated with treatment non-remission (OR = 1.70; 95% CI, 1.24-2.32; P = 0.0009). This study suggests that PPS are negatively associated with the antidepressant treatment outcome in patients with MDD. It is possible that better management in pain conditions when treating depression can benefit the therapeutic effects of antidepressant medication in depressed patients.

Reproductive outcome after in vitro fertilization in endometriosis - key factors and implications.

Endometriosis is a benign chronic disease with a major impact on a woman's quality of life, mainly due to painful physical symptoms. Endometriosis is also a common cause of infertility caused by low ovarian reserve, distorted pelvic anatomy, and severe local inflammation with a direct negative impact on the quality of oocytes, embryos, and endometrium. We conducted a retrospective study between January 2019 and December 2023, including women with a history of surgery for endometriosis who underwent in vitro fertilization (IVF) to achieve pregnancy. Their reproductive outcome was compared with a group of patients with documented tubal obstruction. The aim of our study was to identify the factors associated with a positive impact on the pregnancy rate, specifically age, anti-Mullerian hormone (AMH), ovarian stimulation protocol, and types of gonadotropins used. We analyzed a group of 175 patients with endometriosis compared with 189 patients with tubal obstruction. The average age was similar between the two groups but with a difference in the average AMH value (1.63 ± 1.09 ng/mL vs. 2.55 ± 1.67 ng/mL). The most utilized ovarian stimulation protocol in both groups was the short gonadotropin-releasing hormone (GnRH) antagonist. The clinical pregnancy rate was 27.2% in the endometriosis group and 54.7% in the tubal obstruction group. Our study revealed that treatment with corifollitropin alfa in the endometriosis group was associated with a higher clinical pregnancy rate. AMH and age proved to be significant independent factors for the reproductive outcome.

Impact of painful physical symptoms on first-episode major depressive disorder in adults with subthreshold depressive symptoms: A prospective cohort study

ObjectiveTo investigate the impact of baseline painful physical symptoms (PPS) on subsequent first-episode major depressive disorder (MDD) in adults with subthreshold depressive symptoms, including subgroup analyses to assess whether the associations differ in individuals with and without physical diseases. MethodsA total of 2343 adults with subthreshold depressive symptoms were recruited at 34 primary health care centers. PPS were measured at baseline. First-episode MDD during follow-up was diagnosed by professional psychiatrists using the Mini-International Neuropsychiatric Interview. ResultsBaseline PPS showed independent impacts on first-episode MDD in adults with subthreshold depressive symptoms without physical diseases, but not in those with physical diseases. A non-linear association (P < 0.001) was observed between PPS burden and the risk of first-episode MDD. The HRs for first-episode MDD exhibited a rapidly increasing trend between PPS burden scores of 10–16, and maintained consistently high when scores exceeded 16. The analyses for specific PPS revealed that headache, neck pain, and heart or chest pain were independently associated with first-episode MDD in participants without physical diseases, the HRs were 1.57 (1.15–2.36), 1.53 (1.02–2.30), and 1.69 (1.14–2.50), respectively. Further network analysis demonstrated that heart or chest pain serves as a bridge symptom among the seven specific PPS and first-episode MDD in those without physical diseases. ConclusionPPS burden and heart or chest pain may be significant indicators for first-episode MDD in adults with subthreshold depressive symptoms without physical diseases. Future studies should investigate whether interventions targeting PPS can prevent episode MDD in this subthreshold population.

Effectiveness of contextual schema therapy for emotion regulation and painful physical symptoms in individuals with social anxiety disorder: Single subject study

Introduction: Social anxiety disorder is characterized by intense anxiety in social situations where the person is likely to be evaluated by others. Aim: The present study aimed to investigate the effectiveness of contextual schema therapy on emotion regulation and painful physical symptoms in individuals with social anxiety disorder. Method: This study employed an A-B single-subject design. The statistical population included all the people with social anxiety disorder in Mashhad city, in 2021, and 12 people were selected by convenience sampling method. Then, the contextual schema therapy was conducted during 16 sessions of 1 hour once a week for 12 subjects. The Emotion Regulation Questionnaire (2003) and the Visual Analog Scale (1921) were used in this study. The Subjects answered the questionnaires in the baseline phase, at sessions 4, 8, 12 and 16, and at 3-month follow-up. The data were analyzed using visual analysis, improvement percentage, reliable change index, and non-overlapping effect size. Results: The improvement percentage (25%&lt;), the reliable change index (1.96&lt;) and the non-overlapping data (75&lt;) indicated the significant effect of the treatment in increasing the reappraisal subscale of all subjects (except subject 12), reducing the expressive suppression subscale of all subjects and reducing painful physical symptoms of all subjects (except subject 7). The improvement percentage at the follow-up showed that the intervention was effective in increasing the reappraisal, reducing expressive suppression and painful physical symptoms. Conclusion: Based on the findings, contextual schema therapy was effective in improving emotion regulation and reducing painful physical symptoms by modifying the modes and the third wave methods. Therefore, contextual schema therapy can be suggested as a suitable intervention for social anxiety disorder.

Relationship between the tryptophan-kynurenine pathway and painful physical symptoms in patients with major depressive disorder

ObjectivesTo investigate the relationship between the tryptophan-kynurenine (TRP-KYN) pathway and painful physical symptoms (PPS) in major depressive disorder (MDD). MethodsEighty-four patients with MDD (40 patients with PPS and 44 without PPS) and forty-six healthy controls (HC) were recruited. The serum levels of tryptophan (TRP), kynurenine(KYN), kynurenic acid (KA), quinolinic acid (QA), 3-hydroxy-kynurenine (3−HK), serotonin (5-HT) were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Depression, anxiety and pain were assessed using Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA) and Short-form McGill pain questionnaire (SFMPQ) respectively. ResultsPatients in the MDD group exhibited significantly lower KA and 5-HT levels than HC, whereas MDD patients with PPS showed higher KYN and QA levels, and a higher KYN/TRP ratio than those without. There was a positive correlation between the scores of SFMPQ and QA levels and a negative correlation between the scores of SFMPQ and TRP levels or KA/QA ratios in MDD patients with PPS group. Stepwise multiple regression analysis showed that the KYN/TRP ratios, the KA/QA ratios, and the HAMD scores were significant predictor factors for SFMPQ scores. ConclusionsThese results demonstrated that the TRP-KYN pathway may play a role in the pathophysiology of pain in patients with major depressive disorder, suggesting that further studies of this pathway as a potential biomarker or therapeutic target are required.

The Relationship Between Baseline Clinical Symptom Characteristics and Working Ability in Japanese Patients Treated for Major Depressive Disorder and Painful Physical Symptoms.

PurposeThe objective of this post hoc analysis was to explore the relationship, including changes over time, between baseline clinical symptom characteristics and working ability, judged by investigators, after 12 weeks of antidepressant monotherapy in Japanese patients with major depressive disorder (MDD) and painful physical symptoms (PPS) in a real-world clinical setting.Patients and MethodsThis prospective, observational study in patients treated with duloxetine or selective serotonin reuptake inhibitors was conducted from 2014 to 2016. Both treatment groups were pooled and divided into 2 groups, “working ability recovered” or “working ability not recovered,” based on working ability at the end of the study. Patients were also divided into 4 subgroups by the presence or absence of previous depressive episodes and working ability. Main outcome measures included baseline demographics and clinical characteristics, and the 17-item Hamilton Rating Scale for Depression (HAM-D17).ResultsComparison between “working ability recovered” (n=122) and “working ability not recovered” (n=91) showed that the percentage of patients with complications and psychotherapy at baseline, and baseline HAM-D17 total, insomnia, somatic, and anxiety scores, were significantly different. The results of subgroup analyses were mostly the same as the results analyzed by working ability alone. Although statistical differences were observed for some outcome measures, the differences at baseline, except use of psychotherapy, may not be applicable clinically, and there were no specific trends observed that could predict working ability.ConclusionThis post hoc analysis suggested that most baseline clinical characteristics, including the presence or absence of previous depressive episodes, were not predictive of working ability recovery. However, the use of psychotherapy in parallel with antidepressant monotherapy may be positively associated with working ability recovery. All outcome measures improved over time, reinforcing the importance of continuous treatment and observation to improve and accurately judge working ability in patients with MDD and PPS.

Migraine with active headache was associated with other painful physical symptoms at two-year follow-up among patients with major depressive disorder.

BackgroundFew studies have investigated the associations of comorbid migraine with other painful physical symptoms (PPS) in patients with major depressive disorder (MDD) at the two-year follow-up point. This study aimed to investigate this issue.MethodsAt baseline, 155 outpatients with MDD were enrolled. Migraine was diagnosed at baseline according to the International Classification of Headache Disorders. At follow-up, data of 101 subjects were analyzed. The average intensities of head, bone and/or joints, back, chest, abdomen, neck and/or shoulder, general muscle, and limb pain in the past week were evaluated using a visual analog scale (VAS). At follow-up, active headache was defined as a score on the VAS > 3. Multiple linear regressions were used to investigate the associations of migraine at baseline with other PPS at follow-up.ResultsCompared with the migraine with inactive headache group and the non-migraine group, patients with migraine with active headache had significantly higher intensities of other PPS and a lower remission rate of depression. There were no significant differences in the pain intensities of the other seven PPS between the migraine with inactive headache group and the non-migraine group. Headache intensity was significantly correlated with the intensities of other PPS at baseline and follow-up. Migraine with active headache independently predicted other PPS after controlling for depression and anxiety at baseline.ConclusionsMigraine with active headache among MDD patients could predict other PPS. Prevention and treatment of headache might help to decrease other PPS and improve the prognosis of depression. Integration of treatment for depression and headache is indicated.

Analysis of HAM-D scores and working ability in an observational study of Japanese patients with major depressive disorder and painful physical symptoms treated with duloxetine or SSRI monotherapy.

ObjectiveTo 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.MethodsThis 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.ResultsFor 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).ConclusionIn 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.

Efficacy and safety of duloxetine versus sertraline for Chinese depression patients: a meta-analysis

Objective To systematically evaluate the efficacy and safety of duloxetine and sertraline for Chinese depression patients. Methods The randomized controlled trials (RCTs) comparing the efficacy and safety of duloxetine and sertraline in the treatment of depression were retrieved from databases and the quality of literature was evaluated. Meta-analysis was performed with the software Revman 5.2. Results Eighteen RCTs involving 1 557 Chinese depression patients were included. The results of Meta-analysis showed that there were no significant differences in efficacy and cure rate between duloxetine and sertraline groups (OR=1.28, 95%CI: 0.94-1.73, P=0.11; OR=1.25, 95%CI: 0.97-1.62, P=0.09, respectively). The Hamilton Depression Scale (HAMD) scores were significantly lower in duloxetine group than those in sertraline group at 1, 2 weeks after treatment; however, there were no significant differences at 8-weeks after treatment between duloxetine and sertraline groups. The score of Medical Outcomes Study Pain Measures (MOSPM) in duloxetine group was significantly lower than that in sertraline group (P 0.05). Conclusions Duloxetine has similar long term treatment effect as sertraline, but it has a rapid-action profile. Duloxetine is more effective than sertraline in depression with painful physical symptoms; besides, duloxetine is less likely to induce insomnia. Key words: Duloxetine; Sertraline; Depression; Randomized controlled trial; Meta-analysis

Is Venlafaxine More Effective than Escitalopram and Nortriptyline in the Management of Painful Symptoms in Patients with Major Depression?

Conflicting data regarding the efficacy of antidepressants of different mechanism of action on unexplained painful physical symptoms (UPPS) in depression have been published so far. The aim of this study was to compare the impact of escitalopram (ESC), nortriptyline (NOR), and venlafaxine (VEN) on UPPS in patients with major depression. Sixty patients, participants in the GENDEP study, with a diagnosis of depression according to the ICD-10 criteria were randomly assigned to treatment with ESC (10-30 mg, mean dose 15.2, standard deviation [SD]±9.2) or NOR (50-150 mg, mean dose 106.2, SD±8.2). Additionally, 30 patients who were treated with VEN (75-225 mg, mean dose 181.3, SD±8.8) were included. Before inclusion (day 0) and throughout the study (days 14, 28, 42, 56), the severity of pain was monitored using the visual analog scale. The patients treated with ESC, NOR, and VEN did not differ in the intensity of pain at days 0, 14, 28, 42, and 56. Our results do not support the hypothesis suggesting the superiority of VEN over ESC and NOR in the management of UPPS in major depression.

Comparison of duloxetine and SSRI as a treatment option of painful physical symptoms associated with major depressive disorder.

Comparison of duloxetine and SSRI as a treatment option of painful physical symptoms associated with major depressive disorder.

Functional Impairment and Painful Physical Symptoms in Patients with Major Depressive Disorder Treated with Antidepressants: Real-World Evidence from the Middle East.

Background:The Global Burden of Disease 2010 study reported the relative size of major depressive disorder (MDD) burden to be greater in the Middle East and North Africa than anywhere else. However, little research has been carried out to examine the comparative effectiveness of antidepressants in this region.Objective:To assess and compare functioning levels in Middle Eastern patients with MDD treated with either duloxetine or a selective serotonin reuptake inhibitor (SSRI), and to examine the impacts of depression-related pain on functioning by the type of treatment.Method:This post-hoc analysis, which focused on Middle Eastern patients, used data from a 6-month prospective observational study that included 1,549 MDD patients without sexual dysfunction. Levels of functional impairment and depression-related pain were assessed using the Sheehan Disability Scale (SDS) and the modified Somatic Symptom Inventory, respectively. A mixed model with repeated measures (MMRM) was employed.Results:The mean age of the patients was 37.3 (SD=8.4) years, and 34.6% were female. Patient functioning was, on average, moderately impaired at baseline, but improved substantially during follow-up in both the duloxetine (n=152) and the SSRI (n=123) cohorts. The MMRM results showed a lower level of functional impairment at 24 weeks in the duloxetine cohort than in the SSRI cohort (p<0.001). Pain severity at baseline was positively associated with functional impairment during follow-up only in the SSRI cohort (p=0.003).Conclusion:Duloxetine-treated MDD patients achieved better functioning than SSRI-treated patients. This treatment difference was partly driven by depression-related pain.

Impact of pain and remission in the functioning of patients with depression in Mainland China, Taiwan, and Hong Kong.

The present study analyzes functioning during the course of treatment of a major depressive disorder in Mainland China, Taiwan, and Hong Kong. Data in this post hoc analysis were taken from a 24-week prospective, observational study in 12 countries worldwide. Of these, 422 patients were included from Mainland China (N=205; 48.6%), Taiwan (N=199; 47.2%), and Hong Kong (N=18; 4.2%). Functioning was measured with the Sheehan Disability Scale, pain with the Somatic Symptom Inventory, and depression severity with the Quick Inventory of Depressive Symptomatology Self Report 16. Patients were classified as having no pain, persistent pain, or remitted pain. A mixed model with repeated measures was fitted to analyze the relationship between pain and functioning, adjusting for severity and other factors. At baseline, 40% of the patients had painful physical symptoms. At 24weeks, 6% of the patients had persistent pain. Sixty percent of the patients achieved remission. Patients with pain had a higher severity of depression score and lower functioning (P<.05) at baseline. At 24weeks, patients with persistent pain had lower functioning (P<.05). The regression model found that clinical remission was associated with higher functioning at endpoint and that patients with persistent pain had lower functioning at endpoint when compared with the no-pain group. Patients presenting with pain had lower functioning at baseline. At 24weeks, pain persistence was associated with significantly lower functioning as measured by the Sheehan Disability Scale. Clinical remission was associated with better functional outcomes. The course of pain was related to achieving remission.

Associations among depression severity, painful physical symptoms, and social and occupational functioning impairment in patients with major depressive disorder: a 3-month, prospective, observational study.

PurposeTo investigate associations among depression severity, painful physical symptoms (PPS), and social and occupational functioning impairment in patients with major depressive disorder (MDD) who had achieved complete remission (CR) or partial remission (PR) after acute treatment.Patients and methodsThis was a 12-week, multicenter, prospective, observational study. Patients with MDD treated with an antidepressant medication for the previous 12 weeks (±3 weeks) who had achieved CR (defined as a 17-item Hamilton Rating Scale for Depression [HAM-D17] score ≤7) or PR (HAM-D17 score ≥8 and ≤18) were enrolled. Depression severity, PPS, and impairment in social and occupational functioning were assessed using the HAM-D17, the Brief Pain Inventory (Short Form) (BPI-SF), and the Social and Occupational Functioning Assessment Scale (SOFAS), respectively, at enrollment (Week 12) and after 12 weeks (Week 24).ResultsOverall, 323 Japanese patients with MDD were enrolled (CR n=158, PR n=165) and 288 patients completed the study (CR n=139, PR n=149). HAM-D17 and SOFAS scores were strongly and negatively correlated at enrollment (Week 12; P<0.0001) and Week 24 (P<0.0001). A weak negative correlation between the BPI-SF and SOFAS was observed at Week 24 (P=0.0011), but not at enrollment (P=0.164). Remission status at enrollment (CR or PR) was associated with achieving normal social and occupational functioning (SOFAS score ≥80) at Week 24 in patients who had not achieved normal social and occupational functioning (SOFAS score <80) at enrollment (CR vs PR, OR=0.05 [95% CIs 0.01–0.18], P<0.0001). A greater proportion of patients with CR and no PPS at enrollment achieved SOFAS scores ≥80 at Week 24 than those with CR and PPS.ConclusionOur results suggest that treating both depressive symptoms and PPS is important for achieving a normal level of functioning on a long-term basis in patients with MDD.

Predicting treatment outcomes of major depressive disorder by early improvement in painful physical symptoms: a pooled analysis of double-blind, placebo-controlled trials of duloxetine.

ObjectiveWe determined if early improvement in painful physical symptoms (PPS) can be a predictor of remission in the treatment of major depressive disorder (MDD).MethodsWe included randomized, double-blind, parallel-group clinical trials of duloxetine (40–60 mg/day) versus placebo for the acute treatment of MDD with associated PPS. Only those studies using the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Brief Pain Inventory – Short Form (BPI-SF) were included. Three studies met all criteria and included male or female outpatients aged ≥18 years who met the diagnostic criteria for MDD, had a MADRS total score ≥20, and had at least moderate pain (BPI-SF average pain score ≥3). Positive predictive values (PPVs) and negative predictive values (NPVs) of early improvement in PPS for remission were analyzed. PPVs were the proportion of patients with remission (MADRS total score ≤10) at week 8 out of patients who experienced early improvement in BPI-SF average pain score (≥30% decrease from baseline at week 1, 2, or 4). NPVs were the proportion of patients without remission (MADRS total score >10) at week 8 out of patients who did not experience early improvement in PPS.ResultsData from 1,320 patients were analyzed (duloxetine N=641 and placebo N=679). The overall remission (MADRS total score ≤10 at week 8) rate for the duloxetine group was significantly higher than the placebo group (38.5% vs 21.8%; P<0.0001). For both treatment groups, PPVs of early improvement in BPI-SF (30% improvement from baseline) were higher than the overall remission rate for all weeks examined (weeks 1, 2, and 4); in general, NPVs of early improvement in BPI-SF for nonremission were higher than the overall nonremission rate.ConclusionEarly improvement in PPS can be a useful clinical indicator of subsequent treatment outcome for MDD patients with associated PPS.

An observational study of duloxetine versus SSRI monotherapy in Japanese patients with major depressive disorder: subgroup analyses of treatment effectiveness for pain, depressive symptoms, and quality of life.

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.

An observational study of duloxetine versus SSRI monotherapy for the treatment of painful physical symptoms in Japanese patients with major depressive disorder: primary analysis.

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.

Pain Relief in Depressive Disorders: A Meta-Analysis of the Effects of Antidepressants.

Pain is a common symptom in patients with depressive disorders, which, if present, worsens the prognosis. However, there is little empirical knowledge of the therapeutic effects of antidepressants on painful physical symptoms of patients with depressive disorders. Furthermore, tricyclic/tetracyclic antidepressants (TCAs) have not yet been included in existing meta-analyses. A broad, systematic search of PubMed literature on antidepressant drug treatment of patients with depressive disorders with comorbid pain symptoms was carried out. A random-effects meta-analysis has been performed among 3 different groups of drugs for the 2 end points: pain and depression. Fourteen placebo-controlled studies with selective serotonin-noradrenaline reuptake inhibitors (SSNRIs) could be included, with 3 of them also investigating selective serotonin reuptake inhibitors (SSRIs). Three further placebo-controlled SSRI studies were identified, but only 2 placebo-controlled TCA studies.Both SSNRIs and SSRIs, but not TCAs, were significantly superior to placebo as regards their analgesic effects. However, all effects were small. For SSNRIs, there was a strong positive correlation between their effectiveness for pain relief and their positive effect on the mood of the patients. The analgesic effects of SSNRIs and SSRIs in patients with primary depressive disorders can be interpreted as largely equivalent. Because of a lack of placebo-controlled TCA studies, the results for TCAs would be comparable only to those of SSRIs and SSNRIs, if non-placebo-controlled TCA studies were included. The positive correlation found indicates a close relationship of pain relief and antidepressant treatment effects. These results refer merely to patients with primary depressive disorders, not to patients with primary pain disorders. Further studies comparing the effects of different types of antidepressant drugs on pain in depressive patients are warranted.

The impact of depression among chronic low back pain patients in Japan.

BackgroundChronic low back pain (CLBP) is associated with significant disability and reductions in health related quality of life (HRQoL), which can negatively impact overall function and productivity. Depression is also associated with painful physical symptoms, and is often present in patients with chronic pain. However, the incremental burden associated with depression or symptoms of depression among CLBP patients is not well understood. The objective of this study was to investigate the impact of depression on HRQoL in CLBP and to assess the relationship between depression and work impairment and healthcare use among CLBP patients in Japan.MethodsData were extracted from the 2014 Japan National Health and Wellness Survey (N = 30,000). CLBP was defined by report of diagnosed low back pain ≥3 months duration. Depression was assessed using the Patient Health Questionnaire (PHQ-9). Measurements assessed included pain, HRQoL, labor force participation, work productivity and healthcare utilization. Patients with depression (PHQ-9 ≥ 10) were compared to patients without depression (PHQ-9 < 10) using t-tests for continuous and count variables and chi-square for categorical variables, which were followed by generalized linear models adjusted for covariates. The association between presenteeism and other patient outcomes and characteristics was analysed using nonparametric correlations (Spearman’s rho).ResultsDepressed CLBP patients had significantly more severe pain and higher levels of pain compared with patients without depression (P < 0.001). Depression was associated with worse HRQoL in CLBP patients. Presenteeism, overall work impairment and activity impairment were 1.8, 1.9 and 1.7 times as high, respectively, among those with depression relative to those without depression. CLBP patients with depression had almost twice as many healthcare provider visits in 6 months than those without depression. The pattern of results remained consistent after adjustment for sociodemographic and general health characteristics. Analysis also indicated presenteeism was closely related to overall work impairment (rho = 0.99).ConclusionsDepression among CLBP patients in Japan was associated with higher pain scores and lower HRQoL scores, as well as lower labor productivity and increased healthcare use. Screening for depression in CLBP patients should be an essential part of CLBP patient care.

Factors associated with and impact of pain persistence in Asian patients with depression: a 3-month, prospective observational study

Objective: We investigated the depression outcomes and the factors associated with pain persistence in Asian patients treated for major depressive disorder (MDD).Methods: This observational study enrolled 909 Asian adult inpatients and outpatients. The presence or absence of painful physical symptoms and severity of depression were assessed at baseline and after three months of treatment. Factors associated with pain persistence and outcome of depression were investigated using regression methods.Results: Of the 909 patients enrolled, 684 were included in the analysis and evaluated at three months. Of them, 335 (49%) had no pain at baseline nor follow up, 198 (29%) at baseline but not at follow up and 151 (22%) in both assessments. Pain more frequently persisted in patients who were divorced/widowed/separated, with >1 comorbidity, aged <40 years, with previous MDD episodes, taking pain medications, and with greater depression severity. At three months, response/remission were 84%/73% in the no pain group, 83%/63% in the remitted pain group and 46%/25% in the persistent pain group (differences all p < .0001; all bivariate comparisons were statistically significant with p < .05 except response between no pain and remitted pain). Persistent pain was also associated with less improvement in quality of life and health state.Conclusions: Pain should be taken into account when diagnosing MDD and when tailoring therapy.