Understanding and restoring dopaminergic function in fibromyalgia patients using a mindfulness-based psychological intervention: a [18F]-DOPA PET study. Study protocol for the FIBRODOPA study-a randomized controlled trial.

BACKGROUND: Fibromyalgia (FM) is a very prevalent and debilitating chronic pain disorder that is difficult to treat. Mindfulness-based techniques are regarded as a very promising approach for the treatment of chronic pain and in particular FM. The Mindfulness-Oriented Recovery Enhancement (MORE) intervention, a mindfulness-based group intervention, has shown beneficial effects in opioid-treated chronic pain patients, including reduced pain severity, functional interference, and opioid dosing, by restoring neurophysiological and behavioral responses to reward. The first evidence for a hypodopaminergic state and impaired reward processing in FM has been reported. However, little is known about its impact on dopamine (DA) function and in particular with regard to DA responses to monetary reward in FM. The aim of the present study protocol is to evaluate if MORE is able to restore the DA function in FM patients, in particular with regard to the DA responses to reward, and to reduce pain and mood complaints in FM. METHODS: The present study is a multi-center interventional RCT with 3 time points: before the intervention, after completion of the intervention, and 3 months after completion of the intervention. Sixty-four FM patients will be randomly assigned to either the MORE intervention (N = 32) or a non-intervention control group (N = 32). Additionally, a comparison group of healthy women (N = 20) for PET measures will be enrolled and another group of healthy women (N = 15) will do the ambulatory assessments only. The MORE intervention consists of eight 2-h-long group sessions administered weekly over a period of 8 weeks. Before and after the intervention, FM participants will undergo [18F] DOPA positron emission tomography (PET) and functional MR imaging while performing a reward task. The primary outcome will be endogeneous DA changes measured with [18F] DOPA PET at baseline, after the intervention (after 8 weeks for the non-intervention control group), and at 3 months' follow-up. Secondary outcomes will be (1) clinical pain measures and FM symptoms using standardized clinical scales; (2) functional brain changes; (3) measures of negative and positive affect, stress, and reward experience in daily life using the ambulatory assessment method (AA); and (4) biological measures of stress including cortisol and alpha-amylase. DISCUSSION: If the findings of this study confirm the effectiveness of MORE in restoring DA function, reducing pain, and improving mood symptoms, MORE can be judged to be a promising means to improve the quality of life in FM patients. The findings of this trial may inform health care providers about the potential use of the MORE intervention as a possible non-pharmacological intervention for FM. TRIAL REGISTRATION: ClinicalTrials.gov NCT04451564 . Registered on 3 July 2020. The trial was prospectively registered.

Mood disorders and circulating levels of inflammatory markers in a longitudinal population-based study.

BACKGROUND: There has been increasing evidence that chronic low-grade inflammation is associated with mood disorders. However, the findings have been inconsistent because of heterogeneity across studies and methodological limitations. Our aim is to prospectively evaluate the bi-directional associations between inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α and high sensitivity C-reactive protein (hsCRP) with mood disorders. METHODS: The sample consisted of 3118 participants (53.7% women; mean age: 51.0, s.d. 8.8 years), randomly selected from the general population, who underwent comprehensive somatic and psychiatric evaluations at baseline and follow-up (mean follow-up duration = 5.5 years, s.d. 0.6). Current and remitted mood disorders including bipolar and major depressive disorders (MDD) and its subtypes (atypical, melancholic, combined atypical and melancholic, and unspecified) were based on semi-structured diagnostic interviews. Inflammatory biomarkers were analyzed in fasting blood samples. Associations were tested by multiple linear and logistic regression models. RESULTS: Current combined MDD [ß = 0.29, 95% confidence interval (CI) 0.03-0.55] and current atypical MDD (ß = 0.32, 95% CI 0.10-0.55) at baseline were associated with increased levels of hsCRP at follow-up. There was little evidence for inflammation markers at baseline predicting mood disorders at follow-up. CONCLUSIONS: The prospective unidirectional association between current MDD subtype with atypical features and hsCRP levels at follow-up suggests that inflammation may be a consequence of this condition. The role of inflammation, particularly hsCRP that is critically involved in cardiovascular diseases, warrants further study. Future research that examines potential influences of medications on inflammatory processes is indicated.

[Psychosocial stressors and pain sensitivity in chronic pain disorder with somatic and psychological factors (F45.41)]. / Psychosoziale Stressoren und Schmerzempfindlichkeit bei chronischer Schmerzstörung mit somatischen und psychischen Faktoren (F45.41).

BACKGROUND: Increased pain sensitivity is characteristic for patients with chronic pain disorder with somatic and psychological factors (F45.41). Persistent stress can induce, sustain, and intensify pain sensitivity, thereby modulating pain perception. In this context, it would be favorable to investigate which psychosocial stressors are empirically linked to pain sensitivity. OBJECTIVES: The aim of this study was to examine the relationship between psychosocial stressors and pain sensitivity in a naturalistic sample of patients with chronic pain disorder with somatic and psychological factors (F45.41). MATERIALS AND METHODS: We assessed 166 patients with chronic pain disorder with somatic and psychological factors (F45.41) at entry into an inpatient pain clinic. Pain sensitivity was measured with a pain provocation test (Algopeg) at the middle finger and earlobe. Stressors assessed were exposure to war experiences, adverse childhood experiences, illness-related inability to work, relationship problems, and potentially life-threatening accidents. Correlation analyses and structural equation modeling were used to examine which stressors showed the strongest prediction of pain sensitivity. RESULTS: Patients exhibited generally heightened pain sensitivity. Both exposure to war and illness-related inability to work showed significant bivariate correlations with pain sensitivity. In addition to age, they also predicted a further increase in pain sensitivity in the structural equation model. CONCLUSIONS: Bearing in mind the limitations of this cross-sectional study, these findings may contribute to a better understanding of the link between psychosocial stressors and pain sensitivity.

[Stress-induced hyperalgesia (SIH) as a consequence of emotional deprivation and psychosocial traumatization in childhood : Implications for the treatment of chronic pain]. / Stressinduzierte Hyperalgesie (SIH) als Folge von emotionaler Deprivation und psychischer Traumatisierung in der Kindheit : Konsequenzen für die Schmerztherapie.

It is now widely recognized that in many chronic pain syndromes the intensity and severity of individually perceived pain does not correlate consistently with the degree of peripheral nervous system tissue damage or with the intensity of primary afferent or spinal nociceptive neurone activity. In particular, stress and anxiety exert modulatory influences on pain depending on the nature, duration and intensity of the stressor and developmental influences on the maturation of the stress as well as the pain system. In some chronic pain syndromes, e. g. fibromyalgia, TMD or somatoform disorders, no nociceptive or neuropathic input is detectable. We summarise the studies investigating the neural substrates and neurobiological mechanisms of stress-induced hyperalgesia (SIH) in animals and humans. The review provides new perspectives and challenges for the current and future treatment of chronic pain.

Implications of proposed fibromyalgia criteria across other functional pain syndromes.

OBJECTIVES: In 2010, the American College of Rheumatology (ACR) proposed new criteria for the diagnosis of fibromyalgia (FM) in the context of objections to components of the criteria of 1990. The new criteria consider the Widespread Pain Index (WPI) and the Symptom Severity Score (SSS). This study evaluated the implications of the new diagnostic criteria for FM across other functional pain syndromes. METHOD: A cohort of 300 consecutive in-patients with functional pain syndromes underwent a diagnostic screen according to the ACR 2010 criteria. Additionally, systematic pain assessment including algometric and psychometric data was carried out. RESULTS: Twenty-five patients (8.3%) had been diagnosed with FM according to the ACR 1990 criteria. Twenty-one of them (84%) also met the new ACR 2010 criteria. In total, 130 patients (43%) fulfilled the new ACR 2010 criteria. A comparison of new vs. old cases showed a high degree of conformity in most of the pain characteristics. The new FM cases, however, revealed a pronounced heterogeneity in the anatomical pain locations, including several types of localized pain syndromes. Furthermore, patients fulfilling the ACR 2010 FM criteria differed from those with other functional pain syndromes; they had increased pain sensitivity scores and increased psychometric values for depression, anxiety, and psychological distress (p<0.01). CONCLUSIONS: FM according to the ACR 2010 criteria describes the 'severe half' of the spectrum of functional pain syndromes. By dropping the requirement of 'generalized pain', these criteria result in a blurring of the distinction between FM and more localized functional pain syndromes.

Leukocyte telomere length and hemostatic factors in a South African cohort: the SABPA Study.

BACKGROUND: Incident atherothrombotic disease is predicted by leukocyte telomere length, a marker of biological age, and hemostatic factor levels, indicating a hypercoagulable state. We hypothesized that shorter telomeres are associated with elevated circulating levels of hemostatic factors. METHODS: We examined 171 South African (black) and 182 Caucasian (white) schoolteachers (mean age ± standard deviation, 48.5 ± 9.0 years; 50.4% women). Levels of fibrinogen, von Willebrand factor antigen (VWF:Ag), D-dimer and plasminogen activator inhibitor-1 antigen (PAI-1:Ag) were measured in plasma, and values were log-transformed before analysis. Relative average telomere length (content of telomere PCR product/content of human ß-globin PCR product ratio, i.e. telomere/single-copy gene ratio) was assessed with multiplex quantitative real-time PCRs. Multivariate analyses included demographics, metabolic factors, health behavior, and medication. RESULTS: Africans had shorter mean telomere length (0.82, 95% confidence interval [CI] 0.79-0.86 vs. 1.07, 95% CI 1.04-1.10) and higher fibrinogen (B = 0.085, 95% CI 0.061-0.109) and PAI-1:Ag (B = 0.255, 95% CI 0.206-0.303) levels, but lower VWF:Ag levels (B = - 0.059, 95% CI - 0.089 to - 0.028), than Caucasians. Shorter telomeres were associated with higher fibrinogen (B = - 0.045, 95% CI - 0.088 to - 0.001), VWF:Ag (B = - 0.137, 95% CI - 0.193 to - 0.081) and D-dimer (B = - 0.201, 95% CI - 0.377 to - 0.025) levels, conditional on ethnicity. An interaction emerged between ethnicity and telomere length for VWF:Ag level; that is, shorter telomeres were associated with higher VWF:Ag levels in Caucasians (B = - 0.170, 95% CI - 0.232 to - 0.108) but not in Africans. CONCLUSIONS: Shorter telomeres were associated with increased levels of several hemostatic factors after adjustment for confounding variables, whereby ethnicity partially moderated this effect. A relationship between accelerated biological aging and hypercoagulability might contribute to the risk of premature atherothrombotic events.

Effects of dark chocolate consumption on the prothrombotic response to acute psychosocial stress in healthy men.

Flavanoid-rich dark chocolate consumption benefits cardiovascular health, but underlying mechanisms are elusive. We investigated the acute effect of dark chocolate on the reactivity of prothrombotic measures to psychosocial stress. Healthy men aged 20-50 years (mean ± SD: 35.7 ± 8.8) were assigned to a single serving of either 50 g of flavonoid-rich dark chocolate (n=31) or 50 g of optically identical flavonoid-free placebo chocolate (n=34). Two hours after chocolate consumption, both groups underwent an acute standardised psychosocial stress task combining public speaking and mental arithmetic. We determined plasma levels of four stress-responsive prothrombotic measures (i. e., fibrinogen, clotting factor VIII activity, von Willebrand Factor antigen, fibrin D-dimer) prior to chocolate consumption, immediately before and after stress, and at 10 minutes and 20 minutes after stress cessation. We also measured the flavonoid epicatechin, and the catecholamines epinephrine and norepinephrine in plasma. The dark chocolate group showed a significantly attenuated stress reactivity of the hypercoagulability marker D-dimer (F=3.87, p=0.017) relative to the placebo chocolate group. Moreover, the blunted D-dimer stress reactivity related to higher plasma levels of the flavonoid epicatechin assessed before stress (F=3.32, p = 0.031) but not to stress-induced changes in catecholamines (p's=0.35). There were no significant group differences in the other coagulation measures (p's≥0.87). Adjustments for covariates did not alter these findings. In conclusion, our findings indicate that a single consumption of flavonoid-rich dark chocolate blunted the acute prothrombotic response to psychosocial stress, thereby perhaps mitigating the risk of acute coronary syndromes triggered by emotional stress.

Procoagulant reactivity to laboratory acute mental stress in Africans and Caucasians, and its relation to depressive symptoms: the SABPA study.

The risk of cardiovascular disease is dramatically increasing in Africans (black). The prothrombotic stress response contributes to atherothrombotic disease and is modulated by depressive symptoms. We examined coagulation reactivity to acute mental stress and its relation to psychological well-being in Africans relative to Caucasians (white). A total of 102 African and 165 Caucasian school teachers underwent the Stroop Color-Word Conflict test. Circulating levels of von Willebrand factor (VWF) antigen, fibrinogen, and D-dimer were measured before and after the Stroop. Cardiovascular reactivity measures were also obtained. All participants completed the Patient Health Questionnaire-9 and the General Health Questionnaire-28 for the assessment of depressive symptoms and total psychological distress, respectively. After controlling for covariates, resting levels of VWF, fibrinogen, and D-dimer were higher in Africans than in Caucasians (all p-values ≤0.006). Depressive symptoms and psychological distress were not significantly associated with resting coagulation measures. Stress reactivity in VWF (p<0.001) and fibrinogen (p=0.016), but not in D-dimer (p=0.27), were decreased in Africans relative to Caucasians with Africans showing greater reactivity of total peripheral resistance (p=0.017). Depressive symptoms, but not general psychological distress, were associated with greater VWF increase (p=0.029) and greater fibrinogen decrease (p=0.030) in Africans relative to Caucasians. In conclusion, Africans showed greater hypercoagulability at rest but diminished procoagulant reactivity to acute mental stress when compared with Caucasians. Ethnic differences in the vascular adrenergic stress response might partially explain this finding. Depressive symptoms were associated with exaggerated VWF reactivity in Africans relative to Caucasians. The clinical implications of these findings for Africans need further study.

Atypical depression and alcohol misuse are related to the cardiovascular risk in the general population.

OBJECTIVE: The aims of the present study were to assess the associations between mood, anxiety and substance use disorders, including their subtypes, and the prevalence of cardiovascular risk factors (CVRFs). METHOD: Thorough physical investigations, biological measures and standardized interview techniques were used to assess 3716 subjects of an urban area, aged 35-66 years. RESULTS: Atypical depression was associated with increased prevalence of overweight, diabetes and the metabolic syndrome (OR = 1.5, 95% C.I. 1.1-2.0; OR = 2.0, 95% C.I. 1.1-3.5, OR = 1.6, 95% C.I. 1.0-2.4 respectively), whereas decreased prevalence of overweight was found in melancholic (OR = 0.7, 95% C.I. 0.6-0.9) and unspecified depression (OR = 0.8, 95% C.I. 0.7-1.0). Alcohol abuse was associated with diabetes (OR = 1.8, 95% C.I. 1.1-2.9) and dyslipidemia (OR = 1.3, 95% C.I. 1.0-1.8), alcohol dependence with dyslipidemia only (OR = 1.4, 95% C.I. 1.0-2.0). Almost all mental disorders were associated with a lifetime history of regular cigarette smoking, and atypical depression, alcohol misuse and drug dependence were associated with inactivity. CONCLUSION: To conclude results emphasize the need to subtype depression and to pay particular attention to the atypical subtype. Comorbid alcohol misuse may further increase the cardiovascular risk. Efforts to diminish smoking in subjects with mental disorders could be crucial measures to reduce their high incidence of cardiovascular disease.

[Characteristics of patients with severe eating disorders from a university hospital and therapeutic guidelines]. / Charakteristika schwer essgestörter Patientinnen in einer universitären Einrichtung und therapeutische Richtlinien.

Patients with a severe eating disorder (anorexia, bulimia, other) are rarely subject of systematic studies. However, many of these patients are in need of in-patient treatment on specialized wards applying interdisciplinary treatment modalities. Updated criteria based on which hospitalisation should occur are provided by the recently issued S3-guideline for the treatment of eating disorders. We retrospectively assessed 26 consecutive patients with a severe eating disorder who were admitted to a psychosomatic/internal medicine university hospital in terms of their somatic, psychological, and social characteristics. Based on the S3-guideline, we conclude that hospitalization of these patients, within a multidisciplinary treatment setting, complies with evidenced-based criteria.

Relation of psychological distress to the international normalized ratio in patients with venous thromboembolism with and without oral anticoagulant therapy.

BACKGROUND: Psychological distress might affect the international normalized ratio (INR), but effects might vary depending on oral anticoagulant (OAC) therapy. OBJECTIVES: To investigate the association of psychological distress with INR and clotting factors of the extrinsic pathway in patients with and without OAC therapy. PATIENTS AND METHODS: We studied 190 patients with a previous venous thromboembolism (VTE); 148 had discontinued OAC therapy and 42 had ongoing OAC therapy. To assess psychological distress, all patients completed validated questionnaires to measure symptoms of depression, anxiety, worrying, anger and hostility. INR, fibrinogen, factor (F)II:C, FV:C, FVII:C and FX:C were measured as part of outpatient thrombophilia work-up. RESULTS: In VTE patients without OAC therapy, the odds of a reduced INR (< 1.00) were significantly increased from 1.5 to 1.8 times for an increase of 1 standard deviation (SD) in symptoms of depression, anxiety, worrying and anger, respectively, after adjusting for gender, age, body mass index, socioeconomic status, hematocrit and C-reactive protein. Worrying, anger and hostility also showed significant direct associations with FVII:C. In patients with OAC therapy, INR was unrelated to a negative affect; however, lower FVII:C related to anxiety and worrying as well as lower FX:C related to anger and hostility were observed in patients with OAC therapy compared with those without OAC therapy. CONCLUSIONS: Psychological distress was associated with a reduced INR in VTE patients without OAC therapy. The direction of the association between psychological distress and activity in some clotting factors of the extrinsic coagulation pathway might differ depending on whether VTE patients are under OAC therapy or not.

[Pain disorders in traumatized individuals - neurophysiology and clinical presentation]. / Schmerzstörungen bei Traumatisierten - neurophysiologische Aspekte und klinische Phänomenologie.

This overview portrays the salient physiological mechanisms being involved in the clinical manifestation of chronic pain in traumatized patients. A «hypermnesia-hyperarousal-model¼ is purported to support the neurophysiologic plausibility of the trauma-pain-relationship. We discuss seven characteristic clinical pain entities which alone or in combination can be found in patients with a previous psychological trauma.

The association between inflammatory biomarkers and metabolically healthy obesity depends of the definition used.

BACKGROUND/OBJECTIVES: To assess the distribution of interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) according to the different definitions of metabolically healthy obesity (MHO). SUBJECTS/METHODS: A total of 881 obese (body mass index (BMI) > or =30 kg/m2) subjects derived from the population-based CoLaus Study participated in this study. MHO was defined using six sets of criteria including different combinations of waist, blood pressure, total high-density lipoprotein cholesterol or low-density lipoprotein -cholesterol, triglycerides, fasting glucose, homeostasis model, high-sensitivity CRP, and personal history of cardiovascular, respiratory or metabolic diseases. IL-1ß, IL-6 and TNF-α were assessed by multiplexed flow cytometric assay. CRP was assessed by immunoassay. RESULTS: On bivariate analysis some, but not all, definitions of MHO led to significantly lower levels of IL-6, TNF-α and CRP compared with non-MH obese subjects. Most of these differences became nonsignificant after multivariate analysis. An posteriori analysis showed a statistical power between 9 and 79%, depending on the inflammatory biomarker and MHO definition considered. Further increasing sample size to overweight+obese individuals (BMI > or =25 kg/m2, n=2917) showed metabolically healthy status to be significantly associated with lower levels of CRP, while no association was found for IL-1ß. Significantly lower IL-6 and TNF-α levels were also found with some but not all MHO definitions, the differences in IL-6 becoming nonsignificant after adjusting for abdominal obesity or percent body fat. CONCLUSIONS: MHO individuals present with decreased levels of CRP and, depending on MHO definition, also with decreased levels in IL-6 and TNF-α. Conversely, no association with IL-1ß levels was found.

Quality of life: a potentially useful measure to indicate subclinical flares in Crohn disease.

BACKGROUND: While quality of life (QoL) is a well-recognised outcome measure of Crohn disease (CD) activity, its influence on other outcome measures, including exacerbation of CD is poorly understood. If QoL measures were to be associated with intestinal inflammatory activity, they might be useful for early detection of subclinical flares. AIMS: We hypothesised that low QoL might be associated with subsequent CD flares. METHODS: A cohort of 318 adult CD patients was observed for 1 year after assessment of baseline characteristics. Data were collected in Swiss university hospitals, regional hospitals and private practices. At inclusion, patients completed the Inflammatory Bowel Disease QoL Questionnaire (gastrointestinal QoL; range: 32 to 224 points) and the Short Form-36 Health Survey (general QoL; range: 35 to 145 points). During follow up, flares were recorded. Binary logistic regression was performed to estimate the relation between QoL and the odds of subsequent flares. RESULTS: A twofold decrease in the odds of flares (99% CI: 1.1; 4.0) per standard deviation of gastrointestinal QoL and a threefold decrease (99% CI: 1.5; 6.2) per standard deviation of general QoL were observed. CONCLUSIONS: The close association between QoL and subsequent flares suggests that QoL measures might be useful in detecting upcoming flares before they become clinically apparent.

[Nondermatomal somatosensory deficits in chronic pain patients]. / Nichtdermatomgebundene somatosensorische Defizite bei chronischen Schmerzpatienten.

Nondermatomal somatosensory deficits (NDSDs) are frequently found in chronic pain patients and allude to pain sensitization and pain centralization. In the clinical examination NDSDs are as a rule accompanied by hyposensitivity to touch and heat perception often with a quadrantal or hemibody distribution. The majority of NDSD patients show a trigger episode with a somatic nociceptive trauma in the case history. These somatic findings, however, never fully explain the pain disorder, analogue to the complex regional pain syndrome (CRPS). Most patients with chronic pain disorders as well as those with NDSD often report an antecedent period of high psychobiological stress. The data from functional imaging reveal a complex pattern of a central nervous dysregulation.

[Chronic right-sided pain-associated nondermatomal somatosensory deficit following an accident]. / Halbseitenstörung nach Unfall.

We present the case of a 48-year old man who, eight years after an industrial accident, presents with chronic right-sided nondermatomal pain and hypaesthesia to heat and touch. During symmetric peripheral touch functional magnetic resonance imaging revealed hypometabolism in the left thalamus, somatosensory cortex, and anterior cingulate cortex. Pain-associated nondermatomal somatosensory deficits (NDSDs) localizing to one side of the body are a frequent clinical entity, which are often triggered by an accident. The tendency of NDSDs to extend to adjunct ipsilateral body parts and to become chronic points to maladaptive adjustment of pain-processing areas in the central nervous system. Psychological stress prior to or around the triggering event seems an important risk factor for NDSDs.

[Multimodal therapy of functional gastrointestinal disorders]. / Multimodale Therapie funktioneller Erkrankungen des Verdauungstraktes.

A multimodal approach is state-of-the art for effective treatment of functional gastrointestinal disorders (FGD) like irritable bowel syndrome and functional dyspepsia. Based on the now established view that the pathogenesis of FGD is multicausal, evidence-based therapeutic options comprise education about the nature of the disorder, dietary modifications, relaxation techniques, behavioral changes, and pharmacological treatments. These therapies are variously combined depending on the severity of the FGD and the individual needs of the patient. Our overview portrays the options for the therapy of FGD and proposes that these are best provided by an interdisciplinary team of primary care physicians, gastroenterologists, and psychosomatic medicine specialists.

[Pathogenesis of functional gastrointestinal disorders - an interdisciplinary perspective]. / Pathogenese der funktionellen Erkrankungen des Verdauungstrakts aus interdisziplinärer Sicht.

Functional gastrointestinal disorders (FGD) are highly prevalent worldwide. Recent research demonstrates that complex and interacting biological and behavioral mechanisms contribute particularly to the pathogenesis of irritable bowel syndrome and functional dyspepsia. Dysregulation of the enteral, neuroenteric, visceral-autonomic, and central nervous systems are important biological contributors, whereas the psychological state of a patient may evidently modulate aspects related to biological stress reactivity and somatic perception both playing a role in the clinical manifestation of FGD. Our overview clearly shows that an interdisciplinary perspective of the pathogenesis of FGD may best serve clinicians and patients.

Physician speciality and pain reduction in patients with depressive symptoms under treatment with venlafaxine.

OBJECTIVES: Excessive pain perception may lead to unnecessary diagnostic testing or invasive procedures resulting in iatrogenic complications and prolonged disability. Naturalistic studies on patients with chronic pain and depressive symptoms investigating the impact of medical speciality on treatment outcome in a primary care setting are lacking. METHODS: In this observational study, we examined whether the magnitude of pain reduction in 444 patients with depressive symptomatology under venlafaxine would relate differently to the medical speciality of the 122 treating physicians, namely psychiatrists (n=110 patients), general practitioners (n=236 patients), and internists (n=98 patients). RESULTS: Independent of age, gender, patient's region of origin, comorbidity, severity and duration of pain, and depressive symptoms at study entry, patients seemed to benefit significantly less in terms of pain reduction (p<0.001) and of reduction in severity of depressive symptomatology by psychiatrists as compared to general practitioners (p<0.019) and internists (p<0.002). CONCLUSIONS: The findings suggest that patients referred to psychiatrists are more difficult to treat than those referred to general practitioners and internists, and might not have been adequately prepared for psychiatric interventions. A supporting cooperation and networking between psychiatrists and primary care physicians may contribute to an integrated treatment concept and therefore, may lead to a better outcome in this challenging patient group.