Medically Unexplained Symptoms

Persistent health symptoms which remain unexplained after a complete medical evaluation. A cluster of symptoms that consistently appear together but without a known cause are referred to as a MEDICALLY UNEXPLAINED SYNDROME (MUS).

Also Known As:

Somatic Symptoms; Medically Unexplained Symptom; Somatic Symptom; Symptom, Medically Unexplained; Symptom, Somatic; Symptoms, Medically Unexplained; Symptoms, Somatic; Unexplained Symptom, Medically; Unexplained Symptoms, Medically

Networked: 1149 relevant articles (120 outcomes, 181 trials/studies)

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Disease Context: Research Results

Signs and Symptoms Pathological Conditions
- Signs and Symptoms
  - Medically Unexplained Symptoms: 1149

Related Diseases

1.	Anxiety Disorders (Anxiety Disorder)
2.	Pain (Aches)
3.	Medically Unexplained Symptoms
4.	Sleep Initiation and Maintenance Disorders (Insomnia)
5.	Major Depressive Disorder (Major Depressive Disorders)

Experts

1.	Löwe, Bernd: 31 articles (02/2024 - 11/2012)
2.	Toussaint, Anne: 15 articles (02/2024 - 01/2017)
3.	Maes, Michael: 15 articles (01/2023 - 02/2012)
4.	Huang, Wei-Lieh: 12 articles (05/2024 - 01/2017)
5.	Witthöft, Michael: 12 articles (11/2023 - 06/2012)
6.	Liao, Shih-Cheng: 11 articles (05/2024 - 01/2017)
7.	Fava, Maurizio: 11 articles (03/2016 - 04/2002)
8.	Hung, Ching-I: 10 articles (01/2020 - 03/2012)
9.	Hüsing, Paul: 9 articles (02/2024 - 01/2017)
10.	Fritzsche, Kurt: 9 articles (11/2023 - 11/2017)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Medically Unexplained Symptoms:

1.	Antidepressive Agents (Antidepressants)IBA 04/06/2010 - "Antidepressants have been recognized as an effective treatment for psychological and somatic symptoms in IBS and for depression in HepC, but good quality studies in IBD are lacking despite the promising preliminary findings from animal models and case studies. " 03/15/2015 - "426 outpatients (in primary care and in psychiatric care) with a clinical diagnosis of major depression were included: at the start of antidepressant treatment, the importance of a range of items for being cured from depression (depressive, anxious and somatic symptoms, positive affect, functional impairment, quality of life) was assessed in physicians and patients separately and a ranking was made; after 3 months of treatment, the importance of these items for being cured from depression was re-assessed in the patients. " 01/01/2003 - "The goal of treatment is symptomatic remission, and by current estimates 50% or more of patients treated with antidepressant monotherapy may suffer from residual neurovegetative, cognitive, and somatic symptoms. " 03/01/2005 - "Further study is needed to compare its efficacy with that of other antidepressants, to clarify effects on somatic symptoms, and to assess potential adverse cardiovascular and sexual side effects. " 03/01/2011 - "Patients receiving CBT showed statistically significant improvement on measures of depression (p < .001), anxiety (p < .001) and somatic symptoms (p < .000) as compared to antidepressant alone group. "
2.	Duloxetine Hydrochloride (Cymbalta)FDA Link 09/01/2011 - "These characteristics make Duloxetine the most effective therapeutic choice to improve both psychological and somatic symptoms of depression in order to get higher rates of symptomatic remission on depressive episodes." 01/01/2014 - "Mean changes in efficacy measures were mostly significantly greater (P < .05 in 13 of 16 comparisons) for duloxetine versus placebo within each pretreatment subgroup, with some (P < .05 in 2 of 24 comparisons) significant interaction effects between subgroups on HDRS-17 total and somatic symptoms scores. " 11/01/2007 - "Significant improvement in the HAMD17 Maier subscale was seen in all groups by week 1. In all three groups, placebo was significantly superior to duloxetine at early visits on HAMD17 item 12 (somatic symptoms-GI). " 04/01/2007 - "Duloxetine also improved somatic symptoms, particularly painful symptoms which may have contributed to significantly improved remission rates compared to placebo. " 07/01/2016 - "Of the symptoms studied, psychomotor retardation, general somatic symptoms and sexual problems improved more in the duloxetine group. "
3.	Selective Serotonin Reuptake Inhibitors (Serotonin Reuptake Inhibitors)IBA 01/01/2022 - "Findings are consistent with previous reports linking somatic symptoms to treatment resistance and demonstrating that SSRIs are most effective in treating affective symptoms. " 01/01/2019 - "The management will move away from the outdated notion of "medically unexplained symptoms" to rely on: the acknowledgment of the painful, debilitating and involuntary nature of the symptoms; the proposal of a positive diagnosis acceptable by the patient and an explanatory model compatible with his or her representations, aimed at putting an end to dysfunctional health care utilization; the proposal of therapeutic objectives aimed at functional rather than symptomatic recovery; the negotiation of pharmacological (selective or mixed serotonin reuptake inhibitor if necessary) and non-pharmacological interventions, especially when it comes to limiting the factors that sustain the disorder; the coordination of the various healthcare professionals. " 01/01/2016 - "We tested the hypothesis that SSRIs uniquely alter psychological rather than somatic symptoms of depression and anxiety. " 01/01/2016 - "[SSRIs for adolescents with medically unexplained symptoms]." 03/01/2012 - "To investigate the prevalence of depression among otolaryngology patients with medically unexplained symptoms (MUS) and the outcome of treatment with selective serotonin reuptake inhibitors (SSRIs). "
4.	Diazepam (Valium)FDA LinkGeneric 11/01/1993 - "Patients treated with diazepam showed the most improvement in anxiety ratings during the first 2 weeks of treatment, with somatic symptoms being most responsive. " 06/01/1996 - "The results confirmed those of previous studies reporting that (1) clinical doses of diazepam are effective in attenuating the symptoms of generalized anxiety to a greater extent than placebo during the first 3 weeks of treatment; (2) somatic symptoms are more responsive to diazepam treatment than psychic symptoms; and (3) patients taking diazepam exhibit increased anxiety upon abrupt withdrawal of medication. " 04/01/1992 - "In contrast, diazepam was found to be slightly more effective in reducing somatic symptoms and to positively affect sleep disturbances. " 06/01/1996 - "Twenty-one women with generalized anxiety disorder (GAD) participated in a 6-week, double-blind, placebo-controlled trial to assess the treatment and abrupt withdrawal effects of diazepam on psychic and somatic symptoms of anxiety. " 12/01/1982 - "Diazepam seems more effective in reducing somatic symptoms, while buspirone appears more effective in reducing symptoms associated with cognitive and interpersonal problems. "
5.	Mirtazapine (Rexer)FDA LinkGeneric 01/01/2008 - "A assess the efficacy of mirtazapine in the treatment of depression with somatic symptoms in a 3-months follow-up study. " 01/01/2008 - "Mirtazapine modifies attribution of somatic symptoms in somatizers: in pretreatment assessment, 41.3 % of the sample attributed somatic symptoms to a psychological origin, while at 3 months post-treatment this percentage significantly increased (p<0.05) to 63.94%. " 01/01/2008 - "Effectiveness of mirtazapine in the treatment of depression with associated somatic symptoms." 01/01/2016 - "As a result, improvements in weeks 1 and 2 were associated with sensitivity of 0.82 and 0.99 and specificity of 0.54 and 0.44, respectively, in predicting remission in week 6. Improvements in insomnia late (P = .04) and insight (P = .007) in week 1 and somatic symptoms general (P = .002) and insight (P = .04) in week 2 were associated with remission in week 6. In conclusion, early improvements in insight, insomnia late, and somatic symptoms general, as well as overall depressive symptoms, may serve as specific clinical indicators of subsequent remission in patients with MDD receiving mirtazapine." 09/30/2009 - "The aim of this open-labeled trial was to examine the efficacy of mirtazapine for the treatment of MDD with clinically significant somatic symptoms, as compared with venlafaxine. "
6.	Venlafaxine Hydrochloride (Effexor)FDA LinkGeneric 09/01/2007 - "A post-hoc analysis of pooled data from five placebo-controlled, double-blind, randomized studies in non-depressed GAD patients treated with venlafaxine extended release (ER) or placebo was performed to determine the temporal response of psychic and somatic symptoms to treatment over 8 weeks. " 01/01/2024 - "VaDep patients with somatic symptoms were enrolled and randomly received venlafaxine + tandospirone (Combined Group) or venlafaxine (Monotherapy Group). " 09/01/2005 - "Years of experience with venlafaxine representing a first-line pharmacotherapy for depression and anxiety have benefited patients presenting with somatic symptoms with a robust onset. " 01/01/2004 - "Patients with generalized anxiety disorder treated with venlafaxine XR showed similar absolute rates of response on somatic and psychic symptoms, but relative to patients treated with placebo, more improvement in psychic than somatic symptoms." 01/01/2004 - "We evaluated the relative efficacy of venlafaxine XR on the psychic versus somatic symptoms of anxiety in patients with generalized anxiety disorder as determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. "
7.	Silver Sulfadiazine (SSD)FDA LinkGeneric 01/01/2022 - "The criterion validity was tested by using the Semi-structured Clinical Interview for DSM-5 (Research Version) (SCID-5-RV) for somatic symptom disorder (SSD) as the diagnostic gold standard to explore the optimal cutoff score of the SSS-8. " 01/01/2021 - "The follow-up assessment results of the SSD patients revealed improved performance on the verbal learning and fluency tests as well as improvements in somatic symptoms, anxiety, and depression. " 01/01/2024 - "We investigated the association of established and possible additional psychobehavioral criteria for somatic symptom disorder (SSD) as defined in the DSM-V. The study included 6,491 patients from a psychosomatic outpatient center over a 12-year period. " 01/01/2024 - "This study provides evidence for the concept of SSD related to specific B-criteria associated with somatic symptom reporting, based on a large patient sample. " 01/01/2024 - "This study explored the association between self-compassion, alexithymia, and psychosomatic symptom distress in a clinical sample of somatic symptom disorder (SSD) patients participating in a mindfulness-based cognitive therapy (MBCT) program. "
8.	Paroxetine (Paxil)FDA LinkGeneric 01/01/2016 - "Paroxetine's influence on somatic symptoms appears to be mostly duplicated by placebo." 01/01/2016 - "Paroxetine appears to have a "true" pharmacological effect on the psychological but not on the somatic symptoms of depression and anxiety. " 01/01/2016 - "The difference in score reduction between paroxetine and placebo was more than twice as great for the psychological symptoms compared to the somatic symptoms. " 01/01/2016 - "Specific Pharmacological Effects of Paroxetine Comprise Psychological but Not Somatic Symptoms of Depression." 06/01/2008 - "The aim of this study was to assess the potential utility and tolerability of paroxetine for the treatment of undifferentiated somatoform disorder (USD), using the 15-item Patient Health Questionnaire (PHQ-15) to assess the severity of somatic symptoms. "
9.	Imipramine (Janimine)FDA LinkGeneric 07/01/1989 - "Fifty-seven depressed patients who received tricyclic drug treatment and interpersonal psychotherapy during the acute and continuation phases of the study tolerated this dosage level well (mean dose, 217 mg/day of imipramine), reported few adverse effects on a somatic symptom checklist, and demonstrated a high level of compliance as shown by plasma concentration/dosage (L/D) ratios. " 01/01/1990 - "The results showed that at the end of the trial there was a significant reduction in depressive symptoms severity in both groups and that fluvoxamine was significantly more effective than imipramine in reducing suicidal ideas and anxiety/somatic symptoms. " 06/10/1983 - "Alprazolam was at least as effective as imipramine in relieving depressive symptoms, significantly more effective in relieving somatic symptoms, and showed an earlier onset of activity in some measurements. " 08/01/1988 - "However, alprazolam was more effective in attenuating somatic symptoms, and imipramine was more effective in attenuating psychic symptoms such as dysphoria and negative anticipatory thinking. " 05/01/1997 - "Paroxetine and imipramine affect predominantly psychic symptoms, whereas 2'-chlordesmethyldiazepam affects predominantly somatic symptoms. "
10.	Pregabalin (Lyrica)FDA Link 10/01/2006 - "Pregabalin was effective in more or less severe GAD, on psychic and somatic symptoms of GAD, and in treating the subsyndromal depressive symptoms of GAD. " 09/01/2020 - "To facilitate the understanding of pregabalin and optimize its clinical usage in Hong Kong, an expert panel (11 psychiatrists, one family physician and one anesthesiologist) experienced in treating anxiety and somatic symptoms was invited to establish a set of consensus statements based on several discussion areas. " 02/01/2018 - "A case report of pregabalin use disorder with co-morbid somatic symptom disorder and depression." 09/01/2005 - "Pregabalin was significantly more efficacious than placebo for the treatment of psychic and somatic symptoms of generalized anxiety disorder and was well tolerated by most study patients." 11/01/2008 - "The anxiolytic efficacy of pregabalin had an early onset (by 2 weeks) and significantly improved both psychic and somatic symptoms of anxiety."

Therapies and Procedures

1.	Therapeutics 12/01/2023 - "However, more high-quality randomized controlled trials are needed to determine the efficacy of this therapy on somatic symptoms." 03/01/2022 - "Drawing therapy is effective in improving negative emotions, relieving somatic symptoms, and increasing social communication for pediatric oncology patients. " 10/01/2021 - "Fortunately, the Morita therapy is especially effective for patients who pay excessive attention to somatic symptoms or are hypochondriacal, which is applicable for outpatients using a comparatively short interview that can even be performed in nonpsychiatric clinical settings." 04/01/2024 - "Although current therapies can only treat somatic symptoms, a lentivirus-based hematopoietic stem cell gene therapy (HSCGT) approach has recently achieved improved central nervous system (CNS) neuropathology in the MPSII mouse model following transplant at 2 months of age. " 06/01/2016 - "Multi-component therapy and medication in FAs with medically unexplained symptoms (MUS) improved QoL (SF36 odds ratio: 1.92; 95%CI: 1.08-3.40) and morbidity (CES-D 3.17; 95%CI: 1.27-5.08). "
2.	Enzyme Replacement Therapy 06/01/2014 - "Enzyme replacement therapy (ERT) is effective for the treatment of many somatic symptoms, particularly walking ability and respiratory function, and remains the mainstay of MPS treatment. " 11/01/2011 - "Although enzyme replacement therapy has been developed for 3 types of MPS (types I, II and VI), this treatment was found to be effective only in management of somatic symptoms. " 01/01/2022 - "Enzyme replacement therapy (ERT) is efficacious in treating somatic symptoms but its effect is limited for neurological functions. " 11/16/2018 - "Enzyme replacement therapy is currently considered the standard of care for the treatment of mucopolysaccharidoses (MPS) type I, II, VI, and IV. This approach has shown substantial efficacy mainly on somatic symptoms of the patients, but no benefit was found for other clinical manifestations, such as neurological involvement. " 05/23/2021 - "Currently, the primary treatment is enzyme replacement therapy, which improves the course of the disease by reducing somatic symptoms, including hepatomegaly and splenomegaly. "
3.	Psychology Biofeedback (Biofeedback) 01/01/2023 - "Efficacy of Heart Rate Variability Biofeedback for Somatic Symptom Disorder: A Pilot Randomized Controlled Trial." 01/01/2022 - "The Effects of Cognitive Behavioral Therapy with Biofeedback Therapy on the Quality of Life, Anxiety, Depression and Somatic Symptoms in Patients with Dyssynergic Defecation: A Randomized Controlled Trial." 04/01/2024 - "This study examined the efficacy of a six-week intervention, consisting of weekly one-hour sessions combining heart rate variability and temperature biofeedback, for alleviating mood symptoms, somatic symptoms and sleep disturbance of patients diagnosed with long COVID. " 04/01/2024 - "While a randomized trial merits study, biofeedback appears to be a brief, effective, non-invasive, and low-cost treatment option for patients with chronic somatic symptoms secondary to SARS-CoV-2 infection. " 09/01/2011 - "EEG biofeedback treatment improves certain attention and somatic symptoms in fibromyalgia: a pilot study."
4.	Aftercare (After-Treatment) 05/01/2016 - "Clinically significant levels of somatization before treatment were common (n=138, 27.2%) and were associated with a significant reduction in somatic symptom severity (41.3% reduction; P<0.001) and disability (44% reduction; P<0.001) after treatment. " 10/01/2020 - "After treatment, median Somatic Symptom Scale-8 score was higher in the standard-care group than in the multidisciplinary-care group (10 [IQR 7-7] vs 9 [5-13]; p=0·082). " 11/01/2011 - "Young women and patients with more residual depressive symptoms and less somatic symptoms directly after treatment, were more at risk for recurrence. " 03/01/2024 - "Compared with the pre-treatment period, the scores of restrictions in daily living, medical resource utilization, somatic symptoms, and emotional disturbance were elevated in both groups after treatment, and the combined group had markedly higher scores than the TDCS group (p<0.05). " 12/01/2021 - "Remission of Somatic Symptom Disorder With Comorbid Severe Major Depressive Disorder After Treatment With Electroconvulsive Therapy."
5.	Drug Therapy (Chemotherapy) 12/23/2022 - "Results of regression analysis indicated a significant impact on QoL for chemotherapy (β = 0.140, P < 0.045), psychological-somatic symptom cluster (β = - 0.329, P = 0.013), and social support (β = 0.409, P < 0.001) after adjusting demographic and clinical characteristics. " 01/01/2019 - "MDD patients with PDD had greater severities of depression, anxiety, and somatic symptoms at the three follow-up points as compared with those without; however, these results were of statistical significance only in patients without pharmacotherapy. " 12/01/2018 - "Regarding psychological changes from the beginning to the end of the adjuvant treatment, both age groups reported more somatic symptoms, increased psychological difficulty, reduced coping strategies, and a significant decrease in quality of life at the end of postoperative chemotherapy. " 01/01/2018 - "Findings indicate that reductions in somatic symptoms may be a mediator of improvements for treatments including pharmacotherapy and not CBT. " 12/01/2015 - "The unmet need of current pharmacotherapy and the high occurrence of somatic symptoms and physical illness in depression imply that the 'monoamine hypothesis' is insufficient in approaching the aetiology of depression. "