Painful Physical Symptoms Research Articles

Poster 189: Duloxetine as an Effective Treatment for Improving Painful Physical Symptoms and Functioning Associated With Generalized Anxiety Disorder

Poster 189: Duloxetine as an Effective Treatment for Improving Painful Physical Symptoms and Functioning Associated With Generalized Anxiety Disorder

Duloxetine in the treatment of major depressive disorder: an open-label study

BackgroundMajor depressive disorder (MDD) is a chronic and highly disabling condition. Existing pharmacotherapies produce full remission in only 30% to 40% of treated patients. Antidepressants exhibiting dual reuptake inhibition of both serotonin (5-HT) and norepinephrine (NE) may achieve higher rates of remission compared with those acting upon a single neurotransmitter. In this study, the safety and efficacy of duloxetine, a potent dual reuptake inhibitor of 5-HT and NE, were examined.MethodsPatients (N = 533) meeting DSM-IV criteria for MDD received open-label duloxetine (60 mg once a day [QD]) for 12 weeks during the initial phase of a relapse prevention trial. Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD17) total score ≥18 and a Clinical Global Impression of Severity (CGI-S) score ≥4 at baseline. Efficacy measures included the HAMD17 total score, HAMD17 subscales, the CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQ-SS). Quality of life was assessed using the Sheehan Disability Scale (SDS) and the Quality of Life in Depression Scale (QLDS). Safety was evaluated by recording spontaneously-reported treatment-emergent adverse events, changes in vital signs and laboratory analytes, and the Patient Global Impression of Sexual Function (PGI-SF) scale.ResultsThe rate of discontinuation due to adverse events was 11.3%. Treatment-emergent adverse events reported by ≥10% duloxetine-treated patients were nausea, headache, dry mouth, somnolence, insomnia, and dizziness. Following 12 weeks of open-label duloxetine therapy, significant improvements were observed in all assessed efficacy and quality of life measures. In assessments of depression severity (HAMD17, CGI-S) the magnitude of symptom improvement continued to increase at each study visit, while for painful physical symptoms the onset of improvement was rapid and reached a maximum after 2 to 3 weeks of treatment.ConclusionIn this open-label phase of a relapse prevention study, duloxetine (60 mg QD) was shown to be safe and effective in the treatment of MDD.Trial registrationNCT00036309.

Effectiveness and safety of venlafaxine extended release in elderly depressed patients

The main objectives of this multicenter, naturalistic, open-label study is to evaluate the effectiveness, tolerability and safety of venlafaxine extended release (VXR) in a sample of 59 patients older than 60 years of age diagnosed of depressive disorders in the primary care setting. VXR was administered for 24 weeks at daily doses ranging from 75 mg to 225 mg. Effectiveness measurements included the 17 items Hamilton Depression Rating Scale (HAM-D 17), the Clinical Global Impression Scales for Severity (CGI-S) and Improvement (CGI-I), the Visual Analogical Scale for Pain (P-VAS), and the Mini-Mental State Examination (MMSE) scale. At the endpoint, VXR achieved response and remission rates of 81.6% and 59.2%, respectively. Treatment was associated with a significant improvement of the patient's condition (89.8% of patients were rated by physicians as “much/very much improved”). Painful physical symptoms ( p < 0.0001) and cognitive state ( p = 0.0017) scores decreased along the study. A total of 83% of patients completed the study. Seven adverse events were recorded for four patients (6.8% overall). Data of this study suggest that VXR could be an effective and safe therapeutic option in the treatment of geriatric depression, reducing also the associated painful physical symptoms.

Efficacy of duloxetine in the treatment of generalized anxiety disorder in patients with clinically significant pain symptoms

Anxiety disorders often are accompanied by painful physical symptoms. This report assessed the effectiveness of duloxetine in improving anxiety symptoms, pain severity, and patient functioning in adults diagnosed with generalized anxiety disorder (GAD), who presented with clinically significant pain symptoms. Data were pooled from two multicenter, randomized, double-blind, placebo-controlled clinical studies evaluating the efficacy of duloxetine 60-120 mg once daily compared with placebo in the treatment of GAD. The primary patient population for these analyses was patients with baseline Visual Analog Scale (VAS) overall pain severity score > or =30. Of the 798 randomized patients that had baseline VAS scores, approximately 44.4% of GAD patients were identified as having baseline VAS overall pain severity score > or =30 (duloxetine N=208, placebo N=146). Duloxetine-treated patients had significantly greater improvement compared with placebo-treated patients on anxiety symptoms (measured by Hamilton Anxiety Scale total score), on patient functioning (measured by the Sheehan Disability Scale Global Functional Impairment Score and across all Sheehan Disability Scale domains), and on all VAS pain items. Patients achieving remission at endpoint, and patients with lower scores on the Clinical Global Impression of Improvement and Patient Global Impression of Improvement scales had greater improvement in VAS pain severity scores. These results suggest that in patients with GAD who present with clinically significant pain symptoms, duloxetine is effective in reducing anxiety symptoms, pain severity, and in improving patient functioning.

Duloxetine: Review of Its Pharmacology, and Therapeutic Use in Depression and Other Psychiatric Disorders

The discovery of antidepressant medications has revolutionized the treatment of depression and other psychiatric illnesses. The coming of the selective serotonin (5-HT) reuptake inhibitors (SSRIs) marked a new era in the treatment of depression. These therapies frequently fall short of getting the patient to remission. Agents with a dual action have subsequently been developed which inhibit the reuptake of both 5-HT and NE, getting more patients to remission. Physical symptoms are associated with depression, preventing the patient from obtaining complete recovery. This article provides an overview of the pharmacology, efficacy, and techniques for the clinical use of duloxetine, a dual reuptake inhibitor, which has recently become available. The English literature has been reviewed including both controlled and uncontrolled studies. Duloxetine is a dual reuptake inhibitor with actions on serotonin as well as norepinephrine. It has been shown to have efficacy in treating depressive symptoms including those with painful physical symptoms. Common side effects include nausea, insomnia, and dizziness. The article has been written with clinicians as the target audience, the data suggesting it can be used as a first line agent.

Painful physical symptoms (PPS) in depressed patients: how is the correlation between physician- and patient assessment?

Painful physical symptoms (PPS) in depressed patients: how is the correlation between physician- and patient assessment?

Effectiveness of antidepressants in the treatment of major depressive disorder in Latin America

Objective. Painful physical symptoms occur frequently in patients with major depressive disorder (MDD), and although numerous studies report the effect of antidepressants on emotional aspects of depression, few focus on their effect on physical symptoms. This observational study was conducted, in a clinical practice setting, to determine antidepressant treatment decisions and their outcome on the physical and emotional symptoms of MDD. Methods. Patients with a mean score ≥2 for pain-related items on the Somatic Symptom Inventory (SSI) were classified with painful physical symptoms (PPS +) and differentiated from the remaining patients (PPS −). Severity of depression and physical pain were determined using the 17-item Hamilton Depression Rating Scale (HAMD17) and Clinical Global Impressions of Severity Scale (CGI-S), and Visual Analog Scale (VAS), respectively. Results. At baseline, 72.6% of patients were PPS+. Compared to PPS- patients, PPS +patients were, on average, significantly more depressed at baseline (mean difference [95% CI]: HAMD17 4.6 [3.6, 5.5] and CGI-S 0.3 [0.2, 0.4]; all p<0.0001), and remained more depressed and in greater pain at endpoint (HAMD17p=0.0074, CGI-S P =0.0151, and VAS P <0.0001). In addition, fewer PPS+ patients (65.8%) achieved remission (total HAMD17≤7) compared to PPS- patients (74.6%, P =0.0180). Conclusions. Painful physical symptoms are prevalent in MDD patients, highlighting the importance of addressing both the physical and emotional symptoms of depression.

Duloxetine

Duloxetine (Cymbalta) is an orally administered, selective serotonin and noradrenaline reuptake inhibitor (SNRI) that has been approved for the treatment of major depressive disorder (MDD). Based on a considerable body of evidence, duloxetine at dosages ranging from 40 to 120 mg/day was effective in the short- and long-term treatment of MDD. Significant improvements versus placebo in core emotional symptoms as well as painful physical symptoms associated with depression, were seen in most, but not all, appropriately designed studies; results of meta-analyses suggested that improvements in these efficacy measures were apparent after 1-2 weeks' treatment with the highest recommended dosage of 60 mg once daily. Short-term (< or =15 weeks) administration of duloxetine at fixed or flexible dosages between 60 and 120 mg/day was noninferior to paroxetine 20 mg once daily, noninferior or inferior to escitalopram 10-20mg once daily, and had a similar global benefit-risk (GBR) profile to that of venlafaxine extended-release (XR) 150-225 mg/day in the treatment of MDD. Longer-term (6-8 months) treatment with duloxetine was similar in efficacy to paroxetine and escitalopram. Duloxetine is generally well tolerated, although it may be appropriate to avoid initiating treatment with the 60 mg/day dosage, as this has been associated with a higher discontinuation rate due to adverse events in some (but not all) comparative studies with escitalopram and venlafaxine XR. Definitive comparisons are awaited, although duloxetine seemingly provides a useful alternative to SSRIs and other SNRIs for the treatment of MDD. It also appears to be an attractive option for MDD patients presenting with painful physical symptoms.

Efficacy of duloxetine in painful symptoms: an analgesic or antidepressant effect?

The evidence that the effects of the antidepressant duloxetine on painful physical symptoms in depression and chronic pain disorders are a direct analgesic effect rather than an indirect antidepressant effect is reviewed. Data from placebo-controlled acute studies of duloxetine in major depressive disorder, diabetic peripheral neuropathic pain and fibromyalgia syndrome are included in this review. In placebo-controlled studies of duloxetine in patients with major depressive disorder, non-depressed diabetic peripheral neuropathic pain, and fibromyalgia syndrome, duloxetine has a statistically significantly greater effect on pain than placebo. Path analysis suggests that in these patient populations, approximately 50, 90, and 80%, respectively, of the observed effect on pain is a direct analgesic effect rather than an indirect antidepressant effect. In fibromyalgia syndrome studies, duloxetine had similar and substantial effects on pain regardless of whether patients had comorbid major depressive disorder. Pain is a complex experience, involving both the physiological responses of the nociceptive system and the processing of that information in brain regions associated with emotion. While some effects of duloxetine on painful symptoms can be accounted for by its antidepressant action, the data strongly suggest that duloxetine also exerts a substantial direct analgesic effect over and above its antidepressant effects, in patients with major depressive disorder, diabetic peripheral neuropathic pain, and fibromyalgia syndrome.

Duloxetine in the treatment of major depressive disorder: an assessment of the relationship between outcomes and episode characteristics

Duloxetine, an inhibitor of serotonin and norepinephrine reuptake, has been approved for the treatment of major depressive disorder. In this analysis, data from eight, double-blind, placebo-controlled duloxetine trials were pooled, and the response to duloxetine treatment (40-120 mg/day) was compared between patients experiencing their first episode of depression (n=581) or a subsequent episode (n=1321), and between patients experiencing a depressive episode of short (n=596), medium (n=669), or long (n=649) duration based on tertile divisions. Treatment response was determined on the basis of changes from baseline in the 17-item Hamilton Rating Scale for Depression total score, the Clinical Global Impressions of Severity Scale, and painful physical symptoms (Somatic Symptom Inventory and Visual Analog Scales). Overall, changes on all outcome measures and response and remission rates were significantly greater in duloxetine-treated patients than in placebo-treated patients. Furthermore, the effect of duloxetine was similar across all episode characteristic groups (first/subsequent episode, short/medium/long episode duration). Only for the Somatic Symptom Inventory was the effect of duloxetine significantly different between groups (greater in the subsequent episode group than in the first episode group). Duloxetine was effective in the treatment of first and subsequent episodes of major depressive disorder, and regardless of duration of the current depressive episode.

The association of depression and painful physical symptoms–a review of the European literature

Objective: The presence of painful physical symptoms may confound the diagnosis of major depressive disorder and may worsen patient prognosis. Epidemiological literature was reviewed to investigate the association between depression and painful physical symptoms. Method: MEDLINE and EMBASE database searches were conducted. Studies where a definable organic basis for pain was given were excluded. The search was unrestricted by language but limited to European studies and countries. After filters were applied, 70 eligible studies were reviewed. Results: The majority of studies reviewed showed an association between depression and painful physical symptoms. Over 40% of all studies examining the association between pain and depression were carried out in pain clinics in secondary care. Very few studies were conducted in psychiatric settings. Conclusion: The findings of this review suggest that painful physical symptoms may be an important part of the depressive syndrome. Although the relationship between depression and painful physical symptoms is not yet fully understood, findings suggest that diagnosis and treatment of depression should involve investigating and treating the full spectrum of symptoms (emotional and physical). Further research in psychiatric and generalist settings is needed to elucidate the relationship between depression and painful physical symptoms as experienced by patients and at the clinical level.

Duloxetine for childhood depression with pain and dissociative symptoms

Over two thirds of people suffering from depression complain of pain with or without reporting psychological symptoms. Physical symptoms are more prevalent among the women, the elderly, the poor, and in children population. Successful treatment of depression in children complicated by pain symptoms constitutes a great clinical challenge. Duloxetine has already emerged as a safe and effective treatment option for adult depressed patients with painful physical symptoms. However, no data exist in literature which suggests use of duloxetine in childhood and adolescent population for the same clinical indication. We report a case documenting successful use of duloxetine in a depressed girl child who also had severe pain and dissociative symptoms.

Comorbid painful physical symptoms and depression: Prevalence, work loss, and help seeking

Background Painful physical symptoms (PPS) are frequent in patients with Major Depressive Episode (MDE). Here, the 12-month prevalence and sociodemographic characteristics of PPS were examined taking into account somatic comorbidity; quantitative and qualitative aspects of MDE with or without PPS were investigated as well as their impact on work loss days (WLD). Finally, help seeking and delay in help seeking were explored. Methods In a cross-sectional, population-based study, a representative random sample of non-institutionalised adults from Belgium, France, Germany, Italy, the Netherlands and Spain ( N = 21,425) was interviewed using the World Mental Health Composite Diagnostic Interview (CIDI 3.0 of the WHO). Results PPS were reported by 29% of respondents without MDE and by 50% in those with MDE. Female gender, higher age and lower educational level were predictive of PPS. PPS were more frequent in more severely depressed patients but no qualitative differences were found in MDE with and MDE without PPS. An additive effect of MDE and PPS was found on the WLD score. Whether a comorbid somatic disorder was present or not did not change the findings. Finally, respondents with MDE and PPS had lower rates of help seeking for emotional reasons and show a trend to delay their help seeking longer. Limitations The most important limitation of this study was its reliance on self-report data about somatic disorders. Conclusion Approximately one in two persons with a mood disorder also reported the presence of PPS. MDE and PPS result in decreased productivity and in lower rates of help seeking.

Duloxetine: a new selective and dual-acting antidepressant

Antidepressants that inhibit the re-uptake of serotonin and noradrenaline might offer a chance to reduce the multiple symptoms of depression, as both serotonin and noradrenaline seem to be responsible for the emotional and physical symptoms of depression. The potential superiority of a dual mechanism of action has already been demonstrated in a number of clinical trials. Duloxetine, a novel dual acting, selective serotonin and noradrenaline-re-uptake inhibitor, has demonstrated high remission rates and good efficacy on physical symptoms, especially painful physical symptoms of depression. The results from studies in diabetic neuropathic pain provide further evidence of the effect of duloxetine on pain, independent of its effect on depression. Therefore, duloxetine provides an alternative to current therapeutic options in the treatment of the different symptoms of depression.

Efficacy of duloxetine in achieving response and remission

Deficiencies in the activity of specific pathways for serotonin (5-HT, 5-hydroxytryptamine), and norepinephrine (NE) have long been hypothesized to account for the symptoms of major depressive disorder (MDD). More than 30 years ago, it was noted that pharmacological agents that enhance the availability of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine, produced a clinically meaningful improvement in mood in patients suffering from MDD. This clinical observation led to the development of the so-called 'monoamine hypothesis' of depression, which proposed that functional disruptions in these neurotransmitter systems mediate the behavioural and physiological symptoms (e.g. painful physical symptoms) of depression and related conditions. The pharmacotherapy of MDD has relied principally on the development of agents that alter or increase the functional activity of these classical neurotransmitter systems [1].

P.2.c.034 Escitalopram versus nortriptyline in the treatment of painful physical symptoms in patients with major depression

Despite years of antidepressant drug development and patient and provider education, suboptimal medication dosing and duration of exposure resulting in incomplete remission of symptoms remains the norm in the treatment of depression. Additionally, since no one treatment is effective for all patients, optimal implementation focusing on the measurement of symptoms, side effects, and function is essential to determine effective sequential treatment approaches. There is a need for a paradigm shift in how clinical decision making is incorporated into clinical practice and for a move away from the trial-and-error approach that currently determines the “next best” treatment. This paper describes how our experience with the Texas Medication Algorithm Project (TMAP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial has confirmed the need for easy-to-use clinical support systems to ensure fidelity to guidelines. To further enhance guideline fidelity, we have developed an electronic decision support system that provides critical feedback and guidance at the point of patient care. We believe that a measurement-based care (MBC) approach is essential to any decision support system, allowing physicians to individualize and adapt decisions about patient care based on symptom progress, tolerability of medication, and dose optimization. We also believe that successful integration of sequential algorithms with MBC into real-world clinics will facilitate change that will endure and improve patient outcomes. Although we use major depression to illustrate our approach, the issues addressed are applicable to other chronic psychiatric conditions including comorbid depression and substance use disorder as well as other medical illnesses.

Management of Painful Physical Symptoms Associated With Depression and Mood Disorders

AbstractDepression is a common, recurring illness that continues to be underdiagnosed and undertreated in both psychiatric and primary care settings. It is increasingly being recognized that painful physical symptoms, which commonly exist comorbid with depressive disorders, play a role in complicating diagnosis of depression. Patients tend to discuss physical pain with primary care physicians and emotional pain with psychiatrists, often oblivious to the fact that both may be aspects of one disorder. Those who present with somatic complaints are three times less likely to be accurately diagnosed than patients with psychosocial complaints. However, thorough evaluation of mood and anxiety disorders in primary care is sparse due to the limited time primary care physicians can spend with each patient. Better recognition and treatment of both physical and emotional symptoms associated with mood disorders may increase a patient's chance of achieving remission, which is the optimum therapeutic goal.Abnormalities of serotonin and noradrenaline are strongly associated with depression and are thought to play a role in pain perception. Brain-derived neurotrophic factor, which is increased with antidepressant treatment, appears to influence regulation of mood and perception of pain. Clinical evidence indicates that dual-acting agents may have an advantage in modulating pain over those agents that increase either serotonin or noradrenaline alone. The novel dual-acting agents, such as venlafaxine and duloxetine, are better tolerated than tricyclic antidepressants and monoamine oxidase inhibitors. These agents have demonstrated efficacy in depression and in diabetic neuropathic pain independently. Therefore, unless otherwise stated, all inferences to studies of pain in this monograph refer to neuropathic pain in nondepressed patients.

Patients with depression who also experience painful physical symptoms incur significantly higher healthcare costs than those without such physical symptoms

Patients with depression who also experience painful physical symptoms incur significantly higher healthcare costs than those without such physical symptoms

Duloxetine: pharmacoeconomic implications of an antidepressant that alleviates painful physical symptoms

Major depressive disorder (MDD) is a prevalent, chronic, medical disorder that encompasses a broad constellation of symptoms. The salience of painful physical symptoms in depressive presentations is increasingly appreciated. Duloxetine is a novel, potent, balanced, dual monoamine reuptake-inhibitor antidepressant indicated for the symptomatic relief of MDD. Duloxetine is marketed as an antidepressant that has inherent analgesic properties for depressed patients who present with prominent painful physical symptoms. Taken together, available evidence indicates that duloxetine provides a higher probability of, and shorter time to, remission than some antidepressants (e.g., fluoxetine). Duloxetine also offers symptom relief for painful physical symptoms in depressed patients. Pharmacoeconomic and cost-impact modelling analyses should be reformulated to consider duloxetine’s sym-ptom-alleviating effect on the somatic dimension of depressive illness.

The Dual Transporter Inhibitor Duloxetine: A Review of its Preclinical Pharmacology, Pharmacokinetic Profile, and Clinical Results in Depression

Major depressive disorder (MDD) poses a significant health problem and is estimated to be the third most costly and disabling disorder in the United States. Pharmacotherapy of depression has been successful, but improvements in response rates, remission rates, side effects, compliance and faster onset of therapeutic action have become prime objectives in drug development. There is considerable support for the hypothesis that dysfunctional serotonergic or noradrenergic neurotransmission may be etiological in depressed patients. Duloxetine is a balanced and potent reuptake inhibitor of serotonin (5-HT) and norepinephrine (NE) being studied as an antidepressant medication. In this review, we highlight the preclinical pharmacology, pharmacokinetic profile, and effects of duloxetine in the pharmacotherapy of depression. Evidence for 5-HT and NE reuptake inhibition by duloxetine comes from in vitro and in vivo transporter binding and functional uptake studies. Taken together with efficacy data from in vivo microdialysis, electrophysiological and behavioral studies, it is evident that duloxetine is balanced as a dual serotonin norepinephrine uptake inhibitor in vivo. The clinical efficacy and safety of duloxetine in the treatment of MDD has been studied in 6 multicenter, randomized, double-blind, placebo-controlled trials. In these studies, duloxetine was found to be effective in the treatment of emotional/psychological and painful physical symptoms associated with depression. More importantly, duloxetine appears to have better response rates and remission from depressive symptoms, perhaps due to its ability to treat a wider range of symptoms.