Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine which patients are prone to side effects from interferon beta-1b and which side effects are most troublesome, we studied 72 patients with clinically definite MS who were started on interferon beta-1b after its release and found that the side effects significantly associated with treatment included skin reactions, flu-like symptoms, fatigue, leukopenia, new or worsened depression, and new or worsened headache. Of these, only fatigue and depression were significantly associated with discontinuance of therapy. Moreover, the course of disease before initiation of treatment also had a significant impact on the likelihood of discontinuing medication. Thus, despite an apparently similar therapeutic benefit (as judged by the similarly reduced attack rate in each group), patients with a secondary chronic progressive course were more likely to discontinue treatment (63%) than patients with either a relapsing/progressive course (18%) or a remitting/relapsing course (7%). Indeed, in the final regression equation, the only factors significantly related (r = 0.875) to the discontinuance of therapy were fatigue (p < 0.0001), a fatigue-depression interaction (p < 0.0001), and a chronic progressive course of disease (p<0.0001). Thus, if future clinical trials are to provide useful information on the value of interferon beta-1b in progressive MS, the side effects of fatigue and depression will need to be ameliorated to limit the drop-out rate from such trials.
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PMID:Side effect profile of interferon beta-1b in MS: results of an open label trial. 861 31

This review addresses the importance of studies of human psychoneuroimmunology in understanding the role of psychological factors in physical illness. First, it provides psychologically and biologically plausible explanations for how psychological factors might influence immunity and immune system-mediated disease. Second, it covers substantial evidence that factors such as stress, negative affect, clinical depression, social support, and repression/denial can influence both cellular and humoral indicators of immune status and function. Third, at least in the case of the less serious infectious diseases (colds, influenza, herpes), it considers consistent and convincing evidence of links between stress and negative affect and disease onset and progression. Although still early in its development, research also suggests a role of psychological factors in autoimmune diseases. Evidence for effects of stress, depression, and repression/denial on onset and progression of AIDs and cancer is less consistent and inconclusive, possibly owing to methodological limitations inherent in studying these complex illnesses, or because psychological influences on immunity are not of the magnitude or type necessary to alter the body's response in these cases. What is missing in this literature, however, is strong evidence that the associations between psychological factors and disease that do exist are attributable to immune changes.
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PMID:Health psychology: psychological factors and physical disease from the perspective of human psychoneuroimmunology. 862 35

To test hypotheses about the relationship between negative affect and symptom reports, symptom reports of 4 groups of elderly participants (N = 76; mean age = 73.5 years) were compared: those high on measures of both depression and anxiety, those high on one measure and low on the other, and those low on both measures. Symptom reports were obtained before and after 3 simultaneously given active inoculations (influenza; tetanus toxoid; and keyhole limpet hemocyanin, a neoantigen) and 3 similarly given placebo injections. Cross-sectional analyses replicated associations between negative affect and reports of elevated systemic (flulike) symptoms. Local symptoms (sore arm and redness at injection site) increased significantly from before to after active inoculations. Reports of systemic symptoms declined from before to after for both active and placebo inoculations regardless of affect groups. The results add to previous research showing that negative affect is related to cross-sectional symptom reporting but not to increases in symptom reporting from before to after a symptom-producing inoculation procedure.
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PMID:Negative affect relates to cross-sectional but not longitudinal symptom reporting: data from elderly adults. 881 74

Recombinant human IL-6 (rhIL-6) is a pleiotropic cytokine with stimulatory actions on the hematopoietic system, the immune system and hepatocytes. Clinical interest in the use of this cytokine was raised because of its thrombopoietic properties and also because of its anti-tumor activity, which was shown in vitro and in the preclinical setting. Various studies show that doses up to 10 mu kg/kg/d rhIL-6 before and after chemotherapy are tolerable and the most frequent side-effects encountered consist of flu-like symptoms. Furthermore, a consistent decrease in hemoglobin was reported during rhIL-6 treatment. This was probably due to hemodilution, although a change in ferrokinetics, may also at least partly, explain the anemia. An evident increase of platelets has been observed in various studies. After chemotherapy, rh-IL6 seemed to hasten platelet recovery, without affecting platelet nadir. Preliminary data from studies investigating the value of rhIL-6 as an anti-tumor agent in renal cell carcinoma and melanoma reported low response rates, between 8 and 14%. The results of rhIL-6 in ameliorating chemotherapy induced bone-marrow depression and especially thrombocytopenia, are promising and merit further phase III studies.
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PMID:Potential use of recombinant human interleukin-6 in clinical oncology. 883 92

This paper summarizes the worldwide cumulative experience with copolymer 1 (Copaxone) in 857 patients who were enrolled in open-label (n = 586), double-blind (n = 201), and compassioniate-use studies (n = 70). The results of a phase III study, including previously unpublished information, are employed to delineate adverse events that occur more frequently among patients treated with copolymer 1 than in placebo-treated controls, and to provide qualitative information. In the cumulative database, patients usually had relapsing-remitting multiple sclerosis and typically received a dose of 20 mg by daily subcutaneous injection for at least 1 year, and occasionally for more than 10 years. Withdrawal rates were 8% for copolymer 1 and 2% for placebo. The most common adverse event was mild injection-site reaction, manifested by erythema, inflammation, and induration. The most remarkable adverse event was a systemic post-injection reaction that occurred in 10% of patients. It was manifested by flushing, chest tightness, palpitations, dyspnea, and anxiety, and was acute and transient. The incidence of adverse events associated with interferon beta, such as flu-like syndrome, depression, hematologic abnormalities, cardiotoxicity, and elevated hepatic enzymes, was not increased among patients treated with copolymer 1. Evaluation of the extensive experience with copolymer 1 confirms that it is well tolerated and suitable for self-administration by patients with multiple sclerosis.
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PMID:Safety profile of copolymer 1: analysis of cumulative experience in the United States and Israel. 896 17

This study, conducted in three separate outpatient health care delivery settings, examined the therapeutic expectations of patients with multiple sclerosis (MS) before they initiated interferon beta-1b therapy, the results of current educational procedures to correct unrealistic expectations, and the relationship between post-education expectations and discontinuing therapy. Ninety-nine consecutive patients were seen in a university based outpatient MS clinic, an academic group practice outpatient MS clinic, or a health maintenance organization outpatient neurology clinic. Before the educational sessions, 57% of the patients expressed unrealistically optimistic expectations regarding reduction in attack rate and 34% expressed unrealistically optimistic expectations regarding improvement in functional status. Educational procedures significantly altered unrealistic expectations but the results were sub-optimal since 33% of the patients maintained overly optimistic expectations regarding reduction in attack rate. Post-education unrealistic expectations of improvement in functional status were significantly related to discontinuing therapy within 6 months. Three adverse effects of therapy also were related independently to adherence to treatment: depression and flu-like symptoms were related to discontinuing therapy while soreness at injection site was related to continuing therapy.
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PMID:Therapeutic expectations of patients with multiple sclerosis upon initiating interferon beta-1b: relationship to adherence to treatment. 905 Mar 60

To minimize the symptoms of antidepressant discontinuation, gradual tapering is necessary for all serotonin reuptake inhibitors (SRIs) except fluoxetine, which has an extended half-life. Agents with shorter half-lives such as venlafaxine, fluvoxamine, and paroxetine should be tapered gradually. Discontinuation symptoms, which frequently emerge after abrupt discontinuation or intermittent non-compliance and, less frequently, during dose reduction, are generally mild, short-lived, and self-limiting but can be distressing and may lead to missed work days and decreased productivity. The symptoms may be somatic (e.g., dizziness and light-headedness; nausea and vomiting; fatigue, lethargy, myalgia, chills, and other flu-like symptoms; sensory and sleep disturbances) or psychological (anxiety and/or agitation, crying spells, irritability). Mild symptoms can often be treated by simply reassuring the patient that they are usually transient, but for more severe symptoms, it may be necessary to reinstitute the dosage of the original antidepressant and slow the rate of taper. Symptoms of discontinuation may be mistaken for physical illness or relapse into depression; misdiagnosing the symptoms may lead to unnecessary, costly tests and treatment. Thus, health care professionals need to be educated about the potential adverse effects of SRI discontinuation.
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PMID:Clinical management of antidepressant discontinuation. 981 35

Following infection with influenza virus, animals display decreased locomotor activity and feeding behavior and loss of body weight. It has been suggested that these effects may be mediated by cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), induced by the infection. To assess the potential role of IL-1, we tested the ability of a naturally occurring IL-1-receptor antagonist (IL-1ra) to antagonize the changes in feeding behavior induced by IL-1, endotoxin (lipopolysaccharide, LPS), and infection with influenza virus. Feeding behavior was assessed by measuring the daily intake of food pellets and sweetened milk in a 30-min period. Acute injection of IL-1 beta decreased milk intake, but mouse IL-6 and mouse TNF-alpha did not. However, TNF-alpha decreased food pellet intake slightly, especially when it was injected at the beginning of the dark phase. The reductions in milk intake induced by mouse IL-1 beta were largely prevented by IL-1ra pretreatment (100 micrograms/mouse i.p.). The LPS-induced reductions in milk intake were attenuated, but not blocked, by IL-1ra treatment (300 micrograms/mouse). LPS still induced significant decrements in the presence of the antagonist. In influenza virus-infected mice, IL-1ra was administered either by repeated subcutaneous (s.c.) injections, or by continuous s.c. infusion from osmotic minipumps. These IL-1ra treatments produced small, but statistically significant, attenuations of the depression in milk and food pellet intake in the virus-infected mice. In several experiments, IL-1ra treatment increased the survival of influenza virus-infected mice. Thus the attenuation of the hypophagia may have been caused by this IL-1ra-induced increase in survival. The results suggest that IL-1 contributes to sickness behavior induced by LPS and influenza virus infection, but it is not the only factor involved.
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PMID:The role of cytokines in the behavioral responses to endotoxin and influenza virus infection in mice: effects of acute and chronic administration of the interleukin-1-receptor antagonist (IL-1ra). 943

Interferons (IFNs) are potent biologic response modifiers with antiviral and antiproliferative effects. The successful clinical application of IFNs for the treatment of chronic viral infections and malignancies has resulted in improved quality and quantity of life for thousands of patients, and the number of new indications for IFN therapy continues to grow. However, the therapeutic effectiveness of IFNs, including IFN-alpha, is often compromised by a variety of dose-related side effects that can be dose limiting. These side effects include flu-like symptoms, fatigue, anorexia, and depression, which may be mild or severe. A better understanding of the mechanisms by which IFN-alpha causes these side effects will facilitate the development of effective strategies to lessen their effects on the patient's quality of life and allow the maximum therapeutic dose of IFN-alpha to be administered.
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PMID:A perspective on the clinical effectiveness and tolerance of interferon-alpha. 948 34

Two forms of recombinant interferon-alpha (IFN-alpha2a and IFN-alpha2b) have been approved by the Food and Drug Administration for a variety of clinical indications, including hairy cell leukemia, hepatitis, acquired immunodeficiency syndrome-related Kaposi's sarcoma, chronic myelogenous leukemia (IFN-alpha2a only), and adjuvant therapy for melanoma (IFN-alpha2b only), based on their proven clinical efficacy and acceptable safety profiles. The continued postmarketing monitoring of adverse reactions associated with IFN-alpha therapy has revealed some new toxicities. The most common adverse events associated with IFN-alpha therapy are flu-like symptoms, fatigue, anorexia, and central nervous system and psychiatric reactions. In particular, the incidence of depression has only recently been fully appreciated. Some of these side effects, particularly chronic fatigue, anorexia, and neuropsychiatric reactions, may become dose limiting. New approaches to minimize and manage the side effects of IFN-alpha therapy are needed.
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PMID:Safety profile of interferon-alpha therapy. 948 35


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