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)

Chronic hepatitis C virus infection is a common and serious disease. Although an estimated 2.7 million persons in the United States have this disease, most have not yet been diagnosed. Recent advances in treatment provide successful cure in 50 to 80 percent of cases. Current drug therapy consists of a combination of pegylated interferon and ribavirin. Although all patients with chronic hepatitis C virus infection are potential candidates for treatment, pharmacologic therapy has a number of contraindications. Evaluation of suitability for treatment includes a thorough search for comorbid medical and psychiatric conditions that can be contraindications. Initial testing involves anti-hepatitis C virus antibodies, but definitive diagnosis of active disease requires detection of viral RNA. Most patients require a liver biopsy to determine the amount of hepatic fibrosis and ongoing hepatocellular inflammation. Viral genotype also should be determined: type 1 requires 12 months of treatment and does not respond as well as types 2 and 3, which require only six months of treatment. Common side effects of drug therapy include anemia, anorexia, depression, fatigue, fever, headache, myalgia, nausea, and erythema at the injection site.
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PMID:Management of hepatitis C: evaluating suitability for drug therapy. 1586 91

Psychiatric disorders, particularly depression, and substance-use disorders (SUDs) are common comorbidities in patients who have chronic hepatitis C virus (HCV) infection. Patients who are infected with HCV who are treated with interferon alfa (IFNalpha) are also at significant risk for IFNalpha-induced depression (incidence, ~20-30%) and other neuropsychiatric side effects that can affect treatment adherence, require dose reduction or discontinuation, and impact patient quality of life adversely. Because psychiatric illness and SUD comorbidities are so common, patients who have hepatitis C should be screened for these disorders. If these disorders are present, patients should be referred to a mental health care provider for appropriate treatment before therapy with IFNalpha is considered. Having a comanagement model of care that involves mental health care providers should help identify appropriate candidates for IFNalpha therapy. If preexisting depression responds to antidepressant treatment IFNalpha therapy can then be initiated. Patients who have other active psychiatric disorders can probably be offered IFNalpha therapy safely with appropriate monitoring and management involving a mental health care professional; however, there is a paycity of research in this area, and the few published studies have small sample sizes. If depression develops during IFNalpha therapy, most patients respond to treatment with selective serotonin-reuptake inhibitors, often allowing patients to continue receiving IFNalpha therapy. In addition to screening patients and treating those who have psychiatric disorders before IFNalpha therapy is started, early recognition of psychiatric disorders and neuropsychiatric side effects during IRNalpha therapy through continued screening and monitoring, with appropriate management, can potentially maximize HCV treatment adherence and possibly improve antiviral therapy outcomes.
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PMID:Neuropsychiatric side effects of HCV therapy and their treatment: focus on IFN alpha-induced depression. 1508 Nov 2

Psychiatric and substance use disorders affect most patients with chronic hepatitis C and are the most common reasons for exclusion from antiviral therapies. Suicidal ideation (SI) is often cited as a reason to exclude patients from interferon-based treatment or to terminate antiviral treatment that is in progress. This study examines SI in hepatitis C patients untreated and treated with interferon-alpha2b, a medication commonly associated with depression. Fifty-five subjects with chronic hepatitis C were followed for 24 weeks with three measures of depression, each containing one item assessing SI. A total of 15/55 (27%) subjects reported SI while not on interferon therapy. Of the 42 patients treated with interferon, 18 (43%) endorsed SI at some point during antiviral treatment. However, 17/18 (94%) finished at least a 6-month course of interferon therapy. No subjects attempted suicide. Although SI in some form is common in hepatitis C patients, in most cases it is mild in nature. With adequate support most patients can successfully complete a full course of antiviral treatment.
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PMID:Suicidal ideation during interferon-alpha2b and ribavirin treatment of patients with chronic hepatitis C. 1512 53

Neuropsychiatric side effects are common with interferon-based therapy for chronic hepatitis C, and their prompt recognition and management is essential to effective patient care. Depression induced by interferon has been a significant cause of early treatment discontinuation in clinical trials. The need to monitor for and treat interferon-induced depression is well established, but whether to use antidepressants prophylactically remains controversial. Nonetheless, clinicians should maintain a low threshold for antidepressant therapy. Other significant neuropsychiatric side effects include anxiety, hypomania or mania, fatigue, and cognitive dysfunction. These can be additional sources of patient distress during interferon therapy and require appropriate intervention through patient education, psychotropic medications, support, and behavioral techniques.
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PMID:Managing the neuropsychiatric side effects of interferon-based therapy for hepatitis C. 1546 15

Studies show that administration of interferon (IFN)-alpha causes a significant increase in depressive symptoms. The enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan (TRP) into kynurenine (KYN) and which is stimulated by proinflammatory cytokines, may be implicated in the development of IFN-alpha-induced depressive symptoms, first by decreasing the TRP availability to the brain and second by the induction of the KYN pathway resulting in the production of neurotoxic metabolites. Sixteen patients with chronic hepatitis C, free of psychiatric disorders and eligible for IFN-alpha treatment, were recruited. Depressive symptoms were measured using the Montgomery Asberg Depression Rating Scale (MADRS). Measurements of TRP, amino acids competing with TRP for entrance through the blood-brain barrier, KYN and kynurenic acid (KA), a neuroprotective metabolite, were performed using high-performance liquid chromatography. All assessments were carried out at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. The MADRS score significantly increased during IFN-alpha treatment as did the KYN/TRP ratio, reflecting IDO activity, and the KYN/KA ratio, reflecting the neurotoxic challenge. The TRP/CAA (competing amino acids) ratio, reflecting TRP availability to the brain, did not significantly change during treatment. Total MADRS score was significantly associated over time with the KYN/KA ratio, but not with the TRP/CAA ratio. Although no support was found that IDO decreases TRP availability to the brain, this study does support a role for IDO activity in the pathophysiology of IFN-alpha-induced depressive symptoms, through its induction of neurotoxic KYN metabolites.
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PMID:IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. 1549 6

The frequency of sexual dysfunction (SD) is not very well known in patients with chronic hepatitis C. In this study, the prevalence of SD and its correlations with psychological and biological variables was assessed in 46 HCV positive patients. The mean age of patients was 46.4+/-9.4 y; the mean duration of HCV infection was 43.4+/-34.0 months; 52% were male; 89% were living with a spouse. SD was assessed using the Arizona Sexual Experiences Scale (ASEX), the level of anxiety and depression measured with the Hospital Anxiety and Depression Scale (HADS). Biochemical parameters were also assessed. Overall, as indicated by ASEX criteria, SD was observed in 35% of our patients. Of 24 males, 21% described SD; problems with drive (25%), arousal (17%) and erection (17%) were the most frequent complaints. Of 22 female patients, 50% described SD; problems with drive (55%) arousal (50%), and reaching orgasm (59%) were the most frequent complaints. Total ASEX scores were correlated with age (P<0.07, significant at trend level), education (P<0.001), and was higher in female patients (P<0.02). After controlling for the effects of age, sex, education, duration of HCV and marital status, depression levels could still significantly predict the SD (P<0.05). Moreover, even after controlling the effects of all other variables, gamma glutamyl transpeptidase (GGT) levels could predict the SD status of the patients (P<0.05). Our results indicate that the prevalence of SD was 35% in HCV-infected patients and the level of depression and GGT levels were predictive of patients SD status.
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PMID:Sexual dysfunctions in HCV patients and its correlations with psychological and biological variables. 1551 Jan 90

Hepatic encephalopathy is the most obvious neurological consequence of chronic hepatitis C virus (HCV) infection. There are also case reports of HCV-associated cerebral vasculitis. This review is concerned with the possibility of an effect of HCV on cerebral dysfunction, occurring at an early stage of chronic infection, prior to the development of cirrhosis and unrelated to vasculitis. There is emerging evidence of mild, but significant neurocognitive impairment in HCV infection, which cannot be attributed to substance abuse, coexistent depression, or hepatic encephalopathy. In vivo magnetic resonance spectroscopy and neurophysiological studies have suggested that a biological mechanism may underlie these cognitive findings. The recent detection of HCV genetic sequences in postmortem brain tissue raises the intriguing possibility that HCV infection of the central nervous system may be related to the reported neuropsychological symptoms and cognitive impairment.
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PMID:Central nervous system involvement in hepatitis C virus infection. 1555 29

Tryptophan metabolism is disturbed in mental depression, and the induction of indoleamine 2,3-dioxygenase increases kynurenine production. In order to determine this disturbance in patients with chronic hepatitis C and receiving interferon-based immunotherapy, a new and specific HPLC protocol was elaborated. For tryptophan, the assay was linear from 6.25 to 100 micromol L(-1), and the limits of detection (LOD) and quantitation (LOQ) for the method were 0.7 and 8.0 micromol L(-1). For kynurenine, the linearity of calibration was from 0.0625 to 6.25 micromol L(-1), with LOD and LOQ of 2 and 3 nmol L(-1). Reproducibility and repeatability were satisfactory. The method allowed study of human blood serum.
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PMID:Simultaneous determination of tryptophan and kynurenine in serum by HPLC with UV and fluorescence detection. 1558 4

Since the discovery of hepatitis C virus (HCV) in 1989, significant advances have been made in our understanding of this important viral pathogen. Children at risk for HCV infection include recipients of potentially contaminated blood products and organ transplants, and infants born to HCV-infected mothers. Chronic HCV infection is usually asymptomatic in children but active hepatitis, cirrhosis and hepatocellular carcinoma can occur. The development of treatment strategies for chronic hepatitis C in children has directly evolved from clinical trials in adults. Sustained virologic response, defined by undetectable HCV RNA in serum 24 wk after completion of treatment, occurs in approximately 36% of children treated with conventional interferon alone and in about 50% of those given conventional interferon in combination with ribavirin. Pegylated interferon-based treatment regimens are better than those based on conventional interferon in adults but little is known about pegylated interferon in children. Factors associated with a favorable response to antiviral therapy in children are similar to those in adults and include infection with HCV genotype 2 or 3 and low pretreatment serum HCV RNA levels. Treatment related adverse events in children include 'flu-like' syndrome, fatigue, anorexia, weight loss, depression, anemia, leukopenia and thrombocytopenia.
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PMID:Treatment of chronic hepatitis C in children. 1559 40

Ribavirin has recently been demonstrated to be efficacious in combination with interferon (IFN) alpha-2b for the treatment of relapsed hepatitis C infections. The aim of this study was to evaluate the relationship between the pharmacokinetics and adverse reactions of ribavirin when ribavirin plus IFN alpha-2b were administered to patients affected with chronic hepatitis C. Nineteen patients received intramuscular IFN alpha-2b at a dose of 6 or 10 million units and oral ribavirin at 600 mg or 800 mg daily for 24 weeks. The pharmacokinetic profiles of ribavirin were assessed by the measurement of plasma concentrations. Twelve patients were continuously given both ribavirin and IFN alpha-2b, whereas in 7 patients the therapy was discontinued due to severe adverse drug reactions such as skin eruption, anemia and depression. There were no significant differences in ribavirin dose, Hb, ALT and AST values between the continued and the discontinued therapy groups. In contrast, the pretreatment platelet level and patient age of the discontinued therapy group were significantly different to the continued group. The trough plasma concentration of ribavirin in the discontinued therapy group was significantly higher than that in the continued group at week 1. These results suggest that the monitoring of plasma ribavirin concentrations may be valid for predicting the early phase of adverse drug reactions, thereby providing useful information for the adjustment of the ribavirin dosing for each patient.
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PMID:Assessment of adverse reactions and pharmacokinetics of ribavirin in combination with interferon alpha-2b in patients with chronic hepatitis C. 1568 98


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