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)

Interferon alpha (IFNalpha) is used for the treatment of several disorders, such as chronic hepatitis or malignant melanoma. During the therapy, IFNalpha may cause severe neuropsychiatric syndromes including depression with suicidal ideation, paranoid psychoses, or confusional states. The reasons and management of these side effects are widely unknown. Our aim is to review research evidence for the contribution of IFNalpha for the etiopathology of psychiatric syndromes. Therefore, research findings of neuropsychiatric syndromes induced by IFNalpha treatment, the putative mechanisms underlying those syndromes, and their treatment are-reviewed. Furthermore, neuropsychiatric syndromes in diseases with high IFNalpha levels such as systemic lupus erythematosus (SLE) are discussed. Finally, the question is addressed whether IFNalpha may contribute to the etiopathology of endogenous psychiatric disorders. IFNalpha may cause psychiatric syndromes in a subset of treated patients. The underlying pathogenetic mechanisms include various effects on neuroendocrine, cytokine, and neurotransmitter systems. Research data on the role of IFNalpha in the pathogenesis of endogenous psychiatric disorders are conflicting. Future research should improve our understanding of the role of IFNalpha for the etiopathology of psychiatric syndromes and has an impact on treatment of IFNalpha-induced psychiatric syndromes.
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PMID:Interferon alpha (IFNalpha) and psychiatric syndromes: a review. 1218 6

Ever since a gradual but significant reduction in the estrogenic and progestogenic components of oral contraceptives (OCs) was made, there has been a corresponding decrease in adverse effects associated with the pill. The beneficial effects include prevention of pregnancy, reduction in pelvic inflammatory disease, protection against ovarian/endometrial cancer and benign breast tumors and ovarian cysts, reduction in the occurrence of rheumatoid arthritis among OC users, and regulation of the menstrual cycle. The adverse effects include diseases of the circulatory system (myocardial infarction, venous thromboembolism, subarachnoid hemorrhage, hypertension), possible carcinogenicity (breast, cervix, melanoma), pituitary adenomas, liver disorders, glucose metabolix effects (diabetes), vitamin status alteration, delay in return of menstruation and fertility, and a number of minor side effects (nausea, vomiting). Contraindications to OC use include history of malignancy of the breast or genital tract, venous thromboembolism, cerebrovascular accident, undiagnosed abnormal vaginal bleeding, focal migraine, or familial hyperlipidemia. The following situations require medical assessment before OCs are prescribed, and medical supervision if OCs are prescribed: age 40+, smoking and age over 35, mild hypertension or a history of hypertensive disease of pregnancy (toxemia), epilepsy, diabetes mellitus, history of bouts of depression, history of oligomenorrhea or amenorrhea in nulliparous women, and gallbladder disease. Problems could occur with OC use in the following situations: 1) lactation (ideally, OCs should be withheld until the child is weaned but if not possible, OCs should not be given until lactation is established); 2) drug interaction (other contraceptive form should be used when the patient is taking antibiotics or anticonvulsants); 3) tropical diseases (studies are still underway); 4) adolescence (very young girls should use other contraceptive method until regular menstruation is established); 5) postcoital contraception (limited use of steroids in emergency situation); and 6) hormonal pregnancy tests (use of oral steroids for pregnancy testing is not recommended). The 3 main types of OCs currently used are the combined estrogen and progestagen, the progestagen-only OC, and the triphasic OC. The lowest effective dose of a compound should be used, and healthy women may continue to use OCs for many years.
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PMID:Statement on steroidal oral contraceptives. 1226 73

Immunotherapy with interferon-alpha (IFN-alpha) induces neuropsychiatric side effects, most notably depression. One of the presumed pathophysiological mechanisms is an effect on tryptophan metabolism. As tryptophan is the precursor of serotonin, decreased availability of tryptophan to the central nervous system could result in serotonin deficiency. Tetrahydrobiopterin (BH((4))) is a cofactor for one of the enzymes synthesizing serotonin. We conducted an exploratory study into the serum concentrations of large neutral amino acids (AA), biopterin (BIOP) and neopterin (NEOP), of 67 patients with high-risk melanoma, who were either treated with two different doses of IFN-alpha or were part of an observation-only control group. We found evidence for IFN-alpha to decrease concentrations of all AA except phenylalanine. The decrease in tryptophan concentration was most prominent and consistent. These changes persisted throughout a year of maintenance treatment. Concentrations of NEOP rose sharply, whereas, those of BIOP did not change. Except for the increase in NEOP and the increase in the ratio between phenylalanine (PHE) and tyrosine (TYR), no support for derangement in BH((4)) metabolism was found. The increase in the ratio between PHE and TYR suggests inhibition of the enzyme phenylalanine hydroxylase. Patients with IFN-alpha induced anxiety and depression had higher pretreatment concentrations of NEOP. Changes in tryptophan metabolism may play a role in the pathophysiology of the neuropsychiatric side effects of IFN-alpha, and further research into the predictive potential of NEOP is warranted.
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PMID:Serum amino acids, biopterin and neopterin during long-term immunotherapy with interferon-alpha in high-risk melanoma patients. 1286 Mar 66

The use of interferon (IFN)-alpha for the treatment of viral diseases or cancers is associated with neuropsychiatric side effects in a large number of patients. The mechanisms by which cytokines induce these symptoms, as well as the vulnerability factors for these effects, have not been yet fully elucidated. Systematic clinical studies, combining biochemical approaches, functional brain imaging and treatment intervention, have been initiated to better understand the phenomenology, pathophysiology, and preventive strategies of the neuropsychiatric effects of IFN-alpha in patients with malignant melanoma or chronic hepatitis C. The findings indicate differential phenomenology and treatment responsiveness of the neurovegetative and mood/cognitive symptoms induced by IFN-alpha, suggesting distinct underlying mechanisms. Impaired neuroendocine function, fronto-striatal dysfunction and decreased monoamine were found to contribute to the pathophysiology of core symptoms of IFN-alpha-induced depression, including symptoms of mood alterations, cognitive dysfunction, anhedonia and psychomotor retardation. In addition, some behavioral and biological markers of the vulnerability for IFN-alpha-induced depression were identified. These findings provide important information concerning the relationship between cytokines and depression.
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PMID:[Neuro-immune interactions in psychopathology with the example of interferon-alpha-induced depression]. 1291 Jun 30

Interferon alpha (IFN-alpha), an immunomodulatory cytokine, is used for the treatment of several disorders including chronic hepatitis or malignant melanoma. During the therapy IFN-alpha may cause severe neuropsychiatric syndromes including depression with suicidal ideation, paranoid psychoses or confusional states. The reasons and management of these side effects are widely unknown. The underlying pathogenetic mechanisms include various effects on neuroendocrine, cytokine and neurotransmitter systems. This review summarizes therapeutic strategies against IFN-alpha associated psychiatric syndromes. Zolpidem or Zopiclon can be used for the treatment of sleeping disturbances. Serotonin-reuptake-inhibitors including citalopram or paroxetine were shown to be effective for acute treatment of IFN-alpha associated depression. The efficacy of prophylactic treatment for prevention of IFN-alpha induced depression has to be proven in future trials. In an interdisciplinary setting, psychiatric disorders and drug addiction should not prevent patients from interferon-alpha treatment. Furthermore, interdisciplinary care should improve quality of life, adherence and therapeutic outcome of interferon-alpha treated patients.
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PMID:[Incidence, pathoetiology and treatment of interferon-alpha induced neuro-psychiatric side effects]. 1297 32

Pentostatin (2'-deoxycoformycin, dCF) is a purine nucleoside analog and a product of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of adenosine deaminase (ADA), an enzyme essential in the cellular metabolism of purines. Children with congenital absence of ADA suffer from atrophy of lymphoid tissues and severe combined immune deficiency (SCID) syndrome. It was hypothesized that pentostatin would be lymphocytotoxic and this proved to be true; this finding prompted its investigation in lymphoid neoplasms. It was anticipated that pentostatin would be most active in neoplasms with high intracellular concentrations of ADA, e.g. acute lymphocytic leukemia (ALL), particularly of the T-cell variety. Although pentostatin proved to be active in ALL, large doses were required and major toxic effects outweighed therapeutic benefits. By contrast, pentostatin proved to be exceptionally active in hairy cell leukemia (HCL), a B-cell neoplasm with low intracellular concentrations of ADA. Pentostatin has since been shown to possess activity in chronic lymphocytic leukemia, prolymphocytic leukemia, cutaneous T-cell lymphomas, adult T-cell lymphoma-leukemia, and low grade non-Hodgkin's lymphomas. It potentiates the activity of vidarabine against viruses and against the cells of acute myeloid leukemia. Pentostatin is inactive in melanoma and renal carcinoma, but has not been adequately evaluated in other solid tumors. The toxic effects of pentostatin include renal failure, central nervous system (CNS) depression, immunosuppresion, keratoconjunctivitis, and opportunistic infections. In the absence of pre-existing bone marrow compromise, pentostatin produces only mild myelosuppression. Aside from its use as an antineoplastic agent, pentostatin has potential applications as an immunosuppressive drug, as an antiviral agent, as an antimalarial compound, and in the protection of cells of the CNS from damage induced by ischemia and anoxia. Clinical studies with pentostatin are ongoing, and its roles in the management of neoplastic and non-neoplastic diseases have yet to be fully defined.
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PMID:Deoxycoformycin (pentostatin): clinical pharmacology, role in the chemotherapy of cancer, and use in other diseases. 1465 Dec 24

It has been suggested that patients with subclinical mood symptoms prior to initiating cytokine treatment (as revealed by elevated baseline scores on depression rating scales) are more likely to become clinically depressed during the course of cytokine therapy. The present study was designed to identify which specific preexisting symptoms predict development of depressive symptomatology during treatment with the cytokines, interleukin-2 (IL-2) and/or interferon-alpha (IFN-alpha), in patients with cancer. Thirty-two patients with renal cell carcinoma or malignant melanoma eligible to receive treatment with IL-2 and/or IFN-alpha were enrolled in the study. At baseline and after one month of cytokine therapy (endpoint), depressive symptoms were assessed using the clinician-administered Montgomery-Asberg depression rating scale (MADRS). Illness-related coping strategies, social support, somatic complaints, quality of sleep and demographic factors were also assessed as relevant baseline predictive factors. MADRS scores significantly increased during cytokine therapy. Patients with moderate to marked depressive symptomatology at study endpoint exhibited higher baseline scores in dimensions of the MADRS scale assessing emotional (especially reported sadness), cognitive (especially pessimistic thoughts) and neurovegetative (sleep disturbances) symptoms compared to patients who remained free of depressive symptoms during cytokine therapy. Interestingly, only emotional symptoms and sleep disturbance at baseline, along with low social support, predicted severity of depressive symptoms at the end of the first month of therapy. By documenting specific behavioral vulnerability factors for cytokine-induced depressive symptoms, these findings may help identify patients at risk for mood disturbances during cytokine treatment and help target specific patient populations and specific symptoms for preventative strategies.
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PMID:Baseline mood and psychosocial characteristics of patients developing depressive symptoms during interleukin-2 and/or interferon-alpha cancer therapy. 1505 Jun 47

A quality-of-life study was carried out to test the hypothesis that melanoma patients treated with a 3-cm margin of excision suffer greater impairment of their quality of life than those treated with a 1-cm margin. The secondary aim was to determine the predictors of a poor patient perception of their excision scar. A postal questionnaire study was carried out using Hospital Anxiety and Depression (HAD), Psychosocial Adjustment of Illness Scale-Self-Report (PAIS-SR), Medical Outcomes Survey-Short Form 36 (MOS-SF36), and the Cassileth Scar questionnaires. Data were collected from 426 of the 537 patients who were mailed the questionnaires (response rate 79%). Fourteen percent had clinically significant anxiety and 5% had significant depression. A poor attitude toward quality of health care was associated with youth. Patients treated with a 3-cm margin excision had significantly poorer mental and physical function 1 mo after surgery, which disappeared within 6 mo. The greater difficulties experienced by the 3-cm margin group were particularly in their domestic, sexual, and social roles. Women, younger patients, those with poor physical and mental function after surgery, and those treated by a 3-cm margin were more likely to report a poorer perception of their scar. The poorer scar perception of patients in the 3-cm group persisted throughout the study period. Use of a 3-cm margin of excision for melanoma is associated with significantly more morbidity than use of a 1-cm margin, but this effect disappears in 6 mo. Patients treated by 3-cm excision were more likely, however, to have a persistent poor view of their scar. Youth and being female were also predictors of poor perception of the scar.
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PMID:A quality-of-life study in high-risk (thickness > = or 2 mm) cutaneous melanoma patients in a randomized trial of 1-cm versus 3-cm surgical excision margins. 1508 83

The purpose of this study was to investigate anxiety and depression as predictors for recurrence-free survival in cutaneous melanoma, when corrected for known prognostic factors. The association between known prognostic factors and anxiety and depression were also studied. Consecutive patients (n = 437) completed the Hospital Anxiety and Depression Scale (HAD) approximately three months after diagnosis of melanoma. Neither anxiety, nor depression turned out to be prognostic factors for time to recurrence. A higher proportion of young patients, women, patients without ulcerated tumours, patients with tumours with low mitotic index and Clark's level II tumours scored > or = 8 (possible clinical levels of anxiety) on the anxiety scale. Furthermore, on the depression scale, a higher proportion of young patients scored > or = 8 (possible clinical level of depression). Using the HAD scale, a well-validated instrument for assessing anxiety and depression in patients with somatic diseases, our data did not show any associations between anxiety or depression and outcome in terms of recurrence in patients with localized disease.
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PMID:Anxiety and depressive symptoms measured by the Hospital Anxiety and Depression Scale as predictors of time to recurrence in localized cutaneous melanoma. 1516 64

Mood and anxiety disorders are among the most prevalent psychiatric illnesses and are associated with considerable morbidity and mortality. Selective serotonin reuptake inhibitors (SSRIs) are safe and effective treatments for major depression and anxiety disorders, and have become the most widely prescribed antidepressants worldwide. However, several issues limit SSRI treatment outcomes. Although SSRIs have a wider therapeutic margin and a milder side-effect profile compared to earlier antidepressants, even minor SSRI side effects can have a major impact on treatment outcomes by interfering with patient compliance. Nausea is one of the most common early SSRI side effects, and advances in SSRI delivery systems can diminish this. A controlled-release formulation of paroxetine targets the site of absorption for a more distal region of the small intestine, thereby avoiding the stimulation of upper gastrointestinal serotonin receptors that mediate nausea. The sustained-release characteristics also reduce the amplitude in blood level peaks and troughs, which may lead to diminished side effects and enhanced efficacy. Sexual side effects and weight gain are important sustained SSRI side effects, which affect compliance during continuation and maintenance phases of treatment. Several strategies address SSRI sexual side effects, including the use of adjunctive medication and/or manipulations in the scheduling of drug administration. Depression negatively impacts the management of many medical illnesses, including cardiovascular disease, cancer, and infectious diseases. The recognition and treatment of depression leads to improved outcomes in the management of breast cancer. Prophylactic SSRI treatment significantly reduces the incidence of interferon-associated depression and enhances completion rates in malignant melanoma.
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PMID:Making advances where it matters: improving outcomes in mood and anxiety disorders. 1518 81


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