Clinical experience with venlafaxine in the treatment of hot flushes in women with a history of breast cancer

OBJECTIVE: To obtain practical experience with venlafaxine for hot flushes in breast cancer patients and incorporate this in a treatment protocol. METHOD: Twenty-two women with a history of breast cancer (mean age 49.2 years, range 35-65) were referred for consideration of treatment with venlafaxine for hot flushes. Patients received extensive information on treatment with venlafaxine and were advised to self-monitor the frequency of their hot flushes. RESULTS: Eight women did not start venlafaxine because they had no postmenopausal complaints, were lost to follow-up, had too low a frequency of hot flushes, or refused treatment. Eventually 14 women started venlafaxine. Two of them did not tolerate venlafaxine, four reported some effect but stopped because of side effects, two women had no effect whatsoever. Six women observed a clear ( > 50%) reduction in their hot flush frequency that was maintained at a median follow-up of 13 months. CONCLUSION: The group of patients referred for treatment was more heterogeneous and more patients dropped out because of side effects than expected. Extensive patient education, patient selection and evaluation of the treatment effect (by self-monitoring of hot flush frequency) are mandatory to avoid useless (continuation of) treatment and to prepare patients for side effects. Under these conditions, a substantial minority of patients benefit from venlafaxine

Nitric oxide production and monoamine oxidase activity in cancer patients during interferon-α therapy

Both increased and decreased nitric oxide (NO) synthesis have been reported in patients treated with interferon-α (IFN-α). Animal studies showed that IFN-α administration results in increased levels of biogenic amines, subsequent activation of monoamine oxidases (MAOs), and finally in a change in NO production due to the H2O2 generated by MAOs. We examined the potential relationship between NO production in plasma and MAO-B activity in platelets of 43 cancer patients during 8 weeks of treatment with IFN-α. NO synthesis was quantitated by measuring both the ratio of citrulline and arginine (CIT/ARG-ratio) and total nitrite/nitrate (NOx) levels. Compared to baseline, MAO activity and NOx increased, while the CIT/ARG-ratio decreased. No associations were found between NOx, MAO and CIT/ARG-ratio. Only few associations were observed between changes in the biochemical parameters and changes in psychopathology induced by IFN-α, of which the association between changes in CIT and lassitude was the most consistent. The results suggest that peripheral NO production and MAO activity are unrelated to each other, and that peripheral changes in these biochemical parameters induced by IFN-α are unlikely to contribute to definite psychiatric disturbance

Serum amino acids, biopterin and neopterin during long-term immunotherapy with interferon-alpha in high-risk melanoma patients

Abstract Immunotherapy with interferon-alpha (IFN-a) 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 ) is a cofactor for one of the enzymes synthesizing serotonin. We conducted an exploratory 4 ( ) 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-a or were part of an observation-only control group. We found evidence for IFN-a 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 metabolism was found. The increase in the ratio between PHE and 4 ( ) TYR suggests inhibition of the enzyme phenylalanine hydroxylase. Patients with IFN-a 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-a, and further research into the predictive potential of NEOP is warranted.

Augmentation of Endoxifen Exposure in Tamoxifen-Treated Women Following SSRI Switch

Background and Objective: The anti-oestrogen tamoxifen requires metabolic activation to endoxifen by cytochr

Addressing sickness absence among adolescents and young adults

Background: Sickness absence is associated with lower school achievements and early school leaving. The Medical Advice for Sick-reported Students (MASS) intervention is a proactive school-based intervention focused primarily on early identification and reduction of sickness absence. This study used a program evaluation framework to evaluate the MASS intervention among intermediate vocational education students and Youth Health Care professionals. Outcome indicators were primarily number of sick days, education fit, and school performance, and secondarily, seven health indicators. Process indicators were dose delivered and received, satisfaction, and experience. Methods: The MASS intervention evaluation was conducted in ten intermediate vocational education schools. Students with extensive sickness absence from school in the past three months were included in either the intervention or control condition. Students completed a baseline and a six-month follow-up self-report questionnaire. Linear and logistic regression analyses were applied. Students and Youth Health Care professionals completed an evaluation form regarding their satisfaction and experience with the intervention. Results: Participants (n = 200) had a mean age of 18.6 years (SD = 2.02) and 78.5% were female. The MASS intervention showed positive results on decreasing sickness absence in days (β = -1.13, 95% CI = -2.22;-0.05, p 0.05). A significant interaction revealed a decline in sickness absence in males (p 0.05). Youth Health Care professionals found the application of the MASS intervention useful (n = 35 forms). The mean rating of students for the consultation within the MASS intervention was an 8.3 (SD = 1.3) out of 10 (n = 14 forms). Conclusions: Our study provides some indication that the MASS intervention has positive effects on decreasing both sickness absence and depressive symptoms among intermediate vocational education students. The Youth Health Care professionals who provided the consultation as part of the MASS intervention considered the intervention to be useful and stated that the consultation was delivered as intended in almost all cases. Students were generally satisfied with the intervention. We recommend that future research evaluates the MASS intervention in a large randomized controlled trial with a longer follow-up

Werkhervatting bij kanker: wetenschappelijk onderbouwd

Ruim 400.000 mensen leven in Nederland met kanker. Jaarlijks wordt de ziekte bij 70.000 mensen gediagnosticeerd. De verwachting is dat de incidentie van kanker tot 2015 met 40% en de prevalentie met 90% zal toenemen. De perceptie van kanker als ziekte is veranderd in de laatste decennia. Kanker heeft een chronisch karakter gekregen en de prevalentie daarvan is vergelijkbaar met andere veel voorkomende chronische aandoeningen, zoals hart- en vaatziekten, diabetes, depressie, enzovoort. De prevalentie van kanker bij vrouwen ligt hoger dan bij mannen.1 Kankerpatiënten hechten groot belang aan terugkeer naar werk en economische zelfstandigheid. Op individueel niveau betekent dit vaak de bevestiging compleet hersteld te zijn van de ziekte2 en terugkeer naar het normale leven.3 Toch lukt het niet meer dan de helft van de kankerpatiënten terug te keren naar werk.4,5 De centrale vraag in dit artikel is: wat zijn de voorspellende factoren in de terugkeer naar werk? Het zijn met name de langetermijneffecten van kanker en de behandeling die de kankerpatiënt parten spelen,6,7 zoals fysieke beperkingen, vermoeidheid, angst, depressie en cognitieve problemen. Genderspecifieke aspecten spelen daarbij een belangrijke rol. Daarnaast zijn er in het werk gelegen factoren die van invloed zijn op de werkhervatting. Door het anticiperen op een aantal van deze factoren en het onderkennen van de kwetsbaarheid van deze patiëntenpopulatie kunnen interventies ingezet worden die de terugkeer naar werk voor kankerpatiënten kunnen vergemakkelijken