Dose-dependent development of depressive symptoms during adjuvant interferon-{alpha} treatment of patients with malignant melanoma.

BACKGROUND: Adjuvant IFN-α treatment for patients with malignant melanoma is often complicated by depression. The influence of dosage, however, is unknown. OBJECTIVE: The authors sought to elucidate this dosage effect. METHOD: Using the Zung Self-Rating Depression Scale and the German Bf-S Self-Rating (Affectivity) Scale, the authors prospectively compared the frequency and severity of IFN-α-induced depressive symptoms between a group of 29 patients receiving low-dose and 17 patients getting high-dose induction therapy for 4 weeks. RESULTS: Patients receiving high-dose induction treatment had significantly higher depression scores after 4 weeks, and significantly more patients in the high-dose group developed depression. CONCLUSION: The authors concluded that frequency and severity of IFN-α-associated depression during melanoma treatment are dose-dependent.

Risperidone monotherapy in manic inpatients: an open label, multicentre trial.

OBJECTIVE: The efficacy of risperidone in acute mania has been established in several controlled clinical studies. However, this may not necessarily resemble the clinical effectiveness of this treatment, as patient populations in controlled studies are considered as being not representative. This study examined risperidone monotherapy in a sample of severe manic patients in admission ward settings. METHODS: Open label monotherapy with risperidone was examined for 3 weeks in 30 inpatients. Subjects were evaluated with structured clinical rating scales: Young Mania Rating Scale (YMRS), Clinical Global Impression, bipolar version (CGI-BP), and the Extrapyramidal Symptom Rating Scale (ESRS). In addition, the amount of concomitant use of benzodiazepines was documented. Data were analysed using a last observation carried forward method on all subjects given medication at baseline. RESULTS: Significant improvement from baseline to exit was observed both for the YMRS and CGI-BP. Responder analysis revealed that two-thirds of the patients showed a reduction of 50% in the YMRS score, and 69% of the patients were rated as very much improved or much improved on the CGI-BP mania scale at study exit. Only three patients dropped out due to adverse events, in one case due to extrapyramidal symptoms. CONCLUSIONS: The efficacy of risperidone in the acute treatment of mania as observed in controlled studies could be replicated in this open monotherapy study in a severely manic inpatient population. Considering the mean maximal dosage of 5.5+/-0.9 mg risperidone, the tolerability and safety profile appeared satisfactory.

Pretreatment levels of sTNF-R1 and sIL-6R are associated with a higher vulnerability for IFN-alpha-induced depressive symptoms in patients with malignant melanoma.

Immunomodulatory therapy with interferon-alpha (IFN-alpha) often leads to neuropsychiatric side effects, especially depression. An activation of the immune system is discussed to trigger neurotransmitter changes and depressive illness. So far, few data are available about biologic markers, who may predict the individual risk for developing depressive symptoms during IFN-alpha therapy. The aim of the present study was to investigate the predictive role of certain immunologic markers for the development of IFN-alpha-induced depression. We hypothesized that patients characterized by a proinflammatory and TH1-accentuated immune response before treatment might have an increased risk for developing depressive mood changes. Thirty-three melanoma patients were prospectively investigated during adjuvant treatment with IFN-alpha-2a/2b (3 x 3 Mio units/wk). Depressive mood changes were assessed with the self-rating depression scale (SDS, Zung-scale) before and during IFN-alpha treatment. Serum concentrations of soluble tumor necrosis factor-R1 (sTNF-R1), soluble interleukin-6R (sIL-6R), sIL-4R, and neopterin were measured before and after 3 months of treatment. sIL-6R, which was negatively associated with SDS scores, significantly predicted higher depression scores in the first 3 months of IFN-alpha treatment. sTNF-R1, which was positively associated with SDS scores, significantly predicted the development of late depressive symptoms after 6 months of therapy. In contrast to the initial hypothesis, patients characterized by high sTNF-R1 and low sIL-6R baseline levels, indicating an anti-inflammatory condition before therapy, had a higher vulnerability for depression during IFN-alpha therapy.