Systematic review of depression in patients with multiple sclerosis and its relationship to interferonß treatment.

BACKGROUND: Multiple sclerosis is a chronic disease considered the major cause of neurological disability in young adults worldwide. While depression is considered a determinant factor of impaired quality of life and poorer prognosis among patients with multiple sclerosis, it is very often dismissed and undertreated by physicians. Depression has been related to treatment with some immunomodulatory drugs, such as IFNß. Data from patients who committed suicide during the pivotal study of interferon used as a disease modifying treatment in multiple sclerosis support this association. Moreover, there is plenty of evidence of neuropsychiatric toxicity caused by the use of IFNα as a treatment for other medical conditions. Although this link still remains relatively unknown, the presence of warnings regarding the possible relationship between depression and IFNß led to restriction in medical indications in these patients. The purpose of this paper is to try to understand the reasons for an increased prevalence in depression in multiple sclerosis and to examine the impact that IFNß treatment has on their mood. METHODS: We performed a literature search on MEDLINE and Google Scholar databases applying PRISMA guidelines for systematic reviews. Studies were included if the participants were diagnosed with MS and prescribed IFNß as the main treatment. We excluded non-english and full-text non available papers, as well as the articles where mental health was assessed exclusively as a feature of quality of life. The sample includes articles from 1980 to 2014, although filtration by year of publication was not applied and contains data from IFNß-1a and IFNß-1b. The Cochrane Collaboration Tool assessing risk of bias was used to determine the quality of the studies. RESULTS: Ten studies met full criteria for inclusion and final data extraction. The articles have heterogeneity regarding the samples, the methodology used and the expression of the results. Only three studies support the evidence of a relationship between depression and interferon, which is statistically significant in some patients at the beginning of the treatment. They suggest that only patients on IFNß treatment with a past history of depression may develop a major depression episode during the first six months. The remaining articles reviewed (including BENEFIT, BEYOND, and LTF trials) suggest the absence of an association. CONCLUSION: The reviewed studies conclude that there is not a clear relationship between IFNß and depression. A history of depression is a risk factor for developing depression during the first 6 months of treatment, nevertheless, it is not sufficient to contraindicate it. The development of new strategies is crucial for early detection of depressive symptoms. An adequate treatment can both improve the mood and deal with the neurological disease by increasing treatment adherence and interfering with inflammation. Chronic destructive brain changes and serotonergic depletion due to inflammatory factors have been proposed as the underlying cause of depression in these patients. It is suggested that these patients would have fewer functional reserve remaining to deal with stressful life events, which could precipitate a depressive disorder.

Controversias sobre los niveles plasmáticos de clozapina: revisión a propósito de un caso / Controversies regarding plasmatic levels of clozapine: review and a case report

La clozapina es el fármaco de primera elección en el manejo de la esquizofrenia resistente al tratamiento, y no existe ninguna alternativa terapéutica que haya demostrado mayor eficacia en estos pacientes. Por ello es importante optimizar el tratamiento con clozapina en la esquizofrenia resistente. Una de las herramientas clínicas de las que se dispone es la monitorización de los niveles plasmáticos del fármaco, ya que permite asegurar que el paciente está dentro del rango terapéutico y disminuye el riesgo de efectos adversos. La evidencia disponible concluye en establecer un límite inferior alrededor de los 350 ng/ml. Sin embargo, la cuestión del límite superior del intervalo es más compleja y no existe un acuerdo sobre la concentración sanguínea de clozapina que se asocia a toxicidad. Presentamos un caso clínico de un paciente con esquizofrenia resistente en tratamiento con clozapina, en el cual la monitorización de niveles plasmáticos pudo influir en las decisiones terapéuticas (AU)

Clozapine should be considered as first-line treatment in individuals with a diagnosed treatment-resistant schizophrenia. Despite alternative treatments and augmentation strategies available, there is no consistent evidence that none of these options produce substantive clinical gains when clozapine-treated patients demonstrate a suboptimal clinical response. It is therefore important that we optimize clozapine treatment in these patients. One of the clinical tools to assist in this has been therapeutic drug monitoring of plasmatic levels, because it provides drug concentrations associated with highest probability of response and a low risk of side effects. A number of studies have addressed the therapeutic range of clozapine's plasmatic level, and reviews of this topic have generally agreed that the lower threshold is around 350 ng/ml. In contrast, the issue of an upper threshold is more complex and there is no agreed for an upper limit associated with clozapine toxicity. We report a case of a patient with the diagnosis of treatment-resistant schizophrenia treated with clozapine in which we think that therapeutic drug monitoring of clozapine plasmatic could influence treatment decisions (AU)