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Suicídio e antidepressivos - pesquisa define associação


A idéia de que o uso de medicamentos antidepressivos poderia ser um fator de risco para o suicídio, partiu da observação de pacientes com depressão e que posteriormente atentaram contra suas próprias vidas, após o início da terapia antidepressiva. Mas por que isso ocorreu?

De acordo com pesquisadores americanos, do Instituo Nacional de Saúde Mental em Bethesda, nos Estados Unidos, a resposta está na genética.

A descoberta foi publicada na revista ScienceNOW. Segundo Francis McMahon, chefe da pesquisa sobre o tema, dois genes, o GRIA3 e o GRIK2 estariam relacionados a uma predisposição aumentada de suicídio.

Essa descoberta baseou-se na observação de 1915 adultos com depressão maior, que fizeram uso do citalopram (um antidepressivo inibidor seletivo da recaptação da serotonina - ISRS).

Uma pequena modificação no DNA poderia proporcionar variações nesses genes e conseqüentemente nos receptores de glutamato no cérebro - uma substância química relacionada com a memória e o aprendizado - e predisporia um indivíduo a cometer suicídio, caso fizesse o uso de substâncias como o citalopram.

Para os pesquisadores, aqueles pacientes com alterações no gene GRIA3 teriam um risco duas vezes maior de apresentar pensamentos suicidas e aqueles com modificações no GRIK2, o risco seria oito vezes maior. Quando ambos os genes estão alterados, o risco aumenta para 15 vezes.

O achado sugere, segundo McMahon, que a tendência suicida frente ao uso de antidepressivos, é uma condição g eneticamente determinada. Dessa forma, pesquisas futuras no desenvolvimento de testes de triagem genética, poderão ser utilizadas na identificação das pessoas que estão sob este risco.

O pesquisador Elliot Gershon, da Universidade de Illionois, também acredita que a descoberta permitirá o desenvolvimento de novos tratamentos contra a depressão, baseados nas diferenças genéticas individuais.

Estudos detalhados sobre o tema deverão ser realizados em breve.

Fonte: ScienceNOW Daily News

Despite what the news might have you believe, it is quite rare for a depressed person to exhibit increased suicidal thinking after they have begun treatment with an SSRI, such as citalopram (celexa). According to the statistics, so-called "treatment-emergent suicidal ideation" occurs only in approximately 4% of all people taking citalopram, whereas this same phenomenon also occurs in 2% of all placebo-treated cases. However, in those unusual cases where suicidal ideation does occur as a result of treatment with an SSRI, it can cause a great deal of distress for the people experiencing it, and for their families and close friends. Initially, this phenomenon was thought to only occur in teenagers, but later, it was found to occur at similar rates in the general population, regardless of age. As a result, the FDA-mandated a black box warning that highlighted the potential for suicidal ideation in youths, but this warning was later expanded to include adults. During a series of studies in youths into this phenomenon, it was found that the biggest risk for increased suicidal ideation occurs within a few weeks of initiating treatment with citalopram, or after a dosage adjustment. However, fortunately, none of the study subjects actually completed suicide despite increased suicidal ideation. But to gain a clearer understanding of the potential genetics underlying treatment-emergent suicidal ideation, a study was designed for adult volunteers throughout the USA who were suffering major depression. The purpose of this study was to initiate and document treatment of volunteers with citalopram and to collect and screen volunteer DNA for the identification of genetic markers that might be associated with treatment-emergent suicidal ideation. After analyzing 68 genes, the authors identified several genetic markers, GRIA3 and GRIK2, that were associated with treatment-emergent suicidal ideation, and further, they found that both these markers and treatment-emergent suicidal ideation occurred in a dose-dependent manner. Interestingly, these genetic markers were associated with the glutamate receptor pathway, which is consistent with previous data suggesting that antidepressants affect glutamate signaling. Glutamate receptors form pores through a cell membrane that, when they open, allow excitatory messages to be passed from one nerve cell and another. Also, and of clinical importance, those people who developed treatment-emergent suicidal ideation also were less likely to respond well to citalopram treatment and thus, their treatment paradigms were changed after 14 weeks. Volunteers with the GRIA3 variant showed nearly a doubled risk of developing suicidal thoughts, while volunteers with the GRIK2 variant showed an eightfold increase in risk. Those study volunteers that had both markers -- an extremely rare phenomenon -- showed a 15-fold increase in risk. "The findings suggest part of the tendency to develop this type of reaction to antidepressants might be genetically determined, and this might be used in the future to develop genetic screening tests to identify people who might be at risk," says Francis McMahon of the National Institute of Mental Health (NIMH) in Bethesda, Maryland. McMahon led the study. So does this mean that there will be a test that can predict if a person will react to treatment with a particular SSRI? Perhaps there will be in the future. However, even though the results of this study are promising, these data should be viewed as preliminary only, until further studies can be carried out to replicate the results and also to identify which gene variants are associated with the genetic markers identified by this study. Additionally, it is always important to realize that genetic analyses are no substitute for supportive medical care: people suffering from major depression should be carefully monitored by their family, friends and doctors even after they begin taking antidepressants, and whenever their antidepressant dosage is adjusted. "They are leading the field into the potential for tailoring treatments to individual gene differences and new general targets for the treatment of depression," observed Elliot Gershon, a psychiatric genetics researcher at the University of Chicago in Illinois, who wrote a companion editorial to the study. Source "Genetic Markers of Suicidal Ideation Emerging During Citalopram Treatment of Major Depression" by Gonzalo Laje, Silvia Paddock, Husseini Manji, A. John Rush, Alexander F. Wilson, Dennis Charney and Francis J. McMahon. Am J Psychiatry 164:1530-1538 (October 2007).

Publicado em 10 de Março, 2008


Copyright© Silvia Helena Cardoso