Ketamina: Quo Vadis?

Portas da Percepção

hempadao 17 maio, 2018

“Era o melhor dos tempos, era o pior dos tempos, era a era da sabedoria, era a era da insensatez, era a época da crença, era a época da incredulidade, era a estação da luz, foi a estação das trevas, foi a primavera da esperança, foi o inverno do desespero.”  ― Charles Dickens, A Tale of Two Cities

por Vanusa Maria Bispo

A Ketamina (cetamina) é usada diariamente em unidades de emergência em todos os lugares, para sedação e anestesia. É uma substância presente em kits de emergências médicas, humanas e veterinárias, e é geralmente usado como anestésico.

O mecanismo de ação da Ketamina só foi esclarecido na década de 1980, quando o sistema glutamatérgico e os seus receptores do tipo NMDA foram devidamente descritos e seus importantes efeitos no sistema nervoso central foram reconhecidos. A Ketamina pode agir em uma série de receptores no sistema nervoso central, como os receptores opioides e transportadores de monoaminas, mas o seu principal sítio de ação é o receptor glutamatérgico do tipo NMDA (NMDAr).

Além do uso em medicina humana e veterinária, a ketamina apresenta outro grande uso:  é uma “droga de festa”, mais conhecida como “Special K”. Ela é encontrada nas pistas de dança do mundo, onde milhares de “ravers” a usam. Em 1999, a Drug Control Administration a considerou uma droga suscetível a causar dependência e classificou-a como substância regulamentada da lista III. 

A principal preocupação, na atualidade, é a presença desta em misturas contidas em balas (ecstasy), e também vendida em pó como sendo cocaína, anfetamina e outros estimulantes. São comuns as apreensões de ketamina em falsos comprimidos de ecstasy, o que reflete a verdadeira dimensão do seu consumo e a necessidade de se obter mais e melhor informação acerca deste assunto.

Um importante fator de risco é a baixa confiabilidade das indicações que são dadas acerca da dose quando esta é vendida nas ruas. Na ausência de aconselhamento, os utilizadores de ketamina pela primeira vez tendem a mimetizar os padrões de consumo adotados para outras drogas com as quais estão familiarizados. Esta utilização, sem informação prévia, aumenta o risco de danos físicos e psicológicos. A ocorrência de fenômenos de tolerância gera uma tendência para a administração intravenosa, em detrimento do comum “sniff”, atitude que por si só acarreta uma série de riscos associados à injeção, como infecções.

Efeitos psicológicos e psiquiátricos da Ketamina

Em doses baixas, é um sedativo. À medida que a dose é aumentada, ela se torna o que chamamos de “anestésico dissociativo”, o que significa que o sistema nervoso central está quase desconectado do corpo. Isso permite que um médico ou veterinário realize uma intervenção dolorosa sem que a pessoa ou o animal sinta os efeitos. Estamos falando de dissociar a capacidade mental de responder a estímulos dolorosos. Em uma dose ainda maior, é um anestésico geral que pode levar ao coma.

Por que as pessoas consomem ketamina para festejar?

O efeito anestésico dissociativo é atraente para as pessoas que frequentam raves e festivais porque causam alucinações. Entretanto, conforme a dose utilizada e a sensibilidade do organismo, pode entrar em um “buraco de ketamina” [ K-hole ], que muitos já ouviram falar. Esta é uma gíria de como o indivíduo se sente quando toma uma dose suficientemente alta de ketamina, que sua consciência do mundo ao seu redor e seu controle sobre seu próprio corpo se torna tão prejudicado que ficará temporariamente incapacitado de interagir com os outros – ou o mundo ao seu redor.

A ketamina é uma droga dissociativa. Em termos simples, as drogas dissociativas fazem com que os usuários se sintam desapegados do ambiente, como se não estivessem realmente lá. Esse sentimento de dissociação torna-se mais intenso com dosagens mais altas, o que faz com que os usuários se sintam muito desconectados e inconscientes de seu ambiente – mesmo quando estão tecnicamente acordados. Eles também podem se sentir desconectados ou incapazes de controlar seus próprios corpos, incluindo a capacidade de falar e se mover facilmente. E, desse modo, ficam propensos a quedas e acidentes. .

Uma maneira de pensar sobre isso é que o “buraco k” é um estado entre a intoxicação e o coma. Enquanto a consciência do mundo real diminui em um buraco, um mundo de fantasia de delírios e alucinações pode assumir o controle. Isso geralmente é temporário, embora os usuários em longo prazo possam começar a apresentar sintomas dissociativos e psicóticos contínuos – há perda da percepção precisa do mundo à sua volta mesmo após o desaparecimento da droga no organismo.

Uso da Ketamina para Depressão

A Organização Mundial da Saúde (OMS) lista a ketamina entre seus registros de “medicamentos essenciais” graças ao amplo uso da droga como analgésico e anestésico. Isso permite que os médicos prescrevam a substância “off-label” para transtornos mentais, como depressão clínica. Os resultados são extremamente promissores.

Supostamente mostrando resultados em horas ao invés de semanas, a ketamina afeta os níveis do neurotransmissor glutamato, enquanto os antidepressivos tradicionais, como o Prozac (fluoxetina), concentram-se nos receptores de serotonina. A administração de ketamina por via intravenosa mostrou aumentar rapidamente os níveis dessas proteínas sinápticas, com efeitos significativos observados após duas horas.

Atualmente, em um novo estudo publicado no American Journal of Psychiatry (AJP), uma formulação de um enantiômero derivado da ketamina, em spray nasal, mostrou-se promissora no tratamento rápido de sintomas de depressão maior e pensamentos suicidas.

O estudo duplo-cego comparou o tratamento padrão com uma formulação intranasal de esketamina,  mais um placebo, para tratamento rápido de sintomas de depressão maior, incluindo suicidalidade, entre indivíduos em risco iminente de suicídio. O estudo envolveu 68 participantes distribuídos aleatoriamente em um dos dois grupos – recebendo esketamina ou placebo duas vezes por semana durante quatro semanas. Todos os participantes continuaram a receber tratamento com antidepressivos. Os pesquisadores analisaram os efeitos às quatro horas após o primeiro tratamento, às 24 horas e aos 25 dias.

O estudo foi conduzido por pesquisadores da Janssen Research and Development e Janssen Scientific Affairs, Titusville, NJ, e San Diego, e da Escola de Medicina de Yale, New Haven, Connecticut. Eles encontraram uma melhora significativa nos escores de depressão e diminuição da ideação suicida no grupo esketamina, em comparação com o grupo placebo, às quatro horas e às 24 horas. A medição do risco de suicídio levou em consideração tanto as perspectivas do paciente quanto do clínico.

De acordo com os autores, os resultados do estudo indicam a pulverização nasal de esketamina como um possível tratamento rápido e eficaz para sintomas depressivos em pacientes avaliados em risco iminente de suicídio. A esketamina pode ser um tratamento importante para preencher a lacuna que existe devido ao efeito retardado dos antidepressivos mais comuns. A maioria dos antidepressivos leva de quatro a seis semanas para se tornar totalmente eficaz. Este estudo está na fase 2, e a esketamina ainda deve passar por um estudo de fase 3, antes da possível aprovação pelo FDA (Food and Drug Admistration).

Considerações Finais

A empolgação com a ketamina, e seus derivados, mostra o quanto são necessárias pesquisar novas drogas dentro da psiquiatria. Muitas empresas farmacêuticas fecharam suas divisões de saúde mental nos últimos cinco anos e não houve avanços significativos na medicação para a depressão. Agora as empresas esperam lucrar com o desenvolvimento de variações patenteáveis ​​da ketamina no tratamento da depressão.

Entretanto a ketamina não é a única, mas sim uma das várias drogas cujo efeito terapêutico promissor tem sido confirmado pela neurociência e psiquiatria. Em estudos aprovados pela FDA, doentes com estresse pós-traumático respondem muito bem ao uso de MDMA (Ecstasy). E, pesquisas recentes, também mostram que o LSD e a Psilocibina (o ingrediente ativo dos “cogumelos mágicos”) são efetivos no tratamento de ansiedade em doentes terminais.

E acreditamos que atualmente um grande avanço está acontecendo dentro da farmacologia e ciências farmacêuticas, ao se investigar novos usos terapêuticos para drogas já existentes, e seus benefícios para a saúde publica. Com certeza um grande avanço,  como o exemplo da ketamina, uma droga antiga e até considerada obsoleta no campo da anestesiologia.

Mas algumas questões merecem ser avaliadas e questionadas acerca desses avanços.

1- Porquê não houve um interesse maior em estudar a ketamina na sua forma original?  A resposta poderia ser porque tem custo barato e não pode mais ser patenteada. Diferente da suas formas racêmicas como a esketamina, que poderão ser patenteadas e os custos elevados a padrões altíssimos pela industria dos “antidepressivos” na psiquiatria. 

2- Porquê as industrias farmacêuticas também não investem parte do dinheiro das pesquisas para estudos que avaliem também os potenciais de abuso e os potenciais de riscos e danos? Do uso em suas formas de aquisição ilegal – em centros médicos, veterinários e agropecuárias.
3- Porquê as industrias farmacêuticas também não investem parte do dinheiro das pesquisas em campanhas de educação para jovens que as consomem como drogas recreacionais?

É simples, isso tudo daria muito trabalho e, certamente, pouco lucro. Infelizmente, muitos jovens desconhecem os riscos.

Vanusa Maria Bispo: neurocientista, professora adjunta de neuropsicofarmacologia (UDESC) e editora da página @Redução de Danos e Pscience Blog

Referências para consulta:
Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression A Randomized Clinical Trial
I Used Ketamine to Treat My Depression
Study Shows Fast-Acting Benefits of Ketamine for Depression and Suicidality; Caution on the Potential for Abuse and the Need for Effective Controls
Rave Drug “Special K” Holds Promise for Treating Depression Fast
What is a K Hole?
Todo lo que tienes que saber antes de tomar ketamina



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