*First published in May 8, 2025
*Photograph: Flávio Dutra/JU
Health | Researchers from the Biochemistry Graduate Program found that patients who used the substance in low doses in a hospital setting showed a reduction in symptoms and an improvement in quality of life
In Brazil, where around 11 million people live with depression, an unprecedented approach is emerging as a promising alternative for diagnosing and treating the condition. The study proposes the use of inflammatory biomarkers to identify specific subgroups of patients and the subcutaneous administration of ketamine as a rapid-acting treatment. The proposal is structured around a standardized protocol, based on scientific evidence and clinical practice.
“Understanding mental illness as a broken leg.” Researcher Ana Paula Anzolin was inspired by this metaphor to dedicate her doctoral dissertation, from the Graduate Program in Biochemistry at the Federal University of Rio Grande do Sul (UFRGS), to the study of depression, which is among the fastest-growing illnesses in the country. According to the World Health Organization (WHO), Brazil has the highest prevalence of depression in Latin America and is among the countries with the most reported cases across the Americas.
Anzolin says that the research group she participates in has already observed evidence that Major Depressive Disorder (MDD) could have an organic origin in patients with onset before the age of 30. The researchers analyzed 234 individuals, divided into early and late onset of depression, to investigate this issue. The results showed elevated levels of pro-inflammatory interleukins proteins that act as chemical messengers, regulating and coordinating the immune response in early diagnosis cases, which were also associated with higher rates of suicidal ideation.
In parallel, the group also studied the effects of ketamine, which is used as an anesthetic. The study results showed that, in low doses, ketamine can also be effective in the treatment of depression and suicidal ideation, provided that it is administered by health professionals and in a hospital setting.
Based on these observations, 26 patients from Hospital de Clínicas and Hospital Moinhos de Vento, both located in Porto Alegre, were selected and included in a naturalistic protocol. This protocol aims to establish a standard, that is, a series of stages that, built on scientific evidence and clinical practice, can achieve an outcome and be replicated in public settings.
The administration of ketamine occurred in two phases:
Results and findings
From the initial applications of the protocol, patients showed a significant decrease in suicidal ideation scores, as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS). Ketamine’s rapid response is one of its distinctive features compared to conventional antidepressants, which often take weeks to become effective. A reduction in Montgomery–Åsberg Depression Rating Scale (MADRS) scores, used to assess depressive symptoms, was also observed. Besides the numbers, the reports pointed out significant functional improvements, such as regaining sleep, appetite, and social interaction.
Simultaneously, a proteomic analysis, a technique that allows the identification and quantification of proteins in biological samples to investigate possible alterations associated with inflammation and the antidepressant response, is underway. “One mother told us, ‘You gave me my daughter back.’ That’s something science needs to hear too,” comments Anzolin.
But why subcutaneous administration of ketamine?
The subcutaneous administration method was chosen over more commonly used forms, such as the intravenous route a needle is inserted directly into the vein , because it combines accessibility, prior research, and practical safety. In terms of cost, subcutaneous administration has proven to be cheaper and simpler, especially in resource-limited settings. International studies that served as the basis for the development of the protocol also indicated the effectiveness of this route. From a safety perspective, the method requires less hospital infrastructure and can be safely performed, provided it is conducted by trained professionals.
Treatment implications
During the study, the researchers also documented the first description in the scientific literature of an allergic reaction to ketamine via the subcutaneous route. One patient developed hives on the trunk and face after one of the administrations, but the case was treated with prednisolone and had no further serious complications.
The narrow therapeutic window of the substance was another important point. Doses higher than necessary can cause anesthetic effects, which require precise adjustment and continuous monitoring. Moreover, the team was also concerned with providing a welcoming environment during the treatment, since ketamine can cause psychoactive and dissociative effects, especially at higher doses.
“There were many studies on ketamine, but no clear protocol. Everyone did it in their own way. Our idea was to try to standardize it and offer a viable and safe path.”
Ana Paula Anzolin
Anzolin also highlights the challenges faced by the research team, such as the absence of a similar standardized protocol. Faced with the need to become pioneers, the team was motivated to turn into reality what they had initially only imagined.
Depression continues to increase in today’s world. As studies on this illness advance, alternatives like this one stand out as an important contribution to the physical and mental health of the population. When asked whether the Brazilian Unified Health System (SUS) could replicate this practice, Anzolin states that the research proposes a feasible and more accessible protocol, highlighting that it can be implemented, although nothing has been done about it yet.
“I’ve always wanted to do something that could reach those in need. The dissertation is about this: transforming suffering into care, based on science.”
Ana Paula Anzolin
The dissertation aims to pave the way for a safe and standardized practice, with a scientific basis and practical applicability. The author sees science as a way to directly contribute to the dignity of people who suffer from psychological distress and who often cannot escape this feeling.
Doctoral Dissertation: Neurobiology of depression and suicidal behavior: inflammatory markers and the impact of ketamine (Free Translation)
Author: Ana Paula Anzolin
Advisor: Márcia Kauer-Sant’Anna
Program/Unit: Graduate Program in Biological Sciences: Biochemistry – Institute of Basic Health Sciences (UFRGS)
Translated into English by Cristina Gueths de Aragão, undergraduate student enrolled in the course “Supervised Translation Training II (English)” of the Undergraduate Program in Language and Literature, under the supervision and translation revision of Professor Rozane Rebechi (P.h.D.) – IL/UFRGS.
:: Read in portuguese
Estudo apresenta protocolo inédito para tratamento de depressão com uso de cetamina
