When Nothing Else Works: Ketamine for Treatment-Resistant Depression

April 29, 2024

Reviewed and approved by Clínica Synaptica

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What is treatment-resistant depression?

Major depressive disorder is one of the most common psychological problems today. It can occur at practically any age, in any culture or context and, although there are factors that make one more vulnerable to it, depression is not something that can be reduced to a specific cause or reason. It is therefore a disorder that knows no barriers, and can become very debilitating, causing sick leave, hospitalizations and, in the long run, much suffering for patients and their families.

Although mental health is a topic slowly receiving increasing attention, it is still an area of public health that has been left behind. In Spain, it is estimated that there are 6 psychologists for every 100,000 inhabitants in the public health service¹, a figure indicative of the insufficiency of care in this area. Patients have to wait months for an appointment, and are often forced to attend private appointments, a financial impossibility for many.

It is estimated that 70% of patients with major depressive disorder do not reach remission (complete absence of symptoms). Among these, 20% may respond to treatment (reduction of symptoms) while 50% do not respond at all and have to try another treatment². Although the reduction of symptoms is always a good sign, the goal of treatment is to achieve remission, since residual symptoms make daily life difficult and can turn into chronic depression.

When a patient does not respond to two different treatments over the course of an year, it is usually defined as treatment-resistant depression (TRD; although the consensus on this definition is not yet global, and variations can be found). This often requires months and months of trying different medications. It is usually very expensive, can lead to hospitalization, and causes great suffering for the patient. Fortunately, ketamine has been shown to be highly effective in this population. Here we will evaluate some of this evidence.

The evidence

A recently published study by Oliver and colleagues^.3 (2022) followed 424 patients diagnosed with treatment-resistant depression over several years (between November 2017 and May 2021). Among these, many also suffered from suicidal ideation and generalized anxiety disorder. These patients underwent 6 sessions where intravenous ketamine was administered over 21 days. Depending on the clinical response, maintenance doses were also given over the following months.

Two questionnaires were administered for follow-up: the Patient Health Questionnaire-9 (PHQ-9)⁴ and the Generalized Anxiety Disorder Scale (GAD-7)⁵. These questionnaires were administered before starting treatment, and again several times throughout the sessions and the following years. With the PHQ-9, remission of depressive symptoms was detected after 6 weeks for 20% of patients, and an additional 50% had significant symptom reduction. The number of patients with remission increased with maintenance doses. Additionally, half of the patients with suicidal ideation experienced complete remission after the first 6 infusions, and there was a 30% reduction in anxiety symptomatology (GAD-7).

The authors point out that there is considerable variability in the level of response of the patients, but that there is a high benefit in continuing with the ketamine sessions after the 6 traditionally administered ones. They also point out that if patients show a good level of response but have not yet reached remission after 10 sessions, it may be useful to continue treatment. However, if the level of response has not been good during these first ten sessions, it is not recommended to continue with the treatment.

They found no effect of age or sex on response to treatment, that is, there was no better response depending on these variables. On the other hand, the research did find a better response to treatment for those with greater severity of symptoms at the beginning of the study. Future studies could investigate possible effects of other variables, such as the educational or socioeconomic level of the patient, in order to determine whether these results can be generalized to the entire population.

The great response obtained through ketamine for patients with treatment-resistant depression is great news. Thousands of people who have suffered from this disorder for years could now have access to a medicine that, with the right accompaniment, can bring them the peace they have been searching for. It is encouraging to see that the doors to the use of alternative medications, such as ketamine, are slowly opening to make way for new treatments and new research. We will continue to investigate the use of these substances in other disorders in future posts.