What is treatment-resistant depression?
Major depressive disorder is one of the most common psychological problems today. It can appear at practically any age, in any culture or context, and although there are factors that make some people more vulnerable, depression cannot be reduced to a single concrete cause. It is, therefore, a disorder that knows no boundaries and can become very debilitating, leading to sick leave, hospitalizations, and, in the long term, much suffering for patients and their families.
Although mental health is receiving increasing attention, it remains an area of public health that needs improvement. Here in Spain, it is estimated that there are 6 psychologists for every 100,000 inhabitants in the public health system¹—a figure that highlights the inadequacy of care in this field. Patients must wait months for an appointment and often find themselves forced to turn to private consultations, which are economically impossible for many.
It is estimated that 70 % of patients with major depressive disorder do not achieve remission (complete absence of symptoms). Among these, 20 % may respond to treatment (symptom reduction), while 50 % do not respond at all and must try another treatment². Although symptom reduction is always a good sign, the goal of treatment is to achieve remission, since residual symptoms make daily life difficult and can lead to chronic depression. When a patient does not respond to two different treatments over a year, it is usually defined as treatment-resistant depression (although the consensus on this definition is not yet global, and variations exist). This involves months and months of trying different medications. It is often very costly, may require hospitalization, and causes great suffering for the patient. Fortunately, ketamine has shown high effectiveness in this population. Here we will review some of the evidence in its favor.
The evidence
A very recent study published by Oliver and his collaborators³ (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 in which intravenous ketamine was administered over 21 days. Depending on clinical response, maintenance doses were also administered in the following months.
To carry out the follow-up, two questionnaires were used: 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 in 20 % of patients, and an additional 50 % showed a significant reduction in symptomatology. The number of patients in remission increased with maintenance doses. In addition, half of the patients with suicidal ideation experienced complete remission after the first 6 infusions, and there was a 30 % reduction in anxiety symptoms (GAD-7).
The authors note that there is considerable variability in the level of patient response but that there is significant benefit in continuing ketamine sessions beyond the traditionally administered six. They also point out that if patients show a good level of response but have not yet achieved 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, continuing treatment is not recommended.
No age or sex effect was found in treatment response; that is, there was no better response depending on these variables. On the other hand, the study did find a better response among those with more severe symptoms at the beginning of the study. Future research could explore potential effects of other variables, such as the patient’s educational or socioeconomic level, to determine whether these results can be generalized to the overall population.
The strong response obtained through ketamine for patients with treatment-resistant depression is highly significant news. Thousands of people who have suffered from this disorder for years could now have access to a medication that, when properly supervised, can bring them the peace they have been seeking for so long. It is encouraging to see that the doors to alternative medications, such as ketamine, are slowly opening up to allow for new treatments and new lines of research. We will continue exploring the use of these substances in other disorders in future posts.
References
2 https://pmc.ncbi.nlm.nih.gov/articles/PMC6982454/pdf/ndt-16-221.pdf
