What is Treatment Resistant Major Depression?
Major depression is a medical condition characterised primarily by a state of sadness, feelings of emptiness or depression and a loss of interest in everyday activities. The development of major depression is variable in terms of severity of symptoms, recurrence of depressive episodes and duration of periods of symptomatic remission. However, to be considered major depression, symptoms must cause significant social and occupational impairment for at least two weeks.
More than half of people with depression do not remit after the first treatment and one third fail to remit after multiple treatments. When a person does not respond adequately to two courses of treatment with different drugs, they may develop what is known as treatment-resistant major depression.
- What treatments are available for Treatment Resistant Major Depression?
Clinical practice options for treating people with treatment-resistant major depression include increasing the dose of their usual medication, switching to a different drug, or combining pharmacotherapy with appropriate psychological treatment.
People with highly resistant depression may opt for techniques such as electroconvulsive therapy, repetitive transcranial magnetic stimulation or deep magnetic stimulation. However, these procedures have some logistical limitations that make long-term therapy difficult.
For some years now, studies with ketamine have shown rapid and robust efficacy in the treatment of treatment-resistant major depression, and are considered to be the major pharmacological breakthrough of the last 50 years.
Is ketamine a safe drug?
Ketamine has been used as an anaesthetic in hospital practice for 50 years, demonstrating a level of safety that few other drugs have achieved. The fact that it does not alter the respiratory system or the ability to swallow, and that it produces only mild stimulation of the cardiovascular system, has led to its frequent use in children with congenital heart disease. However, it is not recommended for use in people with severe hypertension. Despite its high safety, ketamine can evoke powerful psychoactive effects when administered at anaesthetic doses, causing a transient state of altered consciousness. This is the main reason why it has not been used indiscriminately in hospital practice. However, the psychoactive effects are minimal at doses commonly used in the treatment of resistant depression.
However, as this altered state of consciousness may be attractive to some people, recreational use of ketamine has become widespread internationally over the last decade. Such use has, in rare cases, led to patterns of daily abuse that have been interpreted as a dependence response to ketamine. However, there is no clear scientific evidence that ketamine produces a psychophysiological dependence, nor a withdrawal syndrome when it is withdrawn. In any case, the pattern of ketamine administration used in the treatment of depression avoids any risk of abuse and dependence.
- What are the differences between ketamine treatment and other antidepressant drugs?
There are three relevant differences between ketamine and classical antidepressants in the treatment of resistant depression.
The most important difference is efficacy. Scientific evidence shows that in those people who do not experience symptomatic relief after going through two different courses of antidepressants, almost half of these patients can improve significantly after a single administration of ketamine.
Another important difference is the speed with which ketamine exerts its antidepressant effect. While conventional drugs take between two and six weeks to take effect, a meta-analysis study has shown that 36% of 561 patients improved significantly within 24 hours, 41% within 24 hours and 48% between 2 and 7 days after a single infusion of ketamine. This is a key factor especially in those at risk of suicide, as rapid dilution of suicidal thoughts can prevent fatal events.
Finally, while antidepressant drugs can cause side effects in some people, such as gastrointestinal problems or decreased sexual desire, ketamine administration does not produce side effects. Exceptionally, cases of ulcerative cystitis have been reported in recreational users who have abused ketamine or used it daily for chronic pain relief. However, to date, there are no clinical cases that have experienced this type of problem with the dosing regimens used in the treatment of resistant depression.
- What psychological effects can be felt during a ketamine infusion?
Although the doses of ketamine used in the treatment of depression are very low, some people may experience feelings that they have not felt before. The most common sensations may be dizziness, distortions in the sensation of one’s own body (such as a slight feeling of buoyancy) or distortions in the visual perception of external stimuli. Other people may connect with significant aspects of their therapeutic process. Although the intensity of these sensations is usually relatively low, they can be experienced positively or negatively depending on the individual. However, the psychological material that may emerge during the acute effects may be relevant from a psychotherapeutic aspect. For this reason, it is not considered that these psychological effects should be avoided, but rather the opposite. In order to promote a state of introspection that favours the connection with the therapeutic process, the patient will lie down in a comfortable armchair, wearing an eye mask and headphones through which he/she will be able to listen to quiet music chosen especially for this purpose.
The patient will be monitored and under medical observation during the 40 minutes of ketamine administration, so that the treatment can be interrupted if the patient wishes. A period of rest may be required afterwards until the person is fit enough to leave the clinic. The estimated time to complete the entire treatment does not usually exceed one and a half hours, and is always an outpatient regimen.
- How long do the antidepressant effects of ketamine last?
In most patients, ketamine produces a rapid and robust, though transient, antidepressant response. However, the prolongation of antidepressant effects is highly variable depending on the individual. Clinical studies show that antidepressant effects can be sustained for one week to three months after administration of a single infusion. However, it is also known that the antidepressant effect of ketamine is cumulative, so it is recommended to follow a pattern of repeated doses. Thus, the antidepressant effects have been maintained for more than 15 months after the last infusion.
However, the prolongation of the antidepressant effects may also depend on the role of the patient in the therapeutic process. Ketamine can facilitate the learning of cognitive and behavioural techniques focused on symptom regulation, so psychotherapeutic support during the period of drug administration is particularly recommended. In this way, pharmacological intervention together with psychotherapeutic intervention can have a catalytic effect that maximises and prolongs the benefits of treatment.