Ketamine: Essential Medicine and Potential Antidepressant?
This dissociative drug is much more than horse tranquilizer.
Many of us struggle to think of the medical potential recreational drugs hold. So, what’s the deal with ketamine?
Ketamine is a dissociative anaesthetic drug. Although it is harmful when used in large and frequent quantities, it is on the WHO’s list of essential medicines.
Why, you ask? It is safer than other anaesthetic drugs because it doesn’t depress breathing or lower blood pressure. This means expensive patient-monitoring equipment isn’t required, making ketamine an essential and life-saving anaesthetic, especially in low and middle income countries.
The WHO Expert Committee on Drug Dependence has stated the medical benefits of ketamine far outweigh the harms of recreational drug use. Though dependence and overdose from ketamine is rare, recreational use is not without harm —for instance, excessive use runs the risk of urinary tract problems.
Recently, there has been an extensive and promising upheaval of research for ketamine being used in treating depression.
As depression is a leading cause of disability worldwide and existing treatment outcomes are still limited, this is incredibly important research.
Why might ketamine be effective for treating depression?
Depression is associated with impairments in the brains reward system. Ketamine appears to target this circuitry through activating synaptic plasticity through disrupting past memories. This means synapses in the brain strengthen, promoting communication between them — this is thought to contribute to improved depression outcomes.
Additionally, antidepressants take a while to initiate effect (around 6 weeks).Whereas, ketamine shows efficacy with rapid acting antidepressant effects (within hours).
So, what does the evidence look like?
Preliminary findings have shown effectiveness for improved suicidal cognition and feasibility for acute treatment of treatment resistant depression.
More recent clinical trials demonstrate administering ketamine intravenously 2 or 3 times weekly for 4–6 weeks achieve a rapid antidepressant onset efficacy in treatment resistant patients.
A systematic review examining the efficacy of ketamine in treatment resistant depression confirms there are significant clinical improvements in depressive symptoms. These improvements are detectable within just an hour of administration.
Although this is very promising, this research isn’t without limitations.
The long-term efficacy of ketamine has not been investigated as these trials are not longitudinal. Meaningful change in depression is impossible to study in just 4–6 weeks — as it is a chronic condition, a longer trial duration or follow-up is needed to truly understand whether ketamine can maintain these effects.
Furthermore, improvements in depression within just an hour of administration may mean the drug effects are more to do with intoxication, rather than long-term change.
There are also important safety considerations for ketamine administration. Sub-anaesthetic doses are used for treating depression (between 0.1 and 1mg/kg). Although a small dose, it can be associated with neurocognitive disturbance, dissociation and short-lived physiological changes such as increased heart rate and blood pressure. It is important to prepare patients psychologically for treatments, as side-effects could be perceived as distressing.
Given ketamine is a recreational drug, there is also the potential for abuse. However, the harms of this are largely minimised due to administering the drug in a clinical setting.
Given the wide range of individual differences in the presentation of depression, it is difficult to predict the efficacy of ketamine. Further research will help us understand and develop screening procedures to appropriately prescribe ketamine for depression.
Research into ketamine for treatment resistant depression is extremely promising. However, it is important to remain mindful that our understanding of this treatment is still limited. Longitudinal studies will help us understand ketamine’s true antidepressant potential and what effects repeated dosing has.
