Consequently, TRD, affecting up to 20% of the population, has become a significant concern, especially in countries like South Africa, where poverty and violence exacerbate depression rates.
Conventional treatments, such as combining antidepressants or augmenting them with atypical antipsychotics and lithium, are not always effective, necessitating alternative approaches.
Ketamine offers a groundbreaking treatment option as the first non-monoaminergic antidepressant. Unlike traditional antidepressants, it targets the glutamate system, particularly the NMDA receptors, promoting rapid neural growth and synaptic plasticity, resulting in fast-acting antidepressant effects.
Additionally, it influences GABAergic interneurons, which contributes to sustained benefits. Despite these promising effects, concerns about ketamine’s long-term safety, efficacy, and potential for abuse remain.
Ketamine has demonstrated clear effectiveness in treating TRD and acute suicidal ideation. Its ability to rapidly reduce suicidal thoughts is particularly notable, with relief often occurring within hours.
This rapid response makes ketamine a valuable alternative to more invasive interventions like electroconvulsive therapy, giving hope to patients in acute crisis. However, research is still ongoing regarding ketamine’s potential in treating other conditions such as post-traumatic stress disorder, obsessive-compulsive disorder, eating disorders, and substance use disorders. Determining its exact role in the treatment algorithm and appropriate patient selection are critical areas of investigation.
Difficult-to-treat depression
The term difficult-to-treat depression is becoming increasingly preferred over TRD. This shift in terminology maintains hope for patients by suggesting that treatment options are still available. TRD is defined as the failure of two antidepressants administered at the maximum tolerated dose for an adequate time (usually two weeks). Given the complexity of TRD, treatment needs to be aggressive and prompt, as prolonged untreated depression becomes more difficult to manage.
Clinicians are advised to adjust treatment strategies if no response is observed within two weeks or if only partial improvement is noted. Tools such as the PHQ-9 help clinicians monitor the severity of depression and track patient progress.
In clinical practice, more than two antidepressants may be tried, and strategies such as medication augmentation and psychotherapy (particularly cognitive-behavioral therapy) play crucial roles in treatment plans. The PHQ-9 is also useful for medical aid submissions and treatment approvals, streamlining the administrative process for patients requiring advanced therapies.
Ketamine’s tolerability and safety are generally positive, though some adverse effects exist. Dissociation, a hallmark effect of ketamine, is a point of debate among clinicians. While European psychiatrists like Dr Rochefri Kasper consider it an undesirable side effect, some American psychiatrists view it as potentially therapeutic.
However, dissociation is not necessary for ketamine’s antidepressant effects. High doses to induce dissociation can increase the risk of addiction, as patients may seek progressively higher doses. Other neurological effects, such as drowsiness and unsteadiness, are common, and ketamine can raise blood pressure due to its cardiac stimulation effects. There are also concerns about ketamine-induced bladder issues, particularly with long-term abuse.
Despite these risks, studies indicate no significant increase in abuse potential when ketamine is properly administered for psychiatric conditions. However, caution is warranted for patients with psychotic disorders, active substance abuse, or uncontrolled hypertension.
Ketamine treatment requires a psychiatrist's oversight
Ketamine treatment typically requires a psychiatrist’s oversight, though administration is often handled by sedation specialists. A safe, private environment is essential during administration due to the dissociative effects of ketamine, and patient monitoring by trained sedationists is critical.
The South African Society of Anaesthesiologists provides detailed guidelines regarding sedation expertise and necessary equipment, including blood pressure and pulse monitors and resuscitation devices.
In addition to medical equipment, comfort measures such as blankets, eye masks, and calming music contribute to a positive patient experience. Music has been shown to reduce dissociation, anxiety, and even hypertensive changes during ketamine administration. Although post-session integration is debated, adequate preparation, including mental and physical readiness, remains key to a successful treatment process.
As the field evolves, ketamine’s role in acute suicidality and potential for maintenance treatments is gaining traction, though further research is needed, especially regarding long-term use and the integration of ketamine-assisted psychotherapy into mainstream clinical practice.
To watch a replay of the webinar, click here.
