Introduction
Depression affects millions of people worldwide and remains a leading cause of disability and diminished quality of life. For those struggling with depression, standard treatment options such as antidepressant medications and psychotherapy can be life-changing. However, these therapies do not work for everyone. Dissatisfaction with current medications often arises from their delayed onset of action, undesirable side effects, or limited effectiveness. Additionally, some individuals may need robust relief quickly, especially when grappling with severe or treatment-resistant depression (TRD).
Others may be hesitant to add more medication to their regimen or are drawn to the potential benefits of novel, science-backed approaches such as psychedelic medicine. Ketamine, a medication originally used as an anesthetic, has emerged as a promising option in this space. This article explores ketamine therapy’s role in treating depression and addresses key questions for those considering this innovative treatment.
Ketamine for Depression
Ketamine, once primarily recognized as an anesthetic, has gained attention over the past two decades for its antidepressant properties. Unlike traditional antidepressants that primarily target serotonin, norepinephrine, and dopamine, ketamine works by modulating the brain’s glutamatergic system, specifically the N-methyl-D-aspartate (NMDA) receptor (Newport et al., 2015). This unique mechanism may explain its rapid onset of action, which often occurs within hours of treatment (Zarate et al., 2006).
Clinical studies have demonstrated ketamine’s efficacy in alleviating symptoms of TRD. In these cases, patients who have not responded to multiple trials of conventional antidepressants often report significant symptom reduction after ketamine therapy (Berman et al., 2000). Additionally, ketamine’s rapid-acting properties make it a valuable option for those experiencing acute suicidal ideation (Canuso et al., 2018).
How Many Ketamine Treatments for Depression?
The exact number of ketamine treatments needed varies by individual and clinical circumstances. Initial treatment protocols typically involve six infusions over two to three weeks. Research has shown that this intensive phase often leads to significant symptom improvement (Phillips et al., 2019). After the initial series, maintenance therapy—which may involve periodic infusions or other ketamine formulations such as intranasal esketamine—can help sustain remission (Wilkinson et al., 2018).
It is crucial to work with a qualified, ideally psychiatry-trained, provider who can tailor the treatment schedule to individual needs and monitor progress. Regular assessments help determine whether additional treatments are necessary or if adjustments to other aspects of the care plan are warranted.
Ketamine Therapy
Ketamine therapy is typically administered in a controlled medical setting under the supervision of trained professionals. The most common route of administration is intravenous (IV), although other formulations, such as intranasal esketamine (approved by the FDA as Spravato™), are also available (Dore et al., 2019).
During a ketamine infusion, patients are monitored for safety and comfort. Sessions usually last about 40 minutes, and most individuals report feeling relaxed or mildly dissociated. These effects generally subside shortly after the infusion. While ketamine therapy is considered safe when administered by trained professionals, side effects such as dizziness, nausea, or temporary increases in blood pressure may occur.
The therapeutic benefits of ketamine often extend beyond its pharmacological effects. Many patients find that the experience fosters introspection, emotional release, and a renewed sense of hope—all of which can complement traditional psychotherapy (George et al., 2021).
Ketamine-Assisted Psychotherapy
Ketamine-assisted psychotherapy (KAP) combines the pharmacological effects of ketamine with structured psychotherapeutic sessions to enhance treatment outcomes. In this approach, ketamine is used to facilitate a state of heightened introspection and emotional openness, which therapists can guide to explore underlying issues contributing to depression or anxiety (Dore et al., 2019).
KAP sessions typically involve preparatory discussions, the ketamine experience itself, and integrative therapy afterward to process insights gained during the session. This holistic approach not only aims to alleviate symptoms but also promotes long-term psychological growth and resilience.
Ketamine Side Effects
While ketamine is generally well-tolerated in clinical settings, it is important to be aware of potential side effects. Common short-term effects include dizziness, nausea, increased blood pressure, and a sense of dissociation or feeling "out of body." These effects typically resolve shortly after the session.
Rarely, ketamine may cause more serious side effects such as bladder irritation or cognitive disturbances, particularly with long-term use or at high doses (Short et al., 2018). Patients with certain medical conditions, such as uncontrolled hypertension or a history of psychosis, may not be ideal candidates for ketamine therapy. A thorough evaluation by a qualified provider can help mitigate risks and ensure the safety of the treatment.
Is Ketamine Addictive?
Ketamine has a history of recreational misuse, raising questions about its potential for addiction. However, the risk of addiction in a therapeutic context appears low. Medical ketamine therapy is administered in carefully controlled settings and at doses far below those typically associated with recreational use (Morgan et al., 2012).
Research suggests that ketamine’s abuse potential is linked to its euphoric and dissociative effects, which are minimal or absent when used therapeutically (Short et al., 2022). Nonetheless, it is essential for providers to screen patients for a history of substance use disorders and to monitor for any signs of misuse during treatment.
Ketamine for Anxiety
In addition to its antidepressant effects, ketamine shows promise in treating anxiety disorders. Studies have indicated that ketamine can reduce symptoms of generalized anxiety disorder (GAD), social anxiety disorder (SAD), and post-traumatic stress disorder (PTSD) (Feder et al., 2014). The mechanisms underlying these effects are thought to overlap with those responsible for its antidepressant properties, including enhanced synaptic plasticity and modulation of glutamate pathways (Vialou et al., 2022).
Patients with comorbid depression and anxiety often experience improvements in both conditions following ketamine therapy. However, more research is needed to establish optimal dosing protocols and long-term outcomes for anxiety-specific treatment.
Is Ketamine a Psychedelic?
Ketamine is often grouped with psychedelics due to its ability to induce altered states of consciousness. However, it differs from classical psychedelics like psilocybin or LSD in both its mechanism of action and subjective effects. While classical psychedelics primarily act on serotonin 5-HT2A receptors, ketamine targets the NMDA receptor (Zanos & Gould, 2018).
The dissociative experience associated with ketamine—sometimes described as a “dreamlike” or “out-of-body” sensation—can be therapeutic in itself, allowing individuals to process emotions and memories from a new perspective (Dore et al., 2019). However, these experiences are distinct from the more expansive or mystical states commonly associated with classical psychedelics.
Summary
Ketamine therapy represents a promising advancement in the treatment of depression, particularly for individuals who have not found relief with conventional approaches. Its rapid onset, unique mechanism of action, and potential to alleviate comorbid conditions like anxiety make it an appealing option for many. However, ketamine therapy is not without risks and requires careful oversight by qualified professionals.
If you are considering ketamine therapy, consult with a licensed provider to discuss whether this treatment is right for you. Together, you can explore the potential benefits and risks, and create a personalized plan to support your mental health journey.
About the Author
Dr. David George is a multiple-board certified, practicing clinician and innovator in the field of integrative psychiatry and neurological health. As the founder of Neuregen Integrative Psychiatry and Neurologic Health Center, and a ketamine clinic near Scottsdale, AZ, Dr. George specializes in cutting-edge treatments for mental health and brain-based conditions. Neuregen offers all forms of ketamine therapy, including ketamine infusions and ketamine-assisted psychotherapy, as part of a comprehensive program tailored to each individual’s unique needs. With a commitment to compassionate care and evidence-based practices, Neuregen empowers patients to achieve lasting well-being.
References
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