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Long-Term Effects of Ketamine Treatment for Bipolar Depression

by | Oct 22, 2024 | bi polar, Ketamine Therapy, Uncategorized | 0 comments

Long-Term Effects of Ketamine Treatment for Bipolar Depression

In our previous blog (“Beyond Mood Swings: Ketamine Therapy for Bipolar Disorder”), we shared information about bipolar depression, the difference between Bipolar I & II, and how we approach the two differently when treating with ketamine.  We wanted to dive deeper into the topic with a more comprehensive overview.  Below, we describe of how ketamine works and considerations pertaining to the long-term effects of ketamine therapy.

How Ketamine Works as a Bipolar Depression Treatment

Ketamine is known for its rapid anti-suicidal effect, often after a single administration.   This is pivotal for treating bipolar disorder, as suicide accounts for 15–20% of deaths in bipolar disorder patients.  Another primary benefit of treating bipolar with ketamine is that it can reduce the cycling pattern of the disorder. By relieving depression symptoms, a patient can stay in a state of euthymia (normal, baseline mood).  This avoids the extreme highs and lows.

The Science – Looking At the Molecular Level

At the molecular level, ketamine impacts the following areas as well:

Antidepressant effect

Many different mechanisms have been proposed for the antidepressant effects of ketamine.

    • Alteration in opioid receptors that allow our own endorphins to work better
    • Changes in glutamate receptors that alter how brain cells relate to one another and promote nerve growth
    • Activation of the BDNF-TrkB cascade (a protein system important for cell health and growth) in certain parts of the brain important for emotion and learning

All of these probably play a role in the long-term antidepressant effects of ketamine.

Neuroplasticity and BDNF

Studies have shown that low levels of BDNF are associated with an increased severity of bipolar episodes.  This suggests the use of ketamine as a viable treatment option for bipolar patients, given that ketamine increases BDNF.

Synaptogenesis

Synaptogenesis is the process of forming connections, or synapses, between cells in the nervous system.  Evidence from preclinical studies has shown that ketamine rapidly induces synaptogenesis and reverses the synaptic associated with chronic stress and bipolar disorder.

Immunological Effects

Multiple epidemiologic studies have found an association between bipolar disorder and immune dysfunction.  Chronic infections, autoimmune disorders, metabolic disorders, and cardiovascular disease occur at higher rates in people with bipolar disorder.  Some researchers have argued that inflammation is an important factor in determining disease severity and progression.  Ketamine has a strong anti-inflammatory effect, especially in specialized immune cells of the brain and spinal cord called microglia.

Microbiota

The brain-gut-microbiota axis has a role in the pathophysiology of depression and bipolar disorder. This occurs through its involvement with the immune system, endocrine system, and vagus nerve.  Evidence suggests that ketamine alters the makeup of the gut microbiome in a manner that decreases inflammation.  It also increases butyrate which has an antimanic effect.

It’s no wonder that ketamine is considered a “game-changer” when treating bipolar depression.  As practitioners, we welcome these positive effects in the short term, while maintaining a long-term view of patient health and well-being.

The Long-Term Effects of Ketamine Therapy

While short-term improvements are well-documented, the sustainability of these benefits and the potential for adverse effects over time remain areas of active research.

Efficacy Over Time:

One of the key concerns with long-term ketamine treatment is the durability of its effects. There are no clinical studies that look at outcomes of many years. Being actively engaged in therapy and behavioral change while getting ketamine treatment helps “rewire” the brain to promote lasting change.

Potential for Dependency:

Another concern that some people have is the potential for abuse, dependency or addiction. While ketamine does not cause physical addiction, its euphoric and dissociative effects can be an appealing escape from everyday life for some people.  Abuse is rare and abuse that begins with treatment even rarer but any medicine can be dangerous if taken outside the appropriate context.  Ketamine treatment in a clinic under the care of a physician and therapist is a structured “set and setting” for therapeutic use of this effective treatment. We do not prescribe ketamine outside our clinic, nor do we recommend using it in any other setting.

Cognitive and Psychological Effects:

Long-term ketamine use may also have cognitive and psychological effects. Some studies suggest that repeated ketamine infusions could impact cognitive functioning, including memory and attention, while others show that the antidepressant effect improves function. There is a risk of exacerbating underlying psychotic symptoms in some individuals so we do not usually recommend ketamine therapy for people with a history of psychosis or a strong family history of psychoses.

Safety and Side Effects:

Ketamine seems to be a very safe medication but long-term studies of therapeutic administration have not been published.  People who abuse ketamine, using high doses over a long period of time, may experience bladder dysfunction, liver toxicity, and cardiovascular issues.

Comprehensive Approach Necessary

Ketamine is an effective treatment for bipolar depression, offering rapid relief from depressive symptoms and suicidal ideation.  Our clinic views ketamine treatment as part of a comprehensive approach that includes monitoring, adjunct therapies, and ongoing evaluation.  Active participation in therapy and close communication with the rest of your health care team leverage ketamine’s short-term effects to create long-term, lasting change.

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