Does Ketamine Help with Bipolar Depression?

Depression is one of the most common reasons people seek ketamine therapy; however, bipolar depression may be more difficult to treat. When ketamine adequately relieves symptoms, the effects rarely last more than a few days.

When ketamine is used to supplement therapy, it can be quite effective. This is more in line with other types of psychedelic-assisted psychotherapy; however, ketamine therapy is frequently absent or limited.

What Causes Bipolar Depression?

There are numerous “causes” behind all complicated mental health issues, ranging from genetic to social variables. While the underlying etiology of the disorder varies from person to person, there are some similar neurological causes behind the symptoms (or “pathophysiology”).

Here are the causes, presented in three sections.

1. Neurotransmitter Signaling: Damage to the flow and production of serotonin and dopamine causes dysregulation of mood and the “reward system.” This makes it difficult to find drive or take delight in accomplishments or positive situations.
2. Abnormal Connections: Through the aforementioned (and most likely other triggers), parts of the brain begin to couple with other networks with which they do not ordinarily interact. Many of the manic and depressed symptoms are most likely caused by this “dysbalance between networks.”
3. Deterioration: “Additional contribution of gray matter alterations and related cognitive deterioration” may develop in some bipolar individuals, leading to a loss in learning and impulse control.

Most research indicates that the cascade processes described above are primarily caused by dopamine deficiency, which is frequent in bipolar and unipolar depression. While we believe dopamine is solely a “reward,” it also serves as a motivator, providing modest quantities in advance of beneficial behaviors like exercise or huge undertakings.

Bipolar depression is likely characterized by decreased dopamine production during depression and increased dopamine sensitivity during manic episodes. While the mechanisms are not fully understood, prolonged periods of low dopamine levels may sensitize receptors to the pleasant sensation during mania.

Ketamine may aid by enhancing the “connections between two brain regions that are involved in the production and regulation of dopamine.” The benefits are only transient, but they may explain why depression symptoms disappear so quickly.

Ketamine Research On Bipolar Disorder

A 2023 review assessed 235 patients with bipolar disorder from all currently available research and discovered an average effectiveness rate of 48%. These primarily concerned “treatment-resistant” patients, which meant that previous treatments had failed.

Some other key findings include

• A range of 26–79% success rates across eight studies.
• Single-dose ketamine’s benefit “did not extend beyond the 2-week mark; however…repeated infusions of ketamine over 2 weeks” may help for up to a month.
• Ketamine may have a major impact on suicidal ideation, providing relief within 4 hours of injections, and repeated doses may be able to sustain the impact.
• Researchers excluded 17 studies (more than double the number included) because they didn’t investigate potentially harmful outcomes of ketamine, pointing to a potential problem of bias in research.
• All but one of the studies involve infusions of ketamine; the outlier investigates the proprietary Spravato nasal spray.
• The Spravato study had a response rate of 68.5% after two doses but only 25.5% after one for participants with bipolar depression.

Ketamine for bipolar depression, like other forms of mental health or psychedelic-assisted psychotherapies, is still in the early stages of research. The studies had small sample numbers and a wide range of outcomes, but they all appear to concur on ketamine’s short-term benefits.

Participants reported significant symptom relief after one or two sessions (depending on the study). We don’t know how beneficial this is or how to maximize the effect. One 2020 study discovered that, while ketamine was effective for 71% of patients for up to two weeks, symptoms increased from the starting level after three.

Can Ketamine Treat Bipolar Depressive Disorder?

Ketamine appears to have a significant, however brief, influence on bipolar and unipolar depressive symptoms. While the benefit appears to last only a week or two, it can still be effective for periods of severe anxiety or despair linked with bipolar disorder.

Unlike unipolar depression, which has a continuous negative influence on mood, bipolar symptoms include alternating spells of excitability and depression. Long periods of intensive concentration and focus might lead to days or weeks of difficulty waking up in the morning.

This disruption in mood regulation can make life extremely difficult without treatment and therapeutic involvement. Ketamine will not “cure” any form of depression, and it’s unlikely that any medicine will do so, given the traumatic, social, and systemic layers that frequently constitute the foundation of the illness.

However, the symptoms of sadness are frequently so overwhelming that the deep mental work required can seem unattainable. Ketamine and mental health drugs are effective at temporarily easing symptoms, making the work simpler but not eliminating the need for it.

Treating bipolar depression, a disorder characterized by strong mood swings, can be perilous when using a substance like ketamine, which significantly affects emotions and perception. Because of the risk of severe anxiety or even paranoia, attempting to self-treat bipolar depression without medical or psychiatric supervision is not recommended.

Most (if not all) research on ketamine for bipolar depression involves individuals quitting due to a negative experience with ketamine. This is usually only a tiny percentage of participants, but there is no way to predict how tough the experience will be ahead of time.

Dosage Schedule for Ketamine Treatment of Bipolar Depression

Dosing schedules usually include several doses per month, occasionally weekly, because ketamine wears off quickly. Off-label clinics that provide intramuscular injections or infusions typically begin new patients with two weekly infusions for the first month or two before reducing the dosage.

Though they are more likely to stick to once a week at most, ketamine telehealth firms may use sublingual lozenges or troches and similar dose methods. It’s important to keep in mind that telehealth providers provide very little therapeutic support, which might be risky when attempting to treat depression of any kind.

Only unipolar depression that is resistant to treatment can technically be treated with Johnson & Johnson’s exclusive nasal spray, Spravato. It would probably require two weekly doses in addition to medication, much like it does for unipolar depression, if it were ever an option for bipolar depression.

Risks and Issues with Ketamine for Bipolar Depression

Ketamine therapy involves potentially negative side effects, toxicity concerns, and the potential for serious adverse events.

Some of the common side effects patients can expect to potentially experience on ketamine include

• Dizziness, nausea, and vomiting
• Blurred vision (potentially lingering for up to an hour after ketamine wears off)
• Loss of coordination or muscle control
• Heavy sedation or body-heaviness
• Cognitive impairment (holes in memory, trouble reasoning or concentrating, etc.)
• Elevated heart rate and blood pressure
• Auditory and visual hallucinations
• Slowed breathing
• Anxiety, paranoia, and agitation

There are also serious concerns surrounding ketamine’s impact on the following:

• Urinary Tract: The most typical side effect of frequent ketamine usage is urinary tract damage, which can result in infections, urinating issues, and other issues.
• Bladder: If ketamine usage persists, untreated urinary issues could damage the bladder and necessitate emergency care.
• Liver: Ketamine addiction is primarily a concern since the liver’s duty is to filter out toxins, and too much of it can lead to infection, malfunction, and other major issues.
• Heart and Lungs: Long-term stress or preexisting medical issues can generate medical concerns, even though the minimal influence on the respiratory and cardiovascular systems is unlikely to cause serious harm.
• Brain: According to some research, ketamine use may have long-term effects that impair one’s capacity for learning and cognition.

Always discuss ketamine treatment with a mental health care provider, preferably not employed by a ketamine clinic, before starting treatment.

People on anti-psychotic, cardiovascular, respiratory, and sedative/impairing medications or drugs should not take ketamine.

Does Ketamine Treatment Make Sense for Bipolar Disorder?

Each person will respond differently to treatment, and ketamine may provide significant, if brief, relief for some. Ketamine therapy is not inexpensive, though, and the regimens may require up to two doses each week, which adds significantly to the cost.

No medication is likely to provide long-term relief from bipolar depression; instead, therapy involvement is necessary. Pharmaceutical treatments typically make it easier to extract the psychological underpinnings of depression symptoms and those of many other mental health illnesses through therapy.

It might be challenging to face the day during depressive periods, let alone attempt to fully engage in a psychological session. Rapid alleviation of depression symptoms can be extremely relieving and beneficial for therapy sessions.

In this approach, ketamine may offer hope to people who suffer from bipolar depression, even though it is not a “cure.” It’s important to keep in mind, though, that there is little evidence on ketamine treatment for bipolar disorder, and the success rates in those studies vary greatly.

Ketamine’s dissociative effects might be overwhelming for some people, and they may eventually make their condition worse. A mental health expert should be consulted in advance by anyone considering ketamine treatment, particularly if they have a mental health condition.