Ketamine Treatment for Bipolar Disorder

Bipolar disorder is one of the most burdensome mental health conditions a person can live with. It affects an estimated one in every two hundred people worldwide and ranks among the leading causes of disability. Yet despite decades of research, many patients continue to suffer through depressive episodes that simply do not respond to available treatments.

At Emerge Ketamine, we work with patients with bipolar disorder who have exhausted standard options and still haven’t found relief. This article will explore why ketamine treatment marks a promising option for these patients, and what the research says about its benefits and risks.

The Treatment Gap in Bipolar Disorder: Why Standard Options Fall Short

Bipolar disorder is most commonly treated with a combination pharmacological (medication-based) and non-pharmacological treatments. Commonly used pharmacological options include:

• Lithium
• Valproate
• Lamotigine
• Quetiapine
• Lurasidone

Antidepressants are sometimes used to help manage depressive episodes, however, they are used with great caution as they also increase the risk of manic episodes.

In the right combinations and doses, pharmacological treatments can have a meaningful impact on reducing the frequency and severity of mood episodes. However, for a substantial proportion of people with bipolar, these interventions have no or little impact, or eventually stop working after initially being effective. According to research published in 2021, around one-quarter of bipolar patients have no meaningful benefits from common medications.

In addition to treatment resistance, medications also pose a limitation because of side effects. Some common side effects of bipolar medications include:

• Weight gain
• Drowsiness or sedation
• Fatigue / low energy
• Tremor or shaky hands
• Blurred vision
• Brain fog / slowed thinking
• Memory or concentration difficulties
• Sexual dysfunction
• Restlessness or agitation
• Sleep changes (insomnia or excessive sleep)

Studies indicate that up to 60% of bipolar patients are at least partially non-adherent to treatment because of these side effects. This means they may miss doses, stop medication for periods of time, or don’t follow the full treatment plan.

How Ketamine Could Offer a Solution for People with Bipolar Disorder

Ketamine has emerged over the past two decades as a breakthrough treatment in psychiatry. It was originally developed, and is still widely used, as a surgical anesthetic. However, later research found the medication had rapid-acting and powerful antidepressant effects when administered at sub-anesthetic doses.

Unlike traditional antidepressants, ketamine works primarily as an antagonist of the N-methyl-D-aspartate (NMDA) receptor. This protein plays a key role in neuroplasticity, the brain’s ability to form and strengthen neural connections.

Studies show that impaired neuroplasticity may underlie some of the core symptoms of bipolar disorder. When the brain is less adaptable, regions involved in emotional regulation can be more easily damaged and likely to lose function. Ketamine may help reverse some of this damage.

Unlike antidepressant medications, ketamine also has rapid-acting effects, with studies showing it can reduce symptoms within hours of administration. This speedy action is particularly beneficial for people with bipolar who may be having a severe acute mental health crisis.

What the Research Shows About Ketamine Therapy and Bipolar Depression

Increasingly, doctors are prescribing ketamine to patients with bipolar depression. Universities have collaborated with clinics and hospitals to track the outcomes of these patients, obtaining real world data about the drug’s safety and effectiveness.

A 2025 study from the Division of Psychiatry at the University of Siena School of Medicine, Italy investigated the impact of intravenous (IV) ketamine treatment in 59 patients with treatment-resistant bipolar type I and II. Following treatment, patients showed a notable improvement in symptoms, including reductions in inner tension, sleep disturbance, and suicidal ideation, which are typically difficult to treat.

A longer-term 2024 study, conducted by researchers at Yale School of Medicine, also tracked the outcomes of patients with treatment-resistant bipolar depression. Following a course of treatment with ketamine or esketamine (a molecule derived from ketamine), 39% of patients showed a clinical response, meaning they had a 50% or greater reduction in depression scores. Moreover, 13.2% achieved full remission, meaning they no longer met the clinical criteria for bipolar depression.

Safety of Ketamine in Bipolar Treatment: Understanding the Risk of Mood Switching

While ketamine offers a promising option for people with bipolar disorder, there are concerns about its risks. Ketamine is psychoactive and induces a state of dissociation, characterized by feelings of separation from one’s body and normal sense of time and space. Some people are concerned this effect could trigger a switch into mania or hypomania, particularly for those with bipolar type II.

The current evidence is reassuring. For both the real-world studies discussed above, no patients experienced a manic and hypomanic episode while actively being treated with ketamine. However, there is still limited data about the safety of ketamine for bipolar patients. More evidence is required from long-term follow-up studies on larger groups of patients.

As well as inducing mania, there are concerns about how ketamine may interact with bipolar medications. Most people with bipolar disorder arrive at ketamine treatment while already on a medication regimen to help prevent manic and depressive episodes from uncontrollably cycling. Discontinuing the use of medications before ketamine treatment may not be a realistic or safe option for some.

While data is somewhat limited, studies suggest that ketamine and lithium, one of the most commonly prescribed bipolar medications, have no significant interactions. However, combining ketamine and benzodiazepines, which are used to manage symptoms of agitation, may increase the risk of sedation and unpredictable cardiovascular effects.

At Emerge Ketamine, we’re vigilant in ensuring patient safety. Before beginning any course of treatment, our clinical team will conduct a thorough screening process, reviewing a patients’ full medication history, current mood stability, and psychiatric background to assess whether ketamine is appropriate and how it can be delivered most safely. Throughout treatment, our staff closely monitor patients, with careful attention to mood changes, dissociative response, and any early signs of mood switching.

Ketamine Treatment for Bipolar Disorder at Emerge Ketamine

Emerge ketamine is an established ketamine provider in the Boston area, offering ketamine infusions in a state-of-the-art clinic for patients living with a range of mood disorders, including bipolar depression.

We provide thoughtfully tailored IV ketamine infusions in a private, comfortable infusion suite, with a compassionate and individualized approach. Every patient who comes to us has a unique clinical history, and we take that seriously.

If you or someone you care about is living with bipolar depression that has not adequately responded to conventional treatment, ketamine therapy may represent a meaningful option worth exploring. We invite you to get in touch with the Emerge Ketamine team to learn more.