Bipolar disorder is often misunderstood as a cycle of unpredictable mood swings. However, for many people living with the condition, depression, not mania, is the most persistent and debilitating symptom. These depressive episodes last for weeks or months, making it difficult to work, maintain relationships, or even care for basic needs.Â
Even more troubling is the fact that many patients do not respond to standard medications. This treatment resistance has led researchers and clinicians to explore new options. Among them, ketamine stands out for its speed, impact, and potential to change lives.
Why Treating Bipolar Depression Is So Difficult
When most people think of bipolar disorder, they picture someone bouncing between extremes. But in real life, it often looks like long stretches of sadness, numbness, and fatigue.Â
According to a 2023 scoping review in Brain Sciences, nearly 25% of people with bipolar depression do not respond to standard treatments. That means one in four patients live with symptoms that medications cannot touch.
The risks are serious. Studies show that people with bipolar disorder are about 20 times more likely to die by suicide compared to the general population. Medications like lithium or antipsychotics can help some, but they often take weeks to kick in and come with side effects. When someone is in crisis, waiting a month for possible relief is too long.
How Ketamine Works Differently
Ketamine does not work like traditional antidepressants. Instead of targeting serotonin, it acts on the brain’s glutamate system. By blocking NMDA receptors, ketamine creates a sudden increase in glutamate. That leads to fast changes in how brain cells connect and communicate. These changes are linked to mood, memory, and resilience.
The result is noticeable. Ketamine’s effects can start within hours. In one pilot study from 2020, researchers gave (R)-ketamine to people with treatment-resistant depression. Seventy-one percent showed major improvement after just one dose. A week later, more than half still felt better. The side effects were minimal.
Ketamine is available in different forms. The FDA has approved (S)-ketamine as a nasal spray called Spravato. It works on the same receptor, just with slightly different chemistry. Some researchers believe (R)-ketamine may have longer-lasting results with fewer side effects, though more studies are still in progress.
What Research Shows About Ketamine and Bipolar Disorder
Most of the early research focused on major depression, not bipolar disorder. That has started to change. The 2023 scoping review in Brain Sciences looked at 10 clinical studies involving ketamine for bipolar depression.Â
These included five randomized controlled trials and five open-label studies. The results were promising. Patients showed significant drops in depressive symptoms and suicidal thinking. Few experienced manic episodes after treatment.
The same review found that some patients felt relief for up to two weeks after a single ketamine infusion. That matters. Most antidepressants take weeks to help and must be taken daily. Ketamine’s quick effect gives it a unique role, especially during crises.
The research also highlights the value of combining ketamine with psychotherapy. When used alongside talk therapy, ketamine may deepen insight and emotional processing. This combination could help people work through difficult memories or thoughts that often feel stuck in place.
Three Ways Ketamine Is Used in Mental Health Care
Ketamine therapy is not one-size-fits-all. There are three main models, and each serves a different purpose.
Biochemical Model
This is the most common setup. It uses low-dose ketamine infusions to target brain chemistry. Patients usually receive a series of sessions over a few weeks.Â
The goal is symptom relief, especially for depression and suicidal thoughts. This model does not require therapy at the same time, although some patients may do both.
Psychotherapeutic Model
In this case, ketamine is used as part of therapy. It helps open the brain to new ideas and connections. That can make therapy more effective, especially for people who struggle to access or express their emotions.
In this model, patients meet with a trained therapist before, during, and after their sessions. This approach is often called ketamine-assisted psychotherapy (KAP).
Psychedelic Model
This version uses higher doses to create a dissociative or altered state. It is not just about brain chemistry. The idea is to give the mind space to explore things from a new perspective.Â
Some patients report a sense of emotional reset, while others describe visual or spiritual experiences. This model requires preparation, support, and careful follow-up. The psychedelic model is best suited for specific situations, not general use.
Risks and Considerations
Like any treatment, ketamine is not perfect. In clinical settings, most side effects are short and manageable. They include nausea, elevated blood pressure, dizziness, and dissociation. These symptoms typically pass within a few hours.
There are bigger risks if ketamine is used outside of a medical setting. Recreational use can lead to addiction, memory problems, and damage to the bladder or kidneys. This is why it must always be administered by a licensed provider.
Another concern is mood stability. For people with bipolar disorder, there is always a risk of swinging into mania. Ketamine does not appear to trigger manic episodes often, but providers still recommend using mood stabilizers before starting treatment.
Trauma history also matters. Some patients with PTSD or dissociative symptoms may experience distressing flashbacks during treatment. In those cases, psychological preparation is essential. A therapist should be involved to help patients stay grounded and process what comes up.
Where to Find Help
Ketamine is not a cure. But for people with bipolar depression who have tried everything else, it offers real hope. The effects come fast. The relief is measurable. For some, it is the first time they have felt like themselves in years.
At Zeam Health & Wellness, we provide comprehensive mental health care that includes ketamine therapy. Our clinical team is trained to deliver this treatment safely and effectively. We also work with patients to develop personalized care plans that include psychiatric support, medication management, and talk therapy.
We offer ketamine and psychiatric treatment at our Sacramento, Roseville, and Folsom locations. If you have been living with bipolar depression and nothing seems to help, reach out to us. We will help you explore whether ketamine is the right next step.
