Ketamine for Bipolar: How it Works, Effectiveness & How to Try It

What Is Ketamine Therapy?

Ketamine therapy is an alternative treatment for several mental health conditions, including bipolar disorder. Even though this psychedelic therapy is not currently FDA-approved to treat bipolar, it is increasingly being used off-label by specialized mental healthcare professionals, especially in cases where suicidality is a concern.

There are several different ways ketamine can be administered, including oral, nasal, and intravenous routes. Typically, treatments are once or twice a week but may be tapered down after the initial 6-8 weeks.

Can Ketamine Help With Bipolar Disorder?

Anecdotal and case reports suggest that for individuals with bipolar disorder who have manic symptoms, ketamine seems to remove the need for urgency and impulsive behaviors. On the depressive side, ketamine has been shown to remove symptoms, both directly and indirectly.

Directly, ketamine creates a euphoric mood and pleasurable feelings and seems to lift the emotional weight depressive symptoms can create. Indirectly, ketamine can reduce the anxiety that holds people back from doing the things they want to do. This can enhance achievement and self-efficacy, thus chasing away depression.

Given that ketamine treatment for bipolar disorder is fairly new, one concern among clinicians is whether it can trigger an affective switch from depression to mania. Initial research suggests that only 2.9%-4.5% of patients with bipolar disorder experience an affective switch as a result of ketamine treatment (also referred to as treatment-emergent hypomania).²

Ketamine for Bipolar I Vs. Bipolar II

A key distinction between bipolar I and bipolar II has to do with the severity and duration of manic symptoms. Ketamine works better for depressive symptoms than manic symptoms and has been shown to be more effective at reducing depressive symptoms for bipolar II.¹ Due to the possibility of an affective switch, One study suggests that ketamine should be only used for bipolar I if a patient is actively taking a mood stabilizer to reduce the risk of manic symptoms emerging.²

Can Ketamine Effectively Treat Bipolar Disorder?

In limited research findings, ketamine has been shown to effectively treat the depressive symptoms of bipolar disorder in 48% of those who try it, but it is still unclear how it affects manic symptoms.² Some preliminary research suggests that it may reduce some manic symptoms, like agitation, anxiety, irritability, and inner tension, and reduce the likelihood of cycling between ups and downs, but this is speculative.³

Can Ketamine Reduce Suicidal Thoughts?

One aspect of bipolar disorder in which ketamine shows considerable promise is suicidality. Suicide risk is elevated in bipolar disorder, with 23%-26% attempting suicide and 5%-10% completing suicide.^{4, 1} A variation of ketamine called esketamine is the only ketamine formulation to be FDA-approved to treat depression and suicidal ideation. Fast-acting ketamine has been shown to reduce suicidal ideation within an hour of administration. However, the long-term use of ketamine for suicidality in bipolar disorder has not been thoroughly studied; ketamine therapy is intended as a shorter-term treatment.

How Fast Does Ketamine Work for Bipolar Disorder?

Ketamine works relatively fast and can start reducing the depressive and anxiety symptoms common to bipolar disorder in the first 40-60 minutes. Some variation in timing may occur between routes of administration. The main thrust of ketamine’s effects lasts for approximately 45 minutes, after which a come-down phase extends anywhere from 20 minutes to the rest of the day.

How Long Do the Benefits of Ketamine for Bipolar Disorder Last?

Bipolar disorder symptoms may remain quiet for about a week post-treatment but then gradually return. There is a risk of manic symptoms emerging as depressive symptoms wane, but it is low. Ketamine is not a treatment for manic symptoms, except for when suicide is a risk.

Combining ketamine treatment with psychotherapy – called ketamine-assisted psychotherapy – increases the likelihood that symptom relief will extend longer and perhaps indefinitely. This is best accomplished when there is an established rapport between therapist and patient before the ketamine treatment begins.⁷

What To Expect During Ketamine for Bipolar Disorder Treatment

Ketamine therapy begins with a comprehensive evaluation to ensure that it is safe and appropriate for your condition. If it is, the preparation stage can then be set to maximize the benefit and minimize side effects in the upcoming treatment. The multi-session active treatment phase is then followed up with a post-treatment stage to determine if booster sessions are required to maintain symptom relief.

Ketamine therapy for bipolar disorder involves the following stages:

Initial Assessment & Evaluation Process

A ketamine provider begins the process with an in-depth evaluation of your bipolar symptoms as well as your medical and family history that will help determine if ketamine is a safe and ideal treatment for you. If it is, the provider will explain the process and which route of administration they use.

Contraindications that may disqualify someone from ketamine therapy include a history of severe psychotic symptoms (as with bipolar type I) or severe hypertension. The provider may recommend being on a mood stabilizer before starting ketamine treatment for bipolar to counteract any manic symptoms, even if it hasn’t been effective for depressive symptoms.

While there are telehealth companies offering at-home compounded ketamine treatment, the FDA cautions against it due to potentially inadequate medical monitoring and safety measures.⁸ This is even more of a concern for bipolar patients who are at risk for shifting mood in response to ketamine. For bipolar disorder, a certified medical setting is the best option for ketamine treatment.

Preparation Phase

The preparation stage is very important for increasing the likelihood that the active ketamine treatment will be beneficial, safe, and pleasant. The ketamine provider – usually a psychiatrist – may meet with you individually or in conjunction with your psychotherapist (for ketamine-assisted psychotherapy). Psychotherapy during a ketamine session has the potential for greater improvement than either treatment alone.⁷

During this phase, the provider explains what to expect during the treatment session and answers any questions or concerns you may have. Intentions are set, auditory stimuli are selected (such as background music or guided meditation), and positioning is discussed (i.e., lying down vs. sitting). Instructions for the day of treatment are provided, covering things to do (e.g., taking routine medication, arranging transportation) and not to do (e.g., eating right before).

Active Treatment Phase

The active treatment phase is when the ketamine is administered. Ketamine effects begin emerging approximately 15 minutes after the full dose is given (although this may vary with administration route). These effects last for about 45 minutes.

A serene, quiet setting is ideal for ketamine therapy. Although it may differ between practitioners, some constants include dim lighting, limited ancillary sound, and comfortable seating for sitting or lying down. Ketamine can be given as a nasal spray, orally, or intravenously. A smaller than-normal dose is usually given for the first session to ensure it is well-tolerated and does not trigger manic symptoms.

During the active phase, the patient’s vitals, mental state, and any side effects are continuously monitored throughout the ketamine session. In some cases, a patient may be unable to verbalize a response to clinician inquiries and may need to respond with a hand or head gesture. Although rare, it is possible that a patient faints or falls into a “k-hole,” in which case appropriate medical care is administered. This is one example of why a medical setting is safer than at-home telehealth ketamine therapy.

Post-Treatment Phase

The come-down phase – gradual reduction of ketamine effects – can be brief for some and extended across hours for others. Even as the come-down phase completes, an “afterglow” period may linger for a day to several days, during which the individual may be more open to psychotherapeutic interventions. As such, this is an ideal time to work with one’s therapist on changing how one engages with their bipolar symptoms and creating new, healthier ways of navigating thoughts and feelings.

How is Ketamine for Bipolar Disorder Administered?

To treat bipolar symptoms, ketamine can be administered through a variety of routes, depending on the provider. Non-invasive methods like oral (sublingual, pill, or lozenge) or nasal (spray) forms are common due to ease of administration. Injectable routes of administration (e.g., intravenous, intramuscular, subcutaneous) may provide a greater ability to fine-tune the amount of ketamine that reaches the bloodstream (with intravenous being the most flexible).

You can discuss the pros and cons with your healthcare provider and seek other ketamine providers if yours doesn’t offer a route you are comfortable with. With any of these ketamine administration routes, sessions are usually once or twice a week for 2-3 months, with each session lasting 2-3 hours. Ongoing maintenance or “booster” sessions to keep bipolar symptoms under control may be needed on an as-needed basis.

Dosages of Ketamine for Bipolar Disorder

There are several factors that will determine the dose, such as route of administration, formulation (e.g., racemic ketamine, esketamine, arketamine, compounded ketamine), and point in treatment. For subcutaneous and intravenous routes, 0.5-1 mg/kg is typical for treating bipolar symptoms, while nasal esketamine doses range from 28 mg (1 spray in each nostril) to 84 mg (3 sprays in each nostril) and even up to 140 mg (5 sprays in each nostril) in some cases. When taken orally, a majority of the ketamine does not make it to the bloodstream (only 20%-25% bioavailability as compared to nearly 100% for intravenous or 50% for intranasal).⁹ As such, oral doses are typically higher, in the realm of 150-250 mg, which can lead to more side effects.

Side Effects of Ketamine for Bipolar Disorder

As with any psychedelic, there is ample variation in the side effects one experiences ketamine. Ketamine does lead to dissociation in most people, and while some may find dissociation pleasant and relaxing, others may find the loss of control anxiety-provoking. When anxiety is a prominent manic symptom of bipolar disorder, an adverse psychological response may be more likely.

Most side effects of ketamine (sub-anesthetic doses) for bipolar symptoms are short-lived and typically resolve within an hour. The more common side effects include dizziness, sleepiness, and blurred vision, but manic symptoms can emerge in a small percentage of bipolar individuals, especially if mood stabilizers aren’t concurrently used. In general, side effects are most common with oral administration.

Potential side effects of ketamine treatment include:

• Affective switch from depression to mania
• Sleepiness
• Dizziness/Lightheadedness
• Blurred vision
• Palpitations
• Flushing
• Poor concentration
• Nausea
• Paresthesia (pins and needles sensation)
• Dry mouth
• Headache
• Dissociation
• Perceptual distortions
• Psychotic-like symptoms
• Elevated blood pressure
• Increased heart rate
• Respiratory depression
• Urinary and bladder symptoms
• Memory impairment
• Psychiatric events
• Ketamine misuse
• Interactions with other comorbidities and medications

Is Ketamine Therapy for Bipolar Disorder Safe?

Ketamine is not approved by the FDA to treat bipolar disorder I or II and comes with its share of risks, as does any treatment. Psychiatrists who have been using ketamine off-label have generally found it to be safe and well-tolerated for bipolar II (and, in some mild cases, bipolar I) with proper monitoring. Using a certified, in-person (not telehealth) provider reduces such risk, especially when treating bipolar disorder.

Given the effectiveness of ketamine for major depression and the overlap in symptoms between bipolar disorder and major depression, it is likely that the FDA will try to expedite the approval of ketamine treatment for bipolar disorder in the coming years following its eventual approval for major depression. However, the clinical data are not as clear-cut for bipolar disorder as they are in support of use with depression and suicidality.

Can Ketamine Treatment Be Addictive?

The addictive nature of ketamine is still unclear; while it is potentially addictive, it also does hold some therapeutic qualities in treating other addictions, such as cocaine, heroin, and alcohol.¹⁰ Addiction is of particular concern with bipolar disorder, given the high comorbidity with substance use disorder (estimated at more than 50%).¹¹ One’s healthcare provider will have to evaluate risks versus benefits.

Risks & Precautions of Ketamine Therapy for Bipolar Disorder

While ketamine has been around for decades and demonstrates a fairly safe profile, there are nonetheless risks, as with any treatment. The best precaution you can take is to find a reputable, certified ketamine provider who you feel comfortable with and have confidence in to do a thorough evaluation of your medical history to determine if it is an appropriate treatment for you.

For any condition, but bipolar especially, it is crucial to be in a monitored medical setting for treatment, not at home (via telehealth or otherwise). Even experienced ketamine patients can fall into a K-hole or have unanticipated side effects, and having medical intervention on-site can mitigate such risks.

Risks of ketamine therapy for bipolar disorder include:

• Include all risks
• Affective switch from depression to mania
• Side effects that mimic symptoms of a panic attack (e.g., heart palpitations, dizziness, shortness of breath)
• Falling into a K-hole
• Brief psychotic episode
• Feeling paralyzed during treatment
• Feeling frightened
• Cardiovascular event
• Bladder and urinary problems
• Motivational impairment

Can Ketamine Be Used Along With Bipolar Disorder Medications?

Ketamine can be used along with bipolar disorder medications. In fact, it is sometimes recommended that a patient with bipolar disorder be on a mood stabilizer during ketamine treatment to reduce the risk of manic symptoms emerging as a result of the treatment (i.e., treatment-emergent mania).

Microdosing Ketamine for Bipolar Disorder

Psychedelic microdosing involves the daily ingestion of doses too small to elicit acute, mind-altering effects (such as dissociation and perceptual distortions). Microdosing has been more extensively researched with other psychedelics like psilocybin but less so with ketamine.

One recent small study found that daily microdoses of ketamine resulted in lower reported stress, anxiety, and depressive symptoms compared with a placebo. On the other hand, there is a general consensus among practitioners that the dissociative state is necessary for ketamine to be effective.¹³ More long-term studies are needed to further elucidate the effects of microdosing ketamine.

Is Ketamine Therapy for Bipolar Disorder Right for You?

If you or someone you care about has bipolar disorder for which conventional treatments have not worked, it may be worth considering ketamine therapy as an alternative or add-on treatment. A psychiatrist can help you determine if it would be safe and effective by evaluating your medical history and the specific bipolar symptoms you are predominantly experiencing.

Even if other bipolar medications have not been effective on their own, it may still be recommended to continue the regimen in combination with ketamine to protect against a potential affective switch to mania during treatment.

Who May Not Be A Good Fit for Ketamine Treatment?

Not everyone with bipolar disorder is a good candidate for ketamine therapy. There are medical (e.g., cardiovascular) and mental health (e.g., psychosis, substance misuse, bipolar type I) conditions that would preclude someone from receiving this treatment. Bipolar symptoms come in all constellations, and while ketamine is effective for many of the depressive symptoms, it may not be good for manic symptoms.

Furthermore, the dissociative sensation induced by ketamine may be anxiety-provoking or aversive for some people; this is especially relevant considering that one’s expectations and mental state leading to treatment can greatly affect the experience and benefit.

Individuals who should not take ketamine treatment include:

• People with high blood pressure
• People with cardiovascular disease
• People with severe bipolar type I disorder who are not on mood stabilizers
• People at high risk for substance use disorder
• Individuals at risk for psychosis (e.g., schizophrenia)¹²
• People who can not be monitored by a medical staff during treatment
• Those who are anxious about dissociating
• Very young or very old individuals

How to Find a Ketamine Therapist for Bipolar Disorder

Ketamine is a medication that must be prescribed by a physician (e.g., psychiatrist or nurse practitioner). To find a provider that specializes in ketamine therapy, you can ask your primary care provider for a recommendation or search directories like The American Society of Ketamine Physicians, Psychotherapists, and Practitioners Directory.

If you are interested in ketamine-assisted psychotherapy (talk therapy while under the influence of ketamine), you can ask your existing therapist (if you have one) if a joint session with a psychiatrist would be possible. If you need to find a therapist, consider searching an online therapist directory for providers in your area. It is best to have psychotherapy sessions prior to a ketamine-assisted therapy session to establish trust and familiarity with issues to work on.

Cost of Ketamine Treatment for Bipolar Disorder

Ketamine therapy for bipolar varies in cost depending on the administration route (IV, oral, intranasal) and frequency necessary. Since ketamine is not FDA-approved to treat bipolar, insurance will likely not cover the cost, which can generally range from $150-$1000 per 60-90 minute session. Talk therapy with a psychotherapist during a ketamine session is typically an additional charge.

Telehealth companies offering at-home treatments are less expensive, typically $100-$200 per session. However, at-home treatments without proper medical monitoring are not recommended, especially for individuals with bipolar disorder.⁸

Other Treatment Options for Bipolar Disorder

Ketamine therapy is not the first line of treatment for bipolar disorder, nor is it intended as a stand-alone treatment. Concurrent medication and psychotherapy are usually the frontline treatment for bipolar, with other options (like ketamine or neuromodulation) considered only if adequate symptom relief is not attained. When suicidality is present, ketamine offers a fast intervention, but otherwise, there are several bipolar disorder treatment options that will likely be tried first.

Other treatment options for bipolar disorder include:

• Medications: There are several medication options for bipolar disorder besides ketamine, with mood stabilizers (like Lamictal) and antipsychotics (like Abilify) being frontline choices.
• Cognitive behavioral therapy (CBT): CBT for bipolar disorder is typically the first line of treatment (together with medication) and focuses on modifying one’s thought pattern and behavior. CBT utilizes techniques like acceptance and commitment therapy and cognitive restructuring. CBT can effectively be combined with pharmacotherapy.
• Interpersonal and social rhythm therapy (IPSRT): IPSRT is a psychotherapy method used to identify and track patterns in a patient’s daily life that lead to positive and negative mood changes. Changing maladaptive patterns or preventing disruption to good patterns can help a patient gain better control over mood fluctuations. IPSRT is particularly useful for bipolar disorder and is typically combined with medication and other CBT or DBT tools.
• Acceptance and commitment therapy (ACT): As an offshoot of CBT, ACT combines mindfulness and meditation techniques with talk therapy to adjust how one perceives and engages with their bipolar depressive and/or manic symptoms. The goal of ACT is to see these symptoms as a natural part of being human, acknowledge their presence, but not let them disrupt your life.
• Vagus nerve stimulation (VNS): VNS can reduce bipolar symptoms by modulating activity along the major nerve connecting your body and brain.¹⁴ This technique may also have the potential to maintain bipolar symptom relief over time.¹⁵ VNS proper is an invasive treatment requiring implantation of a stimulator; however, there are also non-invasive techniques that may also be helpful in calming vagus nerve activity, like humming, vibration, and cold compresses.
• Electroconvulsive therapy (ECT): Delivering an electric current to the head induces generalized seizure activity that can regulate both depressive and manic symptoms in bipolar disorder. Although the procedure itself is non-invasive (no surgery required), anesthesia and muscle relaxants are typically given to prevent movement during stimulation.¹⁵
• Magnetic seizure therapy (MST): As a non-invasive treatment similar to ECT, MST also induces seizure activity in the brain but uses a magnetic field to induce electric current below the skull instead of direct application of electricity to the scalp. Limited research shows the potential of MST for depressive symptoms of bipolar, but no studies at present have explored its efficacy with manic symptoms.¹⁵
• Transcranial magnetic stimulation (TMS): TMS is a non-invasive treatment option that is in its early stages of being used for bipolar. So far, research results are inconsistent, but it does have the potential to reduce depressive versus manic symptoms.¹⁵ TMS for bipolar is intensive, typically requiring daily 20-minute sessions, usually for several weeks. Far from being a frontline option, it may only be worth exploring if other non-invasive options have failed to provide relief.
• Deep brain stimulation (DBS): As an invasive treatment requiring neurosurgery, DBS involves electrical stimulation of specific brain areas that give rise to symptoms. As it is not an FDA-approved treatment for bipolar disorder, it is usually a last resort if no other treatments are effective. While research has shown how DBS can ease depressive symptoms, manic symptoms have not been explored to date.¹⁵