Could ketamine be beneficial for bipolar disorder? - Medical News Today

Some research suggests ketamine may be useful for managing bipolar depression. As such, ketamine has shown promise as a potential experimental alternative treatment for bipolar disorder.

Bipolar disorder causes extreme changes in mood, energy, behavior, and activity. Its main features include manic episodes. These often involve heightened emotions, irritability, erratic behaviors, and actions that may have harmful effects. Other episodes cause very low mood, blankness, and a loss of hope. These are depressive episodes. Mixed episodes involve both manic and depressive features.

Ketamine is a dissociative anesthetic, which means taking it makes people "detach" from their immediate environment and pain. This can cause hallucinations, and some individuals may use it as an illegal recreational drug. However, some doctors prescribe it off-label for depression that is not responding to other treatments.

According to a 2022 review, current evidence supports using some forms of ketamine to help with bipolar disorder.

It is a drug known as an uncompetitive N-methyl-D-Aspartate (NMDA) agonist. Ketamine is a chiral compound, meaning it consists of two different forms that are mirror images of each other. These different forms are known as enantiomers and include S-ketamine and R-ketamine. Racemic ketamine is a type that includes both enantiomers in equal parts.

The Food and Drug Administration (FDA) has already approved S-ketamine as a nasal spray called Spravato for depression that does not respond to other treatments. However, R-ketamine might have longer-lasting and more potent antidepressant effects.

Ketamine works by interacting with several systems in the brain as well as receptors that respond to NMDA. In turn, this releases a surge of a neurotransmitter called glutamate.

Glutamate links closely to the growth of new synapses in the brain and helps different parts of the brain talk to each other. This connects NMDA and glutamate to memory, learning, and neuroplasticity. The latter describes the brain's ability to change and "rewire" itself in response to factors inside or outside the body.

A 2023 article put forward three "paradigms" of short-term treatment through which ketamine might help people with bipolar depression:

• Biochemical: The effects of the medication alone on the body can help reduce bipolar symptoms.
• Psychotherapeutic: Ketamine may support and amplify the effects of talk therapy and promote more open conversations within sessions.
• Psychedelic: Doses of ketamine induce a temporarily altered mental state that may support psychological and spiritual self-exploration, providing a useful tool for future sessions.

The authors recommend that a person already use mood-stabilizing medication before beginning ketamine therapy. The aim is to promote mood stability, not induce a manic episode.

A 2023 review suggests that ketamine may have the following effects as part of bipolar treatment:

It may be particularly helpful during depressive episodes when the risk of suicide is higher. A different 2023 review highlights ketamine's rapid antidepressant effects. It notes it may be quicker than other bipolar disorder medications, such as olanzapine in combination with fluoxetine, which can take 4 to 8 weeks to reduce depressive symptoms.

Intravenous (IV) ketamine, which healthcare professionals administer to the veins, has produced noticeable effects within 2, 4, and 24 hours after a dose. The review authors accept that the evidence is not conclusive around IV ketamine but frame it as a promising future option for rapidly treating severe suicidal ideation.

Ketamine may also cause fewer metabolic side effects than other bipolar disorder medications.

The short-term side effects of using ketamine to treat bipolar disorder might include:

• altered muscle tension
• anxiety
• elevated pulse
• increased blood pressure
• headache
• nausea
• vision changes
• unwanted feelings of dissociation

Over time, ketamine use may contribute to bladder inflammation. Severe adverse effects might include respiratory distress and seizures. Clinicians have expressed concerns about using ketamine while taking substances that increase the risk of high blood pressure, a sedative effect, or respiratory depression.

People with existing substance use disorders may be unsuitable candidates for ketamine treatment. The drug can be a target for misuse due to its hallucinogenic effects and feelings of dissociation. Overdoses on ketamine are also possible and can cause loss of consciousness and slowed breathing.

More conventional treatments for bipolar disorder include the following:

• medications, including mood stabilizers and atypical antipsychotic medications
• psychotherapy to help an individual with bipolar disorder navigate daily life and challenge disruptive thoughts, feelings, and behaviors
• electroconvulsive therapy (ECT), which stimulates parts of the brain to relieve severe bipolar disorder that has not responded to other treatments
• transcranial magnetic stimulation, a slightly less powerful form of ECT that uses magnetic waves instead of electric stimulation
• light therapy for people with bipolar disorder whose symptoms worsen during the winter

As well as the FDA approving S-ketamine for depression, the agency has also approved ketamine as a general anesthetic. However, some doctors might prescribe ketamine off-label for some people with other health problems. Off-label prescription refers to drugs that do not have FDA approval for a specific purpose but may still provide some benefits.

Ketamine may provide benefits for the following:

• Relieving pain: Doctors can use the drug for pain relief as part of general anesthesia during fracture reduction, joint dislocation treatment, or wound repair in people who have issues cooperating.
• Rapidly reducing depression symptoms: However, doctors should consider the risks of ketamine before prescribing it off-label.
• Potentially reducing seizures: This can benefit people with severe epilepsy, although more evidence is necessary before doctors prescribe ketamine widely for this purpose.
• Managing social anxiety disorder: This finding is according to a small clinical trial, although more research is necessary to confirm this benefit.

Ketamine may help quickly relieve suicidal ideation, improve emotional flatness, and reduce anxiety in people living with bipolar depression.

It may achieve this by causing a surge of glutamate and increasing neuroplasticity across several different brain systems. Ketamine may have biochemical benefits, support therapy, and induce hallucinations, and some people may find the drug helpful in controlled settings.

However, ketamine can lead to risks, including headaches, nausea, anxiety, and vision changes. Severe adverse effects, such as seizures and dangerously slow breathing, might also occur. However, people should not self-medicate with ketamine from illicit sources.

A person should only use ketamine for condition management at a recommended dose, in accepted forms, and under clinical supervision.

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