Ketamine is not FDA-approved for the treatment of depression or anxiety.
Spravato (esketamine) is FDA approved for patients with MDD (Major Depression Disorder).
Ketamine is prescribed "off-label" and may help with depression, anxiety, chronic pain and PTSD.
You should not be using ketamine therapy if any of the following apply:
- UNCONTROLLED HIGH BLOOD PRESSURE (HYPERTENSION)
- UNSTABLE HEART DISEASE (SUCH AS ARRHYTHMIAS, CONGESTIVE HEART FAILURE, CORONARY ARTERY DISEASE, ETC.)
- UNTREATED OR UNCONTROLLED THYROID DISEASE (ESPECIALLY HYPERTHYROIDISM)
- ACTIVE SUBSTANCE ABUSE (CURRENTLY ABUSING DRUGS/ALCOHOL)
- IN AN ACTIVE MANIC PHASE OF BIPOLAR DISORDER
- PEOPLE WITH ACTIVE DELUSIONS, HALLUCINATIONS, AND SCHIZOPHRENIA
Here are the most common side effects to be aware of:
Please be aware that ketamine has risks associated with it and prior to participating in this therapy you are fully informed and accepting of this risk:
- Ketamine induced cystitis (mostly occurs in abuse populations but can happen to new users, especially with chronic use of recreational ketamine which should be avoided at all costs as it is often cut with chemicals or fatal drugs like fentanyl).
- Cognitive fog & fatigue after sessions which usually resolves with sleep
- Short-term memory loss (if ketamine multiple times weekly)
- Nausea (rarely vomiting)Emergence reaction (psychosis most common with IM or IV ketamine)
- Rarely elevated liver enzymes have occurredLowered seizure threshold (sparsely reported by physicians)
-Nausea (vomiting is possible but rare. Most common with IV/IM ketamine infusions)
- Increased blood pressure during session (usually about 10 points)
- Sedation or lightheadedness
-Poor coordination and limited physical abilities
-Anxiety or panicking is possible but unlikely in a safe, comfortable setting
- Vivid dreams: These are not unusual, but are well-tolerated by most patients.
- Cardiac issues: At the high doses used for anesthesia, ketamine is a cardiovascular stimulant that can cause hypertension and tachycardia. In contrast, at low doses in patients with chronic pain, it seems to reduce blood pressure. This may result from reduced vasoconstriction due to reduced noradrenergic autonomic stimulation due to reduced pain. One patient incidentally noted that his chronic palpitations resolved after starting low dose ketamine for chronic pain. However, the stimulant effect could theoretically induce a cardiac arrhythmia in susceptible individuals.
- Overexertion: Ketamine increases activity level in most patients. While this effect has mental health benefits and is usually appreciated by patients, it does have risks. For example, patients will push themselves harder than usual after starting ketamine, and often feel sore the next day.
- Dissociative, light, airy feeling
- Distortion of senses and time
-Euphoria or deepened self-reflection
Competition in the Brain:
Some medications prescribed for mood disorders are affecting the same pathways in the brain as ketamine. They may change the efficacy of ketamine, or how well it works. Therefore, they may actually delay and diminish or even boost the positive effects of treatment.
- Benzodiazepines, such as Xanax, Ativan and Klonopin are often prescribed for anxiety, sleep and even muscle spasm. Using this class of medication during the ketamine treatments will mean a longer time to seeing improved mood and more importantly, decrease the overall time of feeling better. Therefore, a booster will be needed sooner. Fortunately, they do not interfere with ketamine treatments for chronic pain.
- Lamotrigine is used both for seizures and bipolar disorder. It works to decrease glutamate release in the brain, whereas ketamine works to increase glutamate. Studies show this direct competition decreases the positive effects of ketamine.
- Lithium, a mood stabilizer used for bipolar disorder, enhances ketamine as they both stimulate the same signaling pathway in the brain. Lithium can improve anti-depressant effects and help protect against some side effects of ketamine.
- Wellbutrin or Buproprion (may cause anxiety and agitation during treatment)
- Stimulants (these can cause anxiety and agitation and blood pressure elevation before treatment)
Competition in the Liver:
The CYP2B6 Liver Enzyme: The cytochrome P450 (CYP450) enzymes reside in the liver and one group, the CYP2B6, is the primary enzyme to break down ketamine to norketamine, the main metabolite. Some medications are also broken down by the CYP2B6 and can actually influence ketamine. What happens if that enzyme is either ramped up or down by other drugs? A study from 2001 explained how some drugs affect this enzyme and can change ketamine levels.
- Orphenadrine (Norflex), a muscle relaxant, inhibits CYP2B6 and slows the breakdown of ketamine which increases the amount of ketamine in the body.
- Dexamethasone, a common steroid, actually induces CYP2B6 and speeds up the breakdown of ketamine. This decreases the amount of ketamine left in your system to work.There is a wide range of variability among people making it difficult to predict who will need more or less ketamine.
The CYP3A4 Liver Enzyme: A second group of enzymes in the CYP450 group in the liver that breaks down ketamine is the CYP3A4, which metabolize about ½ of all drugs on the market. This group is so interesting because there are so many possible drug interactions. For example, drinking grapefruit juice or taking the antibiotic erythromycin can inhibit CYP3A4 from breaking down Xanax, leading to higher levels in the body, with possibly dangerous results. Likewise, ketamine is also affected when taken by mouth (versus IV, nasal or intramuscular). It is given in a lozenge form, which is called a troche. This oral form of ketamine undergoes a “first pass effect” or high rate of liver metabolism.
- Rifampin, a tuberculosis drug that decreases ketamine.
- St John’s Wort, a popular supplement for a variety of conditions which decreases ketamine.
- Ketoconazole, an anti-fungal drug that increases ketamine.
- Cimetidine (Tagamet), an acid reducer for heartburn and peptic ulcers that theoretically increases ketamine.
The dissociative effects of ketamine may increase patient vulnerability and the risk of accidents.To promote positive outcomes and ensure safety, follow these ketamine treatment guidelines:
Do not operate a vehicle (e.g., car, motorcycle, bicycle) or heavy machinery following treatment until you’ve had a full night of sleep.
Refrain from taking benzodiazepines or stimulants for 24 hours prior to treatment.
Continue to take antihypertensive medication as prescribed.
Avoid hangovers or alcohol intake.
Refrain from consuming solid foods within 3 hours prior to treatment and liquids within 1 hour prior to treatment.
Ketamine treatments should never be conducted without a PEER SUPPORT present to ensure your safety.
1. Albott, C S, Shiroma. P R, et al. The Antidepressant Effect of Repeat Dose Intravenous Ketamine Is Delayed by Concurrent Benzodiazepine Use. The Journal of Clinical Psychiatry, vol 78, no 03, 2017
2. Anand, A, Charney D S, et al. Attenuation of the Neuropsychiatric Effects of Ketamine With Lamotrigine. Arch Gen Psychiatry, Vol 57, Mar 2000
3. Chiu, C T, Scheuing, L, et al. The Mood Stabilizer Lithium Potentiates the Antidepressant-Like Effects and Ameliorates Oxidative Stress Induces by Acute Ketamine in a Mouse Model of Stress. International Journal of Neuropsychopharmacology, vol 18, issue 6, April 2015
4. Yanagihara, Y, Kariya, S, et al. Involvement of CYP2B6 in N-Demethylation of Ketamine in Human Liver Microsomes. The American Society for Pharmacology and Experimental Therapeutics, vol 29, no 6, 2001. http://dmd.aspetjournals.org
5. Li, Y, Jackson, K A, et al. CYP2B6*6 Allele and Age Substantially Reduce Steady-State Ketamine Clearance in Chronic Pain Patients: Impact on Adverse Effects. British Journal of Clinical Pharmacology. Feb 22, 2015 vol 80 no 2, pg 276-284