Ketamine Therapy for Treating Major Depression, Bipolar Disorder, and PTSD


How does ketamine therapy work?

Ketamine is a unique, 60 year old anesthetic used widely in Anesthesia and Surgery and in Veterinary Medicine. Ketamine is considered the safest of anesthetics because it doesn’t suppress respiration or decrease the output of the heart, as typically happens with narcotics, propofol, benzodiazapines or inhaled anesthetics. It is thus ideal for burn and trauma victims, obstetric hemorrhage and other high risk surgical procedures.

In higher doses Ketamine can produce what is known as a ‘dissociative state’ where the patient appears to be in an unresponsive trance. Ketamine can produce vivid dreams and a feeling that the mind is separated from the body. This effect, called “dissociation,” is also produced by the related (but illegal) drug PCP. When Ketamine is used in human medicine, it is often given with sedative drugs to offset these effects.

Ketamine therapy is still not completely understood, but appears to produce a reset of the emotional regulatory systems of the brain. Depression and PTSD are complex and thorny problems best addressed with a team approach. It is generally recommended that patients pursue psychotherapy with a trained practitioner, and not depend on the infusions alone.

By Theodore Henderson, MD, PhD, "understanding how ketamine works is essential to appreciating why this approach often fails. Ketamine works by 2 major pathways. The first is the glycogen synthase kinase-3 (GSK-3) pathway, which results in the rapid antidepressant and antisuicidal benefit of ketamine. However, the second pathway is actually much more important. Ketamine activates the production of brain-derived neurotrophic factor (BDNF), which is the brain’s own repair inducer. Not only does ketamine increase BDNF, but it also increases the number of receptors to which BDNF binds.

As a result, over time, there is more repair factor and more receptors available to be activated by the repair factor. The outcome is that over a period of weeks, neuroplasticity and repair occur in the brain. This leads to reduction of depression, because depression is the result of the breakdown in circuits and damage to the brain."

Source >> Theodore Henderson, MD, PhD "Painting Ketamine in a Bad Light"


What factors account for Ketamine therapy cost?

Ketamine itself is an inexpensive generic drug. Supplies and equipment are not expensive. Principle factors that effect the total cost of a procedure are:

- Office rent, utilities and maintenance,

- Salaries and health insurance for a clinic's employees,

- Professional dues,

- Marketing.

Therefore, the cost of Ketamine infusions tend to be higher in the major cities.  However, a quick glance will reveal that pricing is all over the map and perhaps somewhat arbitrary.

It should be noted that although some wealthy people suffer from depression, most patients are not as the disease tends to cause severe financial harm to many patients.  Ketamine infusion is generally not covered by private insurance, Medicaid or Medicare.  Also many patients face large deductibles the days, so cost is a big issue for the majority of patients.  More services are popping up around the country, and competition will eventually improve pricing and quality.  Patients would be wise to shop a bit and decide on the proper compromises between cost and convenience.

Unfortunately, the high cost of legal Ketamine is driving patients to the black market. However, snorting or swallowing illegal rave drugs doesn't produce the same results as Ketamine infusions and also is associated with the risk of buying a drug of questionable quality under risky circumstances and may be cut with some other substance, or not even Ketamine at all.


Does insurance cover Ketamine for use in depression?

In the US, insurance doesn’t cover Ketamine therapy because its not specifically FDA-approved for use in depression.  Since it is OK to prescribe a drug for any purpose once it has been approved for one use, there is rarely motivation to got to the enormous expense of getting it approved for another (or ‘Off-Label’) use.  In order to obtain approval, the FDA requires manufacturers to conduct extensive trials that are hugely expensive, costing billions of dollars. Since Ketamine is unlikely to produce blockbuster profits, no for-profit corporation is likely to invest in FDA trials.  It is possible that the NIH or other government funded research center could fund this important research, but as of now there is no sign of that happening.

"FDA approval simply means that a company has government permission to advertise the drug for a specific disease. For example, aspirin is used to treat headaches, prevent strokes, prevent heart attacks, relieve pain, treat arthritis, and reduce fever; however, it is only approved by the FDA for fever and pain relief. So, utilizing ketamine for depression is no different from using aspirin to prevent strokes and heart attacks." Source >>

In the US, patients still may be able to have a portion of their charges to be covered by their insurance using CPT codes: 90833 -psychotherapy visit, 99214 - medical office visit.


Can I buy ketamine?

Ketamine is legally available only to veterinarians and medical doctors for medical use. Ketamine sold illegally on the street or in clubs is often stolen or diverted. Illegally purchased Ketamine is often cut with other substances or may not be Ketamine at all. Ketamine has been used for its mind-altering effects since the 1970s. In the 1990s Ketamine became known as a “club drug” for its use in the dance club scene. Street names include Special K, K, Ket, Vitamin K, Cat tranquilizers.

Unfortunately, the high cost of legal Ketamine is driving patients to the black market. However, snorting or swallowing illegal rave drugs doesn't produce the same results as Ketamine infusions and also is associated with the risk of buying a drug of questionable quality under risky circumstances and may be cut with some other substance, or not even Ketamine at all.


Who can use Ketamine therapy for treating depression?

Appropriate patients with a major depressive disorder without psychotic features would be those who have been treated with at least 2 different types of medication from two different drugs classes and has not obtained any significant benefit from therapy. In addition, patients who have failed to improve with bilateral ECT and RTMS therapy are also candidates for infusion therapy.


Who can't use Ketamine therapy?

Some individuals with specific medical conditions may not be be appropriate candidates for this type of therapy and they would include anyone with:

- Hypersensitivity (allergy) to Ketamine

- A recent myocardial infarction – less than 6 months ago

- Unstable Angina or Accelerated Hypertension

- Uncompensated congestive heart failure/pulmonary hypertension

- Known or suspected Cerebral Aneurysm or AVM

- A recent hemorrhagic stroke – less than 1 year ago

Several medications are known to compete at the NMDA and/or D2-3 receptor and therefore limited the clinical effectiveness of Ketamine, these include:

- Risperdal (risperidone),

- Zyprexa (olanzapine),

- Lamictal (lamotrigine).

Any patient currently on these medications would require a downward titration leading to a temporary discontinuation for approximately 2 weeks before the infusion series and during the course of Ketamine therapy. The medication may be resumed following completion of the infusion series if clinically indicated.

Also the use of benzodiazepines (Valium, Xanax, etc.), are “relative contraindications” and may need to be reduced prior to treatment for maximal benefit. Benzodiazepines are not exclusionary for Ketamine treatment. However, patients with anxiety may need a lower starting dose and more gentle dose adjustment over the course of treatment.


Will my current medications interfere with my Ketamine infusions?

- Lamictal (generic name Lamotrigine). Patients should allow 12 hours between taking lamictal and the start of their infusion. They should wait 6 hours after their infusion before resuming lamictal.

- Any MAOIs. Some common brand names are Isocarboxazid (Marplan), Phenelzine (Nardil), Selegiline (Emsam), and Tranylcypromine (Parnate). Patients cannot take any MAOIs within 2 weeks of an infusion.

- Patients taking large doses of benzodiazepines will have a reduced response to Ketamine. Some common brand names are Xanax (Alprazolam), Ativan (Lorazepam), Valium (Diazepam), and Klonopin (Clonazepam). You can still receive Ketamine treatment while taking benzodiazepines. It is perfectly safe, we just want to ensure the best possible chances for your success. You may skip a dose 24 hours before the start of your infusion and wait until 6 hours after before resuming your benzodiazepine.

SSRIs and tricyclics do not interfere with Ketamine. There is no need to stop them.If you are taking opiates, muscle relaxers, or anti-inflammatories, there is no need to adjust your dose. You should not adjust your dose or frequency of use of any prescribed medication without first consulting with your prescribing physician.


Does Ketamine therapy help in treating depression?

There are no mass double blind studies that can definitively prove the efficacy of Ketamine as a treatment for depression. Ketamine is long out of patent, and studies of off-label drugs are very expensive. Perhaps the Federal government may fund a study some day. All studies to date are considered anectodotal.

However, many clinical trials from respectable investigators (like the NIH) have shown that Ketamine infusions produce impressive results for up to 70% of patients. Patients with more severe type of treatment resistance including electro-convulsive therapy resistance would certainly require longer duration of treatment and more treatments than patients with mild treatment resistance.


How many Ketamine therapy sessions do I need to receive for treating depression?

Most of the patients who respond to Ketamine see some improvement the day of or after an infusion. Some patients require several infusions before they see a clear benefit.

Most clinics have settled on 6 treatments as a standard. About 30% of patients respond after the 1st treatment and  most of patients respond by the 6th treatment.

However, some clinics are using a different protocol for ketamine administration.

Neuro-Luminance Brain Health Ketamine Infusion Centers are using a once-per-week (or less) infusion protocol. Their patients receive 4.3 ketamine infusions total over their entire treatment course of 5 to 7 weeks. By their extensive experience, the drug does not work any faster when administered with multiple infusions in a week vs a single infusion per week.

Theodore Henderson, MD, PhD, at Neuro-Luminance Brain Health Ketamine Infusion Centers states that the standard protocol of 3 infusions per week over 2 weeks ignores the powerful, long-lasting potential benefit of ketamine as it takes weeks for neuroplasticity to develop fully.


Is ketamine addictive?

The dosages of Ketamine administered in our treatments are a small fraction of the doses used by drug abusers.

Although uncommon as a drug of abuse, Ketamine can be habit forming. Regular users of Ketamine become tolerant to the dissociative effects of the drug, meaning more and more is needed to achieve the same effect. Some people do become addicted, and continue to use Ketamine even when they plan not to or despite its negative effects. It is not clear whether people who are addicted to Ketamine experience any symptoms of withdrawal when they stop taking the drug.


Is Ketamine dangerous?

Ketamine treatment, when administered by a trained physician, has a remarkable record of safety. Side effects may include mild visual hallucinations, feeling of dissociation and ataxia. Patient’s should not drive for at least 4 hours after treatment. Very rarely, symptoms of LUTS (Lower urinary tract symptoms) have been noted. Patients suffering from Bipolar Disorder should avoid the treatment during the Manic Phase.


If not used under the care of health professionals in a medical setting, users of Ketamine put themselves at risk in a number of ways:

- People under its effects may be confused about their surroundings. Ketamine-related injuries and fatalities are often the result of falls and other accidents.

- Ketamine has been labeled a “rape drug.” This is because it can be slipped into someone’s drink without the person’s knowledge, and its effects can render the person unable to resist sexual assault. This is not a risk at normal therapeutic dosages for depression.

- Ketamine raises heart rate and blood pressure, which can increase the risk of stroke or heart attack.

- Frequent use of Ketamine may cause bladder problems (ulcers in the bladder).

- The Ketamine sold at clubs may be mixed with other drugs. Taking Ketamine with other drugs can have unpredictable and sometimes dangerous effects.

- Driving or operating machinery while under the influence of Ketamine, or any drug, increases the risk of physical injury to the user and to others.


There is no known lethal dose of Ketamine. Contrast that with drugs like narcotics or insulin which can easily kill a patient if the drug is either abused or a miscalculation is made. It should be noted that the dosages used for the treatment of depression are minuscule compared to what interests abusers, and that black market prices are actually vastly cheaper. The patients that benefit from Ketamine do not appear to ‘like’ the experience, but rather endure it for the sake of the substantial therapeutic benefits which typically kick in within a day or so of treatment.


How does Ketamine make you feel?

At low doses, Ketamine can have stimulant effects, but most patients describe it as pleasant, relaxing, deep or "spiritual" helping them to see their lives in a new light and  put things into a different perspective.

Most common side effects experienced during the treatment are : sedation, dry mouth, mild euphoria, vivid dreams, nausea and occasional vomiting, blurred vision, dizziness, dissociative experiences, disrupted motor skills, increase in heart rate, increase in blood pressure, deep breathing, increase in blood pressure in lungs, temporary anxiety.

Visual experiences can include blurred vision, seeing “trails,” and mild auditory hallucinations (like hearing a sound similar to a seashell on your ear). Users report a sense of floating, dissociation and numbness in the body. Some report feelings of an “out-of-body” experience. Dissociative experiences during Ketamine treatment are very uncommon and in some cases may be unpleasant. Most patients describe dissociative symptoms as "interesting" , "unusual" or "weird".  High doses can cause dissociation with intense hallucinations which can be frightening and upsetting.


How long does the feeling last?

Ketamine is rapidly metabolized by the body, and is usually mostly worn off within an hour after treatment. The anti-depressant effects however seem to persist, sometimes only for a few weeks, but many patients report efficacy for many months following treatment.


Will I require Ketamine therapy for the rest of my life?

Some patients achieve permanent relief after one series of infusions. Others will find that infusions enhance the impact of antidepressants or provide initial relief that is then sustained by oral medicines, other therapies, and lifestyle choices. If Ketamine therapy is the only solution that works for you, you may be able to space your infusions apart by 3-6 months. After the initial series of infusions restores the brain to a healthy balance, it is generally easier to maintain that balance than it was to attain it in the first place. You may want to receive “booster” infusions on an as-needed basis for maintenance.


What should I expect during my Ketamine therapy sessions?

For mood disorder patients, Ketamine is administered usually over a period of 50 minutes. The amount given will not cause you to lose consciousness. During the infusion, most patients have a mild dissociative experience, with an increased sensitivity to light and sound and an altered perception of time and color. Most patients tolerate these experiences without discomfort and many people find them to be pleasant. In the rare case these side effects are considered unpleasant, other rapid acting medications can be used to relieve or eliminate this discomfort. Once the infusion is complete, the dissociative effects of the drug rapidly dissipate and are often mostly gone within 20-30 minutes. Patients generally are able to leave a Ketamine clinic within 30 minutes following the infusion and aside from mild fatigue, feel much like themselves.


What side effects I should be concerned about?

Patients commonly feel tired following a Ketamine infusion. On rare occasion, some patients experience nausea after an infusion. If you are prone to nausea, a prophylactic might be administered before the infusion to help prevent it. Side effects usually dissipate within a few hours and are completely gone by the following day. There are no known long-term or permanent side effects of IV Ketamine Infusion Therapy.


Can Ketamine therapy make a bipolar patient hypomanic?

Although hypomania is possible, it is uncommon. You may need to postpone Ketamine therapy during the Manic phase of Bipolar Disorder.


What about a new drug Esketamine, or Spravato?

Being rushed through critical reviews, Esketamine was approved by the FDA in March 2019. Janssen, part of Johnson & Johnson, has patented a version of ketamine called Esketamine that doctors would be able to give their patients through the nose.

Spravato is a reformulation of “party drug” ketamine. After the FDA fast-tracked approval of Esketamine in March 2019, Janssen can sell a very low cost drug for almost $800 per dose.

Currently, its wholesale acquisition cost stands between $590 and $885 per treatment session. Costs for the first month of treatment, which includes two sessions per week, could range from $4,720 to $6,785.

“The effectiveness data weren’t particularly good,” said Diana Zuckerman, president of the National Center for Health Research, a nonpartisan institute that studies science and health in Washington. “Especially for men and people over 65, and that’s mostly who the VA serves.”

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