Ketamine Injections for Treatment Resistant Depression
Depression continues to be a disease that is not completely understood. Modern neuroscience has come up with logical and cohesive models, which describe depression as the deficiency or reduced activity of the neurotransmitters Serotonin, Norepinephrine and Dopamine in the brain. All FDA-approved medications affect one of or more of the above neurotransmitters. All available FDA approved medications take about four to eight weeks to reach their maximum effect. About 30 percent of patients continue to suffer from substantial symptoms of Depression despite multiple courses of psychotherapy and medications.
The art of psychopharmacology is to find the right combination of medications that will optimize the activity of the three aforementioned neurotransmitters for a given patient. However, current models of depression do not explain why antidepressants do not work instantly or why antidepressants do not work for all depressed patients. To complicate matters further, current research shows that Ketamine, an old anesthetic, works very quickly in relieving the symptoms of severe depression in patients who had no response to medications and/or ECT. There are several published trials that show that patients with severe treatment resistant depression improved after just one injection of ketamine.
Trifecta treatment philosophy
We screen and diagnose our patients carefully and explain the full range of treatment options. We openly share our clinical thoughts to help patient choose the best pathway for themselves. We create a unique treatment plan for each individual patient. We reassess progress at every session. We charge for each session separately, since it is impossible to predict how many treatments would be necessary. At Trifecta, we strive to make the patient a full partner in the treatment process.
Trifecta Ketamine treatment protocol
- Edward Fruitman, MD, Board Certified Psychiatrist, conducts a diagnostic interview. Prior attempts to treat Depression are analyzed, different treatment options, including psychopharmacology, ketamine, TMS, life style changes and psychotherapy are discussed.
- If Ketamine is chosen as treatment option, then expectations, treatment goals and treatment plan are discussed. First treatment session can be scheduled on the same day.
- During a treatment session, the patient is given two injections, 30 minutes apart. The patient is awake and aware of his or her surroundings, but feels mildly intoxicated. Intoxication is felt 5 minutes after injection and lasts for 15 minutes. Usually, patients report the subjective experience of the Ketamine-induced dissociation as pleasant.
- Patients are expected to stay at Trifecta Health Medical Center for a period of 90 minutes during the procedure. Following the ketamine treatment, the patient is discharged fully awake, oriented and sober.
- 24 to 48 hours after the first Ketamine treatment, patient is expected to feel better. If relief did not occur after the second session, then treatment plan needs to be changed, since Ketamine is not likely to have robust effect. Majority of patients do find that Ketamine helped their Depression and they continue treatment.
- We administer Ketamine under standard sterile conditions, in two divided doses per session, intramuscularly (IM), into the Deltoid muscle, using highly concentrated 100mg/ml solution drawn from sealed stock bottle, with small 28 gage needle. The total dose given in one session depends on patient’s weight, vital signs and ability to tolerate intoxication. Total dose, number of doses and time between doses is individualized to specific patient and is discussed prior to administration. Intravenous and subcutaneous administration is available, but is rarely used. Intranasal administration was used, but is being discontinued due to unpredictable results. Oral administration was never used due to lack of efficacy in research literature.
- The number of treatments is highly individualized, but expected to be between eight and twelve. Treatments are typically offered twice per week at first, and then once weekly.
Cost of Ketamine treatment
$300 per each session, if IM Ketamine is used (this is what worked for most of our patients)
$300 per each session, if SC Ketamine is used (only for patients with extreme needle phobia)
$525 per each session if IV infusion of Ketamine is used (we do not find this to be the best route of administration, but if patient insists on replicating research protocol of published studies, and is willing to tolerate the discomfort and additional risk of IV infusion, then we will perform an infusion of IV Ketamine at fixed dose of 0.5mg per kg)
How does Ketamine work?
The exact mechanism of how Ketamine works for treating depression is not fully known. Ketamine works on a neurotransmitter system called Glutamate (NMDA receptors), which is the most widespread neurotransmitter in the brain. In animal models, Ketamine improved a way in which neurons communicated with each other (neurogenesis through BDNF pathway), which may be the final common pathway through which all anti-depressants work. Most of the human research focused on treatment-resistant Major Depression, treating patients who failed to respond to multiple antidepressants.
Is Ketamine safe?
Ketamine has been widely used as an anesthetic for minor procedures since the 1960s. In many countries, it is used by first aid response workers when dealing with minor trauma. The safety of Ketamine is such that it is used as outpatient anesthetic by non-physicians. The dose used to treat depression is about one quarter (1/4) of anesthetic dose. At Trifecta, we administer a trial injection, followed in 15 minutes by regular injection. This is to minimize the chance of any negative reaction and to reassure the patient. Ketamine is very short-acting. The mind-altering effect is frequently compared to a mild alcohol intoxication and lasts less than two hours.
Most of the negative effects of Ketamine use are associated with medical errors or high chronic doses of Veterinary grade by recreational drug users (Special K). Ketamine is an FDA approved substance, but does not carry an indication for depression treatment.
Is Ketamine FDA approved for treatment of Depression? Is it legal?
Ketamine is an FDA approved schedule III controlled substance that is approved for anesthesia and pain management. Despite growing evidence for its rapid efficacy in treatment of Depression, it is not labeled as an anti-depressant by Food and Drug Administration.
Unfortunately, Ketamine is not likely to ever be recognized by FDA for its anti-depressant effect. This is primarily due to the system through which branded medications are approved for clinical use in this country. Usually, only the substances that carry financial interest from private industry get patented and submitted for FDA approval/indication. This process is fiscally too prohibitive to allow a generic substance, like Ketamine, to be presented to FDA for a new indication. Currently, multiple pharmaceutical companies are looking for substances with similar antidepressant properties to Ketamine. We are looking forward to being able to use a Ketamine-like FDA approved antidepressant. At this point, we are using Ketamine legally, but ‘off label’.
I have my own Psychiatrist, I want to stay with him. Can I still get Ketamine at Trifecta?
Yes. Many of our patients get referred to us by their treating Psychiatrists. We specialize in Treatment Resistant Depression. About one third of all depressed patients do not respond adequately to anti-depressants. Lack of response to multiple medications and psychotherapy is not the fault of treating Psychiatrist. We arrange with referring Psychiatrist the role Trifecta would play during and after the treatment episode. We encourage our patients to stay connected with their treating Psychiatrist if meaningful therapeutic bond has been established.
Who is a good candidate for Ketamine treatment?
Patients who failed to respond to multiple anti-depressants can be considered for Ketamine treatment. Ketamine treatment is safe, but is not FDA approved as an anti-depressant. We administer Ketamine based on available research data, which clearly indicates its usefulness in treatment resistant Depression. If patient has not tried some of the available FDA approved combinations of medications, we usually first prescribe a 6 to 8 week trial of rational psychopharmacology. There are some exceptions, based on suicidal ideation, need for rapid response, acute depression and intolerance of medications.
Who cannot get Ketamine injection?
Individuals with severe heart disease and individuals with severe uncontrolled hypertension should get a clearance from their cardiologist. Individuals who had a negative reaction to ketamine in the past should not get it administered again. Let us know about all of the medications that you are taking and all of your health care conditions prior to first ketamine injection.
Is Ketamine a replacement for anti-depressant medications?
No. Depression is a chronic recurrent illness, we recommend that patients who responded to ketamine continue on an anti-depressant medication regimen to prevent relapse. Frequently, following the treatment, the dosage of medications needed can be reduced and number of different medications can be minimized.
Can Ketamine be used long-term?
Trifecta uses Ketamine to treat acute symptoms and focuses on improvement of current treatment episode. Safety of Ketamine episodically is well established. Depression is a recurrent illness, our strategy is to find safe and effective maintenance treatment, and use ketamine primarily for acute exacerbations.
Is Ketamine addictive?
Ketamine is considered an addictive substance, FDA schedule III. It has an abuse potential and is misused recreationally in very high doses. However, there is no chance that our depression treatment protocol of in-office administration of sub-anesthetic doses of Ketamine under clinical supervision would lead to dependence, abuse or addiction.
Why is Intramuscular (IM) route of administration preferred by Trifecta?
IM administration is similar to IV administration in rapid reaction, effect and dose, but is better tolerated. It avoids the discomfort and risk of IV placement, avoids the risks associated with rapid infusion and is less expensive. Ketamine IM is 93% bioavailable to IV, which can easily be compensated by adjusting the dose. IM ketamine administration can be more flexible, since higher dose can always be administered during the same session, if the first dose was well tolerated and if recovery was rapid. If the first dose felt too intoxicating to the patient, then there is an option of giving two smaller injections with longer time apart. IM administration also allows to gradually increase the total dose administered, for better therapeutic effect, as tolerance to intoxicating effect of ketamine develops.
Why is most published data focuses on IV route of Administration?
Ketamine was FDA approved for anesthesia, so naturally first data came from IV administration of Ketamine. As is typical in research protocols, one tries to keep all of the variables constant, so most of the research on Ketamine for Depression treatment continued to use Ketamine IV. Researchers have to compare ‘apples to apples and oranges to oranges’ in order to keep their research findings relevant to existing fund of knowledge.
Why do some Ketamine infusion centers only offer fixed dose IV Ketamine treatment protocols?
There are multiple reasons why some centers may find that it possible for them to only offer IV Ketamine treatment. Some centers are operated by an Anesthesiologist and do not have a Psychiatrist on staff to assess treatment progress. Then, Ketamine infusion has to be administered in a similar way a pharmacist would fill physician’s prescription: deliver the exact amount of medicine prescribed, do not change the dose or protocol. Depression is a serious illness, so non-psychiatrists have to stay to very strict protocols to avoid making errors. Another reason is that some ketamine infusion centers only offer IV ketamine is that they conduct research and publish their data, so they need to have data that matches methodology of existing published work. Finally, some centers only offer the services that they find economically feasible, something that every private physician has a right to do. Infusion is relatively more expensive and requires greater degree of monitoring, and some centers may decide that it is the only kind of Ketamine treatment that they can offer. Trifecta welcomes all colleagues to join us in offering Ketamine treatment of Depression, at their own level of expertise and range of available options. We prefer to administer IM Ketamine, under observation of Board Certified Psychiatrist, as we find it effective, safe, better tolerated and more affordable to our patients. IV and Subcutaneous routes of administration are available to our patients if clinically indicated.