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Ketamine and Spravato (Esketamine) Therapy

The use of ketamine in psychiatry has been one of the most groundbreaking innovations in decades for those suffering with mood and anxiety disorders. The drug was developed over 60 years ago as an anesthetic medication to help with sedation and pain management but only in the last decade has it found its place as a new tool in helping those with management of difficult to treat psychiatric conditions. Unlike other anesthesia medicines, ketamine at appropriate doses has little impact on breathing, blood pressure, and other important vital body functions. In addition to its use in hospitals for surgical and post-surgical pain and sedation, ketamine is used by medics on the battlefield because it can be administered so quickly and safely and by vetinarians to tranquilize large animals during surgical procedures. Ketamine is also known as a drug of abuse because of the euphorigenic and dissociative effects at high doses.

So how did this medicine find its way into the psychiatrist’s office? Observations from health care professionals that patients who received ketamine for pain or sedation also experienced a rapid improvement in mood and anxiety led to a further examination of its mechanism of action and a number of studies evaluating its’ antidepressant and anti-anxiety effects. The findings of these studies showed that ketamine was well tolerated, worked quickly, and by targeting a chemical in the brain-glutamate- not affected by most traditional medication treatments, seemed to work in those not responsive to many standard antidepressant and antianxiety medications.

So why is ketamine not an FDA approved mediation for depression or anxiety? Ketamine is off patent, meaning that any generic pharmaceutical manufacturer can produce the medication at a very low cost. Therefore, there is no financial incentive for any company to spend the millions of dollars required to go through the regulatory approval process. Fortunately, the medication is readily available but its use is considered off label. Because the necessary studies and extensive government review process have not been done, there still remain unanswered questions about its safety and efficacy in psychiatric disorders.

Recently, a newly patented variation (or isomer for those with a chemistry background) of ketamine has been approved by the FDA called esketamine (brand name-Spravato) for treatment resistant depression given intranasally. Doctors are just learning how to use this form of ketamine. With FDA approval, there is the hope that insurance may cover treatments with this medication and doctors and patients have the added comfort in knowing that experts in the field believe that this treatment option is safe and effective.

Anyone considering ketamine or esketamine should educate themselves about the risks and benefits of such treatments. Keep in mind, there are many effective, FDA approved therapies you should consider first before trying ketamine. While esketamine has been recently FDA approved, there is still limited clinical experience and the indication is only for treatment resistant depression. Ketamine for any psychiatric condition is still an off-label use and should only be an option when other more scrutinized and regulated treatments have bene tried. Your health care provider is ultimately the best resource to see if ketamine or esketamine (Spravato) is right for you.

Your Ketamine Questions Answered Here:

Our ketamine/esketamine clinic is under the direction of Michael Banov MD, a board certified adult and adolescent psychiatrist and board certified clinical research investigator. Dr. Banov has been administering ketamine to patients for several years and was an investigator in the esketamine clinical trials that lead to the approval of that medication. He is one of a handful of psychiatrists nationwide with experience in all routes of administration of ketamine, including intravenous (IV) ketamine. He has also written a paper reviewing the research on ketamine in management of anxiety disorders.

Many ketamine clinics are run by anesthesiologists, family physicians, or other non-psychiatric physicians who may be experienced in the delivery of ketamine but have little to no training in the diagnosis or management of psychiatric disorders. Board-certified psychiatrists with experience in treatment resistant disorders and long track records of delivering ketamine are the most qualified to determine the most appropriate patient for this type of treatment and manage all the nuances in ketamine administration, concurrent use of other psychiatric medication, and deal with any potential psychiatric complications during and after treatment.

The intravenous (IV) delivery of ketamine is the most commonly studied and likely the most effective formulation when treating acutely suicidal and severely depressed patients. Bioavailability, or the amount of drug that gets into the body, is predictable and close to 100% with IV dosing. IV ketamine can be stopped quickly if problems occur and the dose can be easily adjusted during administration. Ketamine is a very short acting medication so once the IV is stopped, any side effects generally resolve within a few minutes. The ketamine dose is usually lower than that given for sedation or pain management, typically between 0.5mg/kg to 0.75 mg/kg given over 40 minutes. Some patients however may require higher or lower doses depending on their response and tolerability.

We also offer intramuscular, intranasal, or oral ketamine in our clinic. Intranasal and oral formulations are most often given in our ketamine assisted psychotherapy program or if someone is not a candidate for IV, reluctant to have IV administration, or unable to afford IV treatment. Intramuscular delivery has a greater absorption rate than intranasal or oral but, in some patients, can trigger more intense and rapid dissociative effects that are can be more difficult to manage due to its quick absorption into the body. All of these formulations can be effective but because the bioavailability is less than that of IV, the amount of medication that gets into the body is less predictable. These delivery forms are typically used for patients where there is less urgency to get better quickly or in those patients with less severe symptoms.

Esketamine (Spravato) is only administrated intranasally and has to be given in a registered Spravato clinic by staff that has undergone training in the safe delivery of this medication. The medication can only be given in office and patients have to be observed for 2 hours post administration to determine whether they have had any adverse reactions.

All patients receiving any formulation of ketamine or esketamine must be escorted home and not drive themselves from the clinic.

he first step is to ask your health care provider whether this may be an appropriate treatment for you. They know your mental health history best and can help you determine whether other traditional treatments you may not have tried may be more appropriate first. Do your own research as well from reliable sources so you are familiar with the risk and benefits of ketamine and esketamine treatment.

 

Anyone considering ketamine in our clinic needs to have a consult with one of our board-certified psychiatrists to determine if they are appropriate candidates for such therapy. This can be done in person, via telemedicine, or by phone. Such consults can range between 30-60 minutes depending on the complexity of the history and psychiatric condition. Esketamine (Spravato) consultations may be covered by insurance but ketamine is not.

Intravenous ketamine is $550 per infusion. Our protocol is for six treatments to be given over two to three weeks. While some people may experience improvement after one or two doses, it may take up to six treatments to find the right dose range and to determine if there is going to be a response.

Intranasal and oral ketamine is $400 per treatment and does not include the cost of the compounded medication, which can run an additional $50-$80 total for six to ten treatments depending on the dose and route of administration. All medications are kept securely in our clinic.

Ketamine assisted psychotherapy (KAT) is $600 per session, which includes medically supervised ketamine administration followed by guided meditation and/or psychotherapy. KAT has been demonstrated to help people who are psychologically “stuck” gain new insights and perspectives in their negative thought patterns and belief system and develop ways to overcome them.

We don’t know the cost of esketamine (Spravato) at this time and wont until the medication is readily available and we have some sense of how it will be covered by health insurance companies.

Ketamine response rates of up to 75% have been reported in those who have not responded to traditional antidepressant therapy. While that is great news, similar to conventional antidepressant therapy, maintenance medication is usually required to continue the positive response and prevent recurrence of symptoms. We do have patients who have not tolerated or have had inadequate response to conventional therapies choose to not use any other medication other than ketamine on a regular basis (every 1-3 months) however the majority of our patients will stay on some type of medication post treatment. Long term maintenance antidepressant therapy is recommended for anyone with three or more lifetime depressive episodes.

 

How long will the positive effects of ketamine last and how frequent maintenance treatments are needed to stay well remains unclear. We know that symptoms quickly return after one or two treatments for many but our protocol of six treatments for 2-3 week then once a week for 4 weeks seems to prolong the positive effects. Many of our patients doing well seem to require periodic booster treatments that can range from every one to six months. We are learning more and more over time about ketamine as a maintenance treatment but for now it appears for many, some medication and possibly future additional ketamine treatments will be required.

We work closely with your doctor, counselor, and anyone else involved in your care to make sure you are getting the most out of your treatment. We encourage everyone receiving ketamine/esketamine (Spravato) treatment to continue with their current treaters or if not under any psychiatric care, we will help you find someone who can follow you during and after treatment. Outside therapists and doctors are welcome to be part of your treatment if you wish as well. Many of our patients have their counselors come in after the treatment to debrief and review the experience.

While all medications have risks associated with them, ketamine and esketamine (Spravato) seem to be relatively safe if administered by trained professionals and monitored carefully during treatment. Common, mild side effects include dizziness, sleepiness, nausea, vomiting, dissociation, and headaches. Less common but more concerning possible side effects include elevations in blood pressure, heart rate, and anxiety from the dissociative experience. We monitor your heart rate and blood pressure before and after treatment and with IV therapy, throughout the entire time the medication is administered. Though infrequently used, we have medications on hand to bring blood pressure and heart rate down during treatment. We typically start treatment at a low dose range to make sure the dissociative effects are minimized. With all forms of ketamine, we can give some antianxiety medicine if needed during treatment and with IV administration, we can stop the infusion and any distressing feelings will go away within a few minutes.   

There are few long term studies of ketamine administration but we do have decades of clinical experience, mostly from pain management clinics. Many have had patients receiving regular IV and other forms of ketamine for years and those clincis have not seen any significant problems emerge. One of the few reported risks of long term ketamine use are bladder and kidney problems. These, however, have generally occurred in those who have abused the drug recreationally in large doses. We carefully monitor our patients during and after treatment and stay current with the scientific literature on any risk that may arise in the future.

Benzodiazepines, a class of anxiety and sleep medicines that include Xanax (alprazolam), Ativan (lorazepam), and Valium (diazepam) to name a few, as well as alcohol may interfere with ketamine effectiveness. Alcohol use typically worsens depression and anxiety disorders despite some temporary relief from self-medicating. Benzodiazepines are not recommended for long tern use and often can have dangerous long term side effects as well as be habit forming. We do not recommend using benzodiazepine or alcohol during ketamine therapy. We encourage anyone with depression and anxiety to stop alcohol consumption and discuss with their doctor tapering off benzodiazepines. You should not stop benzodiazepines on your own without taking with your doctor due to risk of withdrawal symptoms.

Marijuana or THC has been associated with worsening of depression and anxiety long term though many people may feel temporarily relief when using.  Little is known of the effects of combing marijuana/THC with ketamine. We strongly encourage discontinuing any marijuana usage so you can get the most out of the ketamine treatment and minimize any negative effects it may have on your depression and anxiety. Effects of cannibidiol (CBD) with ketamine is unknown. It is unlikely to have a negative impact on ketamine treatment but we ask that you refrain from CBD use the day of ketamine administration.

Cocaine, amphetamines (which includes many medications for Attention Deficit Disorder-ADHD- such as Adderall or Ritalin), or other illicit drugs associated with elevating heart rate or blood pressure should be avoided if getting ketamine treatment. Similarly, we discourage the use of opiate usage during ketamine treatments to minimize any negative impact they may have on ketamine effects, unknown risks of combining these medications, as well as the negative effects opiates have on mood and anxiety disorders.

We do drug test everyone starting ketamine and regularly throughout treatment. A positive drug screen may disqualify you from ketamine treatment based on the staff’s clinical judgment. Please be honest with our staff about drug or alcohol use. We are not here to pass judgement but to help you get better in the safest and most effective way.

Absolutely. Despite high rates of success of ketamine treatment, depression and anxiety is not one condition. This means that not one treatment will work in any given person. Often revisiting a treatment that worked in the past but stopped working may be effective again after a while. Often unique combinations of medications, even ones you have taken before, may work in conjunction with another, even if it didn’t work well alone. There are older medications such as tricyclics antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs) that are not commonly used today but are highly effective for some people. Electroconvulsive Therapy (ECT), Transcranial Magnetic Stimulation (TMS) and a host of new, innovative treatments that have either recently been approved or are in development may provide relief of symptoms. We can help direct you to those resources or you can ask your health care provider for treatment settings, locally and nationally, that have experience with less commonly used treatments. Never give up hope because there are always answers. They just aren’t the same for everyone.

Contact our practice for more information about ketamine treatment options including oral, intranasal, and intramuscular administration or esketamine (Spravato) therapy or if you are just not sure what is best option for you.

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