The following is a quote from the National Institute of Mental Health's website:
"By now, everyone knows that medication
development for mental disorders has hit a wall, pharmaceutical companies have abandoned the search for new medications,
and there are no promising new medications on the horizon. So it is important to take a moment to consider ketamine, an anesthetic
that has been around for decades. Twenty years ago ketamine achieved notoriety as a recreational drug under the moniker "Special
K." But in the past decade, ketamine has emerged as a potential antidepressant.
Recent data suggest that ketamine might be the most important breakthrough in
antidepressant treatment in decades. Three findings are worth noting. First and most important, several studies demonstrate
that ketamine reduces depression within six hours, with effects that are equal to or greater than the effects of six weeks
of treatment with other antidepressant medications. The shift from six weeks to six hours has already transformed what we
could and should expect of antidepressant treatments.
Second, ketamine's effects have been noted in people with treatment-resistant depression. Most of the
studies to date have tested ketamine in people for whom other treatments were not effective, including both medications and
psychotherapy. This promises a new option for people with some of the most disabling and chronic forms of depression,
whether classified as major depressive disorder or bipolar depression.
Third, it appears that one of the earliest effects of the drug is a profound reduction in
suicidal thoughts. Although lithium and clozapine have been reported to reduce suicide risk, we have not had medications that
were specifically anti-suicidal. It is too early to label ketamine as an anti-suicide medication, but the reduction in suicidal
thoughts even prior to the antidepressant effect is promising, especially given the risk of suicide in people with severe,
there is enough potential here that several universities and companies have launched research and development efforts. Reports
of efficacy both obsessive-compulsive disorder and post-traumatic stress disorder have surfaced in the past year. Recently
the Food and Drug Administration awarded breakthrough therapy designation for the development of intranasal ketamine for treating
depression. This is the first time this special designation, usually reserved for drugs targeting an epidemic or a deadly
form of cancer, has been awarded for the development of a medication for a mental disorder. This speaks not only to the
scientific opportunity but the public health need for having a rapid antidepressant.
That need is leading to ketamine clinics using this drug "off-label"
to treat depression. While the science is promising, ketamine is not ready for broad use in the clinic. We just don't know
enough about either efficacy or safety. But with the excitement generated by early results, we will have more information
soon. The doom and gloom surrounding medication development, at least for depression, seems to be rapidly resolving."
Usually there is a delay of weeks to months in treatment
response with conventional antidepressants, which is a major drawback that highlights the need to develop faster
acting agents. This is particularly of paramount importance for depressed patients who present with suicidality,
a major challenge in Treatment Resistant Depression (TRD). So far, Ketamine looks promising as a potentially rapid
acting antidepressant with a novel mechanism of action.
Facts about Ketamine Treatments
- Ketamine, an FDA-approved anesthetic,
has shown promise in rapidly and effectively treating TRD, sometimes in as soon as 2 hours
- Several pharmaceutical companies are working to develop Ketamine isomers or metabolites
to treat TRD. Janssen Pharmaceutical, for example,
has developed a Ketamine enantiomer for intranasal use, called Esketamine, that is currently in phase II clinical trials with
- In August 2016 the FDA put
Esketamine on the fast track to official approval for use in treating
- Duration of benefits following injections varies widely, and more research is needed to help guide
- Reports also suggest Ketamine
may have a role in treating Bipolar depression, severe anxiety, OCD, PTSD, & chronic pain, but more research is needed
in these areas as well.
- Ketamine works primarily
as a glutamate receptor (NMDA) antagonist. It suppresses the excitatory neurotoxicity effects of glutamate, promotes synaptogenesis
in key brain areas involved in depression, and rapidly improves symptoms of TRD, including suicidality. Most of the approved antidepressant medications primarily target
brain monoamine systems (serotonin, norepinephrine, or dopamine) and, unlike Ketamine which acts ultra-rapidly (usually within
two hours of infusion or even quicker), none of these are known to target the glutamate system, which has been implicated
as an important therapeutic target based on recent research in TRD.
- The efficacy of Ketamine in TRD, compared to other antidepressant
medications, stands out in terms of not only its rapidity of effects (within 2–4 hours) but also its ability to rapidly
reverse suicidality in patients with TRD. We are excited to partner with The Georgia Treatment Resisitant Depression Clinic, becoming
one of the few sites in the nation offering this promising new option for patients with TRD!
What to Expect
- Typically, a patient will receive a series of two intramuscular injections in the
2-3 days apart.
- Because Ketamine works
so rapidly, patients will know whether or not they are responding after two injections and then can consult with the Psychiatrist
regarding the option having three additional injections over the next 10-12 days or so.
- We have found that the beneficial effects of a series of 5 injections within a 15-day
period may last anywhere between 5-12 weeks.
the index course of five treatments, patients may choose the gradual tapering of a course of maintenance therapy versus taking
a "wait and see" approach as to how long benefits will last, resuming injections only when the beneficial effects
- At times, injections can rapidly reverse
depressive symptoms to the point they can be adequately treated solely with maintenance antidepressant
medications prescribed by your referring physician.
are generally well tolerated, with nausea, brief dissociation during the first 15 minutes or so, and slight blood pressure
increases being most common.
- The patient
must remain in the office for 60-90 minutes after the injection and must be cleared by the doctor or nurse prior to being
released to drive. it is preferrable to have someone drive you the first visit to see how you repond prior to driving yourself.
Cost of Injections
- Ketamine's use in Psychiatry, while promising, is not yet FDA approved and therefore NOT covered
by any insurance plans.
- The cost of each injection and clinical monitoring is $150.
Ketamine in the Press
Ketamine: The Future of Depression Treatment?
FDA puts Esketamine on Fast-track for Approval
The last decade
has witnessed not only emergence of novel interventions like Ketamine but also the considerable progress which has been made
in examining the utility of the other not-so-new interventions like TMS.
In this section we present an overview of the various key aspects of Ketamine, that is, neurobiology
of the glutamate system in depression and role of Ketamine (and its metabolites) in inducing remission of symptoms of TRD quite rapidly and role of ketamine in
neuroplasticity and synaptogenesis that could possibly explain these rapid effects. One limitation of ketamine is its short
lasting effects. The major mechanisms of action of Ketamine (and its metabolites) in depression are (1) its antagonism of
the NMDA subtype of glutamate receptor, (2) its inhibition of the phosphorylation of the eukaryotic elongation factor 2 (eEF2,
also called CaMKIII) thus resulting in increased synaptic protein synthesis, (3) its action via the mammalian target of rapamycin
(mTOR) dependent synapse formation, (4) its inhibition of the nicotinic acetyl choline receptor (NAR), and (5) its suppression
of the glycogen synthase kinase 3 (GSK-3). Ketamine’s
effect on GSK-3 provides the rationale to combine ketamine with lithium (which suppresses GSK-3 as well) for their possible
synergistic effect on treatment resistant depression.
Ketamine is primarily known to be an antagonist of the excitatory glutamate receptors: it directly blocks
the NMDA subtype of the glutamate receptor and through this it indirectly affects the AMPA receptors, the other subtype. The
neurobiological mechanisms that implicate the glutamate system in TRD and the role of ketamine in it are complex and are dependent
on many factors including the dose of ketamine and locations of the glutamate receptors not only in the key brain areas implicated
in TRD but also with respect to the synaptic junction, that is, presynaptic versus postsynaptic. Many researchers have further
elaborated upon the possible dysfunction of glutamatergic signaling contributing to depression by the involvement of D-serine
which is a key NMDA receptor coagonist that plays a critical role in long term potentiation and also NMDA-induced toxicity
which has been implicated as one of the neurobiological mechanisms of depression. Glutamate evokes the release of D-serine
from astrocytes and neurons, which then acts at the glycine site on the NR1 subunit of NMDA receptors that result in excitotoxicity.
Ketamine, by its antiglutamate actions, is postulated to reverse this neurotoxicity, promote rapid proliferation of the dendritic
spines in key brain areas, and thus rapidly reverse the symptoms of depression.