Ketamine

  • The 2017 Ketamine conference covered in the blog gives us the most up to date information about ketamine infusion from those involved in research and practice.
  • Ketamine infusion is available for our patients through two infusion centers: a new center affiliated with Lenox Hill TMS in San Francisco on Van Ness Street and Paul Wender’s infusion center on the peninsula.
Ketamine at Gateway Psychiatric

This page provides information for current patients about ketamine infusion at Gateway Psychiatric. Because ketamine infusion for depression is experimental (not approved by the FDA) and a relatively recent option for treatment, the content on this page is likely to change considerably over time.

The best source of the most up to date information about ketamine is contained in the section entitled “Ketamine Blog” below, as well as in the Ketamine Advocacy Network page under “Related Pages.”

For potential patients, it is important to understand that we perform ketamine infusion only after a thorough evaluation (see Getting Started above). While the short term results from ketamine infusion are sometimes dramatic, we know much less about the long term effects. For that reason, it is important to consider the other options for treatment resistant depression, including ECT, TMS, and other new treatments.

The section entitled Ketamine Infusion for Chronic Depression talks about details of the process for evaluation and monitoring for ketamine infusion at Gateway.

As part of our comprehensive approach to the treatment of depression and bipolar, we provide access to ketamine infusion for depression.

Before recommending ketamine infusion we complete a comprehensive psychiatric assessment. As part of that assessment we evaluate past treatment response. Other components of the assessment may include…

In order to improve your response to the treatment, all patients receiving ketamine infusion will be seen by a therapist during and after treatment.

  • Studies have found that even patients who have not responded to psychotherapy in the past often respond better to the combination of psychotherapy and ketamine.

After the initial infusion we will assess for changes in depression using the a standard rating scale. This assessment will include –

  • The Inventory of Depressive Symptomatology – Clinician – 30.
  • Presence of dissociative experiences at the time of infusion.
  • Presence of transient hallucinations.
  • Presence of mystical experiences.

All of these help us to predict treatment response.

Typically we expect to see a significant response after two infusions and if this does not happen we may reconsider completing the full course of treatment which is usually 4 – 6 infusions.

ketamine

Ketamine Reduces Suicidal Thoughts

A single infusion of ketamine reduces suicidal thoughts in depressed patients in one day, with benefits lasting for up to one week, according to a meta-analysis reported in the American Journal of Psychiatry. Further, ketamine did not seem to be just treating depression, it seemed to have an effect on suicidal thinking that was greater than its effect on depression “This suggests that ketamine has a specific effect on suicidal ideation that depends only partly on change in overall severity of depressive symptoms,” Samuel T. Wilkinson, M.D., of the Department of Psychiatry and the Child Study Center at Yale School of Medicine and colleagues wrote. Wilkinson and colleagues identified 10 previously published controlled studies on ketamine in depression and, by contacting the authors of those studies, they obtained individual subject data on the 298 patients who participated in these ketamine trials; patients in the control arm of the trials received either saline or ...
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ketamine long term effects

Long Term Effects of Ketamine

One of my patients asked me what the long term effects of ketamine are. She was particularly interested in long-term adverse effects. The last time I did a review of the literature I noted that there seem to be very little information available. This is not surprising with the psychiatric literature since ketamine and its use for chronic depression are experimental and date back only a few years. However ketamine has been used for chronic pain for much longer and so I imagined there would be some literature on this and agreed to do a search. In fact, there is very little in the literature about long-term effects, whether benefits or adverse effects, of repeat ketamine infusions at the doses used for treating chronic depression. Even the pain literature provides us with little data. A recent comprehensive review of the use of ketamine for chronic pain in cancer patients concludes: ...
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Default Mode Network and Depression Treatment – Ketamine and TMS

Interaction between the default mode network and parts of the pre-frontal cortex may explain some depression phenomena and also links to why TMS and ketamine work ...
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Steve Levine, MD - Ketamine Treatment Centers

Ketamine for Depression – 2017

I just got back from an inspiring conference in Berkeley on Ketamine for Depression. I am eager to implement some changes in how we work with people we refer or provide ketamine infusion for that may make the treatment more effective. The conference was organized by Alison McInnes, MD, MS, who is in charge of the Kaiser, San Francisco Ketamine Treatment Program, and included expert speakers from around the world. Dennis Hartman, founder of the the Ketamine Advocacy Network (KAN), organized an inspiring panel of ketamine patients . He also spoke of why he founded the ketamine network. He had a life changing ketamine experience at NIMH as part of a research protocol, and was then told, in essence, now forget the experience and go home... He did not do that, and instead founded KAN to advocate for making this treatment more widely available for those with treatment resistant depression. Steve Levine, MD, who runs ...
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Ketamine Guidelines

Ketamine guidelines have recently been published by American Psychiatric Association Council of Research Task Force on Novel Biomarkers and Treatments. They highlight what we know and what we don't know about this treatment. What We Know "Several studies now provide evidence of ketamine hydrochloride’s ability to produce rapid and robust antidepressant effects in patients with mood and anxiety disorders that were previously resistant to treatment." "To date, the strongest data supporting ketamine’s clinical benefit in psychiatric disorders are in the treatment of major depressive episodes without psychotic features associated with major depressive disorder. Even these data are limited by the fact that most of those studies evaluated efficacy only during the first week following a single infusion of ketamine. However, emerging studies suggest that repeated dosing can extend the duration of effect for at least several weeks... Most studies and case reports published to date on this topic have examined the effects of less than 1 month ...
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Depression Therapeutics and Mechanisms

The September 15, 2016 edition of Biological Psychiatry is devoted to updates in the area of psychobiology that relate to depression and its treatment. In this blog post I will summarize some of those studies to give you a sense of what is going on in the field. Some of these studies may not be replicated in follow-up research, but some of them may end up leading to significant advances in the area of treating depression. Creatine was found to be effective  in augmenting response to serotonin reuptake inhibitors  in women in one recent study, but was found to be no more effective than placebo in another. In this follow up article, Yoon and colleagues used multimodal neuroimaging in a randomized clinical trial of female patients with major depressive disorder and found that the creatine group showed increased prefrontal N-acetylaspartate levels and greater neuronal connections in the prefrontal cortex. N-acetylaspartate levels are thought to be a ...
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Antidepressants Alter Gene Expression

An interesting study looked at similarities and differences in the effects of two medications that have anti-depressant effects and yet are extremely different in terms of how they work: ketamine and imipramine (a tricyclic antidepressant). This industry supported study looked at the effects of these two agents on a reward circuit (involving the prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala - see picture on the right) in the brain. This circuit has been shown to be activated in substance use, and one theory about what causes substance use is the "hijacking" of these circuits so that they respond preferentially to ingestion of the triggering substance and do not respond to environmental cues and rewards. The circuits have been shown to be deactivated in depression - and this deactivation is linked to the loss of pleasure (anhedonia) and motivation associated with depressed mood. The study looked at two groups of mice, one group was ...
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A Better Ketamine

A better ketamine may be coming. That is the conclusion of NEJM Journal Watch Psychiatry reviewer Barbara Geller. A common pathway to identifying new drugs, is looking at metabolites of a medication to see if there is one metabolite that works better than the active drug (desvenlafaxine - one of the metabolites of venlafaxine - may or may not be an example of the success of this approach). Ketamine itself comes in two enantiomeric forms (escitalopram is the "S" enantiomer of citalopram), as do many organic molecules. Researchers have found that, though  the S-enantiomer is more potent at NMDA inhibition, the R-enantiomer has greater antidepressant action. This has called into question the NMDA inhibition theory of how ketamine works as an antidepressant. In this study, the authors go further and show that the metabolism of ketamine to hydroxynorketamine (HNK) is essential for antidepressant effects. And, beyond that, it is specifically ...
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Rapastinel Origin

Rapastinel for Depression

The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to rapastinel, which follows the medication receiving a 2014 Fast Track Designation from the FDA. Rapastinel, an investigational medication for adjunctive treatment of major depressive disorder, is an intravenous drug that is a novel NMDA receptor agonist. It is being developed by Allergan. The Breakthrough Therapy designation is a new category for agents that treat serious medical conditions that have the potential to be a "substantial improvement" over existing medications. It is intended to fast-track development of these agents. Ketamine is the NMDA receptor agonist that has made the topic of agents like rapastinel so exciting as potential treatments for a major depressive disorder. But ketamine comes with a number of side effects.  The origin of rapastinel (formerly known as GLYX-13) is illustrated in the picture to the right and in a press release from the NIMH, which funded some of ...
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ketamine for depression

Ketamine for Depression Update

Probably the most exciting development in psychopharmacology in years is the discovery of the dramatic effects of ketamine on depression. However, a recent report from the American Psychiatric Association (APA) Task Force on Novel Biomarkers and Treatments highlights not only the reason for the excitement about ketamine but also the significant areas of uncertainty that make it not yet ready to implement on a routine basis in the treatment of patients with depression. The studies found very significant immediate effects after ketamine infusion. In most of these studies the effects remained significant, although less pronounced, for at least a week after infusion. The results for bipolar depression were less positive but still significant. There are potential adverse effects of ketamine infusion. The studies that reported blood pressure changes all noted a transient significant increase in blood pressure (of from 8 to 18 mm Hg). And ketamine can lead to an increase in dissociation ...
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The Ketamine Advocacy Network provides some of the best information about this approach to treatment. It discusses the science and also the practical aspects of treatment (how to prepare for your first infusion, for example).

The Treatment of Chronic Depression page on our site discusses various important issues related to the assessment and treatment of chronic or treatment resistant depression.

Our Blog has a number of other articles relevant to depression, both the psychobiology and new treatment approaches.