Ketamine Infusion Therapy in Psychiatric Disorders

KETAMINE INFUSION
THERAPY IN PSYCHIATRIC
DISORDERS : A PROMISING
NOVEL THERAPY
DR DIYA MADHVI RUGHOO
CONSULTANT PSYCHIATRIST
MBBS ,MUHS INDIA
MD PSYCHIATRY , BHU INDIA
WHAT IS KETAMINE?
Ketamine got its start in Belgium in the 1960s as an anesthesia medicine for animals
• The FDA approved it as an anesthetic for people in 1970.
• It was used in treating injured soldiers on the battlefields in the Vietnam War.
• Unlike other anesthetics, ketamine doesn’t slow breathing or heart rate, so patients
don’t need to be on a ventilator to receive it.
KETAMINE MOLECULE
• Ketamine is a racemic mixture of two enantiomers,

• S-ketamine (esketamine)
• R- ketamine
• ketamine -analgesia and sedation
• In addition, ketamine and esketamine can rapidly and transiently alleviate treatment-
resistant unipolar major depression, including suicidal ideation
• This approach is consistent with clinical guidance from the American Psychiatric
Association and other experts.
PARTY DRUG
• Ketamine causes what doctors call a

“dissociative experience”
• A “trip.” That’s how it became a club
drug, called K, Special K, Super K, and
Vitamin K among others.
• Partiers inject it, put it in drinks, snort
it, or add it to joints or cigarettes.
WHEN TO USE KETAMINE
• Mood disorders, such as treatment-resistant depression

• anxiety disorders,
• post-traumatic stress disorder (PTSD)
• suicidal ideation
• 30% and 40% non responders
• 3 or 4 different traditional agents
• evidence-based nonpharmacologic therapies, such as cognitive behavioral therapy
(CBT) or mentalization-based therapy (MBT),
WAY FORWARD TO TREATMENT RESISTANT
• No good current strategies for these non-responders
• so novel agents are being studied — including ketamine
• Evidence based rapidly effective for an array of anxiety disorders, including social
anxiety disorder (SAD) and PTSD,”
HOW DOES KETAMINE WORK?
Ketamine has an affinity for multiple receptors:
. Opioid receptor – Ketamine is an opioid receptor agonist
. Ionotropic glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist.
.Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor

AMPA receptor is also involved in glutamate neurotransmission, and ketamine’s
antidepressant effects
. Glutamate, a widely distributed excitatory neurotransmitter, in mediating response to

stress and the formation of traumatic memories.
SYNAPTIC STRESS RESPONSE
• Its antidepressant and anti-anxiety effects

are presumed to occur through activating
synaptic plasticity by increasing brain-
derived neutrophic factor translation and
secretion and also by inhibiting glycogen
synthase kinase-3 and activating
mammalian target of rapamycin signaling.
SCHEMATIC PRESENTATION OF KETAMINE
ON SYNAPTIC CIRCUITRY
GLUTAMATE BURST
BDNF –SYNAPTIC PLASTICITY –KETAMINE
• Brain-derived neutrophic factor plays a role in behavioral responses to classical

antidepressants, but the impact on synaptic plasticity may take several weeks to
manifest
• In contrast, ketamine-mediated synaptic plasticity changes appear to occur within a
matter of hours after ketamine administration.
• The current thinking is that eventually, 6 to 12 weeks after initiating treatment with
traditional antidepressants, dendritic growth and increased synaptic connections
occur but with ketamine, these can occur within 24 hours of the infusion.
GAD/SAD
• A small study of patients with GAD and/or SAD (n=12) compared 3 ascending
ketamine doses to midazolam. Each was given at 1-week intervals, with midazolam
counterbalanced in dosing position across patients. Ketamine was found to dose-
dependently improve scores on the Fear Questionnaire.
• Moreover, it’s impact on decreasing theta frequency in the right frontal sites assessed
via electroencelphalogram (EEG) was comparable to that of conventional anxiolytics.6
• Glue et al GAD and/or SAD (n=20) and ongoing improvements in social functioning
and/or work functioning during maintenance treatment.
• impact of just one infusion lasted for 14 weeks, suggesting that patient[s] with anxiety
disorders might have longer maintenance of response than patients with major
depression, where the response has been maintained for only one week
ANXIOUS DEPRESSION /SOCIAL -AD
ANXIOUS BIPOLAR DEPRESSION
• Investigators concluded
• A study of patients with anxious and non-anxious bipolar depression (n=21 for both
groups) found that both anxious and non-anxious patients with bipolar depression
had significant antidepressant responses to ketamine
• ketamine’s novel role in the treatment of anxious bipolar depression
SUICIDALITY
ANTIDOTE TO SUICIDE
• Randomized trials have demonstrated that intravenous ketamine and intranasal

esketamine can each rapidly improve treatment-resistant depression, including
symptoms of suicidal ideation.
• To be clear: Casual use is not a treatment for depression. But doctors have developed
a protocol for medically supervised use that may help people who don’t get relief
from other medications.
1. Andrade C. Ketamine for Depression, 6: Effects on Suicidal Ideation and Possible U

se as Crisis Intervention 1.Suicide Risk. J Clin Psychiatry 2018; 79.
2. Trivedi MH. Antisuicidal
Effects of Ketamine: A Promising First Step. Am J Psychiatry 2018; 175:97.
3. Vande Voort JL, Ballard ED, Luckenbaugh DA, et al. Antisuicidal
Response Following Ketamine Infusion Is Associated With Decreased Nighttime W
akefulness in Major Depressive Disorder and Bipolar Disorder. J Clin Psychiatry 2017
; 78:1068.
OCD
• An open-label trial of ketamine in 10 patients with treatment-refractory OCD found

that ketamine’s effects on OCD symptoms, in contrast to depressive symptoms, did
not seem to persist or progress after the acute effects of ketamine had dissipated.
• Another randomized controlled trial (RCT) of 15 patients with OCD found that anti-
OCD effects from a single intravenous dose of ketamine persisted for more than 1
week in some patients with OCD with constant intrusive thoughts, demonstrating
that “a drug affecting glutamate neurotransmission can reduce OCD symptoms
without the presence of an SSRI.
PTSD
• In PTSD, there is “mounting evidence for a role of the excitatory neurotransmitter

glutamate in stress responsiveness, the formation of traumatic memories, and the
pathophysiology of PTSD, raising the possibility of identifying novel glutamatergic
interventions for this disorder.
• One double-blind study demonstrated that infusion of ketamine rapidly and significantly
reduces symptom severity in patients with PTSD compared with midazolam
• Another study found that administration of ketamine immediately after witnessing a
traumatic event has been shown to prevent the enhancement of passive avoidance learning
in mice.
• Ketamine may thus target the mechanisms involved in the consolidation of traumatic
memory and may enable the brain to reconsolidate memory and release trauma.
• A case study of a child with PTSD reported remission from behavioral dysregulation after
receiving procedural ketamine.
PTSD
DRAWBACKS AND POTENTIAL ADVERSE
EFFECTS
. Most side effects are mild and transient
• Potential increases in blood pressure and pulse.”
• Additional adverse events include nausea or vomiting
• Dissociation, or an out-of-body experience- annoying, spiritual ,feelings of unreality; visual
and sensory distortions; a distorted feeling about one’s body; temporary unusual
thoughts and beliefs; and a euphoria or a buzz
• “Dissociative experiences are sometimes seen as a biomarker for insufficient response and
suggest that the dose should be increased.”
• Providers should be aware that cystitis and lower urinary tract pathologies (eg, detrusor over-
activity) have been reported in long-term ketamine users, but typically only at high doses.
KETAMINE FORMS
• FDA has approved as a medication for depression is a nasal spray called esketamine (Spravato)
• . It’s for adults who either haven’t been helped by antidepressant pills, have major depressive disorder,
or are suicidal.
• They continue on their antidepressant and receive esketamine at a doctor’s office or in a clinic, where a
health care provider watches over them for 2 hours after the dose.
• For treatment-resistant depression, patients usually get the nasal spray twice a week for 1 to 4 weeks;
then once a week for weeks 5 to 9; and then once every week or 2 after that.
• Oral ketamine in india (Prof C.Andrade at NIMHANS)
INTRAVEOUS KETAMINE
• 2 infusions a week
• Then 1 infusion a week
• 1 infusion every 2 to 4 weeks.”
Most research stops the initial treatment at 6 weeks. There’s no research to suggest
that more than 6 weeks in a row brings more benefits, though people do go back for
boosters if symptoms return.
MY PATIENTS COMMENTS IN INTEGRATION
SESSIONS
• When people come out of this really profound experience, they have a lot to say, and these are people
who have a lot of baggage and a lot of experiential pain. A lot of times, ketamine leads to an unpacking
of that baggage
• I saw angels
• It was like a spiritual journey. I felt warm, safe, and confident. As the treatment went on, all the weight
of stress was taken off of me in layers. I felt like I had the power of the universe at my fingertips.
• Ene gros poid ine ale depi mo le Coeur
• My head feels lighter, and I don’t have that gloomy, dark, heavy feeling in my mind. And everything
around me looks brighter -- the sun, the lights in my office.”
BOOSTERS
. Ketamine is an intervention, but the notion of ‘treatment’ is much broader than that
• Weeks, months, or years after their first series of six to eight doses, patients may return for a booster.
• There is no standard recommendation for when or if people need a booster.
• They discuss it with their doctor if symptoms of depression start to reappear.
COST
. FDA has not approved IV ketamine for depression, most insurance doesn’t cover it.
Without insurance coverage, an infusion costs about $450.

$3,000 to $4,000 for the research-based six infusions over 3 weeks.
That doesn’t include boosters for whenever symptoms reappear.
TAKE HOME MESSAGES
. Brain health concept rather that mind or mental health shifting paradigm
. Ketamine a novel treatment in many psychiatric illness
. Brain health should be everyone priority especially in such a covid era
. Mauritius health policy and its health insurance users should know their mental
health is a priority as any other physical health and needs to be covered by insurance.

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What is ketamine used for?

What is ketamine used for?

How does ketamine work?

How does ketamine work?

KETAMINE INFUSION

• Ketamine is a racemic mixture of two enantiomers,

• Ketamine causes what doctors call a

• Mood disorders, such as treatment-resistant depression

• No good current strategies for these non-responders

• so novel agents are being studied — including ketamine

Ketamine has an affinity for multiple receptors:

. Opioid receptor – Ketamine is an opioid receptor agonist

. Ionotropic glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist.

.Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor

. Glutamate, a widely distributed excitatory neurotransmitter, in mediating response to

• Its antidepressant and anti-anxiety effects

• Brain-derived neutrophic factor plays a role in behavioral responses to classical

• Randomized trials have demonstrated that intravenous ketamine and intranasal

1. Andrade C. Ketamine for Depression, 6: Effects on Suicidal Ideation and Possible U

• An open-label trial of ketamine in 10 patients with treatment-refractory OCD found

• In PTSD, there is “mounting evidence for a role of the excitatory neurotransmitter

Without insurance coverage, an infusion costs about $450.

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