Introduction to Intranasal Ketamine Treatment
Ketamine was introduced as an anesthetic drug about half a century ago. Ketamine in sub-anesthetic doses has since demonstrated efficacy for other, but off-label, indications in adult and pediatric practice, including the management of pain in emergency settings, the management of postoperative pain, the treatment of medication-refractory headache, the reduction of agitation and violence in pre-hospital and emergency settings, and the mediation of pediatric sedation in various settings, ranging from dentistry to radiology. Ketamine in sub-anesthetic doses has also demonstrated rapid-onset efficacy in patients with severe and even treatment-refractory depression.
You have been diagnosed with Major Depressive Disorder and your doctor has recommended intranasal ketamine treatments to treat symptoms of your depression. Ketamine treatments have shown to have antidepressant effects identifiable at 4 hours post-ketamine and that persisted at a 72-hour assessment with the response and remission rates with one day post treatment at 71% and 29% respectively utilizing infusions. Depending on patient and severity of condition the antidepressant benefits were apparent at 40 minutes and can peak at day 1 with the need to pursue treatment continuously.
Your doctor will review all your medical and depression history to determine if the Intranasal Ketamine treatment is the appropriate treatment for you or not.
The treatment is performed under your psychiatrist’s supervision. Neither anesthesia nor sedation is required. You will be awake and alert during the treatment sessions. The treatment sessions include one initial monitored treatment in office followed by treatments at home as prescribed by your doctor. The initial monitored treatment session in office lasts approximately 2 hours. Your doctor will ask you to maintain your monthly appointments in order to monitor your performance and symptomatology.
What is the Mechanism of Action of Ketamine?
Currently the hypothesis for ketamine’s mechanism of action focuses on a cascade of neurochemical events that are initiated shortly after administration of ketamine. The events then persist in a protracted manner for days following its metabolism and elimination.
Ketamine is a NMDA receptor antagonist. However, the mechanisms underlying this effect remain unclear. Conventional wisdom suggests that ketamine’s effects are mediated through actions on the glutamatergic N-methyl-D-aspartate receptor (NMDAR). Although ketamine has been shown to have effects on several neurotransmitter and neuromodulatory systems, the majority of ketamine’s known pharmacological effects are mediated through the NMDA where it acts as an open channel, noncompetitive antagonist, binding within the ion channel and blocking ion influx.
When Should the Intranasal Ketamine Treatments be Used?
Intranasal Ketamine Treatments are prescribed to a highly selective group of patients who will have a firm diagnosis of treatment resistant depression and who have failed on full or high dose anti depressant treatment of at least 3 different types of prescribed medications for a full course with documented compliance.
It would be expected that these patients will also have received other interventions in the form of psychological therapies e.g. CBT, CAT etc., plus have either received or been considered for ECT and/or augmentation strategies to antidepressant treatment. These patients would be considered for intranasal ketamine treatment as they continue to exhibit a high level of functional impairment with subjective distress with or without suicidal risk. Ketamine is indicated as highly efficacious in patients with bipolar depression and PTSD.
When Should the Intranasal Ketamine Treatments Not be Used?
The abuse potential for ketamine is widely recognized therefore doctors should be fully aware when considering the suitability of the patient for the treatment. Additionally to contraindications, the safety and effectiveness of intranasal ketamine has not been established in the following patient populations or clinical conditions through a controlled clinical trial.
- Non-consenting, non-capacitous persons;
- Contraindication to the use of ketamine, including allergy and current use of medicine contraindicated with ketamine;
- Endocrine or neurological illness;
- Previous history of closed head injury, current head injury associated with possible intracranial hypertension, central nervous system masses, abnormalities, or hydrocephalus, ever had loss of consciousness;
- Previous history of glaucoma or acute globe injury:
- Abnormal nasal physiology which would not allow for adequate medication delivery;
- Any change in psychiatric medication type or dose within the past 30 days;
- Treatment with any MAOI’s currently or within the past 3 months;
- Has had a course of ECT within the past 3 months;
- Has ever used PCP or ketamine;
- Current substance misuse;
- Any Axis I disorder other than MDD that was judged to be the primary presenting problem;
- High risk of suicide;
- Meets DSM-V criteria for Mental Retardation;
- Has ever had Repetitive Transcranial Magnetic Stimulation (rTMS), Vagal Nerve Stimulation (VNS) or Deep Brain Stimulation;
- Is currently hospitalized;
- Has known or suspected schizophrenia, even if currently stable or controlled with medications
- The presence of any abnormal laboratory findings or serious medical disorder or condition
- Female hormonal treatments
Do I need to get off my medication when I start Intranasal Ketamine Treatments?
Patients are allowed to remain on stable doses of psychotropic medication, including antidepressant treatment.
Intranasal Ketamine Safety Information
Safety of the Intranasal Ketamine Treatments was demonstrated in a clinical study involving 20 patients, males and females aged 21 to 65 with a primary diagnosis of major depressive disorder, chronic or recurrent, without psychotic features, as assessed by a trained rater with the Structured Clinical Interview for DSM-IV. ll study treatments were performed at Mount Sinai Medical Center between April 2012 and June 2013. Participants were required to have failed to respond to at least one trial of adequate dose and duration of an antidepressant medication approved by the U.S. Food and Drug Administration. 18 patients completed two treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution in a randomized, double-blind, crossover study. The primary efficacy outcome measure was change in depression severity 24 hours following ketamine or placebo, measured using the Montgomery-Asberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured. Patients showed significant improvement in depressive symptoms at 24 hours following ketamine compared to placebo. 44% of patients met response criteria 24 hours following ketamine administration, compared to 6% following placebo. Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters. This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects.
In this study and other studies there were no deaths in patients who took part in the clinical trial. Possible side effects included dissociation which lasted up to 45 minutes after administration, nausea and headaches that resolves approximately 2 hours post administration.
You can discuss the possible side effects and precautions related to Intranasal Ketamine use with your doctor to determine if any precautions should be taken prior to or during your treatment.
The following side effects may occur:
- Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat
- dry mouth,
- mild euphoria
- vivid dreams
- nausea and occasional vomiting
- blurred vision, inability to control eye movements
- dissociative experiences
- poor coordination
- disrupted motor skills
- increase in heart rate
- increase in blood pressure
- deep breathing, slow breathing, shallow breathing
- increase in blood pressure in lungs
- temporary anxiety
- abdominal discomfort due to increased uterine tone
- high dissociation- normalises within two hours
- muscle stiffness
- pain when urinating
- Occasional low BP and premature ventricular beats which will most likely subside after treatment.
- Very bad headache
Patients have reported the following side effects:
- Abnormal sensations
Advice to Patients
Cautionary advice should be given to females; pains may be felt due to uterine contractions, depending on the stage of their menstrual cycle when treatment is administered.
You may be advised to not drive for 24 hours, not sign legal documents for 24 hours post treatment, not consume alcohol or use illicit drugs, or be left in charge of minors for 24 hours post treatment.
There may/will be other patients in the clinic during treatment however a single room will be allocated to you with a member of staff present throughout your treatment.
In many cases it is recommended that you bring along an escort with you to accompany you to your treatment sessions additionally it is advisable to have an adult to supervise you for up to 24 hours post treatment sessions both in home and after clinic.
It is your responsibility to let your primary care provider and other doctors know about the treatments.
While doing in-home treatments it is recommended to check your blood pressure on a regular basis and it is your responsibility to have regular heart function tests while on treatments (talk to your primary care provider about this).