TEWV Ketamine Protocol for
treatment resistant depression
PHARM-0003-01.v0
Status: Approved
Document type: Protocol
Copyright
reserved.
or by any
stored in
copyright
(c) Tees Esk and Wear Valleys NHS Foundation Trust 2013 All rights
No part of this publication may be reproduced or transmitted, in any form
means, electronic, mechanical, photocopying, recording, or otherwise, or
any retrieval system of any nature, without the written permission of the
holder.
Contents
1.
1.1.
1.2.
2.
2.1.
3.
3.1.
3.2.
4.
4.1.
4.2.
4.3.
5.
6.
7.
8.
9.
9.1.
10.
11.
12.
13.
Introduction....................................................................................................... 3
Governance ....................................................................................................... 3
Why we need this protocol............................................................................... 3
Purpose .............................................................................................................. 3
Objectives ........................................................................................................... 3
Scope................................................................................................................. 4
Who this protocol applies to ................................................................................ 4
Intravenous Ketamine (sub anaesthetic dose) as a treatment option........... 5
Indications .......................................................................................................... 5
Contraindications ................................................................................................ 5
Obtaining consent ............................................................................................ 5
Recording consent .............................................................................................. 5
Advice to patients ............................................................................................... 6
Patient information .............................................................................................. 6
Patient escort .................................................................................................... 6
Prescribing Ketamine ....................................................................................... 6
Treatment process ............................................................................................ 6
Delivering same-sex accommodation ............................................................. 8
Side-effects ....................................................................................................... 8
Patient-reported side effects ............................................................................... 8
Monitoring ......................................................................................................... 9
Termination of treatment .................................................................................. 9
Related documents ........................................................................................... 9
Document control ........................................................................................... 10
Ref: PHARM-0003-01.v0
Page 2 of 10
Title: Ketamine – Protocol for the use of ketamine
in treating severe resistant depression
Approval date
Introduction
Ketamine is a drug commonly used as a sedative and analgesic in emergency medicine as well as
a general anesthetic. It induces a state of dissociation and is used as a recreational drug.
However it also has rapid antidepressant effects occurring within two hours and response patterns
can last from days to weeks with most patients falling into the “rapid relapse” pattern (symptoms
returning within 2 weeks)
Governance
Clinical governance of the ketamine protocol is being led by Dr Angus Bell Senior Clinical Director,
Dr Vinod Chaugule ECT lead for the trust, Dr Richard Cree Consultant Anesthetist for James Cook
University Hospital and Dr Fulford Consultant Urologist at James Cook University Hospital each
bringing their particular expertise with regard to treatment resistant affective disorders,
neuromodulation therapies, anesthesia and urological consequences of ketamine.
In addition Dr Angus Bell is a member of National Red Kite Consortium which is a group of clinical
leaders from across the UK who are linked in to the Red Kite Research Group in Oxford led by Dr
Rupert McShane who are currently running maintenance treatment using ketamine following an
acute treatment trial. This comprises monthly webinars to share documentation and exchange
experience from this consortium. The aim is to have shared patient information documentation
and agreed protocols across multiple sites so that clinical data can be shared and compiled with
the Red Kite project.
1. Why we need this protocol
1.1. Purpose
The purpose of this procedure is to pilot the use of an extended treatment of ketamine infusion to
achieve and then maintain remission in patients with treatment resistant affective disorder.
All of the literature uses the same dose: that of a single sub anaesthetic intravenous dose of
ketamine at 500 micrograms per kilogram given over 40 minutes with continuous vital sign
monitoring.
The pilot will use a modified version of the protocol reported in Biological Psychiatry 2010;
67(2):139-45 using a twice weekly regime within the ECT clinic with a maximum of 6 sessions for
the acute phase of treatment.
Response rates in controlled trials have ranged from 25% to 85% at 24 hours post infusion and
from 14% to 70% at 72 hours post infusion. The mean time to relapse after the acute phase at the
end of the trial was 19 days. A weekly assessment is proposed with a planned further infusion
fortnightly extended to 3 weekly depending on response.
As the use of ketamine for the treatment of severe resistant depression is new, this
protocol will be subject to change as new information becomes available.
1.2. Objectives
Ref: PHARM-0003-01.v0
Page 3 of 10
Title: Ketamine – Protocol for the use of ketamine
in treating severe resistant depression
Approval date
This document aims to provide clinical guidance to ensure safe administration of ketamine (sub
anaesthetic dosage) via Intravenous Infusion.
2. Scope
2.1. Who this protocol applies to


This treatment will only be provided on an approved named patient basis for treatment
resistant depression.
The treatment will only be performed at the Ryedale Suite, Roseberry Park.
Ref: PHARM-0003-01.v0
Page 4 of 10
Title: Ketamine – Protocol for the use of ketamine
in treating severe resistant depression
Approval date
3. Intravenous ketamine (sub anaesthetic dose) as a
treatment option
3.1. Indications
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
prescribed for a full course with documented compliance.
It would be expected that patients will also have received other interventions in the form of
psychological therapies e.g. CBT, CAT, Mindfulness etc. , plus have either received or been
considered for ECT and/or augmentation strategies to antidepressant treatment.
These patients would be very much considered Tertiary Service patients and continue to exhibit a
high level of functional impairment with subjective distress with or without suicidal risk.
The abuse potential of ketamine is widely recognised, clinicians should be fully aware when
considering suitability of the patient for treatment.
3.2. Contraindications
• Non – consenting, non capacitous persons
• Schizophrenia
• Significant cardiovascular disease
• Thyroid disease
• Pregnancy
• Female hormonal treatments
• Raised intra cranial tension/ pressure ? remove
• Glaucoma ?remove
• Current Substance misuse
4. Obtaining consent
This is the responsibility of the referring Consultant & will follow guidance detailed in the Guidelines
for Unlicensed and off- label use of medicines (key themes).
4.1. Recording consent
Consent will be recorded in the electronic care record (eCR) and by signature on a consent form.
Ref: PHARM-0003-01.v0
Page 5 of 10
Title: Ketamine – Protocol for the use of ketamine
in treating severe resistant depression
Approval date
4.2. 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.
Patients must also be advised:




Should not drive for 24 hours
They should not sign legal documents for 24 hours post treatment.
That they should not consume alcohol or use illicit drugs, or be left in charge of minors for
24 hours post treatment.
That there may/will be other patients in the department during treatment however a single
bay will be allocated to the patient with a member of staff present throughout their
treatment.
4.3. Patient information
Patient information leaflets must be supplied to the patient during the consent process a record of
which must be made in the eCR. The patient information leaflet will only contain information
relating to the marketing authorisation of the product. Patients should be counselled as to the
difference between their treatment and the information leaflet. Generic patient information leaflet
about unlicensed and off –label use of medicines is available to support discussions with patients
and carers.
5. Patient escort
In determining the requirement for and level of escort, the patient’s history, presenting behaviour
and level of risk must be taken into consideration. If an escort is required, this will be clearly
documented and the level of escort i.e. qualified or unqualified or responsible adult must be agreed
by the referring Consultant / care coordinator. This must be reviewed at intervals no less than
weekly. Where patients are escorted by an unqualified member of staff or responsible adult it will
be the determining staff (referring Consultant / care coordinator) that will be accountable for that
delegation.
6. Prescribing ketamine
• This will be the responsibility of the referring Consultant in consultation with the Anaesthetist.
• Ketamine will be prescribed on TEVW NHS Foundation Trust medication Kardex.
7. Treatment process
Ref: PHARM-0003-01.v0
Page 6 of 10
Title: Ketamine – Protocol for the use of ketamine
in treating severe resistant depression
Approval date
When
What
Who
Pre-treatment
Physical assessment
 In childbearing age females a pregnancy test must
be performed.
 A full physical examination must be undertaken and
results made available to the Anaesthetist.
 Blood tests>>> RC
 ECG, if age more than 45 years or if clinically
indicated.
Referring team
Psychological assessment
 BPRS
 QUIDS SR: [Quick inventory of depressive
symptoms self report]
 MADRS
 SATEE: [Systematic Assessment for Treatment
Emergent Effects Self report Inventory]
Referring team
Day before
treatment
Clear fluids only allowed, from midnight.
Patient
Contact the patient to confirm appointment time.
ECT Coordinator
Day of treatment
Wherever possible the patient will be treated first.
ECT Coordinator
Administer screening tools – see above and remain
with the patient throughout the treatment.
RMO trainee
Confirm consent
ECT Consultant
Review pre-treatment physical assessment
Anaesthetist
Test urine for substance misuse
ECT Coordinator
Cannulation & setting up of the syringe driver and
ketamine dose calculation.
 Dose: 500 micrograms per kg
 Product: ketamine injection 10mg/ml (Ketalar)
 Diluent:: sodium chloride 0.9%
 Recommended concentration for IV infusion: 1mg/ml
 Recommended infusion rate/method: over 40
minutes by syringe driver.
Anaesthetist
Record the patients BP, TPR and SP02 every 5
minutes during the procedure.
ECT Coordinator
If the patient becomes distressed or significantly increased BPRS scores, the process
should be reviewed. The Anaesthetist will decide if the dose should be reduced 0.125 x
0.80x Ti (time at which symptom first occurred) usually 400 micrograms per kg.
The Anaesthetist and ECT Consultant must remain in the department until treatment is
finished.
Post-treatment
The patient will be observed for 1 hour post treatment
and have observations recorded every 30 minutes post
infusion.
Ref: PHARM-0003-01.v0
Page 7 of 10
Title: Ketamine – Protocol for the use of ketamine
in treating severe resistant depression
ECT Coordinator
Approval date
Discharge from
the Ryedale suite
BPRS, QUIDS SR, SATEE and MADRS will be
performed
RMO trainee
The patient will be offered a light snack.
ECT Coordinator
Discharge will be agreed when vital signs are stable
Anaesthetic/
Psychiatrists
The patient and responsible adult collecting the patient
will receive advice following the administration of an
anaesthetic agent.
ECT Coordinator
If patient returning to an inpatient unit revert to pretreatment observation and monitoring status.
Inpatient staff
8. Delivering same-sex accommodation
 The patient will attend the department wearing their own loose fitting clothes.
 Screens will always be used to ensure patients privacy and dignity while receiving
treatment.
 The patient will be accompanied at all times.
 The referring consultant will alert the ECT team if there any vulnerabilities which would
trigger a traumatic response or memory which the team must consider when planning
treatment sessions
9. Side-effects
The following side effects may occur:
 Abdominal discomfort due to increased uterine tone.
 High dissociation – normalises in two hours.
 BP rise and tachycardia return immediately after infusion.
The above can be managed with diazepam.
 Occasional low BP & premature ventricle beats can occur, all normalise, termination of
treatment not required.
9.1. Patient-reported side effects




Abnormal sensations
Weakness
Fatigue
Headaches
Ref: PHARM-0003-01.v0
Page 8 of 10
Title: Ketamine – Protocol for the use of ketamine
in treating severe resistant depression
Approval date
10. Monitoring
When
What
Who
After final infusion
The patient will be monitored on a weekly basis.
Referring Consultant
After final infusion
If response positive, further maintenance schedule to
be considered
RMO
11. Termination of treatment
Will occur if there is no response to the initial 3 treatment s or if there is a rapid relapse in a shorter
time phase than a week.
12. Related documents
Guidelines for Unlicensed and Off-Label Use of medicines
Medical Devices and Clinical Procedures Policy
Medicine Code
Ref: PHARM-0003-01.v0
Page 9 of 10
Title: Ketamine – Protocol for the use of ketamine
in treating severe resistant depression
Approval date
13. Document control
Date of approval:
Next review date:
This document replaces:
Lead:
Name
Title
Members of working party:
Name
Title
This document has been
agreed and accepted by:
(Director)
Name
Title
This document was approved
by:
Name of committee/group
Date
This document was ratified by:
Name of committee/group
Date
An equality analysis was
completed on this document
on:
Amendment details:
Ref: PHARM-0003-01.v0
Page 10 of 10
Title: Ketamine – Protocol for the use of ketamine
in treating severe resistant depression
Approval date