206 Original article
Repeated subcutaneous racemic ketamine in treatment-
resistant depression: case series
Joseph C.W. Thama,b, André Doc, Jason Fridfinnsond, Reza Rafizadehe,
Jacky T.P. Siuf, George P. Buddg and Raymond W. Lamh
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Interest in the use of parenteral ketamine has been
increasing over the last 2 decades for the management
of treatment-resistant depression (TRD). While
intravenous (IV) ketamine has been the most common
parenteral route of administration, subcutaneous (SC)
and intramuscular options have been described. We
developed a clinical treatment protocol for the use of
repeated SC racemic ketamine (maximum six treatments,
twice per week) in an inpatient psychiatric care setting
with inclusion/exclusion criteria, dosing schedule, and
description of treatment, assessment, and monitoring
procedures. Results from the first 10 consecutive patients
demonstrated the effectiveness of SC racemic ketamine
in relieving symptoms of TRD as measured by the
Montgomery–Åsberg Depression Rating Scale (MADRS)
and Quick Inventory of Depressive Symptomatology, Self-
Report (QIDS-SR16). Response (≥50% reduction in scores
from baseline to endpoint) was achieved in 8/10 cases on
the MADRS and 6/10 on the QIDS-SR16. Remission was
achieved in 8/10 (based on MADRS ≤10) and 5/10 (based
on QIDS-SR16 ≤6). Patients tolerated the treatments
Introduction
Despite decades of research in treatment options, depres-
sive disorders remain a major cause of disease burden
worldwide (James et al., 2018). While antidepressant
options have expanded over the years, the onset of their
therapeutic effect is typically several weeks. As a result,
there has been a growing interest and research around
novel rapid-acting antidepressant agents (Witkin et al.,
2019).
Since the initial report by Berman et al. (2000), the anes-
thetic agent ketamine, at subanesthetic doses, has been
of particular interest with the potential for rapid effect
in treatment-resistant depression (TRD). The mech-
anism of antidepressant action of ketamine is not fully
understood but might involve N-methyl-D-aspartate
receptor antagonism (Trullas and Skolnick, 1990;
Muthukumaraswamy et al., 2015) and downstream mech-
anisms (e.g. mammalian target of rapamycin activation
This is an open-access article distributed under the terms of
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properly cited. The work cannot be changed in any way or used
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0268-1315 Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc
well with only transient blood pressure changes and
dissociative side effects. Repeated SC ketamine
treatments could be a safe, feasible, and effective
alternative to IV ketamine infusions for patients with TRD.
Int Clin Psychopharmacol 37: 206–214 Copyright © 2022
The Author(s). Published by Wolters Kluwer Health, Inc.
International Clinical Psychopharmacology 2022, 37:206–214
Keywords: antidepressant, depression, glutamate, intravenous, ketamine,
N-methyl-D-aspartate, subcutaneous, treatment protocol
a
BC Neuropsychiatry Program, University of British Columbia, bVGH/UBC
Neurostimulation Program, University of British Columbia, Vancouver, cDe-
partment of Psychiatry, Université de Montréal, Montreal, dDepartment of
Anesthesiology and Perioperative Care (VGH and UBC), University of British
Columbia, eBC Mental Health & Substance Use Services, Lower Mainland
Pharmacy Services, fTertiary Mental Health & Substance Use, Lower Mainland
Pharmacy Services, University of British Columbia, gMental Health and
Substance Use Services, Vancouver Coastal Health and hDepartment of
Psychiatry, University of British Columbia, Vancouver, Canada
Correspondence to Joseph C.W. Tham, MD, FRCPC, BC Neuropsychiatry
Program, University of British Columbia Hospital, University of British Columbia,
2255 Wesbrook Mall, V6T 2A1, Vancouver, British Columbia, Canada
Tel: +1 604 822 7541; fax: +1 604 822 7887; e-mail: joseph.tham@ubc.ca
Received 16 February 2022 Accepted 16 March 2022
and brain-derived neurotrophic factor upregulation)
enhancing synaptic plasticity (Maltbie, Kaundinya and
Howell, 2017; Kraus et al., 2020). Other modifications in
brain functioning have been observed in regions involved
in the modulation of mood and stress response, includ-
ing lowering of subgenual cingulate activity (Morris et
al., 2020), and reduced burst activity of the lateral habe-
nula (Yang et al., 2018).
Ketamine for depression is typically administered as
racemic (R, S)-ketamine given in an intravenous (IV)
infusion over 40 min. Racemic parenteral ketamine does
not have regulatory approval, but the S-enantiomer,
esketamine, has been approved as a nasal spray for
adjunctive treatment of major depressive disorder in
Canada (CADTH, 2020) and the USA (FDA, 2019).
Despite the absence of regulatory approval, consensus
(Sanacora et al., 2017) and international expert opinions
for parenteral ketamine treatment have been published
(McIntyre et al., 2021). Recently, the evidence for IV
ketamine efficacy has been reviewed by the Canadian
the Creative Network for Mood and Anxiety Treatments (Swainson
4.0 (CCBY-
provided it is
et al., 2021), suggesting level 1 evidence for single-in-
commercially fusion IV ketamine with level 3 evidence for repeated
infusions.
DOI: 10.1097/YIC.0000000000000409

While much of the research has focused on the IV
infusion route of administration, alternative parenteral
options such as subcutaneous (SC) and intramuscular
(IM) routes, with high (>90%) bioavailability (McIntyre
et al., 2021) and relatively stable rate of absorption, can
achieve plasma concentrations similar to those reported
after IV infusion (Loo et al., 2016). The benefits of these
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alternate routes include ease of administration (no need
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for starting an IV line nor continuous infusion requiring
infusion pump) and reduced staff training in IV medi-
cation administration. The parenteral ketamine dose for
treatment of depression has varied from 0.1 to 1 mg/kg,
with a typical dose of 0.5–1 mg/kg in most studies (Wan
et al., 2015; Andrade, 2017). In the case of subanesthetic
amounts of ketamine dosed at 0.5 mg/kg, an ‘average’
70 kg individual would require 35 mg, or 0.7 ml (50 mg/
ml), which is well within the typical 1.5 ml limit for SC
injection into the abdomen or upper arm with little pain
or injection site adverse effects (Mathaes et al., 2016).
These pragmatic factors suggest that SC ketamine may be
simpler and easier to administer than the IV route while
achieving similar efficacy and safety. However, to date,
only a limited number of reports have been published in
the literature on the use of SC ketamine in the treatment
of depression. A recent systematic review of SC ketamine
(Cavenaghi et al., 2021) including two randomized clini-
cal trials, five case-reports and five retrospective studies
utilizing various dose-titration approaches showed rapid
antidepressant effect. In this report, we present a case
series of patients with TRD utilizing an inpatient clinical
SC ketamine protocol with well-defined dose scheduling,
rigorous psychiatric and side effect monitoring.
Methods
A working group at the University of British Columbia
(UBC) Hospital, Vancouver, Canada, comprised a collab-
oration between the BC Neuropsychiatry Program, UBC
Mood Disorders Centre, and the Vancouver General/UBC
Hospital Neurostimulation Program developed a clinical
protocol with documentation, monitoring, and standard-
ized operating procedures defined for physicians and
nurses. The full clinical treatment protocol was approved
by the Vancouver General/UBC Hospital Pharmacy and
Therapeutics Committee and is available online (Tham
et al., 2022) (OSF link: https://osf.io/ag6u7). The UBC
Clinical Research Ethics Board approved the use of dei-
dentified clinical data for case reporting (H21-02384).
To summarize the protocol, patient inclusion criteria were:
inpatients more than 18 years old; able to provide consent;
diagnosed with diagnostic and statistical manual of mental
disorders-5 major depressive disorder or bipolar disorder
by clinician assessment; and TRD defined as persisting
depressive symptoms not responding to adequate trials of at
least two antidepressants and at least one adjunctive med-
ications (e.g. second-generation antipsychotics, lithium,
Repeated subcutaneous racemic ketamine in TRD Tham et al. 207
thyroid hormone; if bipolar, quetiapine, lamotrigine, or
lurasidone). Exclusion criteria were: current psychosis;
active alcohol and substance use disorders in the preced-
ing 6 months; history of ketamine abuse; significant per-
sonality disorder; unstable medical condition; uncontrolled
hypertension; recent seizure; elevated intracranial pressure,
aneurysmal vascular disease/arteriovenous malformation;
pregnancy/breastfeeding; and sensitivity to ketamine,
esketamine, or related compounds. While not specified in
the inclusion/exclusion criteria, patients could be refractory
to previous psychotherapy to previous electroconvulsive
therapy (ECT) or other neuromodulation techniques.
Preketamine assessment
Clinical history, physical examination, weight, vital signs,
and urine drug screen were done prior to the first treatment
to ensure eligibility, along with bloodwork, including com-
plete blood count, electrolytes, liver function tests, renal
functions, thyroid-stimulating hormone, and pregnancy test
as appropriate. In addition, an electrocardiogram was per-
formed within the previous 30 days. The procedure, risks,
and potential side effects of parenteral ketamine were dis-
cussed with patients, and informed consent was obtained.
Ketamine treatment procedure
Ketamine treatments were conducted twice weekly in the
ECT recovery room. Although the presence of an anes-
thesiologist was not required within the clinical protocol,
ketamine treatments occurred concurrently during ECT
procedures, and an anesthesiologist was available in the
immediate area. Medications potentially affecting keta-
mine response and tolerability including benzodiazepines,
opioid antagonists, and lamotrigine (Anand et al., 2000;
Williams et al., 2018; Andrashko et al., 2020) were held the
night before and the morning before treatments. Patients
were allowed a small breakfast up to 2 h before treatment
with sips of water thereafter. Pretreatment vital signs
including heart rate, oxygen saturation, and blood pres-
sure were documented. Blood pressure was ensured to be
below 140/90 mmHg before ketamine administration.
Racemic ketamine hydrochloride (50 mg/ml) was admin-
istered as SC bolus into the abdomen or upper outer area
of the arm by a nurse/physician. Over the next 60 min,
patients were monitored by a psychiatric nurse in an
adjacent room for the emergence of adverse events. As
required by local best practice, staff certified in Advanced
Cardiac Life Support (ACLS) protocols were available in
the event of severe reactions. Patients were instructed to
relax and could choose to listen to soothing music. After
60 min, patients returned to the inpatient ward to con-
tinue their day and all regular medications resumed.
Dosing algorithm
Although the treatment protocol was approved for both
SC and IM administration, all patients chose SC keta-
mine. The starting dose was 0.25 mg/kg for at least two
 208 International Clinical Psychopharmacology 2022, Vol 37 No 5

treatments. If response was deemed inadequate, the dose
could be increased to 0.5 mg/kg for at least two treat-
ments and then, if needed, further increased to 0.75 mg/
kg (maximum dose). This protocol allowed for up to six
treatments, but the total number of treatments provided
varied depending on clinical response/tolerability, as well
as discussions with the treating physicians and patients.
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Patient average age was 42.3 years with a range between
21 and 72 years. Nine (90%) of the cases had major
depressive disorder with one (10%) diagnosed with bipo-
lar I disorder currently in a persistent depressive episode
of 10 months. On average, the patients reported persis-
tent depression for 23.6 months. At baseline, the patients
experienced high moderate to severe depression (aver-

age pretreatment MADRS and QIDS-SR16 scores of 30.8

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Monitoring and 17.8, respectively).

For the first 60 min following dosing, vital signs including
As a group, these patients had several psychiatric and
blood pressure were recorded every 15 min. At 45 min,
medical comorbidities. Two cases had comorbid con-
the Clinician-Administered Dissociative Symptom Scale
version disorder with seizure-like attacks, one case with
(CADSS-6) (Rodrigues et al., 2021) was administered.
anorexia nervosa, and four cases with medical conditions
In the event of severe emotional distress, lorazepam
demonstrated on neuroimaging (two with multiple scle-
0.5 mg sublingually could be given. Final vital signs were
rosis in remission, one with hypertensive hemorrhage in
recorded at 2- and 4-h posttreatment.
the left basal ganglia 3 years ago, and one with significant
Measurement-based care was followed using depres- small-vessel ischemic changes).
sion, anxiety, and suicidality scales (Hong et al., 2021)
Among the 10 cases, antidepressants tried during this
throughout the treatment course. Depression severity
depressive episode before ketamine treatment included
was assessed with the Montgomery–Åsberg Depression
selective serotonin reuptake inhibitors (fluoxetine, cit-
Rating Scale (MADRS) (Montgomery and Åsberg, 1979)
alopram, and escitalopram), serotonin modulators (vila-
and Quick Inventory of Depressive Symptomatology
zodone and vortioxetine), serotonin and norepinephrine
Self-Report (QIDS-SR16) (Rush et al., 2003). Clinical
reuptake inhibitors (venlafaxine, desvenlafaxine, and
response was defined as at least 50% reduction in scores
duloxetine), TCA (clomipramine), as well as other classes
from baseline to endpoint, whereas remission was
(trazodone, mirtazapine, and bupropion). Augmenting
defined as endpoint scores of MADRS ≤10 (Hawley et
agents already tried among the patients included quet-
al., 2002) and QIDS-SR16 ≤6 (Rush et al., 2003). Self-
iapine, lithium, aripiprazole, brexpiprazole, olanzapine,
reported anxiety was assessed with the Generalized
thyroid hormone, buspirone, lamotrigine, and dextroam-
Anxiety Disorder Scale (GAD-7) (Spitzer et al., 2006).
phetamine. One patient had an index course of ECT (10
The Columbia–Suicide Severity Rating Scale (C-SSRS)
treatments), which failed to elicit a significant response,
(Posner et al., 2011) was used to monitor suicidal ide-
and was switched to the ketamine protocol within 2 weeks
ation. Finally, the CNS Vital Signs computerized neu-
of the last ECT treatment. On average, patients had failed
rocognitive test battery (CNS-VS Cog) (Gualtieri and
to respond with three antidepressants and two augment-
Johnson, 2006) was administered before the first ket-
ing agents during the current depressive episode.
amine treatment and then within 24 h after the last
treatment to measure the change in various cognitive
Ketamine treatment effects
domains.
As per the protocol, treatments were stopped once remis-
sion was achieved with some clinical leeway up to the
Results
maximum of six treatments. None of the patients stopped
Here, we report on the results obtained for the first 10
early due to side effects or intolerability. One case (10%)
consecutive patients with TRD referred from June 2021
responded adequately to two doses of 0.25 mg/kg and
to December 2021. The patients were either admitted
was discontinued. The remainder were treated with the
from the emergency room to inpatient psychiatry or
higher 0.5 mg/kg dose with one (10%) requiring a total of
referred from outpatient psychiatrists requesting inpa-
three treatments, three (30%) had four treatments, one
tient assistance with treatment-resistant cases.
(10%) had five treatments, and four (40%) received the
full six treatments. Of those four patients that received
Patient characteristics
six treatments, only one was increased to the highest
All patients were evaluated by study authors (J.T. and
0.75 mg/kg dose due to inadequate antidepressant effect
A.D.) to satisfy the eligibility criteria. In total, the 10
and absence of psychological/perceptual effects during
patients were evenly balanced with five men and five
treatment at 0.5 mg/kg.
women. Table 1 summarizes key demographics and clini-
cal features including age, duration of current depressive Figure 1 shows the results of the clinician-rated MADRS,
episode, comorbidities and number of treatments with patient-rated QIDS-SR16, and patient-rated GAD-7
antidepressants, adjunctive medications tried during the scores pretreatment and after the indicated number of
current episode, and illness severity as measured with the ketamine treatments for each case. Figure 2 shows the
MADRS, QIDS-SR16, and GAD-7. average MADRS score across the treatment time points.
 Repeated subcutaneous racemic ketamine in TRD Tham et al. 209

Table 1 Clinical characteristics of patients (n = 10) with descrip- did not complain of persistent cognitive change, nor did
tive statistics the data reflect significant differences (Fig. 3).
Characteristic Mean SD Range
Ketamine adverse events
Age (years) 42.3 15.5 21–72
Duration of current episode (months) 23.6 16 10–60 In total, there were 45 individual ketamine treatments
Diagnosis – primary mood disorder performed. Treatments proceeded without any severe
Major depressive disorder 9 ND ND
adverse events. The CADSS-6 dissociative symptom
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Bipolar I depression 1
Diagnosis – comorbid conditions among 10 cases scale captured at 45 min postketamine bolus showed
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Conversion disorder 2 ND
Anorexia nervosa 1
Medical condition affecting CNS
  Multiple sclerosis 2 ND
  Remote hypertensive hemorrhagic stroke 1
  Significant small vessel ischemic changes 1 signs showed only mild and transient elevations in heart
# of antidepressants tried during current 3.4 ND
depressive episode of adequate duration
& dose
# of augmenting medications tried during 1.9 ND
current depressive episode for at least
4 weeks duration
Course of ECT tried before ketamine during 1 ND
this episode
Pretreatment MADRS 30.8 6.7
Pretreatment QIDS-SR16 17.8 3.0
Pretreatment GAD-7 12.5 3.2
CNS, central nervous system; ECT, electroconvulsive therapy; GAD-7, General-
ized Anxiety Disorder scale; MADRS, Montgomery–Åsberg Depression Rating
Scale; ND, no data; QIDS-SR16, quick inventory of depressive symptomatology,
self-rated.
Not all patients required up to the full six treatments
available, reflected in the reduced total numbers by treat-
ments 5/6.
Overall, patients had a significant reduction in MADRS
score from baseline to endpoint (mean change ± SD:
−24.2 ± 10.2). At the end of the treatment course, using
response criterion defined as at least 50% reduction in
MADRS, 8/10 (80%) of patients demonstrated response
and all responders achieved remission with final MADRS
10 or less. The self-reported QIDS-SR16 demonstrated
response in 6/10 (60%) of the cases as defined by at least
50% reduction in the score, with 5/10 (50%) achieving
remission defined as QIDS-SR16 ≤ 6. Similarly, 6/10 (60%)
of cases demonstrated at least 50% reduction in anxiety
scores as measured by the self-rated GAD-7.
Of the eight cases that achieved remission as defined
with the MADRS, four were within two treatments at a
dose of 0.25 mg/kg. The other four achieved remission
with the dose increased to 0.5 mg/kg by four treatments.
Only one patient was given the 0.75 mg/kg dose for treat-
ments 5 and 6 but did not achieve remission.
Suicidal ideation monitored with the C-SSRS showed
that five patients had active ideation pretreatment.
Ideations stopped within 24 h after the first treatment in
4/5 (80%); one case was a nonresponder with persistent
suicidal ideation with no specific plans or intent.
CNS-VS Cog screens of cognitive performance were
available for nine patients (one of the patients was dis-
charged before posttreatment cognitive testing). Patients
ND
only mild symptoms (mean ± SD across all treatments:
0.91 ± 1.2; range, 0–4). No patients required lorazepam for
ND emotional distress. At these subanesthetic SC doses, vital
2–5 rate and blood pressure during the first 60 min (Fig. 4)
with no physical distress reported. There was a tendency
1–3 for cardiovascular effects to peak within 15 min of the
ketamine bolus with mean systolic blood pressure (SD)
ND increased by 8 mmHg (14.8) and heart rate increased by
1.1 bpm (11.6). In addition, analysis of individual treat-
20–44
14–23
ments showed dose-related effect, with mean blood pres-
8–17 sure increasing +6.8 mmHg (16.3, n = 10) at 15 min when
administered at 0.25 mg/kg and +10.2 mmHg (9.9, n = 9)
at 0.5 mg/kg. No patients required pharmacological inter-
vention for the blood pressure increases. By 2 and 4 h,
systolic blood pressure returned to baseline, but heart
rate increased as patients resumed their normal physical
activities.
Feasibility
Without the need for IV access nor an infusion pump,
the protocol was relatively easy to implement at UBC
Hospital. The single SC bolus was simpler to administer
than a 40-min IV infusion and well accepted by patients.
Orientation for inpatient psychiatrists was provided to
familiarize clinicians to the ordering and monitoring pro-
cedures. Likewise, nurses were oriented to the procedures
without issues. Patients found the SC ketamine treatment
and monitoring straightforward. There were no early termi-
nations due to adverse events nor withdrawal of consent.
Discussion
As a clinical work group, we were aware of the issues
regarding the provision of parenteral ketamine as an
off-label treatment including questions around adequacy
of research evidence, the lack of ‘maintenance’ treat-
ments and long-term safety data for those who respond
to an acute treatment series, and the diversion and abuse
potential of ketamine (Singh et al., 2017; Ryan and Loo,
2017). We developed the SC ketamine protocol on the
basis of ensuring the safety of the patients, that due dil-
igence has been performed for appropriate inclusion/
exclusion criteria, and that limitations have been clearly
defined as part of the informed consent process.
The results from these initial 10 cases utilizing SC
racemic ketamine are encouraging. Significant, rapid
reduction in MADRS scores was observed after the first
treatment and was maintained throughout the treatment
 210 International Clinical Psychopharmacology 2022, Vol 37 No 5

Fig. 1
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Individual Montgomery–Åsberg Depression Rating Scale (MADRS); quick inventory of depressive symptomatology, self-rated (QIDS-SR16,);
Generalized Anxiety Disorder Scale (GAD-7) scores across treatment sessions.
 Repeated subcutaneous racemic ketamine in TRD Tham et al. 211

Fig. 2
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Average Montgomery–Åsberg Depression Rating Scale (MADRS) scores across treatment sessions. CI, confidence interval; MADRS,
Montgomery–Åsberg Depression Rating Scale.

Fig. 3

CNS-VS cognitive screen results, pre- and posttreatment standard scores (n = 9). CI, confidence interval; CNS-VS, CNS Vital Signs computer-
ized cognitive battery.

course. Patient-rated QIDS-SR16 depression and
GAD-7 anxiety scales likewise showed a reduction over
the course of SC ketamine treatment. Improvement in
the QIDS-SR16 scores did not appear as rapidly as the
MADRS scores, perhaps as a result of the scale asking
patients to rate symptoms over the ‘last 7 days’ rather
than since the previous assessment. In total, 80% of
patients satisfied criteria for response and remission
on the MADRS, and 60% achieved response with 50%
meeting criteria for remission using the QIDS-SR16.
These results with SC ketamine are comparable to
response rates seen in studies utilizing multiple-dose
IV racemic ketamine protocols (aan het Rot et al., 2010;
Murrough et al., 2013; Singh et al., 2016). All patients who
responded to SC ketamine could be discharged back to
the community within 2 days after the last treatment.
 212 International Clinical Psychopharmacology 2022, Vol 37 No 5
Fig. 4
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Mean elevation in systolic blood pressure and heart rate during 60-min monitoring, 2 h, and 4 h after SC ketamine bolus. BP, blood pressure; CI,
confidence interval; HR, heart rate; SC, subcutaneous.
A surprising observation was that both patients with
comorbid conversion disorder (functional neurologi-
cal disorder) manifesting daily to weekly seizure-like
attacks experienced essentially complete remission and
both have remained free from these physical manifesta-
tions at 3 months follow-up.
Two patients did not show response in either the MADRS
or QIDS-SR16. One patient had comorbid eating disorder
and the other had significant psychosocial stressors at the
time of the treatments. Comorbid factors in the perpetu-
ation of depression may require further evaluation to bet-
ter understand ketamine response and refine inclusion/
exclusion criteria.
There were no safety issues encountered during the
treatments. Elevations in blood pressure and heart rate
were transient within the initial 60-min monitoring
period. Psychological effects of SC ketamine were mild,
including subjectively ‘feeling relaxed’ and ‘more talk-
ative’. Perceptual changes included mild sound sensi-
tivity, apparent brightness and enhanced contrast in the
visual field, altered depth perception, and visual vestibu-
lar latency. Two patients described ‘entheogenic’ effects
such as ‘feeling loved’, or being ‘one with others’ during
the treatments. Psychological and perceptual side effects
reportedly peaked between 15 and 30 min. As such, the
45-min CADSS-6 likely did not capture the peak inten-
sity of dissociative symptoms; nevertheless, none of the
patients reported distress severe enough to stop treatment.
The strengths of this report include the real-world
patients and a simple clinical protocol utilizing standard

measures for measurement-based care. Limitations
of this report include the lack of a control condition,
open-label treatment, and a limited number of cases with
varied comorbidities. Measurements of serum ketamine
level would also be beneficial for correlation with clinical
effect and comparison to IV ketamine studies.
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Characteristics of the SC ketamine protocol including
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the starting dose at 0.25 mg/kg may be reviewed with
further clinical experience. At this time, it is encouraging
that even at this lower starting dose, we have observed
rapid antidepressant effect. A starting dose of 0.5 mg/kg
might be reasonable for most individuals.
Given these encouraging results, SC ketamine is a prom-
ising and feasible alternative to IV ketamine infusions
that may improve accessibility for patients with TRD.
Although we conducted our protocol in a hospital inpa-
tient setting, SC ketamine could be administered in an
outpatient setting if appropriate monitoring and safety
procedures (e.g. availability of ACLS and airway manage-
ment) were in place. Placebo-controlled trials and pro-
spective follow-up studies should be conducted to better
understand the effects and duration of action of SC keta-
mine in clinical use.
Acknowledgements
Cognitive testing results were obtained with the assis-
tance of Samantha Huang and Vanessa Evans.
Conflicts of interest
A.D. was partly supported by an unrestricted fellowship
grant from Janssen Canada. R.W.L. has received honoraria
for ad hoc speaking or advising/consulting, or received
research funds, from: Asia-Pacific Economic Cooperation,
BC Leading Edge Foundation, Canadian Institutes
of Health Research, Canadian Network for Mood and
Anxiety Treatments, Grand Challenges Canada, Healthy
Minds Canada, Janssen, Lundbeck, Lundbeck Institute,
Medscape, Michael Smith Foundation for Health
Research, MITACS, Myriad Neuroscience, Ontario Brain
Institute, Otsuka, Pfizer, Sanofi, Unity Health, Vancouver
Coastal Health Research Institute, and VGH-UBCH
Foundation. For the remaining authors, there are no con-
flicts of interest.
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