Treatment of headaches post-ECT with oxygen therapy; a proof of concept study

In the Netherlands, approximately 700 patients with severe depression and other
psychiatric disorders are treated with electroconvulsive therapy (ECT) each
year. ECT is a safe treatment option, and has few serious side effects.
Nevertheless, approximately half of the patients treated with ECT experience
headache after treatment. These complaints range from mild to severe,
progressively increase after treatment but rarely last longer than 24 hours. In
severe cases, this side effect may be a reason for the patient to refrain from
further ECT treatments.
The etiology of post-electroconvulsive headache is still unclear. The fact that
ECT is associated with vascular changes in the brain, and the pulsating nature
of the headache after ECT with sometimes additional nausea and vomiting,
suggests a vascular origin. This presumption is confirmed by investigations
into the apparent effectiveness of, among others, sumatriptan and propranolol
in headache after ECT. Both drugs are used in the treatment of migraine and
cluster headache, which have probably a vascular origin as well. An effect of
treatment with oxygen on post-electroconvulsive headache can contribute to the
knowledge about the pathophysiology of post-electroconvulsive headache.
Post-electroconvulsive headache is currently symptomatically treated with
analgesics, including paracetamol, NSAID*s and opiates. This treatment is
effective for most patients. For patients with persistent headache after ECT
despite treatment, the above-mentioned agents (propranolol, sumatriptan,
dihydroergotamine) may be an option. In view of side effects, contraindications
and drug interactions, the possibility of a non-medication treatment makes an
important contribution. It is expected that (through shared decision making)
patients will have a strong preference for a non-medication therapy.
Normobare oxygen therapy is the first choice for acute cluster headache. The
mechanism of action of this therapy is unknown, but may be understood through
vasoconstriction of meningeal vessels.
Oxygen therapy does not have any relevant side effects and no drug interactions
are known. There is no absolute contraindication for oxygen administration.
The administration of oxygen through a nasal mask has proved effective in our
clinic in some patients with treatment-resistant headache after ECT. To further
investigate the effectiveness of this treatment, we first want to carry out a
proof of concept study of which we intend to publish the results. If oxygen
therapy appears to be an effective intervention in this study, a
placebo-controlled follow-up study will be conducted.

The purpose of the study is to investigate the effectiveness of oxygen therapy
in headache after ECT.
No research has been conducted into a non-medical treatment of headache after
ECT. Oxygen therapy is potentially a quick, inexpensive, and safe way to
relieve headache after ECT, without any danger to the patient. The intervention
to be investigated is hardly burdensome.

It concerns a proof of concept study.

Every year about 70 patients in the Jeroen Bosch Hospital, unit Hospital
Psychiatry, Elderly and cognition (ZPO), part of Reinier van Arkel, are treated
with ECT. Based on this study, we expect approximately half of this patient
population to have post-ECT headache symptoms. The indication for ECT is set in
a special ECT indication consultation. After this consultation an appointment
is planned with the patient for a preoperative screening which is performed by
an anaesthesiologist at the service of the Jeroen Bosch Hospital.

Both patients starting with ECT and existing ECT patients are approached for
the study. All patients 18 years of age and older who are willing and will be
treated by ECT are asked orally during the ECT intake by their doctor if they
are interested in participating in this study. If the patient is interested in
participation, this will be approached by the researcher. This will inform the
patient in detail about the research. The patient information letter and the
informed consent will be provided to the patient at that time. The study gives
the patient a week of reflection time to decide on participation. A week later
the researcher contacts the telephone to ask if the patient wants to
participate. If the patient needs more reflection time, this is possible.
If the patient wants to participate, he / she is asked to take the informed
consent form signed with them to the first ECT treatment.
In the case of permission, the researcher will check before the start of the
first ECT whether the patient meets the inclusion and exclusion criteria.
If so, the researcher will assign a unique code to the participant. The
overview of the names of the participants with corresponding codes is stored in
a protected folder on the network of Reinier van Arkel. In addition to the
researcher, the ECT nurses and research staff also have access to this file.
After receiving permission, they receive an email with the secured data from
the included patients.

Patients participating in the study will be marked with a sticker on the
patient board at the nursing office, with a reference on the ECT schedule of
that day, and with a clearly colored cover sheet on the ECT folder that is
included with each ECT patient. room and will accompany the patient with each
treatment. The sticker on the patient board, the reference in the ECT roster,
and the cover page in the ECT folder are provided by the research assistant.
The research assistant also ensures that a research protocol and VRS forms are
included in the ECT folder. The oxygen delivery equipment will be prepared by
the duty nurse in the evening shift when, in accordance with the existing ECT
protocol, they also provide other preparations for the ECT treatment the next
day. The VRS form contains the unique patient code and the number of times the
patient participates in the study (each patient is allowed to participate a
maximum of three times).

With every ECT treatment, the ECT nurse will ask whether the patient has used
oily skin on the face that day, as is also the case with the usual ECT
protocol. Because of the possible need to administer oxygen during the ECT
treatment, for example in the event of complications arising from anesthesia,
the use of oily skin is already banned to any patient, regardless of
participation in this study.

Just before the start of the ECT, the research assistant will ask the patient
if he / she suffers from headaches and if so to what extent. Patients are taken
to the recovery room after the ECT. When the patient is awake, the ECT nurse
will take the OK bed to their own room. Upon arrival at the department, the
research assistant is informed that the patient is back in his / her room and
whether he / she is participating in the study. The research assistant goes to
the patient's room and asks for headaches. Headache will be measured by means
of a validated 4-point headache scale that is used, among other things, to
objectify headache symptoms in cluster headache, the Verbal Rating Scale (VRS):
0 = no pain; 1 = mild pain; 2 = moderate pain; and 3 = severe pain.
Patients who have headaches for ECT (VRS score> 0) are excluded from
participation. If there are no headaches before ECT, immediately after ECT, 60
minutes after ECT, and 120 minutes after ECT, headache complaints will be asked
again and scored by the VRS. At a score> 0, the patient will be treated with
100% oxygen, 7 liters per minute for 20 minutes lying on bed by means of a
mask. The oxygen is connected by a nurse in the department. After 20 minutes
the oxygen is shut down by a nurse.
Then another VRS is taken by the research assistant.
When the headache symptoms last longer than 2 hours after oxygen therapy they
will switch to regular pain medication (paracetamol, NSAID) if desired by the
patient. Patients can ask for this themselves.
The VRS form is returned to the ECT folder by the research assistant. When all
patients of that day have undergone ECT treatment, the research assistant will
collect the VRS forms from the folders. The forms are handed over to the
researcher and processed by him.

To exclude random findings, three rechallenges are chosen. This means that one
subject participates a maximum of three times in the study on three different
ECT treatment days, if oxygen treatment takes place. The VRS measurements will
be done after inclusion after each ECT treatment. The repeated measurements
provide insight into the robustness of the effects of oxygen therapy.

The course of the research and the logistical matters are monitored by the
researcher and by the research staff and adjusted where necessary.

As discussed, there are indications for a vascular origin of post-ECT headache.
Due to the fact that cluster headache presumably has a vascular origin as well,
it is decided to treat patients in this study according to the same guidelines
as used in oxygen therapy in cluster headaches:

100% oxygen, 7 liters per minute, for 20 minutes, via a face mask.

- Appearance of fire. The danger is minimized. Smoking is not allowed in the
rooms. In addition, this risk will be communicated to patients, prohibiting
open fire during oxygen treatment.
- There is a risk of hypercapnia in patients with COPD. These patients are
being excluded. If an included patient is not (yet) diagnosed with COPD, but
has it anyway, oxygen treatment for twenty minutes does not constitute a
clinically relevant risk because the condition is likely to be mild in that
case.
- In combination with the oncolytic bleomycin, lung toxicity may occur,
sometimes months after discontinuation of bleomycin. Patients who are currently
be treated with bleomycin, or has been in the last 12 months, are excluded from
the study.


The load of the study consists of the 20-minute bedtime during the oxygen
treatment, where patients could go elsewhere in these 20 minutes and where they
want. This tax is considered to be minimal since patients suffering from
headache complaints are likely to be more comfortable than being stressed.
In addition, a maximum of three times per patient is asked for the degree of
headache. The nurse completes this score on the score form.