Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04478526 |
| Other study ID # |
PSIY-604-18 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 29, 2020 |
| Est. completion date |
May 1, 2021 |
Study information
| Verified date |
April 2024 |
| Source |
Queen's University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Generalized anxiety disorder (GAD) is an extremely prevalent and debilitating mental health
disorder. Currently, the gold standard treatment for GAD is cognitive behavioural therapy
(CBT) and/or pharmacotherapy. The most common medications used to treat GAD are selective
serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors
(SNRIs). While CBT is a gold standard treatment for GAD, it is costly, time-consuming, and
often inaccessible. Fortunately, the electronic delivery of CBT (e-CBT) has emerged as a
promising solution to address these barriers. e-CBT has shown to offer comparable results to
in-person CBT while improving accessibility for patients and time efficiency for clinicians.
The following project aims to investigate the treatment efficacy of e-CBT compared to, and in
conjunction with pharmacotherapy for GAD. This study has been designed using a
quasi-experimental design to allow patients the freedom to choose which treatment modality
they would like to receive. Participants with a diagnosis of GAD will be enrolled in 1 of 3
possible treatment arms: e-CBT, medication, or combination. The e-CBT program will include a
12-week psychotherapy program delivered through the Online Psychotherapy Tool (OPTT), a
secure, cloud-based, digital mental health platform. The treatment efficacy of e-CBT will be
compared to the treatment efficacy of the medication arm and the combination arm.
Conclusions: If e-CBT is shown to either be comparable to medication or that the effects of
both treatments are augmented when used in tandem, these findings could have major
implications on the mental health care system. e-CBT is a more accessible, and affordable
treatment that could increase mental health care capacity by four-folds if proven viable.
Description:
Methodology Research Design. This study has been designed using a quasi-experimental design
to allow patients the freedom to choose which treatment modality they would like to
participate in. This research design aims to be naturalistic by mimicking the decisions made
by patients and physicians regarding course of treatment and type of pharmacotherapy
prescribed within mental health services across Ontario. The treatments provided within the
study also aim to replicate evidence-based best practice clinical guidelines for treatment of
GAD.
Research Participants. Patients will be referred to the study by primary care physicians
within Toronto and Kingston, Ontario. Patients will be referred to the Anxiety Outpatient
Clinic at the Hotel Dieu Hospital site of Kingston Health Sciences Centre or the Mood and
Anxiety Clinic within the Centre for Addiction and Mental Health (both sites herein referred
to as "the clinic"). Upon receiving a referral to the clinic, participants will be contacted
by the study's Research Coordinator and asked to indicate their interest (or lack thereof) in
the study. If interest is indicated and the study's inclusion criteria are met, the patient
will have a study intake appointment scheduled for the same day as their intake appointment
at the clinic. To be considered for inclusion within the study, patients must:
- be 18 years of age or older
- have consistent and reliable access to the internet
- be diagnosed with GAD according to the Diagnostic and Statistical Manual of Mental
Disorders, 5th Edition (DSM-V) by a clinician
- meet the criteria for GAD according to the GAD-7 Screener (GAD-7)
- Be competent to consent to participate
- Speak and read English Patients will be deemed ineligible for participation in the study
if they are in acute distress.
Allocation of Subjects between Arms of the Study. Subjects will be presented with all three
arms of the study within their study intake appointment by the Research Coordinator. After
obtaining informed consent, patients will meet with one of the study's psychiatrists during
their clinic intake appointment and discuss the recommended treatment plan. In collaboration
with the psychiatrist, patients will decide whether or not they would like to begin
pharmacotherapy and/or e-CBT treatment.
Criteria for Discontinuation. Patients' participation in the study will be discontinued if
they are found to be noncompliant to their treatment. This will be defined as stopping
medications all together or reportedly skipping more than two days in a row of medication.
Patients will be found noncompliant with e-CBT treatment if they miss more than two weeks of
e-CBT sessions or fail to complete weekly homework assignments. Patients' participation
within the study will also be halted if they are deemed to be in acute crisis by self-report
or the psychiatrist in charge of their care.
Study Protocol. After being referred to the study by a clinician uninvolved within the study,
patients will be contacted by the Research Coordinator to determine the patient's interest in
participating in the study. If interest is indicated, an intake appointment for the study
will be scheduled for the same date as the intake appointment to the clinic.
Intake appointment. Upon attending the intake appointment, the Research Coordinator will
explain all three arms of the study and review the study's letter of information. After
sufficient time has been provided to ensure the patient understands the study, informed
consent will be obtained by the Research Coordinator and the patient will complete the State
Trait Anxiety Inventory (STAI), a demographics questionnaire, Quality of Life Enjoyment and
Satisfaction Questionnaire - Short Form (Q-LES-QSF), GAD-7 and the 42-item Depression Anxiety
Stress Scales (DASS-42). Following the intake appointment, patients will, in collaboration
with their psychiatrist, decide on which treatment modalities they would like to participate
in (e-CBT and/or pharmacotherapy). Treatment will then proceed according to the arms below,
with patients participating in e-CBT and pharmacotherapy commencing both arms simultaneously
within their clinic intake appointment.
e-CBT. Weekly sessions of e-CBT through OPTT will consist of approximately 30 slides. Each
session is expected to last approximately 50 minutes. The content and format of each weekly
online session was designed to mirror live CBT. The slides will highlight a different topic
each week and include general information, an overview of skills and homework on that topic.
The homework included in each session will be submitted through OPTT and reviewed by the
clinicians with personalized feedback provided by clinicians within three days of submission.
Weekly homework submission for feedback will be mandatory before being eligible for the next
session. Biweekly GAD-7, DASS-42 and Q-LES-SF questionnaires will be completed through OPTT.
A second STAI will be completed in the final week of e-CBT treatment.
Pharmacotherapy. If patients chose to participate in the pharmacotherapy stream of treatment,
they will attend biweekly medication reconciliation appointments with their psychiatrist at
the clinic. If the patient is participating solely in the pharmacotherapy arm, they will
complete the biweekly GAD-7, DASS-42 and Q-LES-SF within each of their appointments. If the
patient is completing both pharmacotherapy and e-CBT, questionnaires will only be completed
through OPTT. Upon attending their clinic intake appointment, the patient's medication
history (including any current medications) will be collected and all medications prescribed
for GAD prior to the study will be switched to the medications suggested in the protocol and
if needed to be continued the dose will be unchanged 6 weeks prior to start of the study and
during the study. Within the patient's clinic intake appointment, they will commence
pharmacotherapy with the medication class decided according the "starting medication"
protocol below, which was developed in accordance with Canada's best practice guidelines for
the treatment of GAD. The pharmacotherapy protocol is summarized in Figure 1.
General 6-week protocol. At the patient's second appointment (2 weeks on the medication),
their medication will be maintained and optimized, regardless of whether or not a response is
reported. At the patient's third appointment (4 weeks on the medication), the medication will
be optimized if a partial response is reported or the medication will be switched according
to the "medication switch protocol" if no response is reported. Partial response will be
defined as an improvement of 20% or greater in their GAD-7 score compared to baseline. If the
medication is switched (the patient reports less than a 20% improvement in their GAD-7 score
compared to baseline), the 6-week protocol will recommence with the new medication. At the
patient's fourth appointment (6 weeks on the medication), their dosage will be optimized if
the patient is responding well to the medication and reports an improvement greater than 50%
if within the primary medication arm, or 20% if within the secondary medication arm, in their
GAD-7 score compared to baseline, the patient will remain on said medication for the
remainder of the 12-week study. If the patient does not report an improvement of more than
20% in their GAD-7 score compared to baseline, the patient's medication will be switched
according to the "medication switch protocol" and the 6-week protocol will recommence with
the new medication. If the patient is within the primary medication arm and reports a 20-50%
improvement in GAD symptoms compared to baseline after six weeks on the new medication, the
medication with be augmented with either olanzapine, risperidone or benzodiazepines.
Starting Medication. If the patient has never taken an SSRI or SNRI, the patient will
commence the primary medication arm. The two classes of medications within the primary arm
will be described to the patient and, with the recommendation of the prescribing
psychiatrist, the patient will begin either an SSRI (sertraline or escitalopram) or
pregabalin/an SNRI (duloxetine or venlafaxine).
If, prior to the beginning of the study, the patient has been deemed unresponsive to either
an SSRI or an SNRI/pregabalin, the patient will commence the primary medication arm. The
patient will start the medication class that they have not been previously deemed
unresponsive to (i.e., if previously unresponsive to sertraline, the patient will commence
the SNRI class). A patient will be considered previously unresponsive if their anxiety did
not improve after treatment with the maximum tolerated dose of the specific medication for an
eight-week duration.
If the patient has been deemed unresponsive to both an SSRI and an SNRI/pregabalin, the
patient will commence the secondary medication arm. The two classes of medications within the
secondary arm will be described to the patient and, with the recommendation of the
prescribing psychiatrist, the patient will begin either bupropion/mirtazepine or
buspirone/imipramine.
Medication switch protocol. If the patient is deemed unresponsive to a medication after 4 or
6 weeks of administration (the patient reports less than a 20% improvement in their GAD-7
score compared to baseline), their medication should be switched to another class. If the
patient has a history of non-response to any of the four medication classes, these classes
should be removed as pharmacotherapy options for their treatment within the study (i.e., if a
patient was deemed unresponsive to SSRIs prior to commencing the study, the patient should
not be prescribed sertraline or escitalopram at any point within the study). If the patient
was started in the primary or secondary medication arm and has not previously demonstrated
non-response to the second class of medications within that arm, the patient should be
switched to the second class of pharmaceuticals within that arm. If the patient was started
in the primary arm and was previously deemed unresponsive to the second class of
pharmaceuticals within that arm, the patient should begin the secondary medication arm if
non-response indicates a medication switch is necessary.
Six Month Follow-up. All patients will be contacted through telephone by the Research
Coordinator 6 months after their 12 weeks within the study have ended to complete follow-up
questionnaires. The patients will complete a third STAI and another Q-LES-SF, DASS-42 and
GAD-7. These measurements will act to determine the longevity of treatment effects.
