Efficacy of Online CBT for GAD Compared to Pharmaceutical Interventions
Efficacy of Online CBT for GAD Compared to Pharmaceutical Interventions
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.
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.
Inclusion Criteria:

 -  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

 Exclusion Criteria:

 - Patients will be deemed ineligible for participation in the study if they are in acute
 distress.