protocolProtocol for a randomised controlled trial investigating the effectiveness of an online e-health application compared to attention placebo or sertraline in the treatment of generalised anxiety disorder

Background: Generalised anxiety disorder (GAD) is a high prevalence, chronic psychiatric disorder which commonly presents early in the lifespan. Internet e-health applications have been found to be successful in reducing symptoms of anxiety and stress for post traumatic stress disorder (PTSD), panic disorder, social phobia and depression. However, to date, there is little evidence for the effectiveness of e-health applications in adult GAD. There are no studies which have directly compared e-health applications with recognised evidence-based medication. This study aims to determine the effectiveness of a web-based program for treating GAD relative to sertraline and attention placebo. Methods/Design: 120 community-dwelling participants, aged 18-30 years with a clinical diagnosis of GAD will be recruited from the Australian Electoral Roll. They will be randomly allocated to one of three conditions: (i) an online treatment program for GAD, E-couch (ii) pharmacological treatment with a selective serotonin re-uptake inhibitor (SSRI), sertraline (a fixed-flexible dose of 25-100 mg/day) or (iii) an attention control placebo, HealthWatch. The treatment program will be completed over a 10 week period with a 12 month follow-up. Discussion: As of February 2010, there were no registered trials evaluating the effectiveness of an e-health application for GAD for young adults. Similarly to date, this will be the first trial to compare an e-health intervention with a pharmacological treatment. Trial Registration: Current Controlled Trials ISRCTN76298775 Background Generalised anxiety disorder is a high prevalence psychiatric disorder that is associated with low rates of treatment. The predominant symptom of GAD is excessive uncontrollable worry in a variety of domains that lasts for a period of at least six months. Associated symptoms include muscle tension, becoming fatigued easily, restlessness, irritability, and sleep disturbance [1]. Lifetime and 12 month prevalence rates have been estimated at between 4.3-5.9% and 1.2-1.9% respectively [2,3]. However, a relatively small percentage of those with GAD seek treatment. Findings from the US National Comorbidity Survey indicated that only 37% of respondents had sought treatment for the disorder [4]. The condition generally follows a chronic course, with symptoms often presenting early in the lifespan and affecting individuals throughout adulthood. There is an estimated delay of treatment following the initial onset of symptoms for the affected individual of between 9 and 23 years [5]. Consequently, the community cost associated with GAD is high [6]. Effective treatment in young adult* Correspondence: Helen.Christensen@anu.edu. au 1 Centre for Mental Health Research, School of Health & Psychological Sciences, College of Medicine, Biology and Environment, The Australian National University, Canberra, Australia Full list of author information is available at the end of the article BioMed Central © 2010 Christensen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Christensen et al. Trials 2010, 11:48 http://www.trialsjournal. com/content/11/1/48 Page 2 of 8 hood has the potential to reduce ongoing disability and costs [7,8]. Young adults (18-30 years) will be the target of the current study, allowing the effects of treatment to be investigated in the age group when GAD commonly first presents. Current Psychological and Pharmacological Treatments for GAD Both cognitive behavioural therapy (CBT) and drug treatments such as selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat GAD [9]. Meta-analyses suggest CBT is an effective treatment for GAD, reducing anxiety and worry in the shortand long-term [10,11]. Sertraline, along with the SSRIs escitalopram and paroxetine, is seen as a first-line pharmacologic treatment for GAD [12]. Randomised, placebo controlled trials have found sertraline efficacious for GAD in adults [13,14], children and adolescents [15,16]. The treatment period ranged from 9 to 12 weeks in these pharmacological trials. A review of antidepressant medication concluded sertraline (along with escitalopram) has the most favourable balance between efficacy, acceptability (side effects and treatment discontinuation) and acquisition cost. Considering these findings, sertraline is a standard choice for treating GAD in clinical settings. While both CBT and SSRIs are beneficial, some evidence suggests that the effects of CBT may be more long lasting [10,17]. Despite the benefits of CBT and SSRIs, many individuals either do not or are not able to access treatment. This is particularly the case for those seeking CBT, which is difficult to obtain due to the small workforce of psychologists and the lack of services in rural and remote regions [18]. Further, there is evidence that many individuals with mental health problems seek confidential services where anonymity is assured [19]. E-health applications providing CBT for anxiety are a potential solution to poor access to services. Considering the preference for confidentiality and anonymity, the low workforce required for dissemination and the lack of intense input needed from mental health professionals, automated e-health programs offer potential for intervention en masse. In the last 10 years, hundreds of e-health applications have been developed. Many have been found to be effective, although the effectiveness of these applications for GAD is not well established relative to applications for other anxiety disorders (see Spence et al [20]) including social anxiety [21], panic disorder [22,23] and PTSD [24], and for depression [25,26], stress [19], insomnia [27] and eating disorders [28] (see http://www.beacon.anu.edu.au[29] for a list of all research). A preliminary case study of an internet self-management program for GAD indicated the promise of such an intervention, with clinically significant improvements found on measures of GAD symptomatology, worry and metacognitions [30]. Recently, the first randomised controlled trial (RCT) of an Internet-based CBT program for GAD was completed with results suggesting the Internet-based program, compared to a waitlist control, resulted in clinically significant reductions in worry and symptoms of anxiety. Efficacy and completion rates were similar to those seen for traditional face-to-face CBT programs [31]. Given the likely importance of these applications in the future, particularly for high prevalence disorders such as GAD, it is important to evaluate their effectiveness relative to gold standard pharmacological treatment and also against a credible attention placebo control [10,17]. Objectives of the Current Study The primary aims of this study are to investigate in individuals with a GAD diagnosis, whether an e-health application (E-couch) (i) is more effective than an attention placebo health application (HealthWatch) in reducing symptoms of anxiety and in lowering the proportion of the sample with a GAD diagnosis, and (ii) produces an equivalent reduction in symptoms compared to the use of the SSRI, sertraline. A secondary aim of the study is to investigate participant characteristics that predict outcome, adherence, satisfaction and acceptability of the intervention. Methods and Design Design The study is a randomised controlled trial of community dwelling young adults. It will consist of a 10 week treatment phase and a 12 month follow-up phase, with measures administered at screening, baseline, post-test, and 6 and 12 months after post-test. The current study has received ethics approval from The University of Sydney (11-2009/12091) and The Australian National University (2008/548) Human Research Ethics Committees and complies with the Helsinki Declaration on human research. Participants and Inclusion/Exclusion Criteria The target population for the GAD treatment trial is adults, male and female, aged 18-30 years with an anxiety diagnosis of GAD. The study aims to recruit 120 participants (40 per condition). Individuals screened positive for GAD symptoms but not found to meet GAD diagnosis using the Mini-International Neuropsychiatric Interview (MINI) [32] will be invited to join a parallel GAD prevention RCT [33]. The eligibility criteria for the GAD treatment trial are listed in Table 1. As there is considerable comorbidity between GAD, other anxiety disorders and depression [34], a secondary diagnosis of an anxiety disorder or major depression is not an exclusion criterion of this study. However, if parChristensen et al. Trials 2010, 11:48 http://www.trialsjournal. com/content/11/1/48 Page 3 of 8 ticipants are found to have a primary diagnosis of one of these conditions, with GAD a secondary diagnosis they will be excluded from the study and offered more appropriate treatment options. These diagnoses will be based on Anxiety Disorders Interview Schedule-IV (ADIS-IV) [35] criteria. Recruitment Procedure Recruitment will take place in three stages. Stage 1 will involve a screening assessment, mailed to individuals in five Sydney electorates who are randomly selected from the Australian Electoral Roll. In Australia it is compulsory for all Australian citizens aged 18 years or older to be registered on the Commonwealth Electoral Roll. Return of the screener will constitute consent to participate in this stage. Randomly selected individuals will be screened for symptoms using the GAD-7 [36]. Stage 2 will involve the administration of the MINI by telephone (after verbal informed consent) to individuals with a GAD-7 score of 5 or more. Individuals who meet criteria for GAD on the MINI interview will be offered a referral to the treatment trial at the Brain & Mind Research Institute (BMRI), The University of