**2.1. Depression**

Treatment of depression with iCBT has been well studied. For example, two meta-analyses of iCBT for adult depression – covering 12 studies and four studies, respectively – found pooled effect sizes of 0.41 (95% CI 0.29, 0.54) [19] and 0.22 (95% CI, 0.03–0.41), respectively, for iCBT compared with any type of control [20]. A third meta-analysis of iCBT, covering nine studies – in university students – showed a standardized mean difference of −0.43 (95% CI −0.63, −0.22) supporting iCBT over non-treatment [15]. When comparing iCBT with treatment as usual, a randomized controlled trial showed a significant effect size (0.2; 95% CI 0.00, 0.50) favoring iCBT [21]. Overall, the present data support iCBT as an effective treatment for depression that could have a greater benefit than standard treatment. (For a more comprehensive review of this literature, please see our CMAJ paper, available at: http://www.cmaj.ca/content/cmaj/ early/2015/11/02/cmaj.150007.full.pdf)

But how can iCBT be done effectively? Could iCBT be offered without any therapist support – essentially, with patients told to use a website or an app? There is strong evidence in favor of therapist support of iCBT, including the results of a meta-analysis comparing iCBT with controls (effect size 0.61; 95% CI 0.45, 0.77) [19] and a Prioritization Summary conducted by the Australian and New Zealand governments (significant improvements in depressive symptoms through 8 months of follow-up; seven included studies) [22].

This raises a question: is self-guided CBT of any benefit? Researchers conducted a meta-analysis evaluating the efficacy of self-guided iCBT for the treatment of depressive symptoms. The authors identified 16 eligible RCTs and obtained patient data of 3876 participants from 13 of the 16 studies. They performed traditional and patient-level meta-analyses. iCBT was more effective at reducing symptom severity than controls, including placebo, no treatment, treatment as usual, or waiting list (β = −0.21; Hedges g = 0.27). iCBT also had a greater treatment response than controls (β = 0.53; odds ratio, 1.95; 95% confidence interval [CI]: 1.52, 2.50). Their analysis also showed an association between higher adherence and greater symptom reductions (β = −0.19; P = 0.001) and treatment response (β = 0.90; P < 0.001). Based on their analysis, the estimated number needed to treat to achieve a 50% reduction in depressive symptoms was eight patients [23]. What is particularly notable about this study is the number needed to treat. As first glance, this number seems too high to be clinically relevant. However, when considering the low expense associated with self-guided iCBT and when applying iCBT to an entire population, the investment could be worth the cost.

a clinically relevant improvement in anxiety symptoms, the pooled RR was 1.09 (95% CI 0.89, 1.34; I<sup>2</sup> = 0%), indicating no significant difference between therapist-supported iCBT and faceto-face CBT. Further, no significant differences were observed in disorder-specific and general anxiety symptoms. While most of the evidence was low to moderate quality, the data suggest that therapist-supported iCBT is an effective treatment for anxiety disorders and could be as effective as face-to-face CBT. However, additional, better-designed studies are needed to

The Internet and CBT: A New Clinical Application of an Effective Therapy

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Given the technological nature of iCBT, do children and adolescents respond well to this intervention? Recently, Ebert *et al*. conducted a meta-analysis of iCBT for anxiety and depression in children and adolescents. They identified 13 RCTs: seven studying anxiety, four studying depression, and two studying both. The studies used non-intervention or placebo controls. 11 studies used therapist-guided iCBT. Compared with controls, iCBT had a mean effect size of 0.72 (95% CI 0.55, 0.90; P < 0.001) on symptoms of anxiety or depression. To get one positive outcome, the number needed to treat was 2.56. Interventions targeted at adolescents had larger effect sizes than those targeted at children (g = 0.95 and 0.51, respectively). While the studies had a variety of treatment strategies and no long-term follow-up, the data seem to indicate that iCBT may be an effective treatment for anxiety and depression symptoms in

One very promising direction for iCBT is its use to treat distress caused by physical illness. In 2013, researchers conducted a systematic review investigating iCBT as an intervention for psychological distress in patients suffering from physical illnesses. Illnesses included irritable bowel syndrome (five trials), tinnitus (four trials), chronic pain (three trials), chronic back pain (three trials), infertility (two trials), as well as for a variety of other diseases (diabetes, HIV, multiple sclerosis, migraines, early breast cancer, with a trial each). At the time of this chapter's writing, the quality of evidence for iCBT was low and few conclusions could be

Since then numerous programs have emerged, especially for patients with cancer [9]. For example, a recent randomized controlled trial compared iCBT versus care as usual in breast cancer survivors with severe fatigue. The iCBT program started with two face-to-face sessions with a therapist followed by eight web-based modules. Therapists tailored modules and supported patients through the program. One final face-to-face session was conducted approximately 6 months after beginning treatment. At 6 months, participants in the iCBT group had significantly lower fatigue scores (mean difference, 11.5; 95% CI 7.7, 15.3) with a large effect size (Cohen d = 1.0) compared with care as usual. The iCBT group also had reduced functional impairment (mean difference, 297.8; 95% CI 145.5, 450.1) and psychological distress (mean difference, 5.7; 95% CI 3.4, 7.9) and increased quality of life (mean difference, 11.7; 95% CI 5.8, 17.7) compared with the care as usual group. Effect sizes of those measures ranged from 0.6 to 0.8 [32]. Some studies of iCBT for use in patients with brain injury, heart disease, and recur-

draw stronger conclusions [29].

children and adolescents [30].

rent headaches is provided in **Box 1**.

**2.3. Physical illness**

drawn [31].

Another question around implementation: can iCBT be adopted for more than one diagnosis? Depression is often comorbid with other psychiatric diagnoses, such as anxiety. To determine the effectiveness of a transdiagnostic and tailored approach for treating adult patients with depression and/or anxiety, Păsărelu *et al*. conducted a meta-analysis of randomized controlled trials. They included 19 trials with 2952 participants. Transdiagnostic and tailored iCBT yielded controlled Hedges' g values of 0.79 (95% CI: 0.59, 1.00) for depression, 0.82 (95% CI: 0.58, 1.05) for anxiety, and 0.56 (95% CI: 0.37, 0.73) for quality of life [24].

A final question around implementation: can iCBT be offered in the primary care setting? Depression, after all, is most often treated in a primary-care setting [25, 26]. One recent randomized controlled trial investigated the long-term effects of iCBT for depression administered through 16 primary-care centers (the PRIM-NET trial). Researchers compared a three-month therapist-supported iCBT program with treatment as usual for depression. Treatment as usual included in-person therapy, pharmacotherapy, sick leave, and any combination thereof. Patients were followed for 12 months. Within group effect sizes for iCBT and treatment as usual were high (Cohen's d = 1.42 and 1.29, respectively, at 12 months). No significant differences in depressive symptoms, quality of life, and psychological distress were observed between iCBT and treatment as usual at 3, 6, and 12 months. These data indicate that long-term iCBT with therapist support may be as effective as treatment as usual in a primarycare setting [27].
