CBT has consistently been shown to be effective as first-line treatments in randomised controlled trials.6
There are basically three types of CBT: individual CBT, group CBT and internet CBT. Recent studies have demonstrated the superiority of individual format CBT over group format,12
and internet CBT has shown comparable effectiveness to group CBT.14
While no clear evidence has shown that the combination of selective serotonin reuptake inhibitor (SSRIs) and CBT is more effective than single-modality treatment,15
CBT has a number of potential advantages over pharmacotherapy in the treatment of anxiety disorder (including individual -based, group -based and internet-based): longer effects, fewer adverse effects, smaller relapse rates and greater acceptability.17–20
Pharmacotherapy has disadvantages such as more side effects and higher rates of relapse with the discontinuation of medication,21
and patients often prefer psychological treatment (even if this is more well known in the depression literature).23
Nevertheless, CBT is used much less frequently in clinical practice because of the limited availability of specialised practitioners and it has received much less promotion from pharmaceutical companies than pharmacotherapy.24
Thus, pharmacotherapy is actually used as a first choice treatment for SAD by most clinicians, even in countries with initiatives to improve access to psychological therapies (eg, the UK, Australia).25–27
With regard to pharmacotherapy, treatment varies according to the subtypes (generalised and non-generalised). However, we focus primarily on treatment options for generalised SAD because currently there is very limited clinical trial-based evidence for the treatment of non-generalised SAD.28
Pharmacotherapy, as a first-line treatment for SAD, currently involves the use of SSRIs. A growing database of randomised controlled trials had demonstrated that SSRIs are effective and well tolerated.7
Further, there is strong evidence that SSRIs are also effective for treating many of the comorbid conditions, such as depression and other anxiety disorders, frequently associated with SAD.
Serotonin-noradrenaline reuptake inhibitors are also recommended for first-line pharmacotherapy. However, there are comparatively few studies on this class of drugs, in comparison with SSRIs, and only venlafaxine has been demonstrated to be effective22
; therefore, fewer countries have approved serotonin-noradrenaline reuptake inhibitors for treating SAD than SSRIs (eg, they have not been approved in Japan).
SSRIs have a relatively flat dose–response curve.34
Nevertheless, evidence suggests that a superior response may be obtained with higher doses of SSRIs.35
Clinical experience also suggests that some patients may require higher than normal starting doses to achieve an optimal response, and may even require maximal doses. SSRI administration should last for at least 12 weeks before its efficacy is assessed.36
Of course, SSRI treatment usually includes some type of non-specific psychotherapy (eg, supportive counselling) from the general practitioner.
Second-line treatment options for SSRI-resistant SAD cases
A significant proportion of SAD patients fail to respond to initial treatment with SSRIs.37
The presence of residual symptoms is known to be associated with higher relapse rates, decreased quality of life and greater functional impairment38
; however, there is no standard approach to their management. On the whole, conventional second-line treatment is based on the clinician’s own judgement. Clearly, it is of increasing importance to consider therapeutic alternatives for patients with SAD who demonstrate resistance to SSRIs. A systematic review has advocated reviewing treatment options with limited evidence, including augmentation with another pharmacological agent or switching to another antidepressant, if patients show little or no response to the initial SSRI treatment after 12 weeks.36
Limited evidence supports the value of augmenting SSRI treatment with buspirone,39
and atypical antipsychotic medications, such as risperidone and aripiprazole.41
A few studies have shown positive results when treatment was switched to a second SSRI or to a serotonin-noradrenaline reuptake inhibitor in SAD patients who failed to respond to initial SSRI treatment.43–45
CBT as a second-line treatment for SSRI-resistant SAD cases
While there is some evidence of the effectiveness of combined pharmacotherapy and CBT, the evidence for an additive effect when combining the two modalities is mixed; further, there is no evidence concerning the effectiveness of combined therapy specific to SSRI-resistant cases.15
Previously published systematic reviews, including case reports with ≥11 cases are not available regarding the use of CBT as a next step for SSRI non-remitters among SAD patients.47
In our preliminary study, most patients with SAD exhibited substantial resistance to SSRIs; however, 73% of the participants in the study were judged to be treatment responders, with 40% meeting the criteria for remission. The within-group effect size, between pre-CBT and post-CBT, on the Liebowitz Social Anxiety Scale (LSAS) total score was also large (Cohen's d=1.71). Thus, this preliminary study suggested that CBT might have potential as a next-step strategy, even for cases of SSRI-resistant SAD.
In summary, this paper describes the study protocol for a randomised controlled trial to evaluate the clinical effectiveness of CBT administered concomitantly with conventional treatment for patients with SSRI-resistant SAD.