Will the RANZCP clinical practice guidelines for the treatment of anxiety disorders assist in making adequate treatment decisions for panic disorder?

Providing a commentary on an ambitious and praiseworthy endeavour such as the Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for the Treatment of Panic Disorder, Social Anxiety Disorder and Generalised Anxiety Disorder (Andrews et al., 2018; Anxiety CPGs) is a daunting task because of the sheer amount of effort that went into it. Therefore, humility is in order when approaching these guidelines. Still, no document is perfect and Anxiety CPGs should be scrutinised with the same critical acumen as any other work. The present commentary will only address certain aspects of panic disorder (PD) in view of both the scope of Anxiety CPGs and the limited space allocated to commentaries.

What are the goals of treatment of PD?

The specific goals of treatment of PD are not stated in Anxiety CPGs. Instead, one finds general goals of treatment of anxiety disorders, including recovery, reducing physical and cognitive symptoms and behavioural avoidance, as well as relapse prevention. Considering patients’ goals and expectations of treatment is listed as a part of comprehensive assessment, but what these goals may involve is not elaborated.

Different therapeutic approaches to PD explicitly or implicitly espouse different goals. Some emphasise elimination and prevention of panic attacks, whereas others consider it more important to focus on the fear of further panic attacks and panic symptoms (i.e. anticipatory anxiety). Still other therapeutic modalities suggest that patients should be taught how to live with their panic attacks.

Clarity about treatment goals in PD is not an academic exercise. This is important to patients, and they should know from the very beginning of treatment what to expect and what not to expect. Furthermore, numerous studies have reported that PD is associated with an increased risk of cardiovascular morbidity and mortality, and the stipulation of treatment goals for PD then carries even more weight. For example, if the persistence of panic attacks is demonstrated to be a risk factor for cardiovascular diseases, prevention of panic attacks might become the main goal of treatment.

Selective serotonin reuptake inhibitors and PD

Along with other treatment guidelines, Anxiety CPGs endorse selective serotonin reuptake inhibitors (SSRIs) as first-line pharmacotherapy for PD. This is controversial for several reasons.

First, SSRIs are not more efficacious for PD than agents such as benzodiazepines. In fact, the only study that directly compared an SSRI (paroxetine) with a benzodiazepine (clonazepam) over a long-term treatment of PD demonstrated that use of clonazepam predicted lower relapse rates (Freire et al., 2017).

Second, SSRIs have numerous side effects, including gastrointestinal symptoms (nausea, diarrhoea, gastric bleeding, dyspepsia), agitation, dizziness, sexual dysfunction, hyponatremia, weight gain, increased suicidal ideation, sleep disturbances, cardiovascular abnormalities, osteoporosis and risk of fractures, sweating, bleeding tendencies, extrapyramidal symptoms and apathy (Carvalho et al., 2016). There is evidence that side effects of benzodiazepines (e.g. sedation) are better tolerated than those of SSRIs during both short-term and long-term treatment of PD.

Third, SSRIs are associated with frequent and severe withdrawal symptoms (e.g. Fava et al., 2015). These symptoms, euphemistically called ‘discontinuation symptoms’, may pose a greater problem than benzodiazepine withdrawal symptoms.

Thus, a decision to replace benzodiazepines with SSRIs as the pharmacotherapy of choice for PD was made without a demonstration of the comparative advantage of SSRIs.

What about benzodiazepines?

The portrayal of benzodiazepines in Anxiety CPGs is predictably negative. They are described as ‘associated with a significant risk of relapse and difficulty discontinuing’ (p. 21), although there is no evidence that they perform worse than SSRIs in these domains. The notion of tolerance to anxiolytic effects of benzodiazepines features in Anxiety CPGs, despite evidence from at least four studies that most patients with PD do not tend to increase the dose of benzodiazepines during long-term treatment.

What is then the role of benzodiazepines? According to Anxiety CPGs, benzodiazepines may only be used short-term, occasionally in an emergency setting and to manage a panic attack. In clinical practice, benzodiazepines are frequently used for PD because of their quick onset of action, relatively good tolerability and sustained effectiveness. It is a paradox that while a long quest for a fast-acting antidepressant is not abating, the fast-acting characteristic of antianxiety agents such as benzodiazepines appears to be perceived as liability, possibly because of its presumed link with dependence.

There is a growing need to reappraise benzodiazepines in the treatment of PD, aiming to maximise their advantages and minimise drawbacks (Nardi et al., 2018). This task calls for an unbiased, evidence-based approach and an effort to distinguish the myth from reality.

Conclusion

The role of clinical practice guidelines is to help clinicians make evidence-based treatment decisions, but they should consider all evidence and be suited to the reality of clinical practice. This commentary demonstrates that Anxiety CPGs may hinder appropriate use of therapeutic modalities for PD, instead of facilitating it.