Chapter 5.2 How effective are current drug treatments for anxiety disorders, and how could they be improved?

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Abstract

Although there are many psychotropic drugs and psychotherapies available for the treatment of patients with anxiety disorders, overall clinical outcomes and the standard of care for most patients with these common, persistent and impairing illnesses are usually far from optimal. The disorders typically follow a chronic or recurring course in which full symptomatic remission is uncommon; they are associated with the temporal accumulation of comorbid disorders and with an increased suicide risk; and treatment responsiveness may diminish over time. This chapter examines the efficacy of current pharmacological treatments in the three main anxiety disorders – generalised anxiety disorder (GAD), panic disorder and social anxiety disorder (social phobia) – and summarises how clinical outcomes might be improved by a number of alternative approaches, including the enhanced use of existing treatments, modifications to existing psychotropic drugs and the development of new targets for anxiolytic pharmacotherapy. It also describes how advances in genetics and neuroscience might lead towards more individualised drug treatments, whilst recognising that theoretical treatment advances can only improve outcomes if used rationally, in collaboration with the patient.

Section snippets

Which pharmacological treatments are efficacious in anxiety disorders?

Systematic reviews and randomised placebo-controlled trials indicate that some selective serotonin reuptake inhibitors (SSRIs), the serotonin-noradrenaline reuptake inhibitors (SNRIs) venlafaxine and duloxetine, some benzodiazepines (alprazolam and diazepam), the tricyclic antidepressant (TCA) imipramine, the 5-HT1A partial agonist buspirone, the novel anticonvulsant pregabalin, the antipsychotic trifluoperazine and the antihistamine hydroxyzine are all efficacious in the acute treatment of

What is the mechanism of action in anxiety disorders?

Investigations of altered serotonergic or noradrenergic function in the pathophysiology of anxiety disorders have produced rather inconsistent findings – whether this is in GAD, panic disorder or social phobia. However, the ‘broad-spectrum’ efficacy of SSRIs, SNRIs and benzodiazepines in anxiety disorders has naturally focused attention on the possible role of enhanced serotonergic and noradrenergic neurotransmission, and altered function of the GABA-benzodiazepine receptor chloride ionophore

Do randomised controlled trials reveal consistent differences in efficacy?

OCD, in which anxiety symptoms are common, appears to show a singular specificity of the acute treatment response, to compounds that primarily inhibit 5-HT reuptake, namely the SSRIs and clomipramine (Fineberg and Gale, 2005), whereas primarily noradrenaline reuptake inhibitors have little or no efficacy. The situation is quite different in the treatment of patients with the anxiety disorders GAD, panic disorder and social phobia, where a wide range of psychotropic drugs with varying

Why don’t randomised controlled trials reveal more differences between treatments?

The inability of randomised controlled trials to reveal consistent clinically relevant differences between pharmacological treatments might simply reflect the limited impact that current approaches have in correcting the underlying pathophysiology in anxiety disorders. Novel treatments could result in improved efficacy and tolerability, but the design of phase II and III studies also needs to be refined, in order to be able to demonstrate potential advances convincingly. The lack of reliable,

Could clinical outcomes be improved with better use of current treatments?

Patients included within randomised controlled trials in anxiety disorders are required by regulators to have low levels of coexisting depressive symptoms or comorbid disorders, are in generally good physical health, have limited use of concomitant medication and have anxiety symptoms that are neither too mild to be able to reveal efficacy nor too severe to comprise their participation in a treatment study. Even in these good prognosis patients who are subject to frequent assessments in a

Can psychological therapies enhance the efficacy of pharmacological treatments?

Cognitive-behavioural therapy (CBT), the most extensively researched form of psychological treatment (Dobson, 2001), is effective in many anxiety disorders (Butler et al., 2006). Based on Beck's early cognitive model it assumes that biases in information processing which favour threat information increase perceptions of threat and danger, and thereby maintain anxiety disorders (Beck et al., 1985; Williams et al., 1997; Mogg and Bradley, 1998). Anxiety is thought to be characterised by the

Could clinical outcomes be improved, with new targets for anxiolytic drugs?

Advances in clinical neuroscience and awareness of the limited efficacy and adverse effects of current treatments for anxiety disorders have together encouraged the identification of many new targets for the development of potential new anxiolytic drugs. As described in detail in previous chapters, many putative anxiolytics are being evaluated, some in phase III studies; others have failed to sustain the promise of early findings and are no longer in development.

As reviewed above, although

Could clinical outcomes be improved through using genetic approaches?

Certain demographic or clinical factors have been found predictive of treatment response or non-response in patients with anxiety disorders, but many individuals with factors that are predictive of a good response will still respond only poorly. Concerted efforts are therefore being made to establish whether a given patient is likely to respond particularly well to a given treatment, on the basis of their genetic profile. For example, genotyping for cytochrome P450 enzymes might be useful in

The insights offered by studies of pharmacological modulation of emotion processing

The similar overall efficacy of pharmacological, psychological and combination treatments raises questions regarding potential common mechanisms that might be involved in the treatment response. Recent years have seen much research involving pharmacological modulation of the dysfunctional cognitive processes proposed to maintain mood and anxiety disorders, and using advanced imaging techniques to probe the functional neuroanatomy of pharmacological and psychological treatments for anxiety

Do neuroimaging studies explain the neuroanatomy of the treatment response?

The number of studies that have used neuroimaging techniques to explicitly evaluate neural correlates of psychological and pharmacological treatment has steadily increased (Roffman et al., 2005). For example, successful behavioural therapy for OCD has been found associated with a decrease in metabolism in the caudate nucleus, consistent with the presumed pathophysiology of the disorder (Saxena et al., 1998). Moreover, both fluoxetine and psychotherapy for OCD appear to uncouple dysfunctional

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