Spotlight: generalised anxiety disorder

Generalised anxiety disorder (GAD) is a disorder whereby patients suffer extreme and uncontrollable worry in a way which is disproportionate to the source of the worry. These symptoms must last a minimum of six months in order for a diagnosis to be made. This worry is generally uncontrollable and has a negative impact on day to day functioning.

These patients may also suffer from physical manifestations of their disorder including insomnia, difficulty concentrating, sweating, tremor, agitation, restlessness, nausea, episodes of shortness of breath and dizziness. GAD is less prevalent in older adults than in younger adults but it remains one of the most common anxiety disorders in the elderly.

DSM-IV criteria

The DSM-IV criteria for GAD are:

 

The DSM-V guidelines are due for release soon and the DSM-V workgroup suggests that there may be some changes to the GAD guidelines, including changing the name from Generalised Anxiety Disorder to Generalised Worry Disorder in order to highlight the prominent feature of the disease. The main changes suggested in the preliminary proposals are a reduction in duration of symptoms to three months for diagnosis, and it also outlines the changes in behaviour that may be seen such as marked avoidance of potentially negative activities and marked procrastination in decision making or repeatedly seeking reassurance due to worries.¹

Diagnosis

The diagnosis of GAD in older adults can be quite a challenge to make. Many older people will not have full blown symptoms or fulfil all of the DSM-IV criteria, but tend to present with physical manifestations of anxiety such as insomnia or multiple vague symptoms that may be misinterpreted as a physical illness or as part of the ageing process rather than as a psychiatric disorder.² Also, older people and healthcare professionals may consider anxiety to be a normal response to their current situation rather than a problem for which they require help. As can occur in patients presenting with depression, there is a danger of normalising the symptoms and therefore under-treating, leading to continued distress. Many of the tools used to diagnose GAD were generated with younger people in mind and therefore may not be appropriate for making the diagnosis accurately in older people.³

There are several psychiatric disorders that may present in a similar way to GAD, including mixed depression and anxiety, obsessive-compulsive disorder, phobic disorders including social phobia and agoraphobia and stress disorder. Most commonly GAD can co-exist with depression;⁴ this comorbidity is associated with increased severity of the underlying depression with a higher suicide risk in these patients. It is therefore very important that clinicians enquire about core depressive symptoms in patients presenting with late onset GAD. There is also noted to be a greater chronicity of either condition if both conditions are present. Studies have shown anything between 13-29% of older people with GAD are also suffering from a major depressive illness.

It has been shown that patients with co-existing depression and GAD are generally more resistant to treatment than those with a single diagnosis. An American study in 2005 showed a remission rate at three year follow up of 48% for patients with pure GAD compared to 27% for patients with co-existing GAD and depression.⁵

Clinicians need to be aware that cognitive impairment is more common in this age group, therefore it is very important to screen for this in patients presenting with GAD as it can have a similar presentation with poor concentration, disturbed sleep, and agitation. In patients with mild cognitive impairment, having insight into this may lead to significant anxiety, in particular when thinking ahead to what their future may hold. The presence of underlying cognitive impairment may also affect the management options for GAD as discussed later. The 6CIT assessment may be used effectively to screen for this.

6CIT

Somatic symptoms

Somatic symptoms seen in GAD may also be caused by several medical conditions including hyperthyroidism, vitamin B12 deficiency and alcohol withdrawal, and also due to medications, either from stimulants such as salbutamol, thyroxine, or withdrawal from depressants such as benzodiazepines, especially early morning anxiety with withdrawal from temazepam, and alcohol withdrawal. There can often be a vicious cycle of symptoms set up with medical comorbidity, for example in the case of chronic obstructive pulmonary disease; excessive worry may precipitate symptoms of shortness of breath which in turn precipitates further anxiety.⁷

Prevalence and risk factors for older people

A survey in 2007 suggested the point prevalence of GAD in adults aged 65-74 years is 3.3%, >75 years is 2.6%. The point prevalence of mixed anxiety and depression in adults aged 65-74 years is 6.4%, >75 years is 5.9%.⁸ Factors which may increase the risk of a patient suffering from GAD tend to be a combination of social, biological and psychological.

Important psychological factors include poor coping strategies and contributing social factors tend to be female sex, childlessness and poor social support network.

Older people with GAD tend to worry more about health and family problems with work-related issues less of a focus as compared to younger patients.

NICE treatment guidelines⁹

Step 1

This is all known and suspected presentations of GAD. Consider the diagnosis of GAD in people presenting with anxiety or significant worry, and in people who attend primary care frequently who:

Step 2

This is diagnosed GAD that has not improved after step 1 intervention (education and active monitoring). Individual self-help strategies and psychoeducational groups are recommended.

Step 3

This is GAD with marked functional impairment or that has not improved after step 2. Offer either psychological therapy eg. CBT or applied relaxation or drug therapy (SSRI first line, suggest sertraline as cost-effective but did not have UK marketing authorisation at time of NICE guidelines). Must only use benzodiazepines as a short-term treatment in a crisis, must not use anti-psychotics.

Step 4

This is input from secondary care, crisis teams, day hospitals, inpatient care. Consider referral to step 4 if the person with GAD has severe anxiety with marked functional impairment in conjunction with:

SSRIs are advised by NICE for use as first-line drug therapy; however, care must be taken in the elderly with these drugs, in particular the increased risk of gastrointestinal bleeding in association with aspirin. There is also a significant risk of hyponatraemia associated with SSRI use in this group of patients in particular. This is because they are often concurrently taking medication such as diuretics which may also lower their sodium, or may have a comorbid condition such as cardiac or renal failure contributing further. SSRIs have been shown to increase the risk of cerebrovascular disease and seizures in older people.¹⁰

There is a risk of activation in patients taking SSRIs and SNRIs, leading to increased anxiety and disturbed sleep, therefore it is important to initiate these at a low dose and gradually increase. Sertraline is not licensed for the treatment of GAD but NICE advises to consider it as it is the most cost-effective drug. Sertraline has been shown to be associated with a lower risk of hyponatraemia and is also considered to be safe in patients with unstable angina or following a myocardial infarction. A recent systematic review of 27 randomised controlled trials looking at the efficacy of drug treatments in generalised anxiety disorder suggested that fluoxetine and sertraline, the former for efficacy and the latter for tolerability, may have an advantage over other drug treatments.¹¹

Treatment should be reviewed over several weeks and a change to an alternative SSRI considered if no benefit is seen after 12 weeks of treatment. If there is improvement noted over the first 12 weeks, once the optimal dose is reached, patients should continue on this for six months and then the dose tapered gradually over a period of time.

Patients should be advised that stopping an antidepressant abruptly may lead to withdrawal symptoms, those most commonly experienced are dizziness, numbness and tingling, GI disturbance, headache, sweating, anxiety and sleep disturbance.

If an SSRI is not effective or not tolerated, venlafaxine, a serotonin and noradrenaline re-uptake inhibitor, may be used. Venlafaxine is useful in the treatment of older patients as it has few known drug interactions and it shows a predictable increase in plasma concentration with dose increases.

There is however a higher risk of withdrawal with venlafaxine, compared with other antidepressants; this needs to be gradually withdrawn over at least four weeks and there is a significant risk of toxicity in overdose.

In patients where SSRIs have not been effective or well-tolerated and due to medical comorbidities such as diabetes, venlafaxine is not appropriate.
Duloxetine may be considered as a third line treatment.¹²

If all treatments above have not been suitable, fourth line consideration would be pregabalin. A placebo-controlled trial¹³ in 2008 has shown pregabalin to be effective in the treatment of GAD in adults aged 65 years and older. This trial has also shown it to be well-tolerated with dizziness being the most commonly reported adverse effect. Pregabalin was shown to have an effect on both the psychological and somatic symptoms of GAD. The beneficial effect of this drug however, as with SSRIs, may take up to two weeks after initiating treatment.

NICE do recommend the short-term use of benzodiazepines, in a crisis only, however these have been found to be associated with an increased risk of falls and hip fracture in a population already at risk. The benefit of prescribing these must be closely weighed up with these significant potential side effects. With regard to pharmacokinetics, lorazepam or oxazepam would be the benzodiazepines of choice in this older population.¹⁴

Antipsychotics are not recommended by NICE for use in GAD. This is due to a significantly increased risk of falls, cerebrovascular accident and overall all-cause mortality in the elderly. Much of the information regarding the pharmacological treatment of GAD in older adults is extrapolated from information known to be true in younger adults as there have been only limited studies in the older age group.

Summary

Generalised anxiety disorder is a common mental health disorder to consider in the elderly who may present in an atypical way. It can often co-exist with other disorders such as depression and physical health problems and lead to a poorer outcome. Treatment is on a step-wise approach, incorporating both pharmacological and non-pharmacological approaches which must be tailored appropriately to the age group involved.

Conflict of interest: none declared.

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