Ep 125 – Generalised anxiety disorder

Generalised anxiety disorder (GAD) is a common condition defined as chronic, excessive worry for at least 6 months that causes distress or impairment, and is hard to control. It is in part a diagnosis of exclusion: physical examination and laboratory studies are generally normal if no co-existing physical or mental health conditions or substance misuse issues exist. Treatment is primarily with psychotherapy (usually cognitive behavioural therapy), serotonergic antidepressants or a combination of these approaches. In this episode, Dr Roger Henderson looks at how best to diagnose GAD, what treatment options should be considered, possible differential diagnoses and the long-term outlook for patients.

Key references

1. NICE. 2020. https://www.nice.org.uk/guidance/cg113.
2. Weeks JW, Heimberg RG. Depress Anxiety. 2005;22(1):41-44. doi: 10.1002/da.20068.
3. Hoge EA, et al. BMJ 2012;345:e7500. doi: 10.1136/bmj.e7500.
4. NHS. https://www.nhs.uk/mental-health/conditions/generalised-anxiety-disorder/.
5. NICE. 2022. https://www.nice.org.uk/guidance/ng215.

Key take-home points

• A syndrome of ongoing anxiety and worry about events or thoughts that the patient generally recognises as excessive and inappropriate.
• Lifetime prevalence of GAD is 5%.
• Risk factors: aged 35–54 years, divorced or separated, living alone or as a lone parent.
• Protective factors: aged 16–24 years, married or cohabiting.
• Diagnosed based on a combination of excessive anxiety and worry (including "apprehensive expectation") that occurs more days than not for at least 6 months and that the person finds difficult to control. Diagnosis also requires symptoms such as restlessness or muscle tension, autonomic arousal, chest or abdominal symptoms, mental state symptoms (fear of dying, dizziness, depersonalisation) and general or non-specific symptoms.
• Differentials include panic disorder, post-traumatic stress disorder, obsessive-compulsive disorder, phobias and acute stress.
• Consensus is that screening tests (such as Beck's Anxiety Inventory) are worth employing in evaluation and treatment.
• NICE says to identify cases early, ask the patient about their treatment preferences and inform them about the condition as much as possible.
• Long-term, best results are from psychotherapy, followed by medication, followed by self-help.
• The placebo response in GAD is 20–50%.
• Only refer the most difficult cases.
• Remember there are frequently co-morbid conditions (depression, drug abuse, etc) that may need treating and NICE recommends that the most severe condition be treated first.
• If a rapid response is needed, try a sedative antihistamine or a benzodiazepine (up to 4 weeks). Buspirone tends to be less sedative and addictive than benzodiazepines but should be used with the same caution. Remember that apparent dependence may be due to genuine dependence or because the disease has returned as the drug is withdrawn.
• Antidepressants can be good at alleviating anxiety, even if no true depression is present. Slower than benzodiazepines but can be used for longer.
• NICE suggests a selective serotonin reuptake inhibitor (SSRI) or venlafaxine as first choice (it advises sertraline first-line, but this is unlicensed for GAD).
• Licensed SSRIs for GAD in the UK are paroxetine and escitalopram. Always inform the patient about potential side effects and time to onset of benefit.
• If there is no benefit after 12 weeks, then try a different class of antidepressant; SSRIs and venlafaxine should be tailed off.
• If the person cannot tolerate SSRIs or serotonin-norepinephrine reuptake inhibitors, consider offering pregabalin (remember pregnancy advice).
• Duloxetine (not mentioned by NICE) is licensed for GAD and can be effective.
• There is no evidence to guide us regarding the effective duration of therapy (it is the prescriber’s call) but NICE suggests continuing effective treatment for at least 1 year as the likelihood of relapse is high.
• Beta-blockers and monoamine oxidase inhibitors are not usually considered appropriate options for GAD.
• In primary care, review medication usually every 4–8 weeks; NICE recommends review every 2–4 weeks for the first 3 months, and then 3-monthly.
• If possible, monitor the outcome with a self-complete questionnaire.