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Generalised anxiety disorder Introduction Generalised anxiety disorder (GAD) has a fluctuating course, but it tends to be a long-term disorder. It affects up to 5% of the population. Diagnostic criteria for GAD include excessive anxiety and pervasive and uncontrollable worry about a number of events or activities, and which occurs for a period of 6 months or longer. Associated symptoms include: • restlessness or feeling ‘keyed up’ or ‘on edge’ • being easily fatigued • difficulty concentrating or mind ‘going blank’ • irritability • muscle tension • sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep). Other criteria are that the focus of the anxiety and worry is not confined to features of another psychiatric disorder; also, that the anxiety, worry or physical symptoms cause clinically significant distress or impairment in social, occupational or other important areas of functioning. There is overlap between GAD and other anxiety disorders, and it often coexists with and may mask major depressive disorder and/or dysthymic disorder. Organic factors (eg hyperthyroidism, caffeine intoxication, stimulant use, alcohol/drug discontinuation syndrome) or adverse effects of prescribed drugs or over-the-counter medication must be excluded. An adjustment disorder, as defined in Adjustment disorder with anxious mood, must also be excluded. When middle-aged or older patients first present with anxiety symptoms, exclude depression or dementia as the primary cause of the anxiety symptoms. On the available evidence, both psychological interventions and pharmacotherapy options are of moderate efficacy. For treatment of GAD in childhood and adolescence, see Anxiety disorders in childhood and adolescence. The first-line treatments for generalised anxiety disorder are psychological. Psychological interventions Initial treatment for generalised anxiety disorder (GAD) should include information about the anxiety disorder and education on relaxation techniques and coping skills. Stress management approaches including activity scheduling, modifying lifestyle factors, problem-focused counselling, and other more specific approaches, such as structured problem solving, are often beneficial. Ongoing supportive psychotherapy is important. More specialised psychotherapies, particularly cognitive behavioural therapy (CBT), can be especially effective. An experienced, trained clinician should provide the CBT. When symptoms are more severe, pharmacotherapy is usually also required. Pharmacotherapy When psychological interventions do not provide sufficient benefit, pharmacotherapy may be added. While many patients with generalised anxiety disorder (GAD) require long-term treatment, a trial of reduction and cessation of medication should be attempted after the patient has been symptom free for at least 6 months. The chance of return of symptoms is reduced if psychological interventions are used concurrently. Selective serotonin reuptake inhibitors (SSRIs) are the most effective pharmacotherapy for GAD. In addition, the serotonin and noradrenaline reuptake inhibitors venlafaxine and duloxetine have demonstrated efficacy for GAD. Both classes of antidepressant take some weeks before efficacy is apparent, similar to the onset of response for depression. Choice of drug should take into account the tendency to produce a withdrawal (discontinuation) syndrome, and likelihood of toxicity in overdose (venlafaxine) as well as the adverse effect profile and potential for drug interactions. Doses required for treating GAD are generally at the lower end of the recommended dose range. If considered appropriate, use: 1 an SSRI orally, see Table 8.1* OR *At the time of writing, citalopram, fluoxetine, fluvoxamine and sertraline are not approved by the Australian Therapeutic Goods Administration (TGA) for treatment of generalised anxiety disorder. See the TGA website <www.tga.gov.au> for current information. Therapeutic Guidelines Limited (www.tg.org.au) is an independent not-for-profit organisation dedicated to deriving guidelines for therapy from the latest world literature, interpreted and distilled by Australia’s most eminent and respected experts. Reproduced with permission from Psychotropic Expert Group. Generalised anxiety disorder [revised 2013]. In: eTG complete [Internet]. Melbourne: Therapeutic Guidelines Limited; 2013. Generalised anxiety disorder 2 duloxetine 30 mg orally, daily initially, increasing according to tolerability and patient response. Maximum dose 120 mg daily OR 2 venlafaxine controlled-release 75 mg orally, in the morning after food, increasing according to tolerability and patient response. Maximum dose 225 mg daily. Tricyclic antidepressants are effective but are not considered first-line treatment due to adverse effects. They should be used with caution if there is coexisting depression or ideas of self-harm because they are toxic in overdose. If considered appropriate, an example would be to use: imipramine 25 mg orally, at night, increasing gradually to 75 mg at night. Buspirone is a further alternative treatment. It has negligible potential for tolerance or dependence and no discontinuation syndrome. Response to buspirone may take 2 to 4 weeks, though initial response may be apparent within 7 to 10 days. The mean effective daily dose of buspirone is 20 to 25 mg daily. If considered appropriate, use: buspirone 5 mg orally, 3 times daily initially, increasing if necessary to 20 mg 3 times daily. Several studies have shown that pregabalin, a presynaptic inhibitor of the release of excitatory neurotransmitters, is effective in the treatment of GAD. The initial dose is 150 mg daily and increases gradually after 1 to 2 weeks to 450 to 600 mg daily. Effects are seen within a week. Adverse effects include somnolence, dizziness and dry mouth, and are more prominent when higher doses (600 mg daily) are used. There is no rebound anxiety when it is discontinued; however, when stopping, gradually decrease the dose to avoid precipitating a seizure. Pregabalin does not have Therapeutic Goods Administration approval for use in Australia for GAD. Existing data and current guidelines do not support the use of second-generation antipsychotics for the treatment of GAD. While monotherapy with quetiapine does seem to be efficacious in reducing symptoms of GAD, this efficacy must be weighed against its possible adverse effects. Data examining the use of second-generation antipsychotics for augmentation treatment have shown limited benefit and greater risk of discontinuation due to adverse effects. Benzodiazepine use may be associated with a variety of adverse effects (eg dependence, cognitive impairment, psychomotor effects including the risk of falls in older patients, somatic symptoms). Benzodiazepines may be used for the treatment of GAD as a short-term measure during crises, when anxiety is severe and disabling or causing the patient unacceptable distress, and taking into account the precautions listed previously (see Anxiety and associated disorders: general information). If necessary, consider use of: diazepam 2 to 5 mg orally, as a single dose, which may be repeated, if required, up to twice daily. Treatment should be for up to 2 weeks followed by gradual reduction of dose to zero within 6 weeks. Some patients can reduce the dose in a shorter period. Subsequent use should be on an ‘as required’ basis. Long-term treatment of GAD with benzodiazepines should only be considered when both psychological interventions and alternative pharmacotherapies have failed to provide significant improvement. If long-term use is contemplated, specialist review and advice should be sought first and a drug with a long half-life should be chosen and the lowest effective dose should be prescribed. If considered appropriate, use: diazepam 2 to 5 mg orally, as a single dose, which may be repeated, if required, up to twice daily. Patients with a diagnosis of an anxiety disorder may, over a period of time, develop depression requiring an antidepressant (see Depression). Therapeutic Guidelines Limited (www.tg.org.au) is an independent not-for-profit organisation dedicated to deriving guidelines for therapy from the latest world literature, interpreted and distilled by Australia’s most eminent and respected experts. Reproduced with permission from Psychotropic Expert Group. Generalised anxiety disorder [revised 2013]. In: eTG complete [Internet]. Melbourne: Therapeutic Guidelines Limited; 2013.