Generalised anxiety disorder

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

anxiety symptoms meeting DSM-5-TR criteria

non-pregnant adults

1st line – cognitive behavioural therapy (CBT)

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1st line –

cognitive behavioural therapy (CBT)

Data to guide clinicians on initial choice of treatment in GAD are limited.[75] Treatment selection should be individualised, and involves a shared decision-making process between patient and clinician.[21] When constructing a treatment approach, consider patient preference, severity of GAD, potential adverse effects, past treatment history, comorbid psychiatric conditions, and treatment availability.[49][65]

CBT is typically considered an equal first-line option to pharmacotherapy, particularly for patients who cannot tolerate or do not want drug therapy. Some treatment guidelines (e.g., UK and Canadian) recommend a stepped approach to treatment, and suggest that non-pharmacological options should routinely be considered as first line.[50][65]

As a general guide, watchful waiting and/or psychoeducation or CBT is recommended for patients with mild anxiety symptoms. CBT (with or without pharmacotherapy) is also recommended for those with moderate anxiety symptoms.

CBT has demonstrated efficacy in treating GAD.[82][83][84][85] One review of 87 studies concluded that 47% of patients with GAD achieved symptom reduction to within normative levels following treatment with CBT.[86] CBT directed at GAD has the additional advantage of improving depressive symptoms, which are frequently comorbid.[85]

CBT may be especially helpful for generalised anxiety in later life, although whether CBT is superior to other commonly available treatments is unclear.[88][89][90][91]

Computer/smartphone-assisted and internet-based interventions may help facilitate access to CBT for people such as those who live in remote locations, or for those on waiting lists in areas where there are long waiting lists for face-to-face treatment. Studies have demonstrated the efficacy of internet-based CBT delivered by individually administered media interventions, although study quality is variable, and frequently low.[92][93] Digital interventions may be more appropriate for those with mild or sub-threshold symptoms of anxiety, and for those who are especially motivated to improve their symptoms.[94][95] Guided interventions (with input from a therapist via email or face-to-face, or via a computer-driven interaction) are associated with larger effect sizes than non-guided interventions.[93][96][97][98][99][100] [ ] There is also evidence for the efficacy of video-conferencing psychotherapy.[101]

Consider – applied relaxation

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Consider –

applied relaxation

Additional treatment recommended for SOME patients in selected patient group

Applied relaxation is an effective therapy using relaxation techniques that do not need in-depth psychotherapy.[80][108][109] UK guidelines recommend that applied relaxation may be used to treat GAD as a stand-alone intervention.[65] It may also be considered as an adjunct. Treatment should be manualised and delivered by a trained practitioner.[65]

Consider – mindfulness or meditation training

Back

Consider –

mindfulness or meditation training

Additional treatment recommended for SOME patients in selected patient group

Mindfulness or meditation training can be used as an adjunct to cognitive behavioural therapy, or as a stand-alone option for patients who are unable or unwilling to do psychotherapy.[102][103][104][105][106][107]

Consider – attention/perception modification

Back

Consider –

attention/perception modification

Additional treatment recommended for SOME patients in selected patient group

Attention/perception modification is effective for treating GAD in university and college students.[105]

Consider – sleep hygiene education

Back

Consider –

sleep hygiene education

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene education can be useful in primary care given the high frequency of sleep disturbance associated with GAD.

Counsel patients to improve sleep hygiene by going to bed and waking up at the same time each day, abstaining from or minimising their use of alcohol, and avoiding caffeine after 3 p.m. Advise them to get out of bed if unable to fall asleep, in order to avoid negative associations with being in bed.[113][114]

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

Consider – self-help

Back

Consider –

self-help

Additional treatment recommended for SOME patients in selected patient group

Self-help treatments, such as books or manuals, have been shown to be more effective than waiting list or placebo.[120][121]

1st line – selective serotonin-reuptake inhibitor (SSRI) or mirtazapine

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1st line –

selective serotonin-reuptake inhibitor (SSRI) or mirtazapine

A number of factors may suggest a need to prioritise initial treatment with medication, including previous non-response to psychological therapy, chronic course of illness, high complexity of illness, and depression comorbidity.[21] There is evidence that antidepressants are more effective in those with severe GAD compared with mild GAD, although the threshold for effectiveness is unclear.[79] Note that UK and Canadian guidelines recommend a stepped approach to treatment, and suggest that medication for GAD should only routinely be offered to people who have not first benefited from non-pharmacological options.[50][65]

As a general guide, pharmacotherapy (with or without cognitive behavioural therapy [CBT]) is recommended for patients with moderate anxiety symptoms, and pharmacotherapy plus CBT is recommended for those with severe or treatment-resistant anxiety.

Base drug selection on the severity of illness/degree of distress, presence of other mental or physical health conditions, past treatment history, substance misuse profile, patient preference, and adverse-effect profile.[131]

Treatment for patients with comorbid depression is similar to that for patients without depression. See Depression in adults.

Patients with severe depression and suicidal ideation may require hospitalisation while therapy takes effect. See Suicide risk mitigation.

SSRIs are considered first-line pharmacotherapy for GAD, given the available evidence regarding efficacy and adverse effects.[49][65][129] Of the SSRIs, escitalopram and sertraline are particularly recommended for GAD by the author of this topic, based on systematic review and meta-analysis data directly comparing pharmacological treatments for GAD, as well as on UK-based guidance from the National Institute for Health and Care Excellence (NICE), which recommends sertraline as having the highest acceptance, risk-to-benefit ratio, and cost-effectiveness profile of pharmacological treatment options for GAD.[65][130][135]

For patients who are unable to take an SSRI (e.g., due to bleeding risk), one option is to offer mirtazapine. Advantages of mirtazapine include its relative safety in older people, and lower rate of drug-drug interactions compared with other pharmacological treatment options for GAD. However, there are few clinical trials assessing mirtazapine for anxiety disorders, and for GAD in particular.[142]

Patients with anxiety may be particularly susceptible to drug adverse effects. The recommended starting dose of antidepressants is typically half of the recommended dose for depression, although the therapeutic dose is the same or even higher.[49] Monitoring for adverse effects, modifying the dose, and switching medications may improve efficacy and patient adherence (e.g., some antidepressants may cause restlessness, which can worsen anxiety symptoms).[133] Response to antidepressant treatment for GAD is relatively slow. The anxiolytic effects of antidepressants should typically begin around 2-4 weeks after initiation, but improvement may continue for weeks to months following this.[134] Maintain the initial starting dose for up to 4 weeks before assessing the treatment response.[49] Benefit should be seen at 12 weeks at a therapeutic dose. If this is not the case, try an alternative.

Once a good therapeutic response is achieved, continue treatment for at least 1 year, after which a trial of discontinuation may be considered. This advice is based on expert opinion and systematic review and meta-analysis data that suggest that treatment with antidepressants for at least 1 year is associated with reduced rates of relapse, and is well tolerated.[48][50][73][170] After that, the patient and prescriber can discuss whether or not to continue, based on adverse effects and other considerations. For example, the patient may wish to try coming off the medication if their level of life stress has decreased.[40] If there is agreement to reduce and stop the antidepressant, do so slowly, and monitor carefully for symptom recurrence.

If a patient chooses pharmacotherapy as a first-line treatment, where possible clinicians should offer a full range of non-pharmacological adjunctive therapies as part of their treatment.[49]

Primary options

escitalopram: 10 mg orally once daily initially, increase gradually according to response, maximum 20 mg/day

sertraline: 25 mg orally once daily initially, increase gradually according to response, maximum 200 mg/day

Secondary options

mirtazapine: consult specialist for guidance on dose

Consider – cognitive behavioural therapy (CBT)

Back

Consider –

cognitive behavioural therapy (CBT)

Additional treatment recommended for SOME patients in selected patient group

Consider adding CBT if symptoms are refractory to drug therapy alone, or from the start of treatment if symptoms are moderate to severe. CBT has demonstrated efficacy in treating GAD.[82][83][84][85] One review of 87 studies concluded that 47% of patients with GAD achieved symptom reduction to within normative levels following treatment with CBT.[86] CBT directed at GAD has the additional advantage of improving depressive symptoms, which are frequently comorbid.[85]

CBT may be especially helpful for generalised anxiety in later life, although whether CBT is superior to other commonly available treatments is unclear.[88][89][90][91]

Both short- and long-term psychodynamic psychotherapy have also been shown to be effective if CBT is unavailable.[110][111][112][204] [ ]

Consider – applied relaxation

Back

Consider –

applied relaxation

Additional treatment recommended for SOME patients in selected patient group

Applied relaxation is an effective adjunctive therapy that uses relaxation techniques that do not need in-depth psychotherapy.[80][108][109] UK guidelines recommend that applied relaxation may be used to treat GAD as a stand-alone intervention.[65] It may also be considered as an adjunct. Treatment should be manualised and delivered by a trained practitioner.[65]

Consider – mindfulness or meditation training

Back

Consider –

mindfulness or meditation training

Additional treatment recommended for SOME patients in selected patient group

Mindfulness or meditation training can be used as an adjunct to pharmacotherapy and if patients are unable or unwilling to do psychotherapy.[102][103][104][105][106][107]

Consider – attention/perception modification

Back

Consider –

attention/perception modification

Additional treatment recommended for SOME patients in selected patient group

Attention/perception modification is effective for treating GAD in university and college students.[105]

Consider – sleep hygiene education

Back

Consider –

sleep hygiene education

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene education can be useful in primary care given the high frequency of sleep disturbance associated with GAD.

Counsel patients to improve sleep hygiene by going to bed and waking up at the same time each day, abstaining from or minimising alcohol use, and avoiding caffeine after 3 p.m. Advise them to get out of bed if unable to fall asleep to avoid negative associations with being in bed.[113][114]

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

Consider – self-help

Back

Consider –

self-help

Additional treatment recommended for SOME patients in selected patient group

Self-help treatments, such as books or manuals, have been shown to be more effective than waiting list or placebo.[120][121]

2nd line – serotonin-noradrenaline reuptake inhibitor (SNRI)

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2nd line –

serotonin-noradrenaline reuptake inhibitor (SNRI)

SNRIs are typically considered a second-line option for GAD, and as such may be considered for patients who have not tolerated or not experienced symptomatic improvement with one to two selective serotonin-reuptake inhibitors (SSRIs).[49] The available evidence suggests that they are effective compared with placebo and compared with other pharmacological treatment options for GAD.[130][143][144][145] However, in the author's clinical experience they may be somewhat less well tolerated than SSRIs.

Venlafaxine and duloxetine are preferred, based predominantly on the results of a large 2019 network meta-analysis that concluded that both drugs were more effective and had better acceptability than placebo, backed by a substantial body of evidence.[130]

Treatment for patients with comorbid depression is similar to that for patients without depression. See Depression in adults.

SNRI treatment of anxiety with major depression has evidence for effectiveness.[172]

Patients with severe depression and suicidal ideation may require hospitalisation while therapy takes effect. See Suicide risk mitigation.

The recommended starting dose of antidepressants is typically half of the recommended dose for depression, although the therapeutic dose is the same or even higher.[49] Monitoring for adverse effects, modifying the dose, and switching medications may improve efficacy and patient adherence (e.g., some antidepressants may cause restlessness, which can worsen anxiety symptoms).[133] Response to antidepressant treatment for GAD is relatively slow. The anxiolytic effects of antidepressants should typically begin around 2-4 weeks after initiation, but improvement may continue for weeks to months following this.[134] Maintain the initial starting dose for up to 4 weeks before assessing the treatment response.[49] Benefit should be seen at 12 weeks at a therapeutic dose. If this is not the case, try an alternative.

After that, the patient and prescriber can discuss whether or not to continue, based on adverse effects and other considerations. For example, the patient may wish to try coming off the medication if their level of life stress has decreased.[40] If there is agreement to reduce and stop the antidepressant, do so slowly, and monitor carefully for symptom recurrence.

If a patient chooses pharmacotherapy as a first-line treatment, where possible clinicians should also offer a full range of non-pharmacological adjunctive therapies as part of their treatment.[49]

Primary options

duloxetine: 30 mg orally once daily initially, increase gradually according to response, maximum 120 mg/day

venlafaxine: 37.5 to 75 mg orally (extended-release) once daily initially, increase gradually according to response, maximum 225 mg/day

Consider – cognitive behavioural therapy (CBT)

Back

Consider –

cognitive behavioural therapy (CBT)

Additional treatment recommended for SOME patients in selected patient group

CBT may be especially helpful for generalised anxiety in later life, although whether CBT is superior to other commonly available treatments is unclear.[88][89][90][91]

Both short- and long-term psychodynamic psychotherapy have been shown to be effective if CBT is unavailable.[110][111][112][204] [ ]

Consider – applied relaxation

Back

Consider –

applied relaxation

Additional treatment recommended for SOME patients in selected patient group

Consider – mindfulness or meditation training

Back

Consider –

mindfulness or meditation training

Additional treatment recommended for SOME patients in selected patient group

Mindfulness or meditation training can be used as an adjunct to pharmacotherapy and if patients are unable or unwilling to do psychotherapy.[102][103][104][105][106][107]

Consider – attention/perception modification

Back

Consider –

attention/perception modification

Additional treatment recommended for SOME patients in selected patient group

Attention/perception modification is effective for treating GAD in university and college students.[105]

Consider – sleep hygiene education

Back

Consider –

sleep hygiene education

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene education can be useful in primary care given the high frequency of sleep disturbance associated with GAD.

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

Consider – self-help

Back

Consider –

self-help

Additional treatment recommended for SOME patients in selected patient group

Self-help treatments, such as books or manuals, have been shown to be more effective than waiting list or placebo.[120][121]

3rd line – buspirone or pregabalin

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3rd line –

buspirone or pregabalin

If there is no or minimal response to first- or second-line treatment options, primary care clinicians should typically consider seeking a specialist opinion from secondary care at this point, if this has not taken place already. The following treatments should typically be initiated only under specialist guidance.

Buspirone or pregabalin may be considered third-line options for GAD.[146][147][148]

Buspirone is considered effective in some patients.[146] It is also non-addictive, which is beneficial in patients with a history of drug or alcohol misuse. However, nausea is common and may limit its use. Recent benzodiazepine use is thought to reduce its efficacy.[131]

Pregabalin can be used alone or as an augmentation agent with other medications where there has been a partial response to the initial choice of treatment.[149] One systematic review found that, in patients with GAD, pregabalin was superior to placebo and comparable to benzodiazepines in clinical response, with a lower drop-out rate than with benzodiazepines.[150] However, caution is required as it may cause renal impairment, especially in patients with risk factors for renal impairment (e.g., older age, substance misuse, concomitant medications such as antihypertensives and some antibiotics), and because of the ongoing risk of confusion.[151] Pregabalin is eliminated principally by renal excretion. Dose adjustment is required in people with compromised renal function. Pregabalin has the potential to be addictive.[152] It should be avoided in patients taking opioids due to an increased risk of sedation, and somnolence and death in overdose. Pregabalin is designated a controlled drug in some countries in order to reduce the increasing number of deaths and dependency associated with its misuse.[153]

Note that, although in general treatment of GAD with comorbid depression is similar to that of GAD without comorbid depression, buspirone and pregabalin are not recommended for comorbid depressive symptoms.

Primary options

buspirone: 7.5 mg orally twice daily initially, increase gradually according to response, maximum 60 mg/day

pregabalin: 75 mg orally twice daily initially, increase gradually according to response, maximum 600 mg/day

Consider – cognitive behavioural therapy (CBT)

Back

Consider –

cognitive behavioural therapy (CBT)

Additional treatment recommended for SOME patients in selected patient group

CBT may be especially helpful for generalised anxiety in later life, although whether CBT is superior to other commonly available treatments is unclear.[88][89][90][91]

Both short- and long-term psychodynamic psychotherapy have been shown to be effective if CBT is unavailable.[110][111][112][204] [ ]

Consider – applied relaxation

Back

Consider –

applied relaxation

Additional treatment recommended for SOME patients in selected patient group

Consider – mindfulness or meditation training

Back

Consider –

mindfulness or meditation training

Additional treatment recommended for SOME patients in selected patient group

Mindfulness or meditation training can be used as an adjunct to pharmacotherapy and if patients are unable or unwilling to do psychotherapy.[102][103][104][105][106][107]

Consider – attention/perception modification

Back

Consider –

attention/perception modification

Additional treatment recommended for SOME patients in selected patient group

Attention/perception modification is effective for treating GAD in university and college students.[105]

Consider – sleep hygiene education

Back

Consider –

sleep hygiene education

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene education can be useful in primary care given the high frequency of sleep disturbance associated with GAD.

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

Consider – self-help

Back

Consider –

self-help

Additional treatment recommended for SOME patients in selected patient group

Self-help treatments, such as books or manuals, have been shown to be more effective than waiting list or placebo.[120][121]

4th line – tricyclic antidepressant (TCA) or quetiapine or benzodiazepine

Back

4th line –

tricyclic antidepressant (TCA) or quetiapine or benzodiazepine

The following treatments should typically be initiated only under specialist guidance. TCAs, quetiapine, or a benzodiazepine (for refractory patients only) are all last-line options for GAD.

Evidence for the effectiveness of TCAs in GAD is scarce, dated, and suggests that imipramine or clomipramine are the TCAs of choice.[129][154][155] Careful consideration of risk in overdose and cardiac adverse effects is required. In practice, safety concerns around TCAs largely limit their use, including the relatively high fatality risk in overdose.[22]

Quetiapine (an atypical antipsychotic) may be considered but carries the risk of metabolic and other significant adverse effects.[156] Quetiapine monotherapy has been found to be more effective than placebo in the treatment of GAD in two systematic reviews and one meta-analysis.[130][156][157] These data showed that quetiapine may be poorly tolerated by patients; patients treated with quetiapine had an increased risk of all-cause discontinuation, discontinuation due to adverse effects, weight gain, and metabolic syndrome. Quetiapine can affect the QTc interval and can increase the risk of metabolic syndrome. Do not offer antipsychotics such as quetiapine as initial treatment for GAD. Note that initial prescription of antipsychotics within primary care is not recommended according to UK guidance, although antipsychotics may be prescribed under shared care arrangements.[65]

While benzodiazepines may be effective in the short term, their continued use is associated with important harmful adverse effects (e.g., falling more often; memory impairment, particularly new learning; increasing the risk of accidents; and dependence with a troublesome withdrawal syndrome).[158][159][160] Some treatment guidelines, such as those from the National Institute of Health and Care Excellence (NICE) in the UK, recommend against the use of benzodiazepines for GAD in primary or secondary care, except as a short-term measure during crises.[65] However, some clinicians consider benzodiazepines to be a useful part of the treatment armamentarium for a sub-section of patients with refractory anxiety disorders in a limited number of additional scenarios.[161][162]

The effectiveness of long-term use of benzodiazepines for GAD is unclear, and the development of tolerance may occur.[49][163][164] The key issue for clinicians and patients is risk versus benefit. Benzodiazepines are more effective in a population with higher baseline severity.[165] They may also have a more favourable adverse effect profile in the management of treatment-refractory anxiety disorders, compared with atypical antipsychotics.[49] They do not generally affect the QTc interval, but they can cause respiratory depression and death in overdose, and/or when used in combination with alcohol or opioids.[166][167] Avoid benzodiazepines if the patient has a history, or is at risk, of substance misuse.[49] Their mortality in overdose is high when used concurrently with opioids.[168]

Benzodiazepines have a rapid onset of action and are generally well tolerated. Physiological dependence can occur in as little as 2-4 weeks. Abrupt discontinuation or rapid tapering schedules can increase risk for withdrawal symptoms (e.g., dizziness, irritability, nausea, sweating, tremors, rebound anxiety, and seizures).

Benzodiazepines should typically only be used on a short-term basis (e.g., 2-4 weeks).[49] Occasionally they are used on a long-term basis to treat refractory anxiety. Long-term treatment with benzodiazepines should be rare, supervised, made with caution, and based on careful consideration of the anticipated risks and benefits of benzodiazepines for the individual patient; specialist input (e.g., from a psychiatrist or addiction specialist) is advisable. Patients using benzodiazepines long term should be regularly offered the opportunity to gradually withdraw from long-term use; treatment at the lowest effective dose is recommended.[169] Longer-acting agents (e.g., diazepam, clonazepam) may be preferable to minimise inter-dose rebound anxiety.

Primary options

imipramine: 25 mg orally three times daily initially, increase gradually according to response, maximum 300 mg/day (100 mg/day in older patients)

clomipramine: consult specialist for guidance on dose

quetiapine: 25 mg orally (immediate-release) once daily initially, increase gradually according to response, maximum 300 mg/day; 50 mg orally (extended-release) once daily initially, increase gradually according to response, maximum 300 mg/day

Secondary options

diazepam: 2-10 mg orally twice to four times daily

clonazepam: 0.25 to 0.5 mg orally twice to three times daily

Consider – cognitive behavioural therapy (CBT)

Back

Consider –

cognitive behavioural therapy (CBT)

Additional treatment recommended for SOME patients in selected patient group

CBT may be especially helpful for generalised anxiety in later life, although whether CBT is superior to other commonly available treatments is unclear.[88][89][90][91]

Both short- and long-term psychodynamic psychotherapy have been shown to be effective if CBT is unavailable.[110][111][112][204] [ ]

Consider – applied relaxation

Back

Consider –

applied relaxation

Additional treatment recommended for SOME patients in selected patient group

Consider – mindfulness or meditation training

Back

Consider –

mindfulness or meditation training

Additional treatment recommended for SOME patients in selected patient group

Mindfulness or meditation training can be used as an adjunct to pharmacotherapy and if patients are unable or unwilling to do psychotherapy.[102][103][104][105][106][107]

Consider – attention/perception modification

Back

Consider –

attention/perception modification

Additional treatment recommended for SOME patients in selected patient group

Attention/perception modification is effective for treating GAD in university and college students.[105]

Consider – sleep hygiene education

Back

Consider –

sleep hygiene education

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene education can be useful in primary care given the high frequency of sleep disturbance associated with GAD.

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

Consider – self-help

Back

Consider –

self-help

Additional treatment recommended for SOME patients in selected patient group

Self-help treatments, such as books or manuals, have been shown to be more effective than waiting list or placebo.[120][121]

5th line – individualised therapy

Back

5th line –

individualised therapy

There is little to no evidence to indicate optimal treatment for symptoms refractory to the above treatments. Consider switching to an alternative drug, combining drug therapy with psychotherapy such as cognitive behavioural therapy (CBT), or combining two medications from different drug classes (if there are no contraindications). Obtain patient consent and agree outcome measures.[49]

Stop treatments that are not working, and ask the patient which symptoms concern them the most. Then agree a reasonable end point (using scales or other agreed outcomes) and treat with an alternative medication, or with combined drug and psychotherapy (e.g., CBT), for 12 weeks. If a particular kind of treatment is not effective, stop it and try another strategy until the most efficacious therapy for the individual patient is found.[49]

Consult a specialist before combining medications.

pregnant adults

1st line – cognitive behavioural therapy (CBT)

Back

1st line –

cognitive behavioural therapy (CBT)

The goal of treatment is symptom remission. Use of a validated screening tool to monitor treatment response is recommended.[191]

Non-pharmacological treatment, in particular CBT, is recommended first line, particularly for those with mild to moderate anxiety.[49][191][192]

If CBT is not available, consider other types of psychotherapy (e.g., psychodynamic counselling).[110][111][112][204] [ ]

Computer/smartphone-assisted and internet-based interventions may help facilitate access to CBT for people such as those who live in remote locations, or for those on waiting lists in areas where there are long waiting lists for face-to-face treatment. Studies have demonstrated the efficacy of internet-based CBT delivered by individually administered media interventions, although study quality is variable, and frequently low.[92][93] Also, note that these studies did not specifically look at anxiety in pregnancy. As a general guide, digital interventions may be more appropriate for those with mild or sub-threshold symptoms of anxiety, and for those who are especially motivated to improve their symptoms.[94][95] Guided interventions (with input from a therapist via email or face-to-face, or via a computer-driven interaction) are associated with larger effect sizes than non-guided interventions.[93][96][97][98][99][100][193] [ ] One meta-analysis found that online 'eHealth' interventions significantly reduced anxiety scores in women with perinatal anxiety who received the intervention, compared with controls.[193] There is also evidence for the efficacy of video-conferencing psychotherapy interventions in treating anxiety.[101]

Consider – applied relaxation

Back

Consider –

applied relaxation

Additional treatment recommended for SOME patients in selected patient group

Consider – mindfulness or meditation training

Back

Consider –

mindfulness or meditation training

Additional treatment recommended for SOME patients in selected patient group

Mindfulness or meditation training can be used as an adjunct to cognitive behavioural therapy, or as a stand-alone option for patients who are unwilling or unable to do psychotherapy.[102][103][104][105][106][107]

Consider – sleep hygiene education

Back

Consider –

sleep hygiene education

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene education can be useful in primary care given the high frequency of sleep disturbance associated with GAD.

Counsel patients to improve sleep hygiene by going to bed and waking up at the same time each day, abstaining from or minimising their use of alcohol, and avoiding caffeine after 3 p.m. Advise them to get out of bed if unable to fall asleep to avoid negative associations with being in bed.[113][114]

Consider – exercise

Back

Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

There is some evidence that exercise interventions can reduce anxiety symptoms, with high-intensity programmes showing greater effects than low-intensity programmes.[115][116][117][118] Yoga is associated with improved anxiety symptoms in the short term, according to one meta-analysis.[119] Exercise programmes may require modification in pregnancy to ensure safety and comfort, depending on the stage of pregnancy and any associated pregnancy-related symptoms.

Consider – self-help

Back

Consider –

self-help

Additional treatment recommended for SOME patients in selected patient group

Self-help treatments, such as books or manuals, have been shown to be more effective than wait-list or placebo.[120][121]

2nd line – pharmacotherapy (with careful selection of suitable drug)

Back

2nd line –

pharmacotherapy (with careful selection of suitable drug)

Pharmacotherapy should be considered for women with severe or disabling anxiety.[49][191] The decision whether to start pharmacological treatment during pregnancy must balance the potential for iatrogenic harm to the fetus (given that antidepressants all cross the placenta) with the potential harm for the mother and fetus from untreated psychiatric illness. In the US, such discussions are frequently carried out by the patient’s obstetrician; obstetricians in the US may seek further specialist treatment advice from Perinatal Psychiatry Access Programs where available.[191] In other locations (e.g., the UK) clinicians should consult a specialist with experience in perinatal mental health when selecting the most appropriate drug for patients.

Treatment is the same regardless of whether comorbid major depression is present or absent.

In general, selective serotonin-reuptake inhibitors (SSRIs) are considered first-line medications for the treatment of both perinatal anxiety and depression.[191] The American College of Obstetricians and Gynecologists (ACOG) note that treatment decisions should be guided by any previous response to treatment but that, for those who have not taken a medication in the past and for those for whom other medications were not effective, sertraline is often preferred in the perinatal period due to its extensive and reassuring safety evaluation in the medical literature. Escitalopram is a reasonable alternative based on efficacy and acceptability data in the general population.[191]

If a woman becomes pregnant while on drug therapy, discuss the options of stopping the medication gradually and switching to a psychological intervention, continuing with medication, and combining medication with a psychological intervention.[53] Depending on the speciality and experience of the decision-maker, clinicians should consider consulting a psychiatrist about the risks and benefits of continuing drug therapy.

Data suggest that continuing SSRIs during pregnancy may prevent risks associated with untreated anxiety symptoms and comorbid depression.[202] Involve the woman in the consultation process, following a careful discussion of the risks versus benefits of pharmacological treatment, and take her preferences into consideration. This is a fast-changing area; updated information about potential harms from antidepressants and other pharmacological therapy is available. UK Teratology Information Service Opens in new window

Newborns should be monitored for the effect of psychotropic medications taken in pregnancy, and breastfeeding should be encouraged.[53] Consult a specialist with experience in perinatal mental health when selecting the most appropriate drug for patients who wish to breastfeed. The Drugs and Lactation Database (LactMed) contains information on the level of medications in breast milk and infant blood and the possible adverse effects in a breastfeeding infant. LactMed Opens in new window

Consider – cognitive behavioural therapy (CBT)

Back

Consider –

cognitive behavioural therapy (CBT)

Additional treatment recommended for SOME patients in selected patient group

CBT may be used in conjunction with pharmacotherapy under specialist guidance.

If CBT is not available, consider other types of psychotherapy (e.g., psychodynamic counselling).[110][111][112][204] [ ]

CBT has demonstrated efficacy in treating GAD.[85]

Computer/smartphone-assisted and internet-based interventions may help facilitate access to CBT for people such as those who live in remote locations, or for those on waiting lists in areas where there are long waiting lists for face-to-face treatment. Studies have demonstrated the efficacy of internet-based CBT delivered by individually administered media interventions, although study quality is variable, and frequently low.[92][93] Also, note that these studies did not specifically look at pregnant women. As a general guide, digital interventions may be more appropriate for those with mild or sub-threshold symptoms of anxiety, and for those who are especially motivated to improve their symptoms.[94][95] Guided interventions (with input from a therapist via email or face-to-face, or via a computer-driven interaction) are associated with larger effect sizes than non-guided interventions.[93][96][97][98][99][100][193] [ ] One meta-analysis found that online 'eHealth' interventions significantly reduced anxiety scores in women with perinatal anxiety who received the intervention, compared with controls.[193] There is also evidence for the efficacy of video-conferencing psychotherapy in treating anxiety.[101]

Consider – applied relaxation

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Consider –

applied relaxation

Additional treatment recommended for SOME patients in selected patient group

Applied relaxation is an effective adjunctive therapy that uses relaxation techniques that does not need in-depth psychotherapy.[80][108][109] UK guidelines recommend that applied relaxation may be used to treat GAD as a stand-alone intervention.[65] It may also be considered as an adjunct. Treatment should be manualised and delivered by a trained practitioner.[65]

Consider – mindfulness or meditation training

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Consider –

mindfulness or meditation training

Additional treatment recommended for SOME patients in selected patient group

Mindfulness or meditation training can be used as an adjunct to pharmacotherapy, or as a stand-alone option for patients who are unable and/or unwilling to do psychotherapy.[102][103][104][105][106][107]

Consider – sleep hygiene education

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Consider –

sleep hygiene education

Additional treatment recommended for SOME patients in selected patient group

Sleep hygiene education can be useful in primary care given the high frequency of sleep disturbance associated with GAD.

Counsel patients to improve sleep hygiene by going to bed and waking up at the same time each day, abstaining from or minimising their use of alcohol, and avoiding caffeine after 3 p.m. Advise them to get out of bed if unable to fall asleep to avoid negative associations with being in bed.[113][114]

Consider – exercise

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Consider –

exercise

Additional treatment recommended for SOME patients in selected patient group

Consider – self-help

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Consider –

self-help

Additional treatment recommended for SOME patients in selected patient group

Self-help treatments, such as books or manuals, have been shown to be more effective than wait-list or placebo.[120][121]

children

1st line – cognitive behavioural therapy (CBT) and non-drug therapy

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1st line –

cognitive behavioural therapy (CBT) and non-drug therapy

For children with mild symptoms, treatment options include psychoeducation, anxiety management training, and CBT. [ ]

For children with moderate or persistent GAD, CBT is recommended before medication.[58][174][175][176]

CBT is an effective treatment for anxiety in children.[175][176][177][178] CBT focused on the primary anxiety disorder also improves comorbid mood and/or behavioural disorders in children and adolescents.[179]

There is good evidence for the effectiveness of e-therapy (i.e., computerised CBT) in children (such as SPARX).[180] SPARX Opens in new window In the UK, the National Institute for Health and Care Excellence (NICE) recommends a number of named guided self-help digital CBT technologies that may be considered as an initial treatment option for children (aged 5-18) with mild to moderate symptoms of anxiety or low mood.[181] CBT can be offered directly to children, or to the parents or carers of younger children. For children aged 5-7, there is evidence to suggest that parent-only CBT may be an effective alternative to CBT involving both parent and child.[182] Equality and diversity should be considered in the provision of CBT; for example, it can be modified for children and young people with autistic spectrum disorder.[183] Of note, many clinical trials involving children and adolescents consider multiple anxiety disorders or symptoms, with or without depression, rather than specifically investigating the population of children with GAD.

Consider – other non-drug therapies

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Consider –

other non-drug therapies

Additional treatment recommended for SOME patients in selected patient group

Applied relaxation techniques, sleep hygiene education, meditation training, exercise, and self-help are all options that can be used in addition to cognitive behavioural therapy.

Some techniques may be more appropriate than others for specific ages. Consult a specialist therapist for advice.

2nd line – pharmacotherapy

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2nd line –

pharmacotherapy

Psychotropic medication can be considered for children with moderate to severe GAD whose symptoms do not improve (or only partially improve) with cognitive behavioural therapy.[58][174] Any psychotropic medication should be initiated and prescribed under the supervision of a specialist mental health service for children and young people.

Selective serotonin-reuptake inhibitors (SSRIs) and, to a lesser extent, serotonin-noradrenaline reuptake inhibitors (SNRIs) are the pharmacological treatment of choice in children, given their favourable risk-benefit ratio compared with other antidepressants.[58][185] Both SSRIs and SNRIs are effective for reducing childhood anxiety symptoms, compared with placebo.[177][186]

There is some meta-analysis evidence to suggest that SSRIs are associated with a greater and more rapid symptomatic improvement than SNRIs.[187] One systematic review from 2016 found limited randomised controlled trial (RCT) evidence for SSRIs in childhood GAD, but SSRIs were associated with adverse events; the review found no RCT evidence on the effects of antipsychotics, benzodiazepines, buspirone, hydroxyzine, or pregabalin for children and adolescents with GAD.[189]

SSRIs are associated with a small increased risk of suicidality in young people under the age of 24. The number needed to harm (NNH) has been estimated at 143, compared with a number needed to treat (NNT) of 3.[188] Close observation for suicidality is recommended, especially in the early months of treatment, and following dose adjustments.[58]

Clinically significant improvement with SSRIs may not be apparent until 6-8 weeks into treatment, with maximal benefit occurring at around 12 weeks.[187] SSRIs should be continued for at least 6 months if they are found to be effective, or for at least 1 year if used to treat a relapse of GAD.[190]

Consider – non-drug therapies

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Consider –

non-drug therapies

Additional treatment recommended for SOME patients in selected patient group

Cognitive behavioural therapy, applied relaxation techniques, sleep hygiene education, meditation training, exercise, and self-help are all options that can be used in addition to pharmacotherapy.

Some techniques may be more appropriate than others for specific ages. Consult a specialist therapist for advice.

anxiety symptoms not meeting DSM-5-TR criteria

1st line – individualised therapy

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1st line –

individualised therapy

Patients who have distressing or troubling generalised worry symptoms, but who do not fully meet the diagnostic threshold set by the Diagnostic and Statistical Manual of mental disorders, 5th edition, text revision (DSM-5-TR) criteria for GAD, may benefit from the same treatments as used for GAD.

Consult a psychiatrist for patients with mixed psychiatric symptoms (e.g., depression, substance misuse).

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Generalised anxiety disorder

Treatment algorithm

anxiety symptoms meeting DSM-5-TR criteria

cognitive behavioural therapy (CBT)

applied relaxation

mindfulness or meditation training

attention/perception modification

sleep hygiene education

exercise

self-help

selective serotonin-reuptake inhibitor (SSRI) or mirtazapine

Primary options

Secondary options

cognitive behavioural therapy (CBT)

applied relaxation

mindfulness or meditation training

attention/perception modification

sleep hygiene education

exercise

self-help

serotonin-noradrenaline reuptake inhibitor (SNRI)

Primary options

cognitive behavioural therapy (CBT)

applied relaxation

mindfulness or meditation training

attention/perception modification

sleep hygiene education

exercise

self-help

buspirone or pregabalin

Primary options

cognitive behavioural therapy (CBT)

applied relaxation

mindfulness or meditation training

attention/perception modification

sleep hygiene education

exercise

self-help

tricyclic antidepressant (TCA) or quetiapine or benzodiazepine

Primary options

Secondary options

cognitive behavioural therapy (CBT)

applied relaxation

mindfulness or meditation training

attention/perception modification

sleep hygiene education

exercise

self-help

individualised therapy

cognitive behavioural therapy (CBT)

applied relaxation

mindfulness or meditation training

sleep hygiene education

exercise

self-help

pharmacotherapy (with careful selection of suitable drug)

cognitive behavioural therapy (CBT)

applied relaxation

mindfulness or meditation training

sleep hygiene education

exercise

self-help

cognitive behavioural therapy (CBT) and non-drug therapy

other non-drug therapies

pharmacotherapy

non-drug therapies

anxiety symptoms not meeting DSM-5-TR criteria

individualised therapy