Generalised anxiety disorder

• Generalised anxiety disorder (GAD) is chronic, excessive, hard-to-control worry about everyday matters, present on most days for at least six months, with restlessness, fatigue, poor concentration, irritability, muscle tension or disturbed sleep, causing real distress or impairment. ^[1][3]
• It is common in primary care; AAFP reports women are affected two to three times (2022) or almost twice (2009) as often as men, Cureus reports about twice, and it frequently travels with depression and other anxiety disorders. ^[1][2][6]
• No special investigation diagnoses it. The diagnosis is clinical, supported by the GAD-7 screen and a targeted search for medical mimics such as thyroid disease, drugs and substances. ^[1][6]
• First-line treatment is cognitive behavioural therapy or an antidepressant (an SSRI or SNRI), chosen with the patient; benzodiazepines are only a short-term bridge in a crisis. ^[1][3]
• If effective, medication is usually continued for at least a year; combining steady psychological and pharmacological care after a partial response is common. ^[1][3]

By the end of this page you should be able to:

1. State the criteria for GAD, including the difference between the six-month adult threshold and the one-symptom rule in children. ^[1][2]
2. Use the GAD-7 (and GAD-2) with their cut-off scores, and know what a positive screen does and does not establish. ^[1][6]
3. List the common medical, substance and pharmacological mimics of GAD and the tests that exclude them. ^[1]
4. Explain how the cognitive and biological models fit the clinical picture. ^[1]
5. Outline the stepped-care pathway, including low-intensity and high-intensity psychological treatments and where drug treatment fits. ^[3]
6. Prescribe first-line and second-line pharmacotherapy with typical adult doses, and list the specific cautions for SSRIs, SNRIs, buspirone, pregabalin and benzodiazepines. ^[2][3][5]
7. Discuss the management of GAD in pregnancy, in children and adolescents, and in older adults. ^[4][5]
8. Describe prognosis, relapse, and when to refer. ^[1][3]

The key idea is that the worry is generalised: it is not confined to one topic such as panic attacks, social embarrassment, contamination, a traumatic reminder or having a serious illness. ^[3] Normal anxiety is short-lived and useful; in GAD it becomes chronic, pervasive and intrusive, occupying hours of the day and often presenting to the clinician through somatic complaints and repeated reassurance-seeking rather than through the word "anxiety". ^[1]

In the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, 5th edition, GAD sits among the anxiety disorders, with criteria reproduced in Table 1 below. ^[1] NICE treats it as a single condition for adults aged 18 and over; the same guidance does not cover children and young people. ^[3]

A vignette captures the typical presentation: a 42-year-old woman reports that for a year she has worried "about everything - the children, work, money, my heart" most days, cannot let the worry go, sleeps badly, feels tired and tense, and has seen her GP four times with palpitations and indigestion that no test has explained. She scores 15 on the GAD-7. ^[1]

GAD is the commonest anxiety disorder in primary care and the anxiety disorder most often missed. Lifetime prevalence in the United States is about 8%, 12-month prevalence in the community is 3.1%, and among people who attend primary care it is 5.3% to 7.6%. ^[1][2] A global primary-care estimate puts the point prevalence at about 8%, with higher rates in women. ^[6]

• Age. Onset is usually in late adolescence or early adulthood, although GAD can present later in life. ^[1] The highest rate in one community series was 7.7% in people aged 45 to 49 years, and the lowest was 3.6% in people aged 60 years or older. ^[2] GAD can nevertheless present for the first time in older age, often with somatic complaints. ^[2]
• Sex. Women are affected roughly two to three times as often as men, although the gap narrows later in life. ^[1][2]
• Comorbidity. GAD commonly occurs with depression, other anxiety disorders, substance use disorder, and suicidal ideation or attempts. ^[1] Anxiety and depressive disorders overlap substantially: in one cohort, 67% of people with a depressive disorder also had a current anxiety disorder, and 75% had a lifetime comorbid anxiety disorder. ^[4]
• Shared causes. The heritability of GAD in twin samples is about 32%. ^[1] Psychological vulnerability (perceiving higher risk in objectively lower-risk situations), environmental adversity, chronic medical illness and a history of mental health problems all raise risk. ^[1][3] There is no single necessary trigger and no modifiable risk factor that guarantees prevention.

GAD is best understood as the product of an interaction between biological vulnerability and psychological and environmental loading. ^[5] Anxiety disorders are associated with dysfunction of serotonin, noradrenaline and other neurotransmitter systems, and the brain circuits that react to threat appear over-responsive while being under-inhibited. ^[1][5] Increasing serotonin neurotransmission is one way these circuits can be quietened, which is part of why serotonergic antidepressants work. ^[1] A childhood history of adversity, chronic stress, a family history of anxiety or depression, and a temperament high in negative affectivity all raise susceptibility. ^[1][5] The mechanisms are probabilistic rather than deterministic: a strong family history increases risk but does not make GAD inevitable, and many patients have no identifiable predisposing factor at all.

Self-medication with alcohol or other drugs is common and worsens the illness; treating any coexisting substance use problem is part of treating the anxiety. ^[1][3]

Worry in GAD behaves like a mental habit that has escaped voluntary control. The person's attention is captured by future threats (health, family, finances, work) and their meaning is appraised as more dangerous and less manageable than the evidence warrants; the worry itself is experienced as a way of preparing for or preventing bad outcomes, so it is hard to stop even though it brings little relief. ^[1] This cognitive load produces muscle tension, restlessness and fatigue; poor sleep then amplifies next-day anxiety.

The biological correlate is a persistently activated threat system: autonomic arousal (tachycardia, sweating, dry mouth, gastrointestinal upset), heightened startle and vigilance, and HPA-axis and muscle activation that outlast the triggering situation. ^[1][5] Serotonin and noradrenaline modulation, and the GABA-benzodiazepine receptor system, are the neurotransmitter targets that the effective drugs act on. ^[2][5] This explains why antidepressants reduce both psychic worry and somatic arousal, but only after a delay of one to four (sometimes six to eight) weeks: receptor adaptation is required. ^[2][5]

Patients rarely say "I am anxious"; they say things like:

• "I worry all the time and I cannot switch it off." ^[3]
• "It is not about one thing - it is everything." ^[3]
• "I keep checking, re-reading, asking the doctor again." ^[1]
• "I am exhausted; my shoulders are always tight; I cannot sleep." ^[1]
• "My heart races and my stomach churns, so I thought it was my heart." ^[1]

Functional consequences are common: restless nights, impaired concentration and memory, avoidance, repeated primary-care visits, and a raised burden for the patient's family. ^[1] Duration, number and severity of symptoms, distress and functional impairment must all be assessed together rather than counting symptoms alone. ^[3]

GAD is associated with suicidal ideation and suicide attempts, especially where depression or substance use coexists. ^[1] Assessment should always include mood, hopelessness, self-harm, substance use (including caffeine, alcohol, cannabis, stimulants), domestic and social supports, and any suicidal plans. ^[1][3]

There may be no abnormal physical findings. Look for motor tension, restlessness, fidgeting, a tremor of the outstretched hands, tachycardia, dry mouth and shallow breathing, but remember that many patients look well. ^[1][2] A careful general medical examination is required not to "prove" GAD but to find the physical conditions that can mimic or worsen it. ^[1] A formal mental state examination documents anxious mood and affect, preserved cognition, no perceptual disorder, and no psychotic symptoms; the absence of thought disorder or hallucinations is the more important negative finding in a first assessment.

Symptoms of GAD can equally well come from physical disease, medication or substance use or withdrawal. ^[1] Every patient therefore needs a systematic search for these before the anxiety disorder is attributed.

GAD overlaps with many conditions. The table separates them by the feature that most reliably distinguishes them. ^[1][2]

There is no test that diagnoses GAD, and brain imaging is not part of the work-up. ^[1]

• First-line. Targeted tests guided by the history and examination: thyroid function, full blood count, glucose or HbA1c, ECG when there are palpitations or chest symptoms, and spirometry when respiratory symptoms are present. ^[1]
• Psychiatric assessment. A structured or semi-structured clinical interview against the DSM-5 criteria (Table 1), plus the GAD-7 or GAD-2, covers most of what is needed. ^[1][6]
• What the tests measure. Targeted tests remove important mimics: an abnormal thyroid function test or ECG redirects the diagnosis, while a normal result does not confirm GAD. ^[1]
• Confirmatory diagnosis. The diagnosis rests on criteria plus clinical judgement; screening questionnaires only identify people who need a fuller assessment. ^[4][6]

Two teaching points make the criteria easier to remember. First, the worry must be about a number of things, not one. Second, the symptoms must be present more days than not; episodic worry for a specific trigger points elsewhere. ^[3]

The GAD-7 is a seven-item self-report scale over the past two weeks: feeling nervous, anxious or on edge; not being able to stop or control worrying; worrying too much about different things; trouble relaxing; being so restless it is hard to sit still; becoming easily annoyed or irritable; feeling afraid as if something awful might happen. Each item is scored 0 (not at all) to 3 (nearly every day), giving a total of 0 to 21. ^[6]

The GAD-2 uses only the first two items and is scored 0 to 6, with a preferred cut-off of 3 or more (original validation: sensitivity 86%, specificity 83%; USPSTF pooled estimates range from 69-86% sensitivity and 83-91% specificity for GAD). ^[6][4] The GAD-7 also performs moderately well for other anxiety disorders - panic disorder (sensitivity 74%, specificity 81%), social anxiety disorder (72%, 80%) and PTSD (66%, 81%) - so a positive screen should be followed by a diagnostic assessment rather than assumed to be GAD. ^[6] A high score is not a diagnosis; specificity is 82% at a cut-off of 10. ^[2]

NICE proposes step-wise case finding in adults: be alert in people with a past anxiety disorder, somatic symptoms or a recent traumatic event, and ask about feelings of anxiety and the ability to stop or control worry using the GAD-2. ^[3]

Two principles underlie the management: GAD is common, treatable and chronic-relapsing, and the least intrusive effective intervention should be offered first. ^[3] Patients need to hear early that anxiety is a medical condition, that symptoms usually ease with treatment, and that the treatment target is full remission rather than mere coping. ^[3][5]

Education and active monitoring may be enough for mild or subclinical presentations. ^[3] Otherwise CBT is the psychological treatment with the strongest evidence, delivered by trained practitioners in 12 to 15 weekly one-hour sessions, with applied relaxation an equally valid high-intensity option. ^[2][3] CBT for GAD targets the worry process itself: self-monitoring of worry episodes and their triggers, cognitive restructuring of predictions and interpretations, relaxation training, and rehearsal of coping skills in real situations. ^[2] It is at least as effective as medication for GAD, with less dropout and more durable effects. ^[2] Combination with a drug can help where there has been a partial response. ^{[3] [1]}

Low-intensity options are worth offering where high-intensity therapy is not available or not wanted: guided self-help on CBT principles over 5 to 7 sessions of 20 to 30 minutes, or psychoeducational groups of six weekly 2-hour sessions with about 12 participants. ^[3]

Non-specific factors matter too: exercise reduces symptoms of anxiety, sleep hygiene and activity scheduling help, and concurrent alcohol, nicotine or stimulant use should be addressed. ^[1][3]

NICE recommends an SSRI first line; WFSBP and AAFP agree that SSRIs and SNRIs are first-line for GAD. ^[3][5][1] Sertraline is recommended first in the UK because it is the most cost-effective drug, although at publication it lacked a UK marketing authorisation for GAD, so informed consent should be obtained and documented. ^[3] Drug classes should be chosen with the patient, taking into account prior response, side effects, drug interactions, suicide risk and toxicity in overdose (especially venlafaxine), withdrawal tendency (especially paroxetine and venlafaxine), comorbid depression and local availability. ^[3]

Key pharmacological points from the guidelines:

• Expect a delay: the anxiolytic effect builds over 1 week or more, and full benefit may take 4 weeks; warn patients about initial activation (anxiety, agitation, insomnia) and sedation. ^[2][3]
• Start low and go slowly in patients with panic features, who are sensitive to serotonergic stimulation. ^[5]
• SSRIs and SNRIs commonly cause nausea, sexual dysfunction, agitation, weight gain and insomnia; these are often mistaken for worsening anxiety. A concurrent short course of a benzodiazepine can bridge the first few weeks where appropriate. ^[2]
• In patients under 30 prescribed an SSRI or SNRI, warn about the small risk of suicidal thinking and self-harm, review within 1 week of the first prescription and monitor weekly for the first month. ^[3]
• SSRIs increase bleeding risk, especially with NSAIDs or aspirin and in older adults; consider a gastroprotective drug in these circumstances. ^[3]
• Venlafaxine and duloxetine help where depression coexists; monitor blood pressure on venlafaxine, and recall the higher overdose toxicity of venlafaxine. ^[3][5]
• High doses of citalopram and escitalopram have been associated with QTc prolongation. ^[5]
• Pregabalin has a rapid onset and good evidence in GAD, but since April 2019 it is a controlled drug (UK schedule 3) and should be avoided or carefully monitored in patients with a history of substance misuse; it may cause weight gain, sedation and dependence. ^[3][5]
• Buspirone is non-sedating and non-addictive and acts as a partial agonist at the 5-HT1A receptor, but its evidence base in GAD is weaker, it takes 1 to 3 weeks to work, it does not treat comorbid depression and it needs dosing two to three times daily. ^[2][5]
• Hydroxyzine is an antihistamine option with evidence in GAD; it is sedating, so it suits patients when sedation is acceptable. ^[2][5]
• Tricyclics such as imipramine have proven efficacy but are not first line because of anticholinergic, sedative and cardiac effects and lethality in overdose; they should be avoided in patients at risk of suicide. ^[2][5]
• Second-generation antipsychotics such as quetiapine have shown anxiolytic effects but are not licensed for GAD in most countries and should be reserved for specialist care. ^[5]
• Review effectiveness and side effects every 2 to 4 weeks during the first 3 months and every 3 months thereafter. ^[3]
• If a drug works, advise continuing it for at least a year, because relapse is likely; NICE advises at least a year while other guidance speaks of 6-12 months or 6-24 months after remission depending on the population. ^[3][1][5]
• If there is no response after an adequate dose for 4 to 6 weeks, change the drug or refer. ^[5]
• Do not offer an antipsychotic for GAD in primary care. ^[3]

NICE advises that a benzodiazepine should not be offered for GAD in primary or secondary care except as a short-term measure during crises, with prescribing following the BNF. ^[3] WFSBP allows benzodiazepines for long-term use only after SSRIs, SNRIs, pregabalin and CBT have failed, and AAFP and the Cochrane data put them behind antidepressants because of tolerance, withdrawal and mortality. ^[1][5]

Cautions to teach and to document:

• They work within minutes and relieve severe anxiety and agitation, and can be co-prescribed briefly with an SSRI to counter initial activation. ^[2][5]
• They are associated with sedation, cognitive slowing, impaired driving, falls, anterograde amnesia and respiratory depression, and the risks are greater in older adults. ^[2][5]
• Low-dose dependence can develop after weeks to months of regular use. ^[5]
• People with a history of alcohol, benzodiazepine or other substance misuse should generally be excluded or treated in specialist settings. ^[5]
• Long-acting agents (diazepam, chlordiazepoxide, clorazepate) accumulate in older adults or hepatic impairment; short-to-intermediate agents (oxazepam, lorazepam, temazepam, alprazolam) are preferred in those groups. ^[2]
• Benzodiazepines are not effective where depression is comorbid, and they should be avoided when there is major depression or substance use disorder. ^[2]
• Discontinue gradually over several weeks in anyone who has received more than four weeks of treatment, to avoid rebound anxiety, agitation, insomnia and other withdrawal symptoms. ^[2]
• Avoid or use extreme caution in pregnancy, especially alprazolam; in breastfeeding, observe the infant for sedation, and discontinue high-dose long-term use. ^[5]

• If GAD has not responded to a full course of high-intensity psychological treatment, offer a drug. ^[3]
• If it has not responded to a drug, offer either high-intensity psychological treatment or an alternative drug. ^[3]
• A partial drug response can be followed by adding CBT. ^[3]
• Complex and treatment-refractory GAD, very marked impairment, self-neglect, persistent suicidal thoughts or multiple comorbidities should be referred to specialist care, where combinations of drugs and augmentation strategies can be supervised. ^[3][5]
• Benzodiazepines are reserved for short-term crisis use or for long-term use only after CBT and other drug options have failed and there are no contraindications. ^[5]

• Relapse is common: about 16% of patients relapse despite staying on antidepressants, and stopping before a year produces relapse in up to 50% of those treated with an SSRI or SNRI. ^[1]
• Chronicity, with fluctuating course and reduced work, role and social functioning. ^[1][2]
• Comorbid major depression, other anxiety disorders and substance use disorder. ^[1]
• Suicidal ideation and suicide attempts, which need routine enquiry. ^[1]
• Repeated (and often unrewarding) medical consultations and unnecessary investigations if medical mimics are not excluded early. ^[1][2]
• Functional impairment equal to that of major depression in several studies. ^[2]

GAD is treatable: most patients improve substantially with CBT, with an antidepressant, or with both. ^[1][5] Complete remission is associated with better functioning and a lower likelihood of relapse, and is the goal stated by NICE. ^[3] The course is, however, often chronic and relapsing, with exacerbations during stress, illness or life transitions; many patients need long-term or intermittent treatment. ^[1][5] The combination of psychological and drug treatment has the best outcomes in most comparisons. ^[5]

There is no consistent evidence for a single prevention strategy for GAD. Education that teaches coping techniques and cognitive restructuring has shown some success in small programs, and regular physical activity reduces anxiety symptoms. ^[1] Addressing alcohol, tobacco and stimulant use removes an important maintaining factor. ^[1]

Screening is now guideline-supported in some settings:

• USPSTF (2023) recommends screening for anxiety disorders in adults aged 64 years or younger, including pregnant and postpartum people (grade B), and states that evidence is insufficient to support routine screening in adults aged 65 years or older (grade I). ^[4]
• The GAD-2 or GAD-7 are the tools with the best replicated accuracy for detecting GAD. ^[4][6]
• NICE recommends that clinicians be alert for anxiety disorders and use the GAD-2 opportunistically in people with a past history, somatic symptoms or recent trauma, rather than screening everyone. ^[3]
• Screening tools alone do not diagnose GAD: a positive screen requires a clinical assessment and a search for other conditions. ^[4][6]
• Where a local health system decides to screen, put in place diagnostic confirmation, evidence-based treatment and follow-up, because screening without access to care does not help. ^[4]

GAD can begin or worsen during pregnancy and the first postpartum year. USPSTF includes pregnant and postpartum people in its screening recommendation. ^[4] Management means weighing the risk of untreated maternal illness (including depression, self-medication and impaired functioning) against the risks of treatment, and considering the unique balance of benefits and harms in the perinatal period. ^[4][5] CBT and other psychological therapies are often the first consideration. If medication is needed, the guidelines note that SSRIs and tricyclics have not shown increased malformation risk in most studies, but that paroxetine and alprazolam should be avoided in women who are pregnant or planning pregnancy. ^[5] Older (pre-2015) FDA pregnancy categories were B for buspirone and C or D for SSRIs, SNRIs and benzodiazepines; current practice follows updated labelling and individual risk-benefit discussion rather than category letters alone. ^[2] In breastfeeding, paroxetine and sertraline usually produce undetectable plasma levels in the infant, and stopping breastfeeding because of an SSRI or tricyclic is generally not warranted; benzodiazepines require caution and avoidance of high-dose long-term use, with observation of the infant for sedation, poor feeding and weight loss. ^[5]

NICE CG113 does not cover children and young people. ^[3] In young people the diagnostic threshold is lower: only one of the six associated symptoms is required alongside the core worry, and onset may be expressed as somatic complaints, irritability or school avoidance rather than as worry in words. ^[1][2] WFSBP recommends SSRIs as first-line pharmacotherapy in this group, with careful monitoring because of concerns about increased suicidal ideation and behaviour, and because comorbid depression and diagnostic uncertainty are common. ^[5] CBT has the best evidence for mild to moderate presentations; combination treatment may be more effective than either alone in more severe cases. ^[5] Involve parents and school where appropriate.

The prevalence of GAD is lower in older age (3.6% in people aged 60 years or older in one series) but the condition is under-recognised because it presents with somatic concerns and is assumed to be "normal ageing". ^[2] Older patients are more sensitive to anticholinergic effects, orthostatic hypotension and paradoxical reactions to benzodiazepines, and benzodiazepines and tricyclics are therefore less favourable, while SSRIs are generally safe but should be started at a lower dose. ^[2][5] The AAFP dose table advises that initial and target doses of antidepressants should be reduced by about half in adults aged 65 or older. ^[2] USPSTF does not presently recommend routine screening in this age group because of insufficient evidence, so case finding and thorough assessment matter more. ^[4] Benzodiazepines in older adults carry a notable risk of falls and fractures. ^[2]

• The diagnosis is clinical; no laboratory test is required to confirm it, and no imaging or specialist referral is needed to start treatment. ^[1]
• GAD-2 takes one minute and is free to use; the GAD-7 is freely available with a 0 to 21 score. ^[6]
• NICE's stepped-care model can be delivered largely by trained generalists: education and active monitoring first, then guided self-help using CBT workbooks. ^[3]
• The cheapest effective drugs in most formularies are generic SSRIs; if a guideline recommends an off-label first-line choice (such as sertraline for GAD in the UK), informed consent and local formulary review are essential. ^[3]
• CBT principles (worry scheduling, challenging predictions, relaxation, exposure to feared situations) can be taught in brief structured sessions even where full therapy is unavailable. ^[2]
• Avoid long-term benzodiazepines in settings without follow-up, and keep treatment courses to the shortest effective duration. ^[3][5]
• Refer only when risk, self-neglect, marked impairment or non-response indicates specialist care. ^[3][5]

• GAD is excessive, generalised, uncontrollable worry present on most days for at least six months, with 3 of 6 associated symptoms and distress or impairment. ^[1][2]
• It is common (lifetime prevalence around 8% in the United States), under-recognised, and more common in women. ^[1][2]
• Always look for medical, substance and medication mimics before attributing symptoms to an anxiety disorder. ^[1]
• Comorbid depression and other anxiety disorders are the rule rather than the exception, and suicide risk must be assessed. ^[1][4]
• The GAD-7 screens and measures severity: 0-4 minimal, 5-9 mild, 10-14 moderate, 15-21 severe; cut-offs of 10 (GAD-7) and 3 (GAD-2) are the usual screening thresholds. ^[6][2]
• First-line treatment is CBT (including low-intensity guided self-help) or an SSRI or SNRI, with patient choice; NICE makes sertraline the first drug in the UK. ^[1][3]
• Typical adult SSRI doses are escitalopram 10-20 mg, paroxetine 20-50 mg, sertraline 50-200 mg daily (WFSBP lists 50-150 mg); SNRIs are venlafaxine extended release 75-225 mg and duloxetine 60-120 mg daily (AAFP 2009: 30-120 mg); pregabalin 150-600 mg daily (AAFP 2009: 200-600 mg). ^[2][5]
• SSRIs improve symptoms only after 1-4 weeks; start low to reduce activation, and warn under-30s about suicidal thoughts, reviewing within 1 week. ^[2][3]
• Benzodiazepines are for short-term crisis use only, because of dependence, falls, cognitive impairment and withdrawal; decline where depression or substance misuse is present. ^[1][3][5]
• If treatment works, continue for at least a year; relapse reaches 50% if withdrawn in the first year. ^[1][3]
• In pregnancy, consider psychotherapy first, avoid paroxetine and alprazolam, and manage benzodiazepines with great care; in children start CBT first and monitor SSRIs closely; in older adults halve antidepressant doses and avoid benzodiazepines. ^[2][4][5]
• USPSTF recommends screening adults aged 64 years or younger in 2023, including pregnant and postpartum people; NICE favours opportunistic case finding. ^[3][4]

Panic disorder and phobias; major depressive disorder; obsessive-compulsive disorder; post-traumatic stress disorder; social anxiety disorder; benzodiazepine and other sedative use; insomnia and sleep disorders; substance use disorders; perinatal mental health; older adult psychiatry.