ICD-116B00	GENERALISED ANXIETY DISORDER (GAD) Generalised anxiety disorder
ICD-10F41.1	Generalized anxiety disorder
DSM-5-TRF41.1	Generalized Anxiety Disorder

1. Definition and nosology

Generalized anxiety disorder (ICD-11: 6B00; DSM-5-TR: F41.1) — a disorder characterized by excessive anxiety that persists for at least several months (≥ 6 months in DSM-5-TR), encompasses multiple life domains (work, family, health, daily topics), is uncontrollable, and lacks sufficient triggers. It is accompanied by significant somatic symptoms (tension, fatigue, sleep disturbance).

2. History

• 1920s–1960s — term ‘anxiety neurosis’, linked to Freud's influence.
• DSM-III (1980) — “anxiety neurosis” → separation of panic disorder and GAD; GAD was a residual category.
• DSM-IV (1994), DSM-5 (2013) — GAD as separate disorder; ≥ 6-month duration; characteristic somatic symptoms.
• ICD-11 (2019) — has formulated the duration requirement for diagnosis as “several months” (less strict than DSM-5).

3. Epidemiology

• Lifetime prevalence: 3–9% (Kessler R.C. et al. WMH surveys).
• Annual prevalence: ~2–3%.
• Sex: 2 times higher in females.
• Onset — bimodal — adolescence and middle age; often chronic course.
• Comorbidity: MDD ~60%, social anxiety, panic, substance use, somatic (irritable bowel, cardiac complaints).

4. Aetiology and pathogenesis

• Heritability 30–40% (Hettema J.M. et al. Am J Psychiatry 2001 meta-analysis).
• Neurobiological — amygdala hyperresponsivity, impaired prefrontal-amygdala regulation; GABAergic and serotonergic dysregulation.
• Personality traits (neuroticism, behavioral inhibition) are high-risk factors.
• Environment — childhood trauma, chronic stress, parental overprotection.

5. Clinical features

5.1 Psychological symptoms

• Uncontrollable worry covering multiple areas.
• “Worry about worry” — meta-worry (Wells A. concept).
• Difficulty concentrating, mind going blank.
• Irritability.

5.2 Somatic symptoms

• Muscle tension.
• Fatigue.
• Sleep disturbance (difficulty falling asleep, difficulty staying asleep).
• Autonomic symptoms (tachycardia, sweating, dry mouth, headache).
• IBS is a common comorbidity, presenting with gastrointestinal complaints.

6. Diagnosis

6.1 Unified diagnostic criteria

A. Excessive anxiety or tension, focused on multiple areas; present most of the time during daily activities; ≥ 6 months (DSM-5-TR) / several months (ICD-11).

B. Difficulty managing anxiety.

C. ≥ 3 symptoms from the following (1 in children):

1. Restlessness, feeling keyed up or on edge;
2. Easy fatigability;
3. Difficulty concentrating;
4. Irritability;
5. Muscle tension;
6. Sleep disturbance.

D. Significant distress or functional impairment.

E. Exclusion of substance or medical condition.

F. Not better explained by another psychiatric disorder.

6.2 Differences between sources

• DSM-5-TR: ≥6 month period; ≥3 somatic symptoms.
• ICD-11: duration “a few months” — less stringent; somatic symptoms are required, but a specific number is not indicated.
• NICE CG113 (Generalised anxiety disorder and panic disorder in adults: management, 2011, 2020 update): Stepped care — psychoeducation + observation → guided self-help → CBT or pharmacotherapy → combination → specialized service in severe case.

6.3 Diagnostic algorithm

1. Clinical interview (areas of concern, triggers, somatic symptoms, avoidance).
2. SCID-5, MINI.
3. GAD-7 (screening, initial indicators and monitoring) — ≥ 10 moderate-to-severe anxiety.
4. HAM-A (Hamilton Anxiety) — clinician-rated.
5. Comorbidity screening (PHQ-9 depression, panic, social anxiety).
6. Exclude somatic causes — TSH, anemia, cardiac, caffeine or stimulant use.

6.4 Differential diagnosis

7. Examination and assessment

• GAD-7, HAM-A, PSWQ (Penn State Worry Questionnaire).
• Medical and laboratory (TSH, complete blood count, caffeine and alcohol use assessment).
• EKG (if cardiac complaint present).

8. Treatment

8.1 Stepped approach (NICE CG113 · CANMAT 2014)

1. Step 1 — psychoeducation and active monitoring.
2. Step 2 — guided self-help (internet-based CBT), psychoeducation groups.
3. Step 3 — high-intensity CBT or pharmacotherapy.
4. Step 4 — specialist service: combination treatment, refractory cases.

8.2 First line

Psychotherapy — cognitive behavioural therapy (CBT). The method with the strongest evidence base; 12–20 sessions. Components:

• Cognitive restructuring — testing beliefs about anxiety: judgements such as “worrying keeps me prepared” are set against the facts.
• Work with intolerance of uncertainty (Dugas M.J. model) — the patient deliberately experiences situations with unknown outcomes and builds tolerance.
• Exposure — stepwise withdrawal of avoidance of anxiety-provoking situations; carrying out postponed decisions.
• Problem-solving training — breaking a real problem into workable steps and accepting what cannot be solved.
• Relaxation — progressive muscle relaxation, diaphragmatic breathing.

Effect: reviews by Cuijpers P. et al. report a medium-to-large effect size; the result is comparable with pharmacotherapy and the relapse risk is lower.

Pharmacotherapy. Effect is assessed at 4–6 weeks; a full response may take 8–12 weeks:

• SSRIs — sertraline, escitalopram, paroxetine.
• SNRIs — venlafaxine, duloxetine.
• The starting dose is low: a temporary increase in anxiety is possible in the first days.

Slee A. et al. (Lancet 2019) network meta-analysis: duloxetine, pregabalin and venlafaxine showed high efficacy; the tolerability profile varies between agents.

8.3 Second line

• Pregabalin — approved for this indication in Europe; acts quickly but carries dependence potential.
• Buspirone — partial effect; as an alternative to benzodiazepines.
• Mirtazapine — adjunct where sleep disturbance accompanies.
• Quetiapine — second line in CANMAT 2014; use limited by metabolic adverse effects.

8.4 Short-term use and limits

• Benzodiazepines — only in the acute period, no longer than 2–4 weeks. Dependence potential is high; continuous use is not recommended.

8.5 Additional methods

• Mindfulness-based stress reduction and cognitive therapy (MBSR / MBCT) — an 8-week group programme; a mild effect in this disorder. Hofmann S.G. et al., J Consult Clin Psychol 2010 meta-analysis.
• Acceptance and commitment therapy (ACT) — instead of fighting the symptom it teaches living by one’s values alongside it; increases psychological flexibility. Randomised trials by Roemer L. et al.
• Applied relaxation (Öst L.G. method) — structured progressive muscle relaxation, applied when an anxiety trigger appears.
• Lifestyle — limiting caffeine, regular physical activity, sleep hygiene, avoidance of alcohol and psychoactive substances.

8.6 Duration of treatment

• Continued for at least 12 months after remission.
• In a chronic course or with multiple relapses, treatment is planned as long-term.
• Withdrawal is stepwise: abrupt discontinuation raises the risk of return.

8.7 Differences between sources

• NICE CG113 (2011, reaffirmed 2020) — stepped approach; SSRIs and SNRIs as first-line pharmacotherapy; benzodiazepines only acutely and briefly.
• APA — has no separate guideline for this disorder; the only document in the family concerns panic disorder (2009, archived status). Reference is therefore made to NICE CG113 and CANMAT 2014.
• CANMAT 2014 (Katzman M.A. et al.) — first line escitalopram, sertraline, venlafaxine, duloxetine; second line pregabalin, buspirone, mirtazapine, quetiapine.

9. Prognosis

• Chronic course; spontaneous remission is low.
• Significant symptom reduction and functional improvement with adequate treatment.
• Comorbid MDD is a marker of poor prognosis.
• Monitoring — GAD-7 monitoring, side effects, compliance, comorbidity.

10. Myths and misconceptions

Myth 1: “Anxiety is a normal life feeling, not a medical condition”

Evidence: A clinical distinction exists between normal anxiety and GAD — severity, duration (≥ 6 months), uncontrollability, somatic components, functional impairment. Clinical diagnosis is made based on specific criteria.

Myth 2: “Benzodiazepines are first-line treatment for GAD”

Evidence: NICE CG113, APA, CANMAT — benzodiazepines only for short-term (2–4 weeks) use; high dependence potential; SSRIs and SNRIs first-line.

Myth 3: “Only relaxation or yoga can cure GAD”

Evidence: They show moderate adjunctive effects, but in moderate-severe cases CBT and/or pharmacotherapy are required.

Myth 4: “Antidepressants are ineffective for anxiety — they are for depression”

Evidence: SSRI and SNRI effective in anxiety disorders; via effect of serotonergic system on amygdala activity. CANMAT 2014, Slee Lancet 2019.

Myth 5: “The patient can learn not to be anxious voluntarily”

Evidence: GAD is a neurobiological dysregulation; CBT or pharmacotherapy acts at the neurobiological level.

Myth 6: “Caffeine restriction is sufficient for GAD”

Evidence: Caffeine can exacerbate symptoms; restriction is an adjunct step, not primary treatment.

Myth 7: “Herbal preparations (kava, valerian, passiflora) can replace standard treatment”

Evidence: Kava severe hepatotoxicity (several fatalities — FDA warning); valerian and passiflora effect weak; St John's Wort interaction.

Myth 8: “Cannabis (CBD) cures anxiety”

Evidence: Preliminary studies exist for CBD, but insufficient for clinical recommendation; THC may exacerbate anxiety or trigger panic attacks.

Myth 9: “You will have to use antidepressants for life”

Evidence: After remission 12 months; then gradual discontinuation possible; restart if relapse.

Myth 10: “Electroconvulsive therapy is effective in refractory GAD”

Evidence: ECT is not indicated for GAD; in refractory cases — medication change, combination, atypical antipsychotic adjunct.

11. Sources

1. WHO. ICD-11. 6B00 Generalised anxiety disorder. 2024.
2. APA. DSM-5-TR. 2022.
3. NICE CG113. Generalised anxiety disorder and panic disorder in adults: management. 2011, 2020 update.
4. Katzman M.A. et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry 2014;14(Suppl 1):S1.
5. Slee A., Nazareth I., Bondaronek P. et al. Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis. Lancet 2019;393(10173):768–777.
6. Hettema J.M., Neale M.C., Kendler K.S. A review and meta-analysis of the genetic epidemiology of anxiety disorders. Am J Psychiatry 2001;158(10):1568–1578.
7. Hofmann S.G., Sawyer A.T., Witt A.A., Oh D. The effect of mindfulness-based therapy on anxiety and depression. J Consult Clin Psychol 2010;78(2):169–183.
8. Spitzer R.L., Kroenke K., Williams J.B., Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med 2006;166(10):1092–1097.
9. Cuijpers P., Sijbrandij M., Koole S. et al. Psychological treatment of generalized anxiety disorder: a meta-analysis. Clin Psychol Rev 2014;34(2):130–140.
10. Dugas M.J., Robichaud M. Cognitive-Behavioral Treatment for Generalized Anxiety Disorder. New York: Routledge, 2007.
11. Meyer T.J., Miller M.L., Metzger R.L., Borkovec T.D. Development and validation of the Penn State Worry Questionnaire. Behav Res Ther 1990;28(6):487–495.
12. Roemer L., Orsillo S.M. An open trial of an acceptance-based behavior therapy for generalized anxiety disorder. Behav Ther 2007;38(1):72–85.
13. Wells A. Metacognitive Therapy for Anxiety and Depression. New York: Guilford Press, 2009.
14. Kessler R.C., Berglund P., Demler O. et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005;62(6):593–602.