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 Generalised Anxiety Disorder; 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 summaries).
• 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).
• Gastrointestinal complaints are common comorbidities in IBS.

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, irritability, feeling of wandering off;
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 Source-specific clarifications

• 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 General principles (NICE CG113 · APA · CANMAT 2014)

1. Stepped approach:
   • Step 1: psychoeducation, observation.
   • Step 2: guided self-help (internet-based CBT), psychoeducational groups.
   • Step 3: High-intensity CBT or pharmacotherapy.
   • Step 4: Specialized service (combination, refractory).
2. CBT first-line psychotherapy — cognitive restructuring regarding anxiety, problem-solving, exposure, reduction of avoidance, relaxation, work with intolerance of uncertainty.
3. First-line pharmacotherapy:
   • SSRIs — sertraline, escitalopram, paroxetine.
   • SNRI — venlafaxine, duloxetine (FDA approval for GAD).
   • Effect 4–6 weeks.
4. Second-line:
   • Pregabalin — In Europe, there is an approved option for GAD that provides rapid effect but carries a potential for dependency.
   • Buspirone — partial effect; alternative to benzodiazepine.
   • Mirtazapine — adjunct, if sleep disturbance present.
5. Benzodiazepines — only short-term (2–4 weeks); high addiction potential; sustained use not recommended.
6. Duration of treatment — after remission ≥ 12 months; long-term in chronic or multiple relapse cases.
7. Adjunct — mindfulness-based stress reduction, applied relaxation, ACT (Acceptance and Commitment Therapy).
8. Lifestyle: Caffeine restriction, physical activity, sleep hygiene, abstinence from alcohol and drugs.

8.2 Source-specific clarifications

• NICE CG113 (2011/2020): Stepped care algorithm; SSRIs and SNRIs are first-line pharmacotherapy; benzodiazepines only for acute, short-term.
• The APA has no separate guideline for anxiety disorders; the only document in this family covers panic disorder (2009, legacy status). For GAD the reference points are NICE CG113 and CANMAT 2014: CBT and SSRIs have the strongest evidence base.
• CANMAT 2014 Anxiety Disorders Guidelines (Katzman M.A. et al.): First-line: escitalopram, sertraline, venlafaxine, duloxetine; second-line: pregabalin, buspirone, mirtazapine, quetiapine.
• Slee A. et al. Lancet 2019 network meta-analysis: duloxetine, pregabalin, and venlafaxine have shown high efficacy in GAD; acceptability profile variable.

Treatment methods

1. CBT (for GAD) — Cognitive restructuring (beliefs about worry), intolerance of uncertainty (Dugas M.J. model), exposure to anxiety-provoking situations, problem-solving training, relaxation. 12–20 sessions. Cuijpers P. et al. reviews — medium-large effect.
2. Mindfulness-Based Stress Reduction / Cognitive Therapy (MBSR / MBCT) — 8-week group program; modest effect in GAD. Meta-analysis: Hofmann S.G. et al. J Consult Clin Psychol 2010.
3. Acceptance and Commitment Therapy (ACT) — Values-based behavior, development of psychological flexibility. Roemer L. et al. RCTs.
4. Applied Relaxation (Applied Relaxation) — Öst (Öst L.G.) — Structured progressive muscle relaxation — used before anxiety trigger.
5. Generalized Anxiety Disorder Scale-7 (GAD-7) — Spitzer R.L., Kroenke K — 7 questions; gold standard screening and monitoring in primary care. Cut-off 10 indicates moderate-severe severity.
6. Hamilton Anxiety Rating Scale (HAM-A) — 14 items; clinician-rated; research and clinical monitoring.
7. Penn State Worry Questionnaire (PSWQ — Penn State Worry Questionnaire) — Meyer (Meyer T.J.) — 16 items; frequency and uncontrollability of worry.

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.