Generalised Anxiety Disorder

DSM V categorise these as seperate disorders

Depressive disorders
Bipolar disorders
Anxiety disorders

Anxiety Disorders

Generalised Anxiety Disorder
Specific Phobia
Agoraphobia
Social Anxiety Disorder
Panic Disorder

This will mainly focus on Generalised Anxiety Disorder and touches on Panic Disorder.

Overview

Generalized anxiety disorder (GAD) can be defined as anxiety and worry about several events and activities for a majority of the day over a 6-month time period. The anxiety and worry associated with GAD can be distinguished from normal anxiety by their excessive nature, the difficulty involved in controlling them, and their interference in everyday life. 10% of people have an anxiety disorder and it is more common in females.

Definition

Phobia: Persistent, irrational, exaggerated, and pathologic fear of a specific situation or stimulus that results in conscious avoidance of the dreaded circumstance
Compulsions: Repetitive behavior or mental acts that a person feels driven to perform in response to an obsession according to a rigid set of rules.
Obsessions: Recurrent and persistent thoughts or images that are experienced as intrusive and inappropriate and cause marked anxiety or distress.
Generalised Anxiety disorder: disorder of chronic uncontrollable worry, compounded by physiological symptoms such as disturbed sleep, muscle tension, and difficulty concentrating.
Panic disorder: Spontaneous occurrence of severe panic attacks (periods of fear which peak within ~10minutes_. These should be accompanied by four or more of tachycardia, sweating, trembling or shaking, shortness of breath, a feeling of choking, chest pain, dizziness, etc.
Panic attack: Discrete period of intense fear or discomfort

Panic disorder (PD) is characterized by episodic, unexpected panic attacks that occur without a clear trigger. Panic disorder can lead to panic attacks which are defined by the rapid onset of intense fear (typically peaking within about 10 minutes) with at least four of the physical and psychological symptoms in the DSM-5 diagnostic criteria.

The hallmark of GAD is excessive, out-of-control worry, and PD is characterized by recurrent and unexpected panic attacks.

Risk Factors

Family history of anxiety or mood disorders
Anxious or behaviourally inhibited temperament
Childhood adversity, trauma or insecure attachment
Chronic stress or major adverse life events
Chronic physical illness or persistent pain
Female sex
Substance or stimulant use
Comorbid depression or another anxiety disorder
Poor social support
Sleep deprivation

Pathophysiology

The cause is multifactorial, involving genetic vulnerability, temperament, environmental stress and learned patterns of worry.
Abnormal processing of uncertainty and threat may cause ordinary events to be interpreted as potentially dangerous.
Altered regulation between the prefrontal cortex and limbic structures, particularly the amygdala, may contribute to sustained anxiety.
Serotonin, noradrenaline, GABA and stress-response systems are thought to be involved, although no single neurotransmitter abnormality explains GAD.
Worry and avoidance may temporarily reduce distress, reinforcing the behaviour and maintaining the anxiety cycle.

Clinical Manifestation

When assessing someone with suspected anxiety make sure to exclude medical causes (hyperthyroidism, cardiopulmonary disease, neurological conditions, TIA) and other psychiatric conditions as well as medication induced (caffeine, decongestants or substance withdrawal).

Watchers

Worry (Core symptom)
Anxiety (Core symptom)
Tension of muscles
Concentration difficulty
Hyper-arousability
Energy loss/easily fatigued
Restlessness
Sleep disturbance

GAD typically present with excessive anxiety about ordinary, day-today situations. The anxiety is intrusive, causes distress or functional impairment, and often encompasses multiple domains (e.g., finances, work, health).

Diagnosis

Generalised anxiety disorder (1 Core symptom + 3 other symptoms)

Worry (Core symptom)
Anxiety (Core symptom)
Tension of muscles
Concentration difficulty
Hyper-arousability
Energy loss/easily fatigued
Restlessness
Sleep disturbance

6 months most days and doesn’t fit another more specific disorder

Complicating the diagnosis of GAD (and PD) is that many conditions in the differential diagnosis are also common comorbidities. Additionally, many patients with GAD or PD meet criteria for other psychiatric disorders, including major depressive disorder and social phobia.

Differential Diagnosis

Hyperthyroidism
Drug induced
Hypoglycemia
Hypoparathyroidism
TIAs/TBIs
AMI/PE/Angina
Palpitations
Sjorgen syndrome

Generalized anxiety disorder is almost always accompanied by another mental disorder; the physician should inquire about symptoms of depression, traumatic stressors, panic attacks, and substance abuse.

Investigation

No laboratory or imaging test confirms GAD. Investigations are guided by the presentation and may include:

FBC: anaemia
UEC, glucose and calcium
TSH: hyperthyroidism
ECG: palpitations or suspected arrhythmia
Toxicology or medication review where substance-induced anxiety is possible
Other targeted tests when cardiac, respiratory, neurological or endocrine disease is suspected

Treatment

Psychotherapy can be as effective as medication for GAD and PD. Cognitive behavior therapy has the best level of evidence. Physical activity is a cost-effective treatment for GAD and PD.

General management

Education and shared decision-making
Regular follow-up
Reduce excessive caffeine, nicotine and stimulant intake
Regular exercise
Consistent sleep routine
Relaxation, breathing or mindfulness strategies
Address alcohol or substance misuse
Treat comorbid depression, insomnia and physical illness

Psychological treatment

Cognitive behavioural therapy—CBT: first-line psychological treatment.
Options for milder disease include:
- Guided self-help based on CBT
- Structured online CBT
- Psychoeducational groups

Pharmacological treatment

First-line

SSRI, such as:
- Sertraline
- Escitalopram
- Fluoxetine
SNRI, such as:
- Venlafaxine
- Duloxetine

Start at a low dose and increase gradually because anxiety, agitation or gastrointestinal symptoms may initially worsen. Clinical benefit generally develops gradually over several weeks.

Other options

Alternative SSRI or SNRI if the first medicine is ineffective or poorly tolerated.
Pregabalin may be considered when SSRIs or SNRIs cannot be tolerated, with attention to sedation, dependence potential and pregnancy risks.
Buspirone may be used in selected patients, depending on local availability and specialist advice.
Benzodiazepines should generally be restricted to brief crisis management because of sedation, tolerance, dependence, withdrawal and falls risk.
Antipsychotics are not routinely recommended for uncomplicated GAD.

To avoid relapse, medication should be continued for 12 months after symptoms improve before tapering.

Pharmacology

Buspirone is a non-sedating nonbenzodiazepine anxiolytic and works as a partial seratoinin 1A agonist. Two to four weeks are required for a successful therapeutic effect, and adverse effects include restlessness, insomnia, and nervousness. Buspirone is as effective as diazepam in treating anxiety. Buspirone does not repress respiration in individuals with lung disease and sleep apnea like benzodiazepines do.

Complications & Prognosis

GAD increases the risk of major depression, so preventive approaches should be put in place.

Complications

Major depressive disorder
Other anxiety disorders
Chronic insomnia
Alcohol or substance misuse
Reduced work, academic and social functioning
Relationship difficulties
Increased healthcare use for somatic symptoms
Medication dependence, particularly with prolonged benzodiazepine use
Self-harm or suicide risk, particularly with severe depression or substance misuse

Prognosis

GAD commonly follows a chronic, fluctuating or relapsing course.
Many patients experience substantial improvement with CBT, medication or both.
Relapse may occur during periods of stress or after treatment is discontinued prematurely.
Poorer outcomes are associated with severe longstanding symptoms, comorbid depression, substance misuse, major functional impairment and poor treatment adherence.

References

National Institute for Health and Care Excellence. Generalised anxiety disorder and panic disorder in adults: management. NICE guideline CG113. London: NICE; 2011. Updated 2022.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed, text revision. Washington, DC: American Psychiatric Association Publishing; 2022.
Andrews G, Bell C, Boyce P, Gale C, Lampe L, Marwat O, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of panic disorder, social anxiety disorder and generalised anxiety disorder. Aust N Z J Psychiatry. 2018;52(12):1109–1172. doi:10.1177/0004867418799453.
Spitzer RL, Kroenke K, Williams JBW, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092–1097. doi:10.1001/archinte.166.10.1092.
Mochcovitch MD, da Rocha Freire RC, Garcia RF, Nardi AE. A systematic review of functional neuroimaging studies in generalized anxiety disorder. J Affect Disord. 2014;167:336–342. doi:10.1016/j.jad.2014.06.041.