Generalized Anxiety Disorder (GAD) is an anxiety disorder characterized by excessive and persistent anxiety and worry about multiple everyday events or activities without a clear or proportionate reason.

The anxiety is difficult to control and is associated with physical, cognitive, and emotional symptoms that interfere with normal functioning, social relationships, occupational activities, and quality of life.

Epidemiology

• GAD is one of the most common anxiety disorders worldwide

• It may occur at any age but commonly begins in adolescence or early adulthood

• It is more common in females compared with males

• The condition often follows a chronic fluctuating course

• GAD frequently occurs together with depressive disorders, substance use disorders, and other anxiety disorders

Risk Factors

Biological Factors

• Genetic predisposition

• Family history of anxiety disorders

• Neurotransmitter dysfunction involving serotonin, norepinephrine, and gamma-aminobutyric acid (GABA)

• Increased sensitivity of stress response systems

Psychological Factors

• Excessive tendency to worry

• Negative cognitive patterns

• Poor coping mechanisms

• Personality vulnerabilities

Environmental and Social Factors

• Chronic psychosocial stress

• Trauma exposure

• Financial difficulties

• Relationship problems

• Major life changes

• Substance misuse

Medical Factors

• Chronic medical illnesses

• Thyroid disorders

• Stimulant use

• Medication-related anxiety symptoms

Pathophysiology

Generalized Anxiety Disorder results from interaction between biological vulnerability, psychological factors, and environmental stressors.

Proposed mechanisms include:

• Dysregulation of neurotransmitter systems including serotonin, norepinephrine, and GABA

• Increased activity of the amygdala and fear-processing pathways

• Abnormal regulation of stress response systems

• Altered cognitive processing leading to excessive threat perception

Clinical Presentation

Patients present with excessive anxiety and worry occurring on most days, often involving multiple areas of life.

Symptoms may include psychological distress, physical manifestations of anxiety, and impaired daily functioning.

Symptoms

Psychological Symptoms

• Persistent excessive worry

• Difficulty controlling worry

• Poor concentration

• Mood disturbances

• Irritability

• Restlessness

• Feeling constantly on edge

Physical Symptoms

• Sleep disturbances

• Muscle tension

• Tremors

• Fatigue

• Palpitations

• Gastrointestinal discomfort

Clinical Signs

Clinical examination may reveal:

• Anxious appearance

• Restlessness

• Tremulousness

• Difficulty maintaining concentration during assessment

• Increased muscle tension

• Sleep-related complaints

• Autonomic symptoms such as sweating or increased heart rate

Differential Diagnosis

Consider:

• Major depressive disorder

• Panic disorder

• Social anxiety disorder

• Obsessive compulsive disorder

• Post-traumatic stress disorder

• Bipolar disorder

• Substance-induced anxiety disorder

• Hyperthyroidism

• Medication-induced anxiety

• Medical conditions causing anxiety symptoms

Diagnostic Criteria

Diagnosis is clinical.

Features include:

• Excessive anxiety and worry about several events or activities

• Difficulty controlling the worry

• Symptoms occurring persistently

• Associated symptoms such as:

  • Restlessness

  • Fatigue

  • Poor concentration

  • Irritability

  • Muscle tension

  • Sleep disturbance

The symptoms should:

• Cause significant distress or impairment in daily functioning

• Not be better explained by another mental disorder

• Not be due to substance use or another medical condition

Investigations

Investigations are guided by clinical suspicion and are mainly performed to exclude medical causes.

Possible investigations include:

• Full blood picture

• Serum electrolytes

• Renal function tests

• Liver function tests

• Thyroid function tests

• Blood glucose

• Substance use screening where indicated

Additional assessment:

• Psychiatric evaluation

• Assessment for depression and substance misuse

Management

Management aims to reduce anxiety symptoms, improve functioning, and prevent complications.

Initial management includes:

• Assess severity and impact on daily activities

• Identify contributing medical, psychological, and social factors

• Provide psychological support

• Initiate psychological and/or pharmacological treatment according to severity

Most patients can be managed as outpatients unless there are significant safety concerns or severe psychiatric comorbidities.

Non-pharmacological Treatment

Recommended interventions include:

• Psychotherapy

• Cognitive Behavioural Therapy (CBT)

• Relaxation techniques

• Stress management

• Coping skills training

• Sleep hygiene advice

• Lifestyle modification

• Social support enhancement

Pharmacological Treatment

Pharmacological treatment is indicated when:

• Symptoms interfere with normal daily functioning

• Anxiety is severe or persistent

• There is associated major depressive disorder

• There is failure of psychological therapy alone

Where there is concomitant drug or alcohol dependence or co-morbid major depressive episode, an antidepressant may be more appropriate.

Acute Management

For acute episodes or intense prolonged anxiety:

Diazepam – 2–5 mg – PO – stat, repeat every 12 hours when required

Duration of therapy:

• Up to 2 weeks

• Taper gradually to zero within 6 weeks

Maintenance Therapy

Amitriptyline – 25–75 mg – PO – at night

Medication should be titrated according to symptom resolution

OR

Citalopram – 10–40 mg – PO – once daily

Medication should be titrated according to symptom resolution

OR

Clonazepam – 0.5–4 mg – PO – once daily

Medication should be titrated according to symptom resolution

OR

Fluoxetine – 20–40 mg – PO – once daily

Medication should be titrated according to symptom resolution

Treatment Notes

• Prolonged treatment with benzodiazepines may lead to tolerance and withdrawal symptoms if discontinued abruptly

• Avoid combining more than one benzodiazepine

• Monitor treatment response and adverse effects regularly

Management According to Underlying Cause

Anxiety Associated with Depression

• Treat the depressive disorder appropriately

• Antidepressants may be preferred when anxiety occurs with major depressive episodes

Substance-Related Anxiety

• Address substance misuse

• Manage withdrawal states appropriately

• Provide relapse prevention support

Medical Causes of Anxiety

• Identify and treat underlying medical conditions

• Review medications that may contribute to anxiety symptoms

Referral

Refer to the next level of care if:

• There is lack of improvement with treatment

• Symptoms are severe or disabling

• There is co-existing major depressive disorder

• There is substance dependence

• There is significant functional impairment

• There are suicidal thoughts or safety concerns

• Diagnosis is uncertain

Complications

Possible complications include:

• Chronic anxiety symptoms

• Depression

• Substance misuse

• Sleep disorders

• Reduced occupational performance

• Social withdrawal

• Impaired quality of life

• Increased healthcare utilization

Prognosis

• GAD often follows a chronic fluctuating course

• Many patients improve with appropriate psychological and pharmacological treatment

• Early intervention improves functional outcomes

• Relapse may occur, especially when treatment is discontinued prematurely

Prevention

Preventive strategies include:

• Early recognition and treatment of anxiety symptoms

• Stress management

• Development of healthy coping strategies

• Adequate sleep hygiene

• Avoidance of excessive alcohol and substance use

• Strengthening social support networks

• Regular follow-up for patients with recurrent symptoms