Generalized Anxiety Disorder (GAD)

Last edited on January 11, 2024

Generalized Anxiety Disorder (GAD) is mental disorder characterized by excessive anxiety and worry about multiple events or activities (e.g. - school or work difficulties, relationships, finances) on a majority of days over at least half a year. There are also associated symptoms, such as restlessness, muscle tension, fatigue, poor concentration, irritability, and sleep changes.

Epidemiology

The lifetime prevalence for generalized anxiety disorder is between 6 to 9%.^[1]^[2]
- There is a bimodal distribution, with onset in late-teens to early twenties and again in the 30s and 40s.
- The median age of onset is 31 years of age, with a peak in middle age.
Individuals from developed countries are more likely to experience GAD than non-developed countries.
- Similarly, individuals of European descent are more likely to experience GAD than non-Europeans, suggesting perhaps a role for social-economic factors in contributing to symptoms.^[3]
Women are 2 to 3 times more likely to have GAD than men.^[4]

Prognosis

Many individuals with GAD report a life-long history of anxiety and nervousness
GAD tends to wax and wane over the course of of the lifespan, and rates of full remission are very low.
- This suggests the GAD may not be a “mental disorder” per se, but rather a diagnostic construct that spans across different dimensions, including other mental disorders, personality disorders, and temperament.^[5]
GAD accounts for over 110 million disability days per year in the United States.^[6]

Comorbidity

Individuals with GAD are more likely to meet criteria for other anxiety disorders and depression.
There is also an increased risk for medical disorders, including pain syndromes, hypertension, and cardiovascular and gastrointestinal disorders.

Risk Factors

Temperamental traits including behavioural inhibition, negative affectivity (neuroticism), and harm avoidance are risk factors for GAD.^[7]
Adverse childhood events and parental overprotection are associated with GAD.^[8]

Cultural

There is significant variation in the expression of generalized anxiety disorder across the world. In some cultures, somatic symptoms may be the predominant presentation, whereas cognitive symptoms may predominate in others.

Criterion A

Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance).

Criterion B

The individual finds it difficult to control the worry.

Criterion C

The anxiety and worry are associated with at least 3 of the 6 symptoms (with at least some symptoms present for more days than not for the past 6 months);

Only 1 item is required in children

Blanking out or difficulty concentrating
Easily fatigued
Sleep changes (difficulty falling or staying asleep, or restless, unsatisfying sleep)
Keyed up, on edge, or restless
Irritability
Muscle tension

Mnemonic

The mnemonic BESKIM can be used to remember the criteria for generalized anxiety disorder.

B - Blank mind
E - Easily fatigued

S - Sleep disturbance
K - Keyed Up/Restless/On-edge
I - Irritability
M - Muscle tension

Criterion D

The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Criterion E

The disturbance is not attributable to the physiological effects of a substance (e.g. - a drug of abuse, a medication) or another medical condition (e.g. - hyperthyroidism).

Criterion F

The disturbance is not better explained by another mental disorder:

Anxiety or worry about having panic attacks (panic disorder)
Negative evaluation (social anxiety disorder)
Contamination or other obsessions (obsessive-compulsive disorder)
Separation from attachment figures (separation anxiety disorder)
Reminders of traumatic events (post-traumatic stress disorder)
Gaining weight (anorexia nervosa)
Physical complaints (somatic symptom disorder)
Perceived appearance flaws (body dysmorphic disorder)
Having a serious illness (illness anxiety disorder)
The content of delusional beliefs (schizophrenia or delusional disorder)

Panic Attack Specifier

Specify if:

Recurrent unexpected panic attacks. An abrupt surge of intense fear or intense discomfort that reaches a peak within minutes, and during which time at least 4 of the following symptoms occur (Note: The abrupt surge can occur from a calm state or an anxious state):

Sweating
Trembling or shaking
Unsteady, dizziness, light-headed, or faint
Derealization (feelings of unreality) or depersonalization (being detached from one self)
Excessive/accelerated heart rate, palpitations, or pounding heart
Nausea or abdominal distress
Tingling, numbness, parathesesias
Shortness of breath
Fear of losing control or “going crazy”
Fear of dying
Choking feelings
Chest pain or discomfort
Chills or heat sensations

Note: The symptoms presented in this specifier are for the purpose of identifying a panic attack. However, panic attacks are not a mental disorder. Panic attacks can occur in the context of any anxiety disorder as well as other mental disorders (e.g. - depressive disorders, posttraumatic stress disorder, substance use disorders) and some medical conditions (e.g. - cardiac, respiratory, vestibular, gastrointestinal). When the presence of a panic attack is identified, it should be noted as a specifier (e.g. - “social anxiety disorder with panic attacks”). For panic disorder, the presence of panic attack is contained within the criteria for the disorder and panic attack is not used as a specifier.

Note: Culture-specific symptoms (e.g. - tinnitus, neck soreness, headache, uncontrollable screaming or crying) may be seen. Such symptoms should not count as one of the four required symptoms.

Individuals may report muscle tension, trembling, twitching, feeling shaky, muscle aches.
Somatic symptoms such as sweating, nausea, diarrhea, and headaches may also occur.

Generalized Anxiety Scales

Name	Rater	Description	Download
Generalized Anxiety Disorder 7 (GAD-7)	Patient	The GAD-7 is a 7-item self-reported questionnaire for screening and a severity measure of generalized anxiety disorder	Download
Beck Anxiety Inventory (BAI)	Patient	The BAI is a 21-question self-report inventory for screening and a severity measure of generalized anxiety disorder	Download

Anxiety is a Broad Term!

Anxiety is also such a broad term that you must explore it in more detail to determine the correct diagnosis when someone says they are “anxious.” If the anxiety is about:

A fear of panicking, dying, or losing control, think panic disorder
Being trapped or being unable to escape, think agoraphobia
Being embarrassed in front of, or judgment by others, think social anxiety
Constant, pervasive worries, and they can't stop worrying, think generalized anxiety disorder
Thinking that something terrible will happen if certain rituals/compulsions aren't performed, or they will never feel “right,” think obsessive-compulsive disorder

Don't Forget About Medical Etiologies

Certain medical conditions can be misdiagnosed as generalized anxiety disorder, or vice versa. Refer to these two papers for an overview to avoid misdiagnosis!

Anxiety disorder due to another medical condition
- The diagnosis of anxiety disorder associated with another medical condition should be assigned if the individual's anxiety and worry are judged, based on history, laboratory findings, or physical examination, to be a physiological effect of another specific medical condition (e.g. - pheochromocytoma, hyperthyroidism). A thorough work up should be considered if there are associated physical exam findings, or ongoing acute symptoms without improvement after treatment.
Substance/medication-induced anxiety disorder
- A substance/medication-induced anxiety disorder is different GAD by the fact that a substance or medication (e.g. - a drug of abuse, exposure to a toxin) is temporally and etiologically related to the anxiety. For example, severe anxiety that occurs only in the context of heavy coffee use would be diagnosed as caffeine-induced anxiety disorder, rather than GAD.
Social anxiety disorder
- Individuals with social anxiety disorder often have anticipatory anxiety about upcoming social situations where they must perform or be evaluated by other. Contrast this with GAD, where individuals worry persistently (whether or not they are being evaluated).
Obsessive-compulsive disorder (OCD)
- Several features distinguish the excessive worry of GAD from the obsessional thoughts in OCD. In GAD, the focus of the worry is about upcoming problems. In OCD, the obsessions are intrusive and unwanted thoughts, urges, or images.

Posttraumatic stress disorder (PTSD) and adjustment disorders
- Anxiety is naturally present in posttraumatic stress disorder. Thus, GAD is not diagnosed if the anxiety and worry are better explained by a diagnosis of PTSD. Anxiety may also be present in adjustment disorder, but this residual category should be used only when the criteria are not met for any other disorder (including generalized anxiety disorder). Also note that in adjustment disorders, the anxiety occurs in response to an identifiable stressor within 3 months of the onset of the stressor and does not persist for more than 6 months after the termination of the stressor.
Depressive, bipolar, and psychotic disorders
- Generalized anxiety/worry is a common associated feature of major depressive disorder, bipolar disorder, and psychotic disorders. Thus, GAD should not be diagnosed if the excessive worry is occurring in the context of these other disorders.
Other disorders of childhood
- According to DSM-5, generalized anxiety disorder may be overdiagnosed in children, and other mental disorders such as separation disorder, social anxiety disorder, and OCD should be explored first.^[9]

Depending on the initial presenting symptoms (e.g. - dizziness, tachycardia), potential investigations can include: CBC, fasting glucose, fasting lipid profiles, electrolytes, liver enzymes, serum bilirubin, serum creatinine, urinalysis, urine toxicology for substance use, thyroid stimulating hormone (TSH).^[10]^[11]
An ECG and beta-HCG should be ordered if relevant.

The following treatment recommendations are based on the 2014 Canadian Clinical Practice Guidelines for anxiety, posttraumatic stress and obsessive-compulsive disorders:^[12]
There is currently no evidence to support combining treatment of psychotherapy and medications. However, when patients do not benefit from one form of treatment, switching or adding a different treatment is recommended.^[13]

Cognitive behavioural therapy (CBT) is an effective first-line option for the treatment of GAD and is as effective as pharmacotherapy. Internet-based and computer-based CBT have also demonstrated efficacy.
The evidence does not support the routine combination of CBT and pharmacotherapy, but when patients do not benefit from CBT, a trial of pharmacotherapy is advisable, and vice versa.

Pharmacotherapy for generalized anxiety disorder

Katzman, M. A. et al. (2014). Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC psychiatry, 14(1), 1-83.

1st line	Monotherapy: agomelatine, duloxetine, escitalopram, paroxetine, paroxetine CR, pregabalin, sertraline, venlafaxine XR
2nd line	Monotherapy: alprazolam, bromazepam, bupropion XL, buspirone, diazepam, hydroxyzine, imipramine, lorazepam, quetiapine XR, vortioxetine
3rd line	Monotherapy: citalopram, divalproex chrono, fluoxetine, mirtazapine, trazodone
Adjunctive therapy	Second-line: pregabalin Third-line: aripiprazole, olanzapine, quetiapine, quetiapine XR, risperidone Not recommended: ziprasidone
Not recommended	Beta blockers (propranolol), pexacerfont, tiagabine

CR = controlled release; XL = extended release; XR = extended release. *Note: Each of these 2nd-line treatments have distinct mechanisms, efficacy and safety profiles. Within these second-line agents, benzodiazepines would be considered first in most cases, except where there is a risk of substance abuse. Bupropion XL should be reserved for later. Quetiapine XR remains a good choice in terms of efficacy, but given the metabolic concerns associated with atypical antipsychotic, it should be reserved for patients who cannot be provided antidepressants or benzodiazepines.

For children and adolescents, psychological treatments are generally preferred over pharmacotherapy, or if warranted combination therapy may be an option. RCTs comparing combined pharmacological and psychological treatments in younger patients with anxiety have demonstrated efficacy equal or superior to either treatment alone.^[14]
Psychological therapies for children often need to be adapted to suit the chronological and developmental ages of young patients and to include parental involvement. Meta-analyses support the efficacy of CBT for the treatment of anxiety and related disorders in children and adolescents.^[15]
When pharmacotherapy is warranted, SSRIs are generally preferred, but all antidepressants should be used with caution in due to the risk for increased suicidal ideation and behaviours associated with antidepressant use in youth.

Generalized Anxiety Disorder Guidelines

Guideline	Location	Year	PDF	Website
Canadian Clinical Practice Guidelines for the Management of Anxiety, Posttraumatic Stress and Obsessive-Compulsive Disorders	Canada	2014	-	Link
Canadian Network for Mood and Anxiety Treatments (CANMAT)	Canada	2012	-	Link
National Institute for Health and Care Excellence (NICE)	UK	2011, 2019	-	Link
Royal Australian and New Zealand College of Psychiatrists (RANZCP)	AUS, NZ	2018	-	Link