Generalized Anxiety Disorder

Generalized anxiety disorder (GAD) is mental disorder characterized by excessive anxiety and worry about multiple events or activities such as school or work difficulties, 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.


The 12-month prevalence ranges from 1-4%, and the lifetime prevalence is 6%. For youth (age 13-18), it is 3%. GAD is more frequent in Caucasians com- pared to other groups. The usual age of onset varies and may be bimodal with the median age of onset being approximately 31 years.


GAD is associated with high rates of comorbid psychiatric conditions including other anxiety or related disorders and MDD.

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
  1. Blanking out or difficulty concentrating
  2. Easily fatigued
  3. Sleep changes (difficulty falling or staying asleep, or restless, unsatisfying sleep)
  4. Keyed up, on edge, or restless
  5. Irritability
  6. 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:


The mnemonic BE SKIM can be used to remember the criteria for generalized anxiety disorder.[1]

  • B - Blank Mind
  • E - Easily Fatigued
  • S - Sleep Disturbance
  • K - Keyed Up/Restless/On-edge
  • I - Irritability
  • M - Muscle Tension

Anxiety can often present as a symptom of a medical illness. It is important to rule out medical causes to avoid misdiagnosis!

Baseline investigations include: CBC, fasting glucose, fasting lipid profiles, electrolytes, liver enzymes, serum bilirubin, serum creatinine, urinalysis, urine toxicology for substance use, TSH. An ECG should be performed for age > 40 years of age, beta-HCG (if relevant), and prolactin levels.[2]

The following treatment recommendations are based on the 2014 Canadian Clinical Practice Guidelines for anxiety, posttraumatic stress and obsessive-compulsive disorders:[3]


Pharmacotherapy for generalized anxiety disorder

1st line Agomelatine, duloxetine, escitalopram, paroxetine, paroxetine CR, pregabalin, sertraline, venlafaxine XR
2nd line Alprazolam*, bromazepam*, bupropion XL*, buspirone, diazepam*, hydroxyzine, imipramine, lorazepam*, quetiapine XR*, vortioxetine
3rd line 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. 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.


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.

Combination Therapy

There is no current evidence to support the routine combination of CBT and pharmacotherapy. However, as in other anxiety and related disorders, when patients do not benefit from CBT or have a limited response, a trial of pharmacotherapy is advisable.

Pediatric Considerations

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.[4] When pharmacotherapy is warranted, SSRIs are generally preferred, but all antidepressants should be used with caution in pediatric patients.

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.[5]

Pharmacotherapy for generalized anxiety disorder in pediatric populations

Antidepressants Fluoxetine, fluvoxamine, sertraline
Benzodiazepines Alprazolam