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Day # 66: Generalized Anxiety Disorder (GAD)

At this point in the curriculum we have covered an introduction to anxiety disorders, clinical pearls for anxiety, mental status exam, medical workup for anxiety, and general treatment options. Now we will move forward and discuss specific disorders. We will start today with generalized anxiety disorder (GAD).

Today’s Content Level: Beginner, Intermediate


Patients with GAD have persistent and excessive anxiety about many aspects of their daily lives. This leads to persistent hyper-arousal and significant distress or impairment. Some of the more common areas of excessive worry include:

  • Minor matters (Will I arrive on time? What if I get lost while driving? What if I can't find a parking spot?).

  • Personal health and safety.

  • The health of their loves ones (parents, friends, children, pets, etc...).

  • Relationships.

  • Money / Paying bills.

  • Work or school.

  • Their future.

  • World events, community affairs, politics, the environment.

  • Appearance.

  • They worry about how much they are worrying.

•Additionally, patients with GAD will often experience somatic symptoms including fatigue, irritability, tense muscles, insomnia, and more.

The diagnostic criteria for GAD are as follows 1:

  • Excessive anxiety and worry occurring more days than not about a number of things.

  • Difficulty controlling the worry.

  • Symptoms ≥ 6 months.

  • Associated with ≥ 3 of the following symptoms (1 in children):

    • Restlessness / keyed up / on edge.

    • Easily fatigued.

    • Difficulty concentrating / mind going blank.

    • Irritability.

    • Muscle tension.

    • Sleep disturbance (difficulty falling/staying asleep or restless/unsatisfying sleep).

These criteria are commonly remembered from the following mnemonic = Worried WWARTS:

  • Worried = anxious

  • Wound up = irritability

  • Worn-out = fatigued

  • Absent-minded = impaired concentration

  • Restless

  • Tense = muscle tension

  • Sleep disturbance

•Also remember that to make any diagnosis you need to determine that it causes significant distress or impairment, symptoms are not attributable to a substance or medical illness, and symptoms are not better explained by another mental disorder.


Epidemiology 2

  • 12-month prevalence ~2.5%.

  • Lifetime prevalence ~5%.

  • Can present at any age, but median age of onset is 31 years old and 95% onset by age 66.

  • Oldest average age of onset of all anxiety disorders.

  • Higher rates in women compared to men (2:1).

Risk Factors 3

  • Childhood adversity including trauma or abuse.

  • Parental overprotection.

  • History of separation anxiety disorder in childhood.

  • Female sex (2:1 ratio). Hypothesized to be related to hormonal differences, cultural expectations, and more willingness to seek treatment.

  • Poverty.

  • Recent adverse events.

  • Chronic medical illness.

  • Major stressor in the past 12 months, especially loss, threat, medical illness.

Pathogenesis 4, 5

  • Some estimate one third of the risk for developing GAD is genetic.

  • Common heritability with MDD.

  • Studies have implicated abnormalities in GABA, serotonin, norepinephrine, alpha-2, and CCK.

  • Short-short (S-S) allele of the serotonin transport polymorphic region is significantly more common in patients with GAD than in controls.



  • Examples of screening questions include -> In the past 2 weeks how often have you felt nervous, anxious, or on edge? Are you a worrier? Have you been unable to stop or control your worry?

  • Remember that some patients with GAD may initially present to primary care for physical complaints (fatigue, muscle tension, etc...).

  • Screen for other anxiety disorders, especially panic and social anxiety disorder. Also screen for depression.

  • Optional Questionnaires: Generalized Anxiety Disorder 7-Item (GAD-7), Hamilton Anxiety Scale (HAM-A), Penn State Worry Questionnaire (PSWQ), Anxiety Symptoms Questionnaire (ASQ), Beck Anxiety Inventory (BAI).

  • Other important features of the clinical interview include:

    • Screen for recent stressful events or trauma.

    • Substance history (including nicotine and caffeine).

    • Family history of anxiety or depressive disorders.

    • Rule out anxiety/panic due to another medical condition (see day 64). Particularly in those with atypical, late-onset or new physical symptoms.


  • Typically gradual onset with sub-syndromal symptoms initially.

  • Earlier onset of symptoms = worse prognosis.

  • Most studies demonstrate GAD as a chronic illness with some periods of improvement and relapse. Rates of complete remission of symptoms, even with treatment, is low.

  • May present primarily or exclusively with somatic symptoms (poor sleep, fatigue, headache, GI distress) with unexplained, chronic physical concerns.

Comborbid conditions 6

  • GAD is highly comorbid with other anxiety, depressive, and substance use disorders.

  • GAD + MDD ~ 42%.

  • GAD often precedes and predicts future MDD.

  • GAD + social anxiety disorder ~ 23%.

  • GAD + panic disorder ~ 22%.

  • GAD + specific phobia ~ 21%.

  • GAD + substance use disorders ~50%. Often alcohol and benzodiazepines.


•Treatment for all anxiety disorders are similar, so we have written a detailed post titled "Treatment of Anxiety Disorders" where we discuss treatment options in detail. Please refer to that post for a more thorough discussion.

•Treatment options for all GAD include psychotherapy, pharmacotherapy, and other alternative treatments. Therapy and medications are both effective separately and together in GAD and the most effective treatment is probably a combination of these approaches.

•Discuss patient’s preference for psychotherapy and/or pharmacotherapy, as studies show that there is no significant difference in efficacy of psychotherapy vs medications in GAD. 7

•For patients who are "psychologically minded" and motivated to better understand their anxiety, psychotherapy may be the treatment of choice.

•There is a stronger preference for pharmacotherapy when depression is comorbid with GAD.


  • Cognitive Behavioral Therapy (CBT): Considered first-line with strong evidence for effectiveness. 8

  • Psychodynamic Psychotherapy (PDP): Less studies overall when compared to CBT but existing evidence supports its efficacy. 9

  • Other options with evidence of effectiveness: Emotion Regulation Therapy; Mindfulness Therapy; Acceptance and Commitment Therapy (ACT); Dialectical Behavioral Therapy (DBT); and Family Therapy.

  • See this post for more details on each of these forms of therapy.


  • SSRIs and SNRIs: Considered first-line treatment of GAD. No specific drug has been shown to have significantly higher efficacy than any other. Effective but takes weeks to see treatment effect. If good response, continue at least 12 months before discontinuing. If poor response after 6 weeks at therapeutic dose, switch to different SSRI. If partial response consider augmentation with benzodiazepine or buspirone.

  • Benzodiazepines: Highly effective and has rapid treatment effect. Risk of tolerance/dependence/addiction and rebound anxiety. Normally for short-term use only. Ideally maximum is 2-4 weeks while initiating SSRI/SNRI, but may be considered as augmentation in severe anxiety. Favor longer half lives for GAD (such as clonazepam) unless slow metabolizers (increased age or liver disease).

  • Buspirone: Partial agonist of serotonin receptors. Sometimes effective. Used to augment SSRI/SNRI, but takes weeks for full effectiveness.

  • Pregabalin/Gabapentin: Often used off-label (pregabalin approved in EU) for treatment or augmentation of anxiety disorders. Studies demonstrate mixed results. Relatively quick onset of action and response may be seen in the first week of treatment.

  • Treatment-Refractory cases: In these cases other medications can be tried, but are not first line due to adverse effects and no evidence of greater efficacy. Examples include: TCAs, MAOIs, mirtazapine, antipsychotics, antiepileptics, hydroxyzine, and beta-blockers.

  • See this post for more details on medication options for treatment of anxiety.


Great work today. Next lesson we will discuss phobia's. If you want more learning resources then check out our recommended resources page.

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