GAD Diagnosis + Treatment

CORE | How is pathological anxiety described in the GAD lecture?

An overestimation of perceived threat or erroneous danger appraisal leading to excessive/inappropriate psychological and physiological responses.

CORE | What is the approximate annual prevalence of GAD given in the lecture?

About 3% of the U.S. population in a given year.

CORE | What is the approximate lifetime prevalence of GAD given in the lecture?

About 6%.

CORE | What is the female:male ratio for GAD?

About 2:1.

DETAIL | What family-history statistic is given for GAD?

About 25% have a first-degree relative with GAD.

CORE | Around what age does GAD commonly begin?

Around age 30, later than many other anxiety disorders; commonly seen in adults 30–60.

CORE | What disorders commonly co-occur with GAD?

Major depressive disorder and substance use disorders.

DETAIL | What proportion of diagnosed U.S. patients with GAD receives treatment according to the lecture?

About 40%.

CORE | What are the six common associated symptoms of GAD?

Restlessness, easy fatigue, difficulty concentrating, irritability, muscle tension, and sleep disturbance.

CORE | How many associated symptoms are required in adults with GAD?

At least 3 of the 6.

CORE | How many associated symptoms are required in children with GAD?

At least 1 of the 6.

CORE | How long must GAD symptoms be present?

More days than not for at least 6 months.

CORE | What is the first DSM-5-TR criterion for GAD?

Excessive anxiety/worry occurring more days than not for at least 6 months about multiple events or activities.

CORE | What control criterion is required for GAD?

The person finds it difficult to control the worry.

CORE | What functional criterion is required for GAD?

The symptoms cause clinically significant distress or impairment in social, occupational, or other important functioning.

CORE | What causation exclusion is required for GAD?

The disturbance is not attributable to a substance/medication or another medical condition such as hyperthyroidism.

CORE | What psychiatric exclusion is required for GAD?

The disturbance is not better explained by another mental disorder.

DETAIL | What GAD symptom is described as a distinguishing feature from MDD?

Muscle tension.

DETAIL | What is described as the most common GAD complaint?

Sleep disturbance.

DETAIL | What GAD symptom can be mistaken for depression?

Easy fatigability/persistent tiredness.

CORE | What medical condition should be ruled out with a TSH in suspected GAD?

Hyperthyroidism.

CORE | What cardiac test is suggested for persistent arrhythmia symptoms?

ECG.

CORE | What lab is suggested for persistent hypoglycemia symptoms?

Fasting blood glucose.

CORE | What lab is suggested to rule out anemia?

Hemoglobin level.

CORE | What substances/medications can mimic or worsen anxiety?

Excessive caffeine, stimulants, albuterol, pseudoephedrine, corticosteroids, alcohol/benzodiazepine withdrawal, and excess thyroid hormone.

CORE | How does panic disorder differ from GAD in the differential?

Panic disorder features discrete/recurrent panic attacks rather than persistent generalized worry.

CORE | What key feature distinguishes MDD in the GAD differential?

Anhedonia.

CORE | What key feature distinguishes OCD in the GAD differential?

Obsessions and compulsions.

CORE | What key feature distinguishes PTSD in the GAD differential?

Trauma-related re-experiencing and associated symptoms.

PHARM | What four neurotransmitter systems are highlighted in GAD pathophysiology?

Serotonin, norepinephrine, GABA, and glutamate.

PHARM | What neural-circuit abnormalities are highlighted in GAD?

Hyperactive amygdala threat processing, insufficient prefrontal inhibitory control, and HPA-axis/cortisol dysregulation related to excessive worry.

CORE | What is the GAD-7 used for?

Screening for GAD, measuring symptom severity over the past 2 weeks, and monitoring treatment effectiveness.

CORE | How many items are on the GAD-7?

Seven.

CORE | What is the GAD-7 score range?

0–21.

CORE | What does a GAD-7 score of 0–4 represent?

Minimal symptoms; monitor, with no specific anxiety treatment indicated in the lecture table.

CORE | What does a GAD-7 score of 5–9 represent?

Mild symptoms; monitor/repeat, psychoeducation, and low-intensity interventions.

CORE | What does a GAD-7 score of 10–14 represent?

Moderate symptoms; possible clinically significant anxiety; active psychotherapy and possible pharmacotherapy.

CORE | What does a GAD-7 score of 15–21 represent?

Severe symptoms; psychotherapy plus pharmacotherapy is warranted in the lecture table.

DETAIL | What depression tools are commonly paired with the GAD-7?

PHQ-9 or PHQ-2.

CORE | How does CBT compare with pharmacotherapy for GAD in the lecture?

CBT has similar effect sizes and a lower relapse rate after discontinuation.

CORE | What CBT approaches are listed for GAD?

Psychoeducation, cognitive restructuring, applied relaxation/breathing, problem-solving training, resuming avoided activities, exercise, and sleep hygiene.

DETAIL | What exercise target is listed for anxiety?

About 150 minutes per week of aerobic activity.

DETAIL | What caffeine limit is suggested in the CBT/sleep-hygiene slide?

Reduce caffeine to less than 400 mg/day.

CORE | What dietary supplements does the GAD lecture say to avoid?

Kava, St. John’s wort, and 5-HTP.

CORE | Why avoid kava?

Liver toxicity.

CORE | Why avoid St. John’s wort or 5-HTP in anxiety treatment?

Risk of serotonin syndrome with serotonergic therapy.

CORE | What are first-line pharmacotherapies for GAD?

Selected SSRIs and SNRIs.

CORE | Why are SSRIs/SNRIs preferred for GAD?

They are effective for GAD and common comorbidities, have a favorable safety profile, and do not cause drug dependence.

CORE | How long does it take SSRIs/SNRIs to show meaningful anxiolytic effect?

About 4–6 weeks, with full effect around 6–8 weeks; anxiety may initially worsen in the first 2–4 weeks.

CORE | What antidepressant boxed-warning point applies in GAD?

Monitor for suicidality in patients under 25, especially children, adolescents, and young adults.

DRUG | Which SSRIs are FDA-approved for GAD in the lecture?

Escitalopram and paroxetine are emphasized as FDA-approved; sertraline, citalopram, and fluoxetine are commonly used off-label depending on the slide/table.

CORE | What common early SSRI adverse effects are emphasized in GAD?

GI upset, insomnia or somnolence, sweating/tremor, dizziness, and sexual dysfunction; some occur especially in the first 2 weeks.

CORE | What serious SSRI adverse effects are emphasized in GAD?

Suicidality in younger patients, serotonin syndrome, bleeding risk, hyponatremia/SIADH, and QT prolongation for selected agents.

CORE | What is the SSRI + MAOI/linezolid/methylene blue interaction?

Excess serotonin/serotonin syndrome; avoid/contraindicated with appropriate washout.

CORE | What is the SSRI + NSAID/anticoagulant interaction?

Increased GI/overall bleeding risk due to platelet serotonin effects; consider monitoring/protection as appropriate.

CORE | Why are paroxetine and fluoxetine problematic with tamoxifen?

CYP2D6 inhibition can reduce formation of active endoxifen and reduce tamoxifen efficacy.

CORE | What QT-related SSRI point is emphasized?

Citalopram has greater QT risk than escitalopram; monitor/limit dose in higher-risk patients.

DRUG | Which SNRIs are FDA-approved for GAD?

Venlafaxine XR and duloxetine.

DRUG | What venlafaxine dose relationship is emphasized in GAD?

Norepinephrine effects become more prominent at doses above about 150 mg/day.

DRUG | What comorbidity favors duloxetine in GAD?

Neuropathic/nerve pain conditions.

CORE | What common SNRI adverse effects are emphasized in GAD?

Nausea/vomiting, dry mouth, insomnia/somnolence, sweating, tremor, sexual dysfunction, and dizziness.

DRUG | What serious adverse effect is particularly emphasized for venlafaxine?

Dose-dependent hypertension; the slide also warns of cardiac toxicity in overdose.

DRUG | What serious adverse effect is particularly emphasized for duloxetine?

Hepatotoxicity; caution also with mydriasis/narrow-angle glaucoma.

CORE | What is the SNRI + MAOI/linezolid/methylene blue interaction?

Serotonin excess; contraindicated with a 14-day washout in the lecture.

DRUG | What major interaction can markedly raise duloxetine exposure?

Strong CYP1A2 inhibition such as ciprofloxacin or fluvoxamine.

DRUG | What class is buspirone?

Azapirone.

DRUG | What is buspirone’s main receptor mechanism?

5-HT1A activity: partial agonism postsynaptically and full agonism at presynaptic autoreceptors in the lecture, producing net serotonergic modulation.

DRUG | Does buspirone have GABA activity?

No.

DRUG | Does buspirone cause benzodiazepine-like dependence or cross-tolerance?

No drug dependence and no cross-tolerance with benzodiazepines are emphasized.

DRUG | How quickly does buspirone work?

About 2–4 weeks in the therapeutics lecture; it is not for acute PRN anxiety.

DRUG | What is a typical buspirone starting dose in the GAD lecture?

7.5 mg orally twice daily, titrated by 5 mg every 2–3 days; maximum 60 mg/day.

DRUG | What are common buspirone adverse effects?

Dizziness, nausea, headache, and nervousness; the slide notes little/no sedation, sexual dysfunction, or weight gain.

DRUG | What CYP enzyme metabolizes buspirone?

CYP3A4.

DRUG | What food interaction can greatly increase buspirone exposure?

Grapefruit juice; the slide cites about a ninefold increase in AUC.

DRUG | What interaction makes buspirone contraindicated with MAOIs?

Risk of hypertensive crisis.

DRUG | What is pregabalin’s mechanism?

Binds the alpha-2-delta subunit of voltage-gated calcium channels and decreases presynaptic release of glutamate, NE, and substance P; it is not a GABA agonist.

DRUG | How quickly can pregabalin work for GAD?

About 1 week, faster than SSRIs in the lecture.

DRUG | What are major pregabalin adverse effects?

Sedation, dizziness, weight gain, peripheral edema, and blurred vision.

DRUG | How is pregabalin eliminated?

Renally; dose-adjust in reduced renal function.

DRUG | What controlled-substance issue applies to pregabalin?

Schedule V with dependence potential.

DRUG | What is hydroxyzine’s main mechanism?

First-generation H1 antihistamine with central H1 antagonism; also weak 5-HT2, D2, and alpha-1 antagonism.

DRUG | Can hydroxyzine be used PRN for anxiety?

Yes; onset is about 15–30 minutes in the GAD lecture.

DRUG | What are common hydroxyzine adverse effects?

Sedation and anticholinergic effects such as dry mouth, blurred vision, constipation, urinary retention, and dizziness.

DRUG | What serious cardiac warning applies to hydroxyzine?

QT prolongation and torsades de pointes risk; avoid/caution with prolonged QT and other QT-prolonging drugs.

DRUG | Why is hydroxyzine problematic in older adults?

The lecture cites Beers criteria because it is strongly anticholinergic.

CORE | Why are TCAs not first-line for GAD?

Many off-target receptor effects, substantial anticholinergic/sedating/cardiac adverse effects, and potentially fatal overdose toxicity.

DRUG | What TCA is highlighted for GAD and insomnia?

Doxepin, although antidepressant/anxiolytic doses are sedating and anticholinergic.

CORE | What is the role of benzodiazepines in GAD?

Fast-onset short-term bridging while SSRI/SNRI therapy takes effect; not first-line long-term therapy.

CORE | What duration of benzodiazepine use is recommended in the GAD lecture?

Generally 2–8 weeks.

PHARM | What is the benzodiazepine mechanism at GABA-A?

Positive allosteric enhancement at the alpha-gamma interface, increasing the frequency of chloride-channel opening in the presence of GABA.

CORE | Do benzodiazepines open the GABA-A chloride channel without GABA?

No; the lecture contrasts this with barbiturates.

CORE | What are common benzodiazepine adverse effects?

Sedation, fatigue, dizziness, ataxia, cognitive/memory/psychomotor impairment, confusion, slurred speech, muscle weakness, and falls/fractures.

CORE | When is benzodiazepine respiratory depression most concerning?

With high doses or combination with opioids, alcohol, or other CNS depressants.

CORE | What is drug tolerance?

Reduced response to the same drug dose after repeated use; the same dose no longer works as well.

CORE | What is physical drug dependence?

Physiologic adaptation such that dose reduction or discontinuation causes withdrawal symptoms.

CORE | What is drug addiction?

Compulsive drug use with impaired control despite harm, typically involving craving and continued use despite negative consequences.

CORE | Which benzodiazepines are listed as preferred in elderly/hepatic impairment under the mnemonic CLOT?

Clonazepam, lorazepam, oxazepam, and temazepam.

CORE | What CYP3A4 inhibitors can increase levels of several benzodiazepines?

Ketoconazole, itraconazole, clarithromycin, ritonavir, and grapefruit juice.

CORE | What CYP3A4 inducers can reduce benzodiazepine levels?

Rifampin, carbamazepine, phenytoin, and St. John’s wort.

DRUG | Why is alprazolam not an ideal long-term GAD drug?

Fast onset but rebound/interdose withdrawal, high potency, tolerance/dependence/addiction risk, difficult withdrawal, cognitive/psychomotor impairment, and symptom-only short-term relief.