What is the recommended medical workup and treatment for anxiety?

Medical Workup for Anxiety

Initial Screening and Diagnosis

Screen all patients presenting with anxiety symptoms using validated instruments, specifically the Generalized Anxiety Disorder-7 (GAD-7), which demonstrates sensitivity of 57.6% to 93.9% and specificity of 61% to 97%. 1

Diagnostic Interview Components

• Conduct a comprehensive diagnostic interview to determine if DSM-5 criteria for specific anxiety disorders are met 2
• Interview should assess for excessive fear or worry that is out of proportion to actual threat, causing clinically significant distress or functional impairment 3
• Symptoms must persist for at least 6 months to distinguish from transient stress reactions 3
• Evaluate for panic-like symptoms (abrupt surges of intense fear with physical manifestations), social fears (marked anxiety about scrutiny by others), anticipatory anxiety, and avoidance behaviors 3

Medical Differential Diagnosis

Laboratory testing is not routine but should be completed when signs and symptoms suggest an underlying medical condition. 2

Medical conditions to systematically exclude include:

• Endocrine disorders: Hyperthyroidism (check thyroid function tests), hypoglycemia (check glucose), diabetes 2, 3
• Cardiovascular conditions: Cardiac arrhythmias, cardiac valvular disease, pheochromocytoma 2, 3
• Respiratory disorders: Asthma, hypoxia 2, 3
• Neurological conditions: Central nervous system disorders, migraine 2, 3
• Other metabolic disturbances: Lead intoxication, systemic lupus erythematosus, allergic reactions, dysmenorrhea 2, 3

Substance-Related Causes to Exclude

• Caffeine excess (caffeinism) 2, 3
• Medication side effects 3
• Illicit drug use or intoxication 3
• Alcohol or benzodiazepine withdrawal 3

Psychiatric Comorbidity Assessment

Use the Parent- and Self-Rated Level 1 Cross-Cutting Symptom Measures or structured interview screening questions to standardize assessment for psychiatric comorbidities. 2

Common comorbidities requiring separate evaluation:

• Depression: Present in approximately 56% of patients with anxiety disorders 3
• Other anxiety disorders (frequently co-occur with each other) 2
• ADHD, bipolar disorder, obsessive-compulsive disorder 2, 3
• Eating disorders, substance use disorders 2, 3
• Post-traumatic stress disorder 3

For patients with symptoms of both depression and anxiety, prioritize treatment of depressive symptoms first. 2

Treatment Algorithm

First-Line Treatment Selection

Start with individual Cognitive Behavioral Therapy (CBT) specifically designed for anxiety as the primary intervention, which demonstrates large effect sizes (Hedges g = 1.01 for GAD). 3, 1

• Individual CBT is preferred over group therapy due to superior clinical effectiveness 4, 3
• If face-to-face CBT is not feasible, self-help CBT with professional support is a viable alternative 4, 3

Pharmacotherapy Indications

Add an SSRI (sertraline or escitalopram preferred) or SNRI (venlafaxine extended-release) if CBT alone is insufficient, if patient preference warrants medication, or for moderate to severe presentations. 4, 3

First-Line Medication Selection

Sertraline or escitalopram should be initiated as first-choice SSRIs due to lower potential for drug interactions and superior tolerability. 4, 3

• SSRIs and SNRIs demonstrate small to medium effect sizes compared to placebo (GAD: SMD -0.55; social anxiety: SMD -0.67; panic disorder: SMD -0.30) 1
• Venlafaxine extended-release is an equally effective alternative to SSRIs and can be used as first-line treatment 4, 3
• Fluvoxamine is approved for anxiety disorders but may have more side effects than sertraline or escitalopram 4

Medications to Avoid

Paroxetine and fluoxetine should be avoided, especially in older adults, due to higher rates of adverse effects. 4, 3

Benzodiazepines are not recommended for routine use. 5

• If benzodiazepines are absolutely necessary for very short-term use, use lower doses with shorter half-lives 4

Dosing for Sertraline (First-Line SSRI)

For adults with anxiety disorders, initiate sertraline at 50 mg once daily (morning or evening), with dose increases as needed up to 200 mg/day. 6

• For children ages 6-12 with OCD: Start at 25 mg once daily 6
• For adolescents ages 13-17 with OCD: Start at 50 mg once daily 6
• Dose changes should not occur at intervals less than 1 week due to 24-hour elimination half-life 6

Combined Treatment

Combined CBT plus SSRI produces superior outcomes compared to either treatment alone for moderate to severe presentations. 3

Treatment Monitoring

Regular Assessment Schedule

Assess treatment response at 4 weeks, 8 weeks, and end of treatment using standardized validated instruments. 2, 3

• For pharmacologic treatment, regularly assess symptom relief, side effects, adverse events, and patient satisfaction 2
• For psychological treatment, mental health professionals should assess treatment response at pretreatment, 4 weeks, 8 weeks, and end of treatment 2

Treatment Adjustment Protocol

After 8 weeks of treatment, if there is little improvement despite good adherence, adjust the regimen. 2, 3

• If first medication fails, switch to another SSRI or SNRI rather than adding additional agents 4, 3
• Consider adding a psychological or pharmacologic intervention to single treatment 2
• If group therapy, refer to individual therapy 2

Treatment Duration

Medications should be continued for at least 6-12 months after symptom remission for a first episode. 4, 3, 5, 7

• For recurrent or chronic presentations, longer-term or indefinite treatment may be necessary 4, 3
• Systematic evaluation demonstrates efficacy maintained for 24-44 weeks depending on disorder type 6
• Periodically reassess the need for continued treatment and consider gradual dose reduction after sustained remission 3, 6

MAOI Considerations

At least 14 days must elapse between discontinuation of an MAOI and initiation of sertraline, and vice versa. 6

• Do not start sertraline in patients being treated with linezolid or intravenous methylene blue due to serotonin syndrome risk 6
• If urgent treatment with linezolid or IV methylene blue is required, stop sertraline promptly and monitor for serotonin syndrome for 2 weeks or 24 hours after last dose, whichever comes first 6

Critical Pitfalls to Avoid

• Do not diagnose anxiety disorder unspecified without systematically ruling out specific anxiety disorders, medical conditions, and substance-induced causes 3
• Do not use benzodiazepines as routine first-line treatment due to abuse risk and adverse effects 5, 7
• Do not discontinue medications prematurely; continue for minimum 6-12 months after remission to prevent relapse 5, 7
• Do not ignore psychiatric comorbidities, as each may require separate treatment and influence anxiety treatment selection 2
• Do not perform routine laboratory testing unless clinical signs suggest specific medical conditions 2