What medications can lower stress hormones?

Medications to Lower Stress Hormones

For anxiety disorders associated with elevated stress responses, SSRIs are the first-line pharmacological treatment, with SNRIs as an alternative, as both classes modulate the stress hormone system through serotonergic mechanisms. 1

Understanding Stress Hormones and Medication Mechanisms

The stress hormone system is primarily driven by corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP), which trigger cortisol release from the adrenal cortex. 2 While no medications directly "lower" stress hormones in the traditional sense, certain psychotropic medications modulate the brain's stress response systems:

SSRIs (Selective Serotonin Reuptake Inhibitors)

SSRIs should be considered the primary pharmacological intervention for stress-related anxiety disorders, as they modulate serotonergic function which plays a key role in the brain's ability to regulate fear, worry, and stress responses. 1

• Mechanism: SSRIs inhibit presynaptic serotonin reuptake, increasing serotonin availability at synaptic clefts, which over time downregulates inhibitory serotonin autoreceptors and enhances serotonergic neuronal firing. 1
• Available agents in the US: Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and vilazodone. 1
• Evidence quality: Moderate to high strength of evidence for improving anxiety symptoms and global function in patients ages 6-18 years with social anxiety, generalized anxiety, separation anxiety, and panic disorders. 1
• Dosing considerations: Most SSRIs permit single daily dosing due to long elimination half-lives, though sertraline at low doses and fluvoxamine may require twice-daily dosing. 1
• Time to effect: Statistically significant improvement may occur within 2 weeks, but clinically significant improvement typically requires 6 weeks, with maximal improvement by week 12 or later. 1

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

SNRIs can be considered as an alternative first-line treatment, particularly when SSRIs are ineffective or not tolerated. 1

• Mechanism: SNRIs inhibit presynaptic reuptake of both norepinephrine and serotonin. Paradoxically, despite norepinephrine's association with the "fight or flight" stress response, noradrenergic medications effectively treat anxiety disorders through complex interactions with serotonin and other neurotransmitters. 1
• Available agents in the US: Venlafaxine, desvenlafaxine, duloxetine, and levomilnacipran. 1
• FDA approval: Duloxetine is the only SNRI with FDA indication for generalized anxiety disorder in children and adolescents ≥7 years old. 1
• Evidence quality: Moderate strength of evidence for improving primary anxiety symptoms (parent and clinician report), response to treatment, and remission. 1
• Dosing: Venlafaxine extended-release, desvenlafaxine, and duloxetine permit single daily dosing; venlafaxine immediate-release may require twice- or thrice-daily dosing due to short elimination half-life. 1

International Guideline Consensus

Multiple international guidelines converge on similar recommendations:

• NICE (UK): Lists escitalopram and sertraline as first-line, with fluvoxamine, paroxetine, and venlafaxine as second-line. 1
• S3 (Germany): Recommends escitalopram, paroxetine, sertraline, and venlafaxine as standard drugs. 1
• Canadian CPG: Lists SSRIs (escitalopram, fluvoxamine, paroxetine, sertraline) and SNRI venlafaxine as first-line, with pregabalin also included. 1

Alternative Agents (Second-Line or Adjunctive)

Pregabalin

• Listed as first-line in Canadian guidelines for social anxiety disorder. 1
• May have a role in generalized anxiety disorder. 3

Benzodiazepines

• Use with caution: While effective for acute anxiety and hyperarousal symptoms, benzodiazepines carry risks of dependence and withdrawal. 4, 5
• Clonazepam and chlordiazepoxide may have fewer distressing withdrawal symptoms. 4
• Substantial evidence supports use in panic disorder and generalized anxiety disorder. 5

Buspirone (Azapirone)

• Effective for generalized anxiety disorder. 3, 5
• May be useful for hyperarousal symptoms when antidepressants are insufficient. 4

Beta-Blockers (e.g., Propranolol)

• May address autonomic arousal symptoms. 4
• Canadian guidelines deprecate atenolol and propranolol for social anxiety disorder based on negative evidence. 1

Important Safety Considerations

Common Adverse Effects

• SSRIs: Dry mouth, nausea, diarrhea, heartburn, headache, somnolence, insomnia, dizziness, vivid dreams. 1
• SNRIs: Diaphoresis, dry mouth, abdominal discomfort, nausea, vomiting, diarrhea, dizziness, headache, tremor, insomnia, somnolence, decreased appetite, weight loss, sustained hypertension, increased blood pressure and pulse. 1

Serious but Uncommon Adverse Effects

• Both classes: Suicidal thinking and behavior (through age 24), behavioral activation/agitation, hypomania, mania, sexual dysfunction, seizures, abnormal bleeding, serotonin syndrome. 1
• Venlafaxine-specific: Greater suicide risk than other SNRIs, overdose fatalities, discontinuation symptoms. 1
• Duloxetine-specific: Hepatic failure (discontinue if jaundice or elevated transaminases occur), severe skin reactions including Stevens-Johnson syndrome. 1

Drug Interactions

• Fluoxetine: Inhibits CYP2D6, requiring caution with TCAs, antipsychotics, and antiarrhythmics; contraindicated with pimozide and thioridazine. 6
• Serotonin syndrome risk: Avoid combining SSRIs/SNRIs with MAOIs, triptans, tramadol, or other serotonergic agents. 6

Clinical Implementation Algorithm

1. First-line: Initiate SSRI (escitalopram or sertraline preferred based on international consensus) at low dose. 1
2. Titration: Slowly up-titrate over 6-12 weeks to avoid exceeding optimal dose, as response follows logarithmic model. 1
3. Assessment: Evaluate response at 6-8 weeks; maximal improvement may require 12+ weeks. 1
4. If inadequate response: Switch to alternative SSRI or trial SNRI (duloxetine or venlafaxine). 1
5. Persistent hyperarousal: Consider adjunctive buspirone or carefully selected benzodiazepine. 4, 5
6. Treatment resistance: Consider combination therapy (e.g., acamprosate + naltrexone for alcohol-related stress, though this is specific context). 1

Critical Pitfalls to Avoid

• Premature discontinuation: Patients and families must be counseled that clinical improvement requires 6-12 weeks, not days. 1
• Inadequate dosing: Ensure therapeutic doses are reached before declaring treatment failure. 4
• Ignoring suicidality monitoring: Close monitoring is essential, especially in patients under age 24 during initial weeks and dose adjustments. 1, 6
• Abrupt discontinuation: Taper medications to minimize discontinuation symptoms, particularly with venlafaxine. 1
• Polypharmacy without rationale: Avoid combining serotonergic agents without careful consideration of serotonin syndrome risk. 6