What management steps should be taken for a 20‑year‑old patient taking atomoxetine (Strattera) 40 mg for ADHD and N‑acetylcysteine for marijuana cravings who is experiencing nausea and vomiting?

Immediate Management of Nausea and Vomiting in a Young Adult on Atomoxetine and NAC

Stop the atomoxetine immediately—nausea and vomiting are common gastrointestinal adverse effects occurring in up to 77% of patients taking atomoxetine for cannabis-related issues, and the drug is likely the primary culprit. 1, 2

Assess the Clinical Scenario

You need to determine whether this patient has:

• Atomoxetine-induced gastrointestinal toxicity (most likely given the temporal relationship)
• Cannabinoid Hyperemesis Syndrome (CHS) if he is still using marijuana heavily
• Cannabis Withdrawal Syndrome (CWS) if he recently stopped marijuana use
• A combination of the above

Key Diagnostic Questions

• Current marijuana use pattern: Is he still using daily (≥4 times/week for >1 year)? This suggests possible CHS. 1, 3
• Recent cessation: Did he stop marijuana within the past 24-72 hours? Withdrawal symptoms peak days 2-6 and include nausea, vomiting, and abdominal pain. 3
• Hot water bathing: Does he take long hot showers/baths for relief? This is present in 71% of CHS cases but also 44% of cyclic vomiting syndrome, so it's suggestive but not definitive. 1, 4
• Timing of atomoxetine: When did he start the 40 mg dose? Gastrointestinal adverse events are dose-dependent and occur early in treatment. 1, 2

Immediate Symptomatic Management

For Nausea and Vomiting Control

First-line antiemetic therapy:

• Haloperidol 5 mg IV is the most effective agent if CHS is suspected, reducing hospital length of stay by nearly 50%. 5, 4
• Add lorazepam 0.5-2 mg IV or PO every 4-6 hours for both antiemetic effect and anxiolysis, which addresses the stress-mediated component. 1, 3

Alternative options if haloperidol is unavailable or contraindicated:

• Promethazine 12.5-25 mg IV (central line only) or PO every 4-6 hours 1
• Ondansetron 8 mg sublingual every 4-6 hours (less effective for CHS but may help with atomoxetine-induced nausea) 1

Avoid opioids entirely—they worsen nausea, carry high addiction risk, and do not address the underlying pathophysiology in either CHS or atomoxetine toxicity. 1, 3, 5

Supportive Care

• Assess hydration status: Check skin turgor, mucous membranes, capillary refill, and mental status. 5
• IV fluids if moderate-to-severe dehydration or intractable vomiting. 5
• Loperamide for diarrhea if present (common in cannabis withdrawal). 3

Medication Adjustment Strategy

Atomoxetine Management

Discontinue atomoxetine immediately. 1, 2

• Nausea and vomiting are among the most common adverse effects, occurring in 77% of marijuana-dependent patients taking atomoxetine. 2
• Gastrointestinal adverse events are dose-dependent and occur more frequently at doses >1.5 mg/kg/day. 1, 6
• The 40 mg dose may be too high for this patient's weight or metabolic profile (7% of the population are poor CYP2D6 metabolizers with significantly higher plasma levels and increased adverse effects). 1

If ADHD treatment must continue:

• Wait 3-5 days after symptom resolution before restarting atomoxetine at a lower dose (10-18 mg daily), then titrate slowly. 1
• Consider alternative ADHD medications with lower gastrointestinal side effect profiles (e.g., extended-release stimulants if no contraindications). 1

NAC Continuation

• Continue NAC for marijuana craving support—it is not associated with significant gastrointestinal adverse effects and may help with cessation efforts. 3

Rule Out Cannabinoid Hyperemesis Syndrome

Diagnostic Criteria for CHS

If the patient is still using marijuana heavily, suspect CHS if:

• Cannabis use >1 year before symptom onset and frequency >4 times/week 1, 3
• Stereotypical episodic vomiting (≥3 episodes annually) 1, 4
• Compulsive hot water bathing behavior (present in 71% of cases) 1, 5
• Abdominal pain accompanying vomiting 1, 3

If CHS is suspected:

• Cannabis cessation is the only definitive cure—symptoms require at least 6 months of continuous abstinence for complete resolution. 1, 3, 4
• Topical capsaicin 0.1% cream applied to the abdomen can provide acute symptom relief by activating TRPV1 receptors. 1, 3, 5
• Long-term prevention: Start amitriptyline 25 mg at bedtime, titrate weekly by 25 mg increments to reach 75-100 mg for prophylaxis. 1, 3, 4

Rule Out Life-Threatening Conditions First

Before attributing symptoms solely to atomoxetine or CHS, exclude:

• Acute abdomen, bowel obstruction, mesenteric ischemia, pancreatitis, myocardial infarction 1, 4
• Basic workup: CBC, electrolytes, glucose, liver function tests, lipase, urinalysis 1

Distinguish Cannabis Withdrawal Syndrome

If the patient recently stopped marijuana (within 24-72 hours):

• Cannabis Withdrawal Syndrome (CWS) symptoms include nausea, vomiting, abdominal pain, irritability, anxiety, insomnia, decreased appetite, and restlessness. 3
• Symptoms peak days 2-6 and resolve within 1-2 weeks. 3
• Management is supportive: Loperamide for diarrhea, ondansetron for nausea (limited efficacy), and consider gabapentin or benzodiazepines for severe withdrawal symptoms. 3, 5
• Avoid opioids. 3

Counseling and Follow-Up

Cannabis Cessation Counseling

• Strongly recommend complete cannabis cessation if CHS is suspected—partial reduction or switching to edibles does not work. 1, 3, 4
• Provide brief motivational intervention (5-30 minutes with individualized feedback) to improve cessation outcomes. 3
• Refer to addiction medicine or psychiatry for severe withdrawal, co-occurring psychiatric disorders, or cannabis use disorder. 3

Monitor for Psychiatric Comorbidities

• Anxiety and depression are common in cannabis users and may emerge or intensify during withdrawal. 3
• Atomoxetine carries a black-box warning for suicidal ideation in children and adolescents—monitor closely for suicidality, clinical worsening, and unusual behavior changes, especially during the first few months or at dose changes. 1, 7

Follow-Up Plan

• Reassess in 48-72 hours after stopping atomoxetine to confirm symptom resolution.
• If symptoms persist beyond 1-2 weeks despite atomoxetine discontinuation, suspect CHS and enforce strict cannabis abstinence for 6+ months. 1, 3
• If ADHD symptoms remain uncontrolled, consider restarting atomoxetine at a lower dose or switching to an alternative agent. 1

Common Pitfalls to Avoid

• Do not continue atomoxetine at the current dose—gastrointestinal adverse events are dose-dependent and will worsen. 1, 2
• Do not prescribe opioids—they exacerbate nausea in both CHS and atomoxetine toxicity and carry high addiction risk in this population. 1, 3, 5
• Do not accept patient denial of the cannabis-symptom link—many patients attribute vomiting to food, alcohol, or stress, which impedes appropriate counseling. 3
• Do not pursue exhaustive investigations once CHS is suspected—focus on early diagnosis and cannabis cessation. 1, 3