Atlas›Domain IX · Biomedical, neuro & digital›Guide 009
Guide IX-009

NMDA-modulating combination antidepressant (dextromethorphan-bupropion)

2022USA
A 25 · L 69 · M 619 interventions in the Trinity explorer
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[source: …] where a claim comes from[uncertain] not confirmed in a primary source[synthesis] the writer's reconstruction

1. Introduction

Version followed: US FDA Prescribing Information for AUVELITY (dextromethorphan HBr and bupropion HCl) extended-release tablets, revised 04/2026, and the accompanying Medication Guide as posted in April 2026; Axsome Therapeutics' approval announcements of 19 August 2022 (major depressive disorder) and 30 April 2026 (agitation associated with Alzheimer's dementia). Status checked as of October 2026.

Dextromethorphan-bupropion is a prescription medicine, not a psychotherapy. A prescriber decides on it, prescribes it and monitors it. A psychotherapist does not deliver it. This guide is for the psychotherapist working alongside the prescriber. General antidepressant collaboration (measurement-based care, adherence conversations, discontinuation concerns, class-wide suicidality warnings) is covered in 001 Antidepressants. This entry covers only what is specific to this combination. [source: FDA label 04/2026; Axsome 2022]

What it is: a single extended-release tablet that combines dextromethorphan and bupropion. The developer describes dextromethorphan as an NMDA receptor antagonist and a sigma-1 receptor agonist, thought to modulate glutamatergic signalling. Bupropion is an aminoketone antidepressant, and it also inhibits CYP2D6, the enzyme that mainly breaks down dextromethorphan. It therefore raises and prolongs dextromethorphan blood levels. The developer states that the exact antidepressant mechanism is unclear. The developer has called it the first oral NMDA receptor antagonist approved for MDD; that is the company's own claim. [source: Axsome press release, 19 Aug 2022]

How change is thought to happen: in labelling terms, the medicine is meant to reduce depressive symptoms (or, in the second indication, agitation) through the pharmacology above. The psychotherapist's work runs in parallel: psychological treatment of the depression, help with informed decisions, watching for the warning signs the labelling lists, and passing them on to the prescriber. [synthesis]

Indications (US): major depressive disorder in adults, approved August 2022. Agitation associated with dementia due to Alzheimer's disease, approved April 2026. Labelling states it is not indicated as an as-needed treatment for agitation. It is not approved for paediatric patients. [source: FDA label 04/2026; Axsome 8-K 30 Apr 2026; Healio 30 Apr 2026]

2. Framework

There are no psychotherapy "phases" belonging to this medicine. The framework below sets out the course of prescriber-led treatment as labelling describes it, and the psychotherapist's tasks at each stage. Session count and format follow whatever psychotherapy the client is already receiving. Nothing here changes that. [synthesis]

Who delivers it and regulatory status

  • United States: prescription-only. It is approved for MDD in adults (19 August 2022) and for agitation associated with dementia due to Alzheimer's disease (approval announced 30 April 2026). Neither component is a controlled substance. A boxed warning on suicidal thoughts and behaviours applies. [source: FDA label 04/2026; Axsome 2022; Axsome 8-K 2026]
  • Prescriber: a licensed prescriber within their scope of practice. Which professions may prescribe is set by state law and is not covered in the sources. [uncertain]
  • EU (EMA), UK (MHRA), Canada, Australia, Germany: none of the sources recorded a marketing authorisation. Clients outside the US should not assume it is available or licensed there. Check the national medicines regulator. [uncertain]
  • Professional guidelines: where guidelines such as CANMAT 2023 place this combination is not verified. [uncertain]
  • ATC code N06AX62. Developmental name AXS-05. Pivotal MDD trials were GEMINI (placebo-controlled) and ASCEND (versus bupropion). The dementia-agitation trials were ADVANCE-1 and ACCORD-2. [source: Axsome 2022; Healio 2026; Wikipedia, secondary]

Stage A: before a prescribing decision

  • Prescriber tasks per labelling: check the contraindications, which are seizure disorder; current or prior bulimia or anorexia nervosa; abrupt discontinuation of alcohol, benzodiazepines, barbiturates or antiepileptic drugs; use with an MAOI or within the labelled interval after one is stopped, including linezolid or intravenous methylene blue; and hypersensitivity. Also assess blood pressure, screen for bipolar disorder and its risk factors, and review all other medicines. [source: FDA label 04/2026]
  • Psychotherapist tasks: suggest a medical review when clinically indicated, share relevant history with consent (eating disorder, seizures, alcohol or sedative use, bipolar features), and support informed consent. [synthesis]
  • Move on when: the prescriber and client have made a decision. The therapist does not judge readiness to start. [synthesis]

Stage B: early treatment and any dose change

  • Labelling: monitor all patients for worsening and emergent suicidal thoughts and behaviours, especially early in therapy and at dose changes. Monitor blood pressure periodically. [source: FDA label 04/2026]
  • Psychotherapist tasks: closer review of mood and risk, a safety plan in place, a low threshold for contacting the prescriber, and side-effect check-ins. [synthesis]

Stage C: continuing treatment

  • Labelling: ongoing vigilance for the listed warnings (seizure, mania, psychosis, angle-closure glaucoma, dizziness and falls, serotonin syndrome, hyponatremia, hypersensitivity). [source: FDA label 04/2026; Medication Guide]
  • Psychotherapist tasks: continue the psychotherapy, monitor and route warning signs, hold adherence and ambivalence conversations, and watch for new medicines, including over-the-counter cough products. [synthesis]

Stage D: changes, stopping, pregnancy

  • The Medication Guide states that stopping suddenly may cause serious side effects. Labelling also lists situations in which the prescriber discontinues the medicine (seizure, symptomatic hyponatremia, serotonin syndrome, pregnancy, before linezolid or IV methylene blue). These are prescriber decisions. [source: Medication Guide; FDA label 04/2026]
  • Psychotherapist tasks: route every wish to change or stop to the prescriber, and keep the psychotherapy going through transitions. [synthesis]

3. Guiding principles

  • The prescriber owns the medicine. Never tell or imply that a client should start, stop, skip or change it. Every medication question goes to the prescriber or pharmacist. [synthesis]
  • Know the labelled warnings well enough to recognise them. Recognising signs and routing them is your role. Diagnosing or managing them is not. [synthesis]
  • Treat the early weeks and dose changes as higher-risk for suicidality. The boxed warning concerns young adults, but labelling says to monitor all patients. [source: FDA label 04/2026]
  • Treat seizure risk as a history-taking duty. Eating-disorder history, seizure history, and abrupt alcohol or sedative withdrawal are contraindications. Make sure the prescriber knows what the client tells you, with consent. [source: FDA label 04/2026; synthesis]
  • Remember that a familiar cough-medicine ingredient is a drug-interaction issue. Dextromethorphan is sold over the counter. Labelling asks patients to tell providers about other bupropion- or dextromethorphan-containing products. [source: FDA label 04/2026; Wikipedia, secondary]
  • Act on serotonin syndrome as an emergency. The Medication Guide directs patients to seek emergency care. [source: Medication Guide]
  • Get consent and share information on a need-to-know basis. Agree in advance what you will share with the prescriber, and when you may share without consent (imminent risk). [synthesis]
  • Keep psychotherapy as an active treatment in its own right. The medicine does not replace psychological work, and the psychological work does not depend on the medicine. [synthesis]
  • Name the limits of evidence and status. Use the company's claims (such as "first oral NMDA antagonist") only when attributed. Do not assume it is approved outside the US. [synthesis]
  • In dementia care, the client system includes caregivers. Non-drug approaches to agitation stay relevant. Labelling says the medicine is not for as-needed use. [source: FDA label 04/2026; synthesis]

4. Intervention inventory

Part A describes the treatment as official labelling presents it, at a descriptive level only, so that you recognise what clients report. It contains no dosing, schedules, or switching or stopping guidance. Those belong to the prescriber. Part B covers the psychotherapist's own interventions. For interventions common to all antidepressants, see 001 Antidepressants.

Part A. How the treatment is delivered (labelling, descriptive)

A1. Formulation and indications

  • Purpose: know what the client is taking and why.
  • Steps: the medicine is an oral extended-release (bilayer) tablet containing both components. It is labelled for adult MDD and for agitation associated with dementia due to Alzheimer's disease, not as an as-needed treatment. It is not approved for children. Dosing, timing and adjustments are set by the prescriber, and labelling requires adjustments for certain kidney or liver impairment, CYP2D6 status and interacting drugs. [source: FDA label 04/2026]
  • Example language (illustrative): "Your prescriber will go through how to take it. I'll keep track of how you're feeling and anything you notice, so you can take that back to them."
  • Watch for: a client who uses it for something it is not labelled for, or who shares it with a family member. Route both to the prescriber. [synthesis]

A2. Boxed warning: suicidal thoughts and behaviours

  • Purpose: the main safety warning for this medicine.
  • Steps: the boxed warning states that antidepressants increased the risk of suicidal thoughts and behaviours in paediatric and young adult patients in short-term studies, and that all patients should be monitored closely for clinical worsening and emergent suicidal thoughts and behaviours. Labelling places particular emphasis on the early period and on dose changes. The Medication Guide lists warning signs to report: new or worse depression, anxiety or panic attacks; agitation, restlessness, insomnia, irritability, anger or aggression; acting on dangerous impulses; extreme increases in activity or talking; other unusual changes in behaviour; and thoughts of suicide. [source: FDA label 04/2026; Medication Guide]
  • Example language (illustrative): "In the first weeks on a new antidepressant, I'll ask more often about how dark things get. That's routine, and it's in the official information too."
  • Watch for: any of the listed signs, especially new agitation or akathisia-like restlessness. Act as in B6 and B7.

A3. Seizure risk

  • Purpose: bupropion-related seizure risk is a defining feature of this medicine's labelling.
  • Steps: labelling describes a dose-related risk of seizure. It is contraindicated in people with a seizure disorder, current or prior bulimia or anorexia nervosa, or abrupt discontinuation of alcohol, benzodiazepines, barbiturates or antiepileptic drugs. Caution is needed with other drugs that lower the seizure threshold. The Medication Guide adds that risk is higher with certain medical conditions, certain other medicines and alcohol. Labelling states the medicine is discontinued and not restarted after a seizure. That is a prescriber decision, after emergency care. [source: FDA label 04/2026; Medication Guide]
  • Example language (illustrative): "Has your prescriber heard about the eating difficulties we've talked about? That history matters for this particular medicine, and they'd want to know."
  • Watch for: an undisclosed eating-disorder history, a client planning to stop drinking abruptly or come off sedatives, and new purging. Encourage disclosure to the prescriber, and share it yourself with consent. Call emergency services for a seizure in session.

A4. Serotonin syndrome and MAOIs

  • Purpose: recognise a potentially life-threatening interaction.
  • Steps: it is contraindicated with MAOIs (including within the labelled interval after one is stopped) and with linezolid or intravenous methylene blue. Labelling states that the risk of serotonin syndrome rises with other serotonergic drugs, for example SSRIs or tricyclics. The Medication Guide's warning signs are agitation, hallucinations, confusion, sweating, flushing, high body temperature, tremor or stiff muscles, fast heartbeat, loss of coordination, blood-pressure changes, seizures, dizziness, and nausea, vomiting or diarrhoea. It directs patients to seek emergency care right away. [source: FDA label 04/2026; Medication Guide]
  • Example language (illustrative): "Those symptoms together need checking now, not at our next session. Let's get you to urgent care, and I'll stay on the line while you call."
  • Watch for: a cluster of these signs, particularly after a new medicine or supplement. Treat it as an emergency. Do not wait to discuss it in session.

A5. Drug interactions as labelling states them

  • Purpose: know which categories make a client's other medicines relevant, so you can prompt a pharmacist or prescriber check.
  • Steps: labelling lists the following. Other serotonergic drugs (monitor for serotonin syndrome). Strong CYP2D6 inhibitors (the prescriber adjusts the regimen). Strong CYP2B6 inducers (avoid). CYP2D6 substrates, whose exposure may increase. Digoxin, whose levels may fall. Drugs that lower the seizure threshold. Dopaminergic drugs such as levodopa and amantadine (CNS toxicity reported). Alcohol (minimise or avoid). Labelling also notes false-positive urine amphetamine screens. Patients are asked to tell providers about all medicines, including other bupropion- or dextromethorphan-containing products. [source: FDA label 04/2026; Medication Guide]
  • Example language (illustrative): "Some cough and cold remedies contain one of the same ingredients. Before using any, it's worth asking the pharmacist whether it's OK with your prescription."
  • Watch for: self-medicating with over-the-counter cough products, new prescriptions from other doctors, and distress over a positive amphetamine drug screen at work or in court. A positive screen can be a labelled false positive. The client should ask the prescriber for documentation.

A6. Other labelled warnings

  • Purpose: recognise the remaining warning signs.
  • Steps: these are the remaining labelled warnings. Raised blood pressure, assessed before and during treatment. Mania or hypomania; labelling requires screening for bipolar disorder and notes the medicine is not approved for bipolar depression. Psychosis and other neuropsychiatric reactions (delusions, hallucinations, paranoia, confusion). Angle-closure glaucoma (eye pain, vision changes, eye swelling or redness). Dizziness, with fall precautions and caution driving or using machinery. Hyponatremia, a 2026 addition: early signs are headache, poor concentration, memory changes, confusion and weakness or unsteadiness, and severe signs are hallucinations, fainting, seizures and coma; risk is higher in older adults, people on diuretics and people who are volume-depleted. Embryo-fetal toxicity based on animal data, so it is not recommended in pregnancy. Breastfeeding is not recommended during treatment or for 5 days after the final dose. Allergic reactions can occur at any time. [source: FDA label 04/2026; Medication Guide]
  • Common adverse reactions (labelling): in MDD, dizziness, headache, diarrhoea, somnolence, dry mouth, sexual dysfunction and hyperhidrosis. In dementia agitation, dizziness and dyspepsia or stomach upset. [source: Axsome 2022; Medication Guide; Healio 2026]
  • Example language (illustrative): "You mentioned you've barely slept for three nights and feel unstoppable. That's something your prescriber needs to hear about today."
  • Watch for: hypomanic signs, new unusual beliefs, eye symptoms, falls, and confusion in older clients. Route as in B6.

A7. Misuse potential

  • Purpose: frame substance-use conversations accurately.
  • Steps: labelling states that neither component is a controlled substance and that dextromethorphan abuse has been reported, mainly in adolescents. Patients with a history of drug abuse should be observed for signs of misuse. Labelling notes that dextromethorphan overdose can cause toxic psychosis, stupor, coma and seizures, and that bupropion overdose can cause seizures, arrhythmias and death. An analysis of spontaneous reports to the FDA (FAERS) by Kwan and McIntyre (2024) found no significant misuse signal for the combination, against a signal for dextromethorphan alone. The authors note the limits of spontaneous-report data. [source: FDA label 04/2026; Kwan & McIntyre 2024]
  • Example language (illustrative): "Given your history with cough syrup, would you be OK with us both letting your prescriber know? It helps them plan safely."
  • Watch for: taking more than prescribed, combining with OTC dextromethorphan, and an overdose risk in a client at suicide risk. For the last, include medicine storage in lethal-means counselling (see B7).

A8. The dementia-agitation indication

  • Purpose: many therapists meet this through family caregivers.
  • Steps: it is labelled for agitation associated with dementia due to Alzheimer's disease, not for as-needed use. Approval rested on ADVANCE-1 (agitation scores at week 5) and ACCORD-2 (time to relapse). Common reactions were dizziness and dyspepsia. Fall risk and hyponatremia in older adults are labelled concerns. It has been described as the first non-antipsychotic approved for this use (Healio, Alzheimer's Association, as reported). [source: FDA label 04/2026; Healio 2026]
  • Example language (illustrative): "Alongside whatever the doctor decides about medication, we can look at what tends to set off the agitation and how you can look after yourself."
  • Watch for: falls, new confusion, and caregiver strain or burnout. Caregivers should report these to the prescribing team. [synthesis]

Part B. The psychotherapist's interventions

All of Part B is [synthesis] built on the labelling content above, unless a source is tagged. For generic antidepressant versions of B2, B4 and B9, see 001 Antidepressants.

B1. Recognising when to suggest a medical review

  • Purpose: get the right questions to the prescriber at the right time.
  • Steps: (1) Suggest a review when depression is not improving with psychotherapy alone, when the client asks about "new" or "fast-acting" antidepressants, or when any Part A warning sign appears. (2) Frame the suggestion as "discuss with your prescriber", never as "ask for this drug". (3) If the client has read advertising, help them write down their questions. (4) Note your suggestion in your records.
  • Example language (illustrative): "Whether this medicine or any other is right for you is a decision for you and your prescriber. What I can do is help you get your questions ready."
  • Watch for: pressure to endorse a product. The review is working if the client goes in with clear questions and an accurate history.

B2. Collaborative care and information sharing

  • Purpose: make sure safety-relevant information reaches the prescriber.
  • Steps: (1) Get written consent to contact the prescriber, and agree what will be shared. (2) Share the history that bears on contraindications (seizures, eating disorder, alcohol or sedative patterns, bipolar features, pregnancy plans) when the client agrees. (3) Agree an urgent route (who to call, when). (4) Explain that imminent risk overrides confidentiality under your professional code and local law.
  • Example language (illustrative): "Can we agree on what I'd pass on to Dr X, and how quickly, if I noticed something worrying?"
  • Watch for: a client who keeps parts of their history from the prescriber. Explore the reasons, and encourage disclosure.

B3. Psychoeducation about the labelling

  • Purpose: an informed client who recognises warning signs.
  • Steps: (1) Point the client to the Medication Guide that comes with the prescription, and go through the warning-sign headings together in plain words. (2) Highlight what is specific to this medicine: seizure contraindications, cough and cold products containing dextromethorphan, serotonin syndrome signs, dizziness and falls, alcohol, the amphetamine-screen false positive, and pregnancy and breastfeeding. (3) Give no dosing or timing advice; send those questions to the prescriber or pharmacist. [source: Medication Guide]
  • Example language (illustrative): "Let's look at the list of symptoms the leaflet says to report quickly, so you know which ones mean 'call today'."
  • Watch for: anxious over-monitoring. Balance it with the fact that most effects listed are uncommon, without minimising them.

B4. Supporting informed consent and shared decision-making

  • Purpose: the client makes an informed choice with their prescriber.
  • Steps: (1) Explore the client's values and preferences about medication, psychotherapy or both. (2) Help them draft questions, for example: Why this option for me? What should I report, and how? How does it interact with my other medicines and with alcohol? What about pregnancy plans? What happens if I want to stop? (3) Leave the decision with the client and prescriber. (4) Record the discussion.
  • Example language (illustrative): "What matters most to you in deciding? We can write that down so it's part of the conversation with your prescriber."
  • Watch for: the client deferring to you or to advertising. Hand the decision back to them.

B5. Conversations about adherence and ambivalence (never advising a change)

  • Purpose: bring the client's doubts to the prescriber rather than acting on them alone.
  • Steps: (1) Explore ambivalence with open questions and reflections. (2) Name that the Medication Guide says stopping suddenly may cause serious side effects, and that changes should go through the prescriber. [source: Medication Guide] (3) Help the client plan the conversation with the prescriber. (4) Do not express a view on whether to continue.
  • Example language (illustrative): "Part of you wants to stop, and part of you is worried about getting worse. That's an important thing to take to your prescriber, and soon, rather than deciding alone."
  • Watch for: secret stopping, skipping doses, or doubling up. Encourage prompt contact with the prescriber.

B6. Monitoring and passing on side effects and warning signs

  • Purpose: an early-warning partner to the prescriber.
  • Steps: (1) At sessions in the early weeks and after dose changes, run a brief structured check: mood, suicidal thinking, agitation, sleep, energy, unusual experiences, dizziness or falls, eye symptoms, new medicines or OTC products, and alcohol. (2) Sort what you find:
    • Emergency (call emergency services, or direct the client to the emergency department): seizure; serotonin syndrome cluster (A4); severe confusion, hallucinations, fainting; signs of a severe allergic reaction; sudden eye pain with vision change; suicidal intent with a plan or recent attempt; suspected overdose (poison centre and emergency care, per the Medication Guide).
    • Same day (contact the prescriber): emergent or worsening suicidal thoughts; new agitation or restlessness; manic or hypomanic signs; new paranoia or unusual beliefs; early hyponatremia signs in an older client; pregnancy.
    • Next routine contact: mild common effects (dry mouth, sweating, headache, sexual effects), mild dizziness without falls. (3) Document what you passed on and when. [source for the signs: FDA label 04/2026; Medication Guide; triage tiers: synthesis]
  • Example language (illustrative): "I'm going to ask a few quick routine questions about the medicine, the same ones each time, so nothing gets missed."
  • Watch for: attributing every symptom to the medicine. You are not diagnosing; you are passing on observations. It is working when warning signs reach the prescriber quickly.

B7. Crisis and safety planning

  • Purpose: manage the suicidality warning period.
  • Steps: (1) Do a standard suicide risk assessment at the start of treatment and at any change. (2) Write a collaborative safety plan: warning signs, coping steps, people and places, professional and crisis contacts, and an agreed route to the prescriber. (3) Include lethal-means counselling. Since overdose of both components is labelled as dangerous, discuss safe storage of medicines, including OTC cough products, and having a trusted person hold supplies when risk is raised. [source: FDA label 04/2026 for overdose toxicity] (4) Increase contact frequency in the early weeks if risk warrants.
  • Example language (illustrative): "Let's add to your plan where your medicines are kept and who could look after them if things get harder."
  • Watch for: rapid activation alongside persistent hopelessness. Escalate.

B8. Alcohol, sedatives and eating-disorder history

  • Purpose: labelling contraindications that therapists often learn about first.
  • Steps: (1) Ask about current drinking and use of benzodiazepines or sleeping medicines. (2) If a client plans to quit alcohol or sedatives, explain that labelling lists abrupt discontinuation as a contraindication. Encourage them to discuss any withdrawal plan with the prescriber first, so withdrawal is medically supervised. Never advise cutting down or stopping on a particular schedule. (3) Ask directly about current or past bulimia or anorexia, including purging. If present, encourage disclosure to the prescriber. [source: FDA label 04/2026; Medication Guide]
  • Example language (illustrative): "It's great that you want to stop drinking. Because of this medicine, the safest first step is talking to your prescriber about how to do it."
  • Watch for: shame-driven non-disclosure, and binge-drinking patterns.

B9. Integrating psychotherapy before, during and after

  • Purpose: keep psychological treatment central.
  • Steps: (1) Before: continue your evidence-based psychotherapy. Medication decisions do not pause it. (2) During: expect symptom change to vary, and use measurement-based monitoring as in 001. Help the client tell medicine effects apart from what they have achieved themselves. (3) After any stop or switch decided with the prescriber: keep sessions going through the transition, watch for return of symptoms, and work on relapse prevention.
  • Example language (illustrative): "Whatever happens with the medicine, the skills you're building here are yours."
  • Watch for: crediting every gain to the pill, or blaming every setback on it.

B10. Working with caregivers (dementia-agitation indication)

  • Purpose: support families when the medicine is used for agitation in Alzheimer's dementia.
  • Steps: (1) Offer caregiver support, assessment of burden, and psychoeducation on behavioural triggers. (2) Help caregivers log agitation episodes, falls, dizziness and confusion, to share with the prescribing team. (3) Reinforce that it is not for as-needed use, so caregivers do not add extra doses during episodes. Questions go to the prescriber. [source: FDA label 04/2026] (4) Address caregiver grief and stress.
  • Example language (illustrative): "Keeping a simple diary of what happens before the agitation, and any falls, gives the doctor really useful information."
  • Watch for: caregiver exhaustion, safety at home, and falls.

B11. Support after treatment ends

  • Purpose: continuity once the medicine is stopped by the prescriber.
  • Steps: (1) Increase session frequency or check-ins around a prescriber-led stop. (2) Review the relapse signature and the safety plan. (3) Report any reaction the client attributes to stopping to the prescriber. (4) Plan follow-up.
  • Example language (illustrative): "Let's agree what early signs would make us call your prescriber, and keep that list handy."
  • Watch for: return of depressive symptoms or suicidality. Route promptly.

5. Handling problems

The labelling does not address psychotherapy, so all of the guidance in this section is [synthesis]. Only the labelled facts it relies on are cited.

  • Client asks you whether to start, stop or change the medicine. Say plainly that this is outside your role. Explore what lies behind the question, and help the client prepare to raise it with the prescriber. Offer to contact the prescriber, with consent. (illustrative) "I can't advise on that, but I can help you make sure your prescriber hears exactly what's worrying you."
  • Client has stopped or is skipping doses without telling the prescriber. Avoid shaming. Name that the Medication Guide warns sudden stopping may cause serious side effects [source: Medication Guide]. Encourage same-day contact with the prescriber or pharmacist, and check risk.
  • Stuck: depression not improving. Review the psychotherapy itself (formulation, dose of therapy, fit), use outcome measures, and with consent share progress data with the prescriber. Do not suggest medication changes.
  • Early activation or worsening suicidality. Do a risk assessment the same day, contact the prescriber, update the safety plan, and use crisis services if risk is imminent. Labelling emphasises the early weeks and dose changes [source: FDA label 04/2026].
  • Possible hypomania. Contact the prescriber the same day. Labelling notes the medicine is not approved for bipolar depression and that screening for bipolar disorder is required [source: FDA label 04/2026]. Share any family history of bipolar disorder you know of.
  • Client using OTC cough products, or misusing dextromethorphan. Use motivational, non-judgemental exploration. Encourage disclosure to the prescriber. Include medicine storage in safety planning. Consider substance-use referral.
  • Positive amphetamine drug screen. Explain that labelling lists false-positive urine amphetamine screens [source: FDA label 04/2026], and direct the client to the prescriber for documentation and confirmatory testing. Help with any related distress at work or in legal settings.
  • Client wants to quit alcohol or come off sleeping pills right away. Support the goal, and route the withdrawal plan through the prescriber first, because abrupt discontinuation is a labelled contraindication [source: FDA label 04/2026].
  • Undisclosed eating-disorder history. Explore shame and fears. Explain that it matters for this medicine's safety. Agree on disclosure to the prescriber.
  • Overwhelm from reading the warnings. Go through the Medication Guide headings together, separate "emergency" from "routine" signs (B6), and use grounding skills if needed.
  • Rupture: the client feels you are "anti-medication" or "pushing pills". Name your neutral role, repair, and re-agree the boundary (you support decisions made with the prescriber, and you hold no preference).
  • Prescriber is hard to reach. Use the pharmacist for medicine questions, out-of-hours medical services for same-day concerns, and emergency services for emergencies. Document your attempts.
  • Pregnancy or planning pregnancy. Labelling says it is not recommended in pregnancy and that the prescriber discontinues it if pregnancy occurs, with alternatives for those planning pregnancy [source: FDA label 04/2026]. Route to the prescriber promptly. Do not advise stopping. Offer emotional support.
  • Client outside the US asking about obtaining it. None of the sources recorded a non-US authorisation [uncertain]. Discourage online purchase from unregulated sources, and direct the client to their own prescriber.
  • Caregiver of a person with dementia overwhelmed, or giving the medicine for "bad days". Offer caregiver support, restate that labelling says it is not for as-needed use [source: FDA label 04/2026], and route to the prescribing team. Assess falls and home safety.

Sources

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