Centrally acting sympathomimetics
Brand names: Atomoxetina Cinfa, Strattera, Atomoxetina Tecnimede, Atamax
Updated · Methodology
Second line
Second-line ADHD therapy in children over 6, adolescents, and adults after stimulant failure or intolerance (methylphenidate, lisdexamfetamine) per 2018, 2019, and Spanish SEPP 2022. Starting dose 0.5 mg/kg once daily, increased to 1.2 mg/kg (max 100 mg/day) after 7–14 days. Full effect at 4–6 weeks. Particularly effective in patients with comorbid anxiety or tics (stimulants exacerbate them).
Sources
ICD-10: F90.0 · ICD-11: 6A05
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Atomoxetine is a selective norepinephrine reuptake inhibitor. It is prescribed only for attention-deficit/hyperactivity disorder (ADHD) in children over 6 and adults ( 2019 and AAFP 2020 guidelines). Healthy students and knowledge workers take atomoxetine as a cognitive stimulant outside an ADHD indication. No clinical studies in healthy adults exist; an effect on cognition in people without ADHD has not been confirmed. The drug has specific risks: boxed warning for suicidal thoughts in children and adolescents, hepatotoxicity with risk of acute liver injury, and elevated blood pressure and heart rate. If atomoxetine is being taken for concentration outside an ADHD indication, consider seeking a second opinion.
Selective norepinephrine reuptake inhibitor (NRI). Unlike methylphenidate and amphetamines, it does not affect striatal dopamine transporters and does not induce euphoria – not a controlled substance, low abuse potential. Raises norepinephrine and dopamine in the prefrontal cortex, improving attention, impulse control, and working memory. Metabolized by CYP2D6 – in poor metabolizers (7–10% of Europeans, 1–2% of Asians) levels are 5-10-fold higher.
Boxed warning
FDA boxed warning 2005: increased suicidal ideation in children and adolescents. Mood and behavior monitoring in the first weeks of therapy, parental education.
AEMPS summary of product characteristics (section 4.6): animal studies in general do not suggest direct harmful effects on pregnancy, embryo-fetal development, delivery or postnatal development. Clinical data on atomoxetine exposure in pregnancy are limited and not enough to show whether or not it is associated with adverse pregnancy outcomes. Atomoxetine is used during pregnancy only if the potential benefit justifies the possible risk to the fetus.
Limited milk excretion data. If therapy is required, discuss switching to non-pharmacological management.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
3 pairs found. Sorted from critical to minor.
Mechanism
Escitalopram prolongs the QT interval in a dose-dependent way (escitalopram summary of product characteristics, SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS). According to its own SmPC, atomoxetine can also prolong QT, which is listed among its adverse reactions. In a dedicated study, the corrected QT interval (QTc) rose slightly as atomoxetine concentrations increased, although at the expected peak concentrations it did not differ from placebo (atomoxetine SmPC, AEMPS). The liver breaks down atomoxetine through the enzyme CYP2D6, which escitalopram inhibits. Escitalopram doubled the plasma concentrations of desipramine and metoprolol, two other substrates of this enzyme (SmPCs of both drugs, AEMPS). With the strong CYP2D6 inhibitors fluoxetine and paroxetine, atomoxetine exposure rose 6- to 8-fold. The US Food and Drug Administration () describes the effect of escitalopram on this enzyme as modest, and no study has tested this exact pair (atomoxetine and escitalopram FDA labels). The atomoxetine SmPC reports serotonin syndrome when atomoxetine was combined with selective serotonin reuptake inhibitors, the group escitalopram belongs to (atomoxetine SmPC, AEMPS).
Symptoms
QT interval prolongation itself causes no symptoms and shows only on the electrocardiogram (ECG). Torsade de pointes, a form of ventricular tachycardia, causes palpitations, dizziness and fainting. With escitalopram, such arrhythmias were reported mainly in women and in people with low potassium, a pre-existing long QT interval or other heart disease (escitalopram summary of product characteristics, SmPC). Higher atomoxetine concentrations raise the risk of its adverse reactions, with larger rises in heart rate and blood pressure (atomoxetine label, US Food and Drug Administration, ). Serotonin syndrome presents with agitation, tremor, muscle jerks and fever (escitalopram SmPC).
Management
The combination is contraindicated. The escitalopram summary of product characteristics (SmPC) forbids its use with other drugs that prolong the QT interval (escitalopram SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS). According to its own SmPC, atomoxetine can prolong QT (atomoxetine SmPC, AEMPS). The US Food and Drug Administration () labels are softer: they carry no QT contraindication and ask for caution when escitalopram is combined with drugs broken down by the enzyme CYP2D6 (escitalopram FDA label). Escitalopram is also contraindicated in people with a history of QT prolongation or congenital long QT syndrome (escitalopram SmPC, AEMPS). If both drugs are still taken, correct low potassium and magnesium before starting escitalopram. In stable heart disease, consider an electrocardiogram (ECG) before the start. If signs of arrhythmia appear, stop escitalopram and record an ECG (escitalopram SmPC, AEMPS). With CYP2D6 inhibitors, atomoxetine may need a slower titration and a lower final dose. If an inhibitor is started or stopped after the atomoxetine dose has been set, reassess response and tolerability (atomoxetine SmPC, AEMPS). Measure pulse and blood pressure before starting atomoxetine, after each dose change and at least every 6 months (atomoxetine SmPC, AEMPS). If serotonin syndrome appears, stop escitalopram and the serotonergic drug at once and start symptomatic treatment (escitalopram SmPC, AEMPS). In this case, the atomoxetine SmPC advises reducing the atomoxetine dose or stopping it, depending on severity (atomoxetine SmPC, AEMPS).
Sources
Mechanism
Both can lengthen the QT interval and the effect adds up. The atomoxetine label asks for caution in patients with congenital or acquired long QT and with a family history. The levofloxacin label warns that fluoroquinolones should be used with caution where QT prolongation risk factors exist, and explicitly mentions concomitant use of QT-prolonging medicines.
Symptoms
Palpitations, dizziness, a feeling of impending faint or syncope. The serious long-QT arrhythmia, torsade de pointes, can present directly with loss of consciousness. Hypokalaemia and hypomagnesaemia, common with vomiting or diarrhoea, increase the risk.
Management
For a common infection, an antibiotic without QT effect avoids the problem; levofloxacin is reserved for when there is no alternative. If the pair is necessary, correct potassium and magnesium before starting and consider an ECG in patients with heart disease, a family history of sudden death or other QT-prolonging drugs.
Sources
Mechanism
Methylphenidate blocks the reuptake of noradrenaline and dopamine (methylphenidate summary of product characteristics, SmPC, Spanish Agency of Medicines and Medical Devices, AEMPS). Atomoxetine selectively blocks the noradrenaline transporter (atomoxetine SmPC, AEMPS). Both drugs raise blood pressure and heart rate, so the SmPCs of both ask for caution with other drugs that raise blood pressure. The atomoxetine SmPC also warns of possible synergistic or additive effects with drugs that act on noradrenaline (SmPCs of both drugs, AEMPS). In a study, giving atomoxetine with methylphenidate did not increase cardiovascular effects beyond those seen with methylphenidate alone (atomoxetine label, US Food and Drug Administration, ). No pharmacokinetic interaction is expected. Cytochrome P450 (CYP) enzymes play no clinically relevant part in methylphenidate metabolism, and methylphenidate does not inhibit them to a relevant extent (methylphenidate SmPC, AEMPS). Atomoxetine causes no clinically important inhibition or induction of the main CYP enzymes (atomoxetine FDA label).
Symptoms
In most people, heart rate and blood pressure rise moderately. With central nervous system stimulants, including methylphenidate, blood pressure rises by about 2–4 mm Hg and heart rate by about 3–6 beats per minute on average (methylphenidate label, US Food and Drug Administration, ). With atomoxetine, heart rate rises on average by less than 10 beats per minute and blood pressure by less than 5 mm Hg (atomoxetine summary of product characteristics, SmPC). Some people have larger rises. With atomoxetine, 8–12% of children and adolescents and 6–10% of adults had heart rate increases of 20 beats per minute or more and blood pressure increases of 15–20 mm Hg or more (atomoxetine SmPC). Palpitations, chest pain on exertion, unexplained fainting and shortness of breath can point to heart disease (atomoxetine SmPC).
Management
Use the combination with caution. The summaries of product characteristics (SmPCs) of both drugs ask for caution with other drugs that raise blood pressure. The atomoxetine SmPC also asks for caution with drugs that act on noradrenaline (methylphenidate and atomoxetine SmPCs, Spanish Agency of Medicines and Medical Devices, AEMPS). In a study, atomoxetine did not add to the cardiovascular effects of methylphenidate, and the documents set no dose adjustment for this pair (atomoxetine label, US Food and Drug Administration, ). Before starting each drug, take a detailed history and examine the patient to look for heart disease (SmPCs of both drugs, AEMPS). Record pulse and blood pressure before treatment, after each dose change and then at least every 6 months (SmPCs of both drugs, AEMPS). If blood pressure rises markedly, review the atomoxetine treatment or the other drug that raises blood pressure (atomoxetine SmPC, AEMPS). Stop methylphenidate in case of recurrent tachycardia, arrhythmia or systolic blood pressure above the 95th percentile, and consider referral to a cardiologist (methylphenidate SmPC, AEMPS). If palpitations, chest pain on exertion, unexplained fainting or shortness of breath occur, refer the patient promptly to a cardiologist (atomoxetine SmPC, AEMPS). Both SmPCs count a concomitant drug that raises blood pressure as a risk factor for cerebrovascular events, so check for neurological signs and symptoms at every visit (SmPCs of both drugs, AEMPS).
Sources
Verbatim lines from the interaction sections, in the language of the label
«Atomoxetina no se debe utilizar en combinación con inhibidores de la monoaminoxidasa (IMAOs). Atomoxetina no se debe utilizar, como mínimo, en las 2 semanas siguientes a la interrupción del…»AEMPS, section 4.3 · Open on CIMA
«CONTRAINDICATIONS: Atomoxetine capsules use within 2 weeks after discontinuing MAOI or other drugs that affect brain monoamine concentrations. (4.2 , 7.1)»FDA, section 4 · Open on DailyMed
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de aparición de convulsiones con atomoxetina. Se deberá tener precaución en aquellos pacientes que estén tratados con medicamentos que…»AEMPS, section 4.5 · Open on CIMA
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de aparición de convulsiones con atomoxetina. Se deberá tener precaución en aquellos pacientes que estén tratados con medicamentos que…»AEMPS, section 4.5 · Open on CIMA
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de aparición de convulsiones con atomoxetina. Se deberá tener precaución en aquellos pacientes que estén tratados con medicamentos que…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: CYP2D6 Inhibitors – Concomitant use may increase atomoxetine steady-state plasma concentrations in EMs. (7.2)»FDA, section 7 · Open on DailyMed
«En los pacientes que reciban estos medicamentos, la exposición a atomoxetina puede ser de 6 a 8 veces mayor y la Css max de 3 a 4 veces mayor, porque se metaboliza por la vía de CYP2D6. Puede ser…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos serotoninérgicos: Atomoxetina debe utilizarse con precaución en combinación con medicamentos serotoninérgicos, inhibidores selectivos de la recaptación de serotonina (ISRS), inhibidores…»AEMPS, section 4.5 · Open on CIMA
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de prolongación del intervalo QT cuando atomoxetina se administra con otros medicamentos que prolongan el intervalo QT (como…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos serotoninérgicos: Atomoxetina debe utilizarse con precaución en combinación con medicamentos serotoninérgicos, inhibidores selectivos de la recaptación de serotonina (ISRS), inhibidores…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos que actúan sobre la noradrenalina: Los medicamentos que actúen sobre la noradrenalina deben utilizarse con precaución cuando se administren conjuntamente con atomoxetina, puesto que…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos serotoninérgicos: Atomoxetina debe utilizarse con precaución en combinación con medicamentos serotoninérgicos, inhibidores selectivos de la recaptación de serotonina (ISRS), inhibidores…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos que actúan sobre la noradrenalina: Los medicamentos que actúen sobre la noradrenalina deben utilizarse con precaución cuando se administren conjuntamente con atomoxetina, puesto que…»AEMPS, section 4.5 · Open on CIMA
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de aparición de convulsiones con atomoxetina. Se deberá tener precaución en aquellos pacientes que estén tratados con medicamentos que…»AEMPS, section 4.5 · Open on CIMA
«Síndrome serotoninérgico: Se ha notificado síndrome serotoninérgico tras el uso concomitante de atomoxetina con otros medicamentos serotoninérgicos (por ejemplo, inhibidores de la recaptación de…»AEMPS, section 4.4 · Open on CIMA
«Medicamentos que actúan sobre la noradrenalina: Los medicamentos que actúen sobre la noradrenalina deben utilizarse con precaución cuando se administren conjuntamente con atomoxetina, puesto que…»AEMPS, section 4.5 · Open on CIMA
«Methylphenidate: Coadministration of methylphenidate with atomoxetine did not increase cardiovascular effects beyond those seen with methylphenidate alone.»FDA, section 7 · Open on DailyMed
«Medicamentos con elevada unión a las proteínas plasmáticas: Se llevaron a cabo estudios in vitro de desplazamiento de medicamentos con atomoxetina y otros fármacos que se unen en gran proporción a…»AEMPS, section 4.5 · Open on CIMA
«Drugs Highly Bound to Plasma Protein: In vitro drug-displacement studies were conducted with atomoxetine and other highly-bound drugs at therapeutic concentrations. Atomoxetine did not affect the…»FDA, section 7 · Open on DailyMed
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de prolongación del intervalo QT cuando atomoxetina se administra con otros medicamentos que prolongan el intervalo QT (como…»AEMPS, section 4.5 · Open on CIMA
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de prolongación del intervalo QT cuando atomoxetina se administra con otros medicamentos que prolongan el intervalo QT (como…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos con elevada unión a las proteínas plasmáticas: Se llevaron a cabo estudios in vitro de desplazamiento de medicamentos con atomoxetina y otros fármacos que se unen en gran proporción a…»AEMPS, section 4.5 · Open on CIMA
«Drugs Highly Bound to Plasma Protein: In vitro drug-displacement studies were conducted with atomoxetine and other highly-bound drugs at therapeutic concentrations. Atomoxetine did not affect the…»FDA, section 7 · Open on DailyMed
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de prolongación del intervalo QT cuando atomoxetina se administra con otros medicamentos que prolongan el intervalo QT (como…»AEMPS, section 4.5 · Open on CIMA
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de prolongación del intervalo QT cuando atomoxetina se administra con otros medicamentos que prolongan el intervalo QT (como…»AEMPS, section 4.5 · Open on CIMA
«Alcohol: Consumption of ethanol with atomoxetine did not change the intoxicating effects of ethanol.»FDA, section 7 · Open on DailyMed
«Inhibidores CYP2D6 (ISRS (p. ej. fluoxetina, paroxetina), quinidina, terbinafina)»AEMPS, section 4.5 · Open on CIMA
«Effect of CYP2D6 Inhibitors on Atomoxetine: In extensive metabolizers (EMs), inhibitors of CYP2D6 (e.g., paroxetine, fluoxetine, and quinidine) increase atomoxetine steady-state plasma concentrations…»FDA, section 7 · Open on DailyMed
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de prolongación del intervalo QT cuando atomoxetina se administra con otros medicamentos que prolongan el intervalo QT (como…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos que actúan sobre el pH gástrico: Los medicamentos que elevan el pH gástrico (hidróxido de magnesio/AEMPS, section 4.5 · Open on CIMA
«Drugs that Affect Gastric pH: Drugs that elevate gastric pH (magnesium hydroxide/FDA, section 7 · Open on DailyMed
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de prolongación del intervalo QT cuando atomoxetina se administra con otros medicamentos que prolongan el intervalo QT (como…»AEMPS, section 4.5 · Open on CIMA
«Salbutamol (u otros agonistas beta2): Existe un riesgo potencial de prolongación del intervalo QT cuando atomoxetina se administra con otros medicamentos que prolongan el intervalo QT (como…»AEMPS, section 4.5 · Open on CIMA
«Medicamentos que actúan sobre el pH gástrico: Los medicamentos que elevan el pH gástrico (hidróxido de magnesio/AEMPS, section 4.5 · Open on CIMA
«Drugs that Affect Gastric pH: Drugs that elevate gastric pH (magnesium hydroxide/FDA, section 7 · Open on DailyMed
«Inhibidores CYP2D6 (ISRS (p. ej. fluoxetina, paroxetina), quinidina, terbinafina)»AEMPS, section 4.5 · Open on CIMA
«Effect of CYP2D6 Inhibitors on Atomoxetine: In extensive metabolizers (EMs), inhibitors of CYP2D6 (e.g., paroxetine, fluoxetine, and quinidine) increase atomoxetine steady-state plasma concentrations…»FDA, section 7 · Open on DailyMed
«Otros medicamentos metabolizados por CYP2D6 : Fluoxetina es un potente inhibidor de la enzima CYP2D6, por lo que los tratamientos concomitantes con medicamentos que sean también metabolizados por…»AEMPS, section 4.5 · Open on CIMA
«Inhibición del isoenzima CYP2D6: Como con otros antidepresivos, entre los que se encuentran otros inhibidores selectivos de la recaptación de serotonina (ISRS), paroxetina inhibe el isoenzima CYP2D6…»AEMPS, section 4.5 · Open on CIMA
«DRUG INTERACTIONS: Clinical Impact: In vitro studies indicate that celecoxib, although not a substrate, is an inhibitor of CYP2D6. Therefore, there is a potential for an in vivo drug interaction with…»FDA, section 7 · Open on DailyMed
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Atomoxetine is evaluated for the following indications with varying evidence strength: ADHD (evidence tier A), Memory and concentration enhancement (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Atomoxetine (≥ 1 in 100): Decreased appetite, Nausea, Abdominal pain, Dry mouth, Fatigue, Decreased libido in adults. See the Safety section for uncommon and serious reactions.
AEMPS summary of product characteristics (section 4.6): animal studies in general do not suggest direct harmful effects on pregnancy, embryo-fetal development, delivery or postnatal development. Clinical data on atomoxetine exposure in pregnancy are limited and not enough to show whether or not it is associated with adverse pregnancy outcomes. Atomoxetine is used during pregnancy only if the potential benefit justifies the possible risk to the fetus.
Limited milk excretion data. If therapy is required, discuss switching to non-pharmacological management.
Atomoxetine is contraindicated in: Hypersensitivity; Closed-angle glaucoma; Pheochromocytoma; MAO inhibitor combination; Severe cardiovascular disease (CAD, severe HF, severe arrhythmias). Full list in the Safety section.
FDA boxed warning 2005: increased suicidal ideation in children and adolescents. Mood and behavior monitoring in the first weeks of therapy, parental education.
Direct links to regulator labels. Open in a new tab.
Bupropion, Caffeine, Choline bitartrate, Citalopram, Duloxetine, Hypericum perforatum, Phenelzine, Sertraline