What to Know About Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs)

Table of ContentsView AllTable of ContentsHow They WorkUsesTypesSide EffectsWarnings and InteractionsNDRI InteractionsGetting Help for Depression

Table of ContentsView All

View All

Table of Contents

How They Work

Uses

Types

Side Effects

Warnings and Interactions

NDRI Interactions

Getting Help for Depression

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Norepinephrine-dopamine reuptake inhibitors(NDRIs) are a class of drugs used primarily for thetreatment of depression. They are also used to treat attention-deficit hyperactivity disorder (ADHD), narcolepsy, and Parkinson’s disease. NDRIs are a newer class of antidepressants and tend to have fewer side effects than other common antidepressant drugs.

What is the most important information I should know about NDRIs?NDRIs can raise your blood pressure.You can develop a dependence on these drugs, leading to withdrawal symptoms upon stopping the medications.NDRIs can interact with other drugs, including MAOIs and antipsychotic medicines.

What is the most important information I should know about NDRIs?

NDRIs can raise your blood pressure.You can develop a dependence on these drugs, leading to withdrawal symptoms upon stopping the medications.NDRIs can interact with other drugs, including MAOIs and antipsychotic medicines.

How NDRIs Work

Norepinephrine is involved in the body’sfight-or-flight response, while dopamine is associated with the reward system. Low levels of these neurotransmitters may contribute to problems with mood and energy, so blocking their reuptake makes more of them available in the brain.

How Reuptake Inhibitor Drugs Work

Uses for NDRIs

NDRIs are typically prescribed whenother forms of antidepressantsdon’t produce effective results or cause bothersome side effects. They are used to treat the following conditions:

Approved Indications vs. Off-Label UseBupropion is FDA-approved for major depressive disorder in adults, seasonal affective disorder, narcolepsy, and smoking cessation. However, it is also sometimes used off-label for other conditions, including ADHD, depression in bipolar disorder, obesity, and sexual dysfunction linked to antidepressant use.

Approved Indications vs. Off-Label Use

Bupropion is FDA-approved for major depressive disorder in adults, seasonal affective disorder, narcolepsy, and smoking cessation. However, it is also sometimes used off-label for other conditions, including ADHD, depression in bipolar disorder, obesity, and sexual dysfunction linked to antidepressant use.

Types of NDRIs

There are currently three main types of NDRIs approved for use in the United States.

Bupropion

Wellbutrin is primarily used to treatmajor depressive disorder. It’s also commonly used off-label to treat ADHD. In 1997, the FDA approved Zyban for use as a smoking cessation aid,to help people with nicotine dependencequit smoking.

A 2016 review on the effectiveness of bupropion as a treatment for depression, found that the medication was highly effective in treating depression symptoms both when used on its own or alongside other depression treatments.Wellbutrin is often used together with an SSRI for treating depression.

Dexmethylphenidate

Dexmethylphenidateis typically used for the treatment of ADHD. It is also sometimes used off-label to help treat certain forms of depression.

A review of several different studies concluded that dexmethylphenidate is effective for treating ADHD in children and adolescents.The review also noted that these drugs are typically well tolerated.

The brand name version of dexmethylphenidate is Focalin. It’s essential to know that Focalin can be habit-forming. So, you shouldn’t take it for longer than prescribed or take more quantities than your prescription advises.

Tell your healthcare provider if you’ve had adependence on drugs or alcoholin the past as patients with this history should be cautious about taking Focalin.

Methylphenidate

Methylphenidate helps to increase the attention span and reduce symptoms of hyperactivity and impulsivity in people with this condition. It is typically used alongside other treatment options, such asbehavior therapy, when used to treat ADHD.

Other NDRIs that are sometimes prescribed, though less frequently than those mentioned above, include:Survector (amineptine)Cleofil (difemetorex)Glucoenergan (fencamfamine)Phenotropil (phenylpiracetam)Catovit (prolintane)

Other NDRIs that are sometimes prescribed, though less frequently than those mentioned above, include:

Side Effects of NDRIs

Norepinephrine-dopamine reuptake inhibitors are sometimes a preferred treatment for depression because they have fewer side effects that are common to other antidepressants, such as those related to sexual dysfunction.

However, NDRIs can cause some side effects that are mostly mild and tend to dissipate within a few weeks of use. Among the potential side effects of NDRIs are:

In rare cases, you might experience more serious side effects when taking NDRIs, such as high blood pressure, vision loss, seizures, and tremors. It’s also possible to experiencesuicidal thoughtswhen taking these types of drugs.

If you are having suicidal thoughts, contact theNational Suicide Prevention Lifelineat988for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.For more mental health resources, see ourNational Helpline Database.

If you are having suicidal thoughts, contact theNational Suicide Prevention Lifelineat988for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.

For more mental health resources, see ourNational Helpline Database.

NDRI Warnings

It’s essential to keep an eye on your blood pressure when using this type of medication, as it might sometimes cause high blood pressure.

Prolonged use of NDRIs can also cause a dependency on the drug, making it difficult for you to stop its use.

If you develop a dependency on NDRIs, your doctor may stop their use or reduce your dosage. When you stop using an NDRI after a dependency has developed, you might experience withdrawal symptoms such as headaches, anxiety, insomnia, tiredness, nausea, and vomiting.

Certain medications can interact with NDRIs. It is important to tell your doctor about any medications, supplements, vitamins, herbal remedies, or other substances that you are currently taking. Drug interactions can affect how well your medications work or lead to side effects.

Using an NDRI while takingmonoamine oxidase inhibitors(MAOIs) is strongly cautioned against. In some cases, combining these two medications can causeserotonin syndrome,a potentially life-threatening condition. Using antipsychotic medications with NDRIs could also increase your risk of seizures.

Other substances that may interact with NDRIs include:

NDRI OverdoseIt is possible to overdose on NDRIs.Symptoms of overdoseinclude seizures, hallucinations, heart failure, and loss of consciousness. If you suspect that you or a person close to you has overdosed on an NDRI, go to the emergency room immediately or call911.911

NDRI Overdose

It is possible to overdose on NDRIs.Symptoms of overdoseinclude seizures, hallucinations, heart failure, and loss of consciousness. If you suspect that you or a person close to you has overdosed on an NDRI, go to the emergency room immediately or call911.

911

Coping with depression can be hard, but talking to your doctor about your symptoms is an important first step. Antidepressant medications such as NDRIs can be an important part of your overall treatment plan.

Your doctor may recommend medication as well as other changes, such as psychotherapy and lifestyle modifications. Cognitive behavioral therapy (CBT), interpersonal therapy (IPT), and dialectical behavior therapy (DBT) are a few effective approaches.

Lifestyle changes, such as eating a healthy diet, getting regular exercise, and findingsocial support, can help you cope and may improve your symptoms.

The Best Online Therapy Services for Depression We Tried and Tested

16 SourcesVerywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Wang P, Yan F, Dong J, et al.A multiple-step screening protocol to identify norepinephrine and dopamine reuptake inhibitors for depression.Phys Chem Chem Phys. 2023;25:8341-8354. doi:10.1039/D2CP05676CLiu Y, Zhao J, Guo W.Emotional roles of mono-aminergic neurotransmitters in major depressive disorder and anxiety disorders.Front Psychol. 2019;9:2201. doi:10.3389/fpsyg.2018.02201American Psychological Association.Depression treatments for adults.Wang P, Fu T, Zhang X, et al.Differentiating physicochemical properties between NDRIs and sNRIs clinically important for the treatment of ADHD.Biochim Biophys Acta Gen Subj. 2017;1861(11 Pt A):2766-2777. doi:10.1016/j.bbagen.2017.07.022Kaufman MB.Pharmaceutical approval update.P T. 2019;44(6):337-339.Chikatimalla R, Dasaradhan T, Koneti J, Cherukuri SP, Kalluru R, Gadde S.Depression in Parkinson’s disease: A narrative review.Cureus. 2022;14(8):e27750. doi:10.7759/cureus.27750Fasipe OJ.Neuropharmacological classification of antidepressant agents based on their mechanisms of action.Arch Med Health Sci. 2018;6(1):81-94. doi:10.4103/amhs.amhs_7_18Clark A, Tate B, Urban B, et al.Bupropion mediated effects on depression, attention deficit hyperactivity disorder, and smoking cessation.Health Psychol Res. 2023;11:81043. doi:10.52965/001c.81043U.S. Food & Drug Administration.Drug approval package: Zyban.Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK.Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant.Therap Adv Psychopharmacol. 2016;6(2):99-144. doi:10.1177/2045125316629071Maneeton N, Maneeton B, Woottiluk P, et al.Comparative efficacy, acceptability, and tolerability of dexmethylphenidate versus placebo in child and adolescent ADHD: a meta-analysis of randomized controlled trials.Neuropsychiatric Dis Treat. 2015;11:2943-2952. doi:10.2147/NDT.S91765U.S. Food & Drug Administration.Focalin XR label.U.S. Food and Drug Administration.FDA updating warnings to improve safe use of prescription stimulants used to treat ADHD and other conditions.Evans EA, Sullivan MA.Abuse and misuse of antidepressants.Subst Abuse Rehabil. 2014;5:107-120. doi:10.2147/SAR.S37917Moss M, Hendrickson RG.Serotonin toxicity: Associated agents and clinical characteristics.J Clin Psychopharmacol. 2019;39(6):628-633. doi:10.1097/JCP.0000000000001121Sathe AR, Thiemann A, Toulouie S, Durant E.A 19-year-old woman with a history of depression and fatal cardiorespiratory failure following an overdose of prescribed bupropion.Am J Case Rep. 2021;22:e931783-1—e931783-5. doi:10.12659/AJCR.931783

16 Sources

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Wang P, Yan F, Dong J, et al.A multiple-step screening protocol to identify norepinephrine and dopamine reuptake inhibitors for depression.Phys Chem Chem Phys. 2023;25:8341-8354. doi:10.1039/D2CP05676CLiu Y, Zhao J, Guo W.Emotional roles of mono-aminergic neurotransmitters in major depressive disorder and anxiety disorders.Front Psychol. 2019;9:2201. doi:10.3389/fpsyg.2018.02201American Psychological Association.Depression treatments for adults.Wang P, Fu T, Zhang X, et al.Differentiating physicochemical properties between NDRIs and sNRIs clinically important for the treatment of ADHD.Biochim Biophys Acta Gen Subj. 2017;1861(11 Pt A):2766-2777. doi:10.1016/j.bbagen.2017.07.022Kaufman MB.Pharmaceutical approval update.P T. 2019;44(6):337-339.Chikatimalla R, Dasaradhan T, Koneti J, Cherukuri SP, Kalluru R, Gadde S.Depression in Parkinson’s disease: A narrative review.Cureus. 2022;14(8):e27750. doi:10.7759/cureus.27750Fasipe OJ.Neuropharmacological classification of antidepressant agents based on their mechanisms of action.Arch Med Health Sci. 2018;6(1):81-94. doi:10.4103/amhs.amhs_7_18Clark A, Tate B, Urban B, et al.Bupropion mediated effects on depression, attention deficit hyperactivity disorder, and smoking cessation.Health Psychol Res. 2023;11:81043. doi:10.52965/001c.81043U.S. Food & Drug Administration.Drug approval package: Zyban.Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK.Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant.Therap Adv Psychopharmacol. 2016;6(2):99-144. doi:10.1177/2045125316629071Maneeton N, Maneeton B, Woottiluk P, et al.Comparative efficacy, acceptability, and tolerability of dexmethylphenidate versus placebo in child and adolescent ADHD: a meta-analysis of randomized controlled trials.Neuropsychiatric Dis Treat. 2015;11:2943-2952. doi:10.2147/NDT.S91765U.S. Food & Drug Administration.Focalin XR label.U.S. Food and Drug Administration.FDA updating warnings to improve safe use of prescription stimulants used to treat ADHD and other conditions.Evans EA, Sullivan MA.Abuse and misuse of antidepressants.Subst Abuse Rehabil. 2014;5:107-120. doi:10.2147/SAR.S37917Moss M, Hendrickson RG.Serotonin toxicity: Associated agents and clinical characteristics.J Clin Psychopharmacol. 2019;39(6):628-633. doi:10.1097/JCP.0000000000001121Sathe AR, Thiemann A, Toulouie S, Durant E.A 19-year-old woman with a history of depression and fatal cardiorespiratory failure following an overdose of prescribed bupropion.Am J Case Rep. 2021;22:e931783-1—e931783-5. doi:10.12659/AJCR.931783

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Wang P, Yan F, Dong J, et al.A multiple-step screening protocol to identify norepinephrine and dopamine reuptake inhibitors for depression.Phys Chem Chem Phys. 2023;25:8341-8354. doi:10.1039/D2CP05676CLiu Y, Zhao J, Guo W.Emotional roles of mono-aminergic neurotransmitters in major depressive disorder and anxiety disorders.Front Psychol. 2019;9:2201. doi:10.3389/fpsyg.2018.02201American Psychological Association.Depression treatments for adults.Wang P, Fu T, Zhang X, et al.Differentiating physicochemical properties between NDRIs and sNRIs clinically important for the treatment of ADHD.Biochim Biophys Acta Gen Subj. 2017;1861(11 Pt A):2766-2777. doi:10.1016/j.bbagen.2017.07.022Kaufman MB.Pharmaceutical approval update.P T. 2019;44(6):337-339.Chikatimalla R, Dasaradhan T, Koneti J, Cherukuri SP, Kalluru R, Gadde S.Depression in Parkinson’s disease: A narrative review.Cureus. 2022;14(8):e27750. doi:10.7759/cureus.27750Fasipe OJ.Neuropharmacological classification of antidepressant agents based on their mechanisms of action.Arch Med Health Sci. 2018;6(1):81-94. doi:10.4103/amhs.amhs_7_18Clark A, Tate B, Urban B, et al.Bupropion mediated effects on depression, attention deficit hyperactivity disorder, and smoking cessation.Health Psychol Res. 2023;11:81043. doi:10.52965/001c.81043U.S. Food & Drug Administration.Drug approval package: Zyban.Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK.Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant.Therap Adv Psychopharmacol. 2016;6(2):99-144. doi:10.1177/2045125316629071Maneeton N, Maneeton B, Woottiluk P, et al.Comparative efficacy, acceptability, and tolerability of dexmethylphenidate versus placebo in child and adolescent ADHD: a meta-analysis of randomized controlled trials.Neuropsychiatric Dis Treat. 2015;11:2943-2952. doi:10.2147/NDT.S91765U.S. Food & Drug Administration.Focalin XR label.U.S. Food and Drug Administration.FDA updating warnings to improve safe use of prescription stimulants used to treat ADHD and other conditions.Evans EA, Sullivan MA.Abuse and misuse of antidepressants.Subst Abuse Rehabil. 2014;5:107-120. doi:10.2147/SAR.S37917Moss M, Hendrickson RG.Serotonin toxicity: Associated agents and clinical characteristics.J Clin Psychopharmacol. 2019;39(6):628-633. doi:10.1097/JCP.0000000000001121Sathe AR, Thiemann A, Toulouie S, Durant E.A 19-year-old woman with a history of depression and fatal cardiorespiratory failure following an overdose of prescribed bupropion.Am J Case Rep. 2021;22:e931783-1—e931783-5. doi:10.12659/AJCR.931783

Wang P, Yan F, Dong J, et al.A multiple-step screening protocol to identify norepinephrine and dopamine reuptake inhibitors for depression.Phys Chem Chem Phys. 2023;25:8341-8354. doi:10.1039/D2CP05676C

Liu Y, Zhao J, Guo W.Emotional roles of mono-aminergic neurotransmitters in major depressive disorder and anxiety disorders.Front Psychol. 2019;9:2201. doi:10.3389/fpsyg.2018.02201

American Psychological Association.Depression treatments for adults.

Wang P, Fu T, Zhang X, et al.Differentiating physicochemical properties between NDRIs and sNRIs clinically important for the treatment of ADHD.Biochim Biophys Acta Gen Subj. 2017;1861(11 Pt A):2766-2777. doi:10.1016/j.bbagen.2017.07.022

Kaufman MB.Pharmaceutical approval update.P T. 2019;44(6):337-339.

Chikatimalla R, Dasaradhan T, Koneti J, Cherukuri SP, Kalluru R, Gadde S.Depression in Parkinson’s disease: A narrative review.Cureus. 2022;14(8):e27750. doi:10.7759/cureus.27750

Fasipe OJ.Neuropharmacological classification of antidepressant agents based on their mechanisms of action.Arch Med Health Sci. 2018;6(1):81-94. doi:10.4103/amhs.amhs_7_18

Clark A, Tate B, Urban B, et al.Bupropion mediated effects on depression, attention deficit hyperactivity disorder, and smoking cessation.Health Psychol Res. 2023;11:81043. doi:10.52965/001c.81043

U.S. Food & Drug Administration.Drug approval package: Zyban.

Patel K, Allen S, Haque MN, Angelescu I, Baumeister D, Tracy DK.Bupropion: a systematic review and meta-analysis of effectiveness as an antidepressant.Therap Adv Psychopharmacol. 2016;6(2):99-144. doi:10.1177/2045125316629071

Maneeton N, Maneeton B, Woottiluk P, et al.Comparative efficacy, acceptability, and tolerability of dexmethylphenidate versus placebo in child and adolescent ADHD: a meta-analysis of randomized controlled trials.Neuropsychiatric Dis Treat. 2015;11:2943-2952. doi:10.2147/NDT.S91765

U.S. Food & Drug Administration.Focalin XR label.

U.S. Food and Drug Administration.FDA updating warnings to improve safe use of prescription stimulants used to treat ADHD and other conditions.

Evans EA, Sullivan MA.Abuse and misuse of antidepressants.Subst Abuse Rehabil. 2014;5:107-120. doi:10.2147/SAR.S37917

Moss M, Hendrickson RG.Serotonin toxicity: Associated agents and clinical characteristics.J Clin Psychopharmacol. 2019;39(6):628-633. doi:10.1097/JCP.0000000000001121

Sathe AR, Thiemann A, Toulouie S, Durant E.A 19-year-old woman with a history of depression and fatal cardiorespiratory failure following an overdose of prescribed bupropion.Am J Case Rep. 2021;22:e931783-1—e931783-5. doi:10.12659/AJCR.931783

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