What Medications Increase Serotonin and Dopamine? A Guide to Psychopharmacology

October 11, 2025 •

4 min read

Over 40 million American adults suffer from a mood disorder, and many can benefit from medications that increase serotonin and dopamine. These medications target key neurotransmitters in the brain to help regulate mood, motivation, and reward, and are used to treat conditions like depression, anxiety, and ADHD. Understanding the different classes of these psychotropic drugs is crucial for effective treatment.

Quick Summary

Several classes of medications affect serotonin and dopamine, including SSRIs, SNRIs, NDRIs, and MAOIs. These drugs work by blocking the reuptake or breakdown of neurotransmitters to increase their availability in the brain, which can help regulate mood, motivation, and other functions. Specific medication choice depends on the patient's condition, symptoms, and side effect profile.

Key Points

SSRIs (Selective Serotonin Reuptake Inhibitors): Primarily increase serotonin levels and are often the first-line treatment for depression and anxiety.
SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors): Boost both serotonin and norepinephrine levels, offering dual action that can also help with certain pain conditions.
NDRIs (Norepinephrine-Dopamine Reuptake Inhibitors): Specifically increase norepinephrine and dopamine, with bupropion (Wellbutrin) being the most common example, known for its focus- and energy-boosting effects.
MAOIs (Monoamine Oxidase Inhibitors): Block the enzyme that breaks down all monoamines, including serotonin, dopamine, and norepinephrine, but require strict dietary restrictions due to risk of hypertensive crisis.
Atypical Antidepressants and Augmentation: Some drugs have unique mechanisms or are used to supplement other medications to modulate serotonin and dopamine activity.

The Role of Serotonin and Dopamine in the Brain

Serotonin and dopamine are two of the most critical neurotransmitters involved in regulating mood, emotion, and behavior. While often referred to as 'happy hormones,' their functions are complex and interconnected. Serotonin is primarily associated with feelings of well-being, happiness, and emotional stability, and plays a role in sleep, digestion, and anxiety. Dopamine is the 'reward and motivation' neurotransmitter, driving pleasure, motor control, and focus. Imbalances in these systems are implicated in various mental health conditions, from major depressive disorder to anxiety and ADHD.

How Medications Increase Neurotransmitter Levels

Medications that increase serotonin and dopamine typically work by blocking the reabsorption (reuptake) or inhibiting the enzymatic breakdown of these neurotransmitters. This process keeps higher levels of the chemical messengers in the synaptic cleft—the space between nerve cells—allowing them to continue transmitting signals. The following sections detail the main classes of medications that modulate these neurotransmitter systems.

Selective Serotonin Reuptake Inhibitors (SSRIs)

As their name suggests, SSRIs primarily and selectively target the serotonin system. They block the reuptake of serotonin by the presynaptic neuron, leaving more serotonin available in the synapse to bind to postsynaptic receptors. While their action is primarily on serotonin, some have a minimal effect on other neurotransmitters at higher doses.

Commonly prescribed SSRIs include:

Fluoxetine (Prozac): One of the oldest and most well-studied SSRIs, used for depression, OCD, and panic disorder.
Sertraline (Zoloft): Known for its effectiveness in treating depression, OCD, and PTSD.
Escitalopram (Lexapro): Has a high specificity for the serotonin transporter and is used for depression and generalized anxiety disorder.
Citalopram (Celexa): A common SSRI, though high doses can be associated with QT prolongation.

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs offer a 'dual-action' approach by blocking the reuptake of both serotonin and norepinephrine. This broader scope of action can be beneficial for patients who do not respond to SSRIs alone or who have comorbid pain conditions, as norepinephrine plays a role in pain perception. While not directly blocking dopamine reuptake, the increase in norepinephrine can indirectly boost dopamine activity in certain areas of the brain.

Commonly prescribed SNRIs include:

Duloxetine (Cymbalta): Approved for depression, generalized anxiety disorder, and chronic pain conditions like fibromyalgia and diabetic neuropathy.
Venlafaxine (Effexor XR): Used for depression, anxiety disorders, and panic disorder.
Desvenlafaxine (Pristiq): An active metabolite of venlafaxine, used for major depressive disorder.

Norepinephrine-Dopamine Reuptake Inhibitors (NDRIs)

NDRIs are a class of antidepressants that work by inhibiting the reuptake of norepinephrine and dopamine, but have no direct effect on serotonin levels. Bupropion is the only NDRI primarily used for depression and is often prescribed to patients who experience sexual side effects from SSRIs or SNRIs. It is also used to treat seasonal affective disorder and as an aid for smoking cessation.

The main NDRI is:

Bupropion (Wellbutrin): Affects mood, energy, and motivation by increasing levels of norepinephrine and dopamine.

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs are an older class of antidepressants that block the monoamine oxidase enzyme, which is responsible for breaking down all monoamines, including serotonin, norepinephrine, and dopamine. This non-selective mechanism leads to significantly higher levels of all three neurotransmitters. Due to the risk of dangerous interactions with certain foods containing tyramine and other medications, MAOIs are typically reserved for treatment-resistant depression.

Examples of MAOIs include:

Phenelzine (Nardil): An irreversible MAOI used for atypical depression.
Tranylcypromine (Parnate): Another irreversible MAOI with potent antidepressant effects.

Atypical Antidepressants and Augmentation Strategies

Beyond the primary classes, some medications have unique mechanisms that affect serotonin and dopamine, or are used to augment other antidepressants.

Serotonin-Dopamine Activity Modulators (SDAMs): Used as add-on therapy for major depressive disorder, these drugs, like brexpiprazole (Rexulti) and lumateperone (Caplyta), modulate both serotonin and dopamine activity.
Mirtazapine (Remeron): An atypical antidepressant that increases norepinephrine and serotonin through a different mechanism and has a sedative effect, often useful for patients with insomnia.
Augmentation with Antipsychotics: In some cases of treatment-resistant depression, a low dose of an antipsychotic medication, such as aripiprazole (Abilify), may be added to an antidepressant to boost its effects by modulating dopamine and serotonin systems.

Comparing Medications That Impact Serotonin and Dopamine


Class	Mechanism of Action	Primary Neurotransmitter Targets	Considerations
SSRIs	Block serotonin reuptake	Serotonin	First-line treatment, fewer side effects than older classes, risk of sexual dysfunction.
SNRIs	Block serotonin and norepinephrine reuptake	Serotonin, Norepinephrine	Good for comorbid anxiety or pain, possible indirect dopamine effects, can affect blood pressure.
NDRIs	Block norepinephrine and dopamine reuptake	Norepinephrine, Dopamine	Minimal sexual side effects, potential for increased energy/focus, can lower seizure threshold.
MAOIs	Block monoamine oxidase enzyme	Serotonin, Dopamine, Norepinephrine, Tyramine	High risk of dangerous food/drug interactions, reserved for treatment-resistant cases.
Atypical/SDAMs	Complex/modulatory mechanisms	Varied (Serotonin, Dopamine, etc.)	Often used as add-ons, specific effects depend on the medication.

Conclusion

Medications affecting serotonin and dopamine play a crucial role in modern psychopharmacology, offering relief for millions suffering from mood disorders and other conditions. The approach to increasing these neurotransmitters has evolved from the broad-spectrum action of MAOIs to the more targeted mechanisms of SSRIs, SNRIs, and NDRIs. For those who need effects on both serotonin and dopamine, options include SNRIs, NDRIs (like bupropion), MAOIs, or augmentation strategies involving atypical antipsychotics. A healthcare provider will determine the most suitable option by considering the patient's symptoms, diagnosis, and potential side effect profile. It is essential to work closely with a professional when starting, switching, or stopping any medication that affects these delicate brain systems.

For more detailed information on specific medications, including drug interactions and side effects, consult authoritative sources such as the National Institutes of Health (NIH) or Mayo Clinic.

Frequently Asked Questions

SSRIs increase serotonin levels in the brain, while SNRIs increase both serotonin and norepinephrine levels. SNRIs offer a broader spectrum of action that can be more effective for some individuals or those with comorbid pain conditions.

Bupropion (Wellbutrin) is an NDRI, meaning it increases the levels of norepinephrine and dopamine in the brain by blocking their reuptake. It does not significantly affect serotonin and is known for fewer sexual side effects than SSRIs.

Yes, MAOIs have significant risks, including the potential for a dangerous rise in blood pressure (hypertensive crisis) if consumed with foods rich in tyramine (like aged cheeses and cured meats) or certain medications. For this reason, they are typically a last-resort treatment.

Yes, augmenting an SSRI with an NDRI like bupropion is a common strategy for treatment-resistant depression or to counteract sexual side effects caused by the SSRI. This should only be done under strict medical supervision.

Lithium, a mood stabilizer often used for bipolar disorder, works by restoring the balance of several neurotransmitters, including serotonin and dopamine, rather than increasing or decreasing them in a specific direction.

SDAMs are a newer class of drugs, such as brexpiprazole and lumateperone, that modulate the activity of both serotonin and dopamine receptors. They are often used as an adjunct treatment for major depressive disorder.

It can take several weeks for the therapeutic effects of these medications to be fully realized. The initial increase in neurotransmitter levels does not immediately result in symptom relief, as the brain needs time to adapt to the new chemical balance.