There are a number of different substances, including medications and supplements, that can increase serotonin levels in the brain. Because low serotonin levels have been linked to depression and anxiety, serotonin drugs are sometimes prescribed to treat mental health conditions. This article explores some of the medications that can increase serotonin levels in the brain. It also discusses the potential risks of interactions when taking more than one type of serotonin drug.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) inhibit the reuptake of serotonin in the brain. Reuptake is a process where neurotransmitters in the brain are reabsorbed and deactivated or recycled for future use. When reuptake of serotonin is inhibited, more serotonin is available in the brain. This leads to an increase of serotonin levels, resulting in improved mood, decreased anxiety, and inhibition of panic. SSRIs are considered the first-line treatment for conditions such as depression and panic disorder. SSRI medications include:

Celexa (citalopram) Lexapro (escitalopram) Luvox (fluvoxamine) Paxil (paroxetine) Prozac (fluoxetine) Trintellix (vortioxetine) Viibryd (vilazodone) Zoloft (sertraline)

SSRIs are approved in the treatment of a variety of mental health conditions including generalized anxiety disorder (GAD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and social anxiety disorder (SAD).

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs inhibit the reabsorption of both serotonin and norepinephrine in the brain. Norepinephrine is a neurotransmitter that influences sleep and alertness. It is believed to be correlated to the fight-or-flight stress response. Some SNRIs include:

Cymbalta (duloxetine) Effexor (venlafaxine) Fetzima (levomilnacipran) Pristiq (desvenlafaxine) Savella (milnacipran)

Triptans

Triptans are a class of drugs commonly used to treat migraine or cluster headaches. They act on serotonin receptors in the brain, thereby affecting serotonin levels. Examples of triptans include:

Amerge (naratriptan)Axert (almotriptan)Frova (frovatriptan)Imitrex (sumatriptan)Maxalt and Maxalt-MLT (rizatriptan)Relpax (eletriptan)Zomig and Zomig ZMT (zolmitriptan)

Tricyclic Antidepressants

Tricyclic antidepressants (TCAs) are named after the drugs’ three-ringed molecular structure. Prior to the introduction of SSRIs in the late 1980s, TCAs were the medication of choice for the treatment of major depressive disorder, panic disorder, and other anxiety disorders. TCAs are also used to treat certain pain syndromes and nocturnal enuresis (bedwetting). Examples of TCAs include:

Elavil (amitriptyline)Tofranil (imipramine)Sinequan (doxepin)Anafranil (clomipramine)

TCAs are used less frequently today in the treatment of depression because they tend to produce more unwanted side effects compared to SSRIs.

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs are a class of antidepressants believed to increase levels of norepinephrine, serotonin, and dopamine (another neurotransmitter) in the brain. They are effective for the treatment of the major depressive disorder, panic disorder, and other anxiety disorders. Examples of MAOIs include:

Nardil (phenelzine)Parnate (tranylcypromine)Marplan (isocarboxazid)Emsam (selegiline)

Other Psychiatric Medications

There are also other psychiatric medications that can influence serotonin levels in the body.

BuSpar (buspirone): BuSpar affects the neurotransmitters serotonin and dopamine. It acts as an agonist on serotonin receptors, which means that it increases the actions of these receptors. As a result, this medication can be useful for relieving symptoms of anxiety. Eskalith (lithium): This medication is a mood stabilizer that is used in the treatment of bipolar disorder. It works by restoring the balance of neurotransmitters, including serotonin.  Desyrel (trazodone): Desyrel is an antidepressant medication that works by increasing the amount of serotonin available in the body. It also has sedative effects, which is why it is sometimes used to treat insomnia.

Analgesics (Painkillers)

A number of analgesic drugs can also affect serotonin levels in the body. These medications are often used to treat pain, but they are also sometimes misused and can lead to dependence and addiction. Some painkillers that act on serotonin include:

Codeine Fentanyl Tramadol

Antibiotic/Antiretroviral Medications

Some antibiotics and antiretroviral medications may also affect serotonin. This can potentially lead to drug interactions when people are taking other medications such as SSRIs or MAOIs. Because of these risks, you should always tell your healthcare provider about other medications, drugs, or supplements you are currently taking.

Zyvox (linezolid): Zyvox is an antibiotic that is sometimes prescribed to treat serious bacterial infections. In addition to inhibiting bacterial growth, this medication also affects serotonin. This affect can be more pronounced when Zyvox is combined with other serotonin medications.Norvir (ritonavir): Norvir is an antiviral medication that is used to treat HIV infection. When combined with other medications, it works to slow the progress of the disease. 

Herbal Drugs/Dietary Supplements

It is important to be aware that some herbal medicines and dietary supplements can have an effect on serotonin levels.

St. John’s Wort

St. John’s wort (hypericum perforatum) is a type of flowering plant that is sometimes used as an herbal remedy, particularly to relieve symptoms of depression. It is also used for other conditions including anxiety, premenstrual syndrome (PMS), menopause symptoms, smoking cessation, and seasonal affective disorder.  Researchers are not entirely sure of exactly how St. John’s wort works to elevate mood, but it is believed to increase neurotransmitter levels in the brain, including serotonin.

Ginseng

Ginseng is a root that is often used as an herbal supplement. Purported benefits include improved immunity, energy, and cognition. Ginseng acts on serotonin and other transmitters and also affects hormones, receptors, and signaling molecules. Research suggests that ginseng is associated with interactions with some psychotropic medications, including SSRI and SNRI antidepressants.

Other Drugs That Affect Serotonin

There are also a number of other substances that can affect serotonin levels in the body.

Amphetamines

Amphetamine stimulants are often prescribed to treat attention-deficit hyperactivity disorder (ADHD). These medications can also increase serotonin levels. While usually not enough to present a risk when taken as prescribed, stimulant medications such as Adderall may increase the risk of serotonin toxicity if they are misused or are combined with other serotonin medications. 

Cocaine

Cocaine blocks the reuptake of serotonin. This can be potentially risky if people use cocaine while they are taking antidepressants, triptans, or other medications that also increase serotonin levels.

LSD

Lysergic acid diethylamide (LSD) is a hallucinogenic drug that affects thinking and moods. These effects are the result of the impact of the drug on serotonin. The drug binds to certain receptors in the brain and changes how the brain responds to serotonin. Combining antidepressant medications and LSD has the potential to produce unwanted effects associated with serotonin toxicity.

Potential Serotonin Drug Interactions

Taking one or more medications that impact serotonin levels can be potentially dangerous. It can lead to a condition known as serotonin syndrome, where high serotonin levels in the brain cause symptoms such as:

Blood pressure changesComaConfusionFeverIncreased heart rateHallucinationsNauseaSeizures

According to the U.S. Food and Drug Administration, there is an increased risk of serotonin syndrome as a result of combining selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors SSNRIs with migraine headache medications called triptans.

A Word From Verywell

When serotonin levels are disrupted, it can result in unwanted symptoms including anxiety or depression. Medications that help balance serotonin levels can help you find relief from these symptoms, but it is important to be aware of how these serotonin medications affect the body and how they may interact with other substances. This list is not meant to be all-inclusive. To avoid increasing your risk of side effects, including serotonin syndrome, tell your healthcare provider about all drugs and dietary supplements you are taking. If you develop symptoms of serotonin syndrome, seek immediate medical attention.