Trintellix alternatives: What can I take instead of Trintellix?

In this article:

• What can I take instead of Trintellix?
• Trintellix alternatives cost comparison
• Top 5 Trintellix alternatives
• Natural alternatives to Trintellix
• How to switch to a Trintellix alternative

In this article

• What can I take instead of Trintellix?
• Trintellix alternatives cost comparison
• Top 5 Trintellix alternatives
• Natural alternatives to Trintellix
• How to switch to a Trintellix alternative

Trintellix (vortioxetine) is a brand-name prescription antidepressant used to treat major depressive disorder in adults. Trintellix has a unique mechanism of action, so it’s considered an atypical antidepressant. However, Trintellix may not work for everyone, or it may cause intolerable side effects, such as eye problems or sexual dysfunction. For some people, the premium price may be a barrier. In those cases, healthcare providers can prescribe lower-priced generic drugs. 

RELATED: Antidepressant coupons and savings

What can I take instead of Trintellix?

Trintellix alternatives for depression include selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and other atypical antidepressants, like Remeron or Wellbutrin. 

Generic Trintellix is not yet available, so it isn’t an option if cost is the biggest hurdle to taking Trintellix.

Trintellix alternatives cost comparison
Drug name	Price without insurance	SingleCare price	Savings options
Trintellix (vortioxetine)	$703 for 30, 20 mg tablets	$491 for 30, 20 mg tablets of brand-name Trintellix at Kroger	See latest prices
Fluoxetine	$67 for 30, 20 mg capsules	$6 for 30, 20 mg capsules of generic fluoxetine at Kroger	See latest prices
Effexor XR (venlafaxine extended-release)	$781 for 30, 150 mg capsules	$6 for 30, 150 mg capsules of generic Effexor XR at Kroger	See latest prices
Remeron (mirtazapine)	$250 for 30, 15 mg tablets	$9 for 30, 15 mg tablets of generic Remeron at Kroger	See latest prices
Wellbutrin SR (bupropion)	$565 for 60, 150 mg tablets	$6 for 60, 150 mg tablets of generic Wellbutrin SR at Kroger	See latest prices
Amitriptyline	$28 for 30, 25 mg tablets	$4 for 30, 25 mg tablets of generic amitriptyline at Walmart	See latest prices

Prescription drug prices often change. These are the most accurate medication prices at the time of publishing in ZIP code 23666 as of March 7, 2026. The listed price without insurance references the price of brand-name drugs (unless otherwise specified). The listed SingleCare price references the price of generic drugs if available.

Top 5 Trintellix alternatives

1. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, Zoloft (sertraline), and Lexapro (escitalopram)

SSRIs are approved by the Food and Drug Administration (FDA) to treat major depressive disorder. In addition to treating depression, most SSRIs are also used to treat other mental health conditions, including anxiety, obsessive-compulsive disorder (OCD), or panic disorder. SSRIs are the most commonly prescribed antidepressants and usually the first medication prescribed to treat depression or anxiety. They work by increasing serotonin levels in the brain, allowing patients more control over their mood.

Because SSRIs are the most commonly prescribed depression treatment, some people taking Trintellix may have previously taken an SSRI. An untried SSRI may be appropriate if there are problems with Trintellix or if cost is an issue. Common side effects of SSRIs include dry mouth, nausea, and insomnia. Sexual side effects and weight gain are also common with SSRIs. 

RELATED: Does Trintellix cause sexual side effects?

2. Serotonin norepinephrine reuptake inhibitors (SNRIs), such as duloxetine, Effexor XR (venlafaxine), and Pristiq (desvenlafaxine)

SNRIs are another first-line therapy for depression and an alternative to Trintellix. Like SSRIs, most SNRIs are FDA-approved to treat various mental health conditions as well, including anxiety. SNRIs work differently from Trintellix in that they increase levels of both serotonin and norepinephrine in the brain. Increased norepinephrine in the brain improves energy, motivation, focus, and mood. Possible side effects of SNRIs include nausea, dry mouth, and dizziness. These antidepressant medications can also cause sexual side effects, such as decreased libido. 

3. Atypical antidepressants, such as Wellbutrin XL (bupropion), Viibryd (vilazodone), and Remeron (mirtazapine)

Atypical antidepressants are antidepressants that don’t fall under the other antidepressant categories. They may work in different ways to balance levels of various neurotransmitters in the brain, including serotonin, norepinephrine, and dopamine. One example is Wellbutrin, a first-line antidepressant that increases norepinephrine and dopamine levels in the brain. Dopamine is the neurotransmitter that powers our “reward centers,” giving us pleasure and a reason to be active. Drugs like Trintellix and Remeron (mirtazapine) work more like SSRIs, but use a different mechanism of action. 

Atypical antidepressants include medications with the least risk of causing sexual side effects. 

4. Tricyclic antidepressants (TCAs), such as amitriptyline, nortriptyline, and Norpramin (desipramine)

TCAs are one of the oldest classes of antidepressants. These antidepressants work by increasing levels of norepinephrine and serotonin, but some TCAs can also affect other neurotransmitters, such as acetylcholine. For example, amitriptyline, nortriptyline, and desipramine all work like SNRIs (they increase serotonin and norepinephrine in the brain), but they also block acetylcholine. That additional effect may help people who aren’t doing that well on first-line antidepressants. 

However, TCAs have additional side effects, as well, including dry mouth and sedation. They also have more drug interactions. For these reasons, healthcare providers typically prescribe a TCA when other antidepressants don’t work well enough or if insomnia is an issue. 

5. Monoamine oxidase inhibitors (MAOIs), such as Nardil (phenelzine), Emsam (selegiline), and Parnate (tranylcypromine)

MAOIs are an older class of antidepressants like TCAs. They work by increasing the levels of neurotransmitters, including norepinephrine, serotonin, and dopamine. MAOIs are effective, but they are rarely prescribed by healthcare professionals because of side effects, potentially hazardous drug interactions, and dietary restrictions.

Clinicians typically turn to MAOIs for treatment-resistant depression, atypical depression (a type of depression where some of the symptoms deviate from the normal diagnostic criteria for major depressive disorder), or when first-line treatments don’t work. 

Natural alternatives to Trintellix

Some people may benefit from natural remedies that have antidepressant effects. However, most healthcare providers will recommend a prescription antidepressant over a natural alternative to Trintellix. Natural remedies are not approved by the FDA for depression and other mental health conditions. It’s important to discuss these alternatives with a healthcare provider before trying them. 

St. John’s wort

St. John’s wort is an herbal supplement that has been used as a traditional medicine for various ailments over the centuries. Studies suggest that St. John’s wort is more effective than a placebo as a short-term option for mild to moderate depression. Not enough data is available to show that St. John’s wort may be effective when used for longer than 12 weeks. St. John’s wort also carries a risk of several side effects and drug interactions. Let your healthcare provider and pharmacist know if you are taking St. John’s wort, as it may have clinically dangerous drug interactions. 

Omega-3 fatty acids

Omega-3 fatty acids are mainly produced from fish oil. Researchers believe that omega-3 fatty acids have anti-inflammatory effects that may help alleviate symptoms of depression, but more studies are needed to determine the effects of omega-3 fatty acids on depression. 

5-HTP

5-HTP is a chemical that the body naturally makes from tryptophan, an amino acid. The body can then convert 5-HTP into serotonin. 5-HTP supplements are produced from the seeds of a tree native to Africa called Griffonia simplicifolia. Studies suggest that 5-HTP supplementation can help boost serotonin levels, which may help relieve depression.

SAMe

S-adenosyl-L-methionine, or SAMe, is a chemical naturally found in the body. People with depression and other health conditions have been previously found to have abnormally low levels of SAMe. A synthetic version of SAMe can be taken as a supplement. Studies show that SAMe may help relieve depression. However, the research on SAMe for depression involves short-term studies. More research is needed to determine the exact effects of SAMe on depression and other medical conditions. 

How to switch to a Trintellix alternative

Do not stop taking Trintellix abruptly, because of the risk of withdrawal symptoms. Get medical advice from a prescribing healthcare provider before stopping Trintellix and switching to a Trintellix alternative. 

RELATED: How long does Trintellix withdrawal last?

In most cases, a healthcare provider will recommend tapering, or gradually decreasing the dose, before switching antidepressants. The process for switching antidepressants may include starting the new drug while tapering the old drug, immediately switching to the new drug after stopping the old drug, or tapering the old drug and then starting the new drug after a few days or weeks. 

Certain factors should be taken into account, including potential drug interactions and possible side effects of new drugs. Most antidepressants can cause serious complications, including bleeding. Some drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs), may not be safe for use with some antidepressants. Talk to your provider and pharmacist about medications, prescribed and over the counter, that you should avoid.

The use of antidepressants can cause an increased risk of suicidal thoughts and behavior. Seek medical attention immediately if you or someone you know who is taking antidepressants is showing signs of worsened depression or suicidal thoughts. 

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