Duloxetine Review: The Most Effective Antidepressant?

Duloxetine Review: The Most Effective Antidepressant?

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Disclaimer: None of the information in this article constitutes medical advice. All statements are merely the opinion of the writer(s). We recommend that patients follow their doctor’s guidance in regard to prescription medication.

Duloxetine is a prescription drug which is FDA-approved to treat major depressive disorder, generalized anxiety disorder, diabetic neuropathic pain, fibromyalgia and chronic musculoskeletal pain.

The full name of the compound is duloxetine hydrochloride, or "duloxetine hcl" for short. 

But is duloxetine proven to work for all of the conditions it's prescribed to treat? Does it cause side effects? Does it cause withdrawals upon quitting? And how do real users rate and describe the effects of this drug?

In this article we’ll answer all of these questions and more, as we analyze clinical studies on duloxetine to determine whether or not it's effective, document its side effects, and share patient reviews of the drug.

Does Duloxetine Work?

Duloxetine is primarily used to treat depression, and it’s proven to be effective for that condition.

An extensive medical review on the efficacy of duloxetine for treating Major Depressive Disorder (MDD) was published in the Depression and Anxiety journal.

The researchers found that duloxetine decreased average depression scores by over 50%, and decreased scores related to suicidal thoughts or ideation by over 50% as well.

Patients took around 9 weeks on average to achieve maximal benefit from the drug, but depression scores decreased by the end of week one.

research review on duloxetine for treating generalized anxiety disorder (GAD), which was published in the Adis Drugs journal, found that the medication was significantly more effective for reducing anxiety than placebo pills.

The above-linked review also measured patient depression levels, and duloxetine was more effective than placebo for improving depression in all analyzed studies.

A 2009 medical review assessed the efficacy of duloxetine for chronic pain management.

In all three clinical trials that the researchers analyzed, duloxetine was more effective than placebo for reducing pain. Impressively, duloxetine was effective at treating pain caused by various medical conditions, such as diabetic neuropathy and fibromyalgia.

We can conclude from the available research that duloxetine is effective for treating depression, anxiety and pain, which is unsurprising given that the medication is FDA-approved for those indications.

The research on duloxetine for depression is the most impressive in our opinion.

Does Duloxetine Cause Side Effects?

As we documented in our Cymbalta side effects article (on the branded version of this medication), duloxetine use has the risk of a number of concerning side effects.

The first side effect worth noting is the increased risk of suicidal behavior and thinking in children, adolescents and young adults as documented on the medication's FDA label.

This side effect is listed as a “black box” warning which is the most severe type of warning issued by the FDA.

Black box warnings indicate side effects that may cause life-threatening effects.

One of the medical trials on duloxetine and anxiety reported on a number of side effects experienced by some users of the drug: 

Acute alcoholic intoxication, alcohol dependency, anxiety, arrhythmia, cellulitis, cerebral hemorrhage resulting in death, depression, diverticulitis, mania, nephrolithiasis, two attempted suicides, one completed suicide, stress, and syncope.

These side effects are rare compared to the more common side effects like nausea or headache.

In light of the severity of these potential side effects, we recommend that patients speak with their doctor about the use of this medication, especially if they have pre-existing medical conditions.

YouTuber Tries Duloxetine

A YouTube creator named Izzy Kornblau published a video sharing her experience using duloxetine and how it relieved her pain. 

She describes side effects she experienced, how the drug worked for different types of pain, and explains at what time of day she takes the drug:

Does Duloxetine Cause Withdrawals?

Duloxetine does appear to cause withdrawal symptoms based on medical research.

A 2005 study documented symptoms experienced after immediate discontinuation of the drug. 

Dizziness was the most common withdrawal symptom, experienced at a frequency of 12.4%. Nausea was experienced at a rate of 5.9% and headache at a rate of 5.3%.

Compared to some other medications we've reviewed on Illuminate Health, these withdrawal symptoms are relatively minor.

The risk of withdrawal symptoms is why it’s so important for patients to speak with their doctor prior to stopping a medication.

Stopping abruptly rather than tapering off can cause worse withdrawal symptoms and may be unsafe. A doctor can create a personalized tapering schedule that makes the drug discontinuation process safer and more pleasant.

Patients Rate Duloxetine

Drugs.com is a website that allows prescription medication patients to rate and review the drugs they're taking.

We cannot verify the accuracy or authenticity of any reviews on this site.

Duloxetine has been reviewed over 2,000 times on Drugs.com at the time of updating this article, with a 6.3/10 rating as an antidepressant and a 5.7/10 rating as an analgesic (pain reliever).

A top positive review of duloxetine for depression comes from a user named “Singer” who gave the drug a 10/10 rating:

“This was the first time I had taken an SNRI and I feel better--I'm calmer, I think more clearly, and things that bothered me a lot seem much more manageable now. If your provider prescribes this medication, at least give it a try.”

A top negative review of duloxetine for depression is written by a user named “jules” who gave the drug a 1/10 rating:

“I took a 30mg [duloxetine] capsule at 9am at 9.30am it was like someone threw a brick at my head then I started to get brain zaps. I thought it would wear off but I started to get cramps, became very thirsty, vomiting, became uncoordinated and then called an ambulance. My sodium level dropped to 118 and I got hyponatremia. they took me straight to emergency dept and gave me a brain scan and a salty drink.”

How Does Duloxetine Work?

Duloxetine is a member of a class of drugs called serotonin and norepinephrine reuptake inhibitors (SNRI).

These medications delay or halt the body’s natural processing of the neurotransmitters serotonin and norepinephrine, which causes artificially elevated levels of these compounds in the brain and body.

While it hasn’t been conclusively proven, researchers theorize that patients suffering from depression may have lower levels of these neurotransmitters than healthy patients, which is why this type of medication may be effective on average.

According to a 2023 medical review, duloxetine also increases dopamine levels in the brain, and does so to an even greater degree in the prefrontal cortex, which directly influences mood.

One of the most popular YouTube videos on duloxetine comes from a channel called "Psychofarm," and is a visually engaging, animated video that breaks down the mechanism of action of this drug:

Negative Interactions

Duloxetine has the potential to negatively interact with a number of other prescription medications and other ingestibles.

Most of the interactions listed on the medication's warning label are fairly specific and uncommon, but information that a doctor should know, like the fact that duloxetine may interact with tricyclic antidepressants.

The interaction that may affect more patients is this drug's interaction with alcohol. Duloxetine's FDA label states the following: 

"Use of [duloxetine] concomitantly with heavy alcohol intake may be associated with severe liver injury. For this reason, [duloxetine] should not be prescribed for patients with substantial alcohol use."

Substantial alcohol use is not defined on the label, but when considering a risk as severe as liver injury, it seems logical to err on the side of caution.

We would recommend that any patients with even moderate alcohol use speak with their doctor about potential alternative medications that do not have this negative interaction risk.

Duloxetine Dosage

The dosage of duloxetine depends on the condition it’s prescribed for.

According to the medical review linked in the section of this article on how duloxetine works, the typical dosage for treating fibromyalgia ranges from 30 milligrams (mg) to 60 mg per day.

The typical dosage for anxiety is 60 mg, and the dose for depression tends to be between 40 and 60 mg per day.

It seems logical to start at a lower dose of a pharmaceutical drug with a side effect profile like duloxetine, because lower doses tend to cause lower risk of side effects.

If the dose is ineffective, a doctor may increase the patient's dose within the effective range until benefits are experienced.

Our Mental Wellness Picks

Brightside Health is our top overall mental wellness pick.

Brightside is an online therapy and medication platform that connects patients with licensed therapists and psychiatrists from the comfort of their home.

medical review published in the Clinical Psychology & Psychotherapy journal found that online therapy was equally effective to in-person therapy for treating depression, anxiety and PTSD.

Mindbloom is our top alternative mental wellness pick.

Mindbloom offers ketamine therapy, and over 88% of patients experienced relief of anxiety and depression symptoms in a clinical trial on the brand.

Stay up-to-date on our research reviews


Duloxetine is proven in clinical research to be effective for treating depression, anxiety and certain types of chronic pain. 

The drug has a risk of side effects as severe as suicidal behaviors and arrhythmia, and may interact negatively with heavy alcohol use and cause liver injury.

Duloxetine does cause withdrawals in some patients, so it's important that patients planning to quit the drug speak with a doctor to establish a tapering schedule rather than quitting abruptly.

This drug is currently better-rated on Drugs.com for its treatment of depression than its treatment of chronic pain.