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. 

Duloxetine is the generic version of a branded drug called Cymbalta. These two drugs (duloxetine and Cymbalta) contain the exact same active ingredient, so we’ll refer to them interchangeably throughout this article.

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 respond to this drug?

In this article we’ll answer these questions and more as we review clinical studies on duloxetine to evaluate whether or not it's effective, document its side effects and share real, unsponsored user 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 2007 in the Depression and Anxiety journal.

The researchers found that duloxetine decreased average depression scores by over 50%, and average 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.

Another research review of 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 a placebo pill. The review analyzed four different placebo-controlled studies on duloxetine and anxiety.

The same four studies also measured patients’ depression levels, and duloxetine was more effective than placebo for improving depression in all studies.

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

Duloxetine Side Effects

As we documented in our Cymbalta side effects article, duloxetine carries 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 Food and Drug Administration (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 users of the drug.

The side effects were: 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 of the medication 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.

Real, Unsponsored Duloxetine Patient Review

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 when she takes the drug:

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 StatPearls, which is one of the largest free medical databases in the U.S., 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:

Duloxetine Dosage

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

According to StatPearls, 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 range from 40 to 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 will often suggest that a patient increases the dose within the effective range. Of course, only a doctor can prescribe dosage to an individual patient.

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%.

For withdrawal symptoms, these 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 side effects and may be unsafe. A doctor can create a personalized tapering schedule that makes the drug discontinuation process safer and more pleasant.

Duloxetine 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 regular alcohol use speak with their doctor about potential alternative medications that do not have this interaction risk.

Our Mental Wellness Platform Recommendation

We recommend a platform called Brightside to patients dealing with mental health issues. It's an online therapy and medication platform that connects patients with licensed doctors and therapists 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. Therapy may be a good first option for patients who want to avoid the side effects of medication to consider.

Brightside also can connect patients with licensed psychiatrists that can prescribe medication. Some patients choose only therapy, some choose only medication, and some choose both. The brand reports that 86% of members feel significantly better within 12 weeks of treatment.

Patients with and without health insurance can use Brightside. For many patients with health insurance, treatment is entirely covered by insurance.

The cost for medication without health insurance is capped at $95/month and the cost for therapy without health insurance is capped at $299/month.

Interested patients can check out Brightside at this link to the brand's website.

Duloxetine User Reviews

Duloxetine has been reviewed over 2,000 times on Drugs.com which is a website where patients can publish reviews of prescription medication.

As we expected based on the results of our clinical research review, the reviews of duloxetine as an antidepressant are more favorable than the reviews of duloxetine for chronic pain. The medication scores 6.2/10 as an antidepressant but only 5.6/10 for chronic pain.

The top positive review of duloxetine for depression comes from a user named “Singer” who claims the drug improved their mental state:

“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.”

The top negative review of duloxetine for depression is written by a user named “jules” who claims the drug caused unpleasant side effects:

“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.”

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 for patients planning to quit the drug to speak with a doctor and establish a tapering down schedule rather than quitting abruptly.

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