Updated: Sep 5
Welcome to the Duloxetine Diaries. This is the second in a series of articles regarding the prescription medication Duloxetine, the generic version of Cymbalta, created by Eli Lilly and Company and approved for treatment of major clinical depression on August 3rd, 2004. This is Brenda’s story, but it is not a unique story. Every two weeks I will release a new article featuring patients and caregivers telling their Duloxetine journey combined with research led, data driven facts regarding the history of this medication. I will use research to show how Cymbalta received FDA Approval with shaky clinical trial data and how, after 5,000 lawsuits filed against Eli Lilly and Company regarding Duloxetine, it is still one of the most prescribed medications in this country today.
Before we get to Brenda’s story…
I want to share what makes Duloxetine so hard to withdraw from and why it is prescribed for pain. Let’s first break down the difference between an SSRI like Fluoxetine (Prozac) and an SNRI like Duloxetine (Cymbalta.)
SSRIs are selective serotonin reuptake inhibitors, meaning they only impact the amount of serotonin in your body. SNRIs are serotonin-norepinephrine reuptake inhibitors, meaning they impact both serotonin and norepinephrine rather than only serotonin.”
In the brain norepinephrine, a monoamine neurotransmitter, increases arousal, alertness, attention, and is an integral part of the formation and retrieval of memory. In the rest of the body, norepinephrine affects heart rate, blood pressure, the release of glucose from energy stores, blood flow to skeletal muscle, blood flow to the gastrointestinal system, voiding of the bladder, and the contraction of the muscles that mix and propel contents in the gastrointestinal tract.
Serotonin is also a monoamine neurotransmitter and controls mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vasoconstriction.
SSRI’s work by blocking the reabsorption of serotonin while SNRI’s block the reabsorption of serotonin and norepinephrine. This boosts the amount of these monoamine neurotransmitters in the brain.
Norepinephrine is involved in decreased sensitivity to painful stimuli (hypoalgesia) and pain relief (analgesia). Less depression, less pain. Not a bad promise.
So What’s the Problem?
Anders Sørenson, a Danish clinical psychologist with a special interest in psychiatric drug withdrawal, authored a paper titled The relationship between dose and serotonin transporter occupancy of antidepressants—a systematic review. In the study Sørenson used brain imaging techniques to visualize how much serotonin transporters are blocked by an antidepressant at a given dose.
According to the graph below, with just a 5mg dose of Duloxetine 40% of the receptors in the brain are blocked. Once a patient reaches a 20mg dose, the receptors are occupied at 70%. The drug effect plateaus at 60mg with an 80% block, so a dose higher than 60mg has diminishing returns, and often the side effects will outweigh the benefits.
And, why is Withdrawal from Duloxetine so Hard?
With the lowest dosage of Duloxetine available being 20mg, the drug manufacturers are asking patients to go from 70% of their receptors being blocked to 0%. That is a dramatic decrease in serotonin and norepinephrine in the brain.
“The problem with withdrawal symptoms, like serotonin levels, is that when you reduce the drug dose, the affected levels of neurotransmitters will reduce faster than the adaptation. There is a time lag there and it’s that period when we’ll experience withdrawal symptoms. The body must readapt to a lower dose and that takes time depending on how much you reduce the dose. Hence the whole idea of gradual tapering, to give the body this task in small pieces”
Visit Healing America Now for a guide on safely tapering off Duloxetine and other antidepressants.
This is Brenda’s Story:
Brenda is not the interviewee’s real name; she asked for her name to be changed to protect her and her family’s privacy.
Brenda was a 48-year-old nurse who worked at a primary care doctors office when Cymbalta was first released by Eli Lilly and Company on August 30th 2004.
That fall she remembers the pharmaceutical representatives bouncing into her office with donuts and coffee, full of smiles, compliments, and an armload of samples. They promoted this miracle drug as something that not only helped depression but had also been approved to treat ‘pain.’ At the time, Cymbalta was only approved to treat major depression and diabetic neuropathy, something those bright eyed pharmaceutical reps declined to mention when they broad stated the word, ‘pain.”
Pharmaceutical representatives are not doctors or scientists, most have a bachelor’s degree, some can get by with a GED.
“Pharmaceutical sales representatives (PSRs), and the free samples they provide, represent the largest spending category for pharmaceutical promotion. Despite widespread belief by physicians to the contrary, PSRs have been shown to influence prescribing. Greater exposure to promotion is associated with higher prescribing volume and costs, and lower quality prescribing. A 2009 United States (US) survey found that 85 % of physicians see PSRs, and PSRs are their first information source for most newly prescribed drugs.”
During the time in her life when Brenda was first introduced to Cymbalta, she was struggling with persistent shoulder pain that eventually morphed into depression. She tried shots, physical therapy, and massage to treat her frozen shoulder, but nothing helped. The pain did not dissipate, and Brenda’s depression only intensified as time passed. It was during a visit to her primary care provider regarding shoulder pain, that Brenda herself mentioned a new drug she had heard about at the office, called Cymbalta. She told her doctor that the pharmaceutical reps said it would help with pain as well as depression.
Brenda’s doctor gave her the prescription for 30mg pills once a day, and her pain went from eight to three. In our conversation Brenda states,
“I thought wow, it does work for pain. I’m not going to negate that…but the thing is, typically when you have a short depression episode, you should try to get off an antidepressant in six to nine months. That’s the goal. But I was on this medication for eighteen years because I could not get off, not because my depression went away.”
If Brenda forgot a dose, she would start to feel dizzy. Luckily, she worked in an office that had a closet filled with samples. If she forgot her morning pill, she could take one at work and avoid the dizzy spells. She states that, “One time I got so dizzy I actually went for a CT scan because I was wondering why I had all these symptoms.” She later realized she had missed a dose of Cymbalta. So, she kept taking it to avoid the withdrawal.
“At one point along the way, I was bumped up to 60mg and could not handle it. I couldn’t sleep, so I dropped back to 30mg.
Enough is Enough
Brenda repeated this pattern until the day came when she felt enough was enough and it was time to get off. “I started opening the pills and dumping the contents out. I didn’t know all the stuff we know now. I’d remove a few beads every day…it didn’t work, so I stayed on for several more years.”
On a second attempt to stop taking Cymbalta, Brenda decided to change medications while weening, which is a common practice. The new prescription was Prozac (generic Fluoxetine, which is also an Eli Lilly drug. This method is not recommended by Healing America Now.) given to take alongside her reduction of Cymbalta. She managed to get off Cymbalta, but continued Prozac for one additional month. After feeling fine off Duloxetine, the next step was to taper off the Prozac as well.
After completing her taper from Prozac, “I started getting headaches that were progressing in intensity. I treated it with Ibuprofen, which made my headaches worse. I ended up going to a neurologist because a new onset headache in your sixties in concerning. The doctor wanted to put me on medication for migraines. I told him, you know what, I think this is from not being on Cymbalta. So, he wrote me a script, and once I started taking the pills my headaches went away." Brenda stayed on for a few more years after this attempt to stop.
In the end, once she was fully committed, it took Brenda four years total to get off Duloxetine. A year to position herself to start tapering, including finding a generic Duloxetine brand that sells capsules which can be opened and the beads removed. Brenda told me that inside some of the pharmaceutical companies 30mg capsules of Duloxetine, there are four beads. To taper from those versions, you would go from 30mg to 25mg, to 20mg, to 15mg, to 10mg to 5mg, and for her, that reduction caused unbearable headaches and body pain.
“On the Cymbalta Hurts Worse Facebook page, a suggested manufacturer was Breckenridge Pharmaceutical, Inc. Breckenridge Duloxetine capsules have one hundred and fourteen beads inside a 20mg pill. I knew I would have to start counting, so I needed a year to get prepared psychologically, mentally, and emotionally.”
The Count Begins
Brenda counted out those one hundred and fourteen beads over the course of three years. The Cymbalta Hurts Worse recommendation is a 5% reduction from the most recent dosage early on and, as you get closer to completion, dropping to a 2% reduction from the previous dosage. This time last year Brenda dropped from three beads to two beads, to one bead out of one hundred and fourteen beads. “One bead is .0175 milligrams. I stayed on one bead for a few months and then dropped to zero. With each bead removal my body pain started. I even went to a rheumatologist and had all kinds of tests done to see if there was anything else causing my body pain. My doctor’s recommendation was to put me on Duloxetine. I told her, you know what I’ve been through a journey with that drug. I’ve been trying to come off for years and just finished. I’m not going back there again. The doctor said she didn’t blame me and gave me steroids for the pain instead. I kept those in my purse and just tried to get through. Just tried to get through.”
After taking her last bead, Brenda suffered eight months of unrelenting body pain. One day she woke up and it simply disappeared. “I woke up one day in July of 2023, and the body pain was just gone.”
Brenda is now enjoying her life Duloxetine and pain free after an almost twenty-year journey. She explained that although she will never be totally the same, feeling complex emotions again has been incredible. After two decades of muted emotions, Brenda is grateful every day for the freedom to feel.
As we closed our conversation, I asked Brenda who she was before taking Duloxetine. I wanted to know what this drug took away from her. “That’s a good question. I’ll tell you this, the big thing that comes to mind is I had a hard time praying. I knew God was holding on to me, but I could not feel that connection to God.”
This is Brenda's story, but it is not the only story. In 2020, the year I was personally prescribed Duloxetine, there were 22,546,920 prescriptions written to 4,461,604 patients. That’s an estimated (based on the same data) $226 per year per patient, or 1 billion in revenue yearly for the 21 pharmaceutical companies approved by the FDA who produce the medicine.
This series aims to educate the public and medical community and advocate for legislation mandating detailed explanation of the serious risks linked to tapering off of antidepressants. It also seeks to make patient understanding explicit through signed acknowledgment before being prescribed these medications.
If you are a current or former Duloxetine patient and want to tell your story, please email me at firstname.lastname@example.org