Little Evidence That Antidepressants Work for Chronic Pain  

By Drs. Hollie Birkinshaw and Tamar Pincus

About one in five people globally live with chronic pain, and it is a common reason for seeing a doctor, accounting for one in five GP appointments in the UK.

With growing caution around prescribing opioids – given their potential for addiction – many doctors are looking to prescribe other drugs, “off-label”, to treat long-term pain. A popular option is antidepressants.

In the UK, doctors can prescribe the following antidepressants for “chronic primary pain” (pain without a known underlying cause): amitriptyline, citalopram, duloxetine, fluoxetine, paroxetine and sertraline. Amitriptyline and duloxetine are also recommended for nerve pain, such as sciatica.

However, our review of studies investigating the effectiveness of antidepressants at treating chronic pain found that there is only evidence for one of these drugs: duloxetine.

We found 178 relevant studies with a total of 28,664 participants. It is the largest-ever review of antidepressants for chronic pain and the first to include all antidepressants for all types of chronic pain.

Forty-three of the studies (11,608 people) investigated duloxetine (Cymbalta). We found that it moderately reduces pain and improves mobility. It is the only antidepressant that we are certain has an effect. We also found that a 60mg dose of duloxetine was equally effective in providing pain relief as a 120mg dose.

In comparison, while 43 studies also investigated amitriptyline (Elavil), the total number of participants was only 3,372, indicating that most of these studies are very small and susceptible to biased results.

The number of studies and participants for the other antidepressants are:

  • Citalopram (Celexa): five studies with 209 participants

  • Fluoxetine (Prozac): 11 studies with 622 participants

  • Paroxetine (Paxil): nine studies with 960 participants

  • Sertraline (Zoloft): three studies with 210 participants.

The evidence for amitriptyline, citalopram, fluoxetine, paroxetine and sertraline was very poor, and no conclusions could be drawn about their ability to relieve pain.

This is particularly important as UK prescribing data shows 15,784,225 prescriptions of amitriptyline in the last year. It is reasonable to assume that a large proportion of these may be for pain relief because amitriptyline is no longer recommended for treating depression.

This suggests that millions of people may be taking an antidepressant to treat pain even though there is no evidence for its usefulness. In comparison, 3,973,129 duloxetine prescriptions were issued during the same period, for a mixture of depression and pain.

In light of our findings, which were published in May 2023, the UK’s National Institute for Health and Care Excellence (Nice) recently updated its advice to doctors on how to treat chronic pain.

The updated Nice guidance now suggests 60mg of duloxetine to treat [chronic primary pain] and the same drug and dose to treat nerve pain.

Limited Treatments Options

GPs often report frustration at the limited options available to them to treat patients experiencing chronic pain. Amitriptyline is cheap to prescribe – only 66p per pack (US 82.5 cents) – which may explain the high number of prescriptions for this drug.

This is an example of how the gap between evidence and clinical practice could harm patients. Although our review was unable to establish the long-term safety of antidepressant use, previous research has highlighted the high rates of side-effects for amitriptyline, including dizziness, nausea, headaches and constipation.

It’s important to bear in mind, though, that pain is a very individual experience, and the evidence in our review is based on groups of people. We acknowledge that certain drugs may work for people even when the research evidence is inconclusive or unavailable. If you have any concerns about your pain medication, you should discuss this with your doctor.

Hollie Birkinshaw, PhD, is a Research Fellow at University of Southampton. She specializes in research involving chronic musculoskeletal pain, and the integration of psychology in pain and health services. Birkinshaw receives funding from the UK’s National Institute for Health and Care Research (NIHR).

Tamar Pincus, PhD, is a Professor of Health Psychology at University of Southampton. Her research focuses on the psychological aspects of chronic pain. Pincus receives funding from NIHR, Medical Research Council and Versus Arthritis.  

This article originally appeared in The Conversation and is republished with permission.

My Daily Persistent Headache

By Warren Cereghino, Guest Columnist

Waking up from my pre-work noontime nap one October day in 2007, I had a headache.  I still have it.

Thinking little of it at the time, I took two acetaminophen capsules (maybe Tylenol; maybe the generic from CVS or Costco) and headed off to work. 

I toiled nightly in a Los Angeles television station’s news department, where I was a news editor contributing to the nightly 10pm newscast.  I liked the work and didn’t mind the night schedule because it kept me out of mischief and off the streets.

That first night, the headache persisted.  And it just never stopped.  Over the next few weeks, I was gobbling pain relievers of one form or another every four hours, all the while trying to find the cause and a cure with all sorts of practitioners.

A little research taught me that this was known as “New Daily Persistent Headache.”  It sure as hell was persistent.

My journey took me to the offices of two different chiropractors who had successfully treated the persistent headaches of two referring friends (one was my daughter-in-law, who is a RN).  Both doctors tried, and both were unable to make it go away. 

Next, I tried acupuncture. That didn’t work, either. 

WARREN CEREGHINO

Meanwhile, I kept gobbling acetaminophen and ibuprofen like they were candy.  Determined to find the cause, I turned to neurologists. Two doctors who were with separate practices in Santa Monica evaluated me, had me undergo a scan and tried to figure it out, but to no avail.

By year’s end, I was still struggling with the debilitating effects of the headache and despairing of ever finding the elusive cause and cure. I had to face the fact that the only avenue open to me appeared to be pain management.  

In January 2008, I went to see David Kudrow, MD, whose neurology practice in Santa Monica specializes in pain management.  He treats patients and conducts research.  Dr. Kudrow gave me a thorough interview and then prescribed a nightly dose of 10mg of Elavil, an anti-depressant.

I cannot remember what he predicted in regard to when it would take effect, but a few weeks later I encountered a young man who’d grown up across the street from me and was now a practicing pediatric neurosurgeon.  He said he agreed with the prescription and told me it would take about a month to take effect.  He was right. 

Over the years, the dosage of Elavil (or its generic amitriptyline) has had to be increased, first from 10mg nightly and then to 20mg.  A couple of years ago Dr. Kudrow bumped it up again to 30mg nightly.

Recently he suggested I try to scale back to 20mg nightly. I tried, but it didn’t work. The 20mg dosage didn’t offer enough pharmacological firepower and I went back to 30mg after about ten days. 

Dr. Kudrow saved my life.  I have other health issues, but without his help in pain management I wouldn’t even be able to address the other issues of hypertension, diabetes and pre-clinical heart disease. I’m two months shy of turning 82 as of this writing.  Without Elavil, I would be dead.

Warren Cereghino is a retired TV news producer, writer and editor who spent 55 years at TV stations in Phoenix, Sacramento, San Francisco-Oakland and Los Angeles.  Warren is a graduate of Arizona State and a military veteran who served during the Berlin Crisis of 1961. 

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.