Insomnia Drugs Risky When Taken With Opioids

By Pat Anson, PNN Editor

Medications commonly prescribed to treat insomnia significantly increase the risk of death for older adults if the drugs are taken with opioids, according to new study.

Zopiclone, zaleplon and zolpidem – collectively known as “Z-drugs” – are sold under brand names such as Ambien, Lunesta and Sonata. Z-drugs are sedative-hypnotics and act in a similar way as benzodiazepines, but are considered safer because they belong to a different class of medication.

But after reviewing the medical records of over 400,000 Medicare patients aged 65 and older, researchers at Vanderbilt University Medical Center found that Z-drugs are nearly as risky as benzodiazepines. Patients using benzodiazepines and opioids had a 221% higher risk of death from any cause, while those taking z-drugs and opioids had a 68% increased risk of dying.

Benzodiazepines such as Xanax and Valium are primarily used to treat anxiety. Until recently, benzodiazepines were often co-prescribed with opioids to pain patients, a practice that is now discouraged because both drugs suppress respiration, which can lead to an overdose.

"Our findings indicate that the risks of benzodiazepine-opioid use go well beyond the recognized hazards of overdose. They also suggest that the z-drugs, thought to have better safety than the benzodiazepines, in fact are dangerous when prescribed in combination with opioid pain medications," said Wayne Ray, PhD, professor of Health Policy at Vanderbilt and lead author of the study published in PLOS Medicine.

"Our findings add urgency to efforts to limit concurrent prescribing of benzodiazepines and opioids. They also suggest that targeted warnings are needed to advise older patients and their providers regarding the potential risks of taking z-drugs with opioids."

Last year the Food and Drug Administration ordering drug manufacturers to update warning labels for benzodiazepines to strongly caution patients and providers about the risk of abuse, addiction, dependence and overdose, particularly when the drugs are used with opioids or alcohol.   

In 2019, the FDA also ordered stronger warning labels for Z-drugs, but in that case it was to caution people about rare side effects such as sleepwalking, sleep driving and other risky behaviors.  

Do Non-Opioid Pain Meds Raise Risk of Suicide?

By Pat Anson, Editor

We received a lot of reader reaction to our story about Sherri Little, the 53-year old chronic pain sufferer who committed suicide with an overdose of medication in her Los Angeles hotel room last year (see “Sherri’s Story: A Final Plea for Help”).

“Numerous prescription medications in the decedent’s name were found throughout the hotel room including a bottle labeled Lyrica on the rim of the bathtub next to the decedent’s body,” reads the coroner’s report.

Lyrica has a warning label that states the anti-seizure drug “may cause suicidal thoughts or actions.” At least two other medications Sherri was taking – the sleep aid Ambien and the sedative Klonopin  -- also have labels warning they may worsen depression or suicidal thinking.

Several readers wondered – as we did – why doctors would prescribe the drugs to Sherri, who had been suicidal for at least two years.

SHERRI LITTLE

“The off label use of antidepressants and anti-seizure meds for pain control is criminal. People are dying! And it's not because they're addicts! It's because the healthcare professionals have become compliant and have agreed to go against all common decency and sense,” wrote Arianne Grand-Gassaway, a chronic pain patient.

Many doctors are turning to non-opioid drugs like Lyrica to manage pain because they’re considered safer and less addictive. Worldwide sales of Lyrica topped $6 billion for Pfizer in 2014, up 19 percent from the previous year.  

“When a suicide occurs it is hard to know with certainty whether medications like Lyrica contributed to the suicide or pain itself was the primary cause,” said Lynn Webster, MD, past President of the American Academy of Pain Medicine and Vice President of scientific affairs at PRA Health Sciences.  “I feel the risk of suicide is many times greater for inadequately treated moderate to severe pain than with patients on these medications.”

Webster says the cocktail of drugs Sherri Little was taking for her pain, anxiety and depression was not unusual.

“It is very common to prescribe an anticonvulsant like Lyrica with a sleep aid. Lyrica is viewed as a safer medication than most options. Most people with moderate to severe chronic pain have difficulty sleeping so drugs like Ambien and Lunesta are routine.  Klonopin is also very commonly prescribed for an anxiety disorder or muscle spasm. It is also used to facilitate sleep," said Webster.

The Food and Drug Administration added suicide to the warning labels for Lyrica and Klonopin  after a review of nearly 200 clinical studies found that patients taking antiepileptic drugs had almost twice the risk of suicidal thought or behavior than patients taking a placebo. 

The risk is small – about 1 in every 500 patients – but don't tell that to the families of the four patients in the clinical studies who killed themselves.

After reading Sherri Little’s story, one reader told us Lyrica made her suicidal.

“I went to my doctor in January after being on Lyrica for a month. It seemed to be helping my nerve pain so she upped my dose to 50 milligrams twice a day,” said Allison Lindsay Shorter. “A couple of days later I started having deep thoughts like I was out of control of my emotions. My anxiety was sky high. I argued for no reason with everyone. I had feelings of hurting myself and whoever got in my way.”

Shorter told her boyfriend she wanted to kill herself and hid his cellphone before swallowing a bottle of muscle relaxers. She was rushed to the hospital and survived.

“I felt out of control when I had all those thoughts and actions, I was scared of myself because I could not control anything. It felt like a demon or evil spirit,” said Shorter. “I knew then it was the damn medication.”

In addition to Lyrica, Shorter was taking 18 other medications to treat a long list of conditions, including fibromyalgia, complex regional pain syndrome, and neuropathy. At one time she was also taking Neurontin (gabapentin), another antiepileptic drug often prescribed for pain that comes with a  label warning of suicide, depression, panic attacks and dangerous impulses.

Why do doctors prescribe medication with such risky side effects?

“Most doctors are probably aware of the suicide risks but the general belief is that risk of suicide from the medication is very low and the risk of suicide from undertreated pain is much greater,” says Webster, who recently wrote a column on patient suicide (see “A Doctor’s Perspective on Patient Suicide”).

“The potential risks have to be continually weighed against the potential benefits.  Lack of treatment carries significant risk too. Suicide is at least three times more likely in the chronic pain population than the general population.  The risk appears to increase with the number of medical diagnoses. In my opinion the risk of suicide due to pain, treated or untreated, far exceeds the risk of suicide from these medications, prescribed alone or in combination.”

Webster fears the current backlash against opioids and efforts to further limit opioid prescribing will lead to more pain going untreated.

“This is a serious topic and I am afraid there are going to be many more suicides due to the anti-opioid movement.  Very sad,” Webster wrote in an email to Pain News Network.  

Ironically, small doses of an opioid may actually reduce the risk of suicide, according to a recent small study in Israel. Researchers at the University of Haifa gave 40 suicidal patients small doses of buprenorphine and found it reduced their suicidal thoughts after just one week.

Just as opioids reduce physical pain, researchers think it can ease mental pain.

“I think they’re onto something. However, buprenorphine acts on a number of different opioid receptors and it’s still unclear which one or ones are playing a role in the anti-suicidal effects,” psychiatrist Joan Striebel told New Scientist.  “I hope this work spurs more interest in what specific molecules could be involved in suicidal thought.”

Sherri’s Story: A Final Plea for Help

By Pat Anson, Editor

“I’ve been thinking about ending my life if I don’t get the help I need.”

Those are chilling words for anyone to hear. And in the last two years of her life, Sherri Little said them often to family, friends and doctors.  After decades of struggling with chronic pain from fibromyalgia, inflammatory bowel disease, severe colitis and other conditions, the 53-year old California woman was desperate and depressed when she checked into the emergency room at Cedars-Sinai Medical Center in Los Angeles on July 3, 2015.

What happened over the next four days is not entirely clear, but we know that Sherri took her own life. Her body was found in the bathtub of a hotel room across the street from Cedars-Sinai on the morning of July 7, with several prescription bottles and an empty bottle of wine nearby. Sherri had been sober for many years.

“I attest this is the first drink of alcohol in 16 years -- just to give me the courage to end my life alone,” Sherri wrote in a suicide note found in her hotel room.

“Several documents found inside the location underscored her pain, suffering and suicidal ideations,” reads the coroner’s report. “A check of the decedent’s laptop also contained a pictured document written by the decedent titled ‘Why I Killed Myself’ by Sherri Little.”

We’re telling Sherri’s story --- with the help of her mother, friends and patient advocate – not in a ghoulish attempt to recreate her final days, but to lend a name, a face and a voice to the untold number of chronic pain sufferers who have also been overwhelmed by pain, depression and loss of hope.  Like Sherri, many felt abandoned by a healthcare system that was unwilling or simply unable to treat them.

sherri little

Over 42,000 Americans killed themselves in 2014 according to the CDC, but experts believe the actual number is higher. Many suicides go unreported or are misclassified as accidental, covered up by grieving family members or accommodating medical examiners.

Sherri’s death was no accident, but it’s taken several months for her mother to come to terms with it.

“I’ve got to get her story out there,” said Lynda Mannion, Sherri’s mother. “She got to the point in the last year or so she could hardly eat solid food at all. She was just drinking her nutrition. I guess she must have lost 20 to 30 pounds in the last year.

“She would say, ‘I can’t go on living like this. If I can’t get some help, if somebody doesn’t believe me, I just can’t go on living like this.’ She didn’t seem to be extremely afraid of dying, considering the alternative, living with the pain she was in. But I never expected her to do it.”

A few months before she died, Sherri gave an interview to Tina Petrova in Toronto for a soon-to-be released documentary called Pain Warriors. 

“Sherri Little and I first became friends on Facebook, united by our common passion of pain patient advocacy. She initially reached out to me after hearing that I had a film in development I was producing on chronic pain and said, ‘Do I have a story for you!’ And indeed, she did,” says Petrova.

In this short clip, Sherri doesn’t talk about suicide and appears hopeful about her future.

But just weeks later, Sherri wrote the following in an email to Petrova:

“I was acutely suicidal last night after being verbally abused by a doctor who can't even get me any pain relief anymore,” said Sherri. “In a last ditch effort to save my life I am going to Cedar Sinai ER in LA with my patient advocate.”

Sherri was referring to Lisa Blackstock, a professional advocate who founded Soul Sherpa to help guide patients through the healthcare system. Blackstock had been a volunteer at Cedars-Sinai for several years and knew her way around one of the most respected hospitals in Los Angeles. 

The day before she went to the hospital, Sherri was still having suicidal thoughts.

“I woke at 3am today, ready to give up the fight and end my life. This is not dramatic or blaming of you, but just a statement of fact: my life has not been worth living for 2 years,” Sherri wrote in an email to Blackstock.

The two women went to Cedars-Sinai together and were in the emergency room for 11 hours before Sherri was finally admitted as a patient with severe abdominal pain on the evening of July 3rd.

Over the next two days, Sherri was examined by doctors and a psychiatrist, who concluded she was a “moderate” suicide risk because she had never actually tried to take her own life.

“Patient is at moderate risk of harm to self, but does not meet criteria for involuntary psychiatric treatment at this time,” the psychiatrist wrote in Sherri’s medical records, which were provided to Pain News Network by her mother.

cedars-sinai medical center

Sherri was scheduled for a colonoscopy on July 6, but never had the procedure.  For reasons that are not clear, she became frustrated with her treatment and left the hospital the night before.

“She left against medical advice,” Sherri’s discharge notes say. “Efforts were made to talk to her about the seriousness of her decision. She explained that she understood but, however, would like to leave against medical advice.”

Lisa Blackstock didn’t learn about Sherri’s release until it was too late.

“Despite a HIPAA release (patient release form) on file naming me as Sherri's contact, the doctor did not contact me and decided there was no reason to place her on a 72-hour involuntary hold,” Blackstock wrote in a letter to the coroner’s investigator. “Sherri was allowed to leave the hospital, in pain and suicidal, and the physicians responsible for her care failed miserably.

“I am a long-term volunteer at Cedars, and, until this incident, had great respect for them.  Changes in healthcare law have resulted in substandard care for many patients depending upon their insurance coverage types, as well as hospital administrators dictating care for patients rather than skilled physicians.”

A spokeswoman for Cedars-Sinai said the hospital was unable to comment and wouldn’t even confirm Sherri had been a patient there.

“State and federal privacy laws prevent hospitals from releasing information about patients without their consent, including whether an individual may or may not be a current or former patient,” wrote Sally Stewart in an email to PNN.

Cocktail of Medications

Long before she was admitted to Cedars-Sinai, Sherri was prescribed a potent cocktail of medications for her pain and depression; including the opioids tramadol and hydrocodone, as well as Lyrica (pregabalin), Ambien (zolpidem), and Klonopin (clonazepam).    

Lyrica, Ambien and Klonopin have all been linked to increased risk of suicide.  

Lyrica has an FDA warning label that states the drug “may cause suicidal thoughts or actions” and Ambien’s label warns that “depression or suicidal thinking may occur.”

Klonopin belongs to a class of sedatives known as benzodiazepines, which are increasingly being linked to overdoses, especially when combined with opioids. Klonopin’s label also warns of “suicidal behavior and ideation.”

Why were doctors prescribing these drugs to someone who was suicidal? And why did Cedars-Sinai release Sherri with the drugs in her possession?

“They discharged her with all of them at Cedars, which I found just incredibly irresponsible,” says Blackstock.

According to the autopsy report, the coroner found only trace amounts of opioids and Ambien in Sherri’s system, but apparently never looked for the other drugs. Her official cause of death is listed vaguely as “combined effects of medications.”

Were the same drugs that Sherri took for her pain and depression – which were ineffective in helping either – used as instruments in her death? 

We may never know the answer.

“I have fought to get help for the disease I am dying of – pseudomembranous colitis – for years without help from anyone,” Sherri wrote in her suicide note. “I do not want to be resuscitated. There is nothing left for me but to be tied to a hospital bed in great pain.” 

Sherri was divorced and did not have any children. But a close circle of friends and loved ones are anxious to have her story told and her memory preserved.

“She was beautiful from the time she was little. She was beautiful up to the day she died.  She looked 20 years younger than she was,” recalls Sherri’s mother, Lynda.

“She loved to help people. She wanted to help people and she couldn’t understand why nobody would help her. She would have been there for anybody.”

“Sherri was one of those rare people that could light up the room upon entering,” recalls her friend, Tina Petrova. “During the all too short time I knew Sherri, her key focus above all was advocating for pain patients, speaking up, getting involved. Her search for treatments for her own painful conditions took a back seat to her passion to help others.

“I can just see her high above us saying, “But you have to DO SOMETHING!’”

Sherri’s advocacy will continue, thanks to a website Petrova created to honor Sherri's memory and the documentary that she’s producing on chronic pain in North America.

What can the rest of us learn from Sherri’s struggle?

Perhaps those lessons are best learned through her own words -- and the advice that Sherri gave to other pain sufferers: