PHOENIX (3TV/CBS 5) -- She could feel the stares. Kammy Pany would have been embarrassed, but she was consumed with concern as she held down her 7-year-old, trying to stop him from hurting himself or someone else.
Tyson's explosive temper was the reason Kammy accompanied him on a field trip to LegoLand Discovery Center in Tempe, Arizona.
Noise from the rides and kids playing on a nearby jungle gym could not drown out Tyson's screams. Other parents on the field trip stood by watching, wanting to help, but helpless.
Trying not to hurt him, Kammy pinned Tyson down using a technique recently taught to her by his psychiatrist. One hand pressed on his chest, her other holding both of his hands. The second-grader was small enough where she could still control him. He didn't use to be like this. Just a couple of months earlier, Tyson was a happy, active little boy.
His transformation was heartbreaking and all-consuming for the family. His once expressive eyes seemed vacant. Tyson began routinely flying into fits of rage over the smallest things. The engaging, inquisitive child, who had been a wonderful big brother, would now erupt into fits of rage at the sound of little sisters' voices.
Every moment for Kammy and her husband Mike was spent preparing for Tyson's next meltdown. Tyson's temper became so volatile, his father arranged to come home from his job at a moment's notice if the situation at home got out of control, which it frequently did.
As Kammy held Tyson down, she had no idea the little pill she was giving him daily, prescribed by his doctor, could be causing her son's mental and emotional problems.
Nearly three years later, Tyson sits calmly on the back patio at the family's Arizona home. He lets out an embarrassed little laugh when asked if he remembers what happened to him.
"You mean when I lost my mind?" he asks with a little giggle.
Tyson is now a sweet, well-mannered kid. The same child Kammy says he was before a prescription for Singulair to treat his allergies and asthma threw the family's life into chaos.
For families like Tyson's, Singulair may trigger a journey of confusion, concern, and turmoil. For others, it ends in death. Suicidal thoughts and actions are one of the known side effects families say they didn't find out about until after their loved ones killed themselves.
Singulair users who died by suicide:
NEW WARNINGS, LITTLE AWARENESS
Warnings the drug could cause depression, aggression, and suicide began appearing in the package insert for Singulair in 2008, a decade after the drug was put on the market, but the risks were not generally advertised.
According to the FDA, side effects for Singulair and its generics including suicidal thoughts and actions, agitation, aggressive behavior or hostility, attention problems, bad or vivid dreams, depression, disorientation, or confusion, feeling anxious, hallucinations including seeing or hearing things that are not there, irritability, memory problems, obsessive-compulsive symptoms, restlessness, sleepwalking, stuttering, tremor or shakiness, trouble sleeping and uncontrolled muscle movements.
In September of 2019, the FDA held a public meeting titled 'Neuropsychiatric Events with the Use of Montelukast in Pediatric Patients.' Montelukast is the generic of Singulair.
The FDA provided data showing more than 10,000 nervous system and psychotic events attributed to Singulair had been reported to the agency through their 'FDA Adverse Event Reporting System." FAERS is a database where the public and health care professionals can report problems with a medication. Some health experts at the meeting believe the thousands of reports represent only a fraction of the actual number of problems experienced by patients.
Acknowledging that many health care professionals and patients are not aware of the risk of mental health side effects, the FDA issued a 'box warning' for Singulair and its generic Montelukast in March of 2020. A box warning is the agency's strongest and alerts patients a drug carries the potential for serious side effects or death.
Included in the FDA's warning:
- Serious mental health side effects have been reported in patients taking Singulair.
- Because of the risk of mental health side effects, the benefits of Montelukast may not outweigh the risk in some patients.
- Singulair should be reserved to treat allergies only in patients who cannot tolerate other medicines.
- Discontinue Singulair immediately if mental health side effect occurs.
The last warning is the source of debate.
Risks are not limited to children. Katie Johnson was taking Singulair for a matter of weeks when she noticed sudden problems controlling her temper. She describes it as being short with her husband and coworkers.
Her issues progressed to daily suicidal thoughts as she drove to work. "There were times I wanted to drive my car off a bridge," says Katie.
According to Katie, her doctor did not warn her about any potential for side effects. Looking for the cause behind the change in her personality, Katie read the warnings for Singulair and found they include the risk of depression and suicide.
Katie says as soon she stopped taking the medication, "It was like a switch went off," and almost instantly, she was back to her old self.
Katie had no problem going off Singulair. The process was much different for Tyson. Months of doctor's appointments left Kammy with no answers as to the source of Tyson's emotional issues. Desperate for answers, Kammy took Tyson to doctor after doctor. One diagnosed him with ADHD; others blamed his age.
Searching everywhere for answers, she put up a post in an online asthma group. A mother responded and told Kammy about Singulair's potential side effects. Kammy and her husband immediately stopped giving Tyson his nightly dose. Some of Tyson's issues started to resolve, others intensified.
The FDA's Box Warning for Singulair advises people to stop taking the drug immediately if mental health problems develop. That approach is disputed by some people who claim stopping the medication caused withdrawals and, in some cases, the onset or worsening of symptoms.
After taking Singulair for more than a year, Kammy says stopping the medication sent Tyson into extreme withdrawal.
"He got to the point where I didn't know if I needed to check him into the ER. We had to strap him into a car seat because his body was flailing out of control," recalls Kammy.
The pharmaceutical company Merck, Singulair's manufacturer, declined to be interviewed for this article.
A spokesperson for Merck provided a statement which reads in part, "We remain confident in the efficacy and safety of SINGULAIR (montelukast sodium), a medicine that has been prescribed to tens of millions of indicated patients with asthma and allergic rhinitis since its approval more than 20 years ago."
The company did not respond to a follow-up request to address specific questions, including whether the manufacturer has studied the effects of stopping the drug cold turkey versus tapering off. The FDA was more open to questions, responding the agency did not find enough evidence to support recommending tapering off the medication.
CBS 5 Investigates dug deeper into what evidence the FDA considered in making that decision. After examining transcripts from the 2019 meeting, the FDA confirmed to CBS 5 their recommendation was based on the examination of just 17 cases of withdrawal reported to the FAERS database.
Kammy is now an administrator for the Facebook group, 'Montelukast (Singulair) Side Effects Support and Discussion Group.' During the FDA's meeting, Kammy gave a detailed presentation. She highlighted the group's experience that withdrawal may not be as rare as believed.
At the time of the 2019 meeting, there were around 7,300 members of the Facebook group. Nearly 5 percent of the group, 362 people, reported going through withdrawal, of which 267 were children.
The Facebook support group focuses on members sharing their experiences about the side effects of Singulair during treatment and recovery. Administrators post the warning in bold letters, "NO MEDICAL ADVICE IS PROVIDED ON THIS PAGE."
In posts, members detail a wide variety of experiences with tapering off versus suddenly stopping the medication. Some report no reaction; others say effects suddenly developed or increased in severity. Families also detail experiences of withdrawal, sometimes lasting weeks to months.
Kammy says Tyson's withdrawal lasted 6 months.
EFFECTS ON THE BRAIN
Shortly after the box warning was issued, CBS 5 began investigating claims Singulair's manufacturer, Merck, had evidence more than 20 years ago, before the drug went to market, that it could affect the brain.
Attorney Kim Beck, with Beck Law Center, is connected to lawsuits based on those same claims. When the black box warning was announced, she says one question stood out, "Why, after twentysomething years, are we just now putting this significant warning on this drug?"
Documents submitted to the FDA for Singulair's approval included animal testing, which showed 24 hours after a dose of the medication was administered, the amount of drug decreased in the lungs but increased in the brain.
Beck says, "These rat studies demonstrate the drug does pass the blood-brain-barrier and Merck had an obligation to, at the very least say, 'Is this a problem?'" Based on the evidence she has seen, Beck says it appears the drug manufacture failed to investigate what effect the drug has on the brain.
Not all drugs cross the blood-brain barrier, a membrane surrounding the brain which prevents harmful substances from entering.
According to the FDA, at the time of approval, although animal testing showed the drug crossed the blood-brain barrier, there were no signs it affected the central nervous system, so the agency did not require Merck to conduct further studies.
A subtle but significant change has now been made to information and warnings provided in the drug's packaging. The word "minimal" has been removed in describing the amount of drug that crosses the blood-brain barrier.
According to FDA spokesperson Chanapa Tantibanchachai, the change was made "so as not to understate the animal findings and to remove as much ambiguity from the labeling as possible."
Also pointed out lawsuits, the Merck applied for a patent for the drug to treat cerebral spasms, a narrowing of the blood vessels in the brain. According to Beck, applying for the patent showed the drug manufacture knew the drug could have an effect on the brain. The patent was filed in 1996, two years prior to Singulair's approval to treat allergies and asthma in 1998.
NO NEW STUDIES
Excitement over the FDA issuing the box warning has led to disappointment for advocates fighting to raise awareness on the side effects associated with Singulair.
Laura Marotta helped lead the charge for stronger warnings after her son Nicholas was prescribed the generic form of Singulair for asthma. After less than a year of taking the drug, Nicholas began experiencing severe symptoms of anxiety, depression, and hallucinations.
Nicholas Marotta detailed his experience with treatment and withdrawal in a video.
In the FDA's 2019 meeting, there was excitement as the agency acknowledged Singulair not only acts on the lungs, for which it is prescribed but also on the brain.
For Laura, that excitement faded within minutes, as the FDA acknowledged they most likely could not force Merck to conduct further studies on the drug's effects on the brain. The reason may come down to money.
Prior to the availability of generic versions, Singulair was Merck's top selling product bringing in $4.2 billion in sales in 2007, $4.3 billion in 2008, and $4.6 billion in 2009.
Dr. Sally Seymour, with the FDA, said it was her opinion that because Singulair is now available as a generic, the company no longer makes a significant profit from the brand name version.
If the FDA required Merck to conduct additional studies on safety, which are expensive, Merck could let their New Drug Application (NDA) expire. That move would leave only generic versions on the market. The FDA cannot force companies who make generic versions of drugs to do studies.
Laura says the system is broken. "We have a medication that is being prescribed for asthma/allergies with an acknowledged direct action on the brain, with no hope for further studies because Merck doesn't have to study it for the brain effects," she said.
Another disappointment for families who say they have been affected by Singulair is the lack of impact from the box warning. The warning was issued in March 2020 and overshadowed by the COVID-19 pandemic.
Posts in the Singulair support group detail doctors continuing to ignore, not recognize, or downplay side effects.
In a post from Holly Davis, she says she recently expressed concern over her 2-year-old son being prescribed Singular. She says her pediatrician responded, "Did you Google it? Don't ever Google it. That will just scare you."
Holly says risks were also played down by her pharmacist, who told her, "almost no one has side effects from this."
Advocates, while frustrated, continue to fight to raise awareness that Singulair can have life-altering side effects. It's a warning they hope will make it not just to the public but also to doctors.
CONSULT A DOCTOR
A wide range of doctors routinely prescribe Singulair, from allergists and pulmonologists to pediatricians and general practitioners.
CBS 5 Investigates spoke with more than a half dozen doctors. Ten months after the box warning was issued, only one was aware of the increased warning.
Dr. Aaron Wilson, a specialist in mental health and addiction, recommends changes to medication should always be made under a doctor's supervision. From the viewpoint of a psychiatrist, he says a cardinal rule in mental health is to avoid treating a condition that is caused by something else. He cautions against the loop of adding medication on top of medication without first looking for the source of the problem.
"If a medication is causing significant depression and anxiety and we put an antidepressant on that, you end up kind of chasing your tail," says Dr. Wilson. Dr. Wilson suggests patients may need to provide information to their doctors.
A recent poll in the online support group asked members prescribed Montelukast after the box warning was issued, if the doctor warned them about possible mental health side effects; 2 members received verbal warnings, 90 members responded they were not given warnings.
The FDA points out there are a number of safe, effective medications that can be used as alternatives to Singulair. The agency recommends health care professionals prescribe montelukast only if patients don't respond to or cannot tolerate other therapies:
"We have reevaluated the risks and benefits of montelukast and have determined it should not be the first choice treatment, particularly when allergic rhinitis symptoms are mild. In addition, many health care professionals and patients/caregivers are not aware of the risk of mental health side effects despite the existing warnings in the prescribing information." -FDA.
The FDA provides extensive information on its website detailing potential side effects and warnings. Patients may want to bring the information with them to their appointment or send their doctors the link.
Adverse effects linked to medications should be reported to the FDA’s FAERS data base.