Therapies For Pain In Parkinson Disease: Concerns Related To A Meta
Department of Oral and Maxillofacial Pathology, Radiology, and Medicine,
New York University College of Dentistry
380 Second Avenue, Suite 301, New York, NY 10010
E-Mail kgr234@nyu.edu
Dear Editor,
As an academic clinical research scientist studying pain conditions for several decades and as a person who has lived with Parkinson Disease for more than 8 years, I was initially delighted to see the review and meta-analysis by Qureshi et al. concerning treatment of pain in PD. Good quality meta-analytic reviews can help to reconcile inconsistent findings and small-sample studies within a field. Evaluating best treatments for pain in PD is particularly important, as pain is the most troublesome nonmotor symptom in early-stage PD . It may often precede the onset of motor symptoms .
Unfortunately, I fear that this meta-analysis does little to advance treatment of pain in PD. Why? Inherently, to justify combining across different studies, an assumption must have been made that “Parkinson’s Pain” is a uniform entity.
The fact that all of these distinct types of pain can be measured on a visual analogue severity scale or other severity scale does not justify collapsing across different types of pain when conducting a meta-analysis. Surveys suggest that the most prevalent type of pain in people with PD is musculoskeletal . Relative high representation of musculoskeletal pain may obscure the efficacy of treatments for less common types of pain in patients with PD.
Innovative Treatment Modalities For Managing Pain In Parkinson’s
Botulinum toxin
Non-dopaminergic pharmacotherapy may benefit patients with PD-related pain. Botulinum toxin , both A and B derivatives, should be considered in patients who do not respond to dopaminergic treatment optimization.1,8 Botulinum toxin injection provides localized treatment by blocking the release of acetylcholine at the neuromuscular junction.4 Local injections of BTX type A or B can be effective for persistent dystonia-related pain and central pain, based on its neuromuscular action in movement disorders plus analgesic mechanism.
A randomized, double-blind, crossover, placebo-controlled trial concluded that BTX-A in patients with PD is safe and potentially useful in treating limb pain.29 The study was conducted in patients with PD over the age of 30 years with painful limbs not responding to the optimization of anti-Parkinsonian medications. Patients were randomized to receive BTX-A injection or placebo, followed by the other treatment per the crossover design. Depending on the location of pain, patients received up to 200 units in upper limbs or up to 300 units in lower limbs. Patients experienced a significant reduction in their self-reported numerical pain score 4 weeks after the BTX-A injection , but not with placebo . There was no difference between the change with BTX-A compared to placebo . This study demonstrated that targeted BTX-A injections are safe in patients with PD.
Cannabinoids
A Critical Reappraisal Of The Worst Drugs In Parkinsons Disease
What are the worst drugs for Parkinson’s disease patients? Couldn’t a simple list be assembled and disseminated to the Parkinson community? Recently Ed Steinmetz, an experienced neurologist in Ft. Meyers, FL pointed out to me, a list approach published in the Public Citizen Newsletter . The approach was to list every drug associated with a single confirmed or unconfirmed symptom of Parkinson’s disease or parkinsonism. Parkinson’s disease is defined as a neurodegenerative syndrome , whereas parkinsonism encompasses a wider net of drug induced and other potential causes. In parkinsonism symptoms are similar to Parkinson’s disease, but patients do not have Parkinson’s disease. Patients and family members confronted with a simple “drug list” approach may falsely conclude that most medicines are bad for Parkinson’s disease, and that any medicine may cause parkinsonism. This concept is in general, incorrect. Although the approach is well-meaning, it is in need of a major revision, as Parkinson’s disease and parkinsonism are too complex to summarize by simple lists. In this month’s column I will try to summarize the key information that patients and family members need to know about the “worst pills,” for Parkinson’s disease and parkinsonism.
A Florida Parkinson’s Treatment Blog by Michael S. Okun, M.D.
UF Center for Movement Disorders & Neurorestoration, Gainesville FL
Pain Is An Unfortunately Common Problem In Parkinsons Disease
Of course, pain is common in the general population, especially among older people. A recent American study found that pain affected about twice as many people with Parkinson’s Disease than those of the same age and gender without PD. About 50% of Parkinson’s Disease patients in that study suffered from painful disorders. Men and women seem to be about equally affected. A very well described scenario is the patient who is followed for a painful frozen shoulder for a year or so before a tremor develops leading to a diagnosis of PD. Pain clearly plays a major role in quality of life. Everyone with chronic pain enjoys life less, leading to a vicious cycle in which pain causes depression or isolation which in turn leads to more pain.
Parkinson patients suffer from the same pain problems that other people have, often amplified by the motor dysfunction, but they also have additional pain problems which are unique to PD.
One recent review classified the types of pain Parkinson’s Disease patients have into: musculoskeletal, in which the pain results from problems with the muscles , bones or joints; dystonic, which is due to abnormal muscle contractions caused by the Parkinson’s Disease or the medications used to treat it; radicular pain, which is feels like the pain caused by pinched nerves; central pain, which is presumed due to abnormalities in the brain, and is a continuously present pain that cannot be explained otherwise; and discomfort related to an unpleasant urge to move.
Lower Back Pain And Back Of The Neck Pain Are Most Common
Pain occurs for a number of reasons and it’s not always clear what the cause is, making it difficult to figure out how best to treat it. I believe that most common pain problems in Parkinson’s Disease are the same as in the general population, but amplified. Low back pain and back of the neck pain are probably the most common pain conditions in PD. The reason Parkinson’s Disease patients have so many problems with their low back and their neck is their posture. Parkinson’s Disease causes a stooped posture. Some of this happens with age anyway, particularly in women after menopause when their bones soften, but is always worse from the PD. All Parkinson’s Disease patients have some degree of stooped posture and many also tilt to one side. Because of the stooped posture, the muscles in the lower back have to pull much harder to keep the spine upright.
Use Of Pregabalin For The Treatment Of Essential Tremor
Review question
The authors of this review tried to assess the effectiveness and safety of pregabalin in people with essential tremor.
Backgound
Essential tremor is the most common movement disorder. Although benign in terms of its effect on life expectancy, it is typically progressive and potentially disabling. Treatment consists primarily of pharmacological agents , which could be ineffective for 25% to 55% of patients. Some specialists have suggested that pregabalin could be a potentially useful drug for treating the condition.
Study characteristics
We found one study comparing pregabalin versus placebo, involving 22 randomised participants with essential tremor.
Key results
The impact of pregabalin on functional abilities and adverse effects is uncertain because the quality of the evidence is very low.
Quality of the evidence
The lack of studies and the significant limitations in the one included trial preclude firm conclusions about the risk-benefit profile of this treatment.
The effects of pregabalin for treating essential tremor are uncertain because the quality of the evidence is very low. One small study did not highlight any effect of this treatment; however, the high risk of bias and the lack of other studies on this topic limit further conclusion.
To assess the effects of pregabalin versus placebo or other treatment for essential tremor in adults.
Parkinson’s Breakthough Could Slow Disease Progression
- Date:
- Northwestern University
- Summary:
- In an early-stage breakthrough, scientists have developed a new family of compounds that could slow the progression of Parkinson’s disease. Parkinson’s is the second most common neurodegenerative disease and there is no treatment to slow the advance of the disease. The compounds are a new class of potential therapeutics.
In an early-stage breakthrough, a team of Northwestern University scientists has developed a new family of compounds that could slow the progression of Parkinson’s disease.
Parkinson’s, the second most common neurodegenerative disease, is caused by the death of dopamine neurons, resulting in tremors, rigidity and difficulty moving. Current treatments target the symptoms but do not slow the progression of the disease.
The new compounds were developed by Richard B. Silverman, the John Evans Professor of Chemistry at the Weinberg College of Arts and Sciences and inventor of the molecule that became the well-known drug Lyrica, and D. James Surmeier, chair of physiology at Northwestern University Feinberg School of Medicine. Their research was published Oct. 23 in the journal Nature Communications.
“These are the first compounds to selectively target this channel,” Surmeier said. “By shutting down the channel, we should be able to slow the progression of the disease or significantly reduce the risk that anyone would get Parkinson’s disease if they take this drug early enough.”
Story Source:
Long Term Users Become Physically Dependent On Lyrica
Lyrica abuse is the most prevalent for those who have been taking it long-term. The body grows more dependent and requires heavier doses to work properly. The larger the dose, the more difficult it is for the body to live without it.
While it’s been tested to produce a good feeling effect on the brain, there is no chemical makeup of the drug that should allow this. Some professionals believe it has something to do with the sudden lack of pain as opposed to a good feeling. It is dangerous to take without the supervision of a doctor and doses shouldn’t be increased on your own.
Chronic use of Lyrica can lead to a physical dependency on it. The withdrawal is said to be like alcohol or benzodiazepines symptoms. How severe the withdrawal depends on how long you’ve been using Lyrica and what your doses are.
Strengthening Exercises Or Stretching May Be Helpful
Imagine that the spine is like a telephone pole or the mast of a sailboat. If the pole is not exactly upright, even a slight tilt requires a great force to keep it from tilting further and falling. In the human body, this means that the lower back muscles are under great stress. It also means that the tension on the back bones is much increased as well. This worsens whatever problems, like arthritis, that are already present. The same process applies to the neck, although the forces are less great. Strengthening exercises or stretching may be helpful. Almost everyone over the age of 60 has arthritis in their spine. Luckily most don’t have pain from it, but those who do will have it worsened by the spine curvature caused by the PD.
PD patients also frequently have an aching discomfort in their muscles, particularly in the thighs and shoulders. I think this is due to the rigidity, or stiffness, that is part of the Parkinson’s Disease syndrome, but I’ve seen many patients with this pain and no apparent stiffness on examination, hence not explained. It is common and it often, but not always, responds to alterations of the usual Parkinson’s Disease medications for movement. Exercise and stretching may be helpful as well and should always be tried first before increasing medications.
Pain is a challenge in PD. We can’t measure it and often cannot find its cause. It is, however, often treatable, and reducing pain improves quality of life.
Time On Lyrica When People Have Libido Increased *:
- < 1 month: 87.5 %
* Approximation only. Some reports may have incomplete information.
Side Effects Requiring Immediate Medical Attention
Along with its needed effects, pregabalin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur while taking pregabalin:
Less common
Applies to pregabalin: oral capsule, oral solution, oral tablet extended release
Additional Information For Patients And Caregivers
- FDA is warning that serious breathing difficulties may occur when gabapentin or pregabalin is taken with other medicines that depress the central nervous system such as opioids, in those patients who have underlying respiratory problems, or in the elderly. There is less evidence supporting the risk of serious breathing difficulties with gabapentinoids alone in otherwise healthy individuals, and we will continue to monitor this population for additional evidence.
- Respiratory problems can be life-threatening, so seek medical attention immediately if you or someone you are caring for experiences the following symptoms:
- Confusion or disorientation
- Extreme sleepiness
- Slowed, shallow, or difficult breathing
- Unresponsiveness, which means the person doesn’t answer or react normally or you can’t wake them up
- Bluish-colored or tinted skin, especially on the lips, fingers, and toes
Pain Management Principles In Parkinson’s Disease
Non-pharmacologic methods with a multidisciplinary pain team should be utilized to provide optimal multimodal treatment in patients with PD.4 Muscle relaxation exercises and walking regularly can improve flexibility and dampen experiences of pain associated with motor symptoms.6 Rehabilitation with a physical therapist can improve gait and balance, targeting pain caused by motor symptoms. Surgical interventions, such as deep brain stimulation or an implanted spinal cord stimulator, may be appropriate for those patients experiencing pain with PD who do not respond to pharmacologic or rehabilitation interventions.1,6,9
Optimization of treatment with levodopa and other antiparkinsonian medications should be the first pharmacological step in managing PD-related pain.6,8 Beyond this recommendation, no evidence encourages the use of specific analgesic agents in any stepwise order, making patient input and assessment of pain type critical to appropriate treatment.
Patients should be prescribed analgesics if optimization of dopaminergic agents is not effective on its own .4
Optimization of Dopaminergic Agents
Safinamide is a selective, reversible MAO-B inhibitor that reduces degradation and reuptake of dopamine to increase levels in the striatum.19 Safinamide also has non-dopaminergic properties that modulate glutamate release via inhibition of voltage-gated sodium channels. This dual mechanism may mitigate pain, especially during “off” periods.
What Are Gabapentinoids And How Can They Help Me
Gabapentinoids are FDA-approved to treat a variety of conditions including partial seizures and nerve pain from spinal cord injury, shingles, and diabetes. Other approved uses include fibromyalgia and restless legs syndrome. Gabapentin was first approved in 1993 and pregabalin was first approved in 2004. Gabapentin is marketed under the brand names Neurontin and Gralise, and also as generics. Gabapentin enacarbil is marketed under the brand name Horizant. Pregabalin is marketed under the brand names Lyrica and Lyrica CR, and also as generics. Pregabalin is a Schedule V controlled substance, which means it has a lower potential for abuse among the drugs scheduled by the Drug Enforcement Administration , but may lead to some physical or psychological dependence.
Patients and caregivers should seek medical attention immediately if you or someone you are caring for experiences symptoms of respiratory problems, because these can be life-threatening. Symptoms to watch for include:
- Confusion or disorientation
- Extreme sleepiness or lethargy
- Slowed, shallow, or difficult breathing
- Unresponsiveness, which means a person doesn’t answer or react normally or you can’t wake them up
- Bluish-colored or tinted skin, especially on the lips, fingers, and toes
Always inform your health care professional about all the drugs you are taking, including prescription and over-the-counter medicines and other substances such as alcohol.
Related Publications That Referenced Our Studies
- de Landaluce, L. O., Carbonell, P., Asensio, C., Escoda, N., López, P., & Laporte, J. R. , “Gabapentin and Pregabalin and Risk of Atrial Fibrillation in the Elderly: A Population-Based Cohort Study in an Electronic Prescription Database”, Drug safety, 2018 Jan .
- Bonnet U, Taazimi B, Grabbe HD, “Pregabalin-Related Hypertriglyceridemia”, Psychosomatics, 2014 Nov .
Pregabalin In The Treatment Of Essential Tremor
| The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| First Posted : March 28, 2008Results First Posted : March 12, 2021Last Update Posted : April 26, 2021 |
- Study Details
Study DescriptionArms and InterventionsOutcome MeasuresEligibility CriteriaContacts and LocationsMore Information
Pregabalin is approved for the treatment of nerve pain as well as an additional therapy in the treatment of seizures. In December 2004, Pfizer gained Food and Drug Administration approval for use of pregabalin in nerve pain associated with diabetes and shingles; making it the first FDA-approved treatment for both of these nerve pain states.
Tremor is uncontrolled trembling in part of the body. Essential tremor is associated with purposeful movement. It occurs most often in the hands and head and also may affect the arms, voice box , trunk, and legs. ET is caused by abnormalities in areas of the brain that control movement. It usually does not result in serious complications.
ET affects approximately 5 million people in the United States. Incidence is highest in people over the age of 60.
- Brushing hair and teeth
- Holding a glass without spilling
- Performing self-care
- Using eating utensils
- Writing and drawing
| Drug: pregabalin Drug: placebo | Early Phase 1 |
Study DescriptionArms and Interventions
Decreased Behavioral Changes Such As Agitation
Is lyrica used for parkinson’s. Your doctor is the best judge of whether this is possible and how to accomplish it. A recent American study found that pain affected about twice as many people with Parkinsons Disease than those of the same age and gender without PD. In my experience Lyrica is much better for the nerve pain.
It is created by eHealthMe based on reports of 31349 people who have side effects when. The symptoms are only remotely suggestive of PD. There are fewer side effects with its later offspring Pregabalin.
Gus January 8 2018 736pm 5. Pamelor is a tricyclic antidepressant and Lyrica is. There is potential for.
Here are 10 things you should know. The American Parkinson Disease Association APDA is the largest grassroots network dedicated to fighting Parkinsons disease PD and works tirelessly to help the approximately one million with PD in the United States live life to the fullest in the face of this chronic neurological disorder. Basically Gabapentin was developed as an anti epileptic drug but discovered to be useful in neuropathic pain by suppressing abnormal signals so I guess that is the effect it is having on tremor.
Azilect mirapex parkinsons disease carbidopa gabapentin. Marvell 9 Oct 2011. Founded in 1961 APDA has raised and invested more than 207 million to provide outstanding.
Further studies are needed to. It is always important to follow directions to decrease the risk of undesirable side effects. And delayed need for long-term care facilities.
Is There A Risk Of Lyrica Abuse Or Addiction
Pregalin is a drug that was FDA approved for convulsions as well as pain caused by nerve damage from diabetes or an injury to the spinal cord. The brand name in the US is Lyrica and its popularity as a pain medication has grown quickly in a short amount of time.
While it hasn’t been on the market for long, as of 2013, it was ranked the 19th most prescribed drug, earning its manufacturer $3 billion annually. As it’s so new on the market, it’s not known to what extend can Lyrica be abused. While the drug is prescribed for those with partial seizure disorders and fibromyalgia, it has been said to help treat anxiety. As increasingly more people are being prescribed Pregabalin, the question remains, is Lyrica abuse possible?
Environmental Toxins And Parkinsons Disease
Parkinson’s disease is said to be because of the loss of dopamine-releasing nerve cells in a small, central part of the brain called the substantia nigra. The substantia nigra produces dopamine, which helps coordinate movement in our body.
But when nigral nerve cells are impaired, less dopamine is released and motor function is affected. And that’s when hallmark Parkinson’s symptoms including tremors, difficulty balancing, and slowed movement start to set in.
Several studies have suggested that environmental toxicants including pesticides, herbicides, and other pollutants are linked to an increased risk of developing Parkinson’s disease.
Here’s how these chemicals are said to play a role in the development of the neurological disorder:
Safe Use To Decrease Unwanted Side Effects Claudia Chaves, MD
Claudia Chaves, MD, is board-certified in cerebrovascular disease and neurology with a subspecialty certification in vascular neurology. She is an associate professor of neurology at Tufts Medical School and medical director of the Lahey Clinic Multiple Sclerosis Center in Lexington, Massachusetts.
Lyrica is an FDA-approved drug that is used to treat fibromyalgia and certain other conditions.?? You may have seen advertisements for Lyrica and want to know more about its benefits and precautions.
It is always important to follow directions to decrease the risk of undesirable side effects. Here are 10 things you should know about Lyrica.
A Case Of Pregabalin Induced Parkinsonism
BC. Ari, F. Mayda Domac, G. Ozgen Kenangil
Location: Agora 2 West, Level 2
Objective: Present a case of parkinsonism after administration of pregabalin, a rare case
Background: Drug induced parkinsonism is the second common movement disorders after Parkinson’s Disease. The most commons are dystonia, akathisia, myoclonus and tremor. It occurs due to the use of not only neuroleptics but also SSRIs, lithium, calcium channel blokers and valproic acid. Pregabalin is a structural analog of gamma amnobutiric acid that binds to the alpha-2-delta subunit of N-type calcium channels, is the antiepileptic drug that is used for epileptic seizures and neuropathic pain. Its use decrease the release of several neurotransmitters. Due to the report of pregabalin induced parkinsonism is rare, we wished to present a case.
Method: Case report
References: 1.Matsuki Y, Tabata M, Nobukawam Y, Sakai M, Yasuca Y, Mizogam M, Shigemi K. Muscle rigidity associated with pregabalin. Pain physician. 2012;15, E349-351, 2.Lloret SP, Amaya M, Merello M. Pregabalin-induced parkinsonism: a case report. Clinical neuropharmacology. 2009;32, 353-354, 3.Shin W, Chung SJ. Drug-induced parkinsonism. Journal of clinical neurology. 2012:8,15-21.
To cite this abstract in AMA style:
Mov Disord.
What Is In Lyrica That Makes It Addictive
The potential for Lyrica abuse or addiction is possible. Pregabalin is a type V substance so it’s not considered to be extremely addictive. On the list of addictive drugs, Lyrica sits in the category of low risk. The point is however that Lyrica abuse potential exists as it is on the list.
While Pregabalin doesn’t produce the same kind of high and addiction rates as other prescription drugs, it does relax you greatly. When compared to highly addictive prescription drugs like oxycodone, which causes a feeling of euphoria, the high you get with Lyrica is slight. Why Lyrica is addictive is due to the loss of pain coupled with a relaxed feeling which does offer a mild high.
Some people may become dependent on escaping their every feelings of pain or anxiety. There has been no proof documenting that you can become chemically addicted to Lyrica but there is risk of psychological dependence. This is especially true for those with addictive personalities or a previous history of addiction to other substances.
What Should Health Care Professionals Do
Health care professionals should start gabapentinoids at the lowest dose and monitor patients for symptoms of respiratory depression and sedation when co-prescribing gabapentinoids with an opioid or other central nervous system depressant such as a benzodiazepine. Patients with underlying respiratory disease and elderly patients are also at increased risk and should be managed similarly.
We recognize that incorporating one or more medications with non-drug therapies is the prevailing approach for optimizing analgesia. However, pairing an opioid with any CNS depressant – a gabapentinoid, benzodiazepine, sedating antidepressant, sedating antipsychotic, antihistamine, or other product – will increase the risk of respiratory depression. Shifting treatment from one CNS depressant to another may pose similar risks. Be aware of the potential additive effects of all these CNS depressants and plan accordingly, by starting with low doses, titrating carefully, and informing patients of the potential for CNS and respiratory depression and their symptoms. The gabapentinoid prescribing information already includes guidance for health care professionals to caution patients about dizziness, somnolence, and the potential for impaired ability to operate a car or complex machinery.
What To Do If Your Senior Has Parkinsons
If you notice Parkinson’s-like symptoms in your older adult, the first thing to do is talk with their doctor. The doctor should review their complete medication history and you should let them know about any other symptoms or changes.
Important: Don’t make any changes to medications without doctor approval – that could cause serious problems.
Side Effects And Risks Of Taking Lyrica
![[Webinar Recording] Pain and Parkinson](https://www.parkinsonsinfoclub.com/wp-content/uploads/webinar-recording-pain-and-parkinsons-davis-phinney.png.webp)
Lyrica abuse and addiction shouldn’t be discounted. It may seem harmless, sitting low on the addiction spectrum, but it can still result in you needing to admit yourself into prescription medication addiction rehab. Lyrica abuse potential grows all the time due to an increasing amount of people being prescribed the medication. Pregabalin was created as an anticonvulsant to treat seizures and pain related to nerve damage. It can also help anxiety but was not FDA approved to do so. This hasn’t stopped doctors from administering it to the public however. It’s not as addictive as the other prescription painkillers which is why doctors feel it’s a safe bet to prescribe. There are risks of Lyrica addiction and abuse however.
What Should I Avoid While Taking Lyrica
While taking Lyrica, it is important not to drink alcohol, as it increases some side effects. Because Lyrica and alcohol affect each other, you may experience increased dizziness or severe drowsiness that can impair your functioning. Until you are familiar with your personal reaction to Lyrica, you should not drive, operate machinery or perform activities that require much coordination. This is because some people who take Lyrica experience unfamiliar drowsiness that can impair their normal reactions. Because Lyrica can cause drowsiness, it may intensify the effects of other medications that have the same effect. Some examples of these medications include: those treating depression, anxiety, allergies, sleep disorders, colds or seizures. Though your doctor will prescribe the correct dosage of Lyrica to fit your needs, it is important not to use substances that cause excess drowsiness while taking Lyrica. Also, avoid abrupt or rapid discontinuation, as this may result in diarrhea, headaches, insomnia or nausea. If you are to stop taking Lyrica, your doctor should gradually decrease your dosage over time rather than discontining abruptly.
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Do Not Stop Without Consulting Doctor
Lyrica should be taken at the prescribed dosage. If a dose of Lyrica is missed and it’s almost time for the next dose, skip the missed dose. Two doses of Lyrica should not be taken together.
Do not stop taking Lyrica without consulting your doctor. You should continue taking the drug even after experiencing pain relief. Also, plan for refills so that the prescription does not run out.
What Safety Concern Is Fda Announcing
The U.S. Food and Drug Administration is warning that serious breathing difficulties may occur in patients using gabapentin or pregabalin who have respiratory risk factors. These include the use of opioid pain medicines and other drugs that depress the central nervous system, and conditions such as chronic obstructive pulmonary disease that reduce lung function. The elderly are also at higher risk.
Gabapentin and pregabalin are FDA-approved for a variety of conditions, including seizures, nerve pain, and restless legs syndrome.
Our evaluation shows that the use of these medicines, often referred to as gabapentinoids, has been growing for prescribed medical use, as well as misuse and abuse. Gabapentinoids are often being combined with CNS depressants, which increases the risk of respiratory depression. CNS depressants include opioids, anti-anxiety medicines, antidepressants, and antihistamines. There is less evidence supporting the risk of serious breathing difficulties in healthy individuals taking gabapentinoids alone. We will continue to monitor these medicines as part of our routine monitoring of all FDA-approved drugs.