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Lyrica Withdrawal & Detox Guide

Medically Reviewed By: Benjamin Caleb Williams RN, BA, CEN

Written By: Phillippe Greenough

Article Updated: 09/25/2020

Number of References: 30 Sources

Lyrica is a prescription medication that is used as an atypical pain reliever, although can still be addictive if taken for too long or in large amounts. The symptoms of Lyrica withdrawal can be quite uncomfortable, and sometimes even dangerous in certain cases. Here we will look at the way this medication works, the symptoms of withdrawal, the timeline involved, and some effective treatments for Lyrica withdrawal symptoms.

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Lyrica Pharmacology & Addiction

Lyrica is commonly used for specific nerve pain conditions although the way it works is very different from normal painkillers such as the more common opioids or NSAIDs like Advil. The active ingredient, pregabalin, is structurally similar to the inhibitory neurotransmitter GABA, however, pregabalin does not stimulate GABA receptors. While the mechanism of action remains unclear, it acts to reduce the release of other excitatory neurotransmitters in an indirect manner. Lyrica does not interact with other neurotransmitter systems per se, but it does affect calcium channels in CNS neurons which, in turn, reduces the neuron’s ability to release a variety of excitatory neurotransmitters.

Through binding to the α-2-δ subunit of certain nerve pathways, Lyrica is able to modulate the release of neurotransmitters. While currently unclear, it is thought that through this primary interaction, Lyrica may be able to inhibit the release of the excitatory neurotransmitters glutamate, norepinephrine, substance P, and CGRP. Regardless of the specific interaction, Lyrica can produce a range of inhibitory effects. These effects include anticonvulsant, anti-anxiety, and analgesic (pain relief) properties. Lyrica’s effects on glutamate are most likely responsible for its anticonvulsant properties, although norepinephrine may play a role here as well. Substance P and CGRP are known to relay pain signals throughout the brain and spinal cord, so inhibition of these neurotransmitters may be a major component of Lyrica’s analgesic effects.

Through continued use of Lyrica, the brain can adapt to the chronic inhibition of excitatory signaling. This is essentially the process of the brain turning up its sensitivity to the neurotransmitters that have been inhibited and is known as upregulation. After upregulation has begun, the brain may undergo further structural changes known as neurological remodeling. Once upregulation has occurred and someone stops using the drug, they will begin experiencing symptoms of Lyrica withdrawal. While upregulation is responsible for the short-term and most intense symptoms, the process of remodeling is responsible for the long-term, less intense symptoms. 1, 2, 3, 4, 5, 6, 7, 8

Symptoms of Lyrica Withdrawal

The symptoms of Lyrica withdrawal can be quite unpleasant and in some cases may even be dangerous. The withdrawal syndrome exhibits both physical and psychological symptoms and these can be both hyperactive and depressive in nature. These symptoms may not necessarily be dangerous in most cases, although they are often very uncomfortable and medical supervision and treatment are frequently recommended.

Some of the symptoms of Lyrica withdrawal include:

  • Sleep Disturbances (usually hypersomnia, but may also exhibit insomnia)
  • Vivid Dreams or Nightmares
  • Increased Anxiety
  • Deep Depression (with or without suicidal ideation)
  • Headaches
  • Fatigue and Lethargy
  • Tremors and Shaking
  • Tachycardia (increased heart rate)
  • Hypertension (elevated blood pressure)
  • Reduced Appetite
  • Nausea and Stomach Pain
  • Vomiting and Diarrhea
  • Diaphoresis (constant sweating)
  • Inability to Concentrate
  • Increased Aggression or Irritability
  • Anhedonia (reduced ability to experience pleasure)
  • Hallucinations (visual, auditory, tactile, or a combination)
  • Delirium and Confusion
  • Strong Cravings for Lyrica
  • Psychosis (rare, but documented) 12
  • Seizure (rare, but documented) 13

The symptoms of Lyrica withdrawal can be similar to GABA agents such as gabapentin or benzodiazepines, although Lyrica withdrawal symptoms are rarely fatal on their own. If someone has underlying health conditions such as impaired kidney function or epilepsy, then they may be at higher risk for dangerous and potentially fatal outcomes. Medical monitoring is recommended in most cases of Lyrica withdrawal to reduce both discomfort and risks. Entering a Lyrica detox center is often the most effective way to treat both the unpleasant physical and mental symptoms of Lyrica withdrawal. 9, 10, 11

Post-Acute Lyrica Withdrawal Symptoms

While the immediate and most intense symptoms of Lyrica withdrawal may only last days to weeks, the more minor but longer-lived symptoms may persist for weeks or months. These symptoms are usually less intense than they may be during the acute phase of withdrawal which occurs immediately after someone stops using Lyrica, although their long duration can present problems of its own.

Some of the post-acute Lyrica withdrawal symptoms include:

  • Depression (with or without suicidal ideation)
  • Increased Anxiety
  • Fatigue and Lethargy
  • Cravings for Lyrica
  • Anhedonia (reduced ability to experience pleasure)
  • Sleep Disturbances
  • Psychosis (very uncommon, but this has lasted for several weeks in rare cases)

While these symptoms may not seem severe, their duration and the likelihood of them interfering with someone’s continued recovery can be detrimental to their chances of long-term sobriety. In addition, the sometimes deep depression that can accompany Lyrica withdrawal may lead to thoughts of suicide or even suicide attempts. These post-acute symptoms should be treated very seriously due to the possibly fatal repercussions they may produce.

Lyrica Withdrawal Timeline

The timeline for the symptoms of Lyrica withdrawal has not been well studied or documented. Based on several case reports, we can make a generalization of this timeline, but there are variables that can affect the half-life of Lyrica and, subsequently, the withdrawal timeline.
On average, the half-life of Lyrica in a healthy adult is about 6 hours. Symptoms of Lyrica withdrawal will begin between 8 to 10 hours after the last dose was taken.

First Week

Within hours of the last use, someone who has developed physical dependence will begin to experience Lyrica withdrawal symptoms. The first to appear are usually increased anxiety and deep depression, sometimes including suicidal thoughts. Excessive sweating and headaches may appear within the first day alongside clouded thinking. Someone’s appetite will often be reduced or totally absent. All of these symptoms usually worsen over the next several days, and the risk of hallucinations, psychosis, or delirium is highest in the first few days after Lyrica cessation. Stomach issues including nausea, cramps, diarrhea, and vomiting are fairly common as is excessive sleepiness. These symptoms often worsen over the three or four days before reaching a plateau and beginning a slow resolution over the next few days.

Second Week

The beginning of the second week often shows much improvement from the first week. While some acute symptoms may still be present, they are usually on their way to resolving. The period of highest risk of experiencing seizures, hallucinations, and psychosis is passed and tremors have usually improved greatly. Stomach issues and diarrhea may still persist, although vomiting and the worst of the stomach cramps have usually dissipated. Hypertension and tachycardia are typically much improved although there may still be some cardiovascular hyperactivity. While the physical symptoms are resolving, the psychological symptoms may still be present at relatively unchanged levels. As the physical symptoms resolve, this can make it seem like the psychological symptoms are intensifying, although this is rarely the case in reality. As the physical symptoms disappear, they can no longer distract as much from the psychological symptoms, so they may seem to intensify.

Third Week

The third week often shows the first signs of real hope for someone experiencing Lyrica withdrawal symptoms. The physical symptoms have usually resolved almost completely by now and while the worst of the physical discomfort may be over, the psychological symptoms are often still present at moderate levels. These symptoms may have shown minor improvement since the second week, but they are almost certainly still present.

Fourth Week and Onwards

By the fourth week, often the only symptoms remaining are psychological in nature. While they may have shown some great improvement since the first week, they should be expected to persist for some time. There is some great variability between individuals as to the duration of post-acute Lyrica withdrawal symptoms, with some people recovering very quickly and others experiencing symptoms for many months. If treatment has not already been sought, it is highly recommended to do so now. The worst may be over, but there is still work to do to build a solid life after Lyrica addiction. 9, 10, 11, 12, 13, 14

Physical Effects of Lyrica Withdrawal

The way that chronic Lyrica use affects the brain can result in a variety of physical withdrawal symptoms. While rarely dangerous on their own, there are some physical symptoms that can increase the risks to someone’s safety, sometimes substantially. Here we will take a look at some of the physical systems that are most greatly affected during withdrawal.

Neurological Effects

The risk of seizure during Lyrica withdrawal is not necessarily common, but it could increase the risk of injury or death substantially if one were to occur. If someone were to suffer a seizure while driving a car, walking down a flight of stairs, or even laying in bed they could suffer injuries secondary to the seizure. The exact cause of the increased risk of seizure during withdrawal is still mysterious, but there are some known contributors.

The receptors for both of the neurotransmitters glutamate and substance P become upregulated through chronic Lyrica use. This means that the sensitivity of the receptors is increased due to the Lyrica-induced reduction in neurotransmitter release. During withdrawal, when these neurotransmitters are released in normal quantities, the increased sensitivity to them causes them to have a much greater impact than they normally would. While the exact role of substance P with regard to Lyrica use is currently unclear, both glutamate and substance P have been shown to exhibit pro-convulsive properties, and substance P is even correlated with status epilepticus, an extremely dangerous and potentially fatal seizure state. 15, 16, 17, 18

Cardiovascular Effects

The cardiovascular hyperactivity during Lyrica withdrawal, while quite common, is not usually dangerous. This is manifested as an increased heart rate and blood pressure, and in the absence of underlying heart health issues, it normally doesn’t present any added risks. The major physical cause of this seems to be the neurotransmitter norepinephrine and its increased impact due to upregulation or its elevated levels due to the psychological stresses of withdrawal.

The neurotransmitter norepinephrine is both a neurotransmitter in the brain and a hormone in the blood. Norepinephrine has multiple roles in both the brain and body and it is a major component of the fight-or-flight response. During withdrawal, this results in increased alertness sometimes likened to a state of hypervigilance as well as increased blood pressure, heart rate, and possibly an increase in blood sugar levels. 19, 20

Psychological Effects of Lyrica Withdrawal

The psychological effects of Lyrica withdrawal, while maybe seeming less severe than the physical effects, can sometimes prove more detrimental to someone’s chances of long-term sobriety. While the physical effects will resolve fairly quickly, often within a week or two of the last drug use, the psychological symptoms can frequently last for months. This can act as a serious barrier to someone building a new life and continuing recovery.

Depression

One of the most common effects of Lyrica withdrawal, depression can range from mild to severe. In the worst cases, someone may have frequent thoughts of suicide and may even act on these thoughts. These symptoms usually fade over time, but medications and therapy can be extremely helpful while the healing process takes place. These effects of depression also have multiple causes including neurological and behavioral.

Since the exact way that Lyrica works is still unclear, there are a lot of unknowns regarding the effects of Lyrica withdrawal. While many of the neurotransmitters affected during Lyrica addiction and withdrawal do not have fully elucidated behavioral impacts, glutamate has some very clear effects on behavior and health and it is somehow impacted by Lyrica use. Glutamate dysregulation is associated with a variety of neurological conditions including major depressive disorder, Alzheimer’s, and Huntington’s disease. Additionally, increased levels of glutamate are correlated with successful suicide attempts, but as usual, correlation does not equal causation. The sometimes profound imbalances in these neurotransmitter systems can produce a deep depression and this is a common effect of Lyrica withdrawal.

From a behavioral standpoint, the loss of a coping mechanism can result in depression. Lyrica use often starts as a minor way to cope, although, this can eventually become someone’s primary means to cope with the stresses of life through chronic use. The extremely powerful anti-anxiety and euphoric effects of Lyrica can be an extremely powerful, although unhealthy, way to cope with problems. When this is suddenly removed, it is common for someone to feel lost, hopeless, and helpless. This can create a deep sense of loss and the feeling that life will never be good again. This is not the case and with continued abstinence, possibly medication, and counseling someone can find some relief while simultaneously developing newer, healthier ways to cope with life and the world. 5, 21, 22, 23, 24, 25, 26

Cravings for Lyrica

Drug cravings are extremely common in almost every drug withdrawal syndrome. That being said, cravings may be especially intense during Lyrica withdrawal. While the exact mechanisms for drug cravings are not clear, it is known that the major excitatory neurotransmitters dopamine and glutamate play a role. Lyrica has no currently identified effect on dopamine transmission, but it most likely does have a major impact on glutamate neurotransmitter systems. Glutamate adaptations and dysregulations have been implicated as major contributors to the phenomenon of drug cravings, and the profound impact with which Lyrica affects these systems seems to play a role. The high incidence and intensity of powerful cravings as an effect of Lyrica withdrawal indicates that glutamate dysregulation may be a major neurological contributor.

There are also behavioral contributions to cravings for Lyrica. Similar to the way behaviors can contribute to depression during Lyrica withdrawal, the use of this drug as a coping mechanism can become an extremely useful and powerful tool to help someone deal with stress. Even though it is extremely unhealthy, Lyrica can become an emotional and behavioral crutch. When this is suddenly removed, someone may feel lost and alone without the comfort that Lyrica used to bring them. Even though these have an overlapping cause, symptoms of depression may also contribute directly to drug cravings during Lyrica withdrawal. The sometimes profound depression felt can intensify someone’s desire to use the drug. Thinking about using Lyrica can become a preoccupation and even a fixation during withdrawal. These cravings often fade with time, but medications and therapy may help someone reduce cravings and develop new coping skills to deal with stress in a healthier way. 27, 28

What Factors Influence the Intensity of Lyrica Withdrawal?

The symptoms of Lyrica withdrawal can exhibit quite a bit of variation in both intensity and duration. Some of the factors that contribute to this variability are based on choices someone makes, such as Lyrica using habits, while others are genetic or health-related and, therefore, are beyond someone’s power to affect. Based on these contributing factors, some people may make a full and swift recovery from mild symptoms, while other people may suffer fairly intense symptoms for months or even years in some cases.

Some factors that can influence both the intensity and the duration of Lyrica withdrawal include:

  • The amount of Lyrica regularly used
  • The duration of Lyrica use
  • Pre-existing physical health conditions (specifically those affecting kidney function)
  • Co-occurring mental illness

The greatest contributor to the intensity and duration of withdrawal is directly related to someone’s Lyrica use habits. The amount of Lyrica someone uses can most readily influence the intensity of Lyrica withdrawal symptoms. The more Lyrica someone uses, the more upregulation (or downregulation, depending) occurs to the neurotransmitter systems it impacts. The more upregulation occurs, the more intense the withdrawal symptoms will be once they stop using the drug. The amount of time someone used Lyrica can also play a role, although this more so affects the duration of withdrawal symptoms. After upregulation has begun, a further process known as neurological remodeling will begin. This is a very slow process and takes time to produce noticeable effects, but the longer someone uses Lyrica regularly, the more complete this remodeling process becomes. As slow as it is to occur, it is just as slow to reverse, so it will take some time after ceasing Lyrica us for this to reverse, thus, the longer someone uses Lyrica the more long-lasting the post-acute withdrawal symptoms will become.

Lyrica and more specifically the active ingredient pregabalin undergoes minimal metabolism and is excreted mainly in the urine via the kidneys. Due to this fact, if someone had impaired kidney function, then the levels of Lyrica in their blood would be higher than in someone with healthy kidney function. This could lead to Lyrica toxicity through continued use, and during withdrawal, this could lead to an extended withdrawal timeline. The half-life of a drug is the amount of time it takes the drug levels in the blood to reduce by half. The half-life of Lyrica is about 6 hours in a healthy person, but this half-life can be greatly extended in those with kidney dysfunction. A longer half-life means a longer withdrawal period, although the symptoms would be less intense as the half-life increases. 29, 30

The existence of mental illness could affect the symptoms of withdrawal both in intensity and duration. This would be an indirect influence, but if someone has struggled with depression or anxiety, then they would likely suffer worse depressive and anxious symptoms during withdrawal. Additionally, these symptoms may last longer or possibly would not resolve as completely as if they had no prior mental health issues.

Lyrica Withdrawal Treatments

While the symptoms of Lyrica withdrawal can be very uncomfortable, there are treatments available to reduce this discomfort. Medications and clinical therapy can provide benefits in both the short-term and the long-term symptoms, and medical monitoring can help manage the risks of dangerous outcomes or complications.

Medications

There are currently no FDA approved medications for the treatment of Lyrica withdrawal symptoms as a whole, but there are effective medications for reducing symptoms individually as they arise. The current medical approach to Lyrica withdrawal is to provide supportive care and risk reduction. Medications can reduce the discomfort and the risks, but the brain must restore the neurotransmitter balance that was disrupted through Lyrica use before the symptoms will resolve. Allowing this to happen safely and as comfortably as possible is the goal of medical interventions regarding Lyrica withdrawal.

Some of the most commonly used medications for treating the symptoms of Lyrica withdrawal include:

  • GABA Agents
  • Glutamate Agents
  • Benzodiazepines (for delirium, psychosis, and seizure risk reduction)
  • Other Anticonvulsants
  • Antidiarrheals
  • Antidepressants
  • Non-Benzodiazepine Anti-Anxiety Medications (like buspirone)
  • Opioid Antagonists (for post-acute symptoms such as cravings)

These are just a few of the classes of medication that are used to treat symptoms of Lyrica withdrawal. Several of these classes have multiple specific medications that may be effective, so there are options. Additionally, everyone responds to medications uniquely, so different people will find specific medications more or less effective. Finding the right one may take time, and having the guidance of medical professionals such as those at a Lyrica detox center can provide an informative and knowledgeable resource to help shorten this time.

Therapy

Aside from medications, there are a variety of clinical therapies that may help reduce the mental discomfort of the psychological and post-acute symptoms of Lyrica withdrawal. While this approach may not provide immediate relief like some medications might, this approach is crucial if someone hopes to have the best possible chance at long-term recovery.

Some therapies commonly used to treat Lyrica withdrawal symptoms include:

  • Behavioral Therapy
  • Coping Skills Development
  • Individual Counseling
  • Group Therapy
  • Support Groups
  • Aftercare Planning

These therapies are just a few effective choices, and similar to medications, different people will find certain therapies more or less effective. Depending on the specific issues someone is dealing with in their life, they may need more customized care. This, again, is where having the professional care of a Lyrica detox center can prove invaluable. Not only can these therapeutic treatment approaches help reduce the psychological discomfort of withdrawal symptoms, but they may also help someone build a solid foundation in recovery. Developing new, healthy coping skills is a major component of recovery, and these therapies can be extremely helpful in this regard.

Lyrica addiction can often take control over someone’s life, causing great harm to them and others in the process. While it may seem hopeless at times, recovery from Lyrica addiction is possible. There is help available in the form of Lyrica detox centers, and others who have struggled with Lyrica addiction and subsequently emerged into a new life, free of Lyrica. Entering a Lyrica detox center is often the first step on the journey of recovery and aside from the immediate benefits these centers provide, they also have connections with recovery fellowships and communities in their local area. Making connections with others who have recovered can be very empowering and can foster hope. Recovery is possible and help is available, all it takes is the courage to reach out and ask for it.

References For This Article

  1. 1 FDA AccessData: Lyrica (pregabalin) Capsules Label
  2. 2 StatPearls: Pregabalin
  3. 3 Epilepsia: Pregabalin Pharmacology and Its Relevance to Clinical Practice
  4. 4 Anesthesia & Analgesia: Pregabalin - Its Pharmacology and Use in Pain Management
  5. 5 Nature - Scientific Reports: Pregabalin - Potential for Addiction and a Possible Glutamatergic Mechanism
  6. 6 Cell and Tissue Research: Substance P and Pain Chronicity
  7. 7 Headache - The Journal of Head and Face Pain: Calcitonin Gene-Related Peptide (CGRP) and Migraine
  8. 8 WHO Expert Committee on Drug Dependence: Critical Review Report - Pregabalin
  9. 9 Turkish Journal of Psychiatry: Pregabalin Dependence - A Case Report
  10. 10 Cureus: Pregabalin-associated Discontinuation Symptoms - A Case Report
  11. 11 Southwest Journal of Pulmonary & Critical Care: Acute Pregabalin Withdrawal - A Case Report and Review of the Literature
  12. 12 Psychiatry and Clinical Psychopharmacology: First-episode Psychosis Induced by Pregabalin Withdrawal - A Case Report
  13. 13 BMJ Case Reports: Seizure Induced by Sudden Cessation of Pregabalin in a Patient with Chronic Kidney Disease
  14. 14 Her Majesty’s Prison Service: Protocol for the Management of Pregabalin and Gabapentin Use in HMP Lewes
  15. 15 PLOS One: Faster Flux of Neurotransmitter Glutamate During Seizure - Evidence from 13C-enrichment of Extracellular Glutamate in Kainate Rat Model
  16. 16 Cold Spring Harbor Perspectives in Medicine: Glutamatergic Mechanisms Associated with Seizures and Epilepsy
  17. 17 Current Neuropharmacology: Substance P Regulation in Epilepsy
  18. 18 Oncotarget: The Role of Substance P in Epilepsy and Seizure Disorders
  19. 19 CNS Drugs: Pregabalin for the Treatment of Drug and Alcohol Withdrawal Symptoms - A Comprehensive Review
  20. 20 Neuroscience & Biobehavioral Reviews: The Brain Norepinephrine System - Stress and Cardiovascular Vulnerability
  21. 21 Drugs: Targeting the Glutamatergic System to Treat Major Depressive Disorder - Rationale and Progress to Date
  22. 22 Frontiers in Psychiatry: Glutamatergic Dysfunction and Glutamatergic Compounds for Major Psychiatric Disorders - Evidence From Clinical Neuroimaging Studies
  23. 23 Neuropharmacology: Towards A Glutamate Hypothesis of Depression - An Emerging Frontier of Neuropsychopharmacology for Mood Disorders
  24. 24 Frontiers in Cellular Neuroscience: The Therapeutic Potential of Targeting Substance P/NK-1R Interactions in Inflammatory CNS Disorders
  25. 25 Dialogues in Clinical Neuroscience: The Role of Substance P in Depression - Therapeutic Implications
  26. 26 Nature - Scientific Reports: The Association Between Substance P and White Matter Integrity in Medication-naive Patients with Major Depressive Disorder
  27. 27 Journal of Psychopharmacology: The Good and Bad News about Glutamate in Drug Addiction
  28. 28 Frontiers in Neuroscience: Glutamatergic Transmission in Drug Reward - Implications for Drug Addiction
  29. 29 NDT Plus: Two Cases of Pregabalin Neurotoxicity in Chronic Kidney Disease Patients
  30. 30 Journal of the American Society of Nephrology: Gabapentin and Pregabalin Use and Association with Adverse Outcomes among Hemodialysis Patients

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