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Lyrica Withdrawal Timeline

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

Written By: Phillippe Greenough

Article Updated: 01/21/2021

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 Withdrawal Symptoms

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. The timeline for the symptoms of Lyrica withdrawal has not been well studied or documented. Based on several case reports involving a 34-year-old man, a 62-year-old woman, and a 61-year-old man, 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.

A generalized overview of the Lyrica withdrawal timeline may look like this:

Week 1

Since the half-life of Lyrica is about 6 hours, someone who has developed physical dependence will begin to experience Lyrica withdrawal symptoms within 12 hours of their last use. The first symptoms 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.

Some symptoms of Lyrica withdrawal that can be expected during the first week may 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)
  • Seizure (rare, but documented)

Week 2

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 usually passed by this point. 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.

Some of the symptoms that may be experienced during the second week of Lyrica withdrawal may include:

  • Vivid Dreams or Nightmares
  • Anxiety
  • Depression (with or without suicidal ideation)
  • Fatigue
  • Minor Tremors
  • Reduced Appetite
  • Clouded or Disorganized Thinking
  • Irritability
  • Mild Anhedonia (reduced ability to experience pleasure)
  • Strong Cravings for Lyrica

Weeks 3 & 4

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. 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.

Some lingering Lyrica withdrawal symptoms that may persist into the third and fourth week may include:

  • Vivid Dreams or Nightmares
  • Anxiety
  • Depression (with or without suicidal ideation)
  • Fatigue
  • Clouded or Disorganized Thinking
  • Irritability
  • Cravings for Lyrica

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.

Post-Acute Withdrawal

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
  • Low Energy Levels
  • Cravings for Lyrica

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.

What Factors Influence the Intensity of 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.

More About Lyrica 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.

The Importance of Detox

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.

Article References (In Addition to 7 in-article references)

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

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