Pregabalin was approved for use in the United States in 2004.  It was originally developed as a successor drug to Gabapentin. Lyrica (Pregabalin) went generic in 2019 and is available in a number of countries worldwide for the treatment of diabetic neuropathy, neuralgia and central neuropathic pain. Evidence does not support Pregabalin being useful in sciatica, low back pain, migraines or cancer-associated neuropathic pain.

Pregabalin was found to be only moderately effective for generalized anxiety disorder but the World Federation of Biological Psychiatry recommends other agents, such as SSRIs as first line treatment for Obsessive-Compulsive Disorder (OCD) and Post Traumatic Stress Disorder (PTSD).

The side effects and withdrawal profile for Pregabalin is similar to Benzodiazepines and a rapid cessation can cause a seizure.  Pregabalin can cause both physical and psychological dependence and abruptly stopping, even after short term use, can cause withdrawal symptoms that include anxiety, diarrhea, flu-like symptoms, major depression, increase in pain, nervousness, convulsions, hyperhidrosis and extreme dizziness. The manufacturer recommends a gradual reduction schedule yet none is provided in the product insert.

Pregabalin can interact with opioids, benzodiazepines, barbituates, alcohol and many other drugs.

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PREGABALIN WITHDRAWAL SYMPTOMS MAY INCLUDE:

anger, anxiety, body aches, chills, crying spells, depersonalization, depression, diarrhea, dizziness, fatigue, flu-like symptoms, headache, hot flashes, irritability, itching, joint pain, mood swings, muscle spasms, nausea, panic attacks, poor concentration, seizures, shortness of breath, sleep issues, stomach pain, suicidal thinking, sweating, vision issues, weight loss 

PREGABALIN SIDE EFFECTS MAY INCLUDE: 

loss of muscle coordination, blurred vision, difficulty concentrating, dizziness, dry mouth, fluid retention in legs, feet, arms, hands, weight gain, infection, decreased blood platelets, constipation, confusion, backache, generalized weakness, excessive saliva production, head pain, increased hunger, inflammation, joint pain, itching, memory impairment, muscle spasm, numbness, twitching, hives, kidney stones, low blood sugar, ringing in ears, suicidal thoughts, wheezing, double vision, behavioral problems, anxiousness, bronchitis, bruising, chest pain, skin rash, vision issues, depersonalization, diarrhea, enlarged breasts, fever, gas, flu-like symptoms, leg cramps, low energy, tremor, nervousness, nausea, pink eye, skin redness, vomiting, breathing issues

PREGABALIN ADVERSE REACTIONS MAY INCLUDE: per PDR 

Severe: visual impairment, angioedema, laryngeal edema, heart failure, oliguria, cholecystitis, pancreatitis, GI bleeding, retinal edema, ocular hemorrhage, suicidal ideation, epididymitis, coma, pulmonary edema, renal failure (unspecified), increased intracranial pressure, pulmonary fibrosis, apnea, ventricular fibrillation, retroperitoneal fibrosis, esophageal ulceration, acute cerebellar syndrome, torticollis, anaphylactoid reactions, skin necrosis, Stevens-Johnson syndrome, skin atrophy, exfoliative dermatitis, papilledema, keratitis, night blindness, optic atrophy, uveitis, keratoconjunctivitis, Guillain-Barre syndrome , rhabdomyolysis, new primary malignancy 

Moderate: peripheral edema, ataxia, blurred vision, amblyopia, euphoria, constipation, peripheral neuropathy, edema, confusion, amnesia, myasthenia, chest pain (unspecified), memory impairment, myoclonia, fluid retention, hypoglycemia, dyspnea, thrombocytopenia, urinary incontinence, skin ulcer, hypotension, hypertension, depression, elevated hepatic enzymes, hematuria, dysuria, orthostatic hypotension, phlebitis, palpitations, ejaculation dysfunction, urinary retention, hyperacusis, oral ulceration, gastritis, colitis, melena, dysphagia, esophagitis, cholelithiasis, hypotonia, hyperalgesia, hyperesthesia, contact dermatitis, blepharitis, photophobia, lymphadenopathy, eosinophilia, anemia, leukopenia, aphasia, dysarthria, hostility, hallucinations, proteinuria, crystalluria, ascites, glycosuria, cervicitis, sinus tachycardia, dyspareunia, stomatitis, dyskinesia, dystonic reaction, trismus, neuritis, exophthalmos, iritis, polycythemia, encephalopath, mania, delirium, psychosis, impotence (erectile dysfunction), hypertonia, nystagmus, conjunctivitis, wheezing, myopathy, physiological dependence, withdrawal, infertility 

Mild: dizziness, drowsiness, weight gain, xerostomia, headache, infection, diplopia, fatigue, tremor, appetite stimulation, pharyngitis, asthenia, sinusitis, arthralgia, nausea, lethargy, hypersalivation, back pain, vertigo, insomnia, flatulence, vomiting, hypoesthesia, anxiety, abdominal pain, diarrhea, amenorrhea, menorrhagia, leukorrhea, cough, syncope, dysmenorrhea, chills, pelvic pain, libido increase, dysgeusia, hyperkinesis, rash, urticaria, alopecia, vesicular rash, xerosis, hirsutism, photosensitivity, xerophthalmia, leukocytosis, irritability, malaise, agitation, hiccups, yawning, parosmia, psychomotor impairment, miosis, ptosis, mydriasis, purpura, paranoia, orgasm dysfunction, muscle cramps, increased urinary frequency, myalgia, libido decrease, fever, tinnitus, paresthesias, pruritus, ecchymosis, breast enlargement, gynecomastia 

PREGABALIN CONTRAINDICATIONS AND PRECAUTIONS:  per PDR

Depression, suicidal ideation 
Antiepileptic drugs (AEDs), including Pregabalin, increase the risk of suicidal ideation, thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomized to 1 of the AEDs had approximately twice the risk (adjusted RR 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behavior compared to patients taking placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately 1 case of suicidal thinking or behavior for every 530 patients treated. There were 4 suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide. The increased risk of suicidal thoughts or behavior was observed as early as 1 week after starting drug treatment and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years of age) in the clinical trials analyzed. The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge consider whether the emergence of these symptoms in any given patient may be related to the illness being treated. Closely monitor patients for emerging or worsening depression or suicidal thoughts/behavior. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. Pregabalin should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose.

Abrupt discontinuation 

Abrupt discontinuation of Pregabalin after prolonged use should be avoided to reduce the risk for withdrawal seizures or adverse effects such as insomnia, nausea, headache, anxiety, hyperhidrosis, and diarrhea. Withdraw pregabalin slowly, using a gradual dose-tapering schedule over a minimum of 1 week.

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According to the FDA (Food and Drug Administration):

Increased seizure frequency or other adverse reactions may occur if LYRICA (Pregabalin) is rapidly discontinued. Withdraw LYRICA gradually over a minimum of 1 week. (5.3)

Antiepileptic drugs,including LYRICA (Pregabalin), increase the risk of suicidal thoughts or behavior. (5.4)

LYRICA (Pregabalin) may cause peripheral edema. Exercise caution when co­ administering LYRICA (Pregabalin) and thiazolidinedione anti diabetic agents.(5.5)

LYRICA (Pregabalin)may cause dizziness and somnolence and impair patients’ ability to drive or operate machinery.

REFERENCES:

https://www.fda.gov/news-events/press-announcements/fda-approves-first-generics-lyrica

https://www.fda.gov/files/drugs/published/Lyrica-Medication-Guide.pdf

https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021446s026,022488s005lbl.pdf

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