Very high dose of pregabalin abuse: A case report

Dear Editor,

Pregabalin is a GABA analog with anticonvulsant, analgesic, euphoric, and antianxiety effects.[1] It is commonly prescribed for disorders like partial-onset seizures, neuropathic pain, anxiety, and fibromyalgia. Pregabalin is emerging as a potential drug of abuse in India, which is very concerning in North India, especially in Punjab.[2]

There is growing evidence from around the world that pregabalin use has surged recently. Previous literature highlighted that young male with substance use disorder, especially those taking opioids, are at “high-risk” of pregabalin abuse. This risk increases further when pregabalin is used in higher doses.[2] Recently, there has been an upthrust in reporting of pregabalin abuse (between dose range 350 mg/day and 12000 mg/day) from India.[3,4,5,6] In one case from West India, an operation theater assistant was taking daily doses of 12000 mg of pregabalin.[5] One recent case report showed pregabalin abuse in Punjab, North India, where patients were taking 1500 mg and 1800 mg of pregabalin daily.[7] Further, we are reporting a rare case of a very high dose (6000 mg/day) of pregabalin abuse from North India. The patient provided written consent for manuscript writing.

A 30-year-old unmarried male from the Malwa region of Punjab presented to the outpatient department of a tertiary health care facility with complaints of anxiety and restlessness. There was no family history of any medical, psychiatric, or substance use disorder. The patient took poppy husk for 10–12 years, 20–30 gm/day. The patient’s ability to obtain poppy husk became increasingly challenging due to issues with affordability and availability. Around three years back he came to know about tramadol, so to quit poppy husk, the patient started taking tablet tramadol 100 mg/day, and the amount of tramadol increased to 2–4 tablets/day during 2–3 months duration. Later his friend introduced him to pregabalin, and due to its easy over-the-counter access patient also started taking capsule “SIGNATURE” (pregabalin 300 mg each) 2–4/day. After taking both drugs, he would feel energetic, euphoric, less anxious, more confident, and used to have a good appetite. During the last 2–3 years, to sustain the same effect, the patient gradually increased the amount of pregabalin to 20 capsules (6000 mg) and tramadol 8–10 tablets daily. Although he was working, the quality of his work was not satisfactory.

Daily procuring both drugs would take a lot of money and effort. In an attempt to stop both drugs, he would experience withdrawals like yawning, restlessness, craving, body ache, lethargy, sadness, anxiety symptoms, fatigue, sleepiness, and decreased appetite. The patient also had 7–8 episodes of generalized tonic-clonic body movements associated with frothing, falling, and tongue bites. The higher dosage of tramadol precipitated these seizure episodes. Due to unaffordability and withdrawals, the patient presented to the OPD for de-addiction. The psychiatric assessment revealed withdrawal symptoms. The routine Liver, kidney, thyroid function tests, electrolyte, and hemogram evaluations were normal.

Due to withdrawal symptoms, a schedule was arranged to terminate pregabalin use by gradually tapering its dose to 150 mg/day. Simultaneously nonpharmacological interventions (psychoeducation and motivational enhancement therapy) were introduced. Following the initial presentation, he was re-evaluated thrice in OPD and could abstain from pregabalin. Later, the dose of tramadol was also gradually decreased and stopped in 2–3 weeks. He remained abstinent for the last month. After stopping tramadol patient resumed his work, and there was no fresh seizure episode.

The index case highlights the easy availability and severity of pregabalin abuse alone and concomitantly with opioid use. Indian literature cannot contribute any large study focused on assessing the extent and pattern of pregabalin abuse. Therefore, it is crucial to report such cases to draw the attention of researchers and policymakers.

Although the mechanism of pregabalin action is not well understood, it has a high affinity for the α2-δ subunit of the presynaptic voltage-gated calcium channel; thus, it dampens the calcium current. This, in turn, downregulate the excitatory neurotransmitters like glutamate, serotonin, nor-adrenaline, and substance P; consequently, there would be less postsynaptic excitability.[8] But there is no effect on dopamine release, which might be the possible mechanism for reward like other substance use disorders. Secondly, pregabalin also increases extracellular GABA levels, leading to relaxation and euphoric effects. Also, GABA mimics property can also explain the addictive behaviors of pregabalin, similar to benzodiazepine.[8] Despite many postulated theories exact mechanism of pregabalin addiction is not precise, which demands further research.

In India, pregabalin abuse is increasing and individuals with a history of substance use disorder specifically opioid users are more prone to pregabalin abuse, similar to the index case.[1,2,3,4,5,6] The reported case from western India, where a 32-year-old man was taking pregabalin (12000 mg/day) to get the euphoric and energetic effect.[5] In another case, an opioid-dependent individual who moved from south India to the middle east country, he had difficulty procuring propoxyphene, so to control the withdrawals, he started taking pregabalin 10–12 gm/day, which was easily accessible.[9] Aneja and Singh in 2022 also reported cases of pregabalin abuse from North India (Punjab), although the pregabalin dose was much lower than the index case.[7]

The easy availability, low cost, and less social stigma are the factors surmised for pregabalin use. The recent capture of a large quantity of pregabalin in Punjab has also alerted the administration. Consequently, pregabalin 300 mg cannot be purchased over-the-counter in Mansa (District of Punjab) according to Office Order No. 2021/FS/FK-2-25645-25711, dated October 12, 2021. Due to the scarcity of literature, pregabalin is not considered a drug of abuse in India. So, reporting pregabalin abuse at higher doses may draw the attention of policymakers and practitioners to be vigilant about this alarming trend.

Healthcare professionals should be sharp-eyed while prescribing gabapentinoids, specifically to high-risk individuals. Indian health institutes must be more proactive in formulating the practice guidance document for the timely prevention and treatment of pregabalin abuse.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.