Pregabalin Use/Misuse: A Source of Consternation in Western Punjab

Sir,

The National Mental Health Survey of India (2015–2016) reported the lifetime prevalence of “any mental morbidity” at 13.67% and it was 22.44% for psychoactive substance use disorders (SUDs). ¹ Furthermore, in the State of Punjab Household Survey (2018), it was found that nearly 15% or 1 in 7 people were using either a licit or illicit substance in a dependent manner. ² This rate was much higher than the global rate of 3.8% for SUDs. ³

We work in a tertiary care hospital that mainly caters to the Western Punjab region and parts of Haryana and Rajasthan. The approximate average number of psychiatry patients examined monthly is 1500–1600, and 8–10 patients/day present with SUDs. Lately, we have encountered patients with SUDs and drug-naïve youth who have been misusing pregabalin. To give a glimpse of this, brief descriptions of two such patients from our center are provided here after obtaining written informed consent from them.

Case 1: A 40-year-old farmer, receiving buprenorphine 2 mg and naloxone 0.5 mg/day for the past one year, was introduced to “Signature” capsules (colloquial term for pregabalin) by a fellow farmer. Pregabalin was initiated at 300 mg/d orally to overcome body pains and enhance work efficiency as it provided euphoria, energy, and “high.” He consumed it in the company of a fellow farmer. Over a period, he had to increase the dose to 1500 mg/d to obtain the same “high.” He denied any significant withdrawal effects and socio-occupational dysfunction except that he sometimes skipped work to procure the drug. He consulted us to quit both buprenorphine+naloxone and pregabalin. He was prescribed duloxetine 40 mg/d, clonazepam 0.75 mg/d, and ketorolac 60 mg/d, all in divided doses. Non-pharmacological intervention in the form of psychoeducation and relapse prevention was attempted, but he dropped out after three visits.

Case 2: A 21-year-old male presented with complaints of anxiety. He reported being stressed due to financial constraints. He operates an excavator machine and often works for long hours. He was introduced to pregabalin by another driver to relieve the day’s tiredness. He also reported achieving “high,” euphoria, remission of aches and pains, and good sleep. He gradually hiked the dose of pregabalin from 300 mg/d to 1800 mg/d (consumed orally in 3–4 divided doses) to obtain the same euphoric effect. He spent ½–1 hour/day to enjoy the euphoric and relaxing effects of pregabalin which he consumed in company of his friends. He often had withdrawal symptoms such as yawning, lethargy, and sadness. He had tried alcohol and poppy husk too, but in view of easy accessibility, cost, and work requirement, he found pregabalin the most suitable. He had limited socio-occupational dysfunction in the form of time spent procuring pregabalin. He was prescribed escitalopram and etizolam for the anxiety symptoms but dropped out of treatment after the initial visit.

Pregabalin is structurally similar to gamma amino butyric acid (GABA) and is quickly absorbed on oral administration, with high bioavailability. However, pregabalin exerts its anti-anxiety action through inhibition of α2δ-subunit-containing voltage-dependent calcium channels that reduce the release of excitatory neurotransmitters such as glutamate, noradrenaline, and substance P, with no effect on dopamine release. ⁴ The latter has been hypothesized to be a common mechanism for the rewarding effects of various psychoactive substances. However, pregabalin is known to lead to dose-dependent increase in extracellular GABA which exerts relaxation and disinhibition analogous to alcohol and benzodiazepines and thus the “liking/euphoric” effect. Hence, theoretically, it may be considered a potent drug with abuse potential. But the exact mechanism of its addiction potential is still elusive and demands further research.

Pregabalin has been approved for partial seizures, neuropathic pain, and fibromyalgia but is also used to manage anxiety disorders and alcohol/opioid withdrawal. Globally, studies have shown that individuals with a history of drug abuse tend to abuse pregabalin and other gabapentinoids in a dose range 3–20 times the therapeutic dosage. ⁵ Moreover, physical dependence to and withdrawal states of pregabalin have also been reported in the literature as observed in case 2 here. ⁶ Epidemiological trends show higher abuse/misuse of pregabalin in younger males, mainly those seeking opioid substitution therapy, or those with a co-existing anxiety disorder, as depicted in cases 1 and 2 described here. ⁷ Consequently, pregabalin has been reclassified as a Schedule V drug in the US, a controlled drug in class C in the UK, and flagged for its misuse potential in other countries too. ⁸

The western region of Punjab may be staring at another vexing public health problem in the form of pregabalin misuse. The severity may be gauged from the fact that seizure of large quantities of pregabalin and other gabapentinoids has occurred in various districts of Punjab, and recently, the district administration of Mansa has prohibited the sale of pregabalin 300 mg without a prescription (vide Office Order No:2021/FS/FK-2-25645-25711, Dated: 12 October 2021).

Akin to the risk factors for other substance abuse, pregabalin abuse is seen in young people and those who have a history of drug abuse or comorbid psychiatric disorders or are on multiple prescriptions. ⁹ Therefore, healthcare workers and policymakers are cautioned about considering pregabalin as a harmless alternative to various analgesics and psychotropics. Also, psychiatrists are advised to actively enquire about abuse of pregabalin and other gabapentinoids in the high-risk drug abuser groups.