Pregabalin dependence: Experiences from liaison psychiatric settings in Kashmir, North India: A case series

Abstract

Pregabalin, a gamma-aminobutyric acid (GABA) analog, is a new-generation antiepileptic that is approved for the treatment of neuropathic pain, fibromyalgia, partial seizures, and generalized anxiety disorder. There is a rising concern regarding its abuse potential, and a handful of case reports have highlighted the same. We present a case series on pregabalin dependence. In contrast to previous case reports, which focused on patients with a history of illicit drug abuse, we present cases of drug-naïve individuals for whom pregabalin was the first substance of abuse. The highlight of the study is that we describe cases of pregabalin intoxication and a rare case of pregabalin withdrawal, which presented as a lethal suicidal attempt to liaison psychiatric settings.

Pregabalin is a widely prescribed gamma-aminobutyric acid (GABA) analog.[1,2] Few case reports have highlighted its abuse potential, particularly in individuals with a preexisting history of a substance use disorder; however, reports in individuals with no prior illicit substance abuse are scarce.[1,3] Herein, we report a series of three cases with no lifetime history of illicit substance abuse that presented to liaison psychiatry with features suggestive of intoxication and a case that presented with a lethal suicidal attempt during pregabalin withdrawal.

CASE SERIES

Case 1

A 19-year-old boy with premorbid personality suggestive of borderline personality traits was referred from internal medicine given a suspected drug overdose. He had presented with an unsteady gait and slurred speech after taking some tablets on a night out with his friends. His urinary drug screen was negative for illicit substances, and his baseline investigations were within normal limits. He denied the use of any illicit substance or club drugs but revealed that he started taking pregabalin 75mg/day 5 months back to feel “high” and to overcome “feelings of emptiness.” He subsequently increased the dose to 600mg/day as he felt “euphoric.” He felt irritable, anxious, and sleepless whenever he did not consume it. For withdrawal management, he was started on chlordiazepoxide 20mg/day initially, along with nonpharmacological interventions like motivational enhancement therapy and, subsequently, dialectical behavioral therapy.

Case 2

A 25-year-old X-ray technician with a well-adjusted premorbid personality was referred for a recent suicidal attempt with organo-phosphide consumption. A detailed history revealed that about 3 months back, the patient was prescribed pregabalin 150mg/day by an orthopedician because of cervical spondylosis. However, he escalated doses himself to 750mg/day as he felt “high.” As time progressed, he started purchasing pregabalin tablets in bulk from a local pharmacist. His family got suspicious that he might be using some “drugs” and seized the cartons. He reported feelings of hopelessness and suicidal ideations after stopping the drug. Four days later, he locked himself in a room and consumed an organo-phosphorous compound, which he had procured secretly. On examination, he was tearful and verbalized his mood as “low,” and his thought sample revealed depressive cognitions, concerns with neck pain, death wishes, and craving for pregabalin. His Ham-D scores corresponded to “moderate” symptoms of depression. His scores on Beck’s suicidal scales revealed a “high” intent. He was managed in in-patient settings and was started on duloxetine 40mg/day, lithium 600mg/day, and chlordiazepoxide 20mg/day, along with nonpharmacological interventions. He was re-evaluated thrice in OPD and reported improvement and abstinence from pregabalin.

Case 3

An 18-year-old male with a history suggestive of attention deficit hyperactivity disorder (ADHD) was referred from medical casualty after he had fainted at a party after consumption of “some capsules.” His urinary drug screen was negative, and his baseline investigations were within normal limits. He denied the use of club or illicit drugs; however, he reported the use of pregabalin capsules. He reported feeling “curious” about trying these capsules, which were introduced to him by his friend. Initially, he started with 300mg/day, further increasing to 1500mg/day to get the desired “high.” For withdrawal management, he was hospitalized, and a schedule was formed to taper and stop pregabalin within a week. On stabilization, he was started on methylphenidate 20mg. After discharge, he was re-evaluated in OPD and could abstain from pregabalin.

DISCUSSION

Pregabalin dependence has been reported in young people, predominantly males, who have opioid use disorder or comorbid polysubstance abuse.[3] The exact mechanism of the abuse potential of pregabalin remains elusive. Theoretically, it can be explained by an increase in the levels of GABA caused by it, which leads to relaxation and disinhibition-analogous to the action of benzodiazepines and alcohol.[4] In addition, pregabalin’s GABA-mimetic properties affect the reward pathway’s dopaminergic neurons. Pregabalin binds to the α2-δ subunit of the voltage-gated calcium channels in the presynaptic neurons. During action potential generation, there is a neuronal influx of calcium, which releases neurotransmitters like serotonin (5HT), substance P, and excitatory neurotransmitters.[4] Pregabalin decreases the CNS excitability by dampening this calcium current.[4]

All three patients reported were young men, but an interesting finding is that none of our patients had a comorbid history of illicit substance use. Two of our cases demonstrated that pregabalin withdrawal can occur even after a brief period of 2 months.

To the best of our knowledge, there are few case reports of agitation and psychosis reported during the discontinuation of pregabalin. However, its association with mood disorders is infrequent.[5] In previous reports, depressive disorder and attempted suicide have been reported during the initiation of pregabalin therapy.[6] However, we presented a rare case of depressive disorder with a “suicidal attempt” during pregabalin withdrawal. The possible explanations could be its effects on serotonergic pathways and downregulation of 5HT.[5] Another possibility could be that sudden pregabalin withdrawal could have unmasked the underlying mood disorder in this patient. Given the temporal relationship between the discontinuation of pregabalin and the onset of symptomatology, pregabalin withdrawal could be postulated as the most likely reason for depression and suicidal attempts in this patient. Two of our cases shed light on the scant evidence of pregabalin dependence in patients taking relatively low doses of pregabalin (less than 1g/day).[7] Other cases reported from our country depict dependence in patients taking doses as high as 6 to 12 g/day.[2,8]

CONCLUSION

Guidelines need to be updated to include pregabalin as a potential substance of abuse. Caution should be exercised as severe psychiatric disorders and suicidality could emerge during withdrawal.

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.

Author’s contribution

A.K. conceptualized the study and prepared the manuscript. R.R., I.A., and A.K. performed data collection. Z.A.W. and Y.H.R. performed manuscript correction. All authors reviewed the manuscript.

Data availability

Data will be made available upon reasonable request.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.