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Letters to the Editor   |    
Potentiation of the Effect of Buprenorphine/Naloxone With Gabapentin or Quetiapine
Roy R. Reeves, D.O., Ph.D.; Mark E. Ladner, M.D.
Am J Psychiatry 2014;171:691. doi:10.1176/appi.ajp.2014.13111526
View Author and Article Information

The authors report no financial relationships with commercial interests.

From the Department of Psychiatry, Jackson VA Medical Center, Jackson, Miss.

Copyright © 2014 by the American Psychiatric Association

Accepted March , 2014.

To the Editor: Although it is an effective treatment for opioid dependence, buprenorphine/naloxone may be misused. We report here a case of potentiation of buprenorphine/naloxone with gabapentin and quetiapine.

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Case Report

“Mr. A,” a 38-year-old man, began misusing heroin and prescription opioids in his late twenties. After being arrested for drug possession, he completed a treatment program and was placed on probation that stipulated periodic drug screens. He was prescribed buprenorphine (8 mg)/naloxone (2 mg), two films sublingually as a single daily dose. He initially appeared to do well. After presenting to his probation officer in an apparently intoxicated state, he was taken back into custody. His urine drug screen was negative.

Mr. A admitted he had been misusing buprenorphine/naloxone in conjunction with other prescription medications as a partial substitute for illicit opiates. He wanted to maintain negative drug screens but also “still get high.” He described taking buprenorphine/naloxone simultaneously with up to 1,000 mg of quetiapine or with up to 2,400 mg of gabapentin. With buprenorphine/naloxone and either additional medication, he experienced a relaxed euphoric state that was not as intense as with illicit opiates but was still quite desirable. He entered another drug treatment program to address this problem.

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Discussion

In a survey carried out in substance misuse clinics, 22% of respondents admitted abusing gabapentin or pregabalin, and of these, 38% abused gabapentanoids to potentiate the high obtained from methadone (1). The possible mechanism of action for the potentiation of an opiate high may be related to gabapentin’s ability to increase the analgesic effect of opiates. Opiates act by bonding to opioid receptors, opening G protein-coupled potassium channels, and closing voltage-dependent calcium channels, thus preventing the release of excitatory amino acids in the spinal cord (2). Gabapentin selectively inhibits voltage-gated calcium channels, increases GABA transmission, and modulates excitatory amino acids at N-methyl-d-aspartic acid receptor sites (3). Thus opiates and gabapentin have certain shared mechanisms affecting analgesia. It has also been hypothesized that an increased analgesic effect of gabapentin and morphine may be contributed to by an increase in gabapentin serum concentration that results from the two medications being given together (2). Gabapentin has demonstrated usefulness in preventing opioid withdrawal, probably by modulating excitatory amino acids, which are increased during withdrawal (3). The interactions of quetiapine’s effects on serotonergic, dopaminergic, and other receptor systems with opiate effects, and possibly nonopiate effects, are speculative.

Clinicians treating opiate-dependent individuals should be aware that some patients may attempt to covertly potentiate the effects of buprenorphine/naloxone by abusing drugs such as gabapentin or quetiapine.

Baird  CR;  Fox  P;  Colvin  LA:  Gabapentenoid abuse in order to potentiate the effect of methadone: a survey among substance misusers.  Eur Addict Res 2013; 20:115–118
 
Eckhardt  K;  Ammon  S;  Hofmann  U;  Riebe  A;  Gugeler  N;  Mikus  G:  Gabapentin enhances the analgesic effect of morphine in healthy volunteers.  Anesth Analg 2000; 91:185–191
 
Salehi  M;  Kheirabadi  GR;  Maracy  MR;  Ranjkesh  M:  Importance of gabapentin dose in treatment of opioid withdrawal.  J Clin Psychopharmacol 2011; 31:593–596
 
References Container
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References

Baird  CR;  Fox  P;  Colvin  LA:  Gabapentenoid abuse in order to potentiate the effect of methadone: a survey among substance misusers.  Eur Addict Res 2013; 20:115–118
 
Eckhardt  K;  Ammon  S;  Hofmann  U;  Riebe  A;  Gugeler  N;  Mikus  G:  Gabapentin enhances the analgesic effect of morphine in healthy volunteers.  Anesth Analg 2000; 91:185–191
 
Salehi  M;  Kheirabadi  GR;  Maracy  MR;  Ranjkesh  M:  Importance of gabapentin dose in treatment of opioid withdrawal.  J Clin Psychopharmacol 2011; 31:593–596
 
References Container
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