Abuse, Dependency and Withdrawal with Gabapentin: A First Case Report

• Introduction
• Case report
• Discussion
• References

Introduction

Gabapentin has not been documented to produce dependency. This is the first case recorded in our institution of a patient having developed dependency while being treated with a high dose of gabapentin.

Case report

The patient, a 67-year-old woman, presented with mood disorders and a history of alcohol abuse leading to polyneuritis. The patient was given 550 mg of naproxen per day and 100 mg of amitriptyline per day, and gabapentin as analgesia. She began taking gabapentin on a daily basis, increasing the dosage progressively because she developed a tolerance to its effect until she was given a prescription of 4800 mg per day, way over the maximal recommended dose (3600 mg per day). In fact, she was actually taking at least 7200 mg per day. In order to obtain her drug, she developed a fraudulent behavior: she asked pharmacists to give it without any medical prescription; she exaggerated her symptoms so as the drug be prescribed more often. She did not behave exactly like a “doctor shopper” or “pharmacy shopper”. She consulted one physician at a time but she often changed when he refused to deal with her demand. In 2005, she consulted an important number of physicians. In April 2005, when she could no longer obtain any prescription and pharmacists refused to give her gabapentin, she developed typical withdrawal symptoms including trembling, sweating, excitation, pallor, and exophthalmia. She was then hospitalized for a global evaluation. When she left, gabapentin was totally stopped and a nurse came home everyday to give her the prescribed drugs: dextropropoxyphene/acetaminophen/120 mg/1600 per day, oxcarbazepine 900 mg per day, alimemazine 40 mg per day, amitriptyline 150 mg per day, and aceprometazine/meprobamate /10 mg/400 per day. At the end of June, she decided to stop smoking and chose nicotine substitution with nicotine chewing gums. On July 16, gabapentin was prescribed again at a dose of 1600 to 2400 mg per day. A new prescription was delivered on August 26, and again 12 days later with diazepam at a dose of 10 mg per day. At the end of September, the patient had resumed her abusive consumption.

Discussion

Drug addiction is defined by 7 items that are listed in the DSM IV. To prove a dependency, the patient must present with at least 3 of these. Our patient presented with tolerance (first item), a withdrawal syndrome (second item), consumption of a more important dose than that prescribed (third item). Furthermore, the patient presented with some characteristics of desocialization such as relational problems. Her behavior was almost fraudulent with exaggerated symptoms and illegal requests to pharmacists.

Approved in France as an anticonvulsive and for the treatment of neuropathic pain, gabapentin increases brain GABA and enhances GABA release when used in the recommended range of 800 to 2400 mg per day (although it has no direct effect on GABA receptors or transporters). Gabapentin was supposed to restore inhibitory GABAergic feedback on ascending dopaminergic projections to nucleus accumbens neurons [10]. It could also influence the synthesis of glutamate. Many of the withdrawal phenomena have been linked to modulation of the glutamatergic and/or the GABAergic system.

Gabapentin was never reported to be associated to dependency or withdrawal problems before 2002. Since 2003, it has been regularly linked to addiction; it is used in the treatment of opiate withdrawal [2] [6]. Gabapentin has also shown potential effects as a treatment for cocaine dependency [9] [10] and for alcohol, benzodiazepine, and pentazocine detoxification [1] [4]. However, a recent study [3] suggests that maintenance on gabapentin (600 or 1200 mg per day) has few overall effects on the discriminative stimulus of smoked cocaine. This suggests that the effects of gabapentin may not be sufficiently strong to attenuate cocaine use. The lack of abuse or addictive potential is an important argument for the use of drugs in addicted patients, during and after detoxification.

In one case, gabapentin was used abusively by the patient to attenuate cocaine withdrawal symptoms [5]. Three published cases demonstrated the development of withdrawal symptoms after abrupt cessation of gabapentin at respective doses of 4800, 3600, and 2400 mg per day [7]. Furthermore, consumer websites report several experiences of gabapentin misuse in order to “feel high”. According to these consumer reports, gabapentin effects are close to those of marijuana and can appear with low doses (with 1600 mg for some users). Our case-report is the first to demonstrate dependency with gabapentin. Genetic factors could be responsible for this. High dosage can also lead to pharmacodynamic modifications, but the specific gabapentin therapeutic mechanisms remain unclear.

Interactions between gabapentin and other drugs can explain new effects: a study using gabapentin on Parkinsonian patients [8] showed improvement of the disease symptoms. The therapeutic effect of gabapentin on Parkinsonism may be explained because striatal GABA-mediated postsynaptic inhibitory activity acts together with dopamine in the striatum through an indirect pathway. However, since all patients were taking at least one dopaminergic agent, it is not possible to rule out a pharmacodynamic synergistic effect or a pharmacokinetic potentialization between gabapentin and concurrent dopaminergic drugs.

Further research must me undertaken to determine the interaction between gabapentin and the dopaminergic system which is particularly implicated in addiction phenomena. The implication of drugs which modulate the GABAergic system in dependency, such as benzodiazepines or other hypnotics, has often been reported.

Dependency is not currently listed as an adverse effect in the drug monograph. Therefore it is essential to communicate with health professionals on this issue and to recommend that a possible increase in dosage be supervised very strictly. More studies are necessary to assess the abuse and dependency potential of gabapentin and its mechanism which seems to provide new options for the pharmacological treatment of dependency.

References

• 1 Bonnet U, Banger M, Leweke FM, Specka M, Muller BW, Hashemi T. et al . Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial.  J Clin Psychopharmacol. 2003;  23 514-519
  CrossrefPubMedSearch in Google Scholar
• 2 Freye E, Levy JV, Partecke L. Use of gabapentin for attenuation of symptoms following rapid opiate detoxification (ROD) correlation with neurophysiological parameters.  Neurophysiol Clin. 2004;  34 81-89
  PubMedSearch in Google Scholar
• 3 Haney M, Hart C, Collins ED, Foltin RW. Smoked cocaine discrimination in humans: effects of gabapentin.  Drug Alcohol Depend. 2005;  80 53-61
  PubMedSearch in Google Scholar
• 4 Kumar P, Jain MK. Gabapentin in the management of pentazocine dependency: a potent analgesic anticraving agent.  J Assoc Physicians India. 2003;  51 673-676
  PubMedSearch in Google Scholar
• 5 Markowitz JS, Finkenbine R, Myrick H, King L, Carson WH. Gabapentin abuse in a cocaine user: implications for treatment?.  J Clin Psychopharmacol. 1997;  17 423-424
  CrossrefPubMedSearch in Google Scholar
• 6 Martinez-Raga J, Sabater A, Perez-Galvez B, Castellano M, Cervera G. Add-on gabapentin in the treatment of opiate withdrawal.  Prog Neuropsychopharmacol Biol Psychiatry. 2004;  28 599-601
  CrossrefPubMedSearch in Google Scholar
• 7 Norton JW. Gabapentin withdrawal syndrome.  Clin Neuropharmacol. 2001;  24 245-246
  CrossrefPubMedSearch in Google Scholar
• 8 Olson WL, Gruenthal M, Mueller ME, Olson MD. Gabapentin for parkinsonism: a double-blind, placebo-controlled, crossover trial.  Am J Med. 1997;  102 60-66
  CrossrefPubMedSearch in Google Scholar
• 9 Raby WN, Coomaraswamy S. Gabapentin reduces cocaine use among addicts from a community clinic sample.  J Clin Psychiatry. 2004;  65 84-86
  PubMedSearch in Google Scholar
• 10 Zullino DF, Khazaal Y, Hattenschwiler J, Borgeat F, Besson J. Anticonvulsant drugs in the treatment of substance withdrawal.  Drugs Today (Barc). 2004;  40 603-619
  CrossrefPubMedSearch in Google Scholar

Correspondence

C. Victorri-Vigneau

Centre d' Evaluation et d' Information sur la Pharmacodependance·Laboratoire de Pharmacologie

9 quai Moncousu

44093 Nantes cedex 1

France

Phone: + 33/2/400/840 96

Email: Caroline.vigneau@chu-nantes.fr

References

• 1 Bonnet U, Banger M, Leweke FM, Specka M, Muller BW, Hashemi T. et al . Treatment of acute alcohol withdrawal with gabapentin: results from a controlled two-center trial.  J Clin Psychopharmacol. 2003;  23 514-519
  CrossrefPubMedSearch in Google Scholar
• 2 Freye E, Levy JV, Partecke L. Use of gabapentin for attenuation of symptoms following rapid opiate detoxification (ROD) correlation with neurophysiological parameters.  Neurophysiol Clin. 2004;  34 81-89
  PubMedSearch in Google Scholar
• 3 Haney M, Hart C, Collins ED, Foltin RW. Smoked cocaine discrimination in humans: effects of gabapentin.  Drug Alcohol Depend. 2005;  80 53-61
  PubMedSearch in Google Scholar
• 4 Kumar P, Jain MK. Gabapentin in the management of pentazocine dependency: a potent analgesic anticraving agent.  J Assoc Physicians India. 2003;  51 673-676
  PubMedSearch in Google Scholar
• 5 Markowitz JS, Finkenbine R, Myrick H, King L, Carson WH. Gabapentin abuse in a cocaine user: implications for treatment?.  J Clin Psychopharmacol. 1997;  17 423-424
  CrossrefPubMedSearch in Google Scholar
• 6 Martinez-Raga J, Sabater A, Perez-Galvez B, Castellano M, Cervera G. Add-on gabapentin in the treatment of opiate withdrawal.  Prog Neuropsychopharmacol Biol Psychiatry. 2004;  28 599-601
  CrossrefPubMedSearch in Google Scholar
• 7 Norton JW. Gabapentin withdrawal syndrome.  Clin Neuropharmacol. 2001;  24 245-246
  CrossrefPubMedSearch in Google Scholar
• 8 Olson WL, Gruenthal M, Mueller ME, Olson MD. Gabapentin for parkinsonism: a double-blind, placebo-controlled, crossover trial.  Am J Med. 1997;  102 60-66
  CrossrefPubMedSearch in Google Scholar
• 9 Raby WN, Coomaraswamy S. Gabapentin reduces cocaine use among addicts from a community clinic sample.  J Clin Psychiatry. 2004;  65 84-86
  PubMedSearch in Google Scholar
• 10 Zullino DF, Khazaal Y, Hattenschwiler J, Borgeat F, Besson J. Anticonvulsant drugs in the treatment of substance withdrawal.  Drugs Today (Barc). 2004;  40 603-619
  CrossrefPubMedSearch in Google Scholar

Correspondence

C. Victorri-Vigneau

Centre d' Evaluation et d' Information sur la Pharmacodependance·Laboratoire de Pharmacologie

9 quai Moncousu

44093 Nantes cedex 1

France

Phone: + 33/2/400/840 96

Email: Caroline.vigneau@chu-nantes.fr