The Summary of Product Characteristics (SPC) and package leaflet for gabapentin-containing medicines (Neurontin and generics in Belgium) have been updated following analyses of the risks of misuse, abuse and dependence.
Reminders and recommendations
Gabapentin (Neurontin and generics) is a gamma-aminobutyric acid (GABA) analogue and a member of the gabapentinoid family (like pregabalin). However, it exerts its inhibitory properties on the nervous system by acting on voltage-dependent calcium channels, not on GABA receptors. In Belgium, gabapentin is indicated for the treatment of partial epileptic seizures with or without secondary generalisation in adults and children aged 6 and over, and for the treatment of peripheral neuropathic pain in adults.
The recommended daily dose of gabapentin is generally between 900 and 3600 mg in three doses for adults with no co-morbidities that would justify a reduced dose (advanced age or renal impairment).
Misuse, abuse and dependence
In recent years, abuse and misuse of gabapentin (and pregabalin, see our previous communication) have been reported. The prevalence of these could be around 1% in the general population and 40 - 65% in patients who are prescribed gabapentin. Misuse and abuse of this medicinal product is usually for recreational purposes, to control mood or anxiety, to reinforce the effect of other psychotropic substances, or for self-harm intentions.
The majority of problematic gabapentinoid users are young adult males, whose median age is steadily decreasing (from 30 in 2010 to 24 in 2019). The risk of abuse, misuse and dependence on gabapentinoids increases in patients with a medical history of substance abuse, chronic pain or psychiatric comorbidities. These risks may also apply to patients with no history of substance abuse who are taking therapeutic doses of gabapentin.
Abuse of gabapentin as a single drug is fairly rare, and it is more frequently used in combination with other psychotropic or sedative substances (benzodiazepines, opioids, antidepressants, Z-drugs, antiepileptics, cannabinoids or alcohol). What's more, multiple use increases the risk of respiratory depression, coma or fatal outcomes, which can occur in overdoses or interactions.
Abuse or misuse of gabapentinoids can lead to dependence, which can manifest itself through physical signs (tolerance and withdrawal), as well as psychological signs (loss of control over consumption, drug-seeking behaviour). Withdrawal symptoms from gabapentinoids are comparable to those from benzodiazepines and alcohol: anxiety, insomnia, nausea, pain, excessive sweating, tremors, headaches, depression, feeling abnormal, dizziness and malaise. For this reason, gabapentin (or pregabalin) should be discontinued gradually.
Some of the gabapentin (and pregabalin) used for abuse and misuse originates from illicit markets, but studies in the UK and USA also show that between 52% and 63% of misused medicines come from healthcare professionals and institutions.
Prescription and delivery
When prescribing and/or dispensing gabapentin, it is important to:
- perform a medical-psychosocial overview to identify patients at increased risk of misuse, abuse and dependence (any cumulative vulnerabilities must be carefully considered);
- respect the dosages recommended in the SPC and not systematically prescribe large quantities;
- in patients already treated with gabapentin, watch carefully for signs of misuse, abuse, development of tolerance with patient-initiated dose increases, dependence and behaviours encouraging the prescription or dispensing of gabapentin;
- pay specific attention to the consumption of other psychoactive substances (risk of reinforcing effects, but also increased risk of respiratory depression or coma);
- consider a dosage reduction for all patients in whom elimination of gabapentin is reduced (renal impairment, advanced age) or for patients suffering from severe respiratory condition.
Interruption of treatment
In the event of necessary discontinuation of gabapentin, the risk of withdrawal symptoms should not be underestimated. It is recommended to stop taking gabapentin gradually, over a period of at least one week, whatever the initial indication.
Reporting abuse or misuse
Patients and healthcare professionals are encouraged to report abuse and misuse to the FAMHP.
Doctors and pharmacists are invited to lodge a complaint with the police if they identify false prescriptions.
Références
- Evoy et al., Drugs. 2021 Jan;81(1):125-156
- Smith et al., Addiction. 2016 Jul;111(7):1160-74.
- Tambon et al., Front Psychiatry. 2021 Feb 3:12:639780.
- Driot et al., Br J Clin Pharmacol. 2019 85:1260–9
- Smith et al., Br J Gen Pract. 2012 Aug;62(601):406-7
- Bonnet et al., Eur Neuropsychopharmacol. 2017 Dec;27(12):1185-1215.