Abrupt withdrawal of benzodiazepine drugs can result in withdrawal seizures. A recent report describes withdrawal seizures in 3 young dogs and I thought we could take this opportunity to review this concept.
What is a benzodiazepine drug?
Benzodiazepine class drugs commonly include diazepam, midazolam and lorazepam. These drugs are GABA agonists in the CNS which results in suppression of activity. GABA activation causes inhibition in the forebrain, cerebellum, and in other parts. So, if you activate an inhibitor, you will suppress activity. Got it?
How long is too long?
Abrupt withdrawal resulting in seizures and other signs of CNS overstimulation can occur after constant rate infusion (CRI) use, or chronic oral use. Use of a benzodiazepine drug as a CRI for more than 12 hours usually warrants tapering. The three dogs in the recent report received one of these drugs for 39, 64, and 48 hours, respectively. After abrupt withdrawal of the drugs they experienced ataxia and seizures within 4- 48 hours. A return of the benzodiazepine CRI at a low dose, followed by a 12-24 hour taper, resulted in a successful wean from the medication and no additional neurologic events. All three of these dogs were also undergoing mechanical ventilation, and received other medications, so there is always the questions about a direct link between the benzodiazepine withdrawal and the seizures, however the authors suggest this link follows an expected pattern with abrupt withdrawal in humans and in animals. I agree.
As a general rule of thumb (based on human literature), if I prescribe a benzodiazepine drug for oral use longer than 7 days I taper the medication. Abrupt withdrawal is sometimes called "Jim jams" which, honestly, is a pretty fantastic term but probably not a fantastic feeling. Withdrawal ataxia, cerebellar signs and seizures can be seen from abrupt discontinuation of a benzodiazepine drug.
How do I taper to avoid withdrawal seizures?
CRI:
Typical dosing range is 0.1-0.5 mg/kg/hr. I reduce the dose by 50% every 12 hours until the pet would be receiving less than 0.1 mg/kg/hr. For example, if we are at 0.25 mg/kg/hr and wish to taper I would start with a reduction to 0.12 mg/kg/hr x 12 hours, then stop, because the dose would then be less than 0.1 mg/kg/hr.
Oral dosing
Typical dosing is 0.25-0.5 mg/kg PO q8-12hours. If the dog receives the drug for more than 7 days, I would recommend a 50% taper for 3-5 days, followed by another 50% reduction for another 3-5 days and the stop. Cats are at risk of acute hepatic necrosis with oral diazepam administration so I rarely use this medication. However, if you find yourself treating a cat on chronic benzodiazepine drugs, a similar taper can be employed.
Thanks for reading and enjoy your summer! Remember, if you're working with a dog or cat with neurologic disease, I'm an email or telephone call away! Better yet, schedule a consult and we can work through the case side-by-side.
https://onlinelibrary.wiley.com/doi/epdf/10.1111/vec.13221