Back Pedaling on Baclofen: Highlighting Concerns Surrounding Baclofen use in Phenibut Withdrawal

To the Editor:

I applaud Drs. Penzak and Bulloch for attempting to organize the sparse phenibut literature into usable clinical information.¹ However, some case information reported within this article requires correction. Additionally, important considerations for baclofen use in withdrawal need to be emphasized.

In the authors' discussion of baclofen use for withdrawal, they state: “This approach has been questioned, especially in patients who may be at risk of seizures. Fortunately, there were no reported seizures in any of the published cases after baclofen initiation.”

This statement is incorrect. It cites a case report, published by our author group, in which a patient has a seizure after being sent home on baclofen for phenibut withdrawal.² Later in the discussion, they do accurately describe our case report, contradicting their own statement.

Next, in the authors' discussion of pharmacotherapy for withdrawal management they comment in table 1 that baclofen “Has been used successfully alone and in combination (usually with a benzodiazepine) for the treatment of phenibut withdrawal.” However, withdrawal management entails various strategies. Some patients may taper from phenibut, while others will undergo abstinence, the two may require different treatment strategies. Those undergoing abstinence may experience more severe acute withdrawal syndromes. In our review, 100% of patients undergoing abstinence were managed inpatient and nearly all required multiple medications to stabilize symptoms.³ The monotherapy use of baclofens in the published literature has only been for aiding a phenibut taper, or after the acute stabilization phase in abstinence (e.g., maintenance).³ The phrasing in this table could be interpreted to suggest baclofen as a monotherapy for patients admitted to handle acute withdrawal during the initial phases of abstinence. Given the risk for severe outcomes in these patients (seizure in 9.1%, intubation in 27.7%), it is important to point out baclofen has no data to support its use as a single agent in this setting.³

Finally, the authors discuss baclofen dosing and highlight a previously suggested dosing regimen of 8-10 mg of baclofen per 1 g of phenibut. This recommendation stems from a single case with no comparator.⁴ Every other case report, which utilized baclofen successfully, is just as valid. The only difference is that these authors proposed a dosing strategy in their text. Despite a total lack of scientific rationale, it has unfortunately become a prevalent discussion point in other texts. This suggested dosing implies baclofen is 100 times more potent than phenibut. However, in vitro data demonstrates baclofen has a 28-fold higher affinity for the gamma amino butyric acid-B receptor than phenibut.⁵ Many patients in this review were taking >20 g of phenibut, which would require more than 200 mg per day of baclofen.¹ While the authors note baclofen has been used safely at very high doses for alcohol withdrawal, it is not without risk.⁶ In our review of all reported baclofen regimens, only four patients required more than 100 mg of baclofen per day and the maximum reported dose was 130 mg.⁴ The safety of such high doses in phenibut withdrawal is truly not known.

The author declares no conflicts of interest.

No funding was provided for this research.