Backpedaling on Baclofen: Highlighting Concerns Surrounding Baclofen Use in Phenibut Withdrawal: Letter to the Editor Response

We thank Dr. Feldman for carefully reading our review on phenibut withdrawal and emphasizing several important points. Our sentence that reads, “Fortunately, there were no reported seizures in any of the published cases after baclofen initiation” likely did not express our intended message.¹ This statement meant to convey that there were no reported seizures that appeared to be precipitated by baclofen in any of the published cases. This leads into our next sentence, which reads, “However, given the known risk for seizures with baclofen, caution should be taken when it is used.” We appreciate the opportunity to make this clarification. As Dr. Feldman also notes, later in our article we discuss the case report by Patt et al. (on which Dr. Feldman is a coauthor) and note that their patient experienced a tonic–clonic seizure within 28 h of being discharged on baclofen monotherapy at 10 mg thrice daily.² This relatively low dose of baclofen was an unlikely cause of this patient's seizure; the seizure was almost certainly precipitated by acute phenibut withdrawal in the absence of anticonvulsant prophylaxis with a benzodiazepine or phenobarbital.

Dr. Feldman also takes exception to the following statement in Table 1 of our paper: “(Baclofen) has been used successfully alone and in combination (usually with a benzodiazepine) for the treatment of phenibut withdrawal.”¹ Dr. Feldman states that “the phrasing in this table could be interpreted to suggest baclofen monotherapy for patients admitted to handle acute withdrawal during the initial phases of abstinence.” As Dr. Feldman correctly explains, there are different stages of phenibut withdrawal: an acute abstinence period followed by a postacute period after the patient has stabilized. Our comment in Table 1 is a comprehensive statement pertaining to the general syndrome of phenibut withdrawal; it was not intended to differentiate between acute and postacute phenibut withdrawal scenarios. We made this clear in our review, which states, “Based on currently available data, the combination of baclofen and a benzodiazepine such as diazepam or lorazepam represents a logical therapeutic approach for treating patients experiencing acute phenibut withdrawal. Once severe symptoms are under control, it may be possible to taper off the benzodiazepine and treat the patient with baclofen monotherapy, using a prolonged taper (ie, over a period of months).”

Lastly, Dr. Feldman appears to suggest that we have placed too much emphasis on a report by Samokhvalov et al., which describes a case where 8-10 mg of baclofen was substituted per 1 g of phenibut to successfully treat a patient experiencing phenibut withdrawal.³ Consistent with Dr. Feldman's comments, and as stated in our review, “…there are no published data on the dose equivalency between phenibut and baclofen.” We go on to state, “If this suggested dose equivalency between phenibut and baclofen is accurate, it may explain why some patients experience breakthrough withdrawal symptoms while being tapered off baclofen regimens that started with a baclofen dose below this ratio.” While our paper presents the baclofen:phenibut dosing ratio highlighted by Samokhvalov et al., we in no way promote it as an established clinical standard. Our purpose in discussing this report was to put forth the idea that some patients being treated for (postacute) phenibut withdrawal may benefit from baclofen daily doses that exceed the manufacturers’ maximum recommended dose of 80 mg per day. We further mention that doses above this threshold have been commonly used in other settings (i.e., for alcohol withdrawal) and are generally well tolerated.⁴ It is worth noting that in Samokhvalov et al., the maximum baclofen dose used was 60 mg, well below the maximum daily dose recommendation.

In the setting of acute phenibut withdrawal, anticonvulsant prophylaxis with a benzodiazepine or phenobarbital (with or without baclofen or other agents) appears to be the most prudent approach. Once the acute phase of phenibut withdrawal has passed, patient-specific factors should guide treatment choices. Given its lower potential for abuse, baclofen may be preferable over benzodiazepines in patients who require prolonged treatment. This is particularly noteworthy considering that patients undergoing postacute phenibut withdrawal (i.e., those who clearly have an addiction history) may be at risk of developing benzodiazepine dependence. Such patients may be better served by “pushing” their baclofen dose above 80 mg per day versus initiating benzodiazepine therapy. Conversely, we freely acknowledge that some patients may be better served by a regimen that includes a benzodiazepine or phenobarbital, or perhaps another agent instead of baclofen. There are countless clinical scenarios of postacute phenibut withdrawal. These include patients who have taken variable phenibut doses over widespread periods of time, patients with polysubstance abuse, and patients with other physical or mental health comorbidities. Specific treatment plans are likely to vary among these patients depending upon their unique clinical situations.

In conclusion, we appreciate Dr. Feldman's comments, as they contribute to a healthy discourse on the treatment options for patients experiencing acute and postacute phenibut withdrawal. In the absence of data from controlled studies, the optimal management of patients undergoing phenibut withdrawal will remain challenging and open for continued discussion.

The authors declare no conflicts of interest.