In 1996, there were reports of clonazepam's efficacy as a treatment for phantom limb pain. However, there are no known studies that confirmed this report until now.
Clonazepam is a drug used to prevent and treat panic disorders, anxiety, akathisia (a movement disorder), and seizures. It is a tranquilizer of the benzodiazepine class. However, clonazepam differs from other benzodiazepines because it binds more to the central than peripheral benzodiazepine receptor sites.
A study recently published on the National Center for Biotechnology Information (NCBI) website showed the details of a retrospective analysis of patients from 2015 to 2018. The researchers analyzed the clinical charts of lower-limb amputees with a mean interval from surgery of about one month.
During the study, a total of 82 individuals with limb loss were hospitalized. Of these, 32 suffered from phantom limb pain, which affects up to 88% of people with limb loss. It is considered a chronic neuropathic pain syndrome, but its cause is still unknown. However, clinical findings suggest that peripheral and central nervous system mechanisms influence the onset of phantom limb pain.
Out of the 32 patients with phantom limb pain, seven were treated with gabapentin, three with NSAIDs, and one with pregabalin. The researchers ended up looking into the details of 23 amputees who were treated with clonazepam as the only drug.
There are no standard guidelines for the pharmacologic management of phantom limb pain. Morphine, a painkiller medication, may be administered for an immediate to long-term treatment effect, as well as a high dosage of gabapentin, typically used for neuropathic pain, for six weeks.
Before the patients were administered clonazepam, they were asked to rate their pain level using the Numeric Rating Scale (NRS) values. The median NRS before the treatment was seven.
The 23 patients were given clonazepam for 31 ± five days. The highest dosage administered was 3.5 mg, and 12 patients reported side effects, like drowsiness, dizziness, and mild fatigue. However, the side effects weren't considered intense enough to reduce the dosage.
After the treatment period, the researchers found that the difference of the NRS was more significant than 1.0, which means that the intensity of phantom limb pain could be reduced by clonazepam treatment. The mean NRS related to phantom limb pain significantly decreased from seven to three in patients treated only with this drug. Furthermore, two patients reported the complete disappearance of phantom limb pain after the treatment.
On the other hand, four patients had no beneficial effects from clonazepam.
The exact mechanism by which clonazepam exerts its effects on phantom limb pain is unknown. An emerging hypothesis suggests that phantom limb pain may depend on structural changes in the corpus callosum of people with limb loss. The corpus callosum is a large bundle of more than 200 million myelinated nerve fibers that connect the two brain hemispheres, permitting communication between the brain's left and right sides.
However, the researchers noted that this retroactive study did not allow a comparison with a control group, which is a limitation. Another limitation is the lack of control for confounding variables such as comorbidities, prosthesis use, and demographic factors.
The bottom line
The study found that clonazepam, a not-so-new drug, can reduce phantom limb pain intensity in individuals with limb loss. The researchers noted that the drug could be used as an alternative treatment as it is considered safe, with low adverse effects. But the researchers deem it necessary to perform further studies to confirm the efficacy of clonazepam in the reduction of phantom limb pain.
If you're suffering from phantom limb pain and are interested in using clonazepam, we encourage you to discuss your options with your primary healthcare provider.