Sublingual ketamine an effective long-term analgesic for chronic non-malignant pain

Sublingual ketamine is a safe and effective long-term analgesic for patients with chronic non-malignant pain including fibromyalgia pain, experience at a NSW pain centre shows.

A case series of 29 patients who had previously received inpatient subcutaneous ketamine infusions at a tertiary pain service between 2012 and 2019, provides some evidence for ketamine use in the long term.

Patients were started on ketamine troches/lozenges at a low 25mg doses three times daily, titrated to tolerability and effect, and reviewed every three months.

The mean total daily dosage varied from 25-600mg in divided doses, with a mean dose of 216 mg per day – higher than the previously considered “safe” daily dose of 150mg per day.

The heterogeneous group of men and women were aged 26-67 years, and had a range of diagnoses including complex regional pain syndrome (24%), trigeminal neuralgia (17%), chronic primary pain (17%), neuropathic pain (14%) and fibromyalgia (7%).

The median duration of pain was over 10 years (126 months).

The retrospective study, published in the Internal Medicine Journal, found the mean pain score, using a 0-10 numerical pain rating scale (NPRS), decreased from 8.71 before therapy to 2.89 after ketamine (p <0.005).

There was a statistically significant, positive correlation between the total daily dose and the NPRS reduction from baseline to the time of data collection (p=0.021).

“There were reductions in the use of opioids, gabapentinoids (GBN) or benzodiazepines (BZD) in 59% (n=17) of patients, with 39% (n=9) having a complete cessation of an analgesic agent (opioids, GBN or BZD),” the study authors said.

Almost a quarter of patients (24%) self-reported adverse events such as excessive daytime drowsiness, light-headedness / dizziness, nightmares and dysphoria with two patients discontinuing treatment due to their drowsiness.

There were no serious adverse events. In particular, there were no reports of renal impairment, cystitis, or hepatotoxicity despite.

The investigators, including neurologist Associate Professor Arun Aggarwal from the Royal Prince Alfred Hospital Pain Clinic, said previous studies indicating that renal impairment and ulcerative cystitis might occur were mainly associated with recreational ketamine doses of more than 1000mg daily.

The study found no correlation between total daily dose of ketamine and frequency of adverse effects reported (p=0.973).

“The principal reason for discontinuation was the inability to obtain ongoing Department of Health authority (n=4) to approve sub-lingual ketamine in 2019 when the approving body was concerned about the lack of evidence for the long-term use of ketamine,” they mnoted

The investigators said despite the retrospective nature of their study and its small size, it nevertheless provided valuable information regarding an under-utilised treatment to manage chronic non-malignant pain.

Ketamine troches have to be formulated by compounding pharmacists and are currently not available on the PBS.

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