Time to pain relief after immediate-release morphine in episodic pain: the TIME study

Background: Cancer-related and non-cancer chronic pain embodies the most frequent challenge in clinical practice. Management of chronic pain and breakthrough pain (BTP) requires adjustments to the analgesic regimen to achieve adequate pain control. Objective: To examine the time to achieve pain relief in patients who experienced intense episodic pain breakouts despite baseline therapy with analgesics. Methods: This study was based on a 14-day observation period. Patients with either cancer-related or non-cancer pain who experienced >2 intensive episodic pain breakouts per day were prescribed immediate-release (IR) morphine sulphate (10 mg to 20 mg as needed) every 4 hours (around-the-clock) and allowed one rescue dose of IR morphine (equal to one additional administration of the dosage taken at fixed times) for any episodic pain breakouts. Patients recorded time of administration and time taken to achieve partial or total relief of episodic pain breakout in daily diaries; in one study centre the diary was managed with the help of specialized medical attendants. Pain intensity and general wellbeing were assessed by a Numerical Rating Scale (NRS) and Karnofsky Performance Scale, respectively. Adverse events and sleep patterns were also recorded. Results: Of 85 patients (mean age 62.67 ± 14.3 years) enrolled, 14 experienced pain from non-cancer degenerative diseases, and 71 had cancer-related pain. Following stabilization of background pain, the intensity of daily pain improved; NRS decreased from baseline to day 14 for cancer (from 5.63 to 1.98) and non-cancer (from 8.00 to 1.00) groups (both p < 0.0001). Patients’ general wellbeing increased concomitantly. Around-the-clock therapy resulted in an immediate decrease in the number of intense episodic pain breakouts per day, with 11.8% of patients achieving total pain relief within 24 hours. The mean number of intense episodic pain breakouts per day decreased steadily in the cancer group, reaching significance at day 14 (p < 0.001 vs baseline). Moreover, the time to achieve partial and total pain relief of intense episodic pain breakouts improved significantly. Adverse events and sleep patterns improved over the 14-day observation period. Conclusions: Stabilization of background cancer-related or non-cancer pain with around-the-clock IR morphine therapy resulted in fewer intense episodic pain breakouts, which were more quickly managed with rescue-dose IR morphine, suggesting that ‘end-dose’ pain should not be classified as BTP.