Study	Treatment	Pain outcome	Other efficacy outcome
Gilron 2005	Morphine: target 120 mg daily Morphine + gabapentin: target 60 mg + 2400 mg daily Gabapentin: target 3200 mg daily Placebo: lorazepam 1.6 mg daily n = 57 (cross‐over)	Participants who completed a treatment period with at least moderate pain relief on maximum tolerated dose Morphine: 35/44 (80%) Gabapentin: 27/44 (61%) Placebo (lorazepam): 13/42 (31%) Question: global pain relief assessed in response to questions from the research nurse on the following scale: pain worse, no relief, slight relief, moderate relief, a lot of relief, or complete relief.	On maximum tolerated dose, mean ± SE: Mean PI (0‐10 NRS) [Baseline: 5.72 ± 0.23] Morphine: 3.70 ± 0.34 Gabapentin: 4.15 ± 0.33 Placebo: 4.49 ± 0.34 McGill Pain Questionnaire PI (10‐cm VAS) [Baseline: 5.0 ± 0.4] Morphine: 3.3 ± 0.4 Gabapentin: 3.5 ± 0.4 Placebo: 3.9 ± 0.4 McGill Pain Questionnaire Present PI (0‐3) [Baseline: 2.40 ± 0.16] Morphine: 1.57 ± 0.16 Gabapentin: 1.64 ± 0.16 Placebo: 2.07 ± 0.16 SF‐36 Bodily Pain (0‐100) [Baseline: 52.1 ± 2.7] Morphine: 64.4 ± 2.9 Gabapentin: 65.6 ± 2.9 Placebo: 56.0 ± 3.0
Gilron 2015	Morphine: target 100 mg daily Nortriptyline: target 100 mg daily Morphine + nortriptyline: target 100 mg + 100 mg daily n = 51 (received treatment) (cross‐over)	Participant‐reported pain relief ≥ 30%: Morphine: 24/47 (51.3%) Nortriptyline: 30/45 (65.8%) Participant‐reported pain relief ≥ 50%: Morphine: 10/47 (25.6%) Nortriptyline: 17/45 (36.8%) PGIC much or very much improved: Participants with at least moderate relief on maximum tolerated dose Morphine: 74.4% Nortriptyline: 70.7% Reports "Overall effect of treatment on global pain relief scores was not significant (P = 0.17)." PGIC very much improved: Not reported	Average daily pain throughout trial ± SE (0‐10 NRS) Morphine: 3.4 ± 0.4 Nortriptyline: 3.1 ± 0.4 Global pain relief (pain worse, no relief, slight relief, moderate relief, a lot of relief, or complete relief) Worst pain (0‐10 NRS) Morphine: 4.4 ± 0.4 Nortriptyline: 4.1 ± 0.4 Nocturnal pain (0‐10 NRS) Morphine: 2.2 ± 0.4 Nortriptyline: 2.0 ± 0.4
Huse 2001	Morphine: target 70‐300 mg daily Placebo n = 12 (cross‐over)	> 25% and ≤ 50% PI reduction Morphine: 1/12 (8%) Placebo: 1/12 (8%) > 50% PI reduction Morphine: 5/12 (42%) Placebo: 1/12 (8%)	At end of treatment phase: Mean PI ± SD (10‐cm VAS) [Baseline: 4.65 ± 1.06] Morphine: 3.26 ± 1.59 Placebo: 3.99 ± 1.23 Data also for sensory pain and affective pain components, not required.
Khoromi 2007	Morphine: target dose 90 mg daily Nortriptyline: target dose 100 mg daily Morphine + nortriptyline: target dose 90 mg + 100 mg daily Placebo (benztropine) 0.25‐1 mg daily n = 55 (cross‐over)	Global pain relief (moderate + a lot + complete relief): Morphine: 13/32 (41%) Nortriptyline: 12/31 (39%) Placebo: 11/28 (39%) Global pain relief (a lot + complete relief): Morphine: 8/32 (25%) Nortriptyline: 10/31 (32%) Placebo: 5/28 (18%)	Average leg pain (scale 0‐10): [Baseline 4.9 ± 2.4] Morphine: 3.4 ± 2.8 (7% reduction) Nortriptyline: 3.0 ± 2.7 (14% reduction) Placebo: 3.7 ± 2.7
Wu 2008	Morphine SR: target dose 180 mg daily Mexiletine: target dose 1200 mg daily Placebo n = 60 (cross‐over)	33% decrease in PI: Morphine: 33/50 (66%) Mexiletine: 16/42 (38%) Placebo: 19/43 (44%) 50% decrease in PI: Morphine: 23/50 (46%) Mexiletine: 11/42 (26%) Placebo: 13/43 (30%)	Any pain‐related outcome: Average reduction in PI from baseline (0‐10): Morphine: 2.8 (95% CI 2.3 to 3.4) Mexiletine: 1.5 (95% CI 0.9 to 2.2) Placebo: 1.4 (95% CI 0.6 to 2.2) No difference between groups for overall functional activity and pain‐related interference with daily activities.