Table 1 Association between investigated factors and opioid non-response reported in 39 studies included in the systematic review

 Age (advanced)

[22, 24, 25, 30, 36, 50, 51, 61, 77]

[53, 63, 83]

[38, 40, 57, 58, 65, 66, 78, 80, 81]

 Gender (male)

[24, 25, 36, 38, 40, 47, 51, 57, 58, 61, 65, 66, 77, 78, 86]

[53, 83]

[22]

 Weight/body mass index

Body mass index [51, 58]

Weight gain (higher or equal to 1 kg) [25]

 Alcohol

Alcoholism [28, 72]

Abuse [56]

 Cancer diagnosis

[23, 24, 36, 38, 51, 58, 62, 77, 83]

Gastrointestinal, lung and ovarian [78]; mesothelioma [41]; lower gastrointestinal tract [25]; breast [53]; head and neck and lung [50]; tongue [46]

Non sex-related cancers [57]

 Biochemical parameters

[35]; Serum creatinine and total bilirubin [53]; sodium, calcium, albumin, creatinine [25]

Alanine aminotransferase [53]; white blood cells count [25]

Total proteins [53]; vitamin D levels [87]

 Cognition (poor)

[51, 65, 66, 88]

[48, 83, 85]

[22]

 Metastasis location

Liver [51]; skeletal [24]

Bone [77, 78]; brain [78]; spinal [81]

Bone [22]; lung [81]

 Psychological distress

[29, 88]; Mood (local questionnaire sad/depressed) [77]; depression (HAD) [22]

EORTC functioning [65, 66]; emotional non-well-being (FACT-G) or anxiety (MHI) [56]; anxiety (preop STAI) or Depression levels (preop BDI) [30]

EORTC functioning [51]

 Sleep disturbance

[77]

[50, 51]

[22]

 Breakthrough cancer pain (presence vs absence)

[22]

[51, 59]

 Incidental (presence vs absence)

[50, 88]

[65, 66]

 Intensity

Self-reported δ VAS [58]

Baseline-intervals [50]; initial pain intensity [83]

Initial worst pain severity [56]

 Pathophysiology (neuropathic pain)

[35, 38, 43, 51, 58, 78]

Presence vs absence [24, 88]; neuropathic versus nociceptive [65, 66]

Presence vs absence [22]

 Analgesics

[72]; NSAIDs [50]; previous [24]

Ketorolac [62]; NSAIDs [78]

 Adjuvants

[35]; Anticonvulsants [22]; gabapentin [51]; antidepressants (vs no antidepressant) [78]

Steroids or non-opioids [51]; steroids [78]; traditional sedatives [81]

 Others

Oncologic treatments [24]; neuromuscular blockade [62]

Antiemetics and beta blockers [25]

PPIs and recent chemotherapy (14 days) [25]; Prophylactic laxative treatments [63]