SUPPLEMENTARY INFORMATION

Table S1: List of terms used to identify relevant conditions Relevant Terms included Terms excluded condition

Neuropathic pain neuropathic pain hereditary neuropathy neuropathy autonomic neuropathy radiculopathy provisional, possible, or query(?) neuropathy nerve entrapment family history of neuropathy not neuropathic pain

Sciatica sciatica provisional, possible, or query(?) sciatica family history of sciatica not sciatica

Chronic pain “chronic” with “pain” provisional, possible, or query(?) chronic pain family history of chronic pain not chronic pain

Back problem back problems provisional, possible, or query(?) back problem back pain family history of back problem lumbar pain not back problem cervical disc disease, prolapse, compression or herniation

Depression depression provisional, possible, or query(?) back problem family history of depression not depression

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Table S2: List of and benzodiazepines included in co-prescribing analyses

Opioids Benzodiazepines

Buprenorphine Alprazolam Bromazepam Clobazam Clonazepam Diazepam Flunitrazepam Lorazepam Nitrazepam Suboxone Oxazepam Temazepam Triazolam

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Figure S1: Pregabalin prescribing by tablet strength

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Table S3: Percentage of men and women with a pregabalin prescription by age Men Women Total* Total in No. with ≥1 Total in No. with ≥1 Total in No. with ≥1 study pregabalin study pregabalin study pregabalin cohort prescription % (95% CI) cohort prescription % (95% CI) cohort prescription % (95% CI) Age group (years) 18-19 20,974 78 0.4 (0.3, 0.5) 31,055 168 0.5 (0.4, 0.6) 52,107 245 0.5 (0.4, 0.5) 20-29 113,241 1,479 1.3 (1.2, 1.4) 190,470 2,189 1.2 (1.0, 1.3) 304,602 3,674 1.2 (1.1, 1.3) 30-39 131,541 3,893 3.0 (2.7, 3.2) 199,447 4,840 2.4 (2.2, 2.6) 331,726 8,737 2.6 (2.4, 2.8) 40-49 134,881 6,569 4.9 (4.6, 5.2) 178,644 9,275 5.2 (4.9, 5.5) 314,019 15,849 5.0 (4.8, 5.3) 50-59 136,292 8,688 6.4 (6.0, 6.7) 170,188 12,746 7.5 (7.1, 7.9) 306,786 21,444 7.0 (6.6, 7.3) 60-69 127,378 10,190 8.0 (7.7, 8.4) 148,960 14,467 9.7 (9.3, 10.1) 276,599 24,661 8.9 (8.5, 9.3) 70-79 90,555 9,283 10.3 (9.8, 10.7) 102,065 13,975 13.7 (13.2, 14.2) 192,755 23,266 12.1 (11.6, 12.5) 80-89 38,785 4,839 12.5 (11.9, 13.1) 52,732 8,649 16.4 (15.8, 17.1) 91,581 13,492 14.7 (14.2, 15.3) 90+ 7,029 750 10.7 (9.8, 11.5) 14,378 2,002 13.9 (13.1, 14.7) 21,448 2,754 12.8 (12.2, 13.5) Total 800,676 45,769 5.7 (5.4, 6.0) 1,087,939 68,311 6.3 (5.9, 6.6) 1,891,623 114,123 6.0 *Excludes n=3008 with missing sex

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Table S4: Prevalence of neuropathic pain in full cohort during study period, March 2012 to February 2018

Number of Number with a patients in recorded diagnosis of cohort neuropathic pain % (95% CI) Age group (years) 18-19 52,107 329 0.6 (0.6-0.7) 20-29 304,602 4,228 1.4 (1.3-1.5) 30-39 331,726 10,005 3.0 (2.8-3.2) 40-49 314,019 16,824 5.4 (5.1-5.7) 50-59 306,786 22,312 7.3 (6.9, 7.6) 60-69 276,599 24,244 8.8 (8.4, 9.2) 70-79 192,755 21,834 11.3 (10.8, 11.9) 80-89 91,581 12,461 13.6 (13.0, 14.3) 90+ 21,448 2,375 11.1 (10.3, 11.8) Total 1,891,623 114,612 6.1 (5.7, 6.4)

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