Table 3.
Studies investigating the association between pharmacogenetics and the effect and safety of antidepressants in pain in vivo (human studies).
| Study | Drug Class | Drug Name | Ethnicity | Study Design | FDA/EMA Status (Indication for Pain) | Outcome Measured | Gene Assessed | Variants | Findings |
|---|---|---|---|---|---|---|---|---|---|
| Wilder-Smith et al. (2005) [93] |
TCA | Amitriptyline | N/A | 30 patients with postamputation pain | Approved | Amitriptyline efficacy | CYP2D6 | PMs and UMs | Lower pain levels in CYP2D6 PMs |
| Chaudhry et al. (2017) [94] |
TCA | Amitriptyline | Black African (n = 21), Caucasian (n = 9), Indian (n = 1) |
31 patients with diabetic peripheral neuropathy | Approved | Amitriptyline treatment response and adverse effects | CYP2D6 | *1/*1, *1/*1xN, *1/*45, *2/*2, *2M/*35, *1/*2, *35/*41, *1/*17, *2/*17, *2/*4, *2xN/*5, *2/*29, *1/*29, *17/*84 | No effect of CYP2D6 phenotype on amitriptyline efficacy. A trend towards more severe adverse effects in CYP2D6 IMs compared to NMs |
| Benavides et al. (2021) [98] |
TCA | Nortriptyline | Caucasian | 25 neuropathic pain patients | Not approved | Nortriptyline treatment response and adverse effects |
CYP2C19
CYP2D6 ABCB1 |
CYP2C19 *2, *3, *4, *5, *6, *7, *8, *17 CYP2D6 rs1065852, *2A, *3, *4, *6, *7, *8, *9, *10, *11, *12, *14, *15, rs28371706, *17, *20, *29, *35, *41, rs1135840, *40, *58, *64 ABCB1 rs1045642, rs2032582 |
ABCB1 rs1045642 C homozygotes showed an improved therapy response in pain conditions under a combined therapy with nortriptyline and morphine |
| Siegenthaler et al. (2015) [104] |
TCA | Imipramine | N/A | 50 patients with chronic low-back pain | Not approved | Imipramine efficacy | CYP2D6 | *6, *7, *8, *10, *41, *3A, *4, *5, *2 | No significant effect of amitriptyline on low back pain reduction |
| Schliessbach et al. (2018) [105] |
TCA | Imipramine | N/A | 50 patients with chronic low-back pain | Not approved | Imipramine response | CYP2D6 | *1, *3, *4, *5, *6, *8, *10, *41 | No overall reduction in low back pain with imipramine. No effect of CYP2D6 phenotype on pain tests results |
| Brasch-Andersen et al. (2011) [119] |
SSRI | Escitalopram | N/A | 34 patients with peripheral neuropathic pain | Not approved | Escitalopram treatment response |
HTR2A, HTR2C, ABCB1, CYP2C19, SLC6A4 |
HTR2A rs6314 GG, GA, AA HTR2C rs6318 GG, GC, CC (women) HTR2C rs6318 G, C (men) ABCB1 rs2032582 GG, GT/AT, TT SLC6A4 5-HTTL polymorphic region L/L, L/S, S/S |
Little evidence for decreased pain relief in HTR2C C allele carriers in male participants |
| Aldrich et al. (2019) [120] |
SSRI | Escitalopram | White Black Other |
248 patients with depression and anxiety | Not approved |
Escitalopram adverse effects | CYP2C19 | CYP2C19*1, *2, *3, *4, *5, *6, *7, *8, *17 | CYP2C19 PMs and IMs showed a higher total number of side effects compared with NMs and UMs |
| Kuo et al. (2013) [121] |
SSRI | Escitalopram | Chinese | 158 patients with massive depressive disorder | Not approved |
Escitalopram adverse effects | CYP1A2 | CYP1A2 rs2069521, *1K, *1F, rs4646425, rs35796837, rs34058039, rs2472304, rs3743484, rs4646427, rs2470890 |
CYP1A2 SNPs rs2069521, rs4646425, and rs4646427 are associated with dry mouth, nausea, and vomiting at week 2, and fatigue at week 1 |
PM = poor metabolizer, UM = ultra-metabolizer, IM = intermediate metabolizer, NM = normal metabolizer, FDA = Food and Drug Administration, EMA = European Medical Agency, TCA = tricyclic antidepressant, N/A = not available, SSRI = selective serotonin reuptake inhibitor.