Table 4. COMT and placebo response.
| Condition | Study design, N | Outcome | Results | Ref. |
|---|---|---|---|---|
| Psychiatric studies | ||||
| Working memory | RCT of tolcapone in healthy normal volunteers N = 68 | N-back | In the placebo group, met-allele homozygotes outperformed val-allele homozygotes on tests of memory and were more risk averse. Tolcapone reversed these effects | [150] |
| MDD | RCT in MDD patients, N = 132 | HAM-D17 and MADRS | Met-alleles showed a statistical trend toward a lower magnitude of placebo response. But in a recent GWAS of a placebo controlled RCT of duloxetine for MDD, COMT association did not reach genome-wide significance | [144,151] |
| Pain and neurological studies | ||||
| Pain | Experimental pain in healthy normal volunteers. Repeated measures, N = 296 | VAS | The COMT met allele plus OPRM1 rs1799971 Asn/Asn associated with placebo analgesic response | [152] |
| Pain | Experimental Pain in healthy normal volunteers. N = 223 | VAS and FOP | Met allele was associated with increased fear of pain but not placebo analgesia | [148] |
| Pain | Experimental Pain in healthy normal volunteers, N = 48 | fMRI measures | Met alleles were linearly associated with stronger experimental placebo analgesia | [153] |
| IBS | RCT in IBS patients with NTC, N = 104 | IBSSS | Met/met had greater placebo response in placebo arm augmented with positive clinical engagement | [149] |
| Cardiometabolic disease studies | ||||
| CVD | RCT in healthy normal women, N = 104 | CVD events | Val allele associated with lower rates of CVD in placebo treatment arm | [52] |
| Energy expenditure and fat oxidation | Green tea (capsules) versus placebo in randomized cross-over study among healthy normals, N = 14 | Energy expenditure and fat oxidation | Differential COMT genetic green tea effects were observed with higher energy expenditure and fat oxidation among met/met participants with placebo compared with val/val participants | [106] |
| Other conditions | ||||
| Inflammatory disease | Meta-analysis of RCTs in asthma and other inflammatory disease | Quality of Life (QOL) | No effect was observed for COMT | [154] |
| Nocebo effects in immunosuppression | RCT of immunosuppression | General side effects | The val-allele was found to be positively associated the perception and reporting of side effects in a study of placebo in immunosuppression | [155] |
Asn/Asn: Asparagine polymorphism in OPRM1; CVD: Cardiovascular disease; FOP: Fear of pain; HAM-D17: Hamilton Depression Rating Scale score; IBS: Irritable bowel syndrome; IBSSS: IBS symptom severity score; MADRS: Montgomery-Asberg and Depression Rating Scales; MDD: Major depressive disorder; met: Methionine; NTC: No-treatment control; RCT: Randomized clinical trial; rs-fMRI: Resting-state functional MRI; val: Valine; VAS: Visual analog pain scale.