#380 Is the secret to treating depression hidden in your genes?
CLINICAL QUESTION
Can genetic testing improve the efficacy and safety of antidepressants?
BOTTOM LINE
Pharmacogenomics testing to guide treatment in patients with depression might increase response and remission rates at 8 weeks by about 5% (example response rate 29% with pharmacogenomics versus 25% usual care), with no clear effects on tolerability. Studies have significant limitations. Cost (up to > $2000) and genes tested vary widely.
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EVIDENCE
- Results statistically significant unless indicated.
- Thirteen systematic reviews of randomized controlled trials (RCTs), past 5 years.1-13 Focusing on the most comprehensive [15 RCTs, 51-1944 participants, different tests used, mostly cytochrome P450 metabolism (example: CYP2D6)]:
- 6213 participants (often with treatment-resistant depression) randomized to pharmacogenomics-guided therapy or usual care.13 At ~8 weeks:
- Response rate: 29% (pharmacogenomics-guided) versus 25% (usual care). Number Needed to Treat (NNT)=25.
- Remission rate: 20% (pharmacogenomics-guided) versus 15% (usual care), NNT=20.
- Discontinuation rates, adverse events: no difference.
- Limitations: RCTs partially/fully industry funded; different populations, outcome definitions and pharmacogenomic tests used; high dropout rates (example: 21% in the largest RCT); Clinicians usually not blinded and might have been influenced by the results.
- Largest RCT, publicly funded: 1944 veterans with moderate-severe depression, 59% with post-traumatic stress disorder. At 24 weeks:14
- Response rates: 32% (pharmacogenomics-guided) versus 28% (usual care), NNT=25.
- Remission rates: No difference.
- Adverse events: Not reported.
- More participants in the pharmacogenomics group prescribed an antidepressant in the first 30 days (75% versus 69%).
- 6213 participants (often with treatment-resistant depression) randomized to pharmacogenomics-guided therapy or usual care.13 At ~8 weeks:
- Recent publicly funded RCT (655 participants), not included in systematic reviews: Similar results but also suggested a reduction in adverse drug reactions (insomnia 2% versus 6%; hypersomnia 7% versus 12%; abnormal liver function 2% versus 5%; loss of appetite 11% versus 15%).15
CONTEXT
- Different pharmacogenomics tests are available, most without RCT evidence.16
- Tests usually evaluate cytochrome P450’s and some pharmacodynamic variants (examples: genes that encode a serotonin receptor or proteins involved in transporting).16,17 Results include guidance regarding expected effect on efficacy and safety.
- Canadian depression guidelines do not recommend routine use of pharmacogenomics testing.17
- 2021 evaluation by the Canadian Agency for Drugs and Technologies in Health: unclear effects.18
- Cost16 between $200-2300.
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genetic testing not cost effective
I think patients will happily pay privately to get the best chance of treating their condition. The cost of not doing it may be greater.
Needs more work to support use for individuals at risk
Generally too expensive for my client base.