#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.
Reading Tools for Practice Article can earn you MainPro+ Credits
Join NowAlready a CFPCLearn Member? Log in
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.
Latest Tools for Practice
#386 The Bland Supremacy: Salt and cardiovascular disease
Does reducing sodium intake or substituting table salt with sodium-potassium alternatives improve cardiovascular outcomes?
#385 Topical minoxidil for androgenetic alopecia: When blood pressure agents make you hairy
How effective is topical minoxidil for androgenetic alopecia?
#384 Treatment of PTSD Nightmares: Is prazosin a dream come true?
How effective is prazosin for nightmares in posttraumatic stress disorder (PTSD)?
Complete Activity
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.
Cost prohibitive for many in my practice, but if someone can afford it, it may help provide a sense of empowerment and better enable the patient to do other things to help themselves like engage in CBT/DBT and exercise
Fun to read an article on the frontiers of medicine. Gazing forward genetic testing may offer some therapeutic benefit
in the management of patient’s with refractory depression (under the treatment of a Psychiatrist)….
I’ve seen a few patients do the IMPACT study via CAMH and it was extremely helpful in choosing medications. If a patient is willing to spend the money to not have to try several different options, i don’t see this as a downside.
I have one patient who did the genetic testing privately , very expensive.
I tried the medication suggested according to the test result , it did not make any difference with his symptoms. Not sure if it is worth to do it
I was hoping that it would have been more successful, hopefully as they continue to research it will be more promising.
Canadian depression guidelines do not recommend routine use of pharmacogenetics testing.