Why it’s a good idea to test your DNA before starting an add-on antidepressant

Ruslan Dorfman, PhD, MBA12 Jun 2024

Did you know that only 30% of people get adequate symptom relief from the first antidepressant they try? The majority end up switching drugs or adding medications to manage their condition. Until recently, depression treatment often involved much "trial and error" to find the right treatment for each individual. However, multiple clinical trials have shown that matching treatment to your DNA can increase your odds of achieving a positive response by 50%. Here we explain how pharmacogenetic testing can help in selecting an appropriate "add-on" antidepressant to augment treatment and accelerate your recovery from anxiety and depression.

Starting depression treatment

The established standard protocol for depression treatment for adults starts with citalopram, escitalopram or sertraline. These drugs are Selective Serotonin Reuptake Inhibitors (SSRIs) and are recommended as the first line of treatment for depression. If these drugs do not work, a switch to an alternative antidepressant is recommended. If you are one of many people who did not achieve adequate response from the first line of treatment, adding another drug might help. However, combining one antidepressant with another prescription or a supplement greatly increases the risks of side effects. Yet, specific antidepressant combinations are more effective for some patients.

Which add-on antidepressants work best?

A recent study evaluated which drugs work better in a combination with SSRIs for depression treatment. This study confirmed that adding mirtazapine, trazodone or mianserin (drugs that block α2-autoreceptors) to an SSRI often works better than other antidepressants. Bupropion is another commonly used add-on medication for depression treatment. Bupropion alone can be an effective depression treatment for people that could not tolerate citalopram, sertraline, paroxetine, fluvoxamine and other SSRIs. However, combinations of bupropion with SSRIs did not provide a better response compared to SSRIs alone.

If the combination of SSRI with one of the four drugs mentioned above did not work for you, a psychiatrist might consider prescribing an antipsychotic, for example, aripiprazole (Abilify), brexpiprazole (Rexulti), or quetiapine (Seroquel XR) as add-on therapies to an antidepressant for treatment-resistant depression.

Before adding another pill, ask yourself why the SSRI did not work

There are multiple reasons why an antidepressant is ineffective or causes severe side effects. Almost all antidepressants are metabolized by liver enzymes called cytochromes P450 (or CYP450 for short). You may be a "fast metabolizer," – i.e. your liver enzymes break down the drug much faster, so it is not effective unless you get very high drug doses. If you are experiencing side effects, there is a high chance that you are a "slow metabolizer," so the drug is building up in your body, leading to toxic effects. Ironically, you can be a "slow" for some medications and a "fast" metabolizer for others, so some antidepressants may be ineffective for you while others may cause intolerable side effects. That's why finding the right prescription can take many months of trial and error.

graphical depiction of the effect of standard dosing on different metabolizer types

Pharmacogenetics increases the chance of success

A DNA test, called a pharmacogenetic test, can assess how your body metabolizes different medications. Recently pharmacogenetic testing has been recognized as an established tool for guiding depression treatment and can increase the odds of achieving remission by 46%.

You and your doctor can better understand how your body clears different antidepressants and other medications based on pharmacogenetic test results. Pharmacogenetic tests with broad coverage, such as Pillcheck, cover the key enzymes that break down antidepressants, antipsychotics, benzodiazepines and other medications used for depression and anxiety treatment. This information can help your doctor find which medications would work better for you and which ones you should avoid, if possible.

What else could help to treat depression?

Leading psychiatrists Drs Roy H. Perlis and Maurizio Fava proposed a new treatment protocol incorporating new treatment options. First, they recommend optimizing SSRI therapy with the help of pharmacogenetics. Digital self-guided Cognitive Behavioral Therapy (CBT) tools should be used along with drug therapy. For people that did not respond to an SSRI, the addition of another drug is recommended. Therapist-guided CBT may be needed as well. A psychiatrist can re-assess your diagnosis and recommend alternative medications. Augmenting treatment with mirtazapine, trazodone, or mianserin can improve your odds of response by about 30%.

Summary

The majority of people suffering from depression do not respond to the first antidepressant tried.
Your DNA determines how your body metabolizes different antidepressants.
Pillcheck pharmacogenetic testing can help your doctor select the right antidepressant before starting an add-on drug.
Certain drug combinations work better – the choice of SSRI and augmenting medication should be matched to your DNA.
CBT should be used along with medications for improving depression treatment.