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What to do When Your Depression Meds Aren’t Cutting It



Major depressive disorder is the most widespread mood disorder in the world. So, it is no wonder that much attention has been dedicated to researching and developing more effective medications that can treat the condition. In the 21st century, scientists have learned a great deal more about the biology behind depression, and as a result, there are new medications that go beyond just targeting certain neurotransmitters.


In the last two decades alone there have been major advances that have created transformative changes in how depression is treated.[1]


With so much progress being made, however, conditions like major depressive disorder can still be tricky to treat. Consider that just 30 - 40% of individuals respond to the first medication they are prescribed! Then of the 60-70% who don’t experience a favorable response, only about 40% of those individuals will respond to a second medication.[2] That leaves a frustrated and bewildered subset of individuals who still are searching for answers.


While those more complicated cases aren’t common, for individuals who are searching for relief, the conundrum can be extremely discouraging. This situation is known as treatment resistance, and it doesn’t just surface for those with major depressive disorder; resistance to certain medications can show up in a whole slew of mental health conditions.


The question remains then – why do medications work for some individuals but not for others? How does both our individual body chemistry and specifically how we metabolize medications, factor into whether we experience side effects or whether we even respond to them?


After all, an endless array of studies is done and serves to be an effective guide for psychiatrists and other medical professionals who help patients manage their conditions. Those patients that fall into a “normal range,” and respond favorably in clinical studies are actually a large slice of the general population. But left behind are the outliers – a small percentage of the population that don’t see results.


Outliers exist because – bottom line – each individual’s chemistry is unique.


How your cousin Joe metabolizes and responds to medication may be drastically different than how your best friend Pat does.


No two individuals have identical responses to medication.


That’s because when someone takes medication, the body breaks it down and metabolizes it so that it can become active in their body. Since every person's genetic makeup dictates that process differently, everyone can have very different responses to the same medication. Understanding that metabolic processes differ between individuals can be a major factor in medication effectiveness; that is where a technology called pharmacogenomic testing come in.

Pharmacogenomic testing can help doctors unpack the mysteries around treatment resistance by analyzing a person’s genetic makeup to understand their different metabolic pathways that determine how they metabolize medication.


Who Can Benefit from Pharmacogenomic Testing?


There are two main clinical patient populations that may benefit from pharmacogenomic testing.


1.) Patients who haven’t responded to multiple medications and therefore haven’t seen adequate results – these patients are likely over-metabolizing the medication. When the body over-metabolizes, individuals end up having less active medication in their system at any time – hence rendering it ineffective.


2.) Patients who have experienced significant side effects from multiple medications – in these situations, the opposite may be true. Their body is under-metabolizing the medication and they have higher than expected amounts of active medication in their system, making them more prone to side effects.


In both patient populations, pharmacogenomic testing can help guide physicians in adjusting the dosage, and/or choosing medications that will be more effectively metabolized and utilized by the patient’s system. Pharmacogenomic testing is like a window that gives doctors a look at the patient’s chemistry to understand how their body interacts with and breaks down medications. As a result, pharmacogenomic testing can help patients receive treatment that is truly individualized to their specific makeup and genetic profile.


A Medical Team that Understands Pharmacogenomic Testing


While relatively few individuals have heard of pharmacogenomic testing, those of us who work to unwrap the mysteries around complicated mental health cases know it can be extremely useful in treatment planning. Having objective evidence to help us decide what medication interventions can help our patients is another tool in our arsenal that can provide patients with the hope that help is within reach.


You might wonder why we don’t use this amazing testing technique on every patient. The answer is that it is simply not necessary. Most of the population (like those I mentioned in the clinical trials above) respond at some point and do see results. But it is those patients who are struggling with treatment efficacy that truly need the extra time and in-depth analysis that pharmacogenomic testing provides.


The practitioners at Clarity use this advanced tool when needed. Opening patients’ eyes to the possibility that there could be a potential genetic component at play gives them confidence that we are doing all we can to maximize results. With technology like pharmacogenomic testing at our disposal, and with an experienced team who can expertly interpret result, a world of possibilities opens!


Those of us practitioners who use this insightful testing are covering all the bases as we look to solve treatment resistance. Yet what many individuals forget is that we still need to evaluate a medication’s clinical response, which is separate from dosing and metabolism. It's not going to necessarily tell us that this medication unequivocally is going to be the one that works for them, but it is going to give us the best chance to find a medication that their body can tolerate, to see an effective response, and in managing their symptoms. So, while pharmacogenomic testing is not a magic bullet, it does help narrow what medications may be best for the patient.


Clarity Provides…Clarity


It isn’t uncommon in our practice to see individuals who in some cases, have more complicated mental health diagnoses. That’s when we put our experience to work and use tools like pharmacogenomic testing to look at every possibility. We expertly evaluate and interpret patient test results and apply those to our clinical decision making. Our vast experience using pharmacogenomic testing in the residential setting puts us at a clear advantage in bringing it to individuals in outpatient treatment.


It's another tool within the holistic diagnostic workup that we can offer to support an individual’s overall diagnosis.


It is true that we are living in a time when there are a plethora of resources, solutions, and objective data that hold promise and possibilities for hope and healing in mental health treatment! That’s why I encourage individuals to carefully choose a treatment team that has their antennas up – and is on the lookout for every possibility for everything available and at our disposal as practitioners to help patients get better.


After all, is there a more important goal for us?


When individuals are searching, I encourage them to consider a group that can guide interventions to provide the best chances of success! With that dogged determination we hold out hope that progress is around the corner.



The Patient Experience in Genetic Testing


For patients who undergo pharmacogenomic testing the process is convenient and easy. Typically, test kits are sent directly to a patient’s home with instructions. Once individuals rub each the inside of their check with a swab to gather tissue, they put the sample in the test tube, seal it, and send it back to the testing company. Generally, within about a week, they get the results of the genetic profile for each of the different groups of medications.


Jeremy’s Case


In one case, we had a patient – Jeremy – who had been prescribed over 15 different antidepressant medications over the years and he had either not responded, or in some cases, he had significant limiting side effects to a majority of those medications. We ordered the testing and found that the results correlated to show that there were significant genetic impacts that affected how Jeremy metabolized his medications. We ultimately found that there were only three of the newer antidepressant medications that fell into the “use-as-directed” category. We chose one of those medications, initiated treatment, prescribed an adequate treatment dose, and followed him closely. Success! Jeremy did not have any significant limiting side effects – which was a first for him in his long history of being engaged in depression treatment.


Hope…with an Asterisk


No matter where an individual is within their treatment journey, I encourage a positive outlook. It helps! But I also like to remind patients to find a balance and to temper high expectations.


Medications are clearly a very important part of the management of the disease process. That is why medication management is standard of care many times. However, there’s no magic pill or perfect fix. A medication doesn’t instantly snap everything back into place and life returns as normal.


When we treat patients, we look at targeting a specific set of symptoms. Many times, it's the physical impact, and symptoms of depression such as lack of energy, low motivation, sleep problems and appetite changes, that tend to respond best to the medications. But we remind patients that psychotherapy plays an important role, and it has been shown to be equally effective as medication.


Medications have to be combined with these other behavioral interventions to support an overall kind of achievement of mental wellness.


The combination of the therapy and medication is better than either one alone, and we counsel patients to factor in healthy nutrition, hydration, and sleep hygiene. We emphasize that behavioral changes are key, including decreasing isolation and making an effort to reengage in social activities.


We give patients the encouragement and even go as far as telling them to fake it till you make it. That motivation will continue to build and allow this process to unfold. Ultimately, medications are only a small piece in the grander scheme of treatment. We never forget that treating mood disorders is a journey.


Your clinician should be your advocate to support you and guide you in that journey with all the tools that we know are going to help you move in the right direction.

[1]Advances in Treatment for Major Depressive Disorder (webmd.com) [2] Khalid Saad Al-Harbi. “Treatment-resistant depression: therapeutic trends, challenges, and future directions.” Patient Preference and Adherence, p. 369-370.

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