Understanding Pharmacogenetic Testing and Major Depressive Disorder

Understanding Pharmacogenetic Testing and Major Depressive Disorder

You may have questions about pharmacogenetic testing and Major Depressive Disorder (MDD). Are these tests scientifically accurate, and can they help determine the best medication choices? At Mid City TMS, because we specialize in treating patients who have Treatment Refractory Depression and optimizing patient outcomes, we see many patients who may have had or are considering having pharmacogenetic testing.  While genetically guided prescribing is promising, it remains controversial because of mixed findings in the research literature. The basic premise appears sound: matching the pharmacological profile of the medication to the patient’s associated DNA profile may reduce trial-and-error prescribing decisions. But the clinical utility of antidepressant pharmacogenetics has yet to be robustly replicated in randomized controlled trials.

Understanding Pharmacogenetic Testing

Also known as drug-gene testing or pharmacogenomic testing, pharmacogenetic testing refers to the examination of genes to determine the body’s anticipated responses to certain medications. The results of pharmacogenetic testing are intended to assist in determining what medications an individual should or shouldn’t take for the treatment of illness, as well as proper dosage amounts. The term “pharmacogenetic” combines pharmacology, the study of medicine and its applications, and genomics, the study of genes and gene function.

Pharmacogenetic Testing and Psychiatry

Along with clinical evaluation and diagnosis, determining the most appropriate treatment methods for psychiatric disorders is a complex process. Pharmacogenetic testing can be potentially helpful in determining the best treatment strategy, especially in those patients with Treatment Refractory Depression.

Is Pharmacogenetic Testing Reliable in Psychiatry?

Pharmacogenetic testing relies on biomarkers to determine the most likely potential outcomes of specific medications on a patient’s treatment. Therefore, this form of genetic testing could prove greatly useful in getting patients on the path to successful medication treatment faster than ever before.

However, there has not been enough reliable data and research to deem pharmacogenetic testing as a replacement to other methods of determining the best treatment pathways in psychiatry. According to recent research, the current literature on the efficacy of these tests has determined the viability of only four genes in delivering actionable clinical results. Further, the main literature that determined the viability of these genes was done by organizations with vested interests in proving the viability of pharmacogenetic testing.

Many pharmacogenetic tests are also currently performed by commercial testing providers that patients can access without a psychiatrist’s recommendation. While third-party testing is not itself abnormal, such methods of receiving test results leads some patients to misunderstand the current state of pharmacogenetic testing in developing psychiatric treatment.

Currently, the FDA has determined that pharmacogenetic testing alone is not a reliable source of determining clinical outcomes or for developing medication treatment plans because it currently does not rely on enough genetic factors to provide accurate results.

Pharmacogenetic Testing and Major Depressive Disorder: Getting Treatment Results

Within the psychiatric community, pharmacogenetic testing is an exciting prospect for the advancement of clinical treatment planning and practices. Much of the current work being done to advance its efficacy is in research involving patients with Major Depressive Disorder. Current numbers indicate that only half of all patients with diagnosed moderate to severe MDD respond positively or at all to their first prescribed medications. The sometimes uncomfortable side effects of certain antidepressants also make finding faster, more successful pathways to treatment a subject of vital importance.

There is strong evidence of the involvement of genes in the development of Major Depressive Disorder. While further research is being done to better explain these genetic connections, questions arise about the viability of using genetic factors to also determine the treatment, rather than just the cause, of MDD.

Recent Research in Pharmacogenetic Testing and Major Depressive Disorder

Although the number of commercially available pharmacogenetic tests has grown, there are ongoing uncertainties and concerns regarding the clinical utility of such tests.

The most commonly expressed criticisms have pertained to study design, as evidence supporting the efficacy of pharmacogenomic testing has stemmed largely from non-randomized, open-label trials or small randomized trials.

To address many of the expressed study design concerns while also evaluating the utility of pharmacogenetic testing in patients with MDD, a comprehensive study published April 2019, compared active treatment guided by pharmacogenetic testing to unguided active treatment in patients with MDD who had failed to respond to at least one adequate prior medication trial. Medications were considered congruent (‘use as directed’ or ‘use with caution’ test categories) or incongruent (‘use with increased caution and with more frequent monitoring’ test category) with test results.   Symptom improvement, response, and remission were monitored over 24 weeks with the primary endpoint at week 8.   At week 8, symptom improvement for guided-care was not significantly different than TAU.  However, improvements in response (26.0% versus 19.9%) and remission (15.3% versus 10.1%) were statistically significant. Patients taking incongruent medications prior to baseline who switched to congruent medications by week 8 experienced greater symptom improvement (33.5% versus 21.1%), response (28.5% versus 16.7%), and remission (21.5% versus 8.5%) compared to those remaining on incongruent medications.

The advancement of pharmacogenetic testing procedures and technologies requires further research—especially independently replicated randomized controlled trials– to produce more firm, more definitive conclusions about its merits. Pharmacogenetic testing should be interpreted as one tool to assist in thoughtful implementation of good clinical care, and prescriptions should not be based exclusively on the pharmacogenetic results. Clinical-demographic factors such as personal and family history, concomitant medications, and lifestyle should be always taken into account when making decisions about which medication is best.

Understand Major Depressive Disorder Treatment Options Through Mid City TMS

At Mid City TMS, we’re dedicated to treating depression with the latest knowledge of transcranial magnetic stimulation and other treatment approaches.  Pharmacogenetics is not yet an established standard of care in psychiatry because of its still limited evidence base.  However, TMS is an established standard of care treatment with a substantial evidence base for both its effectiveness and safety.  TMS can be an especially appropriate treatment choice for those patients who have had extreme sensitivity to the side effects of antidepressant medications and for those patients who have been refractory to antidepressant medications.

For a consultation, call us at 212-517-1867 or contact us through our website.

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