Major depressive disorder (MDD) is a common mental disorder that affects more than 264 million people worldwide and is a leading cause of disability, including death by suicide.1 MDD is a complicated disorder that involves the interaction of social, psychological, and biological factors.1 MDD can prevent patients from living healthy, productive lives and can complicate treatment of other comorbid conditions.1
Although MDD commonly is encountered in primary care settings, its treatment has become integrated into all fields of medicine due to its high prevalence. Cognitive behavioral therapy, interpersonal psychotherapy, and antidepressants, such as selective serotonin reuptake inhibitors and tricyclic antidepressants, are the mainstays of MDD treatment.1
Prescribing an antidepressant may be simple, but that does not make it easy. Efficacy and tolerability of antidepressants vary among patients, which can make it challenging to relieve patients symptoms.2 Although no genes have been associated with depression,3 several genetic variants may help clinicians predict how patients with MDD will metabolize antidepressants.4 Performing genetic testing of patients with MDD and matching patients with an antidepressant class based on identification of genetic variants that convey sensitivity to particular antidepressants could improve response to drug therapy in patients with MDD.5
Current Antidepressant Management
The process of selecting an antidepressant should take into account cost, tolerability, adverse effect profiles, and patient preferences.2 When evaluating treatment options for patients with MDD, the current standard of care is to initiate an antidepressant at a starting dose and reassess effectiveness within 2 to 4 weeks, with adjustments to monitoring frequency dependent on the patient’s suicide and self-harm risk, comorbid conditions, age, and concomitant medication use.2
Several metrics are used to determine whether a selected antidepressant is working:
- Does the patient feel better?
- If not, the clinician should increase dosage to see if the desired effect can be produced.
- If dose titration does not reduce symptoms, the clinician should select another antidepressant.
- If the patient does feel better, is he or she experiencing adverse effects; if so, how tolerable are they?
Clinicians can mitigate adverse effects by decreasing the dosage or switching to a different class of antidepressant. However, several weeks are needed after each change in drug or dose alteration to truly assess response. Finding and settling on a drug that produces a response with minimal adverse effects can take months. During the trial period, patients may become frustrated with the process and stop therapy and/or may be at increased risk for suicide or self-harm.
The study of drug metabolism in patients with MDD is a growing area of interest.3-5 A management approach incorporating pharmacogenetic testing in combination with clinical judgment may be superior to the standard trial and error method for finding an effective antidepressant regimen and could improve patient outcomes.5
Genome-wide association studies are used to identify single nucleotide polymorphisms (SNPs) in genes related to a particular disease or drug metabolism.6 Several laboratory testing companies offer pharmacogenetic panels to evaluate metabolism of drugs used to treat MDD.3 The FDA also has approved direct-to-consumer genetic testing panels (eg, 23andMe), which are widely available to the public without a health care provider’s prescription.7 A concern with these latter tests is that the results of these tests are reported directly from the company to the patient; thus, the patient decides whether or not to present the information to his or her health care provider. Many pharmacogenetic testing panels also include genes that have shown correlations with the pathogenesis of MDD, despite the lack of clinical research replicating the role of these genes in the disorder.3