What to do when Antidepressants Are Not Working


It can be quite challenging when antidepressants are not working. But, the treatment of depression remains one of trial-and-error. When a patient with clinical depression is prescribed an antidepressant, it takes about 4 to 6 weeks to find out if the medication actually works for the patient, during which the patient can suffer from side effects of the medicine. If the medication is not effective, the process has to be repeated with a different medication until the correct one is identified. In everyday clinical practice, psychiatrists have little ability to predict which specific treatment will work best for a patient. “To be ill with depression any longer than necessary can be perilous,” said Dr. Helen Mayberg, M.D., professor of psychiatry at Emory University. “This is a serious illness and the prolonged suffering resulting from an ineffective treatment can have serious medical, personal and social consequences. Our goal is not just to get patients well, but to get them well as fast as possible.” Dr. Friedman, director of the psychopharmacology clinic at the Weill Cornell Medical College, writes eloquently about the hit-and-miss approach he has to use to identify an antidepressant that will work best for a patient. One patient, a successful professional in her late 30’s who had sought help for lifelong depression, was ready to call it quits after three months of trying out different classes of antidepressant – when she mentioned that her father had done well on a specific antidepressant. Within three weeks of trying the antidepressant that had worked for her father, the patient was feeling better and her symptoms improved markedly.

How genetics can help with finding your correct medication

Scientists have identified genetic variations that can potentially predict patients’ response to antidepressants explaining why some patients respond to some drugs but not to others.

Variations in our DNA are associated with predicting treatment response, in terms of efficacy and side effects to medications. Genetic changes in drug-metabolizing genes underlie this differential response, predisposing individuals to enhanced or poor response to medication or to adverse side effects from specific medications. The most studied group of drug-metabolizing enzymes in psychiatry are the cytochrome P450 (CYP) enzyme family which are expressed predominantly in the liver. The genes coding for the CYP enzymes have many DNA variations contributing to the degree of difference in the metabolism of psychotropic drugs. People can be broadly grouped into four categories based on the efficiency of their enzyme activity: poor metabolizers, intermediate metabolizers, extensive metabolizers and ultra-rapid metabolizers. CYP2D6, an important member of the CYP liver enzyme family, is responsible for metabolizing nearly 50% of the most commonly prescribed medications like tricyclic antidepressants, many SSRI, venlafaxine, and antipsychotics. The CYP2D6 gene commonly exhibits variations, with 7% of Caucasians but only 1% of Asians falling into the group of poor metabolizers. When a ‘CYP2D6 poor metabolizer’ is prescribed any of these drugs, the patient is at risk for side effects due to the increased availability of the drug. The drug persists in the biological system as it does not get metabolized and eliminated. On the other hand, a patient who is a ‘CYP2D6 ultra-rapid metabolizer’ would not benefit from the medication either, as it is metabolized and eliminated from the system too quickly for it to be effective. A genetic test, like GeneYouIn’s PillCheck, can identify DNA variations in your drug metabolizing enzymes. Depending on the enzyme affected, a simplified scheme can be used by a physician as a basis to predict responsiveness to pharmacologic treatment, identifying the most effective medication at the optimal dose for an individual and help patients get well…” as fast as possible, using the treatment that is best for each individual.”

What’s next?

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Learn more about role of pharmacogenetics in mental health here