Antidepressants: Understanding and Mitigating the Risks of Side EffectsRuslan Dorfman, PhD, MBA
A universal truth of all medications is that no matter how beneficial they may be, they are always associated with some risks. Perhaps some of the most controversial medications are antidepressants, especially when they are used to treat relatively mild or moderate depression since they can cause serious side effects. Some patients with suspected depression may delay their first visit to a physician or psychologist due to the fear of adverse side effects commonly associated with some antidepressants. Moreover, the prescription of antidepressants can be challenging for physicians and frustrating for patients because there are many medications to choose from but many will not be effective. Understanding of an individual patient’s body chemistry may help physicians and patients make more informed selections of potential treatments for depression.
Antidepressant is a broad term that describes all medications from different classes that are used to treat major depressive disorder, either alone or in combination with other medications. In addition to treating depression, antidepressants are often used to treat other conditions such as anxiety disorders, eating disorders and chronic pain. The most common classes of antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MOIs), which all have differing modes of action. The popular belief is that antidepressants should not be used as the first line of treatment for mild depression and should be reserved for moderate or severe cases. However, this opinion differs between physicians and an individual patient’s preference is often considered.
There are over 70 antidepressants available with no specific medication or class of medications that is most effective for all individuals. While medications from different classes are comparable in efficacy for the population in general, an individual patient’s response is highly variable and it is estimated that only about 1/3 of patients respond to citalopram, which is often the first line of treatment, and the majority of patients try 2-4 different medications at various doses until they find a drug that works. Thus, the prescription of antidepressants often takes a “trial and error” approach that can be both time consuming and discouraging for the patient. Furthermore, this approach may make antidepressants less effective since the more antidepressants a patient has already been given, the less likely they are to work.
All antidepressants are also associated with side effects, many of which can be serious. For example, antidepressant can induce mania, a state mood arousal or irritability, in patients with bipolar disorder. Since many of the symptoms of depression and bipolar disorder overlap, patients may be misdiagnosed and put at risk. Many antidepressants including as citalopram, with is the most commonly used antidepressant, also disrupt appetite and have been associated with weight gain while some result in the opposite effect, depending on their effects on signaling in the brain. Sleep patterns may also be affected with different classes of antidepressants being shown to disrupt REM sleep. Another common side effect of many antidepressants is sexual dysfunction that can be temporary or long-term. One study estimated that between 57-73% of those patients taking SSRIs experienced sexual dysfunction. The risks associated with the use of antidepressants during pregnancy are still unclear. Some studies suggest that antidepressants can cause spontaneous abortion, birth defects and developmental delays in children while other studies argue that they are safe to use during pregnancy. The risk of suicide, especially for young and elderly patients taking antidepressants remains controversial. There is evidence that antidepressant use is associated with an increased incidence of suicide, however why this occurs is still poorly understood. With all the various risks and concerns associated with antidepressants is there anything that can be done to improve their safety?
The risk of certain side effects, including suicide, has been linked to a patient’s ability to metabolize drugs by liver enzymes called cytochromes P450. Genetic variations in these enzymes can be used to determine how an individual will react to a specific medication. For example, patients with reduced CYP2C19 activity clear citalopram and similar drugs slower and are more likely to enter remission at regular dose, but may be also at a higher risk of adverse side effects. Genetic variations in cytochrome enzymes and other proteins can also determine if an individual will not respond to a specific antidepressant, decreasing trial and error time, as well as determine the ideal starting dosage. Similarly, variations in the CYP2D6 gene have been linked to a risk of adverse side effects, particularly the CYP2D6 gene duplication, which is responsible for the ultrafast metabolizer type and has been implicated in the risk of suicide. While it is impossible to remove all the risk of side effects, genetic testing prior to taking antidepressants can be a powerful tool to improve the efficacy and safety of these medications.
If you would like to learn more about depression treatment, continue reading this related blog post: “How To Find The Right Treatment For Depression”.
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- Ruhé, Henricus G.; Huyser, Jochanan; Swinkels, Jan A.; Schene, Aart H. (2006). “Switching Antidepressants After a First Selective Serotonin Reuptake Inhibitor in Major Depressive Disorder”. The Journal of Clinical Psychiatry 67 (12): 1836–55.
- Montejo, AL; Llorca, G; Izquierdo, JA; Rico-Villademoros, F (2001). “Incidence of sexual dysfunction associated with antidepressant agents: A prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction”. The Journal of clinical psychiatry 62 (Suppl 3): 10–21. .
- Picture courtesy of mentalhealthy.co.uk
Learn more about role of pharmacogenetics in mental health here