By Diana Zuckerman, Ph.D., Sarah Miller, RN, Megan Cole, and Madeline Levin, MPH
A look at the risk of suicide and other dangers associated with using antidepressants
Antidepressant medications are widely prescribed in an effort to reduce the debilitating impact of depression and to reduce the risk of suicide. However, a growing body of research indicates that the medications are less effective than expected
When a person’s depression starts to lift, he or she may feel less hopeless and helpless. That sounds like an improvement, but when people feel less helpless but still feel depressed, they may think about suicide as a way out, whereas before they were too immobilized to make a suicide plan. For that reason, a decrease in the symptoms of depression can increase the risk of suicidal thoughts or actions. That risk is well known by mental health specialists, and can occur regardless of the type of treatment that a patient is receiving, or even if the patient is feeling less depressed without any treatment.
As antidepressants became more commonly prescribed for anxiety and obsessive compulsive disorder, the reports of patients’ suicidal thoughts and actions became more worrisome to physicians and family members. If a depressed person on antidepressants is suicidal, that is not so surprising, but if someone who was not depressed and taking antidepressants for other reasons becomes suicidal, that raises questions about the safety of these medications. Researchers found evidence that individuals taking antidepressant medication may be at even higher risk of suicide than individuals whose depression is easing for other reasons. That controversy has not yet been completely resolved.
Antidepressants and children
The risks of antidepressants first became clear in research on children, and in the fall of 2004, the FDA issued a Public Health Advisory warning that children and adolescents taking antidepressant medications might experience increased suicidal thoughts and behaviors. In June 2005, this warning was extended to include young adults up to age 25. In fact, for children and adolescents, studies showed that patients taking antidepressants had nearly double the rate of suicidal thoughts and actions, in comparison to patients taking a sugar pill. This prompted the FDA to require antidepressant drug manufacturers to add a “black box” to the label warning about the increased risk for children. The warning also says that children and adolescents taking the types of antidepressant known as “serotonin reuptake inhibitors” (SSRIs) should be carefully watched for increased depression, suicidal thoughts or behaviors, or “unusual changes in behavior, such as sleeplessness, agitation, or withdrawal from normal social situations.” Placing a black box around a warning, similar to those for cigarettes, is the strongest type of warnings about risks that the FDA requires, and indicates FDA’s great concern.
Antidepressant use among adults
In response to these concerns, researchers brought together data from short-term trials to see if antidepressants increased suicide risk in adults over 25 as well. They found no significant increase in risk of suicide for adults taking antidepressants. On the contrary, depressed adults taking antidepressants appear to be somewhat less likely to have suicidal thoughts and attempt suicide than depressed adults who don’t take them. Antidepressants are even more protective against suicide for depressed individuals 65 and older.
The different results for children, young adults, elderly adults, and other adults suggest that differences in metabolism may be affecting the safety of these medications. If so, that could also have implications for other types of patients that might be at higher or lower risk, such as particular racial or ethnic groups that may metabolize these drugs differently. Studies have shown that genetic differences affect how well antidepressants work for different people and how well people are able to tolerate them.,  Unfortunately, studies comparing the effectiveness of different antidepressants do not have enough participants from racial and ethnic minorities to draw conclusions about which drugs work best for which groups of people.
Suicide risk for different types of antidepressants
When looking at types of antidepressant used, the risk of suicide appears to be the same for all antidepressants. According to data from almost 300,000 adults ages 18 and older who started taking antidepressants between 1997 and 2005, no meaningful difference in risk for suicide was found when comparing the different types of antidepressants. Similarly, there were no differences in suicide attempts or rates among children or adolescents taking different antidepressants, which is why the FDA includes the same black box warning on all antidepressants given to children and adolescents.
Risks vs. Benefits
Antidepressants have been widely prescribed for anxiety and other psychological problems in addition to depression, and it is important to weigh the likely benefits against the known risks. Whether for children or adults, antidepressants have other risks in addition to the possible risk of suicide. Common side effects include nausea, anxiety, restlessness, decreased sex drive, dizziness, weight gain or loss, tremors, sweating, sleepiness, fatigue, dry mouth, diarrhea, constipation, and headaches. More worrisome effects include increased hostility, anger and aggression, insomnia, and feeling of panic. All individuals taking antidepressants should be carefully watched for changes in behavior or suicidal thoughts, especially if it is the person’s first time taking antidepressants. If you notice these behaviors in yourself, a friend, or a family member, it is important to contact a doctor immediately.
It is also important to be aware of the side effects of other drugs that are sometimes used for depression. For example, Seroquel (quetiapine) and Abilify (aripiprazole) are widely prescribed medications that were originally approved by FDA for schizophrenia. They were also approved by the FDA for psychosis from the manic phase of bipolar disorder (also called manic depression). In a controversial decision, the FDA then approved them for use in depression-but only for patients who are taking other antidepressants at the same time and for whom antidepressant medication alone was ineffective. These antipsychotic drugs sometimes help with anxiety and sleeping problems because they can have a sedative effect, making it dangerous for patients to drive or use machinery. It is not clear if these antipsychotic medications help with depressed mood, but insomnia and anxiety are symptoms of depression too. In addition to the questionable benefits, these drugs have serious side effects, such as dramatic weight gain (and potentially diabetes) and “sudden cardiac death.”
Other popular anti-depressants have other risks. Cymbalta (duloxeine) is a serotonin norepinephrine re-uptake inhibitor (SNRI) that has been linked to liver failure, Zoloft (sertraline, an SSRI), is associated with higher rates of diarrhea than other antidepressants, and Effexor (venlafaxine), another SNRI, is more likely to increase blood pressure, heart rate, and nausea, and in one study was linked to gastrointestinal bleeding., 
In addition to these potentially serious risks, most antidepressants cannot be combined with certain drugs or alcohol. One study found that healthy, depressed women using SSRI’s and tricyclic antidepressants are three times more likely to suffer from sudden cardiac death (SCD) than healthy, depressed women not taking antidepressants. It is not clear, though, from the study whether these women suffered from more severe depression (which is a risk for heart disease) and therefore were more likely to take antidepressants or whether they died because the antidepressants caused changes in their heart rhythms.
Antidepressants can negatively interact with many other drugs, including over-the-counter drugs such as cold medicines and pain killers.
Are there effective treatments for depression that are not so risky? A type of therapy called cognitive behavioral therapy has been found to be very effective. It trains the patient to think about their shortcomings or problems in a different way, helping them to focus less on the helpless and hopeless feelings of depression and more on what they are doing well.
So, although antidepressants may improve your life, do not forget that taking them means subjecting yourself to many potential side effects and often serious risks.
For more information go to: http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm096273.htm
 National Institute of Mental Health (2010). Antidepressant Medications for Children and Adolescents: Information for Parents and Caregivers. Retrieved from http://www.nimh.nih.gov/health/topics/child-and-adolescent-mental-health/antidepressant-medications-for-children-and-adolescents-information-for-parents-and-caregivers.shtml
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 Whang W, Kubzansky LD, Kawachi I, Rexorde KM, Kroenke CH, Glynn RJ, et al (2009 March 17). Depression and Risk of Sudden Cardiac Death and Coronary Heart Disease in Women: Results from the Nurses’ Health Study. Journal of the American College of Cardiology, 53(11): 950-958.