Antidepressant medications are widely prescribed to try to decrease the symptoms of depression and to reduce the risk of suicide. However, the medications have risks that outweigh the benefits for more patients than you probably realize.
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 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. That’s because studies showed that children and adolescents taking antidepressants were almost twice as likely to have suicidal thoughts or to attempt suicide, compared to patients taking a sugar pill. The FDA required 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.
The antidepressant Paxil has never been approved for children under 18, and that research shows it has no benefit and can be harmful to anyone under 18. The U.S. government is suing GSK pharmaceutical company for misleading physicians and patients about the effectiveness of Paxil in children, and covering up suicides and suicidal behavior.
Violent behavior is also a side effect of antidepressants. A 2015 Swedish study of their entire population ages 15 and older reported that 11,225 out of 856,493 (1.3%) teens and adults taking SSRIs were convicted of a violent crime compared to 40,384 out of 7.1 million individuals (0.6%) of the same age not taking SSRIs. The risk of being convicted of a violent crime was the highest among the youngest age group: 3.3% of SSRI patients between the ages of 15 and 24 years old were convicted of a violent crime. 77% of these convictions (2,169) were in males in that age group who were taking an SSRI. However, when comparing five of the most prescribed SSRIs (fluoxetine, citalopram, paroxetine, sertraline, and escitalopram), only sertraline (Zoloft) increased the risk of a violent crime conviction.
Since there is no evidence that some antidepressants are more dangerous than others for children, the FDA includes the same black box warning on all antidepressants given to children and adolescents. (See the list at http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm096273.htm)
Antidepressants and Adults
Researchers brought together data from several studies 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. A 2011 study in the United Kingdom (UK), which included over 60,000 patients between the ages of 65 and 100, did not find a significant increase in suicide risk for adults over 65 who take antidepressants. However, the study also reported that mirtazapine and venlafaxine were the antidepressants that were much more likely to be taken by adults who attempted suicide or harmed themselves, or that died from other causes.
A different UK study published in 2015 that included more than 238,000 adults ages 20 to 64 years of age reported that patients reported that patients mirtazapine, venlafaxine, or trazodone were much more likely to commit suicide or attempt suicide/self-harm compared to patients taking a SSRI. In contrast, a study of almost 300,000 adults ages 18 and older who started taking antidepressants between 1997 and 2005 found no meaningful difference in risk for suicide when comparing the different types of antidepressants.
It is hard to make sense of these contradictory different findings for adults. However, since antidepressants like venlafaxine and mirtazapine are often tried only when SSRIs are not effective, the people who take them may have depression that is more difficult to treat with medication. Therefore, the lack of success in treating depression with different medications may be the reason why those patients are more likely to try to kill themselves.
In summary, whether an antidepressant increases or lowers the risk of suicide seems to depend on the type of antidepressant being taken, the individual’s response to treatment, and the age of the person taking them. The different results for children and adults of different ages suggest that differences in metabolism may affect the safety of these medications. Studies have shown that genetic differences affect how well antidepressants work for different people and how well people are able to tolerate them.[7,8] 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.
A 2015 study included over 2.2 million infants born in Denmark, Finland, Iceland, Norway and Sweden, of which more than 36,000 were exposed to an SSRI during pregnancy, reported that SSRIs decreased the risk of heart defects and did not affect neurological defects. In contrast, a previous study conducted by the Centers for Disease Control and Prevention (CDC) reported that Paxil (paroxetine) and Prozac (fluoxetine) taken by pregnant women increase the risks for heart and neurological defects in newborn babies. The study included over 27,000 mothers of infants who had taken an SSRI starting one month prior to pregnancy, and through the third month of pregnancy. Women who took Paxil were 2.5 to 3.5 times more likely to have a newborn with a heart or neurological defect. Those women taking Prozac were 1.9 to 2.0 times more likely to have a newborn with a heart or neurological defect.
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 approved by FDA for schizophrenia and for psychosis from the manic stage 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, but that also makes them dangerous for patients to drive or use machinery. Since insomnia and anxiety are symptoms of depression, these drugs may be beneficial for those symptoms, but not necessarily for improving patients’ depressed mood. 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 antidepressants have other risks. Cymbalta (duloxetine) 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, in addition to the above mentioned increase in suicide, is more likely to increase blood pressure, heart rate, and cause nausea, and in one study was linked to gastrointestinal bleeding.[11,12]
A study that included over 370,000 women reported that non-depressed women taking SSRIs are more than 50% more likely to have a bone fracture than non-depressed women who are not taking them. Another study published in 2012 that included results from thirteen other studies, reported that men and women who take SSRIs are 1.7 times more likely to develop a bone fracture.
In addition, it is not safe to combine most antidepressants 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.
So, although antidepressants may improve your mood, do not forget that taking them means subjecting yourself to many potential side effects, including some serious risks.
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.
All articles are reviewed and approved by Dr. Diana Zuckerman and other senior staff.
- 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.
- UNITED STATES ex rel. GREG THORPE, ET AL. (Consolidated) Plaintiffs, v. GLAXOSMITHKLINE PLC, and GLAXOSMITHKLINE LLC, Defendants.
- Molero Y, Lichtenstein P, et al. Selective Serotonin Reuptake Inhibitors and Violent Crime: A Cohort Study. PLoS Med 12(9): e1001875. doi:10.1371/ journal.pmed.1001875.
- Schneeweiss S, Patrick AR, Solomon DH, Mehta J, Dormuth C, Miller M, et al (2010). Variation in the Risk of Suicide Attempts and Completed Suicides by Antidepressant Agent in Adults: A Propensity Score-Adjusted Analysis of 9 Years’ Data. Achieves of General Psychiatry 67(5): 497-506.
- Coupland C, Dhiman P, et al. Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ. 2011 Aug 2;343:d4551. doi: 10.1136/bmj.d4551.
- Coupland C, Hill T, et al. Antidepressant use and risk of suicide and attempted suicide or self harm in people aged 20 to 64: cohort study using a primary care database. BMJ. 2015 Feb 18;350:h517. doi: 10.1136/bmj.h517.
- Binder, EB; Owens, MJ; Liu, W; Deveau, TC; Rush, AJ; Trivedi, MH; Fava, M; et. al.; Association of polymorphisms in genes regulating the corticotrophin-releasing factor system with antidepressant treatment response; Archives of General Psychiatry, 2010, 67 (4) pp. 369-79.
- Tsai, MH; Lin, KM; Hsiao, MC; Shen, WW; Lu, ML; Tang, HS; Fang, CK; et.al (2010). Genetic polymorphisms of cytochrome P450 enzymes influence metabolism of the antidepressant escitalopram and treatment response; Pharmacogenomics, 11(4) pp. 537-46.
- Furu K, Kieler H, et al. Selective serotonin reuptake inhibitors and venlafaxine in early pregnancy and risk of birth defects: population based cohort study and sibling design. BMJ. 2015 Apr 17;350:h1798. doi: 10.1136/bmj.h1798.
- Reefhuis Jennita, Devine Owen, Friedman Jan M, Louik Carol, Honein Margaret A. Specific SSRIs and birth defects: bayesian analysis to interpret new data in the context of previous reports (2015) British Medical Journal. 351:h3190.
- Abajo FJ & Garcia-Rodrigues LA (2008). Risk of Upper Gastrointestinal Tract Bleeding Associated with Selection Serotonin Reuptake Inhibitors and Venlafaxine Therapy. Archives of General Psychiatry, 65(7): 795-803.
- Agency for Healthcare Research and Quality; Comparitive Effectiveness of Second-Generation Antidepressants in the Pharmacologid Treatment of Adult Depression: Executive Summary; 2007 Retrieved from www.ahrq.org on August 25, 2010.
- Sheu Y, Lanteigne A, Stürmer T, Pate V, Azrael D, Miller M. (2015) SSRI use and risk of fractures among perimenopausal women without mental disorders. Injury Prevention.
- Wu Q, Bencaz AF, Hentz JG, Crowell MD. Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies. Journal of Bone and Mineral Research, 27:1186-1195.
- 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.