Headaches, nausea, feeling on edge, being exhausted and a low sex drive. The irony of antidepressants is that in some cases, side effects can cause symptoms similar to the depression they are supposed to treat. In fact, those side effects are a key reason that people stop taking the drugs.
There are many ways to cope with depression — therapy, exercise, nutrition and more — but some people will find they need the boost of an antidepressant. Be warned, however, that finding the right antidepressant medicine may take some time. It usually takes weeks for a therapeutic effect and sometimes the first antidepressant an individual is prescribed doesn’t work. And when you are ready to stop taking an antidepressant, you’ll have to be weaned off it because they cause dependence.
An estimated 7.1% of adults in the United States — about 17.3 million people — experience at least one episode of major depression each year, and approximately 12.7% of Americans aged 12 and older take a prescribed antidepressant medication. Many patients who take these drugs, however, experience adverse side effects that may influence whether or not they continue taking them. In fact, negative side effects are an important reason that people stop taking antidepressants.
“Side effects for antidepressant medications are not unusual,” said Keith Humphreys, MD, a professor of psychiatry and behavioral sciences at Stanford School of Medicine in California. “Common side effects include getting headaches, feeling nauseous or even throwing up, feeling edgy or agitated, feeling excessively sleepy or low on energy, and experiencing reduced sexual desire or satisfaction.”
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Eskatimine – Spravato
The approval of Spravato, a nasal spray, in March 2019 is controversial as the drug is considered a chemical cousin of ketamine, an anesthetic that some abuse as a party drug due to its hallucinogenic effects. The prescribing label for Spravato contains a “black box warning” about the possibility of abuse and misuse while taking the drug.
There is also a question of how effective the drug is considering that in some late-stage trials, the drug was not better than a placebo in reducing depressive symptoms. Worse, six people died in the esketamine clinical trial program, of which three were suicides. In the matching group that received placebos, there were no deaths.
From MedPage: “This is a drug that will be expensive, has a high potential for abuse, and has a problematic safety profile, if anyone has doubts about that,” Cristea said. “This is compensated by very modest benefits.”
Ketamine has been used off-label for years to treat depression and anxiety in infusion centers. Many who have used ketamine in this setting say the antidepressant effects appear within hours, as opposed to weeks with conventional antidepressants.
Spravato may find a large market considering that about one-third of people in the US with major depressive disorder have a treatment-resistant depression, a kind of depression in which an individual’s symptoms are not alleviate despite trying several antidepressants. Most of the antidepressants available now are selective serotonin reuptake inhibitors (SSRIs).
Spravato is indicated for patients who have tried and failed on at least two prior antidepressants. While taking the drug, patients will also need to take an oral antidepressant. Because of the risk of dissociation (hallucinations) and sedation, Spravato will not be available at pharmacies for patients to use at home. Instead, they will have to go to certified treatment centers where a health care professional will observe them for at least two hours after administration.
SSRIs and SNRIs
Antidepressants are serious medicines that can significantly improve some people’s lives. However, the newer types such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-epinephrine reuptake inhibitors (SNRIs) have also been linked with problems. Research shows that more than half of all people who take antidepressants experience bothersome side effects.
Sexual Side Effects
The sexual side effects are a top concern for both men and women taking antidepressants. In addition to issues with sexual interest and arousal, SSRIs can impede erection or ejaculation in men, and they may interfere with lubrication, genital blood flow or orgasm in women. {Find more information about the side effects of SSRIs, SSNIs, benzodiazapines and triciclic antidepressants in Anxiety Meds: Options, Side Effects & Alternatives}
According to the results of a large survey conducted by Consumer Reports published in 2010, between 23 and 36% of people taking antidepressants reported having had related sexual problems, and some research findings suggest that rates of such side effects could actually be as high as 80%.
Hip Fracture
Recent research has uncovered a number of lesser-known but significant side effects associated with antidepressants. A study in Sweden suggests that older people who start on antidepressant medications are more than twice as likely to experience a hip fracture compared to peers who don’t use the drugs.
Researchers in Sweden looked at a registry of 408,000 patients aged 65 and older, with an average age of 80. Half were prescribed an antidepressant and the other half were not. The patients were followed for two years. The medical records of those who received an antidepressant were examined for one year before and after filling their prescriptions.
Results, entitled Association Between Antidepressant Drug Use and Hip Fracture in Older People Before and After Treatment Initiation and published in JAMA Psychiatry, found that antidepressant users were more than twice as likely as nonusers to have suffered a hip fracture both before and after starting therapy. In the year before starting therapy, 2.8% in the antidepressant group experienced a hip fracture compared to 1.1% in the comparator group. And up to a year after starting on an antidepressant, 3.5% in that group had a hip fracture compared to 1.3% in the other group. Interestingly, the highest odds of experiencing a hip fracture were 16 to 30 days before treatment with an antidepressant.
The researchers, Jon Brännström, MD, Hugo Lövheim, MD, PhD, Yngve Gustafson, MD, PhD, Peter Nordström MD, PhD, note that the Beers Criteria — a list of medications that may not be suitable for seniors because their risks can potentially outweigh their benefits — says that antidepressants should be avoided in people with a history of falls unless other alternatives are unavailable.
“Even if antidepressant drug use does not increase the risk of hip fracture, the prescription of antidepressants to older people should be restrictive, as the evidence for positive effects is limited,” the study’s authors write. “Antidepressants are associated with adverse effects other than falls and fractures, including QT interval prolongation [irregular heartbeat], hyponatremia [low sodium levels in the blood], and gastrointestinal bleeding.”
COPD Interaction
Also a concern for older people, certain antidepressants may increase the risk of death in those with COPD (chronic obstructive pulmonary disease). Researchers analyzed 28,360 new users of serotonergic antidepressants — such as SSRIs and SNRIs — that had COPD and were aged 66 and older, then matched them to 28,360 non-users. The results, published in the European Respiratory Journal, indicated that new users of these antidepressants have a 20% increased risk of death related to respiratory issues, as well as death overall compared to non-users of the medication.
Also, antidepressant use among those with COPD – a progressive lung disease characterized by breathlessness – was associated with a 15% increased risk of hospitalization and emergency room visits due to related symptoms. The results demonstrate a strong association, but not a definite cause and effect, the researchers caution.
According to lead author Nicholas Vozoris, MD, a respirologist at St. Michael’s Hospital in Toronto, the findings were not surprising because “there are biological reasons why antidepressants could lead to respiratory issues. “These drugs can cause sleepiness, vomiting and can negatively impact immune system cells. This increases the likelihood of infections, breathing issues, and other respiratory adverse events, especially in patients with COPD.”
Researchers noted that the findings shouldn’t alarm COPD patients who are currently using antidepressants, but rather increase awareness among users and prescribers.
Weight Gain
Weight gain is another potential problem for some people taking antidepressants. In a study published in The BMJ, people taking antidepressants were far more likely to gain weight than those who didn’t take them. Researchers identified and analyzed nearly 295,000 people aged 20 years or older from the UK’s Clinical Practice Research Datalink, which is a large collection of electronic health records. The participants were of all different weights and had 3 or more BMI measurements. From 2004 to 2014, researchers monitored the patients’ health records in order to track and assess their antidepressant use and weight gain over time. Other factors that could affect weight gain, such as age, diseases and smoking status, were also monitored and taken into account.
The results indicated that patients who used common antidepressants were 21% more likely to have a 5% increase in weight over the next 10 years compared to those not taking the drugs. The greatest weight gain occurred in the second and third years of treatment and “remained elevated” for at least 6 years after the treatment was administered.
Also, certain antidepressants fueled weight gain more than others. For instance, people taking mirtazapine (Remeron) — which is rarely prescribed — had a 50% higher risk of gaining 5% more weight, while those taking citalopram (also known as Celexa) had around a 26% higher risk of gaining excess weight. The researchers also noted that “participants of normal weight showed an increased risk of transitioning to overweight or obesity, and overweight participants were more likely to become obese if they were treated with an antidepressant.”
Trial and Error
“The side effects vary across the different types of antidepressants, and the precise mechanisms are not always understood, but in general, antidepressant medications alter the levels of chemicals in the brain that regulate many different functions,” explained Humphreys. “When they are effective, the result is reduced depressive symptoms and greater quality of life, but because medicine can’t perfectly adjust such a complex organ as the brain, unwanted effects also often occur.”
In addition, though the reasons are unclear, some individuals have a better response to some antidepressants over others, and one drug may work well for one person and poorly for another. Settling on the right one can sometimes take a bit of trial and error.
Your doctor should initially start you on the lowest effective dose of medication and then keep tabs on your response. Keep in mind that it can take up to six weeks before you notice any change as a result of the medication, and it is important to stay on it for about that long — unless you have severe side effects — in order to give it a chance to take effect.
Still, researchers have found that 30 to 50% of people do not improve with the first medication prescribed. So if the first antidepressant doesn’t work, or causes unacceptable side effects, your doctor may need to increase the dosage or switch the medication to another one. Note that means it could be months before you find an antidepressant that works for you. During this time period, you’ll need to take other steps to cope with your depression. Your doctor might suggest cognitive behavioral therapy (it’s the industry standard to partner antidepressants with therapy in any case).
St John’s Wort
Certain supplements (check with your doctor first) are among other non-drug treatments that have also been found beneficial in some people with depression. St. John’s wort, an herbal remedy readily available as a dietary supplement, may treat depression as effectively and with fewer side effects as SSRIs, see ‘It’s a Gamble:’ St. John’s Wort, Depression and Drug Interactions
Researchers in China conducted a meta-analysis — a study of prior studies — of studies conducted between 1966 and April 2015 comparing the efficacy and/or safety of St. John’s wort with SSRIs. A total of 27 such studies accounting for 3,127 people with depression were identified.
Overall, St. John’s wort was found to do as well as SSRIs in terms of reduction in depression symptoms, clinical response and remission of depression. However, St. John’s wort was associated with far fewer adverse events, the researchers wrote in the journal Neuropsychiatric Disease and Treatment.
Also, far fewer patients who were taking St. John’s wort withdrew from trials due to adverse events compared to those on SSRIs. The herbal supplement also had better safety in patients with depression compared to those on an antidepressant.
Many people find acupuncture, exercise and change of diet to be helpful. In fact many researchers suggest trying these alternatives before starting on antidepressants. (See Are Antidepressants Any Better Than a Placebo?)
If you do experience bothersome side effects, other options should generally be considered if they do not fade after weeks or months, advises Humphreys. He points out that many side effects are often temporary, and those that linger should be checked out.
“The best advice is to talk to the prescribing doctor about alternative antidepressant medications,” he said. “Many patients who have unpleasant side effects with one medication will have a better experience on a different medication.” You may ultimately decide that the benefits of a particular medication outweigh any negative effects it may cause.
Know What to Expect
When people experience side effects — or in some cases, when they start feeling better — they may decide to suddenly quit taking their antidepressant. But don’t do it. You should not stop taking the medication without the guidance of your healthcare provider, who will help you taper off of it at a safe pace that will allow your body adequate time to adjust. (See The Right Way to Get Off Antidepressants)
“People don’t get addicted (or “hooked”) on these medications, but stopping them abruptly may also cause withdrawal symptoms,” according to the National Institute of Mental Health. Suddenly quitting these meds may also increase your risk of depression relapse.
Certain symptoms, however, could signal an emergency and require immediate action. You should call your doctor right away if any of the following occur while you are taking antidepressants, particularly if the symptoms are new, getting worse or causing you significant worry:
- Suicidal thoughts or attempts
- New or worsening depression or anxiety
- Feeling very agitated, irritable or restless – symptoms of akathisia
- Panic attacks
- Sleep problems such as insomnia
- Acting aggressively, dangerously, impulsively and/or violently
- A significant increase in activity and talking – symptoms of mania
- Other unusual behavior or mood changes
According to researchers at Boston University and Massachusetts General Hospital/Harvard Medical School in Massachusetts, the “successful management of side effects begins with adequate communication and patient education prior to and throughout treatment with antidepressants.” Physicians should also help you sort out whether symptoms are truly side effects of treatment or symptoms of depression or other medical problems. Diminished sex drive, for instance, can be caused by antidepressant medication, but it can also be a symptom of the depression itself.
Older Antidepressants
The older types of these medications, including tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), are typically associated with more severe side effects. As a result, they are not prescribed as much anymore. Some examples of the TCAs include amitriptyline, amoxapine, desipramine and doxepin, while some of the MAOIs are isocarboxazid, phenelzine, selegiline and tranylcypromine.
Conclusion
Ideally, your doctor will disucss with you a wide range of options such as changes in the dosage or timing of medication, behavioral approaches, possibly a different medication altogether or additional pharmacological strategies. “Sound and resourceful management of side effects is an important component in achieving depressive remission and enhancing patient safety and quality of life,” the Boston researchers concluded.
