Why Your Antidepressants Stopped Working -- and What to Do About It
Some refer to it by its medical term, tachyphylaxis. Others informally call it the "Prozac poop-out." But many patients with mental health conditions simply know it as the scary period when their antidepressants -- which once successfully quelled their anxiety and sadness -- suddenly stop working.
There are many antidepressants on the market, and when prescribed and taken correctly, they can often treat the symptoms of chronic mental illnesses. But just because you've found a medication that works for you doesn't mean that'll always be the case. Studies show that most patients with depression eventually relapse and become depressed again -- even if they're still on the antidepressants that helped them recover in the first place.
Experts say they have theories -- but no definite evidence -- as to why tachyphylaxis occurs. "One of the problems with psychiatry and mood disorders, in particular, is that we don't know what the broken part [in the brain] is," says Dr. Jennifer Payne, director of the Women's Mood Disorders Center at The Johns Hopkins Medicine in Baltimore. "We have a vague understanding of how antidepressants work, but that doesn't mean we totally understand the pharmacology. I don't think anyone can offer a complete biological explanation for why antidepressants stop working. But I will say this: There are [factors] that can influence someone to relapse."
Here are possible reasons your antidepressants aren't working as well as they once did -- and some steps you and your doctor can take to help you feel better.
Noncompliance. It's a common situation: An individual has been taking antidepressants a while and no longer feels depressed. So he or she starts skipping or missing doses, or taking his or her medication at irregular intervals. This can cause depressive symptoms to return, Payne says.
Substance abuse. "More than 50 percent of people with mood disorders have alcoholism or alcohol abuse problems, and many also have substance problems," says Dr. Maria A. Oquendo, a professor of psychiatry at New York-Presbyterian University Hospital of Columbia and Cornell. "Alcohol and other substances wreak havoc on the brain, and also make it hard to respond to medications."
Other medical conditions. "There are a number of other medical conditions that can make it very difficult to respond to medications -- for instance, thyroid disease," Oquendo says. Patients with conditions such as Alzheimer's disease, Parkinson's disease, pancreatic cancer, hepatitis C and multiple sclerosis are also often depressed and may not respond as well to treatment.
Undiagnosed bipolar disorder. Patients with bipolar disorder often report depressive symptoms to their doctors -- but neglect to mention their episodes of hypomania, which they mistake for an elevated mood or irritability. In turn, their physician diagnoses them with clinical depression and prescribes an antidepressant -- not realizing the patient needs a mood stabilizer.
The patient will take the antidepressant for a while; it might initially treat some symptoms, but it could also induce mania and make things worse. In this case, he or she should visit a doctor and receive a thorough clinical evaluation of his or her symptoms, Oquendo says -- or get a second opinion from another physician. If the patient does end up having bipolar disorder, she says, the correct medication can be "life changing."
Stress. Stress can cause breakthrough symptoms of depression to appear -- even if you're on an antidepressant that's been working for you, says Dr. Maurizio Fava, executive vice chair of the Massachusetts General Hospital Department of Psychiatry.
Aging. When you age, your metabolism changes, affecting how you absorb drugs. You might also start taking other medications that interfere with the absorption process -- say, a medication that reduces the acid in your stomach. These might be reasons why your antidepressant has waned in effectiveness over the years, Payne says.
Plus, as you get older, you're more likely to be diagnosed with diseases like cerebrovascular disease, a group of conditions that affect the circulation of blood to the brain. Cerebrovascular disease is a risk factor for depression, Payne notes. "So if you have a history of depression, you've been stable on an antidepressant and you develop cerebrovascular disease, you can have a relapse," she says.
Lowering your dose. Sometimes patients ask their doctor to reduce their antidepressant dosage after they achieve remission from their depressive symptoms. But studies indicate that patients who lower their dosage experience a higher rate of relapse, Fava says.
Past depressive episodes. Even patients who regularly take their antidepressants and check in with their doctors aren't immune to tachyphylaxis. Studies suggest those who stay well the longest continue taking the dosage of the medicine that initially helped improve their symptoms. But research also indicates that if someone's had two or more depressive episodes in the past, they are more likely to have a future relapse, Fava says.
"In general, major depression seems to be a recurrent illness,'' Payne adds. "I think of it like a chronic illness that needs to be managed, kind of like diabetes needs to be managed." She recommends that someone who's had two or more depressive episodes stay on an antidepressant the remainder of his or her life -- although the jury is still out, research-wise, whether antidepressants can serve as a prophylactic for future relapses. In this case, it's important to work with your doctor to find a medication with minimal side effects that you feel comfortable taking for an extended period of time.
Degree of resistance to treatment. "The largest study ever done on depression showed that your odds of relapse on an antidepressant decreased based on how many trials it took you to respond," Fava says. "So if you responded to the first antidepressant you tried, you were more likely to stay well on antidepressants [over time] than if you failed with two tries but finally responded to the third one."
Another factor, he says, is how well the antidepressants treated your symptoms. The more incomplete your response to the medication, the more likely it is you'll relapse in the future.
If your antidepressant is no longer working for you, don't give up. There are options to explore with your doctor.
The most important thing to do is see a psychiatrist who specializes in treating mood disorders, if you aren't already. (Many people are prescribed antidepressants by a primary care physician instead of a licensed mental health professional.) Getting well again might be as simple as bumping up your medication dosage. Or if you've only had a partial loss of response to your antidepressants, your doctor might augment them with another medication. It could take a while to feel a difference -- experts say it takes anywhere from four to 12 weeks for antidepressants to start working -- but some patients see a small improvement early in treatment.
If you're still not feeling better after four to six weeks, you and your doctor should consider a different strategy, like changing medications, Payne says. Physicians used to recommend trying a medication in a different class of antidepressants -- say switching to a selective serotonin norepinephrine inhibitor, or SNRI, if you weren't having luck with a selective serotonin reuptake inhibitor, or SSRI. But recent studies suggest switching to another antidepressant in the same class of antidepressants might also work, Payne says.
Sometimes, non-pharmaceutical treatments like psychotherapy -- or light therapy, if there's a seasonal component to your depression -- can also augment your medication's benefits. And don't dismiss the importance of exercise, Oquendo says.
"Exercise is very helpful for depression and anxiety," she says. "We know from animal studies that it does lead to neurogenesis, or the development of new neurons in the hippocampus -- a particular part of the brain we know is affected in individuals with depression."
Even if you're still feeling fine on your medication, take steps now to prolong your wellness, Oquendo says. "If you're being treated for depression, it's very important to be monitored regularly," she says. "I tell patients to be monitored every two to three months, even if they think they're doing really well. It's a good investment, because often, depression tends to creep up on people."
