Depression is common with conditions like epilepsy, stroke, and Parkinson's disease. Learn how to identify and deal with this mood disorder.

Andrea Paez was a healthy, vibrant 24-year-old when she had a stroke after returning from a vacation in Ecuador. Lying in a hospital bed surrounded by tubes, her left side paralyzed, she sank into a deep depression. "Every morning I woke up stunned by my new reality," she recalls. "Two weeks earlier, I'd been running and swimming in South America. Then suddenly I found myself bedridden with a feeding tube, incapable of eating or dressing myself. I thought, 'Is this what the rest of my life is going to be like?'"

Paez's despair is familiar to many stroke survivors. The rate of depression among stroke patients is about eight times higher than in the general population, according to a 2016 study in JAMA Psychiatry. Of the 135,000-plus patients in the study, 25 percent were diagnosed with depression within two years of their stroke. In that group, more than half developed depression within the first three months after their stroke.

Illustration by Gracia Lam

This correlation extends to other neurologic disorders, including epilepsy and Parkinson's disease. In a small 2017 study published in the Journal of Neurosciences in Rural Practice, 63 percent of adult patients with epilepsy exhibited depressive symptoms. The researchers also noted that seizure type and frequency were predictive of depression. "We don't completely understand the connection, but it appears that with each of these diseases, some of the brain circuits and neurotransmitters involved are also involved with depression," explains Scott E. Hirsch, MD, clinical associate professor of neurology at NYU Langone Medical Center.

"Neurologists are often focused on the neurologic condition itself, so they [may] either miss or dismiss depressive symptoms," says Andres M. Kanner, MD, FAAN, director of the Comprehensive Epilepsy Center at the University of Miami Miller School of Medicine. "But depression involves neurobiologic changes of the brain too."

Depression related to epilepsy, Parkinson's, or stroke seems to have a biological basis. "The relationship between epilepsy and depression goes both ways: People with epilepsy have a higher risk of depression, but people with depression also have a two-fold higher risk of developing epilepsy compared to the general population," says Dr. Kanner. "We think this is because the changes in neurotransmitters that occur during epilepsy are very similar to the changes we see in depression." Both involve increases in glutamate, a neurotransmitter crucial for learning and memory, as well as decreases in the neurotransmitter GABA, which slows brain activity, he says.

Brain biology changes in depression and epilepsy have other similarities. "People with depression produce more stress hormones such as cortisol, which we also see in epilepsy," Dr. Kanner says. Those with epilepsy are also more likely to experience suicidal thoughts and behaviors and are more than twice as likely to die by suicide as people without the condition, according to a 2018 study in JAMA Neurology.

In addition, certain medications used to treat epilepsy can trigger depression. When Brooke Gordon, 59, was diagnosed with epilepsy 40 years ago, her doctor prescribed phenobarbital. Within a couple of months, she began experiencing bouts of depression that continued for years. After a failed suicide attempt at age 26, Gordon landed in a hospital psychiatric ward. It wasn't until four years later, at age 30, that she went to a new epilepsy specialist who switched her to valproic acid (Depakote). Within weeks, both her seizures and depressive symptoms disappeared.

"That makes total sense, as phenobarbital can cause depression in some patients, particularly if you have a genetic predisposition to depression," says Dr. Kanner. "And valproic acid has mood-stabilizing properties." While patients shouldn't shy away from phenobarbital if their doctor recommends it, he adds, they should alert their doctor if they feel any mood changes.

The link between depression and Parkinson's disease appears to be low levels of the neurotransmitter dopamine, says Nikolaus McFarland, MD, PhD, FAAN, acting chief of the movement disorders division at the University of Florida in Gainesville. Dopamine is crucial not only for motor control but for mood, sleep, memory, learning, and concentration, he says.

Depressive symptoms may begin before the advent of Parkinson's motor symptoms. A review published in Neurology in 2015 found that people are three times more likely to be diagnosed with Parkinson's within a year of being diagnosed with depression than those who aren't depressed. "This is probably due to the decrease of dopamine within the brain as Parkinson's disease begins," says Dr. McFarland.

While the risk of poststroke depression is highest the first year, "we also know that about 55 percent of people who've had a stroke will develop depression at some point," says Nada El Husseini, MD, associate professor of neurology at Duke University Medical Center in Durham, NC. "A stroke often damages the amygdala, a part of the brain involved in regulating emotions. It also reduces levels of brain-derived neurotrophic factor (BDNF), a protein that affects mood, and raises levels of the stress hormone cortisol." All of this combines to create a potentially persistent, disabling depression. And depression is associated with poorer recovery after stroke and a higher risk of dying, says Sarah Song, MD, FAAN, assistant professor of neurology at Rush University in Chicago and a stroke specialist.

Psychological factors also can make a person with a neurologic condition more susceptible to depression. "Many of these people have lost their sense of self," says Dr. Hirsch. "They can't do the activities they used to, and they feel worthless. Then, as a coping mechanism, they isolate themselves from others, and it becomes a vicious cycle." The effects seem most pronounced in younger patients, who may not have expected to be diagnosed with a debilitating illness and are also processing grief and shock, says Dr. El Husseini.

Since patients with neurologic conditions may be at increased risk of suicide, their families and physicians—and the patients themselves—need to be aware of warning signs, says Dr. Hirsch. These include talking about death or suicide, exhibiting behavior that might lead to self-harm (for example, purchasing a gun), and talking about feeling hopeless or having no desire to live. If family members or friends notice any of these signs, they should seek help for the person immediately, by calling the National Suicide Prevention Lifeline anytime at 800-273-8255 or by taking them to a psychiatrist or a walk-in psychiatric clinic. (Read more about How to Reduce the Risk of Suicide in People with Neurologic Conditions.)

Despite how common depression is, it often goes undiagnosed. "Not all doctors do a careful assessment or feel comfortable treating related depression or anxiety disorders," says Dr. Kanner.

Screenings are available, though. For example, the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), developed 15 years ago by Dr. Kanner, is a six-item questionnaire that asks patients how often they experience feelings such as guilt, frustration, and difficulty finding pleasure. The patient rates each on a scale of one (never) to four (always or often), and a score of 15 or higher is a red flag for depression, explains Dr. Kanner. One of the first studies to look at the questionnaire, published in 2009 in the journal Seizure, found that it increased detection rates dramatically.

For Parkinson's patients, the most widely used assessment is the Unified Parkinson Disease Rating Scale, says Dr. McFarland. But it devotes only a single question to depression, so Dr. McFarland also uses the Beck Depression Inventory. This 21-question survey asks patients to rate everything from mood and sleep quality to sex drive and energy levels.

While several different scales seem to be effective in detecting depression among stroke survivors, a 2017 scientific statement by the American Heart Association says the Patient Health Questionnaire-9 is among the most practical.

For stroke patient Andrea Paez, it took an intense counseling program while she was in the hospital, followed by years of outpatient therapy and stroke support groups, to get her depression under control. "Doctors have explained to me that my stroke triggered a chemical imbalance in my brain, which led to dark, depressive thoughts," she says. She also credits physical exercise with helping her recover. "When I was at my lowest point, those first few months after my stroke, I made sure I got to the gym every day, even if I couldn't do much," she says. "I found that the more activity I did, the better I felt."

Now 36, Paez is a personal trainer and mom to two sons, Daniel, 10, and Diego, 8. She's almost fully recovered from her stroke, except for a lack of sensation on her left side. She found out later that her stroke was caused by immune thrombocytopenia, or low platelet count, which is controlled by medication.

"I still battle depression at times, but I've learned to get it under control with exercise, volunteering, and spending time with my family," she says. "I'm not just a stroke survivor. I'm a depression survivor, too."

Four Tips for Dealing with Depression

If you experience symptoms of depression, the first step is to notify your neurologist. Then talk to him or her about these treatment options.

Antidepressants. "Research shows that the best treatment is a combination of antidepressant medication and some form of talk therapy," says Scott E. Hirsch, MD, clinical associate professor of neurology at NYU Langone Medical Center. The most common antidepressants for patients with neurologic diseases are selective serotonin reuptake inhibitors (SSRIs); they're considered first-line treatment for depression in patients with Parkinson's, for example, along with cognitive behavioral therapy (CBT), according to a 2017 review in Movement Disorders. Although antidepressants may have warnings that they can worsen or increase seizures, they are generally considered safe for people with epilepsy, says Andres M. Kanner, MD, FAAN, director of the Comprehensive Epilepsy Center at the University of Miami Miller School of Medicine. Talk therapy. Many types of therapy can help, but CBT, where you work with a therapist to identify and reshape thoughts and behavior patterns that contribute to your depression, is one of the most effective, says Dr. Kanner. "It teaches you strategies to cope with situations that can be overwhelming," he explains. Most people require a weekly session for 12 to 16 weeks, and it's often covered by insurance. Mind-body practices. Activities like yoga and tai chi can help relieve depression and anxiety. According to a study of patients with Parkinson's disease published online in JAMA Neurology in April 2019, those who did eight weekly 90-minute sessions of mindfulness yoga—yoga that includes meditation and controlled breathing—had significantly reduced depression and anxiety compared with those who focused on stretching and resistance training. Exercise. "We know physical activity increases levels of serotonin and dopamine, releases endorphins, and lowers stress, which can boost mood," says Nikolaus McFarland, MD, PhD, FAAN, acting chief of the movement disorders division at the University of Florida in Gainesville. One 2017 review published in the journal PLOS One found that Parkinson's patients who engaged in aerobic activity reported more improvement in their Parkinson's symptoms, fewer depressive symptoms, and overall better quality of life than those who were sedentary. Aerobic exercise or strength training for 45 to 60 minutes three to five times a week is recommended.

Therapies for Persistent Depression

Most patients respond well to a combination of antidepressants and talk therapy, but sometimes depression can linger, says Andres M. Kanner, MD, FAAN, director of the Comprehensive Epilepsy Center at the University of Miami Miller School of Medicine. "In general, once your neurologist has diagnosed depression, he or she may refer you to a psychiatrist," he says. A psychiatrist will prescribe different medications, or different combinations, to see what works. If none are effective, talk to your doctor about these alternatives:

Deep brain stimulation. In DBS, electrodes are implanted in the brain to produce electrical impulses. It is approved to treat epilepsy and Parkinson's, and is considered experimental for depression. For patients with epilepsy or Parkinson's who also have resistant depression, it may be good because it addresses both the neurologic disorder and the depression, says Dr. Kanner.

Transcranial magnetic stimulation. Less invasive than DBS, this treatment involves a device pressed against your scalp to pass magnetic waves into your brain. Most people require sessions five times a week for four to six weeks. While it's less risky for persistent depression than other procedures, such as electroconvulsive therapy (ECT), no evidence says it's any more effective than medication, says Scott E. Hirsch, MD, clinical associate professor of neurology at NYU Langone Medical Center.

Electroconvulsive therapy (ECT). An electric current is sent through your brain while you're under general anesthesia, triggering a seizure that releases a surge of neurotransmitters, which can help resolve severe depression, says Dr. Hirsch. Most people need six to 12 treatments, and it's usually regarded as a last resort.