What is treatment-resistant depression?
Experts do not agree on one definition. But in general, this is a type of depression that does not get better even after trying two antidepressants from different types of drugs. „If a third dose is needed, that's the standard threshold,“ Crystal said.
For example, if a person is initially treated with a selective serotonin reuptake inhibitor (SSRI) such as fluoxetine and doesn't respond, doctors may diagnose treatment-resistant depression, he says. The patient is then treated with serotonin and norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine and duloxetine, which also do not respond.
„Drugs act as a kind of filter,“ Crystal says. „If you respond to that, by definition you don't have treatment-resistant depression.“
How to get diagnosed
Crystal says it takes two rounds of antidepressant treatment before a diagnosis of treatment-resistant depression can be made. This usually means it takes him 6 to 8 weeks for each antidepressant to take effect. Also, if the first dose of an antidepressant is not effective, your doctor may increase the amount of the drug you take before switching to another drug.
Crystal Clark, MD, associate professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine, says it's important to maximize the dose of each antidepressant.
„Sometimes you'll have people who have tried several (antidepressants) and they don't work, but they've only tried half their potential dose. That may not necessarily be a failed trial. ”
Doctors may also look for hidden causes that explain why drug treatments don't work. Crystal said there are „a mix of reasons“ why people don't respond to antidepressants, including:
- I don't take medicine every day.
- Your body does not absorb the drug.
- If you have another health condition, such as an underactive thyroid.
External issues can also have an impact. „Some people don't respond[to antidepressants]because they have so much going on in their lives that they experience stress and confusion, which masks or prevents resolution of their depression.“ Crystal says.
What causes treatment-resistant depression?
Clark said there are several theories about genetic and brain differences, but there are no biomarkers or other mechanisms that can identify people who develop treatment-resistant depression. „There's no clear answer to that question.“
Crystal says there are „different demographics“ of people who don't respond to antidepressants. Researchers are trying to figure out the biology behind why. This could lead to more personalized treatments in the future. „That strategy is called precision medicine,“ he says.
Experts are specifically studying how this targeted approach can help certain groups, such as people with treatment-resistant depression and inflammation. Crystal said this includes people with conditions such as arthritis, asthma, heart disease and inflammatory bowel disease, as well as people who are overweight or obese.
In general, if inflammation is ongoing, the chances of depression are higher. And Crystal says there is some evidence that the level of inflammation can predict whether a person will respond to antidepressants. He says there is promising evidence that immunosuppressive drugs that block signals from pro-inflammatory cytokines may help reduce symptoms in certain people with treatment-resistant depression.
symptoms
There is no specific set of symptoms that distinguish treatment-resistant depression from other forms of depression. Experts agree that it would be much easier. But if you wake up every morning thinking, „I don't know how I'm going to get through the day,'' Crystal says antidepressants are definitely not going to help.
If you don't have joy, joy, or excitement in your life, Crystal says, „it's a good time to start talking to a therapist, counselor, or doctor about what's going on.“
Other questions to ask to determine whether antidepressants are effective include:
- To what extent have you returned to your old self?
- Are you sleeping too much or too little?
- Do certain parts of your life not feel right?
- Has your appetite returned to normal?
How to manage treatment-resistant depression
Antidepressants alone may not be very effective. Seek help from your doctor who will give you more options. „I encourage people to see a psychiatrist who is comfortable looking at all areas,“ Clark says. “Someone who has knowledge about more advanced and new treatments, not just oral treatments.”
Treatment options for treatment-resistant depression include:
Auxiliary medicine. Your doctor may also add other medications to your antidepressant. Although it varies from person to person, common choices include antipsychotics, mood stabilizers, anti-anxiety medications, thyroid hormones, or other medications. Your doctor may also suggest pharmacogenetic testing to look for certain genes that indicate how well you handle certain antidepressants.
Talk therapy. There is evidence that psychotherapy can reduce depression in some people who do not respond well to antidepressants. „But often, when we talk about treatment-resistant depression and think about interventions, that doesn't necessarily include cognitive behavioral therapy, family therapy, or supervised occupational therapy,“ Crystal says. These treatments are helpful in the following cases:
- Cognitive Behavioral Therapy: Focuses on thoughts, emotions, and behaviors that affect mood. CBT helps you become aware of your negative thoughts and work on changing them to more positive ones.
- Dialectical behavior therapy: Helps develop problem-solving and acceptance skills. This is especially helpful for people who self-harm or have recurrent suicidal thoughts.
- Behavioral Activation: Slowly reduces avoidance and feelings of isolation, allowing people to participate in things they once enjoyed and activities that make them feel good.
- Group therapy: Other people suffering from depression participate in collaboration with a therapist.
- Family or couples therapy: Works to reduce stress in your relationships with your family, spouse, or partner. This often helps improve depression.
Ketamine. Your doctor may recommend this medication to quickly relieve treatment-resistant depression. It is administered in low doses through an intravenous drip. The FDA has approved a nasal spray called esketamine (Spravato). Doctors usually recommend using oral antidepressants with esketamine or ketamine.
Brain stimulation. Your doctor may recommend this method if nothing else works or if your symptoms are very severe. These steps include:
- Repetitive transcranial magnetic stimulation (rTMS): Magnetic fields are used to stimulate nerve cells in areas of the brain associated with mood and depression.
- Electroconvulsive therapy (ECT): A small amount of electricity is passed to your brain while you sleep. This triggers short bouts that can change brain chemistry and relieve symptoms of severe depression. Side effects such as confusion and memory loss may occur, but are usually not long-lasting.
- Vagus nerve stimulation (VNS): A device with a wire connected to the vagus nerve in the neck is implanted in the chest. Electrical impulses are transmitted from those nerves to areas of the brain that control mood. This may improve your depression. This procedure is usually only attempted if ECT and rTMS do not work.
If you are not 100% better, please consult your doctor. The goals of treatment should be the same as for other health conditions, such as cancer, heart attack, or broken bones, Crystal says. „In other words, we don't go to an orthopedic surgeon and say, 'I broke your leg and I want it to be 60% better.' We say to an orthopedic surgeon, 'I want you to fix my leg.' ”