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Medikationsstrategien bei behandlungsresistenter Depression

von NFI Redaktion

Treating Treatment-Resistant Depression

If you are suffering from treatment-resistant depression, you may have already unsuccessfully tried taking antidepressants. However, you should not give up. It may take some time to find the medication, dosage, or combination of medications that are right for you.

“There are more than two dozen safe and effective antidepressants,” says Jonathan E. Alpert, MD, PhD, Chairman of the Council on Research at the American Psychiatric Association and Professor of Psychiatry at the Montefiore Medical Center.

The challenge lies in the fact that doctors cannot predict exactly how individuals will respond to each medication. “Many different factors contribute to depression, such as genetic predisposition and life stressors,” says psychiatrist Dr. Walter Dunn, Assistant Professor of Health Sciences at UCLA Health. Until a better understanding of the disease is available, finding the right treatment is done through trial and error.

Exploring the Best Approach

You and your doctor can discuss these medication strategies for treatment-resistant depression:

Ensure you are taking your medication as prescribed. Three out of four people do not take their medication as recommended by their doctor. Some skip a day or stop taking a medication when they start feeling better. However, these actions may prevent an antidepressant from working effectively, says James W. Murrough, MD, PhD, Director of the Depression and Anxiety Center at the Icahn School of Medicine at Mount Sinai. Consult with your doctor before making changes to how you take your medication.

Give your current medication more time. Antidepressants usually do not work immediately. It generally takes 6 to 8 weeks for them to reach their maximum effect, according to Murrough. For some individuals, this process may take even longer.

Your body also needs to adjust to the medication. When starting a new antidepressant, you may experience side effects such as dry mouth, headaches, fatigue, or stomach discomfort. However, these symptoms often disappear after a few weeks.

Adjust your medication dosage. People respond differently to antidepressants. You may require more or less of a medication than the standard amount. If you do not feel any different after 2 to 4 weeks, your doctor may increase your dosage, says Alpert.

Switch to a different antidepressant. If your current medication is not working, your doctor may suggest switching to a different one. This is common practice. Studies show that only about one-third of individuals experience relief from their depression after initially taking an antidepressant.


Most antidepressants affect chemicals in the brain called neurotransmitters, such as serotonin, norepinephrine, and dopamine. Each type of antidepressant acts on these chemicals in different ways:

  • Selective Serotonin Reuptake Inhibitors (SSRIs). These are often prescribed as the first line of antidepressant treatment because they have fewer side effects. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro).
  • Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs). Duloxetine (Cymbalta), venlafaxine (Effexor XR), levomilnacipran (Fetzima), and desvenlafaxine (Pristiq) are examples of SNRIs.
  • Atypical Antidepressants. These medications do not fall into the other main categories. Examples include mirtazapine (Remeron), vortioxetine (Trintellix), and bupropion (Wellbutrin SR).
  • Tricyclic Antidepressants. These antidepressants are an older class and cause more side effects. They include imipramine (Tofranil), nortriptyline (Pamelor), amitriptyline, and doxepin.
  • Monoamine Oxidase Inhibitors (MAOIs). If you are taking these medications such as tranylcypromine (Parnate), phenelzine (Nardil), and isocarboxazid (Marplan), you must follow a strict diet as they can cause dangerous interactions.

Your doctor may want to try a medication from the same class or a different one. “Research shows that if you do not respond to one SSRI, another may work,” says Dunn.

Add another medication to your current antidepressant. Your doctor may suggest adding another medication to the one you are already taking, known as augmentation. “If you are feeling better and your symptoms have improved by 30 to 50%, we try to add something additional to balance it out,” says Dunn.

One medication that can be used in combination with an antidepressant is ketamine. Your doctor may recommend it to achieve rapid relief from your treatment-resistant depression. You take it in low doses through an infusion. The FDA has approved a nasal spray form called esketamine (Spravato). Doctors typically recommend taking an oral antidepressant along with esketamine or ketamine.

Your doctor may also prescribe medications for other issues, such as anxiety, antipsychotics, mood stabilizers, and thyroid hormones.

Consider pharmacogenetic testing. These tests examine a sample of your saliva or blood. They analyze your DNA for genes that control specific enzymes or cell receptors. Most of these tests examine how your body metabolizes or breaks down medications. If you metabolize a medication too quickly, you may need a higher dose of an antidepressant, says Dunn. Conversely, if your body takes longer to metabolize a medication, it can lead to an accumulation of the drug and cause side effects.

Pharmacogenetic tests do not indicate which medications work best. However, they can provide insight into the dosage you may need or the risk of side effects, says Alpert.

Each depression is unique. You may need to try multiple medications and dosages before finding the right one. A study shows that 67% of individuals experienced relief after trying the fourth medication. The process can be frustrating, but it is important to keep trying,” says Dunn.

“These medications are not permanent,” he says, “so we have the luxury of trying one and then discontinuing it if it does not suit you.” With time, patience, and communication with your doctor, it is highly likely that you will find the right treatment for your treatment-resistant depression.

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