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Your Guide to Treating Depression

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New Options for Treatment-Resistant Depression

Medically Reviewed By William C. Lloyd III, MD, FACS
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If it seems you’ve tried everything to relieve symptoms of depression, and nothing seems to work, you may have what’s called treatment-resistant depression. This is when standard treatments like antidepressants and psychotherapy don’t help with depression symptoms, or when symptoms partly improve or improve for a short time, only to keep coming back.

But don’t let the name discourage you. Despite the seeming ‘resistance,’ there are still treatment-resistant depression options that offer hope. Whether your symptoms are mild or severe, you may need to try a few different approaches before you land upon the one that makes a difference.

New Medications

The FDA (U.S. Food and Drug Administration) recently approved a new treatment-resistant depression medication, called ketamine, that has shown significant benefits in clinical trials. Marketed under the brand name Spravato, ketamine will come in the form of a nasal spray. Though researchers still don’t understand how it works, preliminary research suggests it may be especially effective at eliminating suicidal thoughts and feelings.

One of the most common side effects of ketamine use is hallucinations. Some doctors believe these hallucinations may be key to the drug’s effectiveness. Other reported effects include out-of-body experiences and profound spiritual realizations, which may help change a person’s outlook or way of thinking. People taking ketamine may also experience sedation and difficulty with attention, judgment and thinking (dissociation).

The FDA has approved ketamine for use only in a certified doctor’s office or clinic, where the patient self-administers the nasal spray and is then monitored for any effects for two hours. Depending on the severity of your depression, you may receive 1 to 2 doses per week. Talk with your psychiatrist or primary doctor about whether ketamine may be worth a try for your symptoms and how side effects are managed.

Changing Medication Strategies

Of course, there are other medication strategies that many find effective when their current regimen is not working.

  • Change your dosage. It may be that you simply have not found the right dose, or need more medication than is typically prescribed. Talk to your doctor before changing your dosage on your own.

  • Give your medication more time to work. It typically takes four to eight weeks to feel the effects from antidepressants and other medications for depression. For some, it may take longer.

  • Switch medications or add an additional drug. Often, it takes several tries to find an antidepressant, or a combination of medications, that works for you. Talk with your doctor about all options that may be helpful for your symptoms.

Other Approaches

When medications aren’t working, or in addition to medication, psychotherapy and other procedures can offer another form of relief.

  • Counseling. If you’ve found that counseling hasn’t been effective in lifting your depression, talk with your psychotherapist about trying a different approach. Or consider seeing someone else. As with medications, it may take several tries to find the right therapist or therapy approach that speaks to you.

  • Electroconvulsive Therapy (ECT). In this type of neurostimulation, electrodes are placed on the head to deliver electrical impulses, causing changes in brain chemistry that can relatively quickly reverse symptoms of major depression. Potential side effects include temporary confusion or temporary memory loss.

  • Vagus Nerve Stimulation (VNS). Another type of neurostimulation, VNS has been approved as an additional treatment for long-term or recurrent depression in adults who have not had success with four or more antidepressant medicines. A device is put into the chest that sends an electrical current to the brain, which may help improve depressive symptoms.

Lifestyle Adjustments

Making changes to your lifestyle can also have a huge impact on depression symptoms, especially if you’ve found that other treatments just aren’t cutting it.

  • Avoid alcohol and drugs. Although some people may find alcohol and recreational drugs provide temporary relief from depression symptoms, eventually they can worsen depression and make it harder to treat. Talk with your doctor if you think you need help stopping alcohol or drug use.

  • Get more sleep. How well or how much you sleep can affect your mood, energy level, and concentration, all of which can make depression symptoms worse. Ask your doctor about advice for improving your sleep habits.

  • Manage your stress. In today’s fast-paced, high-tech world, we face more and more stressors on a daily basis. Working in some kind of de-stress routine, whether it’s yoga, meditation, exercise or journaling, is one of the best ways to keep depression at bay.

  • Consider other illnesses. It’s also important to consider whether your depression may be impacted by other health conditions or illnesses, many of which contribute to stress and fatigue. This may include an additional mental disorder or a different condition altogether, which might explain why you are not getting relief from your current treatment plan or medication.

In most cases, depression is highly treatable. If this hasn’t been the case for you, don’t give up. Work closely with your psychotherapist, psychiatrist, and your primary doctor to revisit your depression and find the best treatment, or combination of treatments for you.


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Medical Reviewer: William C. Lloyd III, MD, FACS
Last Review Date: 2021 Jun 3
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THIS TOOL DOES NOT PROVIDE MEDICAL ADVICE. It is intended for informational purposes only. It is not a substitute for professional medical advice, diagnosis or treatment. Never ignore professional medical advice in seeking treatment because of something you have read on the site. If you think you may have a medical emergency, immediately call your doctor or dial 911.
  1. FDA Approves Ketamine Nasal Spray to Treat Depression. Psychology Today.  
  2. Treatment-resistant depression. Mayo Clinic.
  3. Rapidly-Acting Treatments for Treatment-Resistant Depression. National Institute of Mental Health.
  4. New insights into treatment-resistant depression. Harvard Health Publishing.
  5. FDA approves new nasal spray medication for treatment-resistant depression; available only at a certified doctor’s office or clinic