Treatment resistant depression is usually defined as a case of depression that doesn’t respond to two or more treatments of medication which have been of standard dose and duration. If temporary relief of the symptoms occurs, followed by a recurrence, it is also regarded as treatment resistant depression. A range of other treatments is available, including different medication strategies, psychotherapies, and other procedures.
What Is Treatment Resistant Depression?
Treatment resistant depression is a descriptive term for the various forms of depression that don’t respond to initial treatments As many as 30 to 40% of people who take antidepressants experience only partial relief of symptoms. Although some of these individuals will respond to a different medication or combination of medications, as many as 15% don’t respond to antidepressant treatments at all.1
An incorrect diagnosis of depression is another possible reason for the ineffectiveness of antidepressant medications. There are some symptoms of Major Depressive Disorder which overlap with symptoms of other depressive disorders, such as Bipolar Disorder or Persistent Depressive Disorder. Once a correct diagnosis is made, the optimal medication for that diagnosis can be prescribed.
Signs & Symptoms of Treatment Resistant Depression
The hallmark of treatment resistant depression is the continuation or recurrence of depressive symptoms after taking the optimal dose of an antidepressant medication for the standard duration. It is important to bear in mind that most antidepressants usually take four to eight weeks to have their full effect.4 A case of depression is not normally labelled as treatment resistant unless at least two different medications have been tried without success.
Symptoms of this condition reflect other depressive disorders, and may range from mild to severe, as well as short- or long-term.
Typical symptoms of treatment resistant depression include:5
- Persistent feeling of sadness
- Persistent sleep disturbance
- Persistent low energy
- Sense of apathy or lack of motivation
- Persistent thoughts of death or suicide
- Persistent change in appetite not related to physical illness
- Increasingly severe periods of low mood
- Longer episodes of depressed mood
- High anxiety and low mood
- Frequent irritability
- Difficulty concentrating
- Feelings of hopelessness
What It Feels Like Living With Treatment Resistant Depression
Living with treatment resistant depression can be very discouraging and frustrating. It can take two months to allow for the full benefits of an antidepressant to be felt. Many antidepressants also have adverse effects. Although these negative side effects usually abate over time, their occurrence adds to the time required to know the actual benefit of a medication for the individual. One may begin to feel hopeless about ever finding an effective medication with tolerable or minimal adverse effects.
While managing these symptoms can be a frustrating and discouraging process, it is important to remain hopeful that an effective treatment will eventually be found. There are various treatment options including several that are not medication based. If the initial treatment was prescribed by a physician without a mental health specialty, the next step may be a referral to a psychiatrist.
Causes & Triggers of Treatment Resistant Depression
Treatment resistant depression is a descriptive category and not a distinct form of depression. The causes and triggers of treatment resistant depression may range from having a high level of stress to having a specific physical health condition.
There are a number of possible causes of treatment resistant depression and the specific cause for any individual may remain unknown. One possible cause is genetics, although the exact genetic biomarkers have not been identified.2 Another possible cause is metabolic abnormalities. One study has noted a deficiency in Vitamin B9 (folate) among people with treatment resistant depression, although further research is needed in this area.3 For some individuals, physical health conditions such as thyroid disorders, chronic pain, or heart disease may contribute to depression that is difficult to treat.4
In some cases, the problem is not correctly diagnosed as unipolar depression. For example, if the actual problem is Bipolar Disorder, then antidepressants are not the most effective treatment.
Another possibility is that a unipolar depression is present, such as Major Depressive Disorder, but that other disorders are also present and complicating the process of treatment. Any other possible disorders, such as an eating disorder or a personality disorder, requires its own independent treatment.
Common causes and triggers of treatment resistant depression include:6
- Incorrect diagnosis: a different form of depression is present (for example, bipolar disorder)
- Incorrect diagnosis: a medical condition is causing the symptoms (for example, hypothyroidism, chronic pain, heart disease)
- More than one disorder is present and each disorder needs its own treatment (for example, unipolar depression and anxiety disorder
- Incorrect use of medication that is prescribed (missing doses, giving up and discontinuing the medication before enough time has passed) It is estimated that up to 50% of people who receive prescriptions for antidepressants don’t take them as recommended.
- Incorrect dose of medication (medication may have been started at low dose to minimize side effects, with the plan to increase the dose gradually)
- Worsening of depressive symptoms as an adverse effect of other medications taken concurrently for other medical problems
- Worsening of depressive symptoms due to use of recreational drugs (for example, alcohol)
- Some forms of depression are more difficult to treat, such as long-term depression and severe depression
Management of Treatment Resistant Depression
There are three major types of approaches to the management of treatment resistant depression. These are medication strategies, psychotherapy, and procedural options. For most people, a combination of a medication strategy and psychotherapy is more effective than either approach alone.4 If these combined approaches are ineffective, the procedural options are then considered.
Medication
Experts estimate that about two thirds of antidepressants are prescribed by primary care physicians.6 However, when those prescriptions do not lead to desired improvement in symptoms, the next step is referral to a psychiatrist for medication advice. In certain states, psychologists also have prescription privileges.
A psychiatrist will review the person’s medical history, review all drugs being used currently, and determine whether the medications are being used correctly. They will also consider any relevant physical health conditions that may be contributing to the depressed mood. The psychiatrist will also determine whether there is another mental health condition which is contributing to the problem. Assuming that the current medication has been tried for an adequate time span and at a standard effective dosage, the next step will be the consideration of the following medication strategies.
The most common medication strategies are:6
- Trying a different antidepressant in the same class. Classes include Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), newer antidepressants (affect different serotonin receptors), older antidepressants (tricyclics), and MAO Inhibitors.
- Trying an antidepressant from a different class. For example, the psychiatrist may switch from an SSRI to an SNRI. Or use new FDA-approved medications which target NMDA receptors, such as Auvelity (dextromethorphan-bupropion).
- Continuing the current medicine and adding a new one from a different class (Combination Therapy).
- Continuing the current medicine and adding one that is not typically used to treat depression (augmentation therapy). This method may include antipsychotics, mood stabilizers, anti-anxiety medications, thyroid hormone, or others.4
Psychotherapy
It is strongly advised that a person with treatment resistant depression participates in psychotherapy.4,6 Through counseling with a mental health professional, such as a psychiatrist, psychologist, or social worker, the individual benefits in several possible ways. Benefits include using new coping skills to manage stress, addressing ongoing consequences of any past trauma, and learning new relationship skills. It may also be helpful for individuals who exhibit substance misuse that is contributing to the depressive symptoms.
There are various forms of psychotherapy that have been effectively used for treatment resistant depression.4 Each of these has a different method to bring about changes as well as particular issues for which they are most effective.
Cognitive Behavioral Therapy (CBT)
The focus of CBT is to identify the thoughts, feelings, and behaviors that affect your daily well-being. These new ways of thinking about current problems and new behavioral responses improve mood. It is often the first choice for the psychological treatment of depression. 6
Acceptance and Commitment Therapy (ACT)
This subtype of CBT places the focus on doing what helps, in spite of the negative thoughts or feelings. It is beneficial for those who seek behavior change in the short-term.
Dialectical Behavior Therapy (DBT)
DBT is focused upon problem-solving skills for prevention of self-injury or chronic suicidal thoughts. Benefits include both the positive short- and long-term outcomes that result from learning new skills.
Psychodynamic Psychotherapy
Psychodynamic psychotherapy encourages gaining insight as to the underlying problems or past traumas that may be contributing to depressive symptoms. It is usually a long-term approach, although there are providers who offer short-term psychodynamic psychotherapy.
Family or Couples Therapy
Family and couples therapy are particularly helpful if problems or conflicts in current family or partner relationships are contributing to the ongoing symptoms. This process may be short term, as in Solution Focused Family Therapy, or longer term, as in Family Systems Therapy.
Interpersonal or Person-Centered Therapy
These types of therapy are helpful when relationships outside of the family are creating stress and preventing recovery from depression. For example, a major source of stress may be relationships with peers or coworkers. The length of treatment depends upon the outcomes desired by the client.
Group Therapy
Group therapy is particularly helpful for teens and young adults who respond strongly to the influence of peers. It is often used in addition to one of the other forms of therapy. Most group therapy sessions involve at least a 6-week commitment to attending once per week.
Procedural Options
In those instances in which medication strategies with or without psychotherapy does not provide enough relief of depressive symptoms, a psychiatrist may recommend one of the procedural options. Several of these procedures involve the use of carefully dosed electrical stimulation. Some of these procedures are well established and highly effective, while others are relatively new and still being evaluated for long term effectiveness.
Electroconvulsive Therapy (ECT)
Electrical impulses are passed through the brain to trigger small brief seizures. ECT is usually administered in a series of 6 to 12 treatments over a period of a few weeks.6 This well established procedure often results in the rapid relief of symptoms of severe depression. Possible adverse effects include temporary confusion and temporary memory loss.
Repetitive Transcranial Magnetic Stimulation (rTMS)
Magnetic fields are used to stimulate nerve cells in the brain, by using a small electromagnetic coil placed near the forehead. This procedure is considered safe with few adverse effects. However, it appears to be less effective than ECT.6 For that reason, it is generally used only when ECT is ineffective.4
Vagus Nerve Stimulation (VNS)
Electrical impulses are used to stimulate the vagus nerve, by using a device that is surgically implanted in the chest. It may take up to 9 months to accomplish relief of long-term symptoms of depression. Studies to date suggest that only 1 of 3 people improve. 6 This procedure is usually considered only after failing to get results from ECT and rTMS. 4
Ketamine or Esketamine
Ketamine is an anesthetic which is given intravenously and rapidly relieves of symptoms of depression. However, effects have only been observed in the short-term. 7 Esketamine is a related molecule which has been used as a nasal spray for fast relief of depressive symptoms. It is a new procedure and is used only under supervision of a physician.
How to Get Help for Treatment Resistant Depression
When the problem is treatment resistant depression, it is important to seek help from both medical professionals and mental health professionals. A psychiatrist has both medical knowledge and the awareness of mental health problems, and is usually the person who will evaluate the depressed person and recommend a medication strategy. They may also provide psychotherapy, although more frequently, they will refer to a psychotherapist with a non-medical background (psychologist or social worker) for that part of the treatment.
Locating a provider usually begins with contacting the health insurance carrier and obtaining a list of covered providers in that geographic area. The next step is to contact several of these providers to determine the best fit in terms of their specialty and availability, as well as your costs and any other personal preferences.
How to Get Help for a Loved One
Getting help for a loved one involves similar steps although it may be complicated if the depressed person is feeling discouraged or hopeless about treatment. It may be helpful to take the following steps when getting help for someone else:
- Remind them that only 1 of 3 people who take a first antidepressant get adequate relief from that medication. They are not alone in their struggle to find relief from their depressive symptoms.
- Offer to help them find a provider who is in network with their insurance plan, or who is affordable for them.
- Offer to remind them of their appointment with the physician, psychiatrist, or psychotherapist.
- Remind them of the importance of following the recommended treatment plan, so that the effectiveness of the medication for them may be known.
- Remind them to participate in psychotherapy in addition to their medication strategy.
- Encourage them to remain hopeful that an effective treatment will be found for them.
Living With Treatment Resistant Depression: Coping & Managing Symptoms
It can be very frustrating and discouraging to live with treatment resistant depression. It is important to continue to seek out the treatment that will work for you or your loved one. While persisting with any treatment that is recommended, it is also helpful to consider whether there are some lifestyle changes that you can make.
Several coping strategies work well for those with treatment resistant depression:8
Follow Your Treatment Plan
Don’t skip medications or therapy sessions. If cost or adverse effects become a problem, talk to your pharmacist or psychiatrist to learn about your choices. Talk to your therapist if getting to sessions becomes difficult.
Change Your Alcohol or Recreational Drug Use Habits
Both alcohol and recreational drugs can worsen depression. If you have tried to stop already without success, talk to your physician or therapist. They will be able to suggest treatment programs or support groups to help you stop using these substances.
Learn New Ways to Manage Stress
Stress management is likely to be a major part of the psychotherapy in which you are involved. There are also many stress-management techniques which can be self-taught, such as meditation, mindfulness, journaling, or progressive muscle relaxation.
Establish a Regular Sleep Routine
Getting a good night of quality sleep ensures that you have more energy which can improve your mood.
Exercise Daily
Doing something as simple as a daily walk has been shown to reduce stress and improve the quality of sleep, which correlates with improved mood.
Monitor Your Mood and Behavior
Common early warning signs include increased irritability, social withdrawal, or craving sweet foods. An increase in tiredness and need for sleep may be another early warning sign of a drop in mood. Keeping track of your mood can help you recognize early warning signs of a deeper depression.
Create a Plan That Will Allow Others to Help You If Your Depressive Symptoms Become More Severe
Such a plan could include your emergency contacts, a list of your medications with doses, and the signs that you need others to step in and get help for you. This plan should also include your preferences for treatment and names of the person authorized to make treatment decisions for you.
Tips for Dealing With a Depressive Episode
There may be times when symptoms of the treatment resistant depression become more severe and will require additional steps in the short term. The best coping strategy at these times will differ for each individual depending upon the circumstances and the choices available to them.
The following steps have been helpful to many individuals coping with an increase in symptoms:8
- Contact your psychiatrist, psychotherapist, or physician and let them know that your symptoms have worsened.
- Talk to the person identified in your emergency plan, as described earlier.
- Take some extra time to rest and relax. Cut back on activities if they are keeping you from getting enough rest.
- Use the self-care that works best for you, such as sleep, exercise, and eating a healthy diet.
- Call the National Suicide Prevention Lifeline at 1-800-273-8255 if you are having suicidal thoughts.
- Call 911 if you or a loved one are in immediate danger.
Treatment Resistant Depression Statistics
These statistics are presented to give some perspective on the prevalence of depressive disorders and how they are being treated. The statistics about prevalence of depression in the United States were reported by the NIH based upon results of a survey at the end of 2017. Adults are defined as individuals aged 18 and older.9
Consider the following statistics about treatment-resistant depression:
- An estimated 17.3 million adults in the United States had at least one major depressive episode in 2017. This number represented 7.1% of all U.S. adults.
- The prevalence of adults with a major depressive episode was highest among individuals aged 18-25 (13.1%).
- An estimated 65% of American adults received care by a health professional in addition to medication treatment.
- Treatment with medication alone was least common (6%)
- Approximately 35% of adults with a major depressive episode did not receive treatment.
For those who were treated with antidepressants:1
- Roughly 30 to 40% of people only get partial relief of depressive symptoms from use of antidepressants.
- 15% of people do not get any significant relief of symptoms from antidepressants.
- Two thirds of the antidepressants used have been prescribed by other physicians vs. psychiatrists. 6
For Further Reading
The following are helpful additional resources for anyone impacted by treatment resistant depression:
- Depression and Bipolar Support Alliance: DBSA, see DBSA Chapters/Support Groups in your area.
- National Institute of Mental Health
- National Alliance on Mental Illness
