Treatment Resistant Depression: Signs, Symptoms, & Treatment Options

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 (MDD) that overlap with symptoms of other depressive disorders, such as bipolar disorder or persistent depressive disorder (dysthymia). 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 remember that most antidepressants usually take four to eight weeks to have their full effect.⁴ A case of depression is not normally labeled 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 suicidal ideation
• 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 discouraging and frustrating. It can take two months to feel the full benefits of an antidepressant,and many antidepressants also have adverse effects. Although negative side effects usually abate, their occurrence adds to the time required to know the actual benefit of a medication. One may begin to feel hopeless about ever finding an effective medication with tolerable or minimal adverse effects.

While managing these symptoms can be difficult, 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.

How to Know You Have Treatment Resistant Depression

Treatment resistant depression is more common than people think. A third of those with depression have treatment resistant depression. If you are currently in treatment for depression and you are still struggling most days and having symptoms such as feelings of sadness, sleep issues, and very low mood and energy, you may have treatment resistant depression. It is deemed treatment resistant depression when the individual in treatment for depression does not have sufficient progress in their depression symptoms after initial treatment protocols have been followed consistently.

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. Genetics can influence depression, although the exact genetic biomarkers have not been identified.² Another possible cause is metabolic abnormalities. One study noted a deficiency in vitamin B9 (folate) among people with treatment resistant depression, but further research is needed.³

For some, physical health conditions like thyroid disorders, chronic pain, or heart disease may contribute to treatment resistant depression.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 complicate 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 (i.e., either a different form of depression is present or a medical condition like hypothyroidism or heart disease is causing the symptoms)
• 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 (e.g., missing doses or 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 or 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 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 considered.

Medication to Treat Depression

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, and determine whether the medications are being used correctly. They will also consider any relevant physical health conditions that may be contributing to a depressed mood.

The psychiatrist will determine whether there is another mental health condition that’s 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 that 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 to Treat Depression

It’s strongly advised that a person with treatment resistant depression participates in depression therapy.^{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 help individuals who exhibit substance misuse that contributes to the depressive symptoms.

Here are various forms of psychotherapy used for treatment resistant depression:⁴

Cognitive Behavioral Therapy (CBT)

The focus of CBT for Depression 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)

Acceptance and commitment therapy (ACT) is a subtype of CBT that 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)

Dialectical behavior therapy (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 therapy 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 therapy for families, or longer term, as in family systems therapy.

Interpersonal or Person-Centered Therapy

Interpersonal therapy and person-centered 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.

Procedures to Treat Depression

When medication strategies with or without psychotherapy do 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)

In 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 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

If you’re wondering how to treat depression and treatment resistant depression, seek help from medical and mental health professionals. A psychiatrist has both medical knowledge and awareness of mental health problems. They’re usually the person who will evaluate the depressed person and recommend a medication strategy. They may also provide psychotherapy, although more frequently, they’ll refer to a psychotherapist with a non-medical background (psychologist or social worker).

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 one of three 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

Coping With Treatment Resistant Depression

It can be difficult 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.

Here are several coping strategies that can 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 you are involved in. 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 & 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.

6 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.

Here are six tips for coping with treatment resistant depression:⁸

1. Contact your psychiatrist, psychotherapist, or physician and let them know that your symptoms have worsened
2. Talk to the person identified in your emergency plan, as described earlier
3. Take some extra time to rest and relax. Cut back on activities that keep you from getting enough rest.
4. Use the self-care that works best for you, such as sleep, exercise, and eating a healthy diet
5. Call the National Suicide Prevention Lifeline at 1-800-273-8255 if you are having suicidal thoughts
6. Call 9-1-1 if you or a loved one are in immediate danger

Treatment Resistant Depression Statistics

These depression statistics and resources 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 2017.⁹

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

Final Thoughts on Treatment Resistant Depression

What you are dealing with is unique to you, but you are not alone. Treatment and support can take time to work, but there is hope. Making sure you are trying your best to maintain a healthy lifestyle and are on track with your treatment regimen is critical. Things will start to feel better.