# Treatment-resistant depression: Options when depression doesn't get better



## David Baxter PhD

Treatment-resistant depression: Explore options when depression doesn't get better
By Mayo Clinic Staff
Aug. 27, 2009


_Sometimes depression doesn't get better, even with treatment. Explore why this sometimes happens and what you can do about it._ 

If you've been treated for depression but your symptoms haven't fully improved, you may have treatment-resistant depression. Medications and psychotherapy work for most people. But with treatment-resistant depression, standard treatments don't help much or don't help at all. With treatment-resistant depression, symptoms ? such as feeling sad, hopeless and disinterested in activities ? persist despite treatment. Or, your symptoms improve only to keep coming back. Treatment-resistant depression can range from mild to severe, and generally requires trying a number of treatments to find out what works. 

Use this guide to explore reasons why your depression treatment may not be working and options you might want to consider. 

*What causes treatment-resistant depression?*
Like other types of depression, treatment-resistant depression is most likely caused by a combination of inherited and environmental factors that affect brain chemicals called neurotransmitters. A number of things can contribute to treatment-resistant depression, including: 


*Emotional stress*. If you're feeling stress or anxiety because of situations in your life that aren't getting better, medications alone might not help. Examples include relationship issues, financial problems or inadequate housing. In addition, childhood abuse or neglect can continue to affect you throughout adulthood. Psychotherapy can be especially helpful in coping with stressful situations.
*Not taking medications exactly as prescribed*. Treatment may not work if you stop taking your medication, skip or lower a dose, or forget to take a dose. Many people get off track. This can happen for a number of reasons, including problems with side effects, thinking you don't need medication or that you don't need a full dose of medication because you feel better, or simply forgetting. If you do stop taking your medication, forget to take a dose or make other changes, be honest with your doctor about it so that you can address any problems and get back on track.
*Underlying health problems*. Other medical conditions or illnesses can sometimes mimic or worsen depression. These include thyroid disorders, chronic pain, anemia, heart problems, anxiety disorders, and substance abuse or addiction.
*Another mental health diagnosis*. It's not always easy to diagnose depression, and other mental health disorders may require different treatment. In particular, some forms of bipolar disorder are commonly misdiagnosed as depression if manic phases are mild. In many cases, depression occurs along with other conditions ? such as panic disorder or post-traumatic stress disorder ? which can make depression more difficult to treat. Ask your mental health provider whether your symptoms may be caused by bipolar disorder or linked to another mental health condition.
If you and your doctor or mental health provider pinpoint one of these factors as a possible source of your depression, you can work together to develop a more effective treatment strategy. It may never be clear what causes or worsen your depression, but you're still likely to find treatment that helps through a trial-and-error approach. 

*Who should treat treatment-resistant depression?*
Your family doctor can prescribe antidepressants and give you advice. But if your depression symptoms continue despite treatment, you should see a medical doctor who specializes in mental health (psychiatrist). You may also need to see a psychologist or other mental health counselor. It can be helpful if all of the mental health providers involved in your treatment communicate and work together. 

*What is the goal for treating depression?*
Even though you may find a treatment that's somewhat effective at relieving your symptoms, keep trying to find the best treatment possible. People who find treatment that completely relieves symptoms are less likely to have a relapse of their depression later. That's why it's important to be patient and not settle for a treatment that isn't fully effective. Also, keep trying different treatments if your current treatment causes significant side effects. 

*What are the medication strategies?*
Even if you've already tried antidepressants or other medications for depression and they didn't work, don't lose hope. You and your doctor simply may not have found the medication or combination of medications that works for you. You have several options even if you've tried medications in the past: 


*Trying a medication longer*. Antidepressants and other medications for depression typically take four to eight weeks to become fully effective and for side effects to ease up. For some people, it takes even longer for medication to work, so it helps to be patient.
*Increasing your dose*. Because people respond to medications differently, you may benefit from a higher dose of medication than is usually prescribed. Discuss with your doctor whether this is an option for you. Don't alter your dose on your own.
*Augmentation*. Augmentation means taking an antidepressant along with a medication generally used for another mental health condition. It may take some trial and error since there are numerous medications for use in augmentation, including anti-anxiety medications, anti-seizure medications, mood stabilizers, beta blockers, antipsychotics and stimulants. The downside of augmentation is that some of these medications may cause bothersome side effects or require periodic blood tests.
*Switching*. Switching to a new medication is common when an antidepressant doesn't work effectively. Each person responds to medications differently. In nearly 1 in 3 people, the first antidepressant tried doesn't work at all. You may need to try several antidepressants before you find one that works. You may switch from one antidepressant to another in the same class. Or, you may switch from one class of antidepressants to another.
*Combination*. In the combination approach, different classes of antidepressants are prescribed at the same time. That way they'll be more likely to affect a wider range of brain chemicals that affect mood. For instance, you may take both a selective serotonin reuptake inhibitor (SSRI) and a norepinephrine and dopamine reuptake inhibitor. Or you may combine an older antidepressant such as a tricyclic antidepressant with an SSRI. Regardless of the specific medications, the goal is to target several kinds of neurotransmitters at once, including dopamine, serotonin and norepinephrine.
*Taking L-methylfolate*. This prescription supplement provides a form of the B vitamin folic acid, which is necessary for the production of neurotransmitters in the brain linked to mood. Taking this supplement may help with depression if you lack the enzymes to properly break down folate from foods or from standard folic acid supplements.
*Having the cytochrome P450 (CYP450) genotyping test*. This test checks for specific genes that affect how your body uses antidepressants. It can help predict whether your body can or can't process (metabolize) a medication. This may help identify which antidepressant might be a good choice for you. There is some evidence that other tests for certain genes that regulate the neurotransmitter serotonin may help predict if you're likely to respond to a serotonin antidepressant. These genetic tests aren't widely available, so they're only an option for people who have access to a clinic that offers them.
*What are the psychotherapy options?*
For some people with depression, psychotherapy works as well as medication. The combination of medication and psychotherapy is generally the most effective approach. If you're seeing a psychologist or other psychotherapist and it doesn't seem helpful, consider seeing someone else who has a different approach. As with medications, sometimes it takes several tries before you find out what works. 

Many types of psychotherapy are used to treat depression. They include: 


*Cognitive behavioral therapy*. This type of counseling addresses thoughts, feelings and behaviors that affect your mood. It helps you identify and change distorted or negative thinking patterns and teaches you skills to respond to life's challenges in a positive way.
*Interpersonal psychotherapy*. Interpersonal psychotherapy focuses on resolving relationship issues that may contribute to your depression.
*Family or marital therapy*. This type of therapy involves family members or your spouse in counseling. Working out stress in your relationships can help with depression.
*Group psychotherapy*. This type of counseling involves a group of people who struggle with depression working together with a psychotherapist.
*Psychodynamic treatment*. The aim of this counseling approach is to help you resolve underlying problems linked to your depression. This type of treatment can take longer than other types of psychotherapy because it involves exploring your feelings and beliefs in-depth.
*What other treatments are available?*
If standard depression treatment with medications and psychotherapy haven't been effective for your treatment-resistant depression, you may wish to consult with a psychiatrist who specializes in treatment-resistant depression to discuss these additional treatment options: 


*Electroconvulsive therapy (ECT)*. In ECT, electrical currents are passed through the brain to trigger a seizure. Although many people are leery of ECT and its side effects (such as confusion or amnesia), it typically offers immediate relief of even severe depression when other treatments don't work.
*Vagus nerve stimulation*. This treatment uses electrical impulses with a surgically implanted pulse generator to affect mood centers of the brain.
*Transcranial magnetic stimulation (TMS)*. With this treatment, magnetic fields are used to alter brain activity. A large electromagnetic coil is held against your scalp near your forehead to produce an electrical current in your brain.
*References*


Katon W, et al. Treatment of resistant depression in adults. UpToDate Inc.
Matthew SJ. Treatment-resistant depression: Recent developments and future directions. _Depression and Anxiety_. 2008;25:989.
Carvalho AF. Augmentation strategies for treatment-resistant depression. _Current Opinion in Psychiatry_. 2008;22:7.
Stahl SM. Novel therapeutics for depression: L-methylfolate as a trimonoamine modulator and antidepressant-augmenting agent. _CNS Spectrums_. 2007;12:739.


----------



## Andy

Is TMS actually in use now? I remember watching a documentary on both TMS VNS when they first were trying it on mental health issues but it wasn't approved yet.


----------



## David Baxter PhD

I believe it has limited FDA approval (US).


----------



## busybee

I have been seeing been on a drug called lovan at different levels as an 'anti depressant for over 10 years now. I was always very resistant to taking an anti depressant often due to the stigma attached and the passive aggression visited on me by my husband.  "taken your loony pills today' being one of many remarks.  It was a difficult situation I found myself in and I went on them and benefited from them. They assisted me by taking away the aggressive feelings that I had on wakening each morning and assisted me with coping, to stay in situation and be a good mother. 

I am now out of that situation and have been for just 12 months, and earlier on due to the changes and stresses related with leaving my lovan was increased to 2 X 20mg per day.  12 Weeks ago I was so severely depressed, even though I was on the_ medication. _  The choices and decisions I was making affected me and I sought help.  Had not seen the psychologist for over 3 months.  She discussed having my medication reviewed and I am thinking absolutely NOT, I needed those drugs when I was in a bad situation and I should not need to be on them.  So cold turkey no Lovan for 8 -10 weeks.  

The emotions are difficult to deal with. The negative self talk is very hard.  But ... I am dealing with things that I feel the Lovan just helped me to cope with.  But I did not address the WHY I was making poor choices and decisions.  Yes I am emotional, yes it is difficult. I dont want to take drugs for the rest of my life.  My friends are supportive, but even they are saying I may need to go back on them.  I just want to learn how to do this without using them first.  If I need to be on medication for the rest of my life .... that is okay.  But sometimes I think we rely on the magic of medicine to fix it all up.  
NOT being on Lovan is making me work on things.


----------



## David Baxter PhD

I had not heard the name Lovan before so I looked it up: It's fluoxetine, aka Prozac. The same drug is also marketed as Sarafem and prescribed for Premenstrual Dysphoric Disorder.


----------



## busybee

Does that mean that it is not anti depressant drug.  I never felt the affects of the use of it... I just never woke up feeling angry ... if i am not on it, i am teary all the time, very emotional.


----------



## David Baxter PhD

Oh no, it is an SSRI antidepressant, one of the oldest and for many people one of the best.



> I never felt the effects of the use of it... I just never woke up feeling angry ... if i am not on it, i am teary all the time, very emotional.


 
That's how you should feel on medication when you find the right one at the right dose: It's called "normal".


----------



## gayld

I have been on Effexor XR for many, many years and about a year ago I was seeing a Psychiatrist due to the passing of my 35yr old daughter. I also suffer from Fibromyalgia so the psych dr changed me to Cymbalta. I don't think it is helping with the FM and has done nothing for my mood...all I want is to be happy again!! My other daughters have remarked about how I am very negative about different things (nothing in particular), I never see the funny side of things and I take things to heart when it is supposed to be a joke!!

I have tried CBT and found it to be useless; I also asked my GP about changing my antidepressant again but he said that I was still grieving and my unhappiness was to be expected. Since 1990 my brother and only sibling, my mum and dad and my daughter have all passed away. She was born with Cerebral Palsy and died of aspirated pnuemonia.

I have also been divorced twice, which was my doing and not sorry about that. As I said I suffer from FM and I do get upset that I can't do things that I could once do; such as gardening or even window shopping which leaves me in agony for days! I am on Jurnista for the pain which is helping a bit.

I just want to be happy again......can you offer me some advice please?

Gayl


----------



## AmZ

Hi Gayl,

I'm so sorry to hear about your losses. 

You said that you were seeing a psychiatrist but what about therapy with a psychologist? Maybe this could help you.


----------



## gayld

Thanks for replying so quickly!! I have an appointment next week to see my local Dr and I will ask him about a psychologist!


----------



## AmZ

That sounds great.

It looks like you have a lot to process and deal with so I hope that therapy can help you.

Best of luck, let us know how it goes.


----------



## Always Changing

Maybe you could also look in to support groups for people grieving loss of loved ones.  
It all very well for your doc to dismiss your concerns about your antidepressant not working because you most likely are still grieving, But I wouldn't let that stop you from insisting on a change.   *If you feel* that your depression would be better helped by trying a diff medication, *alongside* getting support from a therapist and or support groups (if you feel up to looking into those that is.), Then I would again ask.

(Of course your doctor knows how long you have been on this med and if it has been long enough to start working, so maybe this is something to ask yourself..  Are you on it _long enough_ for it to be working in some way by now?  sometimes different medications have a longer "kick in" time)


----------



## gayld

I have been on Cymbalta for about a year, so I think if it was going to help me it would have done so by now. You're right about seeing a therapist as well as a med change...I feel the need to talk sometimes but I'm a bit of a loner and support groups freak me out for some reason!


----------



## Always Changing

> I feel the need to talk sometimes but I'm a bit of a loner and support groups freak me out for some reason!


I can relate to this as I cannot handle group situations at all.!   

I do not know if you are aware already..  so going to say it anyway just in case,  therapists and (most) psychologists generally do not prescribe medications,  Only your g.p and psychiatrist can, so either talk again with your g.p or the psych you saw some time ago for a review of the med situation. 

:And while you are waiting for referrals etc.. you can browse the forums here (lots of information and coping tips etc, to be found)  and chat with others who have or are maybe in similar situation as yourself. 

:hug:


----------



## David Baxter PhD

Another suggestion: You don't say why the medication was changed from Effexor XR to Cymbalta but I assume since you were on the Effexor for so long that it helped you, at least for a while. You might talk to your doctor about Pristiq, which is chemically much closer to Effexor.

I have seen that change from Effexor to Cymbalta not work very well before... no idea why yet.


----------



## gayld

I had been on the Effexor for about 8-10 years and I felt that it wasn't helping me anymore, hence the change. I will speak to the Dr about Pristiq when I see him! Thanks everyone for your help!


----------

