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Treatment-Resistant Depression?

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I was diagnosed with major depressive disorder1.5 years ago, precipitating event irrelevant. I have been taking 1cap 60mg Cymbalta PO QD for roughly a year. No significant changes occurred, so I experimented with Mirtazapine to augment the Cymbalta; it caused RLS-like symptoms at bedtime, so I tapered off of it. I have been taking 1tab 300mg Seroquel XR PO QD, expecting to see improvement, but have not noticed any noteworthy. Though my appetite and overall energy have improved, and my panic attacks have weakened in intensity (not frequency), my mood still seems to be suboptimal. As I mentioned panic attacks, I have been prescribed everything in the book; Xanax does work well if I do not catch the attack in time to use other methods, but I do my best to avoid using benzodiazepines. With that being said, I have taken no more than 1mg Xanax in the past 5 months or so. I have been looking into Buspar, and I have heard great things, but I just do not know what the best 'next' thing should be. Will an anxiolytic medication be the best route, or is there something else I should consider to improve my overall mood? I just want to be able to enjoy the things that used to be a integral part of my life; I'm tired of going through the motions.

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If you truly have medication-resistant depression, there are other methods of treatment. Electroconvulsive therapy has improved greatly and is claimed to have very beneficial effects. The risks are minimal but it is time consuming and they only do it for people who they have tried everything else on. It sounds scary but it's not like how it is in 1950's movies. They use muscle relaxants and anesthesia so you're not aware of the shocks. Besides that, there are MAOIs, but those can get dangerous since you can't take things like aspirin or even eat certain foods. Because you've only been treated for 1.5 years, I still have hope that you'll find a medication that suits you. SNRIs, like cymbalta, have proven more effective than SSRIs but you never know. Keep trying new things and give therapy a try too if you haven't already.

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I was diagnosed with major depressive disorder1.5 years ago, precipitating event irrelevant. I have been taking 1cap 60mg Cymbalta PO QD for roughly a year. No significant changes occurred, so I experimented with Mirtazapine to augment the Cymbalta; it caused RLS-like symptoms at bedtime, so I tapered off of it. I have been taking 1tab 300mg Seroquel XR PO QD, expecting to see improvement, but have not noticed any noteworthy. Though my appetite and overall energy have improved, and my panic attacks have weakened in intensity (not frequency), my mood still seems to be suboptimal. As I mentioned panic attacks, I have been prescribed everything in the book; Xanax does work well if I do not catch the attack in time to use other methods, but I do my best to avoid using benzodiazepines. With that being said, I have taken no more than 1mg Xanax in the past 5 months or so. I have been looking into Buspar, and I have heard great things, but I just do not know what the best 'next' thing should be. Will an anxiolytic medication be the best route, or is there something else I should consider to improve my overall mood? I just want to be able to enjoy the things that used to be a integral part of my life; I'm tired of going through the motions.

Standard disclaimer, none of the following is professional medical advice, nor should it replace it. Purely based on my own experience/research :P

How many meds have you tried? It's a bit early to call yourself treatment resistant just because Cymbalta for a year hasn't helped much. If 60mg Cymbalta was still not anywhere near satisfactory after a couple of months, you could've probably asked your pdoc for an increase or to try a new med. Might be worth trying some of the SSRIs like Fluoxetine(Prozac) or Sertraline(Zoloft) if you haven't yet. I've you've already tried SSRIs, you could try Effexor(different SNRI). Mirtazapine RLS can go away after a couple of weeks anyway I believe, so depending on how long you tried it for, it could be an option still.

Aside from that, there's still tricyclics like Amitriptyline (Elavil), Imipramine, Clomipramine, etc. Also MAOIs, some of which don't have dietary constraints like the Emsam patch in the US, Moclobemide (Manerix, Aurorix).

If you really want to stick with the Cymbalta and add more stuff, maybe low dose Amisulpride (supposed to be good for Dysthymia, low grade very persistent depression with loss of enjoyment being one of the common problems), although I'm not sure that's available in the US.

I'd probably try more standalone ADs before trying to add stuff to them if you've only tried a couple, as side-effects for a lot of the addon meds can suck. But there's some ideas for things you could try anyway. I'm also still trying to find something that works, having tried Citalopram, Cymbalta, Lofepramine and currently being on a mixture of Mirtazapine and Reboxetine.

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I was diagnosed with major depressive disorder1.5 years ago, precipitating event irrelevant. I have been taking 1cap 60mg Cymbalta PO QD for roughly a year. No significant changes occurred, so I experimented with Mirtazapine to augment the Cymbalta; it caused RLS-like symptoms at bedtime, so I tapered off of it. I have been taking 1tab 300mg Seroquel XR PO QD, expecting to see improvement, but have not noticed any noteworthy. Though my appetite and overall energy have improved, and my panic attacks have weakened in intensity (not frequency), my mood still seems to be suboptimal. As I mentioned panic attacks, I have been prescribed everything in the book; Xanax does work well if I do not catch the attack in time to use other methods, but I do my best to avoid using benzodiazepines. With that being said, I have taken no more than 1mg Xanax in the past 5 months or so. I have been looking into Buspar, and I have heard great things, but I just do not know what the best 'next' thing should be. Will an anxiolytic medication be the best route, or is there something else I should consider to improve my overall mood? I just want to be able to enjoy the things that used to be a integral part of my life; I'm tired of going through the motions.

Sorry for the double post -- I added a feature to my track pad on my mac book -- and it now has a mind of its own.

But about your question...did something suddenly trigger your MDD 1.5 years ago? I'm one of the people who has tried everything and nothing worked for me except Nardil. I never minded the eating restrictions -- seemed a small price to feel better. For me Nardil fixed everything. For the first time in my life I felt, what I considered, "normal." No anxiety, no depression. I socialized and had no problem leaving my house. Of course, it takes a while to work and you have to be free of SSRIs or SNRIs for two weeks before you can switch.

Good luck and keep us posted.

Edited by Joanee

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At first, I was put on a low dose of Lexapro and worked my way up to the maximum therapeutic dose. It seemed to work for a few weeks, but I'm quite prone to the placebo effect. Not that I'm arguing with it - if it works, it works - but after a while, it doesn't. I switched directly over to Cymbalta from there. After being on it for this long, I feel like my biomedicine options are limited. If I were to switch to an SSRI, I would have to taper off the Cymbalta, which even done safely, I've heard/read it is quite unpleasant. MAOI is not really a territory in which I wish to venture, too many risks. I have been doing psychotherapy ever since I started the medications, and behavior changes have definitely helped the situation. I'm a believer in finding a balance between psychodynamic therapy and biomedicine. I do find myself questioning my motives, or rather my expectations; the success stories one hears about rarely happen, and it is possible that I'm expecting too much from medication. To touch on the Mirtazapine issue, I took 15mg for about 3 weeks, then moved up to 30mg for another 3-4 weeks. The akathesia gradually worsened, so my doctor and I decided to taper off it completely. It was at this point I started seeing a psychiatrist rather than my GP, and he was the one who started me on Seroquel XR, believing that it would prove to be beneficial.

I was diagnosed with major depressive disorder1.5 years ago, precipitating event irrelevant. I have been taking 1cap 60mg Cymbalta PO QD for roughly a year. No significant changes occurred, so I experimented with Mirtazapine to augment the Cymbalta; it caused RLS-like symptoms at bedtime, so I tapered off of it. I have been taking 1tab 300mg Seroquel XR PO QD, expecting to see improvement, but have not noticed any noteworthy. Though my appetite and overall energy have improved, and my panic attacks have weakened in intensity (not frequency), my mood still seems to be suboptimal. As I mentioned panic attacks, I have been prescribed everything in the book; Xanax does work well if I do not catch the attack in time to use other methods, but I do my best to avoid using benzodiazepines. With that being said, I have taken no more than 1mg Xanax in the past 5 months or so. I have been looking into Buspar, and I have heard great things, but I just do not know what the best 'next' thing should be. Will an anxiolytic medication be the best route, or is there something else I should consider to improve my overall mood? I just want to be able to enjoy the things that used to be a integral part of my life; I'm tired of going through the motions.

Standard disclaimer, none of the following is professional medical advice, nor should it replace it. Purely based on my own experience/research :P

How many meds have you tried? It's a bit early to call yourself treatment resistant just because Cymbalta for a year hasn't helped much. If 60mg Cymbalta was still not anywhere near satisfactory after a couple of months, you could've probably asked your pdoc for an increase or to try a new med. Might be worth trying some of the SSRIs like Fluoxetine(Prozac) or Sertraline(Zoloft) if you haven't yet. I've you've already tried SSRIs, you could try Effexor(different SNRI). Mirtazapine RLS can go away after a couple of weeks anyway I believe, so depending on how long you tried it for, it could be an option still.

Aside from that, there's still tricyclics like Amitriptyline (Elavil), Imipramine, Clomipramine, etc. Also MAOIs, some of which don't have dietary constraints like the Emsam patch in the US, Moclobemide (Manerix, Aurorix).

If you really want to stick with the Cymbalta and add more stuff, maybe low dose Amisulpride (supposed to be good for Dysthymia, low grade very persistent depression with loss of enjoyment being one of the common problems), although I'm not sure that's available in the US.

I'd probably try more standalone ADs before trying to add stuff to them if you've only tried a couple, as side-effects for a lot of the addon meds can suck. But there's some ideas for things you could try anyway. I'm also still trying to find something that works, having tried Citalopram, Cymbalta, Lofepramine and currently being on a mixture of Mirtazapine and Reboxetine.

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60mg Cymbalta is the highest dose that showed therapeutic improvement in its research. Also, I did consider, at one time, switching to an SSRI like Prozac. However, Cymbalta is a SNRI, so switching would require tapering off Cymbalta before starting a new SSRI. This can become difficult, as well as dangerous, as I would be on a low dose of serotonin-affective medication before starting a new one. Looking into adjunct treatments was the best route to take, all things considered.

At first, I was put on a low dose of Lexapro and worked my way up to the maximum therapeutic dose. It seemed to work for a few weeks, but I'm quite prone to the placebo effect. Not that I'm arguing with it - if it works, it works - but after a while, it doesn't. I switched directly over to Cymbalta from there. After being on it for this long, I feel like my biomedicine options are limited. If I were to switch to an SSRI, I would have to taper off the Cymbalta, which even done safely, I've heard/read it is quite unpleasant. MAOI is not really a territory in which I wish to venture, too many risks. I have been doing psychotherapy ever since I started the medications, and behavior changes have definitely helped the situation. I'm a believer in finding a balance between psychodynamic therapy and biomedicine. I do find myself questioning my motives, or rather my expectations; the success stories one hears about rarely happen, and it is possible that I'm expecting too much from medication. To touch on the Mirtazapine issue, I took 15mg for about 3 weeks, then moved up to 30mg for another 3-4 weeks. The akathesia gradually worsened, so my doctor and I decided to taper off it completely. It was at this point I started seeing a psychiatrist rather than my GP, and he was the one who started me on Seroquel XR, believing that it would prove to be beneficial.

I was diagnosed with major depressive disorder1.5 years ago, precipitating event irrelevant. I have been taking 1cap 60mg Cymbalta PO QD for roughly a year. No significant changes occurred, so I experimented with Mirtazapine to augment the Cymbalta; it caused RLS-like symptoms at bedtime, so I tapered off of it. I have been taking 1tab 300mg Seroquel XR PO QD, expecting to see improvement, but have not noticed any noteworthy. Though my appetite and overall energy have improved, and my panic attacks have weakened in intensity (not frequency), my mood still seems to be suboptimal. As I mentioned panic attacks, I have been prescribed everything in the book; Xanax does work well if I do not catch the attack in time to use other methods, but I do my best to avoid using benzodiazepines. With that being said, I have taken no more than 1mg Xanax in the past 5 months or so. I have been looking into Buspar, and I have heard great things, but I just do not know what the best 'next' thing should be. Will an anxiolytic medication be the best route, or is there something else I should consider to improve my overall mood? I just want to be able to enjoy the things that used to be a integral part of my life; I'm tired of going through the motions.

Standard disclaimer, none of the following is professional medical advice, nor should it replace it. Purely based on my own experience/research :P

How many meds have you tried? It's a bit early to call yourself treatment resistant just because Cymbalta for a year hasn't helped much. If 60mg Cymbalta was still not anywhere near satisfactory after a couple of months, you could've probably asked your pdoc for an increase or to try a new med. Might be worth trying some of the SSRIs like Fluoxetine(Prozac) or Sertraline(Zoloft) if you haven't yet. I've you've already tried SSRIs, you could try Effexor(different SNRI). Mirtazapine RLS can go away after a couple of weeks anyway I believe, so depending on how long you tried it for, it could be an option still.

Aside from that, there's still tricyclics like Amitriptyline (Elavil), Imipramine, Clomipramine, etc. Also MAOIs, some of which don't have dietary constraints like the Emsam patch in the US, Moclobemide (Manerix, Aurorix).

If you really want to stick with the Cymbalta and add more stuff, maybe low dose Amisulpride (supposed to be good for Dysthymia, low grade very persistent depression with loss of enjoyment being one of the common problems), although I'm not sure that's available in the US.

I'd probably try more standalone ADs before trying to add stuff to them if you've only tried a couple, as side-effects for a lot of the addon meds can suck. But there's some ideas for things you could try anyway. I'm also still trying to find something that works, having tried Citalopram, Cymbalta, Lofepramine and currently being on a mixture of Mirtazapine and Reboxetine.

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Actually tapering off to start an SSRI/SNRI other med may not take that long.

What do you class as dangerous? suicide risk?

People go on and off an ssri/snri everytime the refuse to work.

Plus between these lot of meds you do not need a wash out period.

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I think I'm mainly worried that I'm expecting too much. Psychiatric medications are still in their years of trial and error, so I'm worried that Cymbalta is working well and a change in medication may leave me stranded with a new medication that does not work for me. I fear that I'm expecting to be one of the success stories, someone who feels like an entirely different person. It is difficult for me to differentiate between what medication is capable of doing for me, and what I am hoping it can do for me. Does anyone else struggle with this distinction?

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Can be pretty hard to work out what medication alone can do. For me there's no real underlying reason for my depression (no traumatic events, particularly bad thought patterns, etc) so when I was on the right medication I had pretty complete recovery before it pooped out.

Switching between most SSRI/SNRI meds you can normally just cross taper rather than having to completely taper off first. MAOIs are overly risky considering you've only really tried Cymbalta and Lexapro. Still might be worth trying at least one of Prozac, Zoloft or Effexor at some point if you're unsatisfied. Alternatively there's always the tricyclics, but those probably would require stopping first and they don't have great side-effect profiles. My next step is tricyclics if Mirtazapine doesn't work, since I don't tolerate SSRI/SNRI meds at all well.

I think I'm mainly worried that I'm expecting too much. Psychiatric medications are still in their years of trial and error, so I'm worried that Cymbalta is working well and a change in medication may leave me stranded with a new medication that does not work for me. I fear that I'm expecting to be one of the success stories, someone who feels like an entirely different person. It is difficult for me to differentiate between what medication is capable of doing for me, and what I am hoping it can do for me. Does anyone else struggle with this distinction?

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In my opinion, the risks and restrictions associated with MAOI's are not as bad as people think. One person here mentioned you cannot take aspirin with an MAOI- this is not true, as are a lot of other beliefs about this class of AD's. There is a whole thread in this subforum about people on MAOI's who think these medicines are being underused.

Also, as somebody already mentioned, there is an MAOI patch out called EMSAM that is especially safe, though criminally overpriced.

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