Question: Hello Dr. - I am currently in the midst of an unrelenting depressive episode, that seems to be getting worse each day. It has been going on, actually, for almost 4 years now. I also have some hormone imbalances that we are trying to correct (so I know that plays a major role), however, my question is this: My new Psychiatrist put me on Brintellix about two weeks ago and I'm supposed to be titrating up to anywhere from 10-20mg. I cannot seem to get past the terrible nausea, however, and I'm still very depressed, crying throughout the day, extremely fatigued, etc. I am also concerned that I may be bi-polar instead of MDD. I have been diagnosed with CPTSD- and that we know for a fact. But I know that many SSRI's or SNRI's can actually worsen bi-polar disorder. Within the past 2.5 yrs. I've been on 17 different medications to try an stop this depression.....nothing has worked. Before that, I had only been on 2 or 3 in my life. I suffered a physical, mental, and complete emotional breakdown in the fall of 2013 resulting in adrenal failure and a very slow, smoldering hypothyroid crisis. I was actually on the hyperthryroid side at the time, but that has since changed. Due to my confusing labs results over the past 3 yrs, my doctors are concerned that I may have hyperparathyroidism, but my calcium levels aren't "high enough" yet - according to the Endo. I'm seeking a second opinion currently, but that means going through all the tests and waiting -again. I'm becoming hopeless. How can you tell the difference between a PTSD patient and a bi-polar 2 patient, or determine if this seemingly treatment resistant depression is due to a yet-to-be-determined medical cause? And how much longer should I push through these side effects of Brintillex before just giving up? Oh, and one last thing to top it all off: I have an autoimmune disorder (metabolic/mitochondrial is more succinct) called Acute Intermittent Porphyria. I can pretty much keep it in check by avoiding my triggers, which is why I'm so depserate for help - one of my main triggers are medications of any kind that rely too heavily on the CYP-450 enzyme pathway. So guinea pigging 17+ diff't meds over 2.5 years has not served me well in the area of general health. I...am....desperate. Please don't say go to Mayo - I've tried - they're at XXXXXXX capacity right now and turned me down. I'll keep trying, but honestly, I'm losing the will to keep fighting. I just want to wake up not crying, and have enough energy to care for my daughter again. Most days I can barely get out of bed, much less dressed, clean the house or cook. This depression and fatigue are like nothing I've ever felt before. I've been in a dark depression many times before, and this hands-down has been the worst. I've been "tired" before - like when I had Mono -but this is like I have mono all day every day. (The answer to the question you're asking yourself right now is: Yes.) I have been tested for EBV and was positive for reactivation last year this time. We're also going to retest for Lyme disease this week. All I want right now, though, is some reprieve from this daily, soul-crushing depression. And, maybe a Doctor that will work with me for continuity of care and help me figure this out. If I'm so tired that I cannot even get dressed, how am I supposed to physically get to a doctor anyway? That's the dichotomy I face. My Endo sees me once a month, one the ONE day that I'm able to feel and present well. Therefore, he simply cannot comprehend it when I tell him that something is terribly, terribly wrong - I don't care what the labs say. I care how I FEEL. I know my body very well, and I know when something is biochemically, physiologically wrong. But suffering like this for almost 4 years without any relief is causing me to lose hope. Can you or any one of your colleagues please help me? Sincerely, Cayce B.

Thank you for your prompt answer, Dr. Sheppe. I do have a random question relating to how this whole tele-medicine thing works. When I went through the list of physicians that were currently online and able to "see" me, I specifically chose someone else (please do not take offense to that!). I chose a Psychiatrist with many years of experience under his belt, as well as numerous research publications and a few books written as well. I am looking for someone who can thoroughly evaluate and help me in a way that other doctors cannot. I do very well understand depression to be a physical illness. I didn't mean for it to come across as though I did not understand that. What I meant, was that in my current situation, it cannot be the root cause, but rather a terrible co-factor. Depression doesn't cause unexplained bone density loss and fractures in a 37 yr old woman (when this all began). It also doesn't cause one's ionized calcium levels to elevate beyond normal range, nor does it cause soaking night sweats, month long fevers (with no other symptom), hair loss, and choking on damn near everything. But, what do you think about this: I'll give the Brintellix at 10 mgs one more week, discontinue the Provigil, try to titrate up to 20, if I can? My history of success with antidepressants has always been: if there's no side effects, it always works. I'm just between a rock and a hard place with side effects b/c they so closely mimic a porphyric attack. My BP has been very unsteady (low) this whole time, and I feel that it's too excitatory in the sense that now I cannot turn my brain off - especially at night. So my sleep is now worse, I'm having more anxiety during the day than before when on just the Cymbalta. I was only on 60mg of Cymbalta but got mixed opinions from Dr.'s as to whether or not I could go any higher. One doc says yes, one says no. Who's right? It worked for me, (well, actually) until we added in the Wellbutrin (which also did it's job well - but the two combined were disastrous.) Now I'm tired all day, and wired at night. I need it to be the other way around. All that aside, I can appreciate a younger doctor like yourself for two reasons: 1: the newest info and education is still fresh in your mind, therefore your perspective might be better than someone more advanced in their career, but who may not be keeping up with their CME. And 2: You're new enough to still be curious and have a true desire to help; without the arrogance and narcissism of many Dr's I've encountered over the years. You're still new enough to be kind. (: I'm confused about how to go about seeing you as a patient, though. If it's not through this website, then how does this work? Oh, and one last thing: who vets your responses? (: Oh yeah, and you should read up on the Hyperparathyroidism thing - it can many, many, MANY times be overlooked as the reason for someone's complete psychotic episodes - it has MAJOR psychiatric consequences. So while I'm chasing that rabbit for now, and getting closer, I just thought you'd like to keep that in your back pocket the next time you're making your rounds in the psych-ward. (; Always, always, always, check those labs for a differential diagnosis such as this. Run an Ionized calcium, a serum CA, a Vit D 25-OH, PTH Int, all the T's (forget TSH- it's meaningless most of the time - go by symptoms) and rerun that CA and Vit D once per week for a month. It should yield the truth. Porphyria also causes mental manifestations, but I have yet to meet anyone who knows anything about it, so I manage alone. As for inpatient, I will consider it, but I know enough about how it's done that I would only be comfortable in a private setting and do not know if that is possible financially. Inpatient would be too traumatizing for me. I am looking into intensive outpatient care if I can make that happen. I just want to function again, and right now I'm completely exhausted. Can I ask you this? I know...I KNOW without a doubt that I'm low on Dopamine, and I also suspect low Oxytocin. Have you ever treated a patient with Oxytocin or Ketamine for treatment resistant depression in order to help pull them out immediately?

Ok-sounds good. I split the 10mg into 1/2 this morning due to the nausea a full 10 caused yesterday. I'll slowly try to increase, but I'm still waking up crying each day and only calm down if I take an Ativan. Which I didn't have to do before on the Cymbalta. Should I aim for 10 or 20 as a therapeutic dose?
Regarding the confusion I've caused you about the parathyroid stuff (my apologies)....My ionized Ca has been high for 2 yrs now, BUT, my endo and my other two specialists disagree with one another. My last Ionized Cal came back at 5.6, but PTH was only "high/normal" according to the Endo. My Primary and Pain Mgnt Dr's want me to go to surgical for a referral b/c they disagree with the wait and see approach. Again, depression doesn't cause high calcium, am I right? And given the fact that I've been so non-responsive to all the psych meds over the past couple of years, leads me further to believe that it is a primary thyroid/parathyroid problem, with major depression being secondary. However, I was initially seeking your input on Bi-Polar 2 vs. PTSD and I got off-track, sorry....the criteria you described for a bi-polar (manic) episode was close, but not a perfect fit for me. I, once or twice, have had out of the blue episodes of extreme (for me) hyperactivity, needing much less if any sleep. Only lasting for a couple of days to a couple of weeks. One time, in my early twenties, when I first began taking medication, this happened to me. I snapped out of the depression quickly, and did great for about a 6-8 months I think, possibly a year, but always fell back into a deep depression (usually in the fall, and even while medicated). Some external factor always triggers it, and due to my PTSD, the months of Oct -Jan are terrible for me most years. So my track record with SSRI's is that I'll do great for a while, then slip into a depression, quit my job, relationship, not getting out of bed, whatever it may be, and end up back at the Dr. crying and switching meds again. The longest I ever went on the same medication was about 3 yrs (Celexa) and then took Effexor for another 3 yrs. But with both of them I had some depression that crept in. So, given that info, could it be that I've been hypomanic during those times that I thought I was just "doing well"? That's why I'm so concerned about staying on the Brintellix - it may just be another merry-go-round with the wrong medication due to the wrong diagnosis. I've had to think long and hard about my past, and be very objective and honest with myself about my behaviors and actions in order to think about it this way. Could this be possible? Bi-polar 2 vs. PTSD, or both?

Just sent all the same info + labs I gave to you, to an Endo on this board, and his opinion is: Hyperparathyroidism. So.....it seems to be a matter of opinion to most doctors rather than a cut and dry diagnosis. Very frustrating for a patient like myself who keeps getting worse with each passing day. Nonetheless, I appreciate very much your time and attention. Do you have any colleagues that you might refer me to in FL for counseling (particularly for PTSD)?