Options/ recommendations/ thoughts re TRD (treatment-resistant depression), especially concerning atypical and bipolar spectrum depression.     —Robert D. McMullen, MD   7/28/2019

         THE BIPOLAR SPECTRUM:   atypical depression and Bipolar II Disorder and their treatment.   Atypical Depression often ends up as TRD, sometimes because of the very things used to treat it: serotonin medications.  What is discussed below sometimes applies to typical depression as well.     [Bipolar I Disorder is also called Manic Depression—an  illness where patients sometimes are hospitalized for mania, an extreme high.   Bipolar II Disorder is completely different: the highs are mild or almost non-existent.  Atypical Depression and  Bipolar II Disorder overlap significantly in phenomenology.  The two diagnoses are on a spectrum and treatment is virtually the same.]

The entity we call atypical depression is not atypical since 1/3 to 1/2 of all depressions are “atypical”.    The brain does not read textbooks.  Even if the symptoms are not all classic for Atypical Depression, the depression could be “atypical” and/or in the bipolar spectrum.
These and symptoms do not have to be present now. If they ever occurred in past in depressions– when not particularly depressed–they count.  These symptoms differ significantly from classic depression :

#1:  Hypersomnia (oversleeping) rather than insomnia, sometimes 12 hours or more.

#2: Hyperphagia (overeating) and/or carbohydrate craving  {However, when the depression is especially severe, the appetite may plummet}. In all

#3:  Rejection sensitivity.  If you have a significant romantic disappointment  or loss of a job, you might y plunge into a severe depression, which may be long lasting.     Small perceived rejections also cause a significant shift in mood. If someone you trust and respect becomes a little angry at you about small mistake of theirs, it can easily ruin evening, as you in an ruminate about the situation.   Even if you know the patient well, you may have no idea that this rejection sensitivity exists – unless you ask him/her.

#4: Mood reacts significantly to events.   A good event significantly improves mood—and may even briefly lift him/her out of a major depression. Likewise, bad events cause very significant shifts in mood, more than in others.

#5: Mood is worse in the evening rather than in the morning.

Atypical Depression and  Bipolar II Disorder are close cousins and  overlap in phenomenology.  The two diagnoses are on a spectrum and treatment is similar. Bipolar I Disorder is also called Manic Depression—an  illness where patients have experienced mania, a severe high, which usually results in hospitalization.  Bipolar II Disorder is very different: the highs are mild or barely exist.  Though the highs may be dysfunctional and cause problems (but never hospitalization), sometimes make one more functional than average.   The overwhelming problem is usually chronic depression. .

Serotonin medications [SSRI’s—Prozac/ fluoxetine, Zoloft/ sertraline, Celexa/ citalopram, Effexor/ venlafaxine, Cymbalta/ duloxetine et al] sometimes work well for atypical depression.  Benefit, however, often usually poops out—if not in a few months, then years later.  When one then changes to another SSRI, invariable it does not work, or poops out after brief benefit. Thereafter, all other serotonin medications will not be effective.  The patient may be more depressed than ever.    Have these serotonin  medications caused the depression to become both more severe and more treatment resistant?

SSRI’S may have an immediate negative effect on atypical depression – agitating the patient, inducing anger, cycling them into a mild high and then crashing into depression, increasing suicidal ideation, and causing more depressive episodes in the next year than would have occurred if one had never taken the SSRI.

About 25 years ago, a memorable talk by Jay Amsterdam of Philadelphia had a major impact on me.  He  said we may be misunderstanding what is occurring with patients with TRD (treatment resistant depression). Psychiatrists assume a patient has failed many antidepressants because the TRD is so severe.   He proposed it may be the other way around:  taking  so many different antidepressants  made the patient’s illness more and more treatment resistant.     He seems to have proven this in a recent paper:  Jay D Amsterdam,  Stepwise loss of antidepressant effectiveness with repeated antidepressant trials in bipolar II depression,   Bipolar Disorders, 8 July 2016 [Bipolar II Disorder and atypical depression are close cousins–RDM ]. 

 

Treatment

TMS usually works better then antidepressants. Patients and doctors use it, unfortunately, mainly as a last resort. Nonetheless with TRD patients we have 1/3 euthymia rate in 30 treatments over 6 weeks.  1/3 have zero benefit.  1/3 have significant benefit—usually their graphs are still improving and often extending treatments to 40, 50 or more will bring them to euthymia.

            Lamictal/ lamotrigine and low dose lithium may be the ideal combination to treat atypical depression— or at least for prophylactic/maintenance treatment when the patient reaches euthymia.    This proposition is laid out in detail in an excellent book,   A Spectrum Approach to Mood Disorders: Not Fully Bipolar but Not Unipolar–Practical Management, by James Phelps.  He has been  a clinician for over 30 years, primarily seeing patients. It is a more interesting book than the academics write.  He is university connected, knows the major people in psychiatry, and  the book is well referenced. He says that for  atypical depression the ideal goal should be to have them on Lamictal/lamotrigine and very low dose lithium. Even if they do not work, stay on them long term. There is no downside.  I have had a couple of patients who clearly benefited after over a year of being on lithium 150mg.

Both work, don’t poop out and have virtually no side effects.  I have used Lamictal/ lamotrigine on about ~1200 patients since 1996 because of minimal side effects and efficacy.   No blood tests are necessary on low dose lithium.   . Research decades ago, proved lithium 900 mg worked well for augmentation in depression. Recently we began to realize that low dose lithium often works well for depression– between 150 mg and 600mg. We certainly never imagined lithium 150mg would help. In the last three – four years, 62 of my patients had dramatic and lasting benefit within two weeks of starting 150 mg.

Many interventions may be necessary to stabilize the mood disorder and bring the patient out an episode. But one can still have a goal of using Lamictal/ lamotrigine and lithium along eventually.

Standard antidepressants may be necessary when depression is very severe and/or not responding to lamotrigine, lithium, et al.

The least safe antidepressants for Atypical Depression are in descending order:  tricyclics > dual action SNRI’s (Effexor/ venlafaxine; Cymbalta/ duloxetine) > SSRI’s (Prozac, Zoloft, and many others).

The safest standard antidepressants to use for atypical depression or Bipolar II Disorder are:

#1: Wellbutrin/ bupropion 

#2: TMS (Transcranial Magnetic Stimulation).  This is more likely than an antidepressant to bring the patient to complete euthymia.  I have patients who I have treated for 1-2 decades, who were never quite 100%, though they responded well to antidepressants.  I am thinking of two in particular—one I had treated 22 years, the other 15 years. When they finally had their first severe MDD, we did TMS.  They became completely euthymic for the first time in their life, and their functioning increased dramatically.  Until they were euthymic, neither they nor I was aware of how much their chronic mild depression interfered with their life.

The benefit of TMS is durable, assuming the patient should stay on effective maintenance medication.  For year prior to the Phelps book,  I noted that lamotrigine and lithium are often ideal  maintenance after TMS.  For a relapse,  5-6 treatments are usually enough to restore euthymia.   Another course of 30 treatments is not necessary.

#3: MAOI (monoamine oxidase inhibitor), medication where one must be on a special diet—especially avoid aged cheese lest a large dose of it cause a hypertensive crisis.  Emsam/ selegiline , Parnate/ tranylcypromine , Nardil/ phenelzine , and moclobemide [not in U.S.; easily obtainable from Canada; a reversible MAOI, so following  a special diet is unnecessary]

#4:  atypical antipsychotics frequently help, usually at low doses.  I myself probably underuse them.

THOUGH NOT FDA APPROVED FOR  DEPRESSION, STIMULANTS WORK WELL WITH LITTLE SIDE EFFECTS

#5 Stimulants:  Adderall (amphetamine salts), dextroamphetamine, Ritalin/ methylphenidate, Vyvanse et al.   These are not officially approved for depression.   They are safer to use than serotonin medications or tricyclics.

#6:  Depakote/ divalproate is one of a number of things which works well for bipolar spectrum depression –slowly and steadily. Since 1980, a number of my patients did excellent on Depakote alone [often 500mg] for  1-2 decades or more.

Psychiatrists think of  its excellent benefit in high doses for mania.   As maintenance treatment, research shows that Depakote is better at preventing depression than preventing highs.    Also, it is not widely appreciated how well it works [often slowly] for depression, so is rarely used.  When I started using Lamictal/ lamotrigine extensively in 1996,  I began to use much less Depakote.   However, Depakote often works as well or better—especially  when there are mixed state symptoms—e.g., anger and irritability.  Depakote seems to be superior to the Lamictal/ lamotrigine when treating significant Bipolar II depression.  Lamictal/ lamotrigine is often useless in Bipolar I Disorder.  Patients frequently want lamotrigine instead of Depakote because they have heard about weight gain and hair loss—side effects of which are uncommon at 500 mg. If possible, I go very gradually – 125 mg for at least a week.

For atypical depressions the most powerful antidepressant  is an MAOI (monoamine oxidase inhibitor), which I have not been prescribing often enough recently.   MAOI’s work  well for all depressions. Psychiatrists  avoid using them because if one eats the wrong food– particularly a lot of aged cheese– the blood pressure goes up very high for a few hours, which is  dangerous. I’ve given an MAOI to well over a 100 patients.   Only two patients had a blood pressure incident–both with no harm.    There is now a safer MAO inhibitor called Emsam/ selegiline/ selegiline which comes as a patch.  With the 6mg patch,  one does not  have to follow the diet all. On the full dose, 12mg, you should follow the MAOI diet, but the risk is probably far lower than with other MAOI’s. [Emsam/ selegiline has  a selective inhibitory action on the MAO enzyme in the brain, MAO-B—but not on the MAO-A enzyme in the liver.   High blood pressure is precipitated when the liver cannot metabolize the tyramine from decayed foods. ]

Michael Liebowitz, MD proved MAOI’s work particularly well for social anxiety–and Atypical Depression.

 

 

More treatment options:

IT IS IMPORTANT TO OBTAIN  THE FOLLOWING LAB TESTS:    Fasting not necessary. Send copy to patient:  Comprehensive metabolic panel,  thyroid profile (&TSH),  CBC, Lipids, hsCRP, B12,  homocysteine, vit D 25-OH,  ferritin, and MTHFR gene [The MTHFR test can help with depression treatment.  It can indicate a woman should take L-methylfolate/5-MTHF for pregnancy instead of folic acid to prevent 2 defects.   Don’t pay for it unless you can afford it or unless I say it is critical.  It may cost $150 to $600.  Insurance rarely pays for it. Medicare will not pay.  Medicaid will.].

Also do blood levels of certain medications  if taken:   e.g., Lamictal/ lamotrigine, lithium, Tegretol/ carbamazepine  Depakote/ divalproate, Clozaril/ clozapine.

REASONS FOR THESE LABORATORY  TESTS:

  • TSH: if the TSH (thyroid stimulating hormone)  is >2.5,  the patient is a little hypothyroid and this predicts that adding thyroid hormone [usually Cytomel (liothyronine/T3) 25mcg] will help the depression.
  • cholesterol profile/ lipids: statins for cholesterol help depression.  The best for depression is a high dose of a potent lipid soluble statin—e.g., Lipitor/ atorvastatin 40 to 80mg.
  • hsCRP (highly sensitive C-reactive protein, a measure of inflammation in the body): the CRP should be <1.0.  High levels of inflammation cause more depression.  There are many  ways of decreasing it—the most effective being high dose fish oil [10 – 20 pills per day] or a statin.

If the hsCRP is very high—even >3.0, it pays to do other tests for inflammation and autoimmunity: ANA,   Pr IL-1, IL-6, IL-18,    TNF-alpha.     Infrequently, extremely high inflammation in the brain is causing the disorder.  Two of my patients  are receiving intermittent intravenous immunoglobulins for severe depression, with impressive benefit.   One claims she would be dead if I had not sent her to a neurologist specializing in this [I noted her high CRP, as well as the extreme depression, which was totally treatment resistant].  She had been intensely suicidal with a few serious  attempts.         

  • Vitamin B12.   Many people who are in the low normal range are in a range that is too low for them. This low level may cause them neuropsychiatric symptoms including depression.
  • Vitamin D 25-OH. Low levels of this steroid hormone contribute to depression.   Unless taking vitamin D, everyone in the developed world is low in the steroid hormone. We make it in about five steps and one step involves ultraviolet B light from the sun the skin and convert pre-vitamin D to vitamin D3, which is the form of vitamin we take orally and is sold in every pharmacy.  The level should be approximately 70 ng/mL. To obtain this level, a 125-pound person should take about 5000 I.U.’s per day, a 175-pound person should take 7000 I.U.’s per day and a to 25-pound person should take approximately 10,000 I.U.’s per day. It is usually easier to take 50,000 I.U. pills: three pills per month, four pills per month, and  6 pills per month respectively.
  • Ferritin: When iron is low, or low normal, it can result in significant depression. It is frequently low in menstruating women since  they lose iron every month with their menstrual period.   Men recycle the iron from their red blood cells.
  • MTHFR gene (methylene tetrahydrofolate reductase gene).   About one in five people are homozygous for the C677T gene.  This predicts that  the active folate vitamin [instead of folic acid]  will help their depression.   The dose for depression is 15 mg per day of L-methylfolate, not less. For general health, about 2 mg per day may be sufficient—or one pill of 15 mg once a week. Women who are homozygous for C677T cannot make use of folic acid.   Folic acid is not naturally found in our body or in food. Vitamin companies put folic acid in multivitamins because: #1 folic acid is inexpensive to manufacture;  #2: most of us can gradually convert folic acid to the active folate vitamin, L-methylfolate.

L-methylfolate/5-MTHF can help depression in people who have no anomalous MTHFR (methylene tetrahydrofolate reductase) genes—especially homozygosity C677T.

During pregnancy women with anomalous MTHFR genes  should take L-methylfolate instead of folic acid to prevent neural tube defects in the fetus.

  • TMS (TRANSCRANIAL MAGNETIC STIMULATION) has a very high chance of helping. It is as effective as ECT, except where the depression is psychotic/delusional. In that case, ECT works extremely well. I have only treated one patient with delusional depression, and he did quite well. After 50 treatments this 58-year-old man became euthymic for the first time in his life and remained that way for 3.5 years. With that relapse, things became complicated in getting him to euthymia. But 9  years after the first course of TMS he is retired and has been quite euthymic for a couple of years.
    • Double-blind studies of using TMS for treatment resistant depression (30 treatments over 6 weeks, 5 days per week) consistently show:

#1:  one third go into remission with #30 treatments,  many achieving  euthymia (a normal mood) for the first time in their life. ,

#2:  one third of patients have zero response.

#3:  one third significantly improve, but not to consistent euthymia.  Their scales continue to improve.  The studies abruptly stop after 30 treatments.  A large number of them would reach a normal mood if they were to continue TMS.  And/or it may be necessary to try a different type of TMS machine and/or different parameters  (placement of the coils; types of pulses).    In our first 75 patients, 50% of them went into remission, some requiring ~50 sessions. Another 10% were clearly on their way to remission, with a steep curve of improvement, but stopped treatment after, say, 15 treatments.   They insisted that they were satisfied with being back to their baseline. If they had continued there would’ve been a 60% remission rate. It would be even higher if all of those who had partial responses could have continued much longer.  I have had a number of patients who became euthymic only after a great many treatments – to add about 75 treatments and one at about 300 treatments.  Sometimes they were being treated in more than one place per session, so some would argue that they perceived even more treatments.

  • TMS works even if ECT has failed. We have had quite a few patients who failed on ECT but did well on TMS.  This is not surprising since it is a completely different modality with different reasons for effectiveness.  Also, there are many parameters to try, as well as to quite different machines. Some respond better to one parameter than to others.  Even if one has had no response at all to one type of TMS treatment, seems to have been building up.  When one changes to different parameters, one is not starting out with treatment number one. We had a seriously suicidal 40-year-old therapist who had been suffering for a prolonged time, especially in the previous year. He had no response at all to 40 treatments. We told him to take a two-week break until a new, different machine arrived. After one or two treatments with the new machine, he became completely euthymic. Such a quick response virtually never occurs, so the previous treatments contributed. A quick response is reaching euthymia and 10 to 15 treatments.  There was one more factor. In the two weeks after the conclusion of #40 treatments, his MADRS declined from 40 to 20.  He had a delayed response to the TMS, which is not uncommon.
  • If one parameter [position & type of pulse] of TMS does not work, try another.  There are two main types of machines—the figure 8 machine and Brainsway dTMS (deep TMS).  The first is focal, the 2nd covers the whole left hemisphere and part of the right, penetrating 6 to 7 cm instead of 2-3 cm.  We  have two quite different Brainsway  helmets for depression [H7 and H1].  When one fails to work, we change to the other.  With the figure-8 machine [ours is a Magpro X100 from Magventure with a double cone B80 coil], there are many possible parameters.
  • TMS side effects are minimal. The benefit is durable.   After each treatment, one goes to work or school as usual. When there is a relapse, usually only five or six treatments are sufficient to regain euthymia.
  • VERY HIGH DOSE THYROID [HDT]see dramatic example at bottom. This is a major revolution in psychiatry, I believe  (comparable to Prozac, Lamictal, atypical antipsychotics, and TMS). If it is true that a very high proportion of TRD  patients are hypothyroid in the brain, then this treatment is going to transform many lives.   Using high dose thyroid for depression is a long story which I have been following for almost 30 years.  I used it years ago with dramatic success in a few patients, but never used it frequently because it was seen as such a radical treatment and certainly wasn’t a commonly used treatment.  I can remember four dramatic remissions with HDT in patients who were severely treatment resistant.

The thyroid molecule is large and therefore it is difficult for it to cross the blood brain barrier.  Transthyretin takes it across the blood brain barrier.  A 1999 study by  Jack Gorman et al demonstrated that transthyretin  is quite low in many people with major depression.  The only way to correct this problem is to give people very high doses of thyroid hormone, so that some of it will spill over into the brain. One increases the dose slowly, making sure the resting pulse stays below 100.  A 2018 book by Tammas Kelly, MD gives a detailed description of how to use this treatment and gives the references to the  significant research, especially for the last decade.   This book will help bring this treatment into the mainstream.

NUTRITIONAL and environmental:—[note:  all these are PROVEN  with double blind studies to help depression; I have many patients doing well for years on one of these. They get immediately depressed if they stop it.  In my experience it works better if someone is having at least some benefit from other agents for depression]:

  • A FAT: fish oil pills:  6-10 per day; or even, for a week, try 20 pills/day—I have one man who has been on 18 pills since 1999 and he is mildly depressed if we reduce it.  . If you eat a big salmon steak or tuna steak, it is like taking 4-5 pills. It is inconvenient to eat that much fish.  Only fish fat has an antidepressant effect, so the pills are more convenient. If you spread the pills to five pills twice a day or five pills three times a day it is easier psychologically to take them.  If you use Omegavia, then 10-12 pills are probably enough.  Omegavia is a small 500mg/pill with 500mg of EPA in it.  3 to 4 pills may be enough for depression   It is a smaller capsule, but with more EPA—which is the only fat that helps depression.
  • AN AMINO ACID: NAC (N-acetyl cysteine) — 4 grams per day of caplets or capsules.  Caplets/ tablets may be better than capsules?  Avoid powder, as NAC is rapidly oxidized by oxygen and becomes useless. I have two men and one woman who took 4 g three times a day with great success.
  • A SUGAR FROM FRUIT: inositol 3 to 4 rounded teaspoons twice a day , aim for 20mg grams /day = about 3 teaspoons twice a day,   then you could increase to 20 grams a day which is equal to 10 g twice a day
  • I. BACTERIA: 1-2 probiotics per day— two per day is  better;  Half of probiotics on the shelf have no viable bacteria in them.   Therefore, buy  4 brands, mix all the pills in a bowl, and  pick out any 2 pills per day.  There is  only a 6% chance that you are taking nothing that is active.   If you buy just 2 brands, you have a 25% chance you are taking nothing active,

Probiotics.  This includes VSL 3  is a refrigerated probiotic available in pharmacies.  It  does not need a prescription.   It supposedly  always has  viable bacteria.  If the pharmacist does not have it in stock, he can obtain it.  It is said that probiotics purchased on the internet are fresher and more likely to be viable.  Refrigerate them when you receive them.  Yogurt also helps, especially if it has acidophilus.  50% of probiotics bought off-the-shelf have nothing viable in them.

There was  a randomized controlled study showing that taking a probiotic after a manic episode greatly reduces the risk of subsequent depression and mixed states.   Bacteria release chemicals that easily pass through the colon, reach the brain and can  affect how we feel.    Apparently  increasing the “good” bacteria in the intestine helps crowd out the “bad” bacteria.  The bacteriologists who study the G.I. call the good bacteria “old friends”, because these bacteria were predominant when we were hunter gatherers. Some come from stagnant water and fermenting fruit. We say humans began 2.5 million years ago because that is when the size of the brain became disproportionately large compared to other primates.   We have been horticulturists [and/or herders] for some 10,000 years.  If we were hunter gatherers for four hours, then it is in last second  that we have taken up agriculture and animal husbandry.

  • L-methylfolate/5-MTHF 15mg per day– this is the active folate vitamin. Folic acid is not found in the body or in food. The vitamin companies make it because it is cheap and most of us can convert it to the active L-methylfolate.
  • SAM-E: 200mg twice a day; maximum is 800mg/day;  more effective with folic acid and B12– e.g.,  folic acid  1600mcg/day [or L-methylfolate/5-MTHF ≥ 2mg]  and vitamin B12 500mcg/day  HOW TO TAKE IT:  Do not take it near a meal: it is poorly absorbed with food.    Use an enteric-coated product—it is  better absorbed in small intestine than in stomach.   Use from a blister pack– it oxidizes easily, must be protected from the light.  .
  • B 12 pill: one per day — more likely to work if B12 level is low or low normal.
  • DHEA 25mg/day – it is preferable to get a DHEAS level first– if the level is very low, one might be more aggressive with this. I have only had a couple of significant successes with this, long ago.
  • lithium 150mg: one per day—one can call this nutritional because it is such a low dose.   It is a basic element.  There are no side effects or monitoring at this dose. In areas of the world where there is a lot of lithium in the drinking water, there are better health outcomes, including fewer suicides and much less Alzheimer’s.   59 of my patients had a significant antidepressant effect in ≤ 2 weeks in the last four years.  In others it may help only after many months.  Higher doses sometimes work better, but very high doses have no benefit for depression.   It is extremely good for the brain and one should stand in three years, even if it does not seem to be helping now.
  • Very low dose naltrexone – a medication, a narcotic receptor blocker.
  • Negative ionizer ~250 at cet.org. Michael Terman’s Center for Environmental Therapeutics, more or less a non-profit,  
  • Light box and/or dawn simulator, especially in people who have hypersomnia; also available at  cet.org;  light box is more effective—and in a week if done religiously and early in the morning.
  • SOUND is an antidepressant. Don’t be in home with no sound. Always have music or TV on, at least to 65 decibels—about same as in normal conversation.  It is probably the other way around. Silence causes depression. In our 2.5 million years, no one lived alone in an apartment. No one had a room by himself.   There was constant sound: conversation, babies crying, children playing, people hammering food to make it edible, and people striking stone against on to make tools and arrowheads.
  • Socializehumans need humans. Until recently no one ever lived alone except in  Grimm’s Fairy tales, where a few witches each lived alone in the middle of the forest.  Living alone in a silent apartment is aberrant from our genetic makeup.   
  • Exercise 5 hours of vigorous exercise per week works as well as Prozac/ fluoxetine. 3 hours is minimum for some antidepressant effect.  If the exercise is not vigorous (e.g., walking, it should be more).

 

Example: impressive response to HDT (high dose thyroid)—Cytomel (liothyronine/T3) 125mcg

For 20 years I have been treating—mainly unsuccessfully–this severely ill 61 y.o. man who suffers multiple severe problems, especially rapid cycling Bipolar I Disorder. 

For over 6 months, since Cytomel (liothyronine/T3) was increased to 125mcg, he has been close to euthymia, no mood cycling, no sleeping in the day, and has been productive (he is a talented amateur historian and writes poetry). 

He is a former policeman who retired a few years early b/o back injury. He became a lawyer, but eventually had to cease work because of these disorders.  We only achieved some amelioration of the problems with medication, TMS, et al.  The lithium and Xyrem have been the most useful—now Cytomel (liothyronine/T3) is hitting the ball out of the ballpark.

His Problem list

  • Bipolar I Disorder, rapid cycling
  • OCD (Obsessive-Compulsive Disorder), severe. An SSRI helped but exacerbated the bipolar disorder.
  • Severe Panic Disorder, with severe agoraphobia
  • Social Phobia, severe, generalized contributing to the agoraphobia.  He is a muscular man [who works out with weights], was a policeman for many years and regularly rides a motorcycle.  But he cannot possibly go to NYC  by himself—by car or train.

MEDICAL:

  • Sleep apnea, severe. Extensive surgery was of no benefit.   His snoring ceased, but sleep apneas persist unchanged.
  • EDS (Excessive Daytime Sleepiness) secondary to Sleep Apnea, depression and borderline narcolepsy
  • Borderline NARCOLEPSY: –Xyrem (sodium oxybate)  is of excellent benefit for his years of miserable insomnia.
  • High uric acid—allopurinol was of no benefit for bipolar disorder, and maybe was a negative. In my experience, allopurinol is often excellent for mania.
  • Neurological hives with dermatographia, exacerbated by sweating;   alternates between feeling too hot or too cold;  an autoimmune disorder; excellent benefit from doxepin

Medication: Severe tremor on lithium 900mg, but he immediately goes into mixed state if we decrease it.    ——–7/28/2019–R. McMullen, MD