[7/31/2014:  all 5 of these patients had never been euthymic prior to TMS, and as of now, all of them have been euthymic and with no relapses for over 2 years.  After years of only partial success with medication in someone who has never been euthymic, what are the odds the next medication will make them completely euthymic?  Who would think that these 5 patients would remain euthymic for over 2 years after TMS?   They are on some medication, which is necessary for maintenance, but now it works 100%.]

For cases #1, #3, and #4,  it took more treatments (about 50) than usual to anchor them in euthymia    For my own edification I reviewed their charts to establish the timeline, etc. The results, however, are quite representative.  None of them had ever been euthymic prior to TMS.  Now all have been euthymic 1 to 1½ years after their last “touch up” TMS   treatment.  Also, look at the daughter of patient #1 in the addendum at the bottom of his description. Case #4 is a rapid cycling Bipolar II patient who had 28 treatments and has stayed euthymic for over a year.

Three cases are to some degree bipolar. case #1 is bipolar spectrum [maybe actually bipolar I as he once had a long paranoid psychotic episode].  Case # is bipolar II, but the hypomanias were brief and were not destructive.  Case #5, the most dramatic case, had  severe rapid cycling Bipolar II Disorder from age 12 to her treatment  at22.

[In large part, I bought my first TMS machine for the first man described below.  He had no other hope.    He and his wife would not consider ECT.   They were very discouraged because of the lack of response, the high doses of multiple medications, and all the money and time they had spent seeing psychiatrists without appreciable benefit.  I had treated him 1½ years with enormous doses of medications.  It was inconceivable that I would be able to induce them to go across town to a strange psychiatrist, undergo daily treatment with an weird new magnetic treatment, and pay $10,000 for the privilege.  So I bought a TMS machine and told them I would treat him for free—or what I might get from insurance.]  

 

Case #1:Mr H:  This married 58 y.o. senior engineer,  the father of 5 children,  suffered from lifelong depression with significant associated anxiety and obsessive compulsive symptoms.   He had done reasonably well for some 20 years on Parnate, treated by a psychiatrist who is one of the best (Joel Hoffman).  In early 2008 he had a few weeks of paranoia.  Significant fluctuating depression then gradually worsened, until he was in a severe agitated depression.   He was filled with irrational guilt, unable to function at work, and was in danger of losing his job.  He called his psychiatrist several times a day.   He has never had hypomania, but I believe he is bipolar spectrum.

When his depression proved extremely treatment resistant, his psychopharmacologist eventually thought someone else should go to bat and sent him to me.  [When the patient had stopped responding to Parnate, Dr H tried other agents.  Eventually he re-challenged with Parnate–with no response.]  Then I spent 1½ years trying medication combinations in high doses with virtually no benefit.  He had a dramatic partial response for a few months when inositol [a sugar that is involved in a positive cascade within neurons] was added, but lost it. He was so dysfunctional we could not understand why he was not yet fired.  He was shaking all over.  He could not see clients. He often called me in the morning as he was too frightened to enter his office building.  He locked himself in his office and did nothing.

From 10/6/2010 to 11/17/2010, we did 30 TMS treatments.  In those 6 weeks, his 21-item-Ham-D  dramatically went from 45 to 4. His PHQ-9 went from 24 to 2.  His GAD went from 6 to 1.    He became a cheerful and animated and again became a very suave dresser and a competent senior engineer.  On reflection, he thinks he was never completely euthymic prior to TMS.  Medication had brought him close to normal, but he had always been excessively anxious and, at best, dysthymic.

2.5 months after treatment #30, he began having little relapses.   For the next 9 months, from 2/1/11 to 11/15/11, he had another 20 treatments (1 to 3 treatments here and there) for little relapses.  We then planned one treatment per month as prophylaxis.   He was euthymic at the last 2 treatments, which were a month apart and the beginning of the prophylaxis plan.  But he stopped the prophylaxis, and has stayed completely euthymic for ever since.  [I first wrote this case up 15 months after the last TMS.]

Summary:  His 50 treatments extended from 10/6/10 to 11/15/11.   He became euthymic after 30 treatments in the first 6 weeks.   2½ months later be began having  sudden little relapses and had 20 additional treatments over the next 9 months.   After that he stayed euthymic with no further TMS.  [There was a samll relapse.  A month after treatment #50, he slipped to MADRS 18.   His TSH was 4.95.  I elected not to give him TMS.  Thyroid hormone T3 (Cytomel) 25mcg was added and the depression quickly remitted.]

            On the next two visits, 6/12/2012 and 11/6/2012, he was completely euthymic— cheerful, smiling, and with a new joke for every visit.  He no longer had the overvalued idea/ delusion that he had not learned any work skills in 5 years.   With a wink, he says, “I may not know everything about my profession, but I know enough to check on the work of the people under me.”

He thinks he has never felt this good, this normal.   He was always plagued with dysthymia, anxiety and some obsessive compulsive symptoms.   He had no severe depression in his 20’s, but he was extremely anxious and was probably at least dysthymic.

The last TMS treatment was 11/15/11. .

Addendum re tremor:  Interestingly, he had such severe tremor and shaking that he could not hold a cup of water when I gave it to him—it flew out of his hand.  It was a nightmare for him to say kaddish, especially when he married off a son. With TMS, his shaking stopped and the tremor became minimal!! — though he was on the same medication.   I had thought his tremor was secondary to medication, but apparently it was part of his agitated depression.

RELAPSE:  4/23/15—3 YEARS, 5 months after last treatment he had ~2 weeks of mild to moderate depression and anxiety, and one treatment seemed to be enough.    

 

CASE #2  the 22 y.o. daughter of the above patient  : (She received bilateral Tx.) When I last saw her, I asked about her father.  She said he is a completely different man since TMS—she had never previously seen her father normal.  He had always been anxious and depression.  He has become very active in his synagogue, has many friends, and is quite happy.  I asked her if TMS had made any difference in her.  She said “completely!”   She had never been euthymic prior to TMS, and now she is– though still tortured by OCD intrusive thoughts.   Her MADRS was 31  initially.  She was euthymic after 20 treatments–MADRS  <6.  .  We did another 17 treatments in an unsuccessful effort to diminish her OCD, which was her chief complaint

“It has transformed my life.”     I had not been aware of how pernicious her depression had been, as I met her shortly before the TMS—which she wanted for OCD. I thought I had just happened to treat her when she was in worse depression than usual—but it was her usual state.

11/13/2014:   Exactly three years and one month after her last TMS treatment, she has gone into a mild relapse of depression  in the last week.   We are giving her some touchup treatments, and will try to treat her OCD with a Brainsway  H7 helmet/coil designed for OCD, and we will do R Magpro X100 cTBS for her depression.

 

This was another “difficult” case because it took so many treatments to get to a point where she stayed euthymic without continual maintenance treatments:

Case #3:    Ms C.:  29 y.o.  single woman guidance counselor and French teacher. # 52 Tx’s total; she had #51  from 3/16/11 to    7/26/2011;    3+ months later she had a moderate relapse  that remitted with one treatment on 11/2/11, and no relapse until 3 years and one month later.

I first treated her at 14 y.o. for panic disorder [she was also definitely dysthymic], and have seen her intermittently since for chronic depression.   She is Bipolar II, but the highs are very minor, brief, and infrequent.  The bipolarity is no doubt the reason medications did not work. Antidepressants would help initially and then poop out.  We have used only mood stabilizers, but with only partial benefit.

            Because of a severe MDD (Major Depressive Disorder) with serious suicidal ideation, I started TMS as an emergency late at night on 3/16/11.  Her mother, an MSW therapist who I have known for 30 years, came with her.   The patient was in despair because, in addition to the MDD, she had no romantic relationship, no job and her career was at a standstill.   She was also tired of struggling with “double depression.”   She was at best dysthymic when not in an [infrequent] MDD.

As TMS treatments progressed, she would become euthymic for a while, and then have a severe relapse.  Towards the end I was doing maintenance treatments 2-3x/wk to keep her from being suicidal.  I worried she would need twice a week treatment indefinitely.   She had a total of 50 treatments over  3.5 months [instead of the usual 30 treatments in 1.5 months].   She had two relapses—one was 3 weeks out (7/5/2011), and the other was 4 months out (1/2/11).  Each needed only one TMS treatment for remission. [For these two treatments I started to use the Beam method to find F4, which put the place of treatment 1-2 cm anterior to where we had treated previously per the Neurostar protocol.  This may have made it more effective, as I was surprised she completely recovered with one treatment.]  So there was a total of 52 treatments spread out over 7.5 months.

Her mother is a social worker therapist who I have known well since before the young lady was born.   Six months after her recovery,  playing devil’s advocate,  I said, “Mary, tell me, what is really different about her since the TMS?”    “Robert, you have to be kidding!  She was depressed all her life– and now she normal.”   The patient said  essentially the same.   Even when things were good—e.g., when she had a good job in France, a good circle of friends and a nice boyfriend [still friends, but the romance is over]–she was always, at best, dysthymic.

TMS completely changed the course of her illness–a common outcome with TMS, in my experience.

She had a mild relapse a little over 3 years later and 5 treatments put her in remission again.

 

Case #4    62 y.o. physician with chronic lifelong depression, no doubt secondary to his extremely traumatic childhood.

MADRS 30 initially, which seems to have been his lifelong base line.

MADRS 25  at 15 treatments—not a great improvement for being half way to 30 treatments, but he felt he was definitely on a new plane.

MADRS 15 at 30 treatments.  A significant improvement, but no cigar.  We did an additional 12 treatments:

MADRS 6  at 42 treatments—the equivalent of 8½ week of treatment stretched out over 3.5 months b/o scheduling problems

He subsequently had 4 maintenance treatments for dips into depression in the next 4 months= total of 46 treatments.     In summary, he had a total of 46 treatments over a 7.5 months period.  As of 1 year after the last touch up treatment he was euthymic.

 

Case #5,  a 22 y.o. woman with rapid cycling bipolar II    #28 treatments from 3/28/12 to 5/21/12

Ms K, a 24 y.o. woman was a rapid cycling bipolar II who struggled in high school and college—until she had TMS at 22 y.o.  I had treated her from 16 to 22 y.o. with  mild to moderate success in controlling her depressions and panic attacks.  It was difficult for her to study or concentrate.  We  minimized stimulants for her ADD because of her bipolarity.  She couldn’t hold a part time job.

In the first 2 weeks of 2/2012, she was approximately euthymic—as good as she ever got.  Even when apparently euthymic, she did not function well in school.   With no apparent precipitant,  in the last 2 weeks of 2/2012, she gradually went into a severe mixed state,   including an increase in exercising and staying up until 2-4AM.  At the end of 2/2012, she was severely depressed during the day and hypomanic late at night, and had some brief hypomanic mixed state periods during the day.   During March she was continuously in severe major depression with no hypomania or mixed states.  She cycled only slightly between different degrees of depression.  She had significant passive suicidal ideation.  She had made her only suicide attempt 5 months before.  She was extremely demoralized. “Dr McMullen, how will I ever find a husband?   How will I ever have a career?”   At 22 y.o., she had not completed not a single college course—despite starting many.  Concentration was severely impaired by massive anxiety and depression (even if mild).  She was going to be a chronic mental patient, constantly juggling medications that partially worked, and having continual problems with romantic relationships and jobs.

I told her we must do TMS, and started the next day, 3/28/12.  The 1st treatment was bilateral TMS—excitatory on the left and inhibitory on the right.   That one treatment brought her out of severe depression and into an unpleasant high—although she was suddenly able to study.   Like any antidepressant, the standard TMS treatment for depression–left DLPFC (dorsolateral prefrontal cortex) excitatory treatment—can exacerbate cycling in bipolar disorder.   From then on we only did right DLPFC inhibitory treatment.

She achieved euthymia in a month, after 20 treatments. “MSE: amazingly normal;  she smiles easily, is not hyper-emotional.  She is very afraid of stopping the TMS as it has worked so well.    Analysis:  This has worked amazingly well.   I have never seen her this normal, especially for several days in a row.  We can try to taper her off now.”

We did 8 more treatments over the next 3 weeks—for a total of 28 treatments from 3/28/12 to 5/21/12.   Two months after the last treatment she relapsed into severe depression for a few days, which remitted spontaneously, with no additional TMS.

As of 9/2014, two 2 &1/3 years out, she remains completely euthymic, which she had not experienced in at least 9 years.  The depression, the cycling, and panic attacks ceased.   Her change in scores was dramatic:  CGI (clinical global impression)  5 → 1  [markedly ill →  normal].    MADRS (Montgomery-Asperg Depression Rating scale): 34 → 2;   PHQ-9 [a self-rating scale]:  20 → 4   [severe depression → euthymia].     

We had a long talk in 5/2014,  when she was in the 2nd semester of her 2nd  year of college and two years after the TMS.  She had not missed a single class in 2 years.  In the first year after TMS, she had a lot of anxiety (not panic attack anxiety) about whether she could study and whether she would relapse. She did well in college and decided to become a neonatal nurse.  Attending free lectures at the NY Academy of Medicine aroused an interest in science and medicine.   She disclosed to me that she was now taking physics, calculus and advanced biology, and was aiming higher than nursing school.   Advanced biology was by far the hardest course—with an immense amount to remember.   She was prepared and not stressed, and concentrated on biology for the finals.  A month later she let me know she made a 4.0.

 

ADDITIONAL INFORMATION ON CASE #5, NOT NECESSARY TO READ:

Payment was denied by the insurance company because a reviewer noted that in 6 years she had never taken an antidepressant—and so must be bipolar.   Though not FDA approved for bipolar depression, in my experience it works best for bipolar depression.  Depression and cycling both stopped.

Actually, she did receive an antidepressant—methylphenidate 30mg SR– for her ADD.   It DID seem to cycle her at times.  I highly doubt that avoiding it would have helped much.

She deserves a lot of credit for her recovery.  Things that make her moods temporarily unstable are alcohol, romantic disappointments and PMDD (Premenstrual Dysphoric Disorder).  She made some changes:

#1:.  She rarely has a drink of alcohol now.  A few weekend drinks used to be disastrous for her moods.

#2:  She largely eschews dating.

#3:   She carefully regulates her sleep wake cycle—and studying and exercising..

#4:   She avoids stimulants for her ADD, for fear they will cycle her.   She works at making studying interesting.  Advanced biology was often tedious, so she made it more interesting by looking up the derivations of the scientific terms. .

 A SUMMARY OF THE FACTS:   

DIAGNOSES:  [the first 3 diagnoses are virtually in remission the last 2 years, since TMS]

Ø  Bipolar II, rapid cyclingmainly depression, severely impairing her ability to study in high school and college.  We were never able to keep her mood disorder under control with medication.  She would have a few days of euthymia here and there, but never functioned well.    

Ø  PMDD (Premenstrual Dysphoric Disorder)  for 7-9 days/month  — better  

Ø  Panic Disorder with severe agoraphobia—frequently unable to leave apartment.  Even when the depression was very mild, anxiety impaired her functioning.   Massive free floating anxiety was common.

Ø  Attention Deficit Disorder  –she can overcome this when not depressed or anxious; she finds ways to make the subject more exciting.

Ø  PAST HISTORY: suicide attempt in 2011    mild, infrequent alcohol overuse      mild OCD diathesis    

 TMS Rx:   #28 from 3/28/12 to 5/21/12; 4000 Pulse on R DLPFC 1hz  (inhibitory) 100% of MT.

CHANGE with TMS:   CGI  5 → 1  MADRS: 34 → 2   PHQ-9:  20 → 4.  HAM-D  20 → 7.

MEDICATIONS  are minimal on 6/4/14:  CBZ Lamictal 200 Lithiumgabapentin 100 Estrovera patch        D3 50K I.U. /wk    lorazepam 0    Stimulants 0  b/o risk of mood swings.

MEDICATIONS 4 YEARS AGO WERE Depakote 1250   Lamictal 100 Lithium  300 bid—or more     Metadate 30mg AM  D3 50K  I.U./week      lorazepam 3mg HS

COMMENT:  It is difficult to exaggerate our astonishment over her the completeness of her recovery.   She was fortunate she happened to have one of the few psychiatrists who did TMS.