James Phelps, MD

Do you sometimes have trouble continuing your daily work under the shadow of looming climate change? Wonder about chucking your practice and working exclusively on ending our reliance on fossil fuels? Is someone who devotes his life to arresting climate change a fanatic-or maybe even manic? Let’s take a brief tour through climate science to the story of such a man who acquired such a diagnosis.

 asserts that science is not simply the result of following “the scientific method” of rigorous hypothesis testing. Rather, she believes that science is a process of arriving at a consensus, a current working understanding.

 This is why a physicist may accept the idea that a vaccine increases one’s safety even without being able to deeply evaluate the epidemiologic data, or a geologist accepts speciation by natural selection without examining all the relevant data: they rely on the consensus of scientists who specialize in epidemiology or evolution. Says Orestes, we can think of scientific knowledge as the result of “a jury of geeks.”

Science’s current working understanding of climate indicates that the earth is warming rapidly, sufficient to cause social disasters beyond anything humans have ever seen, during most of our patients’ current lifetimes. If you have any difficulty with this assertion, please do listen to Orestes’ TED talk on science first, then the 

 predicting climate-driven migration of 140 million people by 2050.

Watching humans destroy the very basis of their existence (a stable climate), one man thought “this is insane.” He could not understand how we could persist in our current behaviors. He thought a global awakening to our collective insanity was emergently needed. So he dedicated his life to helping people recognize and respond to the problem of climate change. The result: he was diagnosed as bipolar and given lithium.

Was this man fanatic, or manic? What is the difference? The literature on this question is surprisingly small: there are no references on Pub Med for a search of fanatic manic, or fanatic bipolar, for example. A more substantial work has examined the boundary of religious and delusional beliefs (some of it 

). A lengthy user post and replies on the International Bipolar Foundation (IBPF) website includes many 

 of manic phases and intensified religious thinking.6 Indeed the term “fanatic” has a strong connection etymologically to religion (from fanum, a holy place, sanctuary or temple; and the verb fano, to devote).

But not all fanaticism is religious. Perhaps fanaticism itself is a disease, like alcoholism: a Psychology Today 

 suggests there should be a Fanatics Anonymous.

 Or perhaps fanaticism is like a brain infection, a la the 

 that can infect an ant’s brain and make it climb up a blade of grass where it is more likely to be eaten by the cow that is the parasite’s next life-cycle port of call.

 Perhaps fanaticism is a neurologic problem: combat injury to the frontal cortex is associated with fundamentalist beliefs, according to 

Whatever the etiology, some fanaticism comes very close to the behaviors of bipolar mania: energized devotion to an idea. Sex and money are frequent foci, but also political ideas: see, for example, the complex patterns of bipolar-like behaviors in world leaders, examined by Nassir Ghaemi in his book 

 In this territory of highly uncertain boundaries between passion and determination and mental illness lies the story of the man who had a diagnosis of bipolar mania based on his insistence that humankind itself is insane for continuing to mine and burn fossil fuels. It’s an interesting twist, no?

You must see the documentary of this man, 

. It is a fascinating tour through fanaticism and its consequences, including bipolar diagnosis (in this case, likely over-diagnosis). It’s a polished production, easy to watch, with a message of the utmost importance: that we ourselves are indeed acting insanely and must quickly recognize our own collective “mental illness” with radical behavior change.

Dr Phelps is the Bipolar Disorder Section Editor for 

 to share your views. We might include your letter at the end of this article, possibly with a response from the author. Please include your full name, title, and affiliation for consideration.

This article was originally published on 10/15/18 and has since been updated.

Dr Phelps stopped accepting honoraria from pharmaceutical companies in 2008 but receives honoraria from McGraw-Hill and W.W. Norton & Co. for his books, including 

, which he coauthored with Chris Aiken, MD.

 Department of the History of Science, Harvard University. 

https://histsci.fas.harvard.edu/people/naomi-oreskes

https://www.ted.com/talks/naomi_oreskes_why_we_should_believe_in_science

 World Bank. Climate Change Could Force Over 140 Million to Migrate Within Countries by 2050. 

https://www.worldbank.org/en/news/press-release/2018/03/19/climate-change-could-force-over-140-million-to-migrate-within-countries-by-2050-world-bank-report

https://www.thereluctantradicalmovie.com/

 Iyassu R, Jolley S, Bebbington P, et al. Psychological characteristics of religious delusions. 

 Jost B. Mania and “Hyper-Religiousity.” International Bipolar Foundation. 

http://ibpf.org/blog/mania-and-%E2%80%9Chyper-religiosity%E2%80%9D

 Sherman JE. Fanaticism Is a Disease Like Alcoholism. 

https://www.psychologytoday.com/us/blog/ambigamy/201411/fanaticism-is-disease-alcoholism

https://www.damninteresting.com/a-fluke-of-nature/

 Zhong W, Cristofori I, Bulbulia J, et al. Biological and cognitive underpinnings of religious fundamentalism. 

A First-Rate Madness: Uncovering the Links Between Leadership and Mental Illness

Articles

Whatever the etiology, some extreme views come very close to the behaviors of bipolar mania, as illustrated in a recent documentary.

Bipolar Disorder or Fanaticism?

 bipolar disorder is hard work. In the hopes of maintaining your enthusiasm and determination, let us look at two major trends in our evolving understanding of this complex mood disorder and its treatment, to wrap up 2018 and to consider the year ahead.

Imagine having or treating Type 1 diabetes before pancreatic insulin deficiency was understood, and the excitement that would accompany the discovery of that mechanism. While we are not on the verge of such a discovery in bipolar disorder, at least six seemingly independent mechanisms have been identified (

 reviews are linked below). Imagine what will happen when the way they interact is better understood.

Consider some treatment corollaries for each of these pathways:

Cognitive Behavioral Therapy for Insomnia: Bipolar-Specific (

 lowered rehospitalization rates. Patients with 

Anticipate worsening with prednisone; avoid testosterone; monitor when estrogen and progesterone are introduced, and watch closely for post-partum depression. Thyroid hormone has a 

Incorporate in bipolar-specific CBT: “Clients are educated in identifying increased self-esteem and “positively biased” cognitions as indicators of possible 

Mindfulness-Based Cognitive Therapy for bipolar disorder; initial data positive

End poverty and childhood maltreatment? (a larger project)

Multiple bipolar treatments are neuroprotective: lithium stands out; it may even decrease 

there is no single “cause” of bipolar disorder, just as there is no single gene. Tackling this illness is more complicated than managing diabetes, where the pathways of the disease are known and the corresponding treatments well defined. Ironically, diabetic education is paid for by insurance, but not “bipolar education.” Which brings us to an evolution in bipolar management…

There are now at least 6 bipolar-specific psychotherapies with randomized trial evidence for benefit greater than treatment as usual (or in some cases versus active control treatments). They share common ingredients, as shown in the 

Personal self-monitoring is a central element in most of these therapies, but patients do not easily maintain logs of their activity, sleep, and mood. The process is cumbersome at minimum, even using modern smartphone apps. Worse, it is a daily reminder of their illness. Patients avoid this aversive reminder, understandably wishing to not have bipolar disorder.

However, at least two major research teams have developed 

 monitoring systems. Using a patient’s phone, these programs gather data on number of calls and texts; typing speed and errors; and the time of use. The phone’s accelerometer yields additional data on sleep versus activity.

The BiAffect program is under study at the University of Michigan, where the team reports good correlation between the program’s data and Hamilton Depression Rating Scale (HAM-D) and Young Mania Rating Scale (YMRS) scores.

The MONARCA program also has shown good correlation with HAM-D and YMRS scores.

 Interestingly, it did not improve outcomes when tested against treatment as usual: depression and mania scores did not differ between the two groups.

However, in my view the major value of these programs will not be manifest if the goal is to provide 

 with data to better manage their patients, as in the MONARCA study. Rather, their value will be in enabling 

 to better manage their own mood stability. The phone app is simply a tool to engage patients in a much larger endeavor: implementing key elements of the six bipolar-specific psychotherapies.

I hope that 2019 brings such a transition in the use of these devices. When they are available to the public (the free BiAffect app appears to be 

 for iPhones), pioneering clinicians and patients will figure out how to integrate them into a complete treatment package, paralleling some of the known mechanisms of bipolar disorder. For example:

creating and maintaing a pattern of regular sufficient sleep

avoiding mood-bias driven decisions, by having data on acceleration or deceleration of thought and activity

receiving automatic reminders to use a mindfulness-based relaxation technique

Solving poverty and child abuse may take a bit longer. Onward to 2019!

Dr. Phelps stopped accepting honoraria from pharmaceutical companies in 2008 but receives honoraria from McGraw-Hill and W.W. Norton & Co. for his books on bipolar disorders, including 

, a book he coauthored with Chris Aiken, MD.

1. Nusslock R, Abramson LY, Harmon-Jones E, et al. Psychosocial Interventions for Bipolar Disorder: Perspective from the Behavioral Approach System (BAS) Dysregulation Theory. Clin Psychol. 2009;16:449–469. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790718/

2. Lovas DA, Schuman-Olivier Z. Mindfulness-based cognitive therapy for bipolar disorder: A systematic review. 

3. Zulueta J, Piscitello A, Rasic M, et al. Predicting Mood Disturbance Severity with Mobile Phone Keystroke Metadata: A BiAffect Digital Phenotyping Study. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076371/

4. Faurholt-Jepsen M, Vinberg M, Frost M, et al. Smartphone data as an electronic biomarker of illness activity in bipolar disorder. 

5. Faurholt-Jepsen M, Frost M, Christensen EM, et al. Daily electronic monitoring of subjective and objective measures of illness activity in bipolar disorder using smartphones: The MONARCA II trial. American Psychiatric Association (APA) 2018 Annual Meeting; May 5-9, 2018; New York City. Poster 40.

Let us look at two major trends in our evolving understanding of this complex mood disorder and its treatment, to wrap up 2018 and to consider the year ahead.

Bipolar Disorder: The Year Ahead

Dr Phelps is Medical Director at PsychEducation.org and Bipolar Disorder Section Editor for 

This is Part 3 of a 3-part series on bipolar depression. Part 1 can be found 

“What is the risk of driving thyroid stimulating hormone (TSH) below the lower limit of the normal lab range when using levothyroxine as an adjunct treatment for depression?” Here are new data and associated conclusions on that question posed in the October issue, at the end of 

 hyperthyroidism increases the risk of atrial fibrillation and decreased bone density. Population studies also note an increased risk of congestive heart failure and death.

 levothyroxine (high-dose thyroid [HDT]) may not carry the same risks as endogenous hyperthyroidism (eg, Grave disease).

 for high-risk differentiated thyroid cancer.

 Dr Tam Kelly scrutinized this literature in two 

Two studies followed patients with bipolar disorder for nearly 6 years. Findings from these studies indicate no greater decline in women on HDT than controls matched for age and gender.

 Together these studies followed 43 patients. Yes, that’s a small sample.

Meta-analyses from the much larger cancer literature were 

 by a surgical team (they, too, need to know the risks and benefits of HDT). Thus, “detrimental effects on bone metabolism were very small or not significant in both premenopausal women and men; the results for postmenopausal women were less convincing.”

At minimum, accelerated osteoporosis-if it is a risk at all-is associated with years of exposure, similar to tardive dyskinesia (which does not seem to dissuade us from aggressive use of dopaminergic agents). By comparison, the more immediate and potentially catastrophic risks of atrial fibrillation and cerebral infarction (from atrial clot fragments) may be more likely to drive decision-making by practitioners and patients.

 reiterates and expands his earlier review.

 Trying to follow his analysis is like being back in residency learning how to critique study design, methodology, and statistical methods. I was still hesitant to adopt his conclusions. (Dr Kelly wisely invited me to “be skeptical of your skepticism.”) But an examination of his reviews by other specialists familiar with this literature has just arrived, with additional data on HDT’s cardiac risk.

 published the results of a prospective study of cardiac outcomes in 23 patients on HDT (mean dose 463 µg/d).These patients had already been prescribed HDT for an average of 16 months before cardiac monitoring that included echocardiogram, holter, and stress testing, for an average of an additional 20 months. “None of the assessed cardiac parameters . . . was in a range predictive for cardiac dysfunction.” Again, the sample size was small, with no control group. Nevertheless, this article’s 10 authors, including Dr Peter Whybrow-one of the originators of using HDT for bipolar depression-repeatedly cite Kelly’s analyses in support of the relative safety of HDT.

Art and Science of Thyroid Supplementation for the Treatment of Bipolar Depression

, you should probably hold off on prescribing HDT for bipolar depression. However, while you continue to evaluate this option, 

 may better align your practice with available data on the efficacy and safety of levothyroxine in physiologic doses.

 levothyroxine as an augmentation in depressed patients with a TSH level greater than 2.5 mU/L, especially in bipolar depression (a nifty alternative to adding an antidepressant, with its attendant risks of inducing cycling and mixed states; or to buy time while slowly tapering an antidepressant).

 with higher initial doses, such as 50 Î¼g (“one half pill daily for a week then one daily”), at least for patients with significant depression.

 a TSH level at least down to median for age. As reviewed in Part 2 of this series, remember: 1.5 mU/L to age 50; 1.6 mU/L to age 60; 1.7 mU/L to age 70; and 1.8 mU/L to age 80.

Any level of TSH between 1.0 mU/L and median is easily justified per the available literature. If there is no clearly associated risk, why not get there? Just as we “push” medications to the top of their dosage range (if fully tolerated yet not fully effective), we should suggest levothyroxine to a TSH around 1.0 mU/L to call its trial adequate.

This article was originally posted 8/30/18 and has since been updated.

Dr Phelps stopped accepting honoraria from pharmaceutical companies in 2008 but he receives royalties for his books.

1. Selmer C, Olesen JB, Hansen ML, et al. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. 

2. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. 

3. Kelly T. An examination of myth: a favorable cardiovascular risk-benefit analysis of high-dose thyroid for affective disorders. 

4. Kelly T. A favorable risk-benefit analysis of high dose thyroid for treatment of bipolar disorders with regard to osteoporosis. 

The Art and Science of Thyroid Supplementation for the Treatment of Bipolar Depression

6. Sugitani I, Fujimoto Y. Effect of postoperative thyrotropin suppressive therapy on bone mineral density in patients with papillary thyroid carcinoma: a prospective controlled study. 

6. Pilhatsch M, BerghÃ¶fer A, Mayer-Pelinski R, et al. Long-term treatment with supraphysiologic doses of levothyroxine in treatment-refractory mood disorders - A prospective study of cardiovascular tolerability. 

Three simple steps may better align your practice with available data on the efficacy and safety of thyroid supplementation in physiologic doses.

A New Treatment for Bipolar Depression: Part 3

As with many medical disorders, determining thyroid dysfunction is a matter of degree; the standard range cutoffs are used as guidelines. In a 

 assert that a level greater than 2.5 mIU/L of thyroid stimulating hormone (TSH) is not normal. As discussed in the article, the range of TSH in the general population is not a bell-shaped curve; rather, it is skewed, as shown schematically in the 

. More than 90% of the people with no thyroid problems have a TSH reading of less than 2.5. The middle of the laboratory “normal” range is not the middle of the range! A reading of 2.5 is more like the end of normal than the middle. What does this mean for our clinical practice?

When prescribing thyroid hormone for mood, target a TSH at least around the median for age, as shown in the 

 To remember on the fly: target around 1.5 to age 50, around 1.6 to age 60, around 1.7 to age 70, and around 1.8 to age 80.

Why median for age? It is a nice euphemism for “go low!” Many practitioners will pull up short, pushing TSH into the laboratory normal range and leaving patients’ TSH at 2.5 to 3.0. But in major depression, TSH levels between 2.5 and 4.0 have been associated with more severe symptoms, and some data suggest poorer response to treatment.

, the researchers found “outcomes were relatively poor unless patients had TSH values below the median.”

, one should use doses adequate to get below 2.0 as an initial goal. In follow-up, if target symptoms remain that might respond to thyroid hormone, “a full trial of supplementation may require a 

,” explained Cohen and colleagues1 (emphases mine).

Initial dosing is not 25 mcg of levothyroxine

If your goal is to land the patient’s TSH between 1.0 and median for age, how much levothyroxine should you use? Per Cohen and colleagues,

 “initial doses or increases in dosages can be low, 50 mcg/day for T4.” But watching my colleagues’ prescribing, including that of primary care providers, it seems that clinicians believe 50 mcg is not “low,” it is more like medium-aggressive.

Initial dosing is not 25 mcg of levothyroxine (continued) >

For comparison, we might say that really aggressive is 100 mcg/day to start and increasing by that amount weekly: that is the protocol for the supraphysiologic approach described last month in 

 of this series. (Reviewing briefly, levothyroxine is used as a treatment for bipolar depression at doses sufficient to suppress TSH below the lower limit of normal. Two randomized trials have shown efficacy greater than placebo).

Starting at 75 mcg might be a middle ground, but in my experience most practitioners will find that too alarming, even if the patient’s instructions are “half a pill for a week then one daily.” Let’s try another reference point: recommendations after thyroidectomy. These 

 from 1.6 mcg/kg to 2.1 mcg/kg, although a 

 begins as low as 1.1 mcg/kg for highly overweight patients.

 For a patient who weighs 80 kg, these weight-based doses range from 88 mcg to 168 mcg daily. That gives you some idea of the final dose if you were to take over from the patient’s thyroid gland with your replacement dose.

But your starting dose is not likely to be determined by an algorithm or even your patient’s BMI. It will be determined by your own anxiety about doing harm by overshooting. After all, if you are too low, you will eventually get there using serial TSH measurements.

So, the question about initial dose comes down to the same question with which I left you in 

 of this series: What is the risk of driving TSH below the lower limit of the lab normal range? That is where we will pick up in Part 3. For now, remember: target “median for age” and don’t stop until you get there.

 to share your views. We might include your letter at the end of this article, possibly with a response from the author. Please include your full name, title, and affiliation for consideration. Comments closed two weeks after publication date.

This article was originally published on 8/1/18 and has since been updated.

Dr Phelps stopped accepting honoraria from pharmaceutical companies in 2008 but receives honoraria from McGraw-Hill and W.W. Norton & Co. for his books on bipolar disorder.

Antidepressant-Resistant Depression in Patients With Comorbid Subclinical Hypothyroidism or High-Normal TSH Levels

2. Kahapola-Arachchige KM, Hadlow N, Wardrop R, et al. Age-specific TSH reference ranges have minimal impact on the diagnosis of thyroid dysfunction. 

3. Cole DP, Thase ME, Mallinger AG, et al. Slower treatment response in bipolar depression predicted by lower pretreatment thyroid function. 

4. Ojomo KA, Schneider DF, Reiher AE, et al. Using body mass index to predict optimal thyroid dosing after thyroidectomy. 

5. Elfenbein DM, Schaefer S, Shumway C, et al. Prospective Intervention of a Novel Levothyroxine Dosing Protocol Based on Body Mass Index after Thyroidectomy. 

Dr Phelps puts thyroid dysfunction into clinical context for patients with comorbid mood disorders.

A New Treatment for Bipolar Depression: Part 2

Do you accept the idea that a treatment with no known risks, such as a dawn simulator, requires less evidence for efficacy than a risky medication? That does not appear to be the thinking in recent treatment guidelines, which put high-risk medications first line because of the number of 

 that support their efficacy (quetiapine, olanzapine/fluoxetine, and lurasidone).

But this is not how patients think. Especially in bipolar II, where they have often lived with symptoms for years, they are not looking for immediate efficacy as much as long-term tolerability. A treatment with no long-term risks and very low probability of adverse effects is appealing. By contrast, clinicians know all too well that mentioning a risk of weight gain and diabetes can take a medication right out of contention.

With all this in mind, imagine a new treatment for bipolar depression that:

    • Has not caused medical problems in over 20 years of research

    • Does not cause weight gain or diabetes

    • Has no adverse effects for most people (and if they occur, are short-lived with dose reduction), including no daytime sedation or fatigue, even during titration

Such a treatment would likely be among patients’ top options (unless their depression was severe, in which case, a treatment with strong efficacy data could also be a top consideration).

We might have such a well-tolerated, low-risk medication in our hands now. It has been 

 It has evidence for efficacy at a mechanistic level, and two small positive randomized trials.

 Have I got your attention, then? I certainly hope so.

My goal in Part 1 of this 3-part series is to open your thinking. I’ll admit, I myself am having trouble with this. I’m writing in part to convince myself, or at least explore my hesitations. If this is such a great treatment, I ought to have been using it a lot myself and I have not. I’m still not certain what’s holding me back. But old data have recently been gathered and systematically presented-reinforced by one new study, but perhaps contradicted by another. So it’s time to revisit this story.

What treatment am I talking about? Good old thyroid hormone. With only one randomized trial in bipolar depression when the recent guidelines were prepared, it keeps getting overlooked-almost.

 list adjunctive thyroid hormone as a third-line treatment option for bipolar depression, down there along with monotherapy using divalproex, fluoxetine, and tranylcypromine.

Thyroid hormone has been under study in mood disorders since at least 1981 when Dr Peter Whybrow

 pointed out the connection between thyroid hormone and catecholamines. He and colleague Dr Michael Bauer went on to demonstrate that even mild elevations in thyroid stimulating hormone (TSH) were associated with rapid cycling in bipolar disorder.

 In 1990 they presented 11 cases of refractory rapid cycling they had treated with high doses of thyroid hormone.

 “Levothyroxine was added to the baseline medication regimen, and the dosage was increased until clinical response occurred or until side effects precluded further increase.” TSH was suppressed; and T4 levels went to around 150% of normal, Whybrow reported.

 In the randomized trial, the dose was 300 mcg daily, with a starting dose and weekly increases of 100 mcg.

You’re asking yourself: “How come these patients don’t just become hyperthyroid, if you’re giving them supraphysiologic doses of thyroid hormone?” Of course that’s a key question. Whybrow and Bauer and colleagues have found that patients with rapid cycling bipolar disorder “respond differently to the hormone and tolerate it better than healthy individuals.”

 In other words, despite their TSH of less than 0.1, patients who respond do not develop tachycardia, palpitations, tremor, GI hypermotililty, or weight loss.

This will prove critical. Endogenous hyperthyroidism is associated with decreased bone mineral density and increased rates of atrial fibrillation. Are patients on supraphysiologic thyroid for bipolar depression subject to the same risks?

Suppose they aren’t. Suppose there were no evidence of increased atrial fibrillation, nor decreased bone density, with this well-tolerated treatment that is inexpensive and doesn’t cause weight gain or other metabolic consequences? Would you use it, given one positive randomized trial?

We physicians and psychiatric nurse practitioners are human. We closely monitor social norms, including how our colleagues are treating patients. I suspect that the lack of a psychiatric norm around using supraphysiologic thyroid is the limiting factor here, not an adverse risk-to-benefit ratio. But if you’ll even contemplate this “new”-old-treatment, then I have a book recommendation for you. After publishing detailed reviews of the putative risks of arrhythmias and decreased bone density with supraphysiologic thyroid, Dr Tammas Kelly has written a guide to this approach: 

Kelly’s book may help lower the barriers that impede the use of supraphysiologic thyroid. In any case, it’s a fascinating and well-written summary. I read more than half of it standing right where I removed it from the shipping box. More on this in 

This article was originally published on 7/5/18 and has since been updated.

Dr. Phelps is Director of the Mood Disorders Program at Samaritan Mental Health in Corvallis, Ore. He is the Bipolar Disorder Section Editor for 

 Guzman, F. Bipolar Disorder Treatment Guidelines: A 2018 Update. Psychopharmacology Institute. 

https://psychopharmacologyinstitute.com/guidelines/bipolar-disorder-guidelines

Rapid cycling bipolar affective disorder: II: treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study

Levothyroxine effects on depressive symptoms and limbic glucose metabolism in bipolar disorder: a randomized, placebo-controlled positron emission tomography study

Walshaw PD, Gyulai L, Bauer M, et al. Adjunctive thyroid hormone treatment in rapid cycling bipolar disorder: a double-blind placebo-controlled trial of levothyroxine (L-T4 ) and triiodothyronine (T3 ). 

 Yatham LN, Kennedy SH, Parikh SV, et al. 

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

 Whybrow PC, Prange AJ Jr. A hypothesis of thyroid-catecholamine-receptor interaction: its relevance to affective illness. 

 Bauer MS, Whybrow PC, Winokur A. Rapid cycling bipolar affective disorder: I: association with grade I hypothyroidism. 

 Bauer MS, Whybrow PC. Rapid cycling bipolar affective disorder: II: treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study. 

 Whybrow PC. The therapeutic use of triiodothyronine and high dose thyroxine in psychiatric disorder. 

https://www.amazon.com/Science-Thyroid-Supplementation-Treatment-Depression/dp/1979168415

Old data have recently been gathered and systematically presented-reinforced by a new study, but perhaps contradicted by another. So it’s time to revisit this story.

A New Treatment for Bipolar Depression: Part 1

Slideshows

A rare but serious reaction to this treatment can have immunological consequences. As with all medications, however, the latest alert does not change how psychiatrists manage the risks.

New FDA Warning

 express concern about antidepressant withdrawal syndrome. These articles raise the question: 

how many people who begin taking an antidepressant will have severe difficulties when they try to taper off?

Surprisingly, this has not been directly studied (per an hour’s negative search on PUB MED, consistent with work by a UCLA 

 Several clinical trials underway will generate relevant data

but they are still not designed specifically to answer this crucial question.

For further insight, we can look at online communities referenced in the 

. If testimonials might sway your opinion about the potential severity of antidepressant withdrawal difficulties, this site has hundreds.

Testimonials are easy to dismiss. But regardless of your opinion of testimonials as evidence, the posts at 

 make one thing clear: venlafaxine is among the most difficult of the antidepressants to discontinue. The large steps between dosage strengths require alternative intermediate strategies, but the large number of beads in each capsule make subdivision difficult (one member describes using a grass seed counter to count individual beads). See the 

 for a representative post and notice that the author “is capable of differentiating their [sic] own symptoms," eg, insomnia, from withdrawal symptoms.

We have other reasons to avoid venlafaxine. Unlike SRIs, it can raise blood pressure, worsening hypertension, an all-too-common comorbidity with depression. Venlafaxine has also been found 

 to cause manic symptoms, in patients with bipolar disorder, than other antidepressant such as sertraline and bupropion.

How many people who take an antidepressant truly have severe difficulties when they try to taper off? Or, is it “all in their mind”?

Author | James Phelps, MD

Articles

New content coming soon, please check back later.