How does lithium work?

Ah, lithium; it’s been our gold-standard treatment for bipolar disorder for many years, and can work for people who have failed other drug trials. It is also one of the only drugs known to decrease the risk of suicide1. But how does it work?

It’s a bit more complicated to understand than, for example, an SSRI (which, ultimately, increases serotonin in the synapse, through a fairly intelligible mechanism of stopping reuptake). Despite knowing since 1949 that lithium was an effective treatment for bipolar disorder, we still don’t fully understand its mechanism of action.

There are a lot of signalling pathways in the brain.

One of the difficulties in determining this is that lithium goes everywhere in your body. Within the brain, it can cause an absurd number of changes through numerous signalling pathways. Like other drugs, it can cross the brain-blood barrier (an important quality for psychiatric medications, since they target the brain) but, uniquely among psych meds, it can also enter your intracellular space — hiding inside your cells, instead of just floating around in your blood.

It is excreted by the kidneys in urine, although it is also known to be excreted in human sweat and tears2. (I’ve had hyper-salty tears caused by lithium every so often.)

Lithium appears to increase the concentration of some neurotransmitters (potentially serotonin and GABA) while moderating the effects of dopamine and norepinephrine through its effects on voltage-gated channels3. This action causes a broad cascade of effects throughout the entire brain that restores balance in people with bipolar disorder. Lithium can get into any cell in your body, and it goes inside your neurons (brain cells) too. This is how it affects voltage-gated channels and moderates the activity of all neurotransmitters.

Although we usually call it a mood stabilizer, it’s not related to any other drug we put in this class, since it is not an anticonvulsant. Lithium is probably most accurately classified as a neuroprotective drug4, like memantine (a drug typically used for Alzheimer’s disease). There is even some speculation that memantine could augment the effect of lithium, due to its similar mechanism of action, but specific to the NMDA receptors.

A key point to understanding the pharmacodynamics of lithium is that lithium, in the human body, can use the same transporters as sodium. It fits where sodium should go — therefore, it exits cells through active transport systems designed for sodium, but at about half the speed of sodium. The similarity of lithium and sodium explains why lithium is excreted by the kidneys and not metabolized by the liver.

a) lithium salts; b) sodium salts

This is also why activated charcoal will not absorb lithium. Your body sees it as a metallic salt (it has a positive charge), and metals (or charged ions) are not attracted to charcoal. In addition, the similarity of sodium and lithium creates a sort of sodium-lithium ecosystem in your body; if you maintain a steady dose of lithium but drastically reduce your intake of sodium, your lithium levels can rise to toxicity.

References

  1. Kessing, L. V., Søndergård, L., Kvist, K., & Andersen, P. K. (2005). Suicide risk in patients treated with lithium. Archives of General Psychiatry, 62(8), 860–866. https://doi.org/10.1001/archpsyc.62.8.860
  2. Fraunfelder, F. T., Fraunfelder, F. W., & Jefferson, J. W. (1992). The effects of lithium on the human visual system. Cutaneous and Ocular Toxicology, 11(2), 97–169. https://doi.org/10.3109/15569529209042704
  3. Lenox, Robert H., H. C.-G. (2000). Overview of the Mechanism of Action of Lithium in the Brain: Fifty-Year Update. 61.
  4. Gray, J. D., & Mcewen, B. S. (2013). Lithium’s role in neural plasticity and its implications for mood disorders. Acta Psychiatrica Scandinavica, 128(5), 347–361. https://doi.org/10.1111/acps.12139

Happy World Bipolar Day!

I am bipolar type 1. 🎭 That is the most severe form of bipolar disorder. (Bipolar 2 can have very severe depression, but because it doesn’t have severe mania it doesn’t progress along the same course. Something like that.) I’ve been inpatient 18 times, and I’ve been discharged from the ER a few additional times as well.

Interestingly, I don’t have what most people would think of if you said “classic bipolar disorder”. I have mostly dysphoric manias (and sometimes euphoric hypomania), so no grandiose delusions or belief that I can see the flow of energy that connects all things. Just bugs that… may or may not be real. 🐜 But, the dysphoric mania type is actually sliiiiiightly more common than euphoric (feel-good) mania in real-world bipolar 1 people, according to one study1

The main reason my bipolar is unusual is that it is so FAST. My psychiatrist describes it as “brittle” — a medical term often applied to highly unstable diabetes patients, where blood sugar skyrockets but then drops with intervention but then skyrockets again. It follows the same kind of course.

Blood sugar in brittle diabetes

Usually, I think my cycle (including both mania, which almost always comes first for me, and then depression — most bipolar people have one type of episode almost always come first, but it’s a 50/50 split which one2) is 2 to 4 weeks long. If it’s a lot faster than that it’s considered a mixed episode.

I rarely ever have euthymic (normal mood) periods and I don’t have any asymptomatic periods. (I have persistent problems with memory and executive functioning and other stuff.) 

💊 Currently every day I take: lithium, Thorazine (chlorpromazine), Zyprexa (olanzapine), Valium (diazepam), and Adderall (amphetamine salts). 💊

What causes bipolar disorder?

A lot of research links bipolar disorder to various things:
a) circadian instability, sleep problems ⏰
b) inflammatory processes in the brain 🔥
c) epilepsy 📈 — they have a lot in common, and medications used to treat epilepsy are often used to treat bipolar disorder; I think you can think of bipolar as being similar to some kind of epileptogenic brain activity but on a more macro scale. Similarities to Temporal Lobe Epilepsy include age of onset and genetic cause among other things and they do have a very very high comorbidity rate.
d) genetics 🧬 — 97% of bipolar disorder is explained by genetic variance alone and it is more heritable than autism or schizophrenia (I believe it might be the most heritable psychiatric disorder in DSM-5)

Most people get bipolar disorders in their 20s, but I got it early. I had suicidal depression sometime before the age of 10 and had my first clear hypomanic episode when I was 16. My parents were anti-psychiatry, so I wasn’t in treatment until I went to college and I almost became an emancipated minor because I was still 17 and it was that serious 🙃

Unlike autism, which is a fairly new concept (although autistic people have almost certainly existed for thousands of years) bipolar disorder is a very old idea for a distinct illness that occurs in all cultures that I know of. Other English names for it have been “manic depression” (a term I actually prefer), “manic-depressive psychosis”, “circular insanity” 🔁, all referring to a highly organized and unusually patterned occurrence of severe disturbances in mood.

That’s actually what I study now in my PhD program! I’m looking for patterns in bipolar disorder. I’m very good at patterns 🧩

References

1.  Grant BF, Stinson FS, Hasin DS, et al. Prevalence, correlates, and comorbidity of bipolar I disorder and axis I and II disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 2005;66(10):1205-1215. doi:10.4088/JCP.v66n1001

2. Koukopoulos A, Reginaldi D, Tondo L, Visioli C, Baldessarini RJ. Course sequences in bipolar disorder: Depressions preceding or following manias or hypomanias. J Affect Disord. 2013;151(1):105-110. doi:10.1016/j.jad.2013.05.059


Rebranding psychiatry

A lot of people with conditions that are defined in the DSM (Diagnostic and Statistical Manual of Mental Disorders) disagree with what their condition is called. In this post, I’m going to muse over changing the names of psychiatric disorders.

Manic Depression -> Bipolar Disorder -> Manic Depression

When the DSM-III was published, the DSM committee decided that the term “manic depression” had become overly stigmatized and abused. There was little to no change in the diagnostic features or description of the disorder (which has actually been fairly consistent for a very long time!), the only reason for changing the terminology was political. Many years later, I feel this has resulted in the term “bipolar” being just as stigmatized as “manic depression” ever was — except it’s even more abusable, since “bipolar” can be used as an adjective to describe many things, famously including the weather.

It should’ve been obvious that the stigma of manic depression didn’t originate from the term “manic depression” — and therefore not shocking that the same stigma followed, not the term that was used, but the people who live with the disorder. It was always the people, never the term. On top of that, I feel “manic depression” is more accurate as the term “bipolar disorder” doesn’t portray the common reality of mixed episodes and mixed mood presentation. “Bipolar” seems to imply a state of bistability, where two states representing opposite ends of one dimension (mania and depression) are cleanly and abruptly switched between; bipolar can be like this, but it is often messier.

Attention Deficit/Hyperactivity Disorder -> Executive Dysfunction Developmental Disorder

ADHD is a controversial term for some advocates and it’s understandable why. While attention and hyperactivity/impulsivity are characteristics that are used to diagnose the disorder, they’re downstream of the real difference experienced by people who live with the condition — which is developmental effects on executive functioning. Broadening the term to define it by its root cause would probably feel more accurate of the experience of living with the condition.

Inadvertently, if the diagnostic criteria were changed accordingly to reflect other developmental disorders of executive dysfunction, there may be groups of people who didn’t meet the criteria before who now do. This is something to be interested in, of course. Attention and hyperactivity/impulsivity could still be used as specifiers, and the developmental history aspects would probably still be required so that people with executive dysfunction of non-developmental origin aren’t accidentally included. Additionally, we know that autism is associated with some kinds of executive dysfunction and this change would probably blur the lines between them even more — but in reality, those lines are pretty blurry.

Autism Spectrum Disorder?

There is a lot of controversy over this one, and to be honest I don’t have all of the answers. I think “Asperger’s” was a term of limited utility because many studies could not find clear differences between “Asperger’s” and “High Functioning Autism” even though supposedly the Asperger’s group had no language delay and the HFA group did. Their outcomes, though, were the same. So it was decided that we would collapse autism into one diagnosis that represents a gradient or spectrum of features and levels of impact on the person’s life.

However, I actually agree with some advocates who say that this has proven obtrusive for people with high support needs as the common conception of autism drifts further and further from Rain Main to Sheldon Cooper. There are many people out there who no longer believe autism is a disability. I can’t fully reconcile myself with this stance when we’re talking about a nonverbal adult with an IQ of 40: this person’s life is much, much different than mine, and I genuinely want to help them in the most effective way I can. At this venture, I believe we need a term for people with high support needs. But, the options thus far have been problematic (for example, I do see the reasons why “high functioning” and “low functioning” are much too simplistic to capture meaningful differences).

In the end, the best I can come up with right now is to include Verbal IQ score as a specifier. It’s not perfect (we know IQ means something specific, and can’t be generalized to “intelligence”), but it’s one of the better indicators we reliably have of how disabled this person is, how many barriers they’re going to face to get treated fairly and with respect. And, it doesn’t create a competition where someone is more or less autistic than I am. We’re both autistic; it’s just that one of us has an IQ of 40 and that information isn’t trite. Despite the risks of increasing discrimination, I think we’ve seen with the bipolar fiasco that changing terms merely to avoid stigma (which is attached to people, not to terms) is not a good idea.


After a suicide attempt

Caution: this post contains explicit discussion of suicide

Two days ago (on September 10th) was World Suicide Prevention Day. Although it is important to address prevention of suicide attempts, the strongest predictor of a fatal (or “completed”) suicide is a history of previous, non-fatal suicide attempts. The risk factors for suicide attempts are more diverse and include: family history of suicide, early onset of bipolar disorder, extent of depressive symptoms, increasing severity of affective [mood] episodes, the presence of mixed affective [mood] states, rapid cycling, comorbid Axis I disorders, and abuse of alcohol or drugs1

Most suicide prevention effort focuses on people who are naive to psychiatric treatment and have reached a crisis point: people who don’t already have a psychiatric point of contact, and usually people who have never been treated in an inpatient setting before. In my experience, most people do not continue using crisis lines or similar services after they have been hospitalized once. Surmounting the fear and stigma around hospitalization itself is a primary reason crisis lines exist. Crisis lines are staffed by severely underqualified volunteers, who are usually following a script, and only have two action moves: call an ambulance, or tell you to go talk to someone else (sometimes your health insurance company). Yet, people find calling a crisis hotline less formidable than simply admitting themselves voluntarily.

But what about those of us with chronic illnesses, with volumes of psychiatric history, who have been admitted many times? This service is clearly not meant for me. If I spoke to a crisis line on what to me is an an average day, I might find myself being dragged to the ER and with an $800 ambulance fee to boot. There is no exception for chronicity. The stakes of a mistake are high, and the crisis line operator is equipped with a high school diploma.

There’s a gap between services for first-episode patients and services for profoundly disabled people who live in an institutional setting. After my close-to-fatal suicide attempt about two and a half years ago, I had to navigate what exactly life looks like after a serious suicide attempt. I consumed an amount of lithium equal to the 50% lethal dose in rats, and an antidepressant that is also a potent anti-emetic (anti-vomiting) drug. I knew I would absorb more of the lithium if I delayed the onset of (inevitable) severe vomiting.

I was hospitalized for only 16 days. The attending physician treating me thought I should go to a residential treatment program, but I was supposed to be at an academic conference and I begged to be realized in time to go. The head of the clinic evaluated the situation and decided to release me. I was discharged within hours of my flight to Europe. After the conference, I was enrolled in a partial hospitalization day program. The official length of the program was 8 weeks; I was probably enrolled for 4 months. My psychiatrist met with me nearly every day.

We tried a lot of medications, but for quite some time I was not permitted to take lithium. This was unfortunate, because lithium is probably the single most effective drug I take. I have cycled through almost every atypical antipsychotic: Seroquel, Abilify, Vraylar, Zyprexa, Saphris, Geodon… I’m sure I’ve forgotten something, it’s more than I can keep track of. I tried Depakote and Lamictal. Nothing has the same effect as lithium. Ironically, lithium also has a specific anti-suicide effect.

I continued to be suicidal throughout and beyond the partial program. I am lucky that my psychiatrist works well with me.

Chronic suicidality is probably more common than people realize. It doesn’t appear in the media. It’s taboo. You fear to acknowledge it exists somewhere. When we talk about improving mental health services, let’s give a little more attention to the people for whom posting a status update with the s-word in it is reason to panic and report it to Facebook headquarters.

References

  1. Hawton, K., Sutton, L., Haw, C., Sinclair, J., & Harriss, L. (2005). Suicide and Attempted Suicide in Bipolar Disorder: A Systematic Review of Risk Factors. The Journal of Clinical Psychiatry, 66(6), 693–704. https://doi.org/10.4088/JCP.v66n0604


Bipolar disorder and media consumption

Recently, on Twitter, I confessed that I had not been able to complete reading NeuroTribes (a very interesting book, and also a lengthy one). The other person insisted that a PhD student should be able to read a book and accused me of lacking academic integrity — basically, that I am lazy and don’t deserve my PhD.

I’m here to say that attitude is inherently ableist. But to give the benefit of the doubt, perhaps most people don’t know that bipolar disorder actually can affect your ability to read. I learned to read early as a child — I was a prolific consumer of text, and I had a college reading level in elementary school (this is called hyperlexia). But after being medicated for bipolar disorder, my ability to sustain focus and momentum while reading a long document has been very limited.

Lithium is probably the biggest offender. It kind of affects how you see words on the page — like a pseudo-dyslexia, the words seem kind of blurry and distorted. It can be impossible to read full books. I can still read journal articles because they generally have a defined structure and an abstract. I can also read poetry, which I enjoy. I recommend seeking out these kinds of texts if reading is something you struggle with.

Most of all, I want you to know that this is common, you are not alone in having an acquired inability to read and you still deserve your career, whatever that may be. It’s not a matter of “intellectual thoroughness”; it’s part of a disability, and it’s more common than you think.

I also find it difficult to watch videos, TV, or movies. The information conveyed through video media covers many modalities — sound (music), speech, visuals, movement (spatial), and the overall plot you’re supposed to be following. Sitting for the length of a movie is hard, but it’s also just hard to follow so many things at once. My brain gets overwhelmed with too much information of different kinds to process (evidence of poor sensory integration, a symptom of autism). But it helps to reduce the overload by using captions (combining speech with visuals, thus reducing the number of information modalities) or watching something animated, which compresses the demands of visual and spatial information greatly.

Have you ever had trouble consuming media?

What strategies have you used?


Psychiatric disorders and discrimination by medical professionals

There is much that could be written about the damage done by bad psychiatrists, but this post will specifically focus on non-psychiatric medical professionals: doctors, nurses, everyone involved with it.

Once I presented to the ER with a large abscess from a skin infection, and in great pain. I told the triage nurse that I had this abscess, and showed it to her (it was not subtle). She proceeded to look through my chart and started asking me about my bipolar disorder. I told her what she asked, and of course we got to “Are you planning to hurt yourself?” and I said no, because I wasn’t, I just really needed my abscess to be drained by a doctor.

Naturally, then, she put me in psychiatry and had a psychiatrist come speak to me. I told the psychiatrist what I told the nurse and showed him the abscess. He was horrified by it, and said he’d call my psychiatrist. After he spoke to her, he moved me to the medical area and gave his psychiatric stamp of approval. Finally, a medical doctor arrived and drained my abscess.

In retrospect, is it a big problem? I think it is. What if my condition were even more time-sensitive? They wasted significant time getting me a psych eval when I was not presenting with any major psychiatric symptoms, I just happen to have a chronic mental illness that I will have in my chart forever. What if I was having a heart attack? Would I have to get a psych eval because I’m bipolar?

If you have a label like “bipolar disorder type 1” they will always look for a psychiatric cause for your symptoms, even when the evidence doesn’t suggest it’s psychiatric (like, the huge abscess). They assume you are professionally crazy and anything you say is cause for suspicion, instead of an honest report of symptoms. Putting patients presenting with tangible physical illness in the psych area just because they have a diagnosis, but are not presenting with symptoms, is discrimination.


Anxiety and mania

Recently, The Mighty published an article about the differences between anxiety and hypomania. However, I wanted to complicate the discussion by bringing up something that breaks the juxtaposition of anxiety and mania: primarily anxious mania, which is most likely a mixed episode associated with bipolar type 1.

The author describes how her anxiety leaves her “immobilized”. This can actually happen in mania, too — but usually not in hypomania. Hypomania is often very productive. Full mania is no longer productive — it’s frantic, potentially confused, and may be characterized by manic stupor. Emil Kraepelin used this term to describe a flight of ideas and elevated mood (not necessarily happy, but revved-up) combined with psychomotor slowness or immobility. I’ve been in this state, and I experienced it subjectively as intense feelings of anxiety paralyzing my every move. This might also be referred to nowadays as catatonia, and something similar can occur in severe depressive states; however, the catatonia that coincides with mania is likely excited catatonia (characterized by purposeless movements rather than being completely still).

Hypomania isn’t rare, exotic, or exciting to me. It’s just part of my life, and I take advantage of it when it comes around — which it will, no matter what. But, to me, full mania is to be avoided. Anxiety is also a daily part of my life, but the anxiety and paranoia I experience during a manic episode is even more excruciating than it usually is. Juxtaposing them as discrete, separate states can only take you so far in understanding what mania is and how it affects people.


One bipolar person’s drug regimen

Currently, I take 8 medications for psychiatric reasons. I’ve also been on many others — including most of the atypical antipsychotics, several anticonvulsants, antidepressants, and more. These are my current drugs ranked in terms of how essential they are (if, for example, I could only get some of them, perhaps due to a catastrophe):

  1. Lithium — Big Pharma has yet to come up with something better. It could never be patented, it wasn’t paid for by anybody. It actually works. And it’s all-natural. But also, it sucks. Nature is brutal.
  2. Haldol — Indispensable, though I might be switching to Thorazine in the near future. I don’t picture myself living without an antipsychotic again. Typicals seem to work better for me than atypicals did, though I’ve notably NOT tried Risperdal (even though it’s a good fit for my symptoms) or clozapine. Both were considered, though.
  3. Ativan (lorazepam) — My symptoms tend to cluster around anxiety, insomnia, and irritability — maybe paranoia — all things helped by benzodiazepines. If it were not so problematic, I might have ranked it #2. It’s the best immediate symptom relief I can get aside from maybe sublingual Zyprexa (olanzapine).
  4. Adderall — I would never actually achieve anything in life without Adderall. That said, my need to do something with my life is inherently superseded by my need to be alive, which is why it ranks #4.
  5. Lamotrigine (Lamictal) — An anticonvulsant medication. It seems to be doing something, because I become depressed without it. Though I’m not exactly sure what it’s doing.
  6. Gabapentin — I’m supposed to be using it for anxiety to offset my lorazepam use. It’s also useful for severe headaches. I still feel the pain, but I kind of don’t care, like the pain just doesn’t command my attention.
  7. Clonidine — It’s a blood pressure med, but I’m using it for insomnia. I cycle through medications for insomnia because they all lose their effectiveness eventually. I haven’t been on clonidine before so I don’t know how long it will be useful for. Other drugs I’ve used for sleep: Trazodone, Remeron, Ativan, Seroquel (and other atypical antipsychotics)…
  8. Diphenhydramine (Benadryl) — An OTC drug! The original antihistamine. I take it as 50mg softgels (two of them, which is slightly more than the bottle indicates — consult your doctor). Sometimes works for sleep, not super reliable and fades quickly. Useful if I have a cold or flu because Sudafed is not the best choice for my wiring. Also potentially protective against Haldol-induced side effects. So overall, something I take regularly, but not every day.

Anyone want to share their regimen?



I’m lucky to have my bipolar disorder

There are times that I’ve felt cursed by having ultra-rapid-cycling, somewhat-atypically-presenting bipolar 1 disorder. My mood episodes are short (sometimes as short as one day, although usually lasting a few days to a week) and they can be very intense. I also suffer from mixed episodes, which are agonizingly painful to experience, and at times I have had profound suicidality that has led to multiple suicide attempts — one of which left me in a coma for three days and nearly claimed my life. Doctors said I wasn’t going to make it. But I did.

During the worst of times I’ve wished to have “classic” bipolar disorder instead of my bipolar disorder. In truth, “classic” features may be relatively rare; but it conjures the idea of long, bleak depressions punctuated by shorter, but still somewhat long, grandiose and euphoric manias. Separate and distinct periods of each, usually lasting for months at a time, with bouts of clean euthymia (wellness) in between.

I haven’t really experienced prolonged euthymia, instead merely catching glimpses of it over the course of my continuous ups and downs. My manias are “dirty” and dysphoric, tainted with depressive themes. My hypomanias are very productive; but if my mood spikes too high, my thoughts become dark and gruesome. If I were to jump off a building, it would be to kill myself, not because I believed I could fly.

And I’m also a researcher. Without a doubt, my research in the area of bipolar disorder draws upon my insights as a bipolar person. If I had “classic” bipolar disorder, the research I have done (some of it relying theoretically upon data collection of my own personal changes in mood) would not have been possible. Because I’m an ultra-rapid-cycler, I was able to capture long-term patterns that might take many years to become evident in “classic” bipolar disorder. I believe the same patterns exist in both, but when moods last for months at a time, it is harder to see those patterns.

My ability to detect patterns has served me well in life (including in my professional career) and to some extent, my bipolar disorder trained me to do it. Predicting my own mood was not only possible, thanks to the accelerated timeframe, but essential to my ability to cope with them. Part of the devastation of mixed episodes came with the loss of my ability to predict with reasonable accuracy when moods would peak or change and in what direction. Even so, I learned new patterns and slowly became able to tell what a “mixed episode” felt like, and whether I was experiencing one. This was not something I could do at first.

Insight into the emotions, cognitions, and memory issues that come along with my bipolar disorder developed over time, starting at an early age (as I first developed symptoms around the age of 10). In turn, this level of insight has allowed me to hypothesize connections no other researcher has yet seen. I understand firsthand how bipolar disorder intersects with changes in thinking and memory.

I have the opportunity to discern cause and effect in relation to changes in my mood much more easily than someone with “classic” bipolar disorder, thanks to the immediacy of any reactions. Upon hearing from my psychiatrist that nitrates in beef jerky were causally linked to mania, I took note of my own reactions. I had known for quite some time that beef jerky had a stimulant-like effect on me, but I was surprised to learn it did not have this effect on everyone. (Too bad!) I experience this stimulant-like effect almost instantly, while I’m still eating. The temporal proximity of the cause and the effect makes them easier to distinguish.

My bipolar disorder is a blessing and a curse. I have struggled immensely to control it, but I wouldn’t trade it for “classic” bipolar disorder or no bipolar disorder at all. The knowledge and abilities I have gained as a result of my battle with bipolar disorder — my bipolar disorder, not someone else’s — have actually, truly been indispensable to my life and my career. Plus, that excessively productive hypomania is pretty good too.