Review: Reconsideration of bipolar disorder as a developmental disorder
Reconsideration of bipolar disorder as a developmental disorder: Importance of the time of onset
Pierre Alexis Geoffroy et al, J Physiology Paris, 2013
Eight admixture studies have demonstrated three homogeneous subgroups of patients with bipolar disorder, identi?ed by their age at onset (early, intermediate and late age at onset), with two cutoff points, at 21 and 34 years.
The early onset group had more: Suicide attempts, rapid cycling, drug and alcohol abuse, psychotic symptoms, panic disorder, OCD, and a positive family history for affective disorder. Early onset illness should be recognized and treated earlier.
Lithium Is Unparalleled in It Range of Efficacy in the Mood Disorders
Most clinicians are aware of lithium’s superiority over other mood stabilizers in bipolar illness prophylaxis. New data suggests this might also apply to the atypical antipsychotics.
Lithium is also not only an effective adjunct to antidepressant in unipolar depression, but has some of the best data for its use in long term prevention. In bipolar disorder prophylaxis it is particularly effective in those with classical presentations of discrete episodes of euphoric mania, treatment early in the course of illness, lack of anxiety and substance comorbidities, and a positive history of mood disorder in first-degree relatives.
New data indicates that it is also effective in childhood onset mania, and open long term follow ups indicate that it is more effective than other mood stabilizers or atypical antipsychotics.
Despite the compelling effectiveness data and many ancillary benefits, survey data indicates very low levels of current lithium use in both adult and child bipolar disorder. The conventional view, shared by most patients and many clinicians, underestimates its range of effectiveness and potential benefits while overestimating it is side effects. A more balanced view is needed as neglect of wider use of lithium is detrimental to the long term outcome of immense numbers of patients.
Robert M. Post, MD
Lithium vs Anticonvulsants Lamotrigine and Valproate on 10 year physical illness
In a study by lars Kessing in (European Neeuropsychopharmcology Volume 84, July 2024, Pages 48-56) on 169,285 patients taking either lithium or the anticonvulsants Lamotrigine (LTG) or Valproate (VPA) for at least 10 years, there was no difference in physical outcome in any physical outcome, including chronic kidney disease, except for a higher incidence of myxedema.
Other diagnoses that showed no difference included stroke, arteriosclerosis, angina pectoris, myocardial infarction, diabetes mellitus, osteoporosis, dementia, Parkinson’s disease, chronic kidney disease and cancer (including subtypes).
Editors Note: This data further supports an already robust existing literature that lithium is not more likely to cause chronic kidney disease or other physical illnesses than other anticonvulsant treatments with the exception of hypothyroidism. Patient should be made aware of these and the related long term data that lithium is no more likely to cause chronic kidney disease than other treatments and, in some cases, these other treatments cause more end-stage renal failure. The misapprehension that lithium is more toxic than other treatments has led to the vast underutilization of this treatment. Lithium is the treatment of choice for bipolar illness and should be used earlier, more often, and more persistently. When this is done illness outcomes and patient’s well being are significantly improved.
Quotes from Kay Jamison, PhD, Professor of Psychiatry at the Johns Hopkins School of Medicine
“There’s this notion that mania and depression are uncommon or certainly that mania is uncommon, and that is not true. The bipolar illness spectrum is associated with a lot of very damaging things, most importantly suicide, but also alcohol and drug use and violence. It’s a very early onset illness, so unlike dementia or heart disease, which hit people much later in life, these hit people when they’re young. They have to cope with [bipolar disorder] when they’re young, and they don’t have the experience of life to help them out. That tends to be overlooked, what it does to people and their families, and how devastating it is. First and foremost, I would want people to know that it’s treatable, imperfectly treatable, but treatable, and it’s important to get it treated….It’s completely reasonable to extend hope to somebody who has bipolar illness but to also make it very clear that it’s hard. But draw upon what you know. Read, read, read. Learn about it. Badger your doctors. Why are they doing this? What’s the point of this drug rather than that drug? Always question what’s happening to you. “
Editor’s Note: One of the most important things that people with mood disorder can do, is to every night chart chart their mood, functioning, sleep, medications, and other symptoms so that this graphic longitudinal assessment can be shown to their physician/therapist at each visit. This will help most efficiently refining the treatment regimen for an optimal long term outcome. See www.bipolarnews.org (click on Personal Calendar or Life Chart) for a good format for doing these daily ratings.
Parents of children (age 2-12) with mood and behavioral disorders can each week rate the severity of their child’s symptoms of anxiety, depression, ADHD, oppositional behavior, and mania on a secure website. This can be printed out to assist physicians with the assessment of need for treatment and of how well treatment is working. Informed consent for this system is available at www.bipolarnews.org (click on Child Network).
LITHIUM IS VASTLY UNDER-UTILIZED IN BIPOLAR DISORDER LEADING TO PREMATURE DEATH AND DISABILITY: WE WANT YOU TO HELP REVERSE THIS ANOMALOUS TREND
We are looking for people who have had a good course of illness with lithium included in their treatment regimen to help spread the word that lithium works extremely well and its side effects are erroneously overestimated.
We are hoping that you, as a good responder to lithium, will start a positive chain letter to fellow patients, family members, and friends suggesting that earlier and greater use of lithium would be overwhelmingly likely to improve the lives of many individuals with bipolar illness.
Why do we need you? It is because every expert in the treatment of bipolar illness of whom I am aware of has long advocated for greater and earlier use of lithium, but with little success. Lithium is widely recognized as a first line and treatment of choice for bipolar disorder, yet its use remains miniscule. In the US somewhere between only 10 to 27% of bipolar patients are given lithium. This has tragic consequences.
Treatment outcomes of the illness remain poor with vast numbers of patients experiencing pain, disability, memory loss, and loss of many years of life expectancy from suicide, cardiovascular disease, and many other psychiatric and medical disabilities. Compared to the general population, people with bipolar illness lose between 10-15 years of life expectancy. A new study by Carvalho et al (Psychother Psychosom, 2024) of more than 50,000 patients with a first episode of mania compared to more than 250,000 matched controls have a significantly higher rate of all cause mortality and a 10 fold increase of suicide. Those treated with lithium have a significantly lower rate of both all cause mortality and of suicide.
In addition, lithium has many other assets, besides the treatment of mania, of which most people are unaware and the liabilities of its side effects profile are over estimated. Some of the positive’s of lithium are listed below. Please print this ‘list of assets of lithium out and give it to everyone who might be interested. Patients with bipolar disorder should also print it out for their treating physicians, particularly if they do not as yet have lithium in their treatment regimen.
At the same time lithium’s side effects are over emphasized. The biggest concern is that lithium causes end stage kidney dysfunction eventually leading to dialysis. This is likely based on findings that individuals with bipolar disorder have an increase in most medical illnesses including chronic kidney disease compared to the general population. However, two very large trans-national studies of bipolar patients in Denmark and in Israel have found that bipolar patients treated with lithium are no more likely to get end stage renal disease than those treated with anticonvulsants such as valproate (Depakote). Lithium does cause low thyroid function in 15-25% of patients, but this is easily corrected with replacement of thyroid hormone. Many other side effects of lithium such as tremor can be managed by using lower doses.
Bottom line: Lithium gets a bad rap.
Please tell everyone you know about the new data on lithium’s relative safety and its many assets including reducing all cause mortality and suicide and restoring many years of lost life expectancy. 14 of 15 studies indicate that if lithium is started early in course of bipolar disorder it is more effective than starting it after many episodes or rapid cycling have occurred. It also works well in youngsters with bipolar disorder and better in comparison to other treatments (Hafeman et al 2020). In addition, after a first mania, patients randomized to a year of treatment with lithium do better on all outcome measures than those given a year on quetiapine (Seroquel) including manic and depressive severity, functioning, cognition, and normality of brain imaging (Berk et al 2017).
One more conceptual breakthrough: Lithium is literally the original salt of the earth. It was generated just 20 minutes after the big bang origin of the universe and is considered an essential element. Common table salt, sodium chloride, emerged only many millions of years after the big bang. Also in six studies across multiple countries, higher minute levels of lithium in the drinking water have been shown to reduce the incidence of suicide in the general population. A very low dose of lithium 150-300mg/day has also been shown to reduce the progression of mild cognitive impairment in otherwise well elderly volunteers.
Do a good thing for other people. Relay this new view of lithium to everyone you can think of in hope that they will help get the word out to many others and improve the life, functioning, and longevity of those with bipolar disorder.
Suggest and promulgate a new mantra:
“LITHIUM PREVENTS EPISODES OF BIPOLAR ILLNESS, AND PROTECTS THE BRAIN AND BODY”
Bipolar I patient show dramatic reductions in white matter integrity
Thiel et al in Neuropsychopharmacology (2024) reported that “Compared with HC [healthy controls], BD-I patients exhibited lower FA [fractional anisotropy] in widespread clusters (ptfce-FWE?< 0.001), including almost all major projection, association, and commissural fiber tracts. BD-II patients also demonstrated lower FA compared with HC, although less pronounced (ptfce-FWE?=?0.049).”
Editors Note: These data once more emphasize the importance of using lithium (Li) in bipolar disorder as it can ameliorate the deficits in white matter integrity that are so prominent in the illness. Li also improve the loss of cortical grey matter volume that evolves with illness progression. Li prevents episodes of depression and mania and reduces the incidence of suicides. That Li can reverse or ameliorate brain abnormalities in bipolar disorder is one more piece of evidence that Li should be considered a disease modifying drug (DMD) and started early in the course of illness in almost all bipolar patients. The new mantra for patients and clinicians is: Use more lithium and prevent illness progression.
Smoking Pot While Pregnant is a No-No
Mom, Don’t Think Smoking Pot When Pregnant is Harmless for your Child
In a new article in Science, Jasmine Hurd reports on a large sample of mothers who smoked pot while pregnant. Their offspring were more anxious, hyperactive, and aggressive and had higher levels of the stress hormone cortisol in their hair at ages 3-6.
When Superstorm Sandy hit, mothers who were stressed and smoked pot while pregnant had children 31 times more like to have oppositional defiant disorder and 7 times more likely to have an anxiety disorder. Stress may interact negatively with the effects of pot.
In fetuses aborted after being exposed to pot while in utero had decreased dopamine receptors in the their amygdala and n. accumbens, a reward center in brain. In animal studies, pregnant mother rodents who were exposed to THC had offspring more likely to use heroin.
DADS’ BEHAVIOR COUNTS TOO. Dad’s exposure to THC as an adult also led to offspring who preferred opiates. This was based on epigenetic changes passed on in the sperm. To the extent that this also happens in humans, one could ask how much of the current opiate epidemic is based on parental use of marijuana. Mom’s and dad’s smoking pot could make their offspring more vulnerable to opiate addiction.
Cannabis and Cannabinoids Don’t Work for Pain or Posttraumatic Stress Disorder
Aaron S. Wolfgang, MD and Charles W. Hoge, MD reviewed data on cannabis in JAMA Psychiatry and found that there were big placebo effects and no evidence for effectiveness of cannabis in military personal.
This negative data, along will all the liability of cannabis potentially causing or triggering psychosis, bipolar disorder, and schizophrenia (as well as possibly contributing to cognitive dysfunction, worsening anxiety and depression in patients with mood disorders) makes the use of pot for medical purposes an entirely foolhardy proposition, as well as a waste of money.
Legalization of pot has helped people avoid jail but precipitated a rash of use and over use.
So the bottom line from this editor is: Get Your Priorities Straight. Cannabis and Cannabinoids Don’t Work for Pain or Posttraumatic Stress Disorder and they Worsen Most Everything Else. Save your Money and Do Something Nice for Yourself and Others Instead.
More Data that Long Term Lithium Treatment Does NOT CAUSE RENAL TOXICITY (more than those on valproate).
In a recent meeting, Mark Weiser of Sheba Medical Center analysed data from “from the Clalit Health Services (CHS) database, the largest provider of health insurance in Israel, n=4.8 million, representing over 50% of the Israeli population. This study examined lithium use between the years 2000 and 2022, focusing on its impact on kidney and thyroid function…(and) compared all patients receiving lithium (n=19,433) to all patients receiving valproic acid (n=44,524). There was no different in the life-time rates of dialysis between patients treated with lithium and patients treated with valproic acid (1.03% vs 0.99%, p = 0.683). A lifetime diagnosis of hypothyroidism was more common in patients receiving lithium (21.84%) in comparison to patients treated with valproic acid (8.83%, p = <0.0001). Conclusions: In this large population study, treatment with lithium was not associated with decreased kidney function but was associated with a clinical diagnosis of hypothyroidism. These factors should be taken into account when considering treatment with lithium.”
Editors Note: In patients on lithium, overtime there are small decreases in estimated glomerular filtration rate (eGFR), but these do not differ from those seen in physiological age adjusted eGFR in the general population. These data are convergent with the large national studies of Kessing et al in Denmark and indicate that the long-held view of lithium causing undo renal toxicity are not accurate and are based on inappropriate suppositions without an adequate control group. They found more end-stage renal dysfunction in bipolar patients treated with anticonvulsants than with lithium.
THERE IS A GRAVE UNDERUTILIZATION OF LITHIUM DUE IN LARGE PART TO THE FALSE ASSUMPTION THAT IT CAUSES EXCESS RENAL TOXICITY. PATIENTS AND CLINICIANS SHOULD BE MADE AWARE OF THE NEW DATA THAT THIS IS LIKELY RELATED TO POOR METHODOLOGY AND BEGIN TO MORE FREQUENTLY THINK ABOUT USING LITHIUM — UNEQUIVOCALLY THE BEST DRUG FOR THE TREATMENT OF BIPOLAR DISORDER. LITHIUM ALSO HAS THE BEST DATA FOR REDUCING EPISODES OF BOTH DEPRESSION AND MANIA AND FOR HAVING POSITIVE EFFECTS IN PREVENTING SUICIDE. USING LITHIUM MORE OFTEN WILL UNDOUBTEDLY MARKEDLY IMPROVE PATIENTS WELL BEING AND SURVIVAL. THIS EDITOR BELIEVES THAT GIVEN LITHIUM’S MULTIFACETED ROLE IN AMELIORATING ALMOST ALL ASPECTS OF THE COURSE OF BIPOLAR DISORDER, IT SHOULD BE CONSIDERED A “DISEASE MODIFYING DRUG.” THERE ARE MULTIPLE DISEASE MODIFYING DRUGS FOR TREATMENT OF MULTIPLE SCLEROSIS, AND EXPERTS IN THAT FIELD BELIEVE THAT DISEASE MODIFYING SHOULD BE STARTED AS EARLY AS POSSIBLE AFTER FIRST DIAGNOSIS. A SIMILAR CONCLUSION WOULD NOW APPEAR APPROPRIATE FOR LITHIUM.
Of note is the other widely held reason for not using lithium more often is that it causes hypothyroidism. While this is clearly correct based on the Weiser study and many other data, patients should be aware that this well-known condition is readily correctable with thyroid hormone replacement and does not produce an undo burden on patients.
Since lithium has many other assets including: increasing hippocampal volume; protecting memory; and increasing the length of telomeres (critical to sustaining good medical and psychiatric health), its wider use in bipolar disorder should be a no brainer. However, it is likely (like most revisions in medical lore) to take 10 years or more before this re-evaluation of lithium has an impact on conventional treatment decisions, so physicians should make very active and conscious decisions about changing their routine choices of treatment for each patient with bipolar disorder.
FDA Warns of Potentially Lethal Reaction to Seizure Meds
Megan Brooks reports:
“The antiseizure drugs levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam, generic) and clobazam (Onfi, Sympazan, generic) can cause a rare but serious drug hypersensitivity reaction that can be life threatening if not detected and treated promptly, the US Food and Drug Administration (FDA) warns in an alert issued today.
Known as drug reaction with eosinophilia and systemic symptoms (DRESS), it may start as a rash but can quickly progress and cause injury to internal organs, the need for hospitalization, and death, the FDA notes.
Three cases occurred in the US, and 29 occurred abroad. In all 32 cases, the patients were hospitalized and received medical treatment; in two cases, the patients died.
The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4). The median time to onset of DRESS in the levetiracetam cases was 24 days; times ranged from 7 to 170 days. The reported signs and symptoms included skin rash (n = 22), fever (n = 20), eosinophilia (n = 17), lymph node swelling (n = 9), and atypical lymphocytes (n = 4)…. DRESS symptoms resolved when levetiracetam was discontinued.”
