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.”
Cannabis Contributes to 15% of Case of Schizophrenia
A study in Psychological Medicine (May 2, 2023) reported on ” Danish registry data spanning five decades and representing more than 6.9 million people in Denmark to estimate the population-level percentage of schizophrenia cases attributable to (cannabis use disorder) CUD. A total of 60,563 participants were diagnosed with CUD. Three quarters of cases were in men; there were 45,327 incident cases of schizophrenia during the study period. The researchers estimate that in 2021, about 15% of schizophrenia cases among males aged 16 to 49 could have been avoided by preventing CUD, compared with 4% among females in this age range. For young men aged 21 to 30, the proportion of preventable schizophrenia cases related to CUD may be as high as 30%, the authors report.”
Editors Note: Other data also support an increased risk for bipolar disorder in those abusing cannabis. The notion that cannabis use carries few risks is baloney. Making pot legal does not make it safe.
Assets of Exercise
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Ben Goldstein of the University of Toronto gave a plenary talk on the benefits of exercise.
He found poor aerobic fitness in 19 of 20 young bipolar patients. They had low cerebral blood flow in proportion to the severity of their exhaustion after exercise. He noted the importance of stressing an endpoint of fitness for exercise rather than weight loss. Using an exercise coach and running with family and friends was helpful in motivating patients for consistent exercise.
The Need for Psychotherapy for Bipolar Disorder
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Greg Murray gave a talk on effectiveness of multiple types of psychotherapy for bipolar disorder and suggests that the choice be designed for each individual.
He describes 10 core elements of each type of therapy. These included dealing with:
- 1. Knowledge, acceptance, and adherence
- 2. The presence of anxiety in some 90% of patients
- 3. Suicidality and crisis management
- 4. Skills: monitoring, relapse prevention, life time events, recognition of early symptoms
- 5. Identity, cognitive restructuring, dealing with stigma, train action and achievement, confronting perfectionism, CBT
- 6. Sleep and circadian rhythms
- 7. Trauma, child adversity, PTSD
- 8. Emotion regulation
- 9. Relationships: social, family, occupational roles (family or group)
- 10. Substance use and avoidance, access, motivational interviewing, impulsivity
Childhood Bullying and Maltreatment Yield A Worse Course of Bipolar Illness
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Georgina Hosang of Bart’s & The London, Queen Mary’s School of Medicine reported that bullying and maltreatment together were associated with more suicidal behaviors than either childhood experience alone.
Cognitive Function and White Matter Integrity in Individuals With Bipolar Disorder
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
Jennifer McDowell reported that they found “significantly reduced FA (fractional anisotropy) values in 85 bipolar probands compared to 66 controls” in multiple (n=8) white matter tracts. There were significantly lower scores in bipolar probands compared to controls on composite scores, ( p = 0.007), verbal fluency, ( p < 0.001), and symbol coding, (p = 0.023). They concluded that: “ Impacted connectivity in critical fiber tracts may be key to understanding the neural underpinnings of deficits, like cognition, observed in this clinical population.”
Editors note: It is of interest that lithium has been shown to normalize some white matter abnormalities in youngsters and help preserve cognitive function in older individuals. On this and many other accounts, way too little lithium is being used in the treatment of patients with bipolar disorder. Lithium not only increases neurogenesis (new grey matter neurons) and hippocampal volume, but also has positive effects on white matter tracts and even increases the length of one’s telomeres (which keeps you more healthy). In other ungrammatical words, “If your brain is not connected right, it don’t work right.”
LITHIUM’S AMAZING DIVERSITY OF ASSETS
Editor’s Note: Lithium is vastly underutilized. There is wide spread ignorance about its many assets and misconceptions about its few side effects. Here is an update that should be of interest to potential users, family members, and clinicians.
Lithium:
- Prevents unipolar and bipolar depression
- Augments effects of antidepressants in unipolar depression
- Potentiates the effects of atypical antipsychotics in treating mania and depression
- Reduces inflammation
- Normalizes some aspects of cardiovascular risk
- Normalizes secretions for monocytes and leukocytes
- Increases neurogenesis, BCl-2, and hippocampal and thalamic volumes
- The increases in neuroprotective factors occurs at brain levels below typical therapeutic dosages
- Protects against memory deterioration
- Lowers dementia risk in old age
- Reduces suicide clinically and at minute concentrations in the water supply
- Lengthens telomeres and increases longevity
- Reduces size of lesions in models of stroke, AIDS, and Huntington’s chorea
- Normalizes circadian rhythms
- Reduces manic-like behavior induced by clock gene mutations
- Prevents calcium currents and increased firing rate in stem cells from bipolar patients
- Induces minimal to no weight gain on long term follow up
- Does not increase risk of kidney failure when given at blood levels of .6 to .8 blood levels
- Protects against spine and hip osteoporosis
Conclusion: With so many assets and so few liabilities, physicians and patients should reconsider the benefits of lithium and use it more often, not only in the few who respond to it as a monotherapy, but as a adjunct to the many other treatments of bipolar disorder. This should be a “no brainer” as lithium will very likely help some have fewer problems from their illness and may even help them live longer.
Many of these points are summarized in the open access publication: Robert M Post, The New News About Lithium: An Underutilized Treatment in The United States, Neuropsychopharmacology accepted article preview 4 October 2017; several new updates have been added from the International Society on Bipolar Disorders meeting, Chicago, June, 2023.
Even Psychotic Mania Does Not Preclude Remarkable Success
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Major (Two Star) General Gregg F. Martin described his lifetime hyperthermia (high energy) as a youngster morphing into full-blown mania and then a fulminatory psychotic mania. This was undiagnosed and untreated for almost 20 years and was accompanied by anxiety and Iraq war-induced PTSD and, eventually, terrifying delusions and hallucinations; all the while he was somehow functioning at a very high level and getting repeated promotions.
When finally and properly diagnosed, he was told he had to resign. He was treated with lithium and other agents, and achieved a complete recovery. He is now lecturing about his experience with bipolar illness and working on efforts directed at better illness recognition, treatment, and destigmatization. He is not only a war hero, but also an illness hero.
The Systematic Treatment Optimization Program for Early Mania
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
A. Rathseesh and L. Yatham reported on the importance of systematic vigorous treatment of a first manic episode. If more episodes occurred, losses in cognition did not fully recover. All patients remitted within 1 year of their first mania. Recurrence occurred in 58% by year 1 and 74% by year 4. Predictors of functional recovery included sustained euthymia, especially absence of depressive symptoms, good cognitive functioning, and maintaining a normal weight. More aggressive treatment to prevent relapses in years 1-4 after a first manic episode appears needed and how exactly to achieve this requires further study.
