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FDA: Lamotrigine Linked to Potentially Life-Threatening Adverse Reaction

5/18/2018

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SOURCE: MPR

The Food and Drug Administration (FDA) has issued a safety alert regarding the use of lamotrigine and the possibility of hemophagocytic lymphohistiocytosis (HLH), a rare but serious immune system reaction. 

According to the FDA, 8 cases of confirmed or suspected HLH associated with lamotrigine have been reported worldwide (2 in the US). All of these cases were reported to have serious outcomes, with 1 reported death. Symptoms of HLH had occurred within 8 to 24 days after starting treatment with lamotrigine. In the 6 cases that reported dosing information, the doses ranged from 25mg every other day to 250mg once daily. In all but one case, HLH had improved after treatment (i.e., steroids, intravenous immunoglobulin, blood products, chemotherapy) and discontinuation of lamotrigine. While all 8 cases reported concomitant medications, none of these medications were associated with HLH.

Prompt recognition of HLH is important as severe inflammation can lead to multi-organ failure resulting in hospitalization and death. As per the FDA communication, a diagnosis of HLH can be made if a patient has ≥5 of the following symptoms:
  • Fever and rash
  • Splenomegaly
  • Cytopenias affecting ≥2 of 3 lineages in the peripheral blood (hemoglobin <90g/L [in infants <4 weeks: hemoglobin <100g/L; platelets <100 x 109/L; neutrophils <1.0 x 109/L)
  • Hypertriglyceridemia (fasting triglycerides ≥265mg/dL) and/or hypofibrinogenemia (≤1.5g/L)
  • High levels of blood ferritin (≥500µg/L)
  • Hemophagocytosis identified through bone marrow, spleen, or lymph node biopsy
  • Decreased or absent Natural Killer Cell activity
  • Elevated blood levels of CD25 showing prolonged immune cell activation (≥2400 U/mL)

Lamotrigine is indicated for the treatment of seizure disorders as well as bipolar I disorder. The FDA is requiring that a new warning be added to the prescribing information for all lamotrigine products to alert of this possible side effect. Patients should be counseled on the symptoms associated with HLH and should be advised to seek medical attention immediately if they experience these symptoms while on lamotrigine therapy.
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The Origin of Spousal Resemblance for Alcohol Use Disorder

5/12/2018

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SOURCE: JAMA Psychiatry

Key Points
What causes spouses to resemble one another in their risk for alcohol use disorder?

Findings 
In this population-based registry study, the increase in risk for a first onset of alcohol use disorder in a married individual after the onset of alcohol use disorder onset in his or her spouse was large and rapid. When an individual was married in either order to serial partners with vs without alcohol use disorder, the risk for alcohol use disorder was substantially increased when the partner had an alcohol use disorder registration and decreased when the partner did not have an alcohol use disorder registration.

Meaning 
A married individual’s risk for alcohol use disorder is likely directly and causally affected by the presence of alcohol use disorder in his or her spouse.

Abstract
Importance  Although spouses strongly resemble one another in their risk for alcohol use disorder (AUD), the causes of this association remain unclear.

Objectives  
To examine longitudinally, in first marriages, the association of a first registration for AUD in one spouse with risk of registration in his or her partner and to explore changes in the risk for AUD registration in individuals with multiple marriages as they transition from a spouse with AUD to one without or vice versa.

Design, Setting, and Participants  
Population-wide Swedish registries were used to identify individuals born in Sweden between 1960 and 1990 who were married before the end of study follow-up on December 31, 2013. The study included 8562 marital pairs with no history of AUD registration prior to their first marriage and an AUD registration in 1 spouse during marriage and 4891 individuals with multiple marriages whose first spouse had no AUD registration and second spouse did or vice versa. Final statistical analyses were conducted from August 15 to September 1, 2017.

Exposures  
A spousal onset or history of AUD registration.

Main Outcomes and Measures  
Alcohol use disorder registration in national medical, criminal, or pharmacy registries.

Results  
Among the 8562 marital pairs (5883 female probands and 2679 male probands; mean [SD] age at marriage, 29.2 [5.7] years) in first marriages, the hazard ratio of AUD registration in wives immediately after the first AUD registration in their husbands was 13.82, which decreased 2 years later to 3.75. The hazard ratio of AUD registration in husbands after the first AUD registration in their wives was 9.21, which decreased 2 years later to 3.09. Among the 4891 individuals with multiple marriages (1439 women and 3452 men; mean [SD] age at first marriage, 25.5 [4.2] years), when individuals transitioned from a first marriage to a spouse with AUD to a second marriage to a spouse without AUD, the hazard ratio for AUD registration was 0.50 (95% CI, 0.42-0.59) in women and 0.51 (95% CI, 0.44-0.59) in men. After a first marriage to a spouse without AUD, the hazard ratio for AUD with a second marriage to a spouse with AUD was 7.02 (95% CI, 5.34-9.23) in women and 9.06 (95% CI, 7.55-10.86) in men. These patterns were modestly attenuated when moving from second to third marriages. Controlling for AUD registration prior to first marriage or between first and second marriages produced minimal changes in risk.

Conclusions and Relevance  
The increase in risk for AUD registration in a married individual following a first AUD registration in the spouse is large and rapid. When an individual with serial spouses is married, in either order, to partners with vs without an AUD registration, the risk for AUD registration is substantially increased when the partner has an AUD registration and decreased when the partner does not have an AUD registration. These results suggest that a married individual’s risk for AUD is directly and causally affected by the presence of AUD in his or her spouse.
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KETO DIET IN HEALTHCARE - # 16 Summary & Conclusions

5/8/2018

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Recently, as I've been exploring the role of an individual's diet in Integrated Psychiatry, I've seen a growing body of research to support the use of a Ketogenic-style diet to enhance brain functioning and help people achieve a healthy weight. There is additional research, which theorizes such a diet could be helpful for a number of mental health conditions from ADHD and depression to Alzheimer's Disease.

Just a few of the articles I've been looking at: 
  • Article: Long-term effects of a ketogenic diet in obese patients 
  • Article: The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies
  • Article: Dietary ketosis enhances memory in mild cognitive impairment​
  • Article: The antidepressant properties of the ketogenic diet​
Dr. David Unwin, a family physician in England, has been treating patients with low carb diets since 2012. He is offering this online course that will cover very practical tips for doctors, like how to effectively discuss the low-carb lifestyle with patients, how to handle medications, safety, patient motivation, etc. 

Transcript for Video #16 is HERE
The full course can be found: HERE
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KETO DIET IN HEALTHCARE - # 15 Common problems & Troubleshooting

5/1/2018

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Recently, as I've been exploring the role of an individual's diet in Integrated Psychiatry, I've seen a growing body of research to support the use of a Ketogenic-style diet to enhance brain functioning and help people achieve a healthy weight. There is additional research, which theorizes such a diet could be helpful for a number of mental health conditions from ADHD and depression to Alzheimer's Disease.

Just a few of the articles I've been looking at: 
  • Article: Long-term effects of a ketogenic diet in obese patients 
  • Article: The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies
  • Article: Dietary ketosis enhances memory in mild cognitive impairment​
  • Article: The antidepressant properties of the ketogenic diet​
Dr. David Unwin, a family physician in England, has been treating patients with low carb diets since 2012. He is offering this online course that will cover very practical tips for doctors, like how to effectively discuss the low-carb lifestyle with patients, how to handle medications, safety, patient motivation, etc. 

Transcript for Video #15 is HERE
The full course can be found: HERE
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