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.

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.

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

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

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 #14 is HERE
The full course can be found: HERE

SOURCE: PubMed
AUTHORS: ​​Susan J. Hewlings, Douglas S. Kalman

Abstract
Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose of this review is to provide a brief overview of the plethora of research regarding the health benefits of curcumin.

SOURCE: Psychopharmacology Institute

This is a first line drug for the treatment of acute mania in geriatrics and this is despite concerns about renal effects and toxicity with rapid dose escalation.

Clearance of lithium is directly proportional to GFR. You are advised to dose this drug in the elderly on a once nightly basis with an immediate acting formulation to allow the kidneys time to recover before the next nightly dose.

Serum levels are checked seven days after a dose change from eight to 12 hours after the last dose. That is a trough level.

​In geriatrics, lithium serum levels are kept on the low side, between 0.4 and 0.8 mEq/L, even for the treatment of acute mania. This is so despite a poor correlation of serum levels with brain levels in elders.

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 #13 is HERE
The full course can be found: HERE

SOURCE: FDA

FDA approves first once-monthly buprenorphine injection, a medication-assisted treatment option for moderate-to-severe opioid use disorder

Agency encourages safe adoption and more widespread use of FDA-approved treatments to help combat opioid addiction

The U.S. Food and Drug Administration today approved Sublocade, the first once-monthly injectable buprenorphine product for the treatment of moderate-to-severe opioid use disorder (OUD) in adult patients who have initiated treatment with a transmucosal (absorbed through mucus membrane) buprenorphine-containing product. It is indicated for patients that have been on a stable dose of buprenorphine treatment for a minimum of seven days.

Buprenorphine for the treatment of OUD is currently approved to administer as a tablet or film that dissolves in the mouth, or as an implant. Sublocade provides a new treatment option for patients in recovery who may value the benefits of a once-monthly injection compared to other forms of buprenorphine, such as reducing the burden of taking medication daily as prescribed (medical adherence). An independent FDA advisory committee supported the approval of Sublocade at a meeting held last month.

"Given the scale of the opioid crisis, with millions of Americans already affected, the FDA is committed to expanding access to treatments that can help people pursue lives of sobriety. Everyone who seeks treatment for opioid use disorder deserves the opportunity to be offered the treatment best suited to the needs of each individual patient, in combination with counseling and psychosocial support, as part of a comprehensive recovery plan,” said FDA Commissioner Scott Gottlieb, M.D. “As part of our ongoing work in supporting the treatment of those suffering from addiction to opioids, the FDA plans to issue guidance to expedite the development of new addiction treatment options. We’ll continue to pursue efforts to promote more widespread use of existing, safe and effective FDA-approved therapies to treat addiction.”

Improving access to prevention, treatment and recovery services, including the full range of medication-assisted treatments (MAT), is a focus of the FDA’s ongoing work to reduce the scope of the opioid crisis and one part of the U.S. Department of Health and Human Services’ Five-Point Strategy to Combat the Opioid Crisis.

OUD is the diagnostic term used for a chronic neurobiological disease characterized by a problematic pattern of opioid use leading to significant impairment or distress and includes signs and symptoms that reflect compulsive, prolonged self-administration of opioid substances for no legitimate medical purpose or, if another medical condition is present that requires opioid treatment, the opioid is used in doses far greater than the amount needed for treatment of that medical condition.

MAT is a comprehensive approach that combines approved medications (currently, methadone, buprenorphine or naltrexone) with counseling and other behavioral therapies to treat patients with OUD. Regular adherence to MAT with buprenorphine reduces opioid withdrawal symptoms and the desire to use opioids, without causing the cycle of highs and lows associated with opioid misuse or abuse. At proper doses, buprenorphine also decreases the pleasurable effects of other opioids, making continued opioid abuse less attractive. According to the Substance Abuse and Mental Health Services Administration, patients receiving MAT for their OUD cut their risk of death from all causes in half.

Sublocade should be used as part of a complete treatment program that includes counseling and psychosocial support. Sublocade is a drug-device combination product that utilizes buprenorphine and the Atrigel Delivery System in a pre-filled syringe. It is injected by a health care professional (HCP) under the skin (subcutaneously) as a solution, and the delivery system forms a solid deposit, or depot, containing buprenorphine. After initial formation of the depot, buprenorphine is released by the breakdown (biodegradation) of the depot. In clinical trials, Sublocade provided sustained therapeutic plasma levels of buprenorphine over the one-month dosing interval.

The safety and efficacy of Sublocade were evaluated in two clinical studies (one randomized controlled clinical trial and one open-label clinical trial) of 848 adults with a diagnosis of moderate-to-severe OUD who began treatment with buprenorphine/naloxone sublingual film (absorbed under the tongue). Once the dose was determined stable, patients were given Sublocade by injection. A response to MAT was measured by urine drug screening and self-reporting of illicit opioid use during the six-month treatment period. Results indicated that Sublocade-treated patients had more weeks without positive urine tests or self-reports of opioid use, and a higher proportion of patients had no evidence of illicit opioid use throughout the treatment period, compared to the placebo group.

The most common side effects from treatment with Sublocade include constipation, nausea, vomiting, headache, drowsiness, injection site pain, itching (pruritus) at the injection site and abnormal liver function tests. The safety and efficacy of Sublocade have not been established in children or adolescents less than 17 years of age. Clinical studies of Sublocade did not include participants over the age of 65.

The FDA is requiring postmarketing studies to assess which patients would benefit from a higher dosing regimen, to determine whether Sublocade can be safely initiated without a dose stabilization period of sublingual buprenorphine, to assess the feasibility of administering Sublocade at a longer inter-dose interval than once-monthly and to determine a process for transitioning patients with long-term stability on a transmucosal buprenorphine dose to a monthly dose of Sublocade without the use of a higher dose for the first two months of treatment (loading dose).
​
Sublocade has a boxed warning that provides important safety information, including the risks of intravenous self-administration. If the product were to be administered intravenously rather than subcutaneously, the solid mass could cause occlusion (blockage), tissue damage or embolus (solid material that is carried in the blood and can become lodged in a blood vessel, which can lead to death). Sublocade must be prescribed and dispensed as part of a Risk Evaluation and Mitigation Strategy (REMS) to ensure that the product is not distributed directly to patients. Sublocade will be provided to HCPs through a restricted program, administered only by HCPs in a health care setting, and will require health care settings and pharmacies that dispense Sublocade to complete an enrollment form attesting that they have procedures in place to ensure that Sublocade is dispensed only to HCPs and not directly to patients.

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 #12 is HERE
The full course can be found: HERE

SOURCE: JAMA
DATE: February 26, 2018

Association of Coprescription of Triptan Antimigraine Drugs and Selective Serotonin Reuptake Inhibitor or Selective Norepinephrine Reuptake Inhibitor Antidepressants With Serotonin Syndrome

Key Points
Questions  What is the risk of serotonin syndrome associated with concomitant use of triptans and selective serotonin reuptake inhibitor or selective norepinephrine reuptake inhibitor antidepressants and how did the use of these drugs change after the 2006 US Food and Drug administration warning about this risk?
Findings  In this data registry study of 47 968 patients prescribed triptans, the incidence of serotonin syndrome was 0 to 4 cases per 10 000 person-years of exposure to coprescription of triptans and selective serotonin reuptake inhibitor or selective norepinephrine reuptake inhibitor antidepressants. The proportion of patients who were coprescribed these drugs ranged from 21% to 29% and remained stable before and after the warning.
Meaning  Serotonin syndrome was rare in patients who were coprescribed triptans and selective serotonin reuptake inhibitor or selective norepinephrine reuptake inhibitor antidepressants; those with coexisting affective disorders and migraine need not forgo management of one condition to treat the other.

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 #11 is HERE
The full course can be found: HERE

SOURCE: DocGuide - Stroke
DATE: January 2018

BACKGROUND AND PURPOSE
Intravenous thrombolysis (IVT) improves outcomes after acute ischemic stroke but is underused in certain patient populations. Mental illness is pervasive in the United States, and patients with comorbid psychiatric disease experience inequities in treatment for a range of conditions. We aimed to determine whether comorbid psychiatric disease is associated with differences in IVT use in acute ischemic stroke.
METHODS
Acute ischemic stroke admissions between 2007 and 2011 were identified in the Nationwide Inpatient Sample. Psychiatric disease was defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes for secondary diagnoses of schizophrenia or other psychoses, bipolar disorder, depression, or anxiety. Using logistic regression, we tested the association between IVT and psychiatric disease, controlling for demographic, clinical, and hospital factors.
RESULTS
Of the 325 009 ischemic stroke cases meeting inclusion criteria, 12.8% had any of the specified psychiatric comorbidities. IVT was used in 3.6% of those with, and 4.4% of those without, psychiatric disease (P<0.001). Presence of any psychiatric disease was associated with lower odds of receiving IVT (adjusted odds ratio, 0.80; 95% confidence interval, 0.76-0.85). When psychiatric diagnoses were analyzed separately individuals with schizophrenia or other psychoses, anxiety, or depression each had significantly lower odds of IVT compared to individuals without psychiatric disease.
CONCLUSIONS
​Acute ischemic stroke patients with comorbid psychiatric disease have significantly lower odds of IVT. Understanding barriers to IVT use in such patients may help in developing interventions to increase access to evidence-based stroke care.

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 #10 is HERE
The full course can be found: HERE

SOURCE: DocGuide - JAMA Psychiatry 
DATE: February 2018

Importance
Duration of untreated psychosis (DUP) has been associated with poor outcomes in schizophrenia, but the mechanism responsible for this association is not known.
Objectives
To determine whether hippocampal volume loss occurs during the initial 8 weeks of antipsychotic treatment and whether it is associated with DUP, and to examine molecular biomarkers in association with hippocampal volume loss and DUP.
Design, Setting, and Participants
A naturalistic longitudinal study with matched healthy controls was conducted at Shanghai Mental Health Center. Between March 5, 2013, and October 8, 2014, 71 medication-naive individuals with nonaffective first-episode psychosis (FEP) and 73 age- and sex-matched healthy controls were recruited. After approximately 8 weeks, 31 participants with FEP and 32 controls were reassessed.
Exposures
The participants with FEP were treated according to standard clinical practice with second-generation antipsychotics.
Main Outcomes and Measures
Hippocampal volumetric integrity (HVI) (an automated estimate of the parenchymal fraction in a standardized hippocampal volume of interest), DUP, 13 peripheral molecular biomarkers, and 14 single-nucleotide polymorphisms from 12 candidate genes were determined.
Results
The full sample consisted of 71 individuals with FEP (39 women and 32 men; mean [SD] age, 25.2 [7.7]years) and 73 healthy controls (40 women and 33 men; mean [SD] age, 23.9 [6.4]years). Baseline median left HVI was lower in the FEP group (n = 57) compared with the controls (n = 54) (0.9275 vs 0.9512; difference in point estimate, -0.020 [95% CI, -0.029 to -0.010]; P = .001). During approximately 8 weeks of antipsychotic treatment, left HVI decreased in 24 participants with FEP at a median annualized rate of -.03791 (-4.1% annualized change from baseline) compared with an increase of 0.00115 (0.13% annualized change from baseline) in 31 controls (difference in point estimate, -0.0424 [95% CI, -0.0707 to -0.0164]; P = .001). The change in left HVI was inversely associated with DUP (r = -0.61; P = .002). Similar results were found for right HVI, although the association between change in right HVI and DUP did not achieve statistical significance (r = -0.35; P = .10). Exploratory analyses restricted to the left HVI revealed an association between left HVI and markers of inflammation, oxidative stress, brain-derived neurotrophic factor, glial injury, and markers reflecting dopaminergic and glutamatergic transmission.
Conclusions and Relevance
An association between longer DUP and accelerated hippocampal atrophy during initial treatment suggests that psychosis may have persistent, possibly deleterious, effects on brain structure. Additional studies are needed to replicate these exploratory findings of molecular mechanisms by which untreated psychosis may affect hippocampal volume and to determine whether these effects account for the known association between longer DUP and poor outcome.