SOURCE: JAMA Psychiatry

Key PointsQuestions  Can digital cognitive behavioral therapy for insomnia improve functional health, psychological well-being, and sleep-related quality of life, and does a reduction in insomnia symptoms mediate these potential improvements?
Findings  In a 2-arm, parallel-group randomized clinical trial that included 1711 persons, digital cognitive behavioral therapy significantly improved insomnia symptoms, functional health, psychological well-being, and sleep-related quality of life at 4, 8, and 24 weeks after initiation of treatment. Improvements at 8 and 24 weeks were mediated by improvements in insomnia at week 4 and 8, respectively.
Meaning  Treating insomnia with digital cognitive behavioral therapy could be a therapeutic pathway for addressing self-reported health, well-being, and quality of life.

AbstractImportance  
Digital cognitive behavioral therapy (dCBT) is a scalable and effective intervention for treating insomnia. Most people with insomnia, however, seek help because of the daytime consequences of poor sleep, which adversely affects quality of life.
Objectives  
To investigate the effect of dCBT for insomnia on functional health, psychological well-being, and sleep-related quality of life and to determine whether a reduction in insomnia symptoms was a mediating factor.
Design, Setting, and Participants  
This online, 2-arm, parallel-group randomized trial comparing dCBT for insomnia with sleep hygiene education (SHE) evaluated 1711 participants with self-reported symptoms of insomnia. Participants were recruited between December 1, 2015, and December 1, 2016, and dCBT was delivered using web and/or mobile channels plus treatment as usual; SHE comprised a website and a downloadable booklet plus treatment as usual. Online assessments took place at 0 (baseline), 4 (midtreatment), 8 (posttreatment), and 24 (follow-up) weeks. Programs were completed within 12 weeks after inclusion.
Main Outcomes and Measures  
Primary outcomes were scores on self-reported measures of functional health (Patient-Reported Outcomes Measurement Information System: Global Health Scale; range, 10-50; higher scores indicate better health); psychological well-being (Warwick-Edinburgh Mental Well-being Scale; range, 14-70; higher scores indicate greater well-being); and sleep-related quality of life (Glasgow Sleep Impact Index; range, 1-100; higher scores indicate greater impairment). Secondary outcomes comprised mood, fatigue, sleepiness, cognitive failures, work productivity, and relationship satisfaction. Insomnia was assessed with the Sleep Condition Indicator (range: 0-32; higher scores indicate better sleep).
Results  
Of the 1711 participants included in the intention-to-treat analysis, 1329 (77.7%) were female, mean (SD) age was 48.0 (13.8) years, and 1558 (91.1%) were white. Use of dCBT was associated with a small improvement in functional health compared with SHE (adjusted difference [95% CI] at week 4, 0.90 [0.40-1.40]; week 8, 1.76 [1.24-2.28]; week 24, 1.76 [1.22-2.30]) and psychological well-being (adjusted difference [95% CI] at week 4, 1.04 [0.28-1.80]; week 8, 2.68 [1.89-3.47]; week 24, 2.95 [2.13-3.76]), and with a large improvement in sleep-related quality of life (at week 4, −8.76 [−11.83 to −5.69]; week 8, –17.60 [−20.81 to −14.39]; week 24, −18.72 [−22.04 to −15.41]) (all P < .01). A large improvement in insomnia mediated these outcomes (range mediated, 45.5%-84.0%).
Conclusions and Relevance  
Use of dCBT is effective in improving functional health, psychological well-being, and sleep-related quality of life in people reporting insomnia symptoms. A reduction in insomnia symptoms mediates these improvements. These results confirm that dCBT improves both daytime and nighttime aspects of insomnia, strengthening existing recommendations of CBT as the treatment of choice for insomnia.

Full Text
Introduction
Insomnia disorder, comprising reports of poor sleep with associated daytime effects occurring 3 or more nights per week for 3 or more months,1 presents in 10% to 12% of adults.2-4 In addition, insomnia is associated with mental health disorders,5 cardiovascular disease,6 and type 2 diabetes.7,8 Increased fatigue, impaired work productivity, reduced quality of life, and relationship dissatisfaction are also common in those with insomnia.9-11 Such impaired functioning is an important driver for help-seeking behavior.12
The recommended intervention for insomnia is cognitive behavioral therapy (CBT),13-16 a psychological treatment designed to break patterns of maladaptive thinking and behavior. Cognitive behavioral therapy comprises a behavioral component (stimulus control, sleep restriction, and relaxation) combined with a cognitive (managing sleep-related worries, racing mind, and intrusive thoughts) and an educational (sleep hygiene) component. Meta-analyses indicate that CBT has moderate to large and durable effects on sleep quality, sleep efficiency, sleep-onset latency, and wake time after sleep onset.17-19 Moreover, recent meta-analyses indicate that digital CBT (dCBT), delivered using automated web platforms or a mobile app,20 is also efficacious.21,22 The effects of CBT and dCBT on the nighttime symptoms of insomnia, therefore, appear robust. However, daytime symptoms are a core part of insomnia disorder, integral to its clinical presentation. Improving constructs such as functional health, psychological well-being, and quality of life may therefore be crucial to treating insomnia satisfactorily.

 SOURCE: JAMA Psychiatry
Author: Jennifer L. Gordon, PhD, et al.
Citation: JAMA Psychiatry. 2018;75(2):149-157. doi:10.1001/jamapsychiatry.2017.3998

Key Points
​Question  Is 12 months of transdermal estradiol and intermittent micronized progesterone more effective than placebo in preventing the development of depressive symptoms in the menopause transition and early postmenopausal period?
Findings  In this randomized clinical trial that included 172 perimenopausal and early postmenopausal women, 32.3% of women receiving placebo developed clinically significant depressive symptoms, while 17.3% of women taking transdermal estradiol and intermittent micronized progesterone did so.
Meaning  If confirmed in future research, clinicians may consider prescribing hormone therapy to mitigate the increased risk of clinically significant depressive symptoms that accompany the menopause transition and early postmenopausal period.

Abstract
Importance  The menopause transition and early postmenopausal period are associated with a 2- to 4-fold increased risk for clinically significant depressive symptoms. Although a few studies suggest that hormone therapy can effectively manage existing depression during this time, to our knowledge, there have been no studies testing whether hormone therapy can prevent the onset of perimenopausal and early postmenopausal depressive symptoms.
Objective  To examine the efficacy of transdermal estradiol plus intermittent micronized progesterone (TE+IMP) in preventing depressive symptom onset among initially euthymic perimenopausal and early postmenopausal women. A secondary aim was to identify baseline characteristics predicting TE+IMP’s beneficial mood effects.
Design, Setting, and Participants  Double-blind, placebo-controlled randomized trial at the University of North Carolina at Chapel Hill from October 2010 to February 2016. Participants included euthymic perimenopausal and early postmenopausal women from the community, aged 45 to 60 years.
Interventions  Transdermal estradiol (0.1 mg/d) or transdermal placebo for 12 months. Oral micronized progesterone (200 mg/d for 12 days) was also given every 3 months to women receiving active TE, and identical placebo pills were given to women receiving placebo.
Main Outcome Measures  Scores on the Center for Epidemiological Studies–Depression Scale (CES-D), assessed at baseline and months 1, 2, 4, 6, 8, 10, and 12 after randomization, and the incidence of clinically significant depressive symptoms, defined as a CES-D score of at least 16.
Results  Of 172 participants, 130 were white (76%), and 70 were African American (19%), with a mean household income of $50 000 to $79 999. The mean age was 51 years, and 43 developed clinically significant depressive symptoms. Women assigned to placebo were more likely than those assigned to TE+IMP to score at least 16 on the CES-D at least once during the intervention phase (32.3% vs 17.3%; odds ratio [OR], 2.5; 95% CI, 1.1-5.7; P = .03) and had a higher mean CES-D score across the intervention period (P = .03). Baseline reproductive stage moderated the effect of treatment (β, −1.97; SEM, 0.80; P for the interaction = .03) such that mood benefits of TE+IMP vs placebo were evident among women in the early menopause transition (β, −4.2; SEM, 1.2; P < .001) but not the late menopause transition (β, −0.9; SEM, 0.3; P = .23) or among postmenopausal women (β, −0.3; SEM, 1.1; P = .92). Stressful life events in the 6 months preceding enrollment also moderated the effect of treatment on mean CES-D score such that the mood benefits of TE+IMP increased with a greater number of events (β, 1.22; SEM, 0.40; P = .003). Baseline estradiol levels, baseline vasomotor symptoms, history of depression, and history of abuse did not moderate treatment effects.
Conclusions  Twelve months of TE+IMP were more effective than placebo in preventing the development of clinically significant depressive symptoms among initially euthymic perimenopausal and early postmenopausal women.

Full Test
Introduction
Depression risk is known to increase among women in the menopause transition and early postmenopausal period, with rates of major depressive disorder1 and clinical elevations in depressive symptoms2-4 roughly doubling to tripling compared with premenopausal and late postmenopausal rates. Increased sensitivity to the extreme estradiol fluctuation that characterizes the menopause transition has been implicated.3,5,6 Although a few trials suggest that estrogen therapy, with7,8 or without9,10 progesterone, which might act to minimize estradiol fluctuation and/or withdrawal, is an effective treatment for perimenopausal depression, to our knowledge, this is the first study to examine the efficacy of hormone therapy, in this case, transdermal estradiol plus intermittent micronized progesterone (TE+IMP), in preventing the development of depressive symptoms in initially euthymic perimenopausal and early postmenopausal women.
This study further sought to identify baseline characteristics predicting TE+IMP’s effect on mood. Several factors known to be associated with an increased vulnerability to perimenopausal depression and/or other reproductive mood disorders, including recent life stress,1,2 a positive history of depression,1,3,11 a history of physical or sexual abuse,12,13 and more severe vasomotor symptoms,3,4,14 were therefore considered as potential moderators of TE+IMP’s effects. Indicators of the preintervention hormonal environment, including menopausal stage, were also considered.

SOURCE: JAMA Psychiatry
Author: J. Cobb Scott, PhD, et al. 
Citation: JAMA Psychiatry. 2018;75(6):585-595. doi:10.1001/jamapsychiatry.2018.0335

Full Article

Introduction
Substantial shifts in the legality and public perceptions of cannabis have recently occurred in the United States. Cannabis use has increased, while the perception of its harms has decreased.1,2 In view of these trends, it is of considerable public health importance to delineate potential risks of cannabis use. However, scientific debates about physical and mental health consequences of cannabis remain unresolved. A critical question concerns potential cognitive dysfunction associated with cannabis use during adolescence and early adulthood, when use typically begins and substantial neurodevelopment continues to occur. To address this question, we conducted a meta-analysis specifically examining studies of cognitive functioning in adolescent and young adult cannabis users.

Adolescence is a period of dynamic neurobiological and behavioral changes. Substantial increases in cognitive capacities, particularly in executive functioning,3 occur alongside marked neurodevelopmental changes (eg, maturation of prefrontal networks) that continue into the mid-20s.4,5 Because of this prolonged neurodevelopmental period and the potential involvement of the endocannabinoid system in such changes,6,7 concerns have increased regarding use of cannabis during this putative critical period of brain development.8,9

While there is consensus that acute cannabis intoxication results in cognitive deficits, residual cognitive effects from cannabis (ie, ones that persist after acute intoxication) are still debated, particularly after a period of abstinence. Numerous studies in adolescents and young adults have reported associations between frequent or early-onset cannabis use and poorer cognitive performance in tasks requiring executive functioning, attention, and episodic memory.10-14 However, findings are somewhat inconsistent,15,16 with several explanatory and confounding variables contributing to variability; these include psychiatric and substance use comorbidities, frequency of cannabis use, and length of abstinence.17-20

SOURCE: The Carlat Report
​Author: Joe Simpson, PhD, MD

If you are interested in part-time correctional work, the best place to start is often the local jail—as opposed to a prison. What’s the difference between the two? A jail is a criminal justice facility operated by a city or county. It houses people who are awaiting trial or who have received short sentences, typically one year or less. In contrast, a prison is operated by a state (or the federal government) and houses inmates who are usually serving long sentences for felonies. Virtually every county has some type of jail facility, often located in large cities. Prisons, on the other hand, are usually remote from urban centers, making part-time employment less feasible.

There is a high demand for psychiatric care in U.S. correctional facilities. At any given time, about 1% of the adult population is incarcerated (Appelbaum PS, Psychiat Serv 2011;62:1121–1123), and many of them have a psychiatric disorder of some sort. One study found that 49% of jail inmates had symptoms of both mental illness and a comorbid substance abuse disorder (James DJ and Glaze LE, Mental health problems of prison and jail inmates. Washington, DC: Bureau of Justice Statistics; 2006. www.bjs.gov/content/pub/pdf/mhppji.pdf), while other studies have found rates of severe mental disorders, including psychotic disorders, bipolar disorder, and major depression, ranging from 10% to 27% of jail and prison inmates (Lamb HR et al, Psychiat Serv 2007;58:782–786).

Diagnostic challenges
Jail psychiatry tends to be fast-paced; for example, your initial intake interview will probably be 30 minutes or less with each new patient. Newly arrived inmates are often very tired and irritated. Many were homeless and abusing drugs or alcohol prior to arrest, and have spent hours waiting in lines, holding tanks, or court lock-ups. They may be very annoyed about having been arrested. By the time they cross your path a day or two after being picked up by the police, they often don’t want to engage in a lengthy interview. This reluctance may continue at your follow-up visits, when you will have even less time to spend with them.
Diagnosing jail inmates poses special challenges. There are various complicating factors, including severe and chronic substance abuse, medical comorbidities, developmental delay and/or low education, personality disorders, and secondary gain issues. While many inmates are legitimately in need of psychiatric care, you will run across others who do not have severe mental illness or even any diagnosis, but who are embellishing, exaggerating, or outright manufacturing psychiatric symptoms for a variety of reasons. The motivations for this kind of malingering vary.
Medication-seeking is common, though you might be surprised at what medications are abused in jail—more on that later. Some inmates may also view you as a way to receive a diagnosis that might shield them from impending punishment for an infraction of jail rules. Others may be hoping you can get them moved to a different part of the jail to avoid threats from other inmates or for opportunities to pass along messages.

Jailhouse prescribing: Art and science
There is one key factor that makes prescribing in a jail setting more challenging than prescribing in a community environment: The selection of medications in your toolbox is severely limited. Given the high rates of substance abuse disorders in the incarcerated population, you will rarely, if ever, prescribe potentially abused drugs. This issue is most relevant to patients who present with ADHD, anxiety, or insomnia.

ADHD
ADHD in jail inmates may be left untreated as many jails won’t allow you to prescribe stimulants. Atomoxetine (Strattera) is a potential choice, although it may not be on formulary, thus requiring the prescriber to go through a prior approval process. Off-label alternatives, such as venlafaxine (Effexor), are sometimes helpful, especially if a patient has both ADHD and depression or anxiety. 

Anxiety and insomnia
Avoid benzodiazepines due to their high risk of abuse and diversion. For anxiety (and depressive symptoms), your primary go-to meds will be selective serotonin reuptake inhibitors (SSRI) such as sertraline (Zoloft) and citalopram (Celexa), as well as the non-SSRI mirtazapine (Remeron). While waiting for these to start working in an anxious patient, you might offer antihistamines such as diphenhydramine (Benadryl) or hydroxyzine (Atarax, Vistaril). These are also commonly used to treat insomnia. High doses of diphenhydramine, up to 150 mg or even 200 mg qhs, are surprisingly well-tolerated by many inmates—perhaps because many have abused sedating substances in the past and have developed tolerance to their effects. You will have to be cautious about prescribing trazodone to a male inmate, due to the risk of a delay in access to appropriate medical care if the inmate develops priapism. Obviously, this is not a concern for female inmates.

On the topic of sexual side effects, you will discover that many male inmates, especially the younger ones, are particularly bothered by the sexual dysfunction induced by SSRIs. For this reason, you are likely to find that you are prescribing mirtazapine much more than you do in your community practice. Many inmates appreciate its sedating qualities, and they often do not mind the side effect of increased appetite. These factors are less relevant for female inmates, who for the most part do not care about decreased libido while in jail, but who are just as concerned about weight gain as are women in the community.

Commonly abused medications
At this point, you may be wondering why I have not mentioned bupropion (Wellbutrin) as an option either for depression or as a non-stimulant alternative for ADHD. While bupropion does not hold much attraction as a drug of abuse in the “free world,” it is one of the most commonly abused medications in jails and prisons. Inmates stockpile doses to take several at once, sometimes crushing the pills and snorting them, to obtain an amphetamine-like high. Bupropion is so sought-after that it is a form of currency, bartered like cigarettes once were before the smoke-free era. For this reason, most jail psychiatrists are very wary of prescribing it, and some institutions have removed it from their formularies. Venlafaxine (Effexor) can also be abused for a stimulant-like rush, but this is significantly less common and only the more savvy inmates are aware of the abuse potential.
Buspirone (BuSpar) might seem like a good option as a non-habit forming treatment for anxiety, but it is also abused by jail inmates, though not to the same extent as bupropion. Gabapentin (Neurontin) also has a tendency to be abused, and is not available in many correctional facilities. For medications with potential for abuse or diversion, if you absolutely need to give them, you can either order a liquid formulation, or if there is no liquid form, order it to be crushed and mixed in water or juice (or another medication that is available in liquid form that the patient is also taking) prior to administration.
When it comes to antipsychotic medications, in addition to all of the typical antipsychotics such as fluphenazine (Prolixin) and haloperidol (Haldol), most jails will have on formulary several of the standard atypicals, including aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), risperidone (Risperdal), and ziprasidone (Geodon). You will quickly discover that quetiapine rivals bupropion as an abused medication. Inmates prize its effects on sleep, and it also seems to provide a relaxing effect. Many inmates will claim to have psychotic symptoms in an effort to obtain quetiapine. For some reason, they don’t seem as interested in olanzapine.

Case example: Is This Inmate Malingering?
Your patient is a muscular man in his late 40s. He reports that he is hearing and seeing things because he doesn’t have his medications. He is able to engage in conversation, his thought process is linear, and he does not appear distracted by hallucinations. He says his regular medications are “Seroquel, Wellbutrin, Depakote, and Xanax.” He then says that he can’t be housed with anyone else (ie, he needs a single cell) because he becomes paranoid, thinks others are trying to kill him, and would get into a fight with a cellmate.
The patient goes on to tell you that he receives SSI disability for mental illness and lives in a board-and-care home. You quickly scan the electronic medical record of his previous stays in your facility and find that during one of them he was prescribed risperidone. You ask him for more details of his hallucinations. He tells you that when he stares at your desk he sees “strippers,” then starts laughing.
As you consider your treatment plan, you suspect that there is an element of malingering in the patient’s presentation. He describes atypical visual hallucinations which do not bother him, and his linear thought process and intact attention are not particularly consistent with a diagnosis of schizophrenia. Three of the medications he claims to take are notorious drugs of abuse in jail (quetiapine, bupropion, and alprazolam).
On the other hand, he is requesting divalproex sodium, which is not a medication that inmates typically seek out. In addition, he appears somewhat agitated, and his repeated arrests, receipt of SSI, and placement in a board-and-care home suggest genuinely impaired function.
In jail, the distinction between authentic symptoms and malingering is rarely black and white. You decide that the patient is most likely exaggerating the hallucinations and the paranoid ideation in an effort to obtain two things: his preferred medications and a safer housing location. However, you also conclude that he most likely does have some type of treatable condition, perhaps bipolar disorder, antisocial or other personality disorder, and/or an impulse control disorder. Since he mentioned divalproex, you decide to start by prescribing that, with a plan to observe him over time to see if his behavior is more consistent with a genuine psychosis or if it reveals evidence more consistent with exaggerated or manufactured psychotic symptoms.

Treating psychosis
Sadly, American jails house a significant number of people with schizophrenia (Lamb HR and Weinberger LE, J Am Acad Psychiatry Law 2013;41:287–293). Many have not committed significant crimes, but have been arrested for minor offenses like trespassing. This population tends to be homeless and to have particularly poor insight into their illness and need for treatment. In order to counter their tendency to “cheek” and then spit out their medications, you will often use liquid or crushed antipsychotics. For similar reasons, the liquid form of the mood stabilizer valproic acid (Depakene) is a good choice in patients with mania, despite being more irritating to the stomach than divalproex sodium (Depakote). In addition, a mood stabilizer like valproic acid/divalproex, or perhaps oxcarbazepine (Trileptal), is often used for inmates who don’t have classic symptoms of bipolar disorder but who are agitated and aggressive, whether due to schizophrenia, traumatic brain injury, developmental disability, severe personality disorder, PTSD, or an impulse-control disorder.

What if your patient with psychosis demonstrates poor compliance with medication? If it is a matter of poor insight and lack of motivation to report for pill call, a long-acting injectable antipsychotic may be a good choice. However, it is critical to realize that jail inmates have the same right to refuse medication as any outpatient. Thus, if your patients refuse medication, you won’t be able to force them to comply. Although jails can have varying policies about patients who require involuntary medications, most of the time these patients must be transferred to a hospital setting. If you are working in a large jail, the facility may have a licensed hospital section where patients can be involuntarily hospitalized and given medications.
​
Conclusion
There are many unique and complicated aspects of diagnosing and prescribing in jail. I touched on some of the more important issues in this article, but space constraints prevented a discussion of managing suicidality, aggression, and detox (for more information on correctional psychiatry, a good resource is Psychiatric Services in Correctional Facilities 3e. American Psychiatric Association. Arlington, VA: 2015). You’ll also learn a lot about treating inmates on the job, especially as you discuss cases with colleagues, including correctional staff, other mental health professionals like psychologists and social workers, and psychiatrists. It’s likely that you will find the work to be intellectually stimulating, extremely interesting, and professionally rewarding.

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.

REFERENCE
Bongiorno, D. M., Daumit, G. L., Gottesman, R. F., & Faigle, R. (2018). Comorbid Psychiatric Disease Is Associated With Lower Rates of Thrombolysis in Ischemic Stroke. Stroke, 49(3), 738-740.

SOURCE: DocGuide

BACKGROUND AND OBJECTIVE
​Anorexia Nervosa (AN), Bulimia Nervosa (BN) and their variants are characterized by persistent alteration of eating behaviour, such as restricted intake or bingeing and purging, as well as excessive concerns about body shape and body weight. Purging behaviour may include self induced vomiting and/or abuse of laxatives, diuretics and physical hyperactivity. Unlike other psychiatric disorders, patients suffering from AN and BN have a high prevalence of many different medical complications, through the sequelae of undernutrition and purging, often with a serious impairment of health status and quality of life. This article describes the main diagnostic and clinical aspects of medical complications in AN and BN.

RESULTS
The medical complications of ED are extremely variable and can occur with only modest biological and physical damage up to extremely serious and life-threatening conditions; the mortality rate of young subjects with AN is 4 - 11% with a risk of death about 12 times higher than that of subjects of the same age of the general population. The management of the medical-internship aspects of AN and BN is rightly placed within complex and articulated programs of interdisciplinary treatment with different levels of intensity of care (outpatient, semi-residential/residential, hospital in cases of emergency/medical and/or psychiatric emergency).

CONCLUSION
The results of the investigations carried out, describe the functions of the various organs and apparatuses and the alterations detected, the possible complications and physiological adaptations to malnutrition.

REFERENCE:
​Gravina G, Milano W, Nebbiai G, Piccione C, Capasso A; Endocrine, in Metabolic & Immune Disorders Drug Targets (May 2018)

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).
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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.