SOURCE: BMJ - British Medical Journal

SOURCE:  Psychopharmacology Institute

Summary of Presentation

• Prazosin is recommended as a first-line agent in sleep disturbances in PTSD with an average dose for men at 16 mg and for women, 7 mg titrated over 5 weeks.
• Trazodone can be used in patients with initial-sleep insomnia with PTSD at a starting dose of 50 mg.
• Avoid benzodiazepines due to its abuse potential. Also, its cognitive side effects may negatively affect psychotherapy effectiveness.
• Quetiapine should not be used first-line in the treatment of insomnia. It is associated with weight gain, which is not dose-related.

Transcript
Today we will be talking about pharmacotherapy of post-traumatic stress disorder, aka PTSD. We will take a particular focus on the treatment of sleep disturbances. We will do this with the help of snippets from Dr. David Osser’s lecture on PTSD algorithms available on our website. Dr. Osser is an Associate Professor of Psychiatry at Harvard Medical School. He is also the founder of the psychopharmacology algorithm project, a useful resource that I have personally used during my residency training. Details on the project will be covered later.

Now, before alarm bells start ringing in youhead when we begin talking about medications in PTSD, I want to make it clear that PTSD, as we know, is associated with both psychological and biological disturbances. There are effective and approved psychosocial treatments for it. Our focus is for the clinician that chooses to use psychotropics, but that does not by any means undermine the importance of psychosocial interventions.

According to the DSM 5, there are 4 main symptom clusters of PTSD; one, avoidance symptoms, two, re-experiencing (like nightmares and flashbacks), three, negative changes in mood and cognition and four, arousal symptoms (like hypervigilance and insomnia for example). OK, now that’s out of the way get ready for some statistics.
Did you know that up to 90% of PTSD patients experience insomnia? Did you also know that up to 70% experience more than 5 nightmares per week? THAT is pretty devastating and you could pretty much be that patient’s hero if you can prescribe correctly to reduce or rid them of nightmares altogether. Also, treating PTSD sleep symptoms can improve daytime core symptoms.

Great! Dr. Osser will now explain the mechanism by which sleep symptoms arise.

Dr. Osser:
Regarding pathophysiology, a word about the pathophysiology of the sleep problems, because that’s going to help you understand our recommendations for treating it. There seems to an increased noradrenergic activity during sleep in patients with PTSD. While trying to fall asleep, this might be what is also making things difficult. The adrenaline is just flowing, it’s a fight or flight feeling much like they had when they were exposed to the original traumas. So it would be good if we have medication that could reduce noradrenergic activity in the brain, but the main treatments usually recommended for PTSD, indeed the only FDA approved treatment, SSRIs, actually exacerbate these symptoms and can make sleep worse. But there is a class of drugs, one of which is prazosin, that are adrenergic blockers, and they target the impaired sleep in PTSD patients. And as it does so, it also produces substantially larger effect sizes in improvement in other symptoms of PTSD even during the day.
And this is where we start our interesting relationship with prazosin. So, because of prazosin’s alpha-adrenergic blocking abilities, it theoretically can improve sleep. Take note that prazosin is not a sedating agent in itself.

Dr. Osser:
After you’ve ruled out or managing other causes of sleep disturbances, and if the patient has PTSD-related nightmares or disturbed arousals, we recommend you consider a trial of prazosin as the first-line medication treatment.

What is the evidence behind this?

Dr. Osser:
To discuss the efficacy issues with prazosin, we’re at a critical point in this lecture today because this evidence is somewhat mixed as I am about to share with you. There are five placebo-controlled randomized trials with prazosin. They’re all from Dr. Raskind’s group in Washington, affiliated with the University of Washington. The four published studies were all very positive. The impact on PTSD symptoms was mostly twice as great with the drug as on placebo which can be translated to an effect size of 1 or 1.0. If you look just at the effect on nightmares though, it was a 200% increase over placebo for the effect size on nightmares. That would translate to a 2.0 effect size. Now to put into contrast, what do you think the effect size of SSRIs are on PTSD symptoms? In a 2015 meta-analysis of all the SSRI studies in PTSD, the effect size was 0.23. That was the mean effect size of all the SSRIs. That’s only 23% better than placebo.
The effect size of prazosin is really quite impressive. But it’s not all fun and games with prazosin, first in terms of its side-effect profile and second because of the looming, dark shadow that the 5th study has cast upon us. Enough suspense? Not quite! Let’s review the side effect profile first!

You may already know this but prazosin was classically used to treat hypertension. So one of its prominent side effects in causing hypotension. Hypotension in the elderly can cause an increased likelihood of falls and fractures. This can be of particular concern in patients who are already on antihypertensives. Dr. Dana Wang asks Dr. Osser about monitoring.

Dr. Wang:
How do you monitor the BP when starting prazosin? I have asked my patients to buy the BP cuff and monitor daily in the beginning before the dosage is stabilized, is this necessary?

Dr. Osser:
I do not do that. I don’t monitor blood pressure routinely. I only do it if they develop possible dizziness or other signs that might suggest they’re having blood pressure problems. And sometimes, it can be unclear whether this is a blood pressure related symptom or whether it’s another kind of problem like sedation. So the blood pressure is useful there. So I guess it would be good for them to have a blood pressure cuff handy if they’re doing this at home so that they could check it and help determine the cause of any symptoms they’re having.
So, Dr. Osser does not generally recommend monitoring blood pressure routinely.
Be sure to check the full interview which will be released soon on our website for all our listeners. So, watch this space.

Now, the results of this 5th trial came out in February 2018 by Dr. Raskind and his team. It was conducted on nearly 300 military veterans with chronic PTSD. Half were given prazosin and half were given placebo, titrated over 5 weeks. The results revealed that prazosin did not alleviate distressing dreams OR improve sleep quality compared to placebo. Quite a disappointing result. I emailed Dr. Osser about this study and he wrote, “But it [this result] doesn’t negate the results of the other positive placebo-controlled studies plus numerous observational studies and recorded clinical experiences with prazosin which is positive – very positive.”

According to a commentary by Dr. Peter Roy-Byrne, he said, quote, “These findings may have been negative because participants were relatively stable, nonsuicidal veterans without substance dependence who were not deemed ill enough by their treating clinicians to treat openly with prazosin… Also, participants were not screened for sleep apnea, which could have interfered with prazosin’s effects.”
He also went on to propose that perhaps this group of patients had a subtype of PTSD that was less adrenergically driven. The rest of the commentary is referenced in the transcript of this podcast. And despite this latest evidence, Dr. Osser’s algorithm still recommends using prazosin as a first-line treatment for PTSD-related sleep disturbances.
Now let us speak a bit about the dosing of prazosin.

Dr. Osser:
A couple of studies have been published showing that 85% to 90% of patients who are put on prazosin are given a subtherapeutic dose and the clinicians give out prematurely. The reason seems to be just lack of knowledge of what the protocol was that Raskind used in his four studies for dosing the patients. I’m gonna share that with you right now. But there is also another barrier besides knowing the protocol and that is that this protocol takes some time to administer.

So, here’s how it was. First of all, there’s two different protocols for the men and the women. We don’t know why but for men, you seem to need significantly more to get the same effect. So first of all, where are you going? You’re going for a mean average dose at endpoint of 15.6 or about 16 mg. That was the average of Raskind’s fourth and final published study in 2013. That meant that half of the veterans needed more and half needed less than 16. And how did he get there? He went with 1 mg at bedtime for two nights, then 2 mg for five nights. Then, 4 for seven nights, 6 for seven nights, 10 for seven nights, 15 for seven nights. So in other words, it took five weeks to get to the average dose and then 25 after seven nights on 15. That’s the maximum he used in that study.
Now, the protocol for women is roughly half of that at the end, although it starts the same. Ten was the maximum that they used in that study. The median dose that was effective was 7.

So the average dose for men is about 16 mg and for women 7 mg, titrated over a period of 5 weeks. Also, patients were given a mid-morning dose for daytime symptoms. The mean mid-morning dose was 4 mg for men and 2 mg for women in that protocol.
Dr. Osser:
The goal of treatment is to eliminate these disturbed awakenings and give them a smooth night of sleep. And that’s one of the reasons people stop at earlier doses. Maybe they’ve been having a nightmare every night, maybe two or three times a night for years. And now after they get up to 4 or 6 of prazosin, it’s down to only two or three nightmares a week. Wow, the patient is very happy. And the doctor may be happy too, but not realizing that if they keep going, the nightmares could be eliminated altogether.
So, aim for complete remission of nightmares.

Now, to recap, we have touched upon how sleep disturbances may arise in PTSD, and how that relates to prazosin. We have also reviewed the efficacy studies and side effects of prazosin as well as the dosing for both men and women. Now let’s briefly see what alternatives we have.
What if your patient still has disturbed sleep, particularly in initiating sleep? Well, according to the algorithm the next step you could do is to introduce our good old friend, trazodone.

Dr. Osser:
Our first-choice hypnotic for helping them fall asleep is trazodone. I’m sure you’re familiar with trazodone. It’s a sedating antidepressant. It’s shown some effectiveness for sleep disturbances in PTSD, but really only in open-label studies. It has been described, though, as an ideal hypnotic agent by Stephen Stahl in an article he wrote a few years ago because of its triple sleep-promoting actions on the 5-HT2A, alpha one, and H1 receptors. It also has a short half-life, no weight gain, low risk of dependence, no problems with sexual side effects, so it’s got a lot of things that make it a relatively ideal choice for many patients.
Any evidence supporting its use in PTSD?
Dr. Osser:
Now, as far as what evidence we do have with trazodone, there is that one open-label study. What I do offer, though, is two studies of using trazodone versus placebo for SSRI-induced insomnia. SSRIs, as noted, often cause insomnia as a side effect, maybe 15 or 20% of patients, and in two randomized controlled trials, trazodone was an excellent treatment for that. It also has been compared with zolpidem for primary insomnia. It was in a large trial which also had a placebo control, and it proved comparable in efficacy for primary insomnia. So, there’s a variety of lines of evidence that trazodone is a reasonable insomnia treatment that you might apply in this situation.
The ideal starting dose is 50 mg. If the patient finds it too sedating you can halve the dose to 25 mg or even 12.5 mg at night. When I prescribe trazodone, I let my male patients know about one of its rare, but rather disturbing side effects, which is… you guessed it, priapism.

Dr. Osser:
The side effects of trazodone include excess sedation, dizziness, orthostatic problems occur from time to time, and syncope occasionally. So, you do have to be cautious for worrying about and watch for that. Now, perhaps the most often-mentioned side effect, though, in males is priapism, and that is a concern. It’s an infrequent concern. Serious priapism only occurs in one in 2000 or 3000 patients, but you do need to warn people about it, and in theory the risk of priapism may be increased if you combine trazodone with prazosin, which has a very rare, sometimes not even mentioned in typical patient information sheets that prazosin has been associated with priapism. So, some have thought that you shouldn’t combine prazosin with trazodone, because of a possible increased risk of priapism. So far, there hasn’t been any reported cases of priapism in this commonly-used combination. Nevertheless, extra caution with warning about priapism is certainly necessary in combining them, and we do that routinely.
We are nearing the end of this review of the treatment of sleep symptoms in PTSD. Before I go, there are a couple of important things for you to know; one about benzodiazepines and the other about prescribing quetiapine for sleep.

Dr. Osser:
Now, what about benzodiazepines? Benzodiazepines have high potential for abuse in patients with PTSD. A big study showed that; more than other anxiety disorders, and this is with or without comorbid substance use disorder in those patients. So certainly if the patient has a history of substance abuse you certainly would want to avoid them. But if you, for some reason, did prescribe, be sure it would be a small quantity to test their ability to use it appropriately. They could be considered if there’s a past history of clear response without significant abuse or misuse. You should know, though, that in the few studies, benzos have no efficacy for the primary symptoms of PTSD. Another problem is that they may reduce the short or longterm effectiveness of psychotherapies for PTSD, such as exposure therapy. That’s another significant concern: if you can’t remember the therapy, then it’s not going to do that much good. At least that’s what seems to be the mechanism proposed in these studies.

And that leaves us, finally, with quetiapine which is widely prescribed for sleep in PTSD. It deserves a lot more time than I have today to tell you why you shouldn’t be doing it, but I will refer you to a review article on reports of using quetiapine for sleep in various patient populations that concluded that, quote: The benefits did not justify the risks. And it should not be used as a first-line treatment for any kind of insomnia. It’s interesting to note that the weight gain from quetiapine is not dose-related. Unlike other antipsychotics like olanzapine, where the weight gain is dose-related, it is not with quetiapine. So you can get the Seroquel munchies is what some of my veterans refer to it, this running into the kitchen about a half hour after you take it and having a couple of peanut butter and jelly sandwiches. Night after night, so they can gain a lot of weight on 25 or 50 milligrams for sleep and this definitely is not a great thing for these patients.
So it would be better to avoid benzos and watch out for those Seroquel munchies!
Be sure to check out Dr. Osser’s algorithms at psychopharm.mobi and the full lecture on our website.

Key Points

• Sleep disturbances in PTSD may be due to increased noradrenergic activity during sleep.
• Prazosin is an alpha-adrenergic blocker which explains why it can improve sleep symptoms.
• Prazosin is recommended as a first-line agent in sleep disturbances in PTSD with an average dose for men at 16 mg and for women, 7 mg titrated over 5 weeks. The mean mid-morning dose is 4 mg for men and 2 mg for women.
• Prazosin can cause hypotension but generally does not require routine monitoring. It is also theoretically associated with an increased risk of priapism when used with trazodone.
• Trazodone can be used in patients with initial-sleep insomnia with PTSD at a starting dose of 50 mg.
• Avoid benzodiazepines due to its abuse potential. Also, its cognitive side effects may negatively affect psychotherapy effectiveness.
• Quetiapine should not be used first-line in the treatment of insomnia. It is associated with weight gain that is not dose-related.

References

1. Koffel, E., Khawaja, I. S., & Germain, A. (2016). Sleep disturbances in posttraumatic stress disorder: updated review and implications for treatment. Psychiatric Annals, 46(3), 173-176.
2. Raskind, M. A., Peskind, E. R., Chow, B., Harris, C., Davis-Karim, A., Holmes, H. A., … & Romesser, J. (2018). Trial of prazosin for post-traumatic stress disorder in military veterans. New England Journal of Medicine, 378(6), 507-517.
3. https://www.jwatch.org/na46003/2018/02/07/prazosin-ineffective-chronic-ptsd-military-veterans
4. http://psychopharm.mobi/algo_live/

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.