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found that a combinational pharmacogenetic test was a better predictor of medication blood level and patient outcomes than single-gene testing alone.

Common psychiatric medications for depression and anxiety can react with patients’ genes in ways that inhibit the drugs’ effectiveness. It is possible to test single genes for potential interactions, but Myriad Genetics has developed a test that 

 The study found that testing variations in multiple genes led to better, more predictive results.

The study’s lead author was Anthony J. Rothschild, MD, Irving S. and Betty Brudnick Endowed Chair and Professor of Psychiatry at the University of Massachusetts Medical School. In the article, he and his coauthors explained the importance of the findings as follows: “This evaluation of clinical validity shows that only the combinational pharmacogenomic test was significantly associated with improved patient outcomes. In addition, the combinatorial pharmacogenomic test was a superior predictor of medication blood levels across a larger group of medications relative to guidelines focused on only CYP2C19 and CYP2D6.”

The study was based on data from the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial.

 Between 2014 and 2017, the GUIDED trial drew participants from 60 psychiatry and primary care centers around the United States. In order to be eligible, participants needed a major depression disorder diagnosis and a score of 11 or more on the 16-item Quick Inventory of Depressive Symptomatology Scale at screening. They also needed at least 1 failed trial of psychotropic medication during their current depressive episodes.

 Participants were placed blindly into the pharmacogenomic-guided care or conventional treatment arms of the trial for 8 weeks. The researchers then measured and analyzed their outcomes.

The GUIDED trial did have some limitations. It was not a controlled pharmacokinetics study, meaning “blood levels were not controlled for time of intake or medication adherence.”

 As blood levels were only collected at screening, they could not be directly linked to adverse events or other outcomes. Still, the results were promising.

“This analysis demonstrates that the combinatorial approach of the GeneSight test more accurately predicts blood drug levels and identifies more patients with significant gene-drug interactions who would be missed by single-gene testing,” Mark Pollack, MD, chief medical officer of Myriad Neuroscience, said in a statement to the press. “Combinatorial pharmacogenomics like the GeneSight test should become the standard-of-care to help physicians understand gene-drug interactions that could improve care for people with depression, anxiety and other conditions.”

1. Rothschild AJ, Parikh SV, Hain D, et al. Clinical validation of combinatorial pharmacogenomic testing and single-gene guidelines in predicting psychotropic medication blood levels and clinical outcomes in patients with depression. 

2. GeneSight psychotropic test’s combinational approach proves better than single-gene testing at predicting patient outcomes and medication blood levels. 

February 8, 2021. Accessed March 4, 2021. 

https://www.globenewswire.com/news-release/2021/02/08/2171246/0/en/GeneSight-Psychotropic-Test-s-Combinatorial-Approach-Proves-Better-than-Single-Gene-Testing-at-Predicting-Patient-Outcomes-and-Medication-Blood-Levels.html

A study finds that testing genetic variations can predict outcomes and medication blood levels in patients with depression. 

How Will Patients React to Medications? The Answer May Be in Their Genes

How often do your patients share with you the positive and negative effects of medications?

All About Adverse Effects: Psychotropics Poll

Literature is emerging on the effects of the coronavirus disease 2019 (COVID-19) pandemic on patients with bipolar disorder. This is part of the much larger literature on assessment and management of mental disorders during the 

Our group of 11 clinicians at the US Department of Veterans Affairs Bipolar Disorders Telehealth Program recently 

 of lessons learned from using telehealth modalities (videoconferencing and telephone contact) with more than 3000 veterans whose caregivers submitted consultation requests.

 is the way many, if not most, patients currently are being seen by clinicians. Many patients will continue to use this method even after the pandemic has waned. Telehealth has some specific effects on patients with bipolar disorder.

Video sessions and calls generally are very much welcomed by patients who are isolated to various degrees because of COVID-19. Their usual social outlets are diminished, and their access to in-person visits with clinicians is much reduced or eliminated. Hence, contact with an upbeat, thorough, authoritative, and supportive consulting clinician can have a tremendous effect in reassuring patients that help is available. In fact, 

 may diminish immediately during the call.

Effort must be made, however, to deal effectively with wireless connectivity issues that may render speech garbled with dropped words or pronunciations that are difficult to understand.

 It is important to slow down the conversation, adjust volume or microphone or video placement, be mindful of the time lag that can occur between speech and the transmission of the speech, and avoid interrupting the patient by responding too quickly. Video and phone transmission might make it difficult to determine if the patient is becoming tearful or 

, and it is important to ask if this is occurring.

Another issue associated with the pandemic is the loss of usual routines of behavior associated with previous mood states before isolation can result in new outlets (eg, buying online instead of in stores during manias). The clinician should be prepared to ask questions to uncover new syndromic behaviors.

 issues that are relatively unique to the COVID-19 era were summarized in a recent review by experts from Spain.

 Medication adherence is often reduced during isolation, so it is important (after establishing a therapeutic alliance using some of the previously noted suggestions) to inquire about adherence. Similarly, after examining the possible causes of nonadherence (eg, real or feared adverse effects, the feeling of being controlled by the medication, missing periods of euphoria), clinicians should educate their patients about the importance of adherence. Help may be needed from significant others in the household to monitor adherence, with the patient’s permission.

Substance use disorders may increase in severity in the isolation setting, and these should be ruled out or managed, if necessary. Patients may be fearful of initiating new medications without an in-person encounter, especially if bloodwork is required or patients have concerns about entering a medical facility for

 The importance of lithium levels and kidney function tests will need to be reiterated and the benefits weighed against the risks associated with going to get the tests, which can be minimized with appropriate social distancing and masks.

 with medications used in the treatment of patients who have COVID-19, if the patient requires hospital treatment.

 Dexamethasone can induce mood switches to mania or depression. Dexamethasone’s metabolism is induced by carbamazepine and, to a lesser extent, by oxcarbazepine. Initiation of these anticonvulsant mood stabilizers should therefore be avoided if possible. They also induce the metabolism of remdesivir, and carbamazepine may add to the risk of liver dysfunction caused by this antiviral agent. If the patient is already on one of these mood stabilizers, appropriate dosage adjustments of the COVID-19 drugs and lab monitoring will be needed. Chloroquine and hydroxychloroquine should be avoided in patients with COVID-19 and bipolar disorder because they increase risk of mania, psychosis, and 

is associate professor of psychiatry, Harvard Medical School, and co-lead psychiatrist at the US Department of Veterans Affairs, National Telemental Health Center, Bipolar Disorders Telehealth Program, Brockton, Massachusetts.

1. Bojdani E, Rajagopalan A, Chen A, et al. 

COVID-19 pandemic: impact on psychiatric care in the United States

2. Burgess C, Miller CJ, Franz A, Abel EA, et al. 

Practical lessons learned for assessing and treating bipolar disorder via telehealth modalities during the COVID-19 pandemic

4. Hernández-Gómez A, Andrade-González N, Lahera G, Vieta E. 

Recommendations for the care of patients with bipolar disorder during the COVID-19 pandemic

As we learn about the effect of COVID-19 on patients with bipolar and other psychiatric disorders, clinicians should be prepared to ask questions to uncover new syndromic behaviors.

COVID-19 Pandemic’s  Effects on Assessment & Psychopharmacological Management

John J. Miller, MD, shares information on a topic he is passionate about: serum levels. 

is medical director, Brain Health, Exeter, NH; editor in chief,

; staff psychiatrist, Seacoast Mental Health Center, Exeter, NH; consulting psychiatrist, Exeter Hospital, Exeter, NH; consulting psychiatrist, Insight Meditation Society, Barre, MA.

Serum Levels in Psychiatric Medications

Cannabis is gaining wider acceptance as a therapeutic for mental health issues. California-based Royal Emerald Pharmaceuticals is currently pursing Federal Drug Administration approval to research, develop, and manufacture medicines derived from cannabidiol (CBD) and tetrahydroncannabinol (THC).

In this Mental Health Minute, founder and CEO of Royal Emerald Pharmaceuticals Mark Crozier reveals the motivation behind his quest to make non-addictive medicines for PTSD, pain, anxiety, depression, opiate addiction, and other conditions.

is the Founder and CEO of Royal Emerald Pharmaceuticals. Crozier has 40 years of experience in the military and law enforcement with the bulk his career

was spent in criminal intelligence. He is a former Army Ranger and a retired federal police chief.

Would you prescribe non-addictive cannabis treatments? 

Share comments with your colleagues by emailing 

. Comments may be shared online pending review and editing for style.

Research on a new kind of cannabis treatment prepares to move forward. 

Cannabis-Based Medicine Without the Addiction Risks?

When the email from “Sam” arrived asking about adding a natural weight loss product to his more mainstream prescription medications, I was not surprised. Binge eating was his bête noire. A onetime college athlete who lost his scholarship because of an ankle injury, he had since sat around eating while watching sports on TV and lamenting his lost career. He desperately wanted to shed unwanted weight, but treatments that control bingeing do not guarantee weight loss. He had tried 

 with no success. So, when he heard about a new natural weight loss concoction, he was understandably excited yet skeptical because he knew of the government’s crackdown on hoodia.

Sam forwarded me a laundry list of ingredients without hoodia but with 

 (Pausinystalia yohimbe). Years had passed since I had seen that word in print.

“Was it safe?” was all he wanted to know. Whether it worked seemed to be a secondary concern. My short answer was no, and I promised a longer explanation at his next appointment. In the interim, flashbacks of another patient from long ago popped up. Although psychopharmacology has quickly evolved in the decades since the 

, that related case was too dramatic to forget.

I remember the frantic call from the ED staff, begging me to see their patient posthaste.

“Maybe you can prescribe lithium or haloperidol or something like that. We cannot contain him here, but we have nowhere to send him,” said the pressured voice on the phone. “He saw a psychiatrist, but that is all we know.”

It was Sunday midmorning, late summer, when many Manhattanites escape town leaving side streets empty and opening tables at New York City’s unending array of eateries. Uninterrupted by impatient New Yorkers demanding seats, out-of-towners could enjoy unhurried brunches, fussed over by glamorous waitstaff who were patiently anticipating their Broadway debuts. The tidy townhouses lined side by side behind the hospital conveyed an extra sense of calm that contrasted with rowdy Saturday nights.

 which was nearly abandoned. I peered through the window of the make-do quiet room and could see that the doctor who called the consult was not exaggerating. A tanned, middle-aged man stood a few feet behind the door. He looked to be 50-something, but he jumped and hopped like a child, in sync to the beat of an invisible drum. His thinning silver hair swung wildly. Most strikingly, his suit jacket was draped around his waist, hiding his backside and little else. Empty sleeves looped across the front, dangling like a loincloth, albeit one with a shiny—probably pricey—silk lining. Where he left his pants, shoes, socks, and shirt was anyone’s guess. All I knew is that he wore nothing else.

Per protocol, I checked the chart before walking into the room, not just for safety’s sake but to

 by skimming the demographics. He was, in fact, middle-aged, married, and, in hindsight, possibly a vestige of the 

 had not aired yet. For that matter, sildenafil had not been invented, nor had the now-ubiquitous second-generation antipsychotics that are often used to treat bipolar disorder. Per the intake sheet, “Mr Smith” was a senior vice president at a name-brand advertising firm, even if his present posture suggested otherwise.

The history mentioned that his private psychiatrist, who had retreated to the Hamptons for the summer, referred all emergencies to the hospital, as per his answering machine message. Before leaving, said psychiatrist started him on lithium, then carbamazepine, maybe even 

, but now everything spiraled out of control. Experience told me that advertising executives with bipolar disorder tendencies are not uncommon, because advertising takes high energy, unabashed enthusiasm, and lots of chutzpah, which are abundant in 

. Yet it was also unlikely that someone with uncontrolled bipolar disorder could rise so high through the corporate ranks, even if his prescriptions screamed bipolar. It was also unlikely that this behavior represented garden-variety bipolar disorder, because the nurse noted that he was disoriented to time and place, distracted, and responding to unseen stimuli. His rapid, jerky movements put me on high alert for impending seizures, even though a cursory 

I scrolled through the medication list, checked the charted vital signs, scanned all labs listed, and looked for clues to explain this seemingly sudden deterioration. Even the toxicology screens were negative. The medications included several antihypertensives, which opened the possibility of a recent cerebrovascular accident secondary to hypertension, but he was moving all 4 limbs without restrictions, and his frenetic, dancelike activity functioned as a makeshift 

 stress test, making it unlikely (but not impossible) that his strange symptoms followed hypoperfusion. There was only 1 odd entry, a little, nearly illegible word: Yocon.

In those days, we checked prescription pharmaceuticals through big, bulky Physicians’ Desk Reference editions with thin pages and small print. And that was where I found the culprit: that little word was the trade name for 

, a reputed (but disputed) aphrodisiac used in fertility rituals in Cameroon, Central Africa, according to a memorable medical school ethnopharmacology lecture. I called the man’s internist, who had hospital privileges and even made rounds on weekends. The internist checked his chart and confirmed that a urologist had started the man on prescription yohimbine a few weeks earlier. The doctor noted that he added more antihypertensive medications soon after, which made sense, given that this herb can increase blood pressure and interfere with the efficacy of blood pressure medications.

The nurses crowded outside the room, eager for an explanation, and appreciative of the colorful story behind this mystery. Yohimbine was an α1-adrenergic agonist, a product of an East African tree with a similar name. It was marketed as an 

 and subsequently approved for this purpose, despite equivocal evidence. Whether yohimbine helped in this regard was unclear, but its psychoactive properties were apparent. I wondered whether prescriptive yohimbine (or nonmedicinal yohimbe bark) directly increased libido as advertised, or whether it simply induced 

 in susceptible individuals, with the attendant hypersexuality of mania.

That theory was within the realm of possibility, especially because recent reports confirm that the stimulant especially affects individuals who are predisposed to bipolar disorder, as well as schizophrenia, panic disorder, and 

. Even popular online consumer medical websites warn against its use in cases of depression because it can precipitate manic reactions.

 The National Institute of Health’s National Center for Complementary and Alternative Medicine, now the National Center for Complementary and Integrative Health, has since taken a 

, warning against its use in individuals with any psychiatric history.

Over time, we learned much about yohimbine and its positive and negative effects. Although it fell into disuse after the invention of the much more predictable 

 indicated for erectile dysfunction, online marketers still promote it for a wide range of problems, including appetite suppression and obesity. Yohimbine gained greatest use as a veterinary antidote to animal tranquilizers. It has been misused by some humans, as was the case with ketamine, a onetime animal tranquilizer turned club drug that has recently been repurposed as a treatment for depression. No comparable success stories have been reported for yohimbine, although bodybuilders cite anecdotal evidence that the herb enhances exercise endurance. In contrast, forensic medicine journals 

 and note that yohimbine can cause delirium, hallucinosis, seizures, and sometimes deaths. An 

article in American Journal of Psychiatry

confirms that it can switch depression into mania.

Importantly, dangerous interactions can occur with 

—so it was fortunate that the patient quieted down with a dark, soundless room and intravenous diazepam, prescribed by the neurologist to stop seizures should they occur. Aided by the tincture of time, and a short stay upstairs once a bed opened, he reportedly returned to baseline. When I checked on him a few days later, he did not recall this episode.

In hindsight, our mystery man escaped easily. Who knows what tragedies could have occurred had strong psychotropics been added to his medication mix without stopping the clandestine culprit? At worst, lethal medication interactions could have followed. And, at best, he would have been condemned to a lifetime’s treatment for a condition that might not have emerged without this botanical boost.

, and we must consider the big picture, without reflexive and thoughtless prescriptions for psychotropics—even if the general public, as well as other medical professionals, assume that is all we do. As for Sam, I expect him to appreciate this warning story about yohimbine, even if the negative studies about its efficacy for weight loss disappoint him.

is assistant clinical professor of psychiatry and behavioral sciences at Icahn School of Medicine at Mount Sinai, New York, NY.

Three cases of manic symptoms following yohimbine administration

2. Yohimbe. National Center for Complementary and Integrative Health. Updated November 2020. Accessed December 21, 2020. 

3. Anderson C, Anderson D, Harre N, Wade N. 

Case study: two fatal case reports of acute yohimbine intoxication.

As physicians first, psychiatrists must consider the big picture, without reflexive and thoughtless prescriptions for psychotropics—even if many, including medical professionals, assume that is all we do.

Never Forget the Fine Print: From Fertility Rites to “Miracle Med”

Available evidence indicates that benzodiazepines are commonly used to treat various disorders including anxiety, insomnia, agitation, alcohol withdrawal, and seizures.

 of benzodiazepine use among older adults in the United States is approximately 8.7%

; but it has been noted that approximately 44% of the prescriptions for benzodiazepine among older adults are potentially inappropriate.

2019 American Geriatrics Society Beers Criteria

 identifies benzodiazepines as potentially inappropriate medications for use among older adults.

) Factors associated with long-term use of benzodiazepines include the following: female sex, a diagnosis of Alzheimer disease (AD), schizophrenia, bipolar disorder, depression, coronary artery disease, and asthma/chronic obstructive pulmonary disease.

 is known to be associated with poor outcomes.

 One study found that benzodiazepine use was associated with greater risk for hospitalizations, emergency department visits, outpatient visits, and higher health care costs.

 Another study found the overdose death rate increased due to benzodiazepine use from 0.58 to 3.07 per 100,000 adults between 1996 and 2013.

 Benzodiazepines use is also associated with an increased risk of falls among older adults.

 Additionally, the use of benzodiazepines is associated with a 60% to 80% increase in the risk of traffic accidents.

 The co-ingestion of benzodiazepines and alcohol is associated with a 7.7-fold increased risk for traffic accidents.

Now, there is also emerging evidence that the use of 

 may increase the risk for developing dementia among older adults.

 This review evaluates the evidence from the literature on the association between benzodiazepine use and the risk for developing dementia.

A review of the literature indicates that there is a total of 15 studies that have evaluated the association between benzodiazepine use and the development of dementia.

 Four of the 15 studies were published prior to 2010

 and 11 of the studies were published since 2010.

Although there are no randomized controlled trials (RCTs) looking at the association between benzodiazepine use and the risk for dementia, 6 prospective cohort studies,

 and 1 retrospective cohort study18 explore the relationship. Two studies had both a prospective cohort and a case control component.

 Three of the studies were conducted in France,

 and 1 each in Sweden,14 the United States,

Of the 15 studies, 8 showed a positive association between benzodiazepine use and the development of dementia.

 Of these 8 studies, 2 were prospective cohort studies,

 had a prospective cohort and a case control arm to the study.

Four studies found benzodiazepines were not associated with the development of dementia.

 The negative studies included 2 case control studies,

 and 1 study that had a prospective cohort and a case control arm.

 One study found that previously using benzodiazepines was associated with the development of dementia, but current use was not.

 The other study found that short-term use of benzodiazepines was associated with the development of dementia, but long-term use was not.

 Finally, 1 prospective cohort study found that the use of benzodiazepines had a protective effect against the development of dementia.

More than half of the studies (8 out of 15, 53%) identified in the literature search showed a positive association between benzodiazepine use and the development of dementia. It is unclear whether there is any significant difference between men and women. This is true with higher doses; when the duration of use is shorter; for current users; for shorter-acting drugs; and study design (eg, cohort studies). (see 

Despite the evident association between benzodiazepine use and the development of dementia, a causality cannot be established, as none of the identified studies were RCTs.

Three important reviews have evaluated the association between benzodiazepine use and the development of dementia.

 In the first review, the investigators evaluated 3 studies that found an increased risk of cognitive decline among those using benzodiazepine, and 2 studies that found a lower risk of cognitive decline in former or ever users of benzodiazepines, and 2 studies that found no association between the use of benzodiazepines and the development of dementia.

 In another review that evaluated 10 studies, the investigators found that 9 studies showed an increased risk of dementia among those who used of benzodiazepines.

 The investigators opined that the risk of dementia increases with cumulative doses of medication, longer treatment duration, and when long-acting agents are used. In the third review that evaluated data from 11 studies, the investigators 

 positive association between benzodiazepine use and the development of dementia from 9 studies.

 One study found a protective effect for benzodiazepine use, and 1 study found no effect for benzodiazepine use and the development of dementia.

Three recent meta-analyses evaluated the risk of developing dementia among individuals who use benzodiazepines.

, which included data from 6 studies, the investigators found the pooled adjusted risk ratios (aRRs) for the development of dementia was 1.49 for those who have used benzodiazepines, 1.55 for those who recently benzodiazepines, and 1.55 for those who have previously used benzodiazepines, when compared with never users of benzodiazepines.

 The researchers stated the risk for dementia increased by 22% for every additional 20 defined daily doses of the drug per year (aRR=1.22).

that included data from 10 studies found the odds for developing dementia was higher by 78% among users those who were using benzodiazepines when compared to those who were not (OR=1.78)

 The investigators found a higher association when the studies were from Asia (OR=2.40), and a moderate association when the studies were from North America and Europe (OR=1.49).

 that included data from 12 prospective and retrospective cohort studies and case-control studies found that benzodiazepines can be a risk factor for the development of dementia (OR=1.38).

 The investigators concluded that the current evidence lacks the power to differentiate between the risks for the development of AD versus vascular dementias (VD), the risks when using long-acting versus short-acting benzodiazepines, and the risks based on the duration and the doses of the drugs that are used.

 Carl Salzman, MD, provided a counterpoint to the question on whether benzodiazepines cause AD.

 Salzman stated that “there is little doubt that benzodiazepines like other sedative hypnotics may be associated with impaired cognition which is usually mild and dose-dependent.” He reported that the usual recommendations include only short half-life benzodiazepines at low doses and, if clinically possible, for brief periods of time. Salzman opined that future studies are needed regarding benzodiazepines’ and other medications’ possible associations with the development of late-life cognitive disorders. Until then, he advised that we must assume that the appropriate use of benzodiazepines will not lead to the development of AD. One caution with this editorial is that it cites a limited number of studies evaluating the association benzodiazepines and AD, and it is difficult to develop any definitive conclusions based on these studies.

The available evidence for the association between benzodiazepine use and the development of dementia should be evaluated based on the heterogeneity between the studies and limitations of each of these studies. These studies were conducted in different countries and had differing methodologies. In addition, many studies did not control for confounding variables including educational attainment, the presence of depression, anxiety, insomnia, and alcohol use. Also, 4 studies used the older DSM III-R criteria for the diagnosis of the dementia, causing concerns regarding the validity of the diagnosis. It is unclear whether the observed association between the use of benzodiazepines and the development of dementia is really a causal effect, or the result of unmeasured confounding variables, as none of these studies were RCTs.

 occurs when a pharmaceutical agent has been inadvertently prescribed for an early manifestation of a disease that has not yet been diagnostically detected. A prolonged lag phase between the first appearance of brain pathology associated with dementias, the development of clinical symptoms that may be risk factors for dementias including anxiety and depression, and the actual clinical diagnosis of dementia has led to investigators citing protopathic bias or “reverse causality” as the main area of controversy regarding the association between benzodiazepine use and the development of dementia.

 To prove a definitive association between benzodiazepine use and the development of dementia, the studies would have to be approximately 3 decades long given the prolonged life course of neurodegenerative disorders like dementias.

There are 3 possible mechanisms that have been postulated for the association between benzodiazepine use and the development of dementia.

 For one, benzodiazepines possibly decrease activity of β-amyloid precursor protein-cleaving enzyme 1 (BACE-1) and c-secretase activity, thus promoting β-amyloid accumulation in the brain. Secondly, astrocytes near the β-amyloid accumulation in the brain secreting γ-aminobutyric acid (GABA), thereby promoting the negative cognitive effects of benzodiazepines. Finally, benzodiazepines may reduce the cognitive reserves by lowering brain activation levels.

Available evidence indicates a positive association between the use of benzodiazepines and the development of dementia, although causality cannot be inferred from this data. Despite the lack of evidence proving causality, the association between benzodiazepine use and the 

 is a major cause for concern given the prevalence benzodiazepine use among older adults. The prescription of benzodiazepines to older adults must be carefully reviewed given the lack of data regarding their long-term efficacy and their significant adverse effects including the risk for developing dementia.

is the chairman of the department of psychiatry and behavioral sciences, Cleveland Clinic Akron General, Akron, OH.

is a psychologist in the Department of Psychiatry and Behavioral Sciences, Cleveland Clinic Akron General, Akron, OH

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

1. Lader M. Benzodiazepines revisited--will we ever learn? 

3. Dionne PA, Vasiliadis HM, Latimer E, Berbiche D, Preville M. Economic impact of inappropriate benzodiazepine prescribing and related drug interactions among elderly persons. 

4. By the 2019 American Geriatrics Society Beers Criteria® update expert panel. 

American Geriatrics Society 2019 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults

5. Taipale H, Koponen M, Tanskanen A, et al. Long-term use of benzodiazepines and related drugs among community-dwelling individuals with and without Alzheimer disease. 

6. Bachhuber MA, Hennessy S, Cunningham CO, Starrels JL. Increasing benzodiazepine prescriptions and overdose mortality in the United States, 1996-2013. 

7. Díaz-Gutiérrez MJ, Martínez-Cengotitabengoa M, Sáez de Adana E, et al. 

Relationship between the use of benzodiazepines and falls in older adults: a systematic review

8. Dassanayake T, Michie P, Carter G, Jones A. Effects of benzodiazepines, antidepressants and opioids on driving: a systematic review and meta-analysis of epidemiological and experimental evidence. 

9. Verdoux H, Lagnaoui R, Begaud B. Is benzodiazepine use a risk factor for cognitive decline and dementia? A literature review of epidemiological studies. 

Benzodiazepines and risk of Alzheimer disease

11. Bocti C, Roy-Desruisseaux J, Hudon C, Roberge P. Benzodiazepine and dementia: a time for reflection. 

12. Fastbom J, Forsell Y, Winblad B. Benzodiazepines may have protective effects against Alzheimer disease. 

13. Lagnaoui R, Bégaud B, Moore N, et al. Benzodiazepine use and risk of dementia: a nested case-control study. 

14. Lagnaoui R, Tournier M, Moride Y, et al. 

The risk of cognitive impairment in older community-dwelling women after benzodiazepine use

15. Wu CS, Wang SC, Chang IS, Lin KM. The association between dementia and long-term use of benzodiazepine in the elderly: nested case-control study using claims data.

16. Wu CS, Ting TT, Wang SC, et al. Effect of benzodiazepine discontinuation on dementia risk.

17. Gallacher J, Elwood P, Pickering J, et al. Benzodiazepine use and risk of dementia: evidence from the Caerphilly Prospective Study (CaPS). 

18. Chen PL, Lee WJ, Sun WZ, etal. Risk of dementia in patients with insomnia and long-term use of hypnotics: a population-based retrospective cohort study. 

19. Billioti de Gage S, Bégaud B, Bazin F, et al. Benzodiazepine use and risk of dementia: prospective population based study. 

20. Billioti de Gage S, Moride Y, Ducruet T, et al. Benzodiazepine use and risk of Alzheimer disease: case-control study. 

21. Imfeld P, Bodmer M, Jick SS, Meier CR. 

Benzodiazepine use and risk of developing alzheimer disease or vascular dementia: a case-control analysis

22. Shash D, Kurth T, Bertrand M, et al. Benzodiazepine, psychotropic medication, and dementia: a population-based cohort study.

23. Gray SL, Dublin S, Yu O, et al. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. 

24. Biétry FA, Pfeil AM, Reich O, et al. Benzodiazepine use and risk of developing alzheimers disease: A case-control study based on Swiss claims data. 

25. Nafti M, Sirois C, Kröger E, et al. Is benzodiazepine use associated with the risk of dementia and cognitive impairment-not dementia in older persons? The Canadian study of health and aging. A

26. Osler M, Jørgensen MB. Associations of benzodiazepines, z-drugs, and other anxiolytics with subsequent dementia in patients with affective disorders: a nationwide cohort and nested case-control study. 

27. Verdoux H, Lagnaoui R, Begaud B. Is benzodiazepine use a risk factor for cognitive decline and dementia? A literature review of epidemiological studies. 

28. Billioti de Gage S, Pariente A, Bégaud B. Is there really a link between benzodiazepine use and the risk of dementia?

29. Pariente A, de Gage SB, Moore N, Bégaud B. 

The benzodiazepine-dementia disorders link: current state of knowledge

Association between benzodiazepine use and dementia: a meta-analysis

31. Islam MM, Iqbal U, Walther B, et al. 

Benzodiazepine use and risk of dementia in the elderly population: a systematic review and meta-analysis

32. Lucchetta RC, da Mata BPM, Mastroianni PC. 

Association between development of dementia and use of benzodiazepines: a systematic review and meta-analysis.

Nearly half of the prescriptions for benzodiazepine among older adults are potentially inappropriate, so how best to do no harm?

Psychopharmacology

How Will Patients React to Medications? The Answer May Be in Their Genes

All About Adverse Effects: Psychotropics Poll

COVID-19 Pandemic’s Effects on Assessment & Psychopharmacological Management

Serum Levels in Psychiatric Medications

Cannabis-Based Medicine Without the Addiction Risks?

Never Forget the Fine Print: From Fertility Rites to “Miracle Med”

Benzodiazepine Use and the Risk of Dementia

Discussions With Patients: Medical Marijuana

An Uplifting Experience: Can Botulinum Toxin Address Depressive Symptoms?

Assessing and Addressing Synthetic Cannabinoids and Cathinones in Neuropsychiatric Toxicological Emergencies