Monday, July 15, 2019

Nabaximols Nasal Spray May Reduce Cannabis Use By Some Patients


A study published today in JAMA Internal Medicine reports that the cannabinoid agonist nabiximols can reduce cannabis use among people with cannabis dependence when combined with behavioral therapy. Nabiximols is a nasal spray composed of purified tetrahydrocannabinol (THC) and cannabidiol (CBD)—two of the primary active components of cannabis.

Study participants who received a combination of nabiximols and behavioral therapy reported using cannabis about 33% fewer days than those allocated to placebo and behavioral therapy, noted Nicholas Lintzeris, M.B.B.S., Ph.D., of Australia’s Drug and Alcohol Services and colleagues. “The reductions in illicit cannabis use and a safer route of administration … suggest the harm-reduction benefits of cannabinoid agonist treatment,” the authors wrote.

Lintzeris and colleagues enrolled 128 adults with cannabis dependence (as defined by the International Classification of Diseases, 10th Revision, or ICD-10) who were seeking treatment to participate in a 12-week trial. As part of the trial, the participants received either nabiximols or placebo nasal spray for daily use and were offered six individual cognitive-behavioral therapy sessions over the course of the trial. Each individual nabiximols spray contains 2.7 mg of THC and 2.5 mg of CBD, and participants could take up to 32 sprays daily.

At baseline, the participants reported using cannabis about 25 of the past 28 days. During the 12-week trial, adults in the placebo group reported significantly more days using cannabis (53 of 84 days) compared with those in the nabiximols group (35 of 84 days). Although there was no statistical difference between the groups in the number of participants who achieved cannabis abstinence (defined as at least 28 consecutive days without use), more adults in the nabiximols group were able to cut their cannabis use by 50% or more (54.1% vs. 28.9%).

The authors noted several limitations of the study, including the finding that only about half of the patients in the placebo and nabiximols groups stayed in treatment throughout the 12-week study. “Although our treatment retention of 46.9% at 12 weeks is comparable with prior randomized clinical trials of cannabinoid agonist treatment (55% at 11 weeks and 67% at 12 weeks), the limited treatment retention across these studies highlights the fact that cannabinoid agonist treatment is not effective for or acceptable to all patients,” Lintzeris and colleagues wrote. “Whereas nicotine-agonist and opioid-agonist treatments are considered frontline therapies, our findings suggest a more cautious approach for cannabinoid agonist treatment at this time.”

For related information, see the Psychiatric News article “Medications May Ease Cannabis Withdrawal But Fail to Achieve Abstinence” and the Psychiatric Services article “Thinking Carefully About Marijuana Legalization: Public Health Considerations for State Policy Makers.”

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Friday, July 12, 2019

Study Pinpoints Activities Associated With Reduced Risk of Cognitive Decline


Mentally stimulating activities like using a computer, playing games, crafting, and participating in social activities were associated with a lower risk of mild cognitive impairment in older people, a study published in Neurology has found. People with mild cognitive impairment, which is not the same as dementia, may have memory loss or have difficulty following conversations or understanding complex information.

Janina Krell-Roesch, Ph.D., of Mayo Clinic’s Translational Neuroscience and Aging Laboratory, and colleagues analyzed five-year data from 2,000 participants in the population-based Mayo Clinic Study of Aging. The participants were at least 70 years old at the beginning of the study, and none of them had mild cognitive impairment when they enrolled. Participants completed a questionnaire about how often they took part in five types of mentally stimulating activities during middle age (ages 50 to 65) and in later life (age 66 and older). The activities were reading books, crafting such as pottery or sewing, doing computer activities, playing games like cards or crossword puzzles, and engaging in social activities such as going out with friends. Participants then took thinking and memory tests every 15 months. Over the course of five years, 532 participants developed mild cognitive impairment.

The researchers found that using a computer in middle age was associated with a 48% lower risk of developing mild cognitive impairment and that using a computer in later life was associated with a 30% lower risk. Engaging in social activities and playing games in both middle age and later life were each associated with a 20% lower risk. Craft activities were also associated with a 42% lower risk, but only in later life.

The more activities in which people engaged during later life, the less likely they were to develop mild cognitive impairment. Engaging in two activities was associated with a 28% lower risk, engaging in three activities was associated with a 45% lower risk, engaging in four activities was associated with a 56% lower risk, and engaging in five activities was associated with a 43% lower risk.

“Persons that engage in mentally stimulating activities may have a higher likelihood of exhibiting other healthy lifestyle behaviors that may be protective against cognitive decline, such as physical activity or a healthy diet,” they wrote. “Engaging in leisure activities may also be associated with better emotional health, which in turn is associated with cognitive health.”

For related news, see the Psychiatric News article “New Insights Into How Staying Active May Delay Onset of Alzheimer’s.”

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Thursday, July 11, 2019

Non-Concussive Head Impacts Not Linked to Cognitive Decline in Young Football Players, Study Finds


Youth aged 9 to 18 years who played tackle football for two seasons did not experience significant, short-term changes in cognition from repeated head impacts that did not cause a concussion, according to a study in Journal of Neurotrauma.

However, younger age and a history of attention-deficit/hyperactivity disorder (ADHD) did predict decline in cognition among the young football players. Longer-term effects are unknown and require further research.

“The study is showing us that sub-concussive impacts don't seem to be associated with changes in neurocognitive function over two seasons of youth football,” said lead author Sean Rose, M.D., a pediatric sports neurologist and co-director of the Complex Concussion Clinic at Nationwide Children's Hospital in Columbus, Ohio. “And we're finding that other factors, such as ADHD and younger age, are more predictive of worsening scores on our pre- and post-season tests.”

Rose and colleagues studied a sample of 166 youth tackle-football players over two seasons: 70 primary-school players aged 9 to 12 years and 96 high-school players aged 15 to 18 years. Sensors were placed in their helmets to record the number as well as the intensity of impacts to the head. All participants completed assessments on a variety of neurological, cognitive (including memory and attention), and behavioral outcomes before and after each football season.

In the subgroup of 55 youth who played in both seasons, neither cumulative impact nor impact intensity predicted change scores from preseason 1 to post-season 2 on any outcome measure. However, younger age did predict worse outcomes in some measures, though these changes were independent of head impacts. Also, a history of ADHD was associated with reduced scores on several cognitive measures and an ADHD symptom self-reporting scale.

“When trying to determine the effects of repeated, sub-concussive head impacts, prospective outcomes studies are an important addition to the existing retrospective studies,” said Rose in a prepared statement. “We designed this study to include a wide variety of neurocognitive outcomes tests to give us new insights into how repeated hits might influence outcomes.”

Despite the study findings, Rose said the longer-term effects of repeated impacts from tackle football on young people’s brains is unknown “We remain concerned about repetitive head impacts in children, and longer follow-up times are necessary to look for delayed effects on neurocognition,” he said.

>For related information, see the Psychiatric News article “Age When Football Hits Began May Determine Future Cognitive Problems.”

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Wednesday, July 10, 2019

CBT Program Reduces Addictive Internet Behaviors in Men, Study Finds


A 15-week treatment program that incorporates principles of cognitive-behavioral therapy (CBT) is effective at reducing problem gaming and other addictive internet behaviors in men, according to a study published today in JAMA Psychiatry

“Despite the heterogeneity of the treatment group, we found that our CBT program was effective … regardless of age, comorbidity, or treatment center,” wrote Klaus Wölfling, Ph.D., of the University Medical Center of the Johannes Gutenberg-University in Mainz, Germany, and colleagues. “These findings support a unitary concept of [internet addiction] and point to the flexibility of the STICA [short-term treatment for internet and computer game addiction].”

Internet- and gaming-related addiction is an emerging concept: Internet gaming disorder is listed in the DSM-5 under conditions for further study, and gaming disorder is included in the 11th Revision of the International Classification of Diseases (ICD-11).

Wölfling and colleagues recruited 143 men (average age 26) with addictive behaviors related to the internet and gaming from outpatient psychiatry clinics at university medical centers in Germany and Austria. The problem behaviors reported by the men included online gaming (82 men), offline gaming (9 men), online pornography (23 men), and generalized internet addiction (29 men). Participants were evaluated using the Assessment of Internet and Computer Game Addiction (AICA) scale; AICA is derived from the DSM-5’s proposed criteria for internet gaming disorder but expanded to multiple online activities.

Of the participants, 72 received STICA, which teaches patients to be cognizant of why they engage in dysfunctional internet use and provides skills to help them reduce and control their use. The treatment involved 15 weekly group sessions interspersed with eight individual sessions to aid in patient motivation and monitor participants for any emergent distress. The other 71 men were placed on a wait list and received STICA after 15 weeks.

After 15 weeks, 69% of men who received STICA achieved remission of their addiction (defined as an AICA score of 7 or less) compared with 24% of men on the wait list. The STICA group also reported less time spent online on both weekends and weekdays, fewer depression symptoms, and improved social functioning. 

“The study shows that STICA can be effective in treatment of IA [internet addiction],” Wölfling and colleagues concluded. “Further trials investigating the long-term efficacy of STICA and addressing specific groups and subgroups compared with active control conditions are required.”

For related information, see the American Journal of Psychiatry article “Internet Gaming Disorder: Investigating the Clinical Relevance of a New Phenomenon.”

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Tuesday, July 9, 2019

‘Secret Shopper’ Study Highlights Barriers Faced By Patients Seeking Buprenorphine


Patients seeking treatment for heroin use in areas of the United States hardest hit by the opioid epidemic may experience several barriers to care when reaching out to publicly listed “buprenorphine-waivered” prescribers, according to a study published in the July issue of the Annals of Internal Medicine. Such barriers include prescribers not accepting new patients and waits of a week or more between first appointments and buprenorphine induction.

The findings were based on a “secret shopper” study, in which callers to physicians, nurse practitioners, and physician assistants listed on the Buprenorphine Practitioner Locator website posed as a patient covered by Medicaid or without insurance in the District of Columbia, Maryland, Massachusetts, New Hampshire, Ohio, and West Virginia.

“In six [jurisdictions] with the highest burden of opioid-overdose mortality in the United States, 38% to 46% of callers who reported current heroin use were denied an appointment from a buprenorphine prescriber, and only 50% to 66% of [prescribers] booking a new appointment allowed buprenorphine induction at the first visit,” wrote senior author Michael L. Barnett, M.D., M.S., of the Harvard T.H. Chan School of Public Health and Brigham and Women’s Hospital and colleagues. “Nevertheless, among those who were accepting new patients, wait times were not long, suggesting an underused capacity for buprenorphine treatment in areas with great need.”

From July to November 2018, callers attempted to contact 1,076 publicly listed buprenorphine prescribers twice, posing as a 30-year-old woman who was using heroin and seeking to start buprenorphine-naloxone treatment. During one call, scheduling staff was told the patient was covered by Medicaid; in the other, scheduling staff was told the patient was uninsured but willing to pay for care. For each prescriber, the callers made three attempts during business hours to reach a live scheduler.

From the initial sample of 1,076 prescribers in six jurisdictions, 530 were excluded for reasons such as invalid contact information, they were inactive prescribers, or they requested information such as a Medicaid number that the caller could not provide. The callers were also unable to reach a live scheduler for 77 prescribers, while 89 prescribers were reached once but not for both scenarios, resulting in a final sample of 849 contacts for 469 prescribers. The authors found that an appointment was offered in 233 of 432 contacts (54%) by the Medicaid callers and 258 of 417 (62%) by the uninsured–self-pay callers. The median wait time to the first appointment was six days for Medicaid callers and five days for uninsured–self-pay callers.

Additionally, 27% of Medicaid callers and 41% of uninsured–self-pay callers were offered an appointment with the possibility of buprenorphine prescription at the first visit. The median wait time from first contact to possible induction was eight days for Medicaid callers and seven days for uninsured–self-pay callers.

The researchers noted several limitations of the study, including callers’ focus on publicly listed buprenorphine prescribers in five states and the District of Columbia, which limits the generalizability of the findings.

Nonetheless, Barnett and colleagues concluded, “[E]very day without treatment carries an elevated risk for escalating opioid use and overdose. Patients must be in active opioid withdrawal to initiate buprenorphine treatment safely, which makes the timing of induction critical.”

For related information, see the Psychiatric News article “What Psychiatrists Can Do to Address the U.S. Opioid Crisis.”


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Monday, July 8, 2019

Cognitive Decline After Onset of Psychosis Varies Across Cognitive Functions


Patients with schizophrenia and related psychotic disorders continue to experience cognitive decline for years after illness onset, according to a study in AJP in Advance.

“While large deficits in processing speed are already apparent at the first episode [of psychosis], deficits in verbal knowledge and memory continue to increase,” wrote Jolanta Zanelli, Ph.D., of King’s College London and colleagues. Understanding these differences can help guide cognitive remediation therapy in patients, the authors noted.

These findings were based on data collected as part of the Aetiology and Ethnicity in Schizophrenia and Other Psychoses (AESOP) study—a study that tracked changes in cognitive function in patients following a new diagnosis of psychosis. The study included 187 adults with first-episode psychosis or another psychotic disorder (for example, psychotic depression or persistent delusional disorder) who sought care in southeast London, Nottingham, or Bristol, and 177 healthy controls. All study participants were given a series of neuropsychological tests at enrollment and about 10 years later. Full 10-year data was available for 106 patients and 103 controls.

The baseline data showed that all patients with psychosis performed worse on tests measuring intellectual ability (IQ) as well as specific cognitive functions compared with controls, with patients with schizophrenia showing the greatest impairment. Approximately 10 years later, patients with schizophrenia showed worsening IQ, memory, and verbal skills compared with controls; their processing speed and visual-spatial memory did not decline. In contrast, patients with another psychotic disorder did not exhibit continued IQ decline compared with controls and only worsened in only certain memory functions.

Schizophrenia patients with severe symptoms at baseline showed greater cognitive decline over time than patients with mild or moderate symptoms; there was no evidence for an association between symptom severity and cognitive changes among patients with other psychoses. “While this subgroup was small (21% of the overall group), the magnitude of decline in the memory domain was large. Thus, this finding points to a potential subgroup of schizophrenia patients who may greatly benefit from being specifically targeted for cognitive remediation,” Zanelli and colleagues wrote.

To read more about this topic, see the Psychiatric News article “Could Cognitive Assessments Enhance Ability to Detect Transition to Psychosis?

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Friday, July 5, 2019

Statins May Reduce Symptoms of Depression, Meta-Analysis Suggests


A class of cholesterol-lowering drugs collectively known as “statins” may improve symptoms of depression in people who have been diagnosed with the disorder, according to a meta-analysis in the Journal of Affective Disorders.

Megha S. Yatham, B.Sc., of the University of Manchester and colleagues reviewed data from 10 clinical trials of statins in which participants were randomized to at least one statin or placebo. The trials measured depressive symptoms using scales such as the Hamilton Depression Rating Scale, Beck Depression Inventory, and Geriatric Depression Scale, among others. The primary outcome was the difference in end-of-trial depression scores between participants who took statins and those who took placebo. Participants in three of the trials had been diagnosed with depression, and seven of the trials were conducted in nondepressed participants. In total, 1,348 participants received statins in the trials and 1,169 received placebo.

Yatham and colleagues found that statin use was associated with significantly lower scores on depression rating scales compared with placebo, but only among participants who had been diagnosed with depression. Although statin use was associated with improved scores in nondepressed participants as well, this difference was not enough for the researchers to consider the improvement statistically significant.

“Although the exact mechanisms by which statins might improve depressive symptoms is unknown, the leading theory is that statins decrease the inflammation and oxidative stress reported to be commonly associated with depression,” the researchers wrote. “While the results of the current meta-analysis are very promising and supportive of [the] benefits of statin therapy, further research and trials with larger sample sizes need to be conducted in order to fully explore the benefits of statins in depressed and nondepressed populations.”

For related news, see the American Journal of Psychiatry article “The Effect of Concomitant Treatment With SSRIs and Statins: A Population-Based Study.”

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Wednesday, July 3, 2019

Patients on Isotretinoin Should Get Regular Psychiatric Screenings, Study Suggests


Patients who take isotretinoin for severe acne may be vulnerable to several psychiatric conditions, according to a study published today in JAMA Dermatology. Specifically, depressive disorders, anxiety disorders, and mood swings were among the most common psychiatric adverse events in patients taking isotretinoin reported to the Food and Drug Administration (FDA) over a 20-year period.

Although previous studies and media reports have highlighted an association between suicidality and depression in patients taking isotretinoin, “our results suggest that other, underappreciated psychiatric adverse events may be linked to its use,” wrote senior author Arash Mostaghimi, M.D., M.P.A., M.P.H., of Brigham and Women’s Hospital, and colleagues. The findings suggest the importance of incorporating regular psychiatric screenings as part of follow-up care of patients taking isotretinoin, they noted.

The researchers analyzed reports of 17,829 psychiatric adverse events with isotretinoin as the primary suspect drug in the FDA’s Adverse Event Reporting System from 1997 through 2017. There were 7,547 reports of depressive disorders (42.3% of all adverse event reports); 2,962 reports of emotional lability, such as mood swings and irritability (16.6%); and 2,412 reports of anxiety disorders (13.5%). Additionally, there were 2,278 reports of suicidal ideation, 602 reports of attempted suicide, and 368 reports of completed suicide. Among the 13,553 adverse events that reported patient age, more than half occurred in patients aged 10 to 19.

Additional analysis of suicide data from patients enrolled in an isotretinoin risk-management program known as iPLEDGE in 2009 and 2010 revealed rates of completed suicide per 100,000 persons were 8.4 in 2009 and 5.6 in 2010. (iPLEDGE requires patients meet with physicians monthly to confirm medication is being taken correctly.) The authors noted that these rates were lower than the national suicide rates in the general population and in those aged 15 to 24 during those years.

“Although no causal link has been established between isotretinoin and psychiatric adverse events, it is important to recognize that there are data that suggest patients using this drug may be vulnerable to a number of psychiatric conditions,” the authors wrote. “Mandated monthly visits under the current iPLEDGE infrastructure may provide an opportunity to screen patients for psychiatric conditions and improve patient outcomes.”

For related news, see the Psychiatric News article “Psychiatrists Work to Tease Apart Psychosomatic Aspects of Skin Disease.”

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Tuesday, July 2, 2019

Many Youth With ADHD Fail to Take Stimulants as Prescribed, Study Suggests


More than half of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) may not be taking stimulant medications as prescribed, according to a report in Psychiatric Services in Advance.

“These findings [underscore] the need for active efforts to better understand the problem and develop approaches to help mitigate it, especially in primary care settings,” wrote lead author Joseph Biederman, M.D., chief of the Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD at Massachusetts General Hospital, and colleagues.

The researchers analyzed prescription and sociodemographic data from the Partners Health Care Research Patient Data Registry of Massachusetts General Hospital for 2,206 patients aged 4 to 17 years who had been prescribed any of the following stimulants between January 1, 2015, and December 31, 2016: amphetamine/dextroamphetamine, dextroamphetamine, dexmethylphenidate, lisdexamfetamine, or methylphenidate. The researchers included medications prescribed as a single prescription (30-day supply) and medications with prescriptions postdated by up to three months (60- or 90-day supply).

The researchers defined a patient as being “adherent” if a single index prescription was followed by a second prescription within 90 days.

In cases in which index prescriptions were postdated by two months (that is, two prescriptions written the same date), a patient was deemed adherent if a third prescription was filled 31 to 120 days after the first prescription. In cases in which index prescriptions were postdated by three months, a patient was considered adherent if the fourth prescription was filled 61 to 150 days after the first prescription.

Of the 2,206 patients, 95% had single index prescriptions, 4.9% had prescriptions that were postdated by two months, and 0.5% had prescriptions postdated by three months. Only 46% (n=1,023) of patients met the researchers’ criteria for medication adherence, indicating that they refilled their stimulant prescriptions quickly enough to be considered consistently medicated.

Patients who received prescriptions from psychiatric clinics rather than nonpsychiatric clinics had a small but significantly greater likelihood of adherence to treatment. Additional analysis revealed that children tended to adhere to the medication regimen somewhat more than adolescents and adherence was slightly better in boys than in girls.

Biederman and colleagues noted that low adherence may reflect several factors: the complexity of renewing prescriptions for stimulants, which are schedule II medicines; negative side effects of stimulants, such as lack of appetite and difficulty sleeping; or parents’ ambivalence about their child taking medications for ADHD.

“Low adherence may also stem from misinformation or biases about stimulants in the media,” they wrote. “More research is needed to clarify the causes of low medication adherence in ADHD to develop appropriate measures to mitigate them.”

For related information see the American Journal of Psychiatry article “Continued Benefits of Methylphenidate in ADHD After 2 Years in Clinical Practice: A Randomized Placebo-Controlled Discontinuation Study.”

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Monday, July 1, 2019

Study Identifies Different Classes of Childhood Irritability


Irritability is known to be a feature of several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD) and disruptive mood dysregulation disorder. A study of irritability in children published today in AJP in Advance suggests there are several forms of irritability, including a “neurodevelopmental/ADHD-like” type with onset in childhood and a “depression/mood” type with onset in adolescence. These findings could have implications for diagnosis and treatment.

Lucy Riglin, Ph.D., of Cardiff University and colleagues assessed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a long-running, longitudinal study of families in Avon, England, in which children were born between April 1, 1991, and December 31, 1992. This analysis included data from the mothers of 7,924 children, who were asked to assess their children’s irritability (severe temper tantrums, touchy and easily annoyed, and angry and resentful) at ages 7, 10, 13, and 15 using the Development and Well-Being Assessment. Total irritability scores could range from 0 (none) to 6 (high).

The researchers identified five distinct developmental trajectory classes of irritability for these children:
  • Low (81.2%); characterized by irritability scores of less than 1 throughout childhood
  • Decreasing (5.6%); characterized by irritability scores of around 3 at age 7 that gradually went down to less than 1 by age 13
  • Increasing (5.5%); characterized by irritability scores of less than 1 until age 10, then rising to a score of around 4 by age 15
  • Late-childhood limited (5.2%); characterized by irritability scores rising from around 1 to 3 between the ages of 7 to 10, then dropping back below 1 by age 15
  • High-persistent (2.4%); characterized by irritability scores of 4 or more throughout childhood

The decreasing group, high-persistent group, and late-childhood limited group were more likely to be male. In contrast, the increasing trajectory group was about 60% female. The decreasing group, high-persistent group, and late-childhood limited group were also significantly associated with an ADHD diagnosis in childhood. In contrast, the increasing trajectory group was more strongly associated with a diagnosis of depression during adolescence.

“In conclusion, our study identified different developmental trajectories of irritability, including one with characteristics typical of neurodevelopmental/ADHD-like problems—early onset, male preponderance, and clinical and genetic links with ADHD—and one with characteristics typical of depression/mood problems—later onset, female preponderance, and clinical and genetic links with depression,” Riglin and colleagues wrote. “Both groups were associated with risk of adolescent depression, and both were associated with ADHD genetic risk scores. Overall, these findings suggest that the developmental context of irritability may be important in its conceptualization, and this has implications for treatment as well as nosology.”

For related information, see the Psychiatric News article “Irritability in Childhood May Point to Teens At High Risk for Suicide.”

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