Bipolar Patients More Likely to Take Nonpsychotropic Meds Than Psychotropic Meds

A study in Psychiatric Services in Advance finds that patients with bipolar disorder may be more apt to take medication for a general medical condition than for their bipolar disorder, though adherence to taking any kind of medication was low in general.

Although some previous studies have shown that data for nonadherence among patients with bipolar disorder extends to all medication types, little information is known regarding the relationship between their medication-taking behaviors for psychotropic and nonpsychotropic medications.

To help fill this gap, researchers in the Department of Psychiatry at Case Western Reserve University School of Medicine gathered patient-reported data from 88 patients with type I or type II bipolar disorder who reported psychotropic nonadherence (defined as having missed 20 percent or more of their current bipolar medication treatment for either the past week or month, as assessed by the Tablets Routine Questionnaire). Patients were asked questions regarding the presence or absence of comorbid general medical conditions and depression and mania symptoms, as well as their adherence to prescribed psychotropic and nonpsychotropic medications.

The analysis showed that the median proportion of days with missed doses was 53.6 percent for psychotropic medications compared with 33.93 percent for nonpsychotropic medication. In addition, the researchers found that the presence of more severe psychiatric symptoms was significantly associated with nonadherence to nonpsychotropic medication. The most common drugs taken by the participants to treat comorbid conditions included drugs intended for hypertension, cholesterol, and diabetes.

“Our finding that an individual may adhere to one medication over another suggests that nonadherence is at least in part intentional,” the study’s lead author Jennifer Levin, Ph.D., an assistant professor of psychiatry at Case Western, told Psychiatric News. Levin, a clinical psychologist, hypothesized that the significant difference found between nonadherence to psychotropics and nonadherence to nonpsychotropics may include patients’ fear of notable side effects associated with adhering to psychotropics, patients’ perceiving their symptoms as less severe than than they really are, and stigma associated with taking drugs for mental illness.

Levin concluded that the findings highlight the need for mental health professionals to address issues concerning both mental health and physical health by asking patients about adherence to all their prescribed medications.

To read more about medication adherence among patients with mental illnesses, see the Psychiatric News article "Antipsychotic Nonadherence More Common for Mood Disorders Than Schizophrenia."

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Some Ultra-High Risk Subgroups Are at Higher Risk of Psychosis Than Others

Since the mid-1990s, clinicians have classified individuals as being at ultra-high risk (UHR) for psychosis if they met at least one of three criteria: the presence of attenuated psychotic symptoms (APS), the presence of positive symptoms at full psychotic intensity for brief, limited time points (known as BLIPS), and/or a combination of genetic risk or schizotypal personality disorder accompanied by functional decline (known as genetic risk and decline syndrome [GRD]). However, the risk of psychosis of these different groups has remained unknown.

A meta-analysis published today in JAMA Psychiatry now offers evidence that some ultra-high risk subgroups carry a higher risk of psychosis than others.

Paolo Fusar-Poli, M.D., Ph.D., of King’s College and colleagues analyzed the outcomes of 33 independent studies, including over 4,000 UHR individuals monitored for psychosis progression. The researchers found that people with BLIPS had the highest risk of conversion to psychosis (39% after 24 months), followed by APS (19%) and GRD (3%). In addition, patients who had both APS and GRD had a similar risk of conversion to psychosis as those with only APS across all time points studied—suggesting GRD may not be a valid component of the UHR profile.

“There is meta-analytical evidence of heterogeneous levels of risk of psychosis in [clinical high risk] samples,” the study authors wrote. “Authors of future CHR studies are advised to stratify their findings across these different subgroups.”

In a related editorial, Barbara Cornblatt, Ph.D., M.B.A, and Ricardo Carrión, Ph.D., of the Zucker Hillside Hospital, North Shore–Long Island Jewish Health System, describe the clinical and research implications of the study. “The findings of Fusar-Poli et al. challenge the way prodromal identifications have been made for the past 20 years and will undoubtedly have a positive effect on high-risk research and future criterion modifications,” they wrote.

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Antipsychotic Discontinuation After Functional Recovery in FEP Linked to Relapse, Study Shows

Antipsychotic discontinuation following functional recovery in patients after a first episode of psychosis (FEP) appears to be associated with a very high rate of relapse compared with those who maintain antipsychotic treatment, according to a report that appears in The Journal of Clinical Psychiatry.

Moreover, the time to relapse was faster for those who discontinued medication compared with those who relapsed on maintenance treatment, say researchers.

“In clinical practice, physicians very often face the dilemma of discontinuing or maintaining antipsychotics in those patients who have fully recovered from their initial episode of psychosis,” they wrote. “In those individuals who are willing to discontinue medication, a planned medication withdrawal strategy with follow-up should be established to prevent unrestrained treatment disengagement. Clinicians should provide accurate information to patients and relatives concerning the risks and benefits of withdrawing medication.”

Study participants were drawn from an ongoing longitudinal intervention study for FEP in Spain. Inclusion criteria for the study were receiving 18 months of treatment with antipsychotics, meeting clinical remission criteria for 12 months and functional recovery criteria for six months, and being stabilized on the lowest antipsychotic dose for three months. A total of 46 individuals opted to discontinue medication, and 22 remained on maintenance medication; the primary outcome measures were relapse rate at 18 and 36 months and time to relapse.

In the discontinuation group, 31 patients (27 relapses and four cases of deterioration in symptoms) relapsed. In contrast, among patients in the maintenance group, just seven patients relapsed over the three-year period. The average time to relapse in the maintenance group was 608 days compared with 209 days for those who relapsed in the discontinuation group.

“[T]he rate of symptom recurrence in functionally recovered FEP patients following the self-elected discontinuation of treatment is extremely high,” the researchers state. “Relapsed individuals had a greater severity of symptoms and lower functionality [during the three-year follow-up period] compared with those patients who did not relapse during the follow-up.”

For more on this subject, see the Psychiatric News article, “Does Aggressive Treatment of Psychosis Mean Sustained Use of Antipsychotics?”

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Will Emerging Technology Change Treatment of Psychiatric Illness?

The development of new technologies to facilitate disease management is a burgeoning field, but experts say that more research is needed to determine how effective such products will be for patients with psychiatric illness and how best to incorporate these products into a treatment plan.

In a recent Psychiatric News article, APA Director of Research Phillip Wang, M.D., Dr.P.H.; John Kane, M.D., of Zucker Hillside Hospital and Massachusetts General Hospital; Dror Ben-Zeev, Ph.D., of the Geisel School of Medicine at Dartmouth; and Ken Weingardt, Ph.D., scientific director at the Center for Behavioral Intervention Technologies at Northwestern University, address several ways digital resources might be leveraged to support psychiatric care.

The article describes the results of a study by Kane and colleagues, which evaluated the feasibility and safety of a digital health feedback system (DHFS) in 12 patients with bipolar disorder and 16 patients with schizophrenia. The system includes pills embedded with tiny ingestible sensors that emit a signal after being swallowed, alerting caregivers and clinicians that the medication has been ingested. (For the purposes of the study, the pill with the embedded DHFS was not pharmacologically active.)

No adverse events occurred due to the ingestion sensor, and none of the study participants developed worsening of psychosis due to use of the DHFS. Of the 27 patients who completed the study, 19 found the DHFS concept easy to understand, 21 said they would like to receive reminders on their cell phone if they forgot to take their medications, and 24 said they believed it would be useful to them. (The DHFS device is pending approval by the Food and Drug Administration.)

In another study, Ben-Zeev and colleagues examined the feasibility and acceptability of a mobile phone application called FOCUS by 33 individuals with schizophrenia or schizoaffective disorder over a one-month period. The app offers users prescheduled and on-demand resources to facilitate symptom management, mood regulation, medication adherence, among other things

Of the 33 study participants, 32 used the system on 86.5% of days they had the device, an average of 5.2 times a day. Approximately 62% of use of the FOCUS intervention was initiated by the participants, and 38% of use was in response to automated prompts. Approximately 90% of participants rated the intervention as highly acceptable and usable. The study also revealed significant reductions in psychotic symptoms, depression, and general psychopathology after one month of FOCUS use.

To read the full Psychiatric News article, see “Technologies Promise to Aid Medication Adherence, but Effectiveness Varies.”

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Resilience Intervention Helps Entire Military Family

Military families benefited from an intervention program designed to reduce psychological symptoms, increase resilience, and improve family functioning, according to Patricia Lester, M.D., a professor of psychiatry at the University of California, Los Angeles, and colleagues. Their study appears in the January 2016 issue of the Journal of the American Academy of Child and Adolescent Psychiatry.

The researchers studied 2,615 families, which included 1,426 service-member parents, 2,073 civilian parents, and 3,810 children. At least one parent in the family had been deployed to the wars in Iraq and Afghanistan.

Lester et al. employed FOCUS (Families OverComing Under Stress), an eight-session program that included an initial assessment, family psychoeducation and parenting guidance, a narrative component looking at key family transitions, and resilience skill building.

At follow-up, both parents and children showed reduced symptoms of anxiety, depression, and PTSD, wrote Lester. Parents reported better family functioning, and children had improved social behaviors.

Many parents joined the program hoping to help their children but eventually found that participation benefited the whole family, said Lester. “Taken as a whole, this evaluation study suggests that participation in the intervention provided durable improvements in parent and child psychological health outcomes.”

The FOCUS trial was conducted with families living on U.S. military bases, but it and other interventions should be tested in other settings, given that Reserve and National Guard personnel make up 43 percent of the Armed Forces, wrote Bonnie Ohye, Ph.D., and Eric Bui, M.D., Ph.D., in an accompanying editorial.

For more in Psychiatric News about military family issues, see “Troops Face Complex, but Not Inevitable, Mental Health Issues.” Also see Care of Military Service Members, Veterans, and Their Families, available from American Psychiatric Association Publishing.

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Study Suggests Mental Disorders Increase Risk of Subsequent Chronic Physical Conditions

Findings from a study published today in JAMA Psychiatry suggest that mental disorders increase the odds of later developing a wide range of chronic physical conditions, with chronic pulmonary disease and chronic pain disorders being most prevalent.

Researchers from the University of Otago in Australia analyzed retrospective data generated from the World Health Surveys of more than 47,000 adults in 17 countries. Survey participants were asked to report the year of onset of their mental illness diagnosis (based on DSM-IV criteria) as well as any chronic physical condition (e.g., heart disease, cancer, chronic pulmonary disease diabetes mellitus, and arthritis) and the year it was diagnosed.

The single physical condition most strongly associated with an earlier diagnosis of a mental disorder was chronic pulmonary disease, followed by chronic pain disorders, peptic ulcers, heart disease, and diabetes mellitus. Cancer had the weakest association with an earlier diagnosis of a mental disorder.

“The study findings need to be confirmed in prospective designs, but they suggest that the deleterious effects of mental disorders on physical health (if causal) accumulate over the life course,” the study authors wrote. “If this is the case, then given the early onset of most mental disorders and the similarly early etiopathogenesis of many chronic physical conditions, treatment of all mental disorders should optimally incorporate attention to physical health and health behaviors, with this parallel focus on physical health beginning as early in the course of the mental disorder as possible.”

For related information, see the Psychiatric News article “Board Approves Statement on Role in Reducing Physical Health Disparities.”

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Psychiatrists Report High Satisfaction Working in Integrated Care Teams, Study Shows

Psychiatrists participating in integrated care teams report high satisfaction with their work, saying a collaborative care model allows them to leverage their expertise to reach a large number of patients in a variety of practice settings, according to a survey of 58 psychiatrists working in integrated care teams. The survey results were published in Psychiatric Services in Advance.

“The ability to reach more people in need of behavioral health treatment through the psychiatrist-supported approach in the collaborative care model was viewed as a very rewarding experience,” coauthor Lori Raney, M.D. (pictured above), vice chair of APA's Council on Healthcare Services and Financing, told Psychiatric News.

Raney and colleagues from the University of Washington School of Medicine surveyed 58 psychiatrists working in integrated care teams. Psychiatrists were recruited from two sources—an online list developed to increase connections between such providers and from participants in previous national training sessions in integrated care implementation. Only psychiatrists working in integrated care settings at least five hours a week were included in the analysis.

The survey was composed of 36 multiple-choice questions addressing integrated care practice characteristics, team composition, common consultation questions, and systems issues. Six open-ended questions assessed the psychiatrists’ opinions and experiences.

The results were overwhelmingly positive. The analysis highlighted four themes in respondents’ subjective experiences: working in a patient-centered care model, working with a team, the psychiatrist’s role as educator, and opportunities for growth and innovation. Some strengths of the model highlighted by those surveyed were that it fosters patient-centered care and offers benefits of working in a team—for example, “mutual support and efforts when helping patients who have a complex clinical presentation.”

Raney said, “Continued efforts to engage more psychiatrists in this work are needed, and this study provides the first report of the core tasks and satisfaction experienced working in this exciting new area of psychiatric practice.”

For related information, see the Psychiatric News article “APA Receives Federal Grant to Train Psychiatrists in Integrated Care.”

(Image: Lori Raney, M.D.)

School-Based Mindfulness Program May Help Urban Children Deal With Negative Stress

Many urban youth are repeatedly exposed to significant negative stressors including violence, poverty, and substance use. A study published last week in Pediatrics suggests that a school-based mindfulness program may ameliorate some of the effects of these stressors and improve social and behavioral functioning.

Researchers from Johns Hopkins School of Medicine randomly assigned 300 middle school students (grades 5 through 8) from two Baltimore City Public Schools to participate in a 12-week mindfulness-based stress-reduction (MBSR) program or a standard health education program covering such topics as nutrition, exercise, and adolescence, during the regular school day.

After 12 weeks, the MBSR students reported significantly lower levels of depression, rumination, negative coping, self-hostility, and post-traumatic stress disorder (PTSD) symptoms than the students who had participated in the health education class.

Although the authors noted that additional studies are needed to explore the long-term effects of mindfulness-based programs, “[t]his trial provides convincing evidence that high-quality, school-based MBSR instruction for youth in urban public schools is feasible, acceptable, and leads to improvements in psychological symptoms, coping, and posttraumatic stress symptoms,” they wrote.

To read more about the potential value of mindfulness-based care, see the Psychiatric News article “Mindfulness, Relaxed Breathing Can Amplify Good Patient Care,” by Gary Weinstein, M.D.

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Low-Dose Buprenorphine Found to Decrease Suicidal Ideation, but Experts Remain Cautious

Short-term use of very low doses of buprenorphine may help to decrease severe suicidal ideation in some patients, but this finding should be interpreted cautiously, Yoram Yovell, M.D., Ph.D., co-director of the Institute for the Study of Affective Neuroscience at the University of Haifa, Israel, and colleagues wrote in a study published today in AJP in Advance.

A total of 88 patients (aged 18 to 65) who reported clinically significant suicidal ideation (a score of greater than or equal to 11 on the self-report Beck Scale for Suicide Ideation for at least one week) were randomly assigned to receive sublingual buprenorphine lozenges, starting at 0.1 mg once or twice a day (n=57), or placebo (n=31) for four weeks. Once a week, at the decision of the study psychiatrists, the daily dose could be raised in 0.1 to 0.2 mg increments, to a maximal daily dose of 0.8 mg.

At two weeks and four weeks, scores on the Beck Scale for Suicide Ideation dropped significantly for the patients who received the low-dose buprenorphine (mean final dosage=0.44 mg/day) compared with those taking placebo. The effects of buprenorphine on suicidal ideation did not differ between patients who were concomitantly treated with antidepressants and those who were not. Patients with and without borderline personality disorder also had similar responses to buprenorphine.

The researchers noted that despite buprenorphine’s “favorable safety profile, [the medication] is potentially addictive and possibly lethal.” They cautioned, “This is a single, time-limited trial of an experimental treatment for suicidal ideation rather than suicidal behavior, and its results do not support the widespread, long-term, or nonexperimental use of buprenorphine for suicidality.”

In an accompanying editorial, former APA President Alan Schatzberg, M.D., a leading psychopharmacology researcher and professor of psychiatry at Stanford University School of Medicine, also noted the risks of addiction or diversion of buprenorphine. He drew an analogy about “the abuse liability, long-term risks, and social cost” in the use of ketamine to treat depression.

“The potential gain of some patients versus the overall societal cost needs to be addressed, and guidelines need to be promulgated for any such use [of buprenorphine],” wrote Schatzberg. “The time has come for the specialty and regulators to begin to formally address the issues associated with the potential off-label use of drugs of potential abuse for severely ill and refractory patients.”

For related information, see the Psychiatric News article “APA Task Force to Address ‘What’s Next?’ for Ketamine.”

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Early-Life Depression May Alter Brain Development, Study Suggests

The brains of children diagnosed with major depressive disorder (MDD) early in life may develop differently from those of children unaffected by the disorder, suggests a study published Wednesday in JAMA Psychiatry.

Early in childhood, the brain experiences rapid neurogenesis and related increases in gray matter volume, followed by a process of selective elimination and myelination in early puberty, resulting in volume loss and thinning. The findings of the current study suggest that children who experience depression early in life may experience steeper declines in cortical gray matter volume and thickness over the course of development compared with those who have no history of depression early in life.

Joan Luby, M.D., a professor of child psychiatry at Washington University School of Medicine, and colleagues analyzed data collected from 193 children aged 3 to 6 (including 90 diagnosed with MDD) who underwent behavioral assessments and multiple MRI scans as they aged into early adolescence. A total of 116 children received three waves of neuroimaging scans (the first wave scans took place when the children were under 9, and final scans were taken when the children were 12 to 15).

The scans revealed marked decreases in thickness of cortical gray matter and in the volume of the right hemisphere (with marginal significance on the left hemisphere) associated with mean level of depression symptom scores and MDD diagnosis experienced from preschool to school age. Children with depression symptom scores two standard deviations above the mean had a reduction in volumes of gray matter at almost twice the rate of those with no childhood depression symptoms. Similarly, cortical thickness also decreased more rapidly at almost the same rate.

“The study findings … provide the first data, to our knowledge, demonstrating depression-related alterations in volume and thickness of cortical gray matter evident as early as middle childhood,” the researchers wrote. “Whether these early alterations serve as an endophenotype of risk for later depressive episodes or chronic course is a question of interest as the study sample is followed up through adolescence.”

In a related editorial that describes several ways that longitudinal neuroimaging research can inform the understanding of psychiatric disorders, Ian Gotlib, Ph.D., and Sarah Ordaz, Ph.D., of Stanford University offered multiple questions raised by Luby's study: “Does each depressive episode alter neural trajectories and increase the likelihood of subsequent depressive episodes? Do trajectories change more markedly through puberty? How can peers, parents, and treatments counteract maladaptive developmental trajectories?”

They concluded, “We now have the analytic tools to answer these and other questions; the next few years promise to yield information that we can use to determine how best to treat and, ultimately, prevent the occurrence of brain-based disorders.”

For related information, see the Psychiatric News article “Researchers Develop Composite Image of Brains of Youth With MDD.”

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Survey Finds U.S. Teens Continue to Decrease Alcohol, Cigarette Use

The National Institute on Drug Abuse (NIDA) today released data from its Monitoring the Future survey, revealing that U.S. teens are using alcohol, cigarettes, and some illicit drugs less than they did in 2014. Despite this trend, the survey found that marijuana use by youth remained constant.


Since 1975, the Monitoring the Future survey has been tracking trends in substance use by annually surveying over 40,000 8th, 10th and 12th graders across United States about their use of alcohol, tobacco products, and illicit drugs, as well as their attitude toward such products.

This year’s survey, which included 44,892 students from 382 U.S. public and private schools, found that alcohol use by teens declined, with an average of 22.1% of those surveyed reporting past-month use of alcohol, down from 23.3% in 2014 and 27.9% in 2010. Average rates for past-month cigarette use also declined for the three grades combined, dropping from 13.3% in 2010 and 8.0% in 2014 to 7.0% in 2015.

Past-month marijuana use for youth surveyed in 2015 was 3.4%—a percentage that remained unchanged since 2014. However, for the first time in the history of the survey, daily marijuana use exceeded daily tobacco use among 12th graders, with approximately 6% reporting past-month, daily use of marijuana compared with 5.5% reporting daily use of cigarettes. According to the survey, the perception by 12th graders that marijuana use is risky continues to decline, with 31.9% expressing the opinion that regular marijuana use is harmful compared with 36.1% in 2014 and 46.8% in 2010.

Other major findings highlighted in the NIDA report included downward trends in youth’s past-year use of synthetic cannabinoids, MDMA (Ecstasy or Molly), heroin, and prescription opioids.

“We are heartened to see that most illicit drug use is not increasing, non-medical use of prescription opioids is decreasing, and there is improvement in alcohol and cigarette use rates,” Nora D. Volkow, M.D., director of NIDA, said in a statement. “However, continued areas of concern are the high rate of daily marijuana smoking seen among high school students, because of marijuana’s potential deleterious effects on the developing brains of teenagers, and the high rates of overall tobacco products and nicotine containing e-cigarettes usage.”

For coverage of the 2014 Monitoring the Future Survey, see the Psychiatric News article “Teen Alcohol, Tobacco Use Down, E-cigarette Use Up.”

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High Benzodiazepine Use for Schizophrenia Increases Risk of Death

Chronic, high-dose use of benzodiazepines among patients with schizophrenia appears to be associated with a markedly higher overall mortality rate than is seen in patients with schizophrenia who have not been exposed to benzodiazepines, according to a report in AJP in Advance.

The report also found a lower overall mortality rate among patients with schizophrenia who received antipsychotics and/or antidepressants.

“The results indicate that any amount of antipsychotic and antidepressant usage is associated with overall mortality rates 15% to 40% lower compared with no use of these medications,” the researchers wrote. “In contrast, benzodiazepine exposure revealed a clear dose-response curve for mortality, where high exposure was associated with a 70% higher risk of death compared with no use.”

The authors prospectively compared all-cause and cause-specific mortality in individuals aged 16 to 65 who had been diagnosed with schizophrenia (N=21,492) in Sweden. All-cause and cause-specific mortality rates were calculated as a function of cumulative low, moderate, and high exposure to antipsychotics, antidepressants, and benzodiazepines from 2006 through 2010. The cohort participants were identified from two nationwide Swedish health care registers.

The researchers found that antipsychotic exposures at any dose were associated with substantially lower overall mortality. Moreover, moderate antidepressant exposure was associated with a lower mortality, and high exposure to antidepressants was associated with even lower mortality. But exposure to benzodiazepines showed a dose-response relationship with mortality.

“The association between benzodiazepine exposure and mortality may be explained by several mechanisms,” the authors noted. “Although long-term benzodiazepine use may be a marker for more severe illness and coexisting substance abuse, it is also plausible to assume that prescribing of high doses for long periods may lead to tolerance and dose escalation. This could result in fatal interactions with concurrent use of alcohol and illicit drugs, and worsening of polysubstance dependence may result in a less healthy lifestyle in general. In addition, high-dose benzodiazepine use may also contribute to daytime sedation and proneness to accidents.”

For related information, see the Psychiatric News article “Benzodiazepines: Experts Urge Balance.”

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Language Software May Help Identify, Evaluate Patients with Alzheimer's

Language processing software may one day offer clinicians an additional tool to identify and evaluate patients with Alzheimer’s disease, reports a study published in the Journal of Alzheimer's Disease.

Researchers from Toronto Rehabilitation Institute examined the speech samples (transcripts and audio files) of 167 patients diagnosed with “possible” or “probable” Alzheimer’s disease as well as 97 healthy controls who were asked to describe a picture during an interview. Based on a comprehensive analysis of the samples obtained, the researchers found that they could create a language software program that was able to distinguish people with Alzheimer’s disease from those without with about 82% accuracy.

The program examined 370 elements of speech, though maximum accuracy was achieved using a set of 35 speech features that primarily fell into four categories: semantic impairment (using overly simple words), acoustic impairment (speaking very slowly), syntax impairment (using less complex grammar), and information impairment (not clearly identifying the main aspects of the picture).

“Although memory impairment may be the definitive symptom for the diagnosis of AD, it is not necessarily the most sensitive index of cognitive function and response to intervention,” the study authors wrote. “Computational analyses of naturalistic language may ultimately provide a means to monitor changes in cognitive status over the course of the disease, as well as responsiveness to interventions, and can thus serve as a useful clinical tool for purposes well beyond diagnosis.”

To read about additional research into early detection and diagnosis of Alzheimer's, see the Psychiatric News article “Cardiovascular Risk Factors May Serve as Early Indicator of Cognitive Decline.”

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One Dose of Propanolol Decreases Pre-Existing Phobia

Researchers from the Netherlands have used a familiar drug to counteract a pre-existing phobia, with effects lasting up to one year.

For the last 15 years, neuroscientists have been interested in the reconsolidation period, when memories are recalled and can be modified, wrote Marieke Soeter, Ph.D., and Merel Kindt, Ph.D., of the Department of Psychology at the University of Amsterdam, in the December 15 issue of Biological Psychiatry.

Thirty participants who were afraid of spiders were exposed to a caged tarantula for two minutes to reactivate their fears, and then asked to report their level of fear or anxiety. Afterwards, in a double-blind procedure, half of them were given a single 40 mg dose of the beta-blocker propanolol and half a placebo. A third cohort of 15 spider-fearful participants who were not exposed to the caged tarantula also received a single dose of 40 mg propranolol.

When tested three months and one year later, the group that was exposed to the tarantula and who also took the propanolol had less fear of spiders compared with the others. The researchers also observed that the behavioral reduction of the participants’ fear preceded any articulation of the same effect.

The experiment, wrote Soeter and Kindt, “suggests that disrupting reconsolidation targets the affective value of the fear memory.”

They continued, “The current finding challenges one of the fundamental tenets of cognitive-behavioral therapy that emphasizes changes in cognitions as central to behavioral modifications. Disrupting reconsolidation instead acts in reverse order: it targets the fear behavior and subsequently the cognitions may change.”

“The applicability of reconsolidation blockade and memory updating to full-blown mental disorders remains to be seen,” wrote Roger Pitman, M.D., of Massachusetts General Hospital in a related commentary. “But in light of this article, the prospects seem more promising than ever.”

For more in Psychiatric News about fear and memory, see “Context Is Critical in PTSD Fear Learning.”

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Prenatal Choline Supplements May Decrease Later Attention, Social Problems in Children

Children born to mothers who take a high-dose choline supplement during pregnancy may be less likely to experience attention and social problems later in life, according to a study published Monday in AJP in Advance.

“The main significance of our findings is that we’ve shown that it is potentially possible to intervene prenatally to improve brain development in a safe way that is reflected in behavior that predicts increased resilience and decreased psychiatric illness later in life,” lead author Randal Ross, M.D., a professor of psychiatry at the University of Colorado School of Medicine, told Psychiatric News. “The earlier in development you intervene, the greater the potential benefits and lower the costs.”

Past studies suggest that children who later develop psychiatric disorders with an attentional component (such as attention-deficit/hyperactivity disorder, autism spectrum disorder, and schizophrenia) display developmental deficits from an early age. For instance, diminished auditory response inhibition in newborns has been found to be associated with their parent’s psychosis, the greatest risk factor for future psychotic illness.

In a previous study, Ross and colleagues found that newborns born to healthy mothers who had taken prenatal phosphatidylcholine supplements (3,600 mg each morning and 2,700 mg each evening) were more likely to display healthy adult levels of auditory inhibition than those whose mothers had taken a placebo throughout pregnancy. As a follow-up to this study, the researchers asked the parents to rate the behavioral development of their children at age 40 months.

Of the 100 pregnant women enrolled in the initial trial, 86 delivered children from whom researchers recorded auditory evoked potentials at 1 month. The parents of 49 of these children later completed the Child Behavior Checklist, where they rated their 3-year-olds on measures of attention, aggression, withdrawal, and more.

Parent ratings on the Child Behavior Checklist attention and withdrawn subscale were significantly lower in those children who had been treated with choline compared with those who had been treated with placebo. The 40-month Child Behavior Checklist ratings were also related to newborn auditory response inhibition, with significant effects on scores for both the withdrawn subscale and total problems.

“The outcome of the fetal stage of brain development has lifelong consequences for mental function, and there is little prospect of reversing these developmental problems later in life when mental illnesses appear,” Ross and colleagues wrote. “Thus, perinatal intervention, even before individuals at risk for mental illness can be identified, is the only opportunity for potentially reversing this initial major aspect of the pathogenesis of mental illness. A primary, low-cost, low-risk intervention during fetal development will not prevent all cases of mental illness, but even a partial decrease in their incidence or severity would have substantial global value.”

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PQRS Penalty Correction

Information that was published in this week’s Psychiatric News Update regarding the deadline to avoid a penalty related to the reporting of Physician Quality Reporting System (PQRS) measures was incorrect. Based on your practice’s Medicare patient volume, it may not be possible to take action to avoid a penalty at this time. For more information about PQRS, click here.

Novel Compound Found to Be Safe, Effective at Reducing Symptoms of MDD

The results of a clinical trial published yesterday in Molecular Psychiatry suggest that a novel compound found to increase the production of cells may help to relieve symptoms of major depressive disorder (MDD).

Previous animal studies have suggested that NSI-189, a benzylpiperizine-aminopyridine, stimulates neurogenesis in the hippocampus. In the current study, a group of researchers led by Maurizio Fava, M.D., director of the Clinical Research Program at Massachusetts General Hospital, evaluated the effectiveness, safety, and tolerability of NSI-189 in a phase 1B clinical trial that included 24 patients with recurring symptoms of MDD.

Patients were randomly divided into three cohorts, with six patients in each cohort receiving active drug (40 mg doses once, twice, or three times daily) while the remaining two patients received placebo. After 28 days of treatment, which was conducted in an inpatient setting, patients were followed for an additional 56 days.

The Symptoms of Depression Questionnaire (SDQ), Montgomery–Åsberg Depression Rating Scale (MADRS), Cognitive Global Impression-Improvement (CGI-I), and the Massachusetts General Hospital (MGH) Cognitive, and Physical Functioning Questionnaire (CPFQ) were used to assess participants’ depressive symptoms throughout the trial.

The authors found NSI-189 to be well tolerated with significantly greater antidepressant effects than placebo in two (SDQ and CPFQ) of four depression outcome measures. The most common adverse events associated with NSI-189 use included headache, dizziness, and somnolence.

“The significant benefits on the SDQ and the trends for improvement on the MADRS and CGI-I were maintained steadily beyond the acute phase of the double-blind administration and were still present at day 84, with the exception perhaps of the 40 mg [once-daily] regimen,” the study author wrote. “This finding is in sharp contrast to the rapid return of symptoms typically observed following discontinuation of standard antidepressants.”

The study authors added that while the sample size of study was small, “each cohort [treated with NSI-189] seemed to have consistently shown an antidepressant effect and the overall effect sizes were quite robust.”

Fava, in press statement, said that if the efficacy of NSI-189 is confirmed in larger trials, it “could be an important new option for patients not helped by currently available medications.”

To read more about non-SSRI therapies currently in the pipeline to treat depression, see Psychiatric News article “Ten Non-SSRI Antidepressant Drugs Bring Hope Psychotropic Pipeline.”

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Distinct ‘Biotypes’ Identified That Cross Clinical Psychosis Diagnoses

Three neurobiologically distinct psychosis “biotypes” have been identified that appear to cross clinical diagnostic boundaries for schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis, according to a report appearing online today in AJP in Advance. The study illustrates how distinct neurobiological biotypes can, through multiple pathways, lead to clinically similar psychosis manifestations. And the findings may lead to more individualized treatment options, the authors say.

Carol Tamminga, M.D. (pictured at left), who is the Lou and Ellen McGinley Distinguished Chair in Psychiatric Research at the University of Texas Southwestern Medical Center, and colleagues recruited 800 patients with schizophrenia, schizoaffective disorders, and psychotic bipolar disorder, along with 1,000 of their family members and 250 healthy controls, to complete a battery of neurocognitive and perceptual tasks. The researchers then characterized the participants according to biomarkers corresponding to cognition, auditory stimulation, brain electrical function as measured by electroencephalogram, and oculomotor movements, among other variables.

Using statistical analyses, the researchers identified three neurobiologically distinct subgroups of psychosis, each including patients representing all DSM psychosis categories.

“These data suggest that we have been grouping people in non-biologically homogeneous groups up until now,” Tamminga told Psychiatric News. “We anticipate that each of these biotypes will have a distinctive genetic profile; moreover, if these groups differ in their biological substrate, then unique medications ought to be available to treat each biotype.”

The findings also “illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard,” the study authors wrote.

For related information, see the Psychiatric News article “Cortisol, Inflammatory Biomarkers May Predict Treatment Response in Schizophrenia.”

(Image: David Hathcox)

Hostility Levels May Predict Treatment Discontinuation Among Patients With Schizophrenia

Higher levels of hostility are linked with earlier treatment discontinuation in people with schizophrenia, reports a new study published in European Psychiatry. According to the study authors, the findings highlight the importance of establishing a strong physician-patient relationship while managing symptoms of hostility.

To investigate the effects of hostility on treatment discontinuation as well as predictors and correlates of hostility, the study authors pooled data from two large schizophrenia clinical trials—the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and the European First Episode Schizophrenia Trial (EUFEST)—which provided them with comprehensive medical information from 1,154 patients.

After six months of treatment, more than 60% of patients rated with high hostility had discontinued their medication compared with about 30% of patients with low hostility levels. The greater a patient’s positive symptoms, impaired insight, and/or drug or alcohol consumption, the more likely they were to have heightened hostility. Young age and low adherence to pharmacological treatment also increased risk for higher hostility.

Though the researchers did not identify a mechanism linking hostility and discontinuation, they did note that patients who took olanzapine had the lowest all-cause rates of treatment discontinuation in both the CATIE and EUFEST studies, which might suggest that this medication is the most effective at treating hostility symptoms.

“Alcohol and drug use, impaired insight, low adherence to treatment, and positive symptoms are dynamic, modifiable variables that are associated with hostility in schizophrenia, and might have a causal role in its development and maintenance,” the study authors wrote. “The clinical implications of the results point to the importance of detection and management of hostility, as well as to the treatment of comorbid substance use disorders.”

To read about more recent findings arising from the CATIE study, see the Psychiatric News article “Study Identifies Factors Predictive of Response to Risperidone,” which describes the AJP in Advance article “Differential Response to Risperidone in Schizophrenia Patients by KCNH2 Genotype and Drug Metabolizer Status.”

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Study Points to Risk Factors That May Predict Suicidal Behavior Within 12 Months of ED Visit

Prior self-injury and alcohol abuse are among the variables identified as predictive of suicidal behavior 12 months after an initial positive screen for suicide risk in the emergency department (ED), according to a report published this week in Psychiatric Services in Advance.

Researchers from several institutions, who presented the findings at a meeting of the American College of Emergency Physicians in Chicago last year, analyzed data from the Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE). The latter was an eight-center study designed to test an approach to universal screening for suicide risk and post-visit telephone intervention among ED patients.

At baseline, 577 out of 874 participants (66%) had suicidal ideation only, whereas 297 (34%) had a suicide attempt in the past week. In the 12 months after the index ED visit, 195 (25%) had documentation of having attempted or died by suicide.

The researchers found that participants were more likely to have suicidal behavior if, at the index ED visit, they reported that their highest level of education was high school completion or less, were unemployed, had a history of chronic health conditions, had a history of depression, had an ED visit within the past six months, or had a high suicidal ideation severity score on the Columbia Suicide Severity Rating Scale. In addition, individuals reporting at least one past suicide attempt, a history of non-suicidal self-injury, or indicating suicidal ideation with intent or intent with a plan were significantly more likely than others to engage in future suicidal behavior.

Greg Simon, M.D. (pictured above), a psychiatrist and senior investigator at the Group Health Research Institute (who is also on the editorial board of Psychiatric Services), told Psychiatric News the new data confirm that people who seek care for suicidal ideation are at high risk for suicide attempt over the next year. “Suicidal ideation reflects an enduring vulnerability—rather than just a short-term crisis,” he said.

For related information, see the Psychiatric News article “Clinicians’ Language in Notes May Show Signs of Patients at Risk for Suicide.”

(Image: Group Health Research Institute)

Antidepressants Do Not Increase Breast Cancer Recurrence in Women Taking Tamoxifen

Women taking tamoxifen to reduce their risk of breast cancer recurrence also frequently take antidepressants to help counter tamoxifen’s side effects, which include hot flashes, night sweats, and depression. However, some previous studies have suggested antidepressants may reduce the effectiveness of tamoxifen, thus raising the risk of breast cancer recurrence.

A new assessment of the medical records of nearly 17,000 breast cancer survivors published this week in the Journal of the National Cancer Institute suggests there is no increased risk of subsequent breast cancer in women who concurrently took tamoxifen and antidepressants.

The study examined 16,887 women in California who were diagnosed with breast cancer from 1996 to 2007 and treated with tamoxifen (all women were insured by Kaiser Permanente Southern California, who conducted this study). Of this group, 8,809 also took antidepressants, including paroxetine, fluoxetine, and tricyclics. The participants were stratified based on the degree of overlap in days taking tamoxifen and antidepressants.

Over the course of the study, 2,946 women developed breast cancer. The study authors found no statistically significant difference in breast cancer recurrence in women taking tamoxifen only and those also taking antidepressants—even in women who had a 75% or greater overlap in days taking both medications.

“Given that thousands of breast-cancer survivors struggle with depression, sleep disturbances, and other side effects while on tamoxifen, our study should help alleviate any concerns physicians have about prescribing antidepressants to their breast-cancer patients to help improve their quality of life,” said lead author Reina Haque, Ph.D., M.P.H., a research scientist at Kaiser Permanente Southern California, in a press statement.

To read more about treating depression in patients with cancer, see the Psychiatric News article by Jesse Fann, M.D., M.P.H., titled “Integrated Psychosocial Care for Cancer Patients.”

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Study Suggests Escitalopram May Reduce Inflammatory, Neurotoxic Biomarkers

In addition to alleviating symptoms of depression in some people, the selective-serotonin reuptake inhibitor (SSRI) escitalopram may protect against some inflammatory and neurotoxic biomarkers associated with the mood disorder, a study in the Journal of Psychiatric Research reports.

Angelos Halaris, M.D., Ph.D., a professor of psychiatry and behavioral neurosciences at Loyola University Chicago Stritch School of Medicine, and colleagues compared blood samples from 30 adults with MDD taking 20 to 40 mg of escitalopram daily for 12 weeks with those obtained from 27 controls. The researchers assessed plasma levels of inflammatory biomarkers and tryptophan/kynurenine metabolites for both groups at baseline and for patients with MDD again 4, 8, and 12 weeks after initiating treatment with escitalopram. Clinical assessments during the studied period were also carried out at each visit using the Hamilton depression (HAM-D), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI) scales.

The researchers found that baseline plasma concentrations of all studied inflammatory biomarkers were higher in the MDD cohort compared with controls, with four biomarkers reaching statistical significance (hsCRP, TNF-alpha, IL6, and MCP-1). However, 12 weeks of escitalopram treatment was associated with reduced levels of TNF-alpha as well as significant reductions in total scores on the HAM-D, BDI, and CGI rating scales. In addition, 8 to 12 weeks of treatment with escitalopram was associated with a statistically significant decrease in the neurotoxic metabolites 3-hydroxykynurenine and quinolinic acid.

“Although it is not certain at this point whether these biomarker changes are the cause or effect of the clinical improvement achieved at week 8, one clear observation is that, at week 8, escitalopram monotherapy induced reduction of both clinical symptom scores and inflammatory and neurotoxic biomarkers,” the study authors noted.

For related information, see the Journal of Neuropsychiatry and Clinical Neurosciences article “Psychopharmacological Neuroprotection in Neurodegenerative Disease: Assessing the Preclinical Data.”

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Media Often Frame Opioid Analgesic Abuse as Criminal Justice Issue, Not a Health Condition

Evidence-based treatments for opioid analgesic abuse are well known, but a study of U.S. media coverage appearing today Psychiatric Services in Advance suggests the news media more often frame the problem as a criminal justice issue and not a treatable health condition.

Over the past two decades, the rates of opioid abuse, addiction, and overdose have climbed steadily in the United States. According to most recent estimates, some 4.5 million Americans use prescription pain relievers (the majority of which are opioid analgesics) for nonmedical purposes, and 1.9 million nonmedical users are dependent on these drugs. Additionally, about 16,000 people are believed to die each year from overdose deaths involving these drugs—more than deaths caused by heroin and cocaine combined.

To better understand how this issue has been framed in public discourse, Emma McGinty, Ph.D., an assistant professor of health policy and management and mental health at the Johns Hopkins Bloomberg School of Public Health, and colleagues analyzed 673 print and television news stories from 1998 to 2012.

About 57% of news stories that mentioned a cause for opioid abuse said that illegal drug dealing was the main cause. Physician-related causes were also frequently mentioned: 45% of news stories that noted any cause mentioned that it was easy to get a prescription for an opioid analgesic from a doctor, and 28% mentioned that doctors prescribe painkillers at inappropriately high doses or prescribe more pills than necessary.

Just over half (51%) of the news stories mentioned possible solutions to opioid analgesic abuse, with law enforcement efforts to arrest and prosecute drug dealers mentioned most frequently (64% of new stories). Only 3% and less than 1% of news stories mentioned expanding substance use treatment and harm-reduction policies, respectively, as potential solutions.

However, the authors noted, attitudes appeared to change over time. “The proportion of news stories mentioning law enforcement solutions decreased over the study period, from 70 percent in 1998–2000 to 57 percent in 2010–2012, and the proportion of stories mentioning prevention-oriented solutions increased from 10 percent in 1998–2000 to 55 percent in 2010–2012,” wrote McGinty and colleagues. “The findings underscore the need for a concerted effort to reframe opioid analgesic abuse as a treatable condition addressable via well-established public and behavioral health approaches.”

For more in Psychiatric News about opioid abuse, see “Opioid Use Found to Be Decreasing, While Opioid-Related Deaths Increase.” For additional information, read the recent blog post “How the APA Is Helping Address America’s Opioid Crisis,” by APA CEO and Medical Director Saul Levin, M.D., M.P.A.

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