SOURCE: HealthDay News
June 18, 2014  | Steven Reinberg

Teen suicide attempts rose nearly 22 percent after the U.S. Food and Drug Administration (FDA) warned about dangers of antidepressants, a new study finds.

In 2003, the FDA mandated a "black box" warning -- the most serious type of warning in prescription drug labeling -- on popular antidepressant medications called selective serotonin reuptake inhibitors (SSRI), signaling a possible risk of suicidal thoughts among children and teens. Examples of these drugs include Celexa, Paxil, Prozac and Zoloft.

Following the warnings, antidepressant prescriptions for young people fell by more than a fifth. At the same time, suicide attempts rose, possibly because depression was being undertreated, according to background information in the study.

"We found a substantial reduction in use of antidepressants in youth, and also in adults -- who were not targeted by the warning," said lead author Christine Lu, an instructor in population medicine at the Harvard Pilgrim Health Care Institute in Boston.

Lu attributes the drop in prescriptions to the FDA's warning and resulting media coverage. "To a certain extent, the FDA's black box warning was legitimate, but the media emphasis was really on suicide without noting the potential risk of undertreatment of depression. Because of that, there has been an overreaction, and that overreaction has sent alarming messages to parents and young people," she said.

Although the initial studies showing an increased risk of suicide in teens taking antidepressants prompted the black box warnings, researchers never proved that the medications were the cause of the increased risk of suicide, only that there was a link.

Likewise, though the current research finds a strong association between the uptick in suicides and the drop in antidepressant use, Lu and her colleagues weren't able to definitively show that a decrease in antidepressant prescriptions was directly responsible for the recent increase in suicide attempts.

Antidepressant use dropped more than 20 percent after the warnings were issued in young adults. For adults -- who weren't included in the warnings -- antidepressant use went down by more than 14 percent, according to the study.

This decrease may have left many depressed young people without appropriate treatment. That in turn may have driven an increase in suicide attempts, Lu noted. The study didn't find an increase in completed suicides for any age group.

Coverage of the warning may have had unintended consequences, Lu said. Doctors may have been less willing to prescribe antidepressants and parents may have been fearful of letting their children take them, she said.

The lesson, Lu said, is that the media and the FDA should strive for the right balance so potential overreactions don't occur.

Lu noted that over time people have become less reluctant to use these drugs.

The FDA now recommends that doctors consider both the risk of prescribing an antidepressant and the risk of not prescribing the drug. Doctors should also monitor patients for suicidal thoughts.

Undertreating depression is worse than the slight increase in suicidal thoughts antidepressants may cause, Lu said. "It's also a reminder for doctors to weigh the risk of a drug with the risk of not treating or undertreating the condition," she said.

For the study, Lu and colleagues used the Mental Health Research Network to collect medical claims data from 11 U.S. health plans from 2000 to 2010. This database includes records for 1.1 million teens, 1.4 million young adults and 5 million adults.

To measure suicide attempts, the researchers used records of overdose with mind-altering drugs, such as marijuana, amphetamines, tranquilizers and Ecstasy.

They found that suicide attempts rose 21.7 percent among teens and 33.7 percent among young adults.

SOURCE: HealthDay News
July 10, 2014 | Steven Reinberg

Stress, hostility and depression may increase the risk for stroke, a new study suggests.

The study found that depression seemed to raise the risk of a stroke or a transient ischemic attack (TIA) by 86 percent. It also found that stress apparently raised stroke or TIA risk by 59 percent. And hostility doubled the risk, the researchers said. A TIA is a mini-stroke caused by a temporary blockage of blood flow to the brain. However, it's important to note that the study only found an association between the risk of stroke and negative emotions. It wasn't designed to prove that negative emotions can cause strokes.

Still, "chronic stress and negative emotions are important psychological factors that affect one's health, and findings from this study link these factors to brain health in particular," said the study's lead author, Susan Everson-Rose, an associate professor of medicine at the University of Minnesota.

"Patients and their health care providers should be aware that experiences of chronic stress and negative emotional states can increase risk for stroke," she noted. The findings were published online July 10 in the journal Stroke.

For the study, Everson-Rose and her colleagues collected data on nearly 7,000 adults, aged 45 to 84, who took part in the Multi-Ethnic Study of Atherosclerosis. The study included people from six different sites in the United States.

Participants filled out questionnaires asking about chronic stress, depressive symptoms, anger and hostility. None of the patients had heart disease or a history of stroke at the beginning of the study.

After an average follow-up of about 8.5 years, just under 3 percent of the original group had suffered either a stroke or a mini-stroke -- 147 participants had a stroke and 48 had a mini-stroke, according to the study.

The researchers found that those who reported the highest levels of emotional problems were at the greatest risk for a stroke or mini-stroke, compared with those with the lowest levels of stress, hostility and depression. These associations remained significant even when the researchers took into account age, race, sex, health behaviors and other known risk factors for stroke, Everson-Rose and colleagues noted.  Interestingly, anger didn't appear to significantly increase the risk for stroke or mini-stroke, the investigators found.

The researchers didn't ask about people's coping strategies. So they don't know if how people coped with their emotions could have had an effect on stroke risk.

For those concerned about reducing their stroke risk, classic risk factors -- such as smoking and high blood pressure -- are important. But, this study suggests that people also need to pay attention to stress and emotions and how they affect health, Everson-Rose said.

Dr. Richard Libman, chief of vascular neurology at North Shore-LIJ Health System in Manhasset, N.Y., said, "Psychological factors have been long thought to play a role in heart disease and stroke." Depression isn't just a consequence of stroke, but predicts a higher risk of stroke years in advance, he said.

"Chronic stress has been thought to be a risk factor for stroke. In other studies, acute stress has also been found to be a trigger for stroke, that is to say that strokes occur immediately after a stressful event more often than would be expected," Libman explained.  "This study reopens a neglected field in stroke research, that is the psychological aspects of our lives, which can have a profound impact on our health," he said.

Dr. Jeffrey Borenstein, president and CEO of the Brain & Behavior Research Foundation in New York City, said that for overall health, it's important that people suffering stress and depression get professional help. "People shouldn't suffer in silence, they should seek help, whether it be talk therapy, medication or a combination of the two," he said.

SOURCE: HealthDay News
July 3, 2014 | Randy Dotinga

Whether drugs used to treat attention deficit hyperactivity disorder boost the risk of heart conditions in children remains a subject of concern. Now, research from Denmark suggests medications such as Ritalin and Concerta make rare cardiac problems twice as likely, although still uncommon.

"The risk of adverse cardiac effects of ADHD medication is real and should not be forgotten," said study lead author Dr. Soren Dalsgaard, an associate professor at Aarhus University.

However, doctors and parents should not be alarmed and take kids off stimulant medication if they have benefits from it and no cardiac symptoms, he said. "But we should continue to monitor cardiovascular status," he added. The findings aren't definitive because they don't prove cause-and-effect and they seem to conflict with some previous research that looked at fewer heart conditions over shorter periods of time.

The inattention, hyperactivity and impulsivity associated with ADHD can make it hard for children with the disorder to learn and socialize. Stimulant drugs taken on a daily basis can help control these behaviors. Worldwide, the number of children and teens with ADHD who take stimulant medications is increasing, according to background research in the study. Experts say these drugs can boost heart rate and blood pressure.

"The most common cardiac effects are benign -- very small, clinically insignificant increases in heart rate or blood pressure," said Dr. Andrew Adesman, chief of developmental and behavioral pediatrics at Cohen Children's Medical Center of New York in New Hyde Park.

Alarms sounded because of reports of sudden deaths, heart attack and stroke related to ADHD drugs, which has led some physicians to assess heart health before starting young people on the drugs.  But a 2011 study of U.S. children and young adults published in the New England Journal of Medicine found no link between ADHD drugs and heart attacks, sudden death and stroke. And in 2012, a study in the Journal of the American Medical Association found no sign of a link in young and middle-aged adults either.

The new study, published online recently in the Journal of Child and Adolescent Psychopharmacology, followed 714,000 children in Denmark, born from 1990 to 1999, for an average of 9.5 years. Of those, 8,300 were diagnosed with ADHD after age 5.  Of the total with ADHD, 111 kids -- or a little more than 1 percent -- had a heart problem such as high blood pressure, cardiac arrest, irregular heartbeat or general cardiovascular disease.

When the researchers adjusted their statistics to take into account certain differences, they found those who took methylphenidates such as Ritalin or Concerta -- whether diagnosed with ADHD or not -- were about twice as likely to suffer from heart problems.

The researchers didn't examine whether ADHD itself could be linked to heart problems.

In a news release, journal editor Dr. Harold Koplewicz said the study "confirms the small but real risk we have understood for some time through prior reports and clinical experience." Koplewicz is president of the Child Mind Institute in New York City.

The findings raise the question of whether the benefits of the drugs outweigh the possible harms. In the big picture, few children who took the drugs actually developed heart problems, study lead author Dalsgaard said.

"Indeed, the benefits from ADHD medication can be worth the risk of adverse effects, but we should not underestimate the risk of cardiac effects," he said.

Adesman emphasized the rarity of heart problems in ADHD patients. Parents may wish to talk to a pediatric cardiologist if their child has an existing heart problem and they wish to put them on a stimulant for ADHD, he said.

"In my experience, most cardiologists will support treatment with stimulant medication for most children with congenital heart disease -- even for kids who have had open heart surgery to repair a malformed heart," he said.

More research is planned, Dalsgaard said, especially to unravel an unusual finding in the study. Children seemed at higher risk of heart problems if their doctors had lowered their drug dosage. It's not clear if the change in dose contributed to the heart issues or whether there's another explanation.

SOURCE: Everyday Health
June 30th 2014 | Vanessa Caceres

The right doctor or therapist can treat depression effectively and offer support and encouragement. Here's what to look for in a mental health professional.

Consider your mind like a muscle: When searching for the right doctor or therapist to treat your depression symptoms, find someone who will be like a personal trainer to help you get into better mental shape.

“A doctor or therapist for depression is a lot like a physical trainer, only for the psyche,” says Amy Przeworski, PhD, an assistant professor in the department of psychological services at Case Western Reserve University in Cleveland. “A good doctor or therapist recognizes where a person is now and helps to gently stretch his or her psychological muscles while not pushing too far outside of his or her comfort zone.”

How do you find the right mental health professional for your depression treatment? In addition to considering the person's credentials and training, it's important to feel comfortable with that person. Attend a few office visits to see if there’s a good fit. You'll likely have to speak with more than one specialist to find the right person for you, according to the Anxiety and Depression Association of America.

How to Find the Right Depression Specialist for You

Use this checklist to make sure you find a doctor or therapist who can put you on the right track to manage depression:

1. Select someone who can provide the services you want. For example, psychiatrists can prescribe medication, but many psychiatrists today don’t meet with patients every week for talk-therapy sessions, Przeworski says. In contrast, she says, psychologists, social workers, and counselors don’t prescribe medication, but they usually provide ongoing therapy services. Many people with depression will see both a psychiatrist and a talk therapist.

2. Make sure you feel a good connection. Przeworski says you should feel comfortable working with the person. “The bond between you and your doctor or therapist is extremely important, so finding someone with whom you click is essential,” she says. Your doctor or therapist should guide you to step outside your comfort zone somewhat and help you discover something new about yourself. “If that doesn’t feel like the right fit after a handful of sessions, that person may not be right to treat you.”

3. Find out about the person's approach to therapy. For example, a therapist using cognitive behavioral therapy will teach you techniques to help you change your behavior. A therapist with an interpersonal approach will help you explore how your relationships might contribute to your depression. A therapist with a psychodynamic focus will analyze how childhood experiences laid a foundation for your depression, Przeworski says.

4. Seek a collaborative approach toward your goals. “This doesn’t mean that you and your doctor or therapist can’t disagree on certain treatment goals,” Przeworski says. “Sometimes one of you may identify a goal early on and that changes as time wears on. Therapy may involve revising therapy goals and tasks periodically.”

5. Look for someone who will challenge you. You don’t want a doctor or therapist who’ll just tell you everything is going to be okay, says Patrick McGrath, PhD, a clinical psychologist and the director of the Center for Anxiety and Obsessive Compulsive Disorders at Alexian Brothers Behavioral Health Hospital in Hoffman Estates, Illinois. “You want to be treated by someone who’s going to make you feel uncomfortable sometimes," he says. That’s because when you’re depressed, your motivation to try new things is lower, so you need a doctor or therapist who’ll prompt you to step out of your shell. The right person should be supportive but challenging, McGrath says.

6. Find someone with a clear treatment approach. If you ask how your doctor or therapist plans to treat your depression and they say something like “a mixed approach,” that could be a warning sign that they're not sure how to treat you, McGrath says. A good depression doctor or therapist usually has a clear-cut, evidence-based technique for working with depression symptoms.

7. Expect homework. Depression treatment isn’t just something that happens during your office visits. “Therapy happens all the time,” McGrath says. “If you’re not applying it in your life, then why bother?” He says he gives people “homework” for managing depression to do outside of his office and asks if they've done the work when they return. “If they didn’t do it, then we don’t progress in therapy,” he says.

In addition to these signs of a good doctor or therapist for depression, you’ll want to check on your insurance coverage before making a decision. See if your insurance covers mental health treatment, and find out if a specific depression specialist works with your health insurance company. If you’re paying any fees out of pocket, the Anxiety and Depression Association of America recommends asking if there's an adjustable fee scale based on income.

SOURCE: Columbia University’s School of Public Health
July 8, 2014

Maternal inflammation, as indicated by the presence in maternal blood of early gestational C-reactive protein, appears to be associated with greater risk for schizophrenia in offspring, according to a study published in the online edition of the American Journal of Psychiatry.

Alan Brown, MD, Columbia University’s Mailman School of Public Health, New York, New York, and colleagues conducted an analysis of data from the Finnish Prenatal Study of Schizophrenia, a large, national birth cohort with an extensive bio-bank. They tested for the presence of C-reactive protein in the maternal blood of 777 offspring with schizophrenia and compared the findings with those from 777 control subjects. Maternal C-reactive protein levels were assessed from archived maternal serum specimens.

They found that increasing maternal C-reactive protein levels were significantly associated with development of schizophrenia in offspring and remained significant after adjusting for potential confounders such as parental history of psychiatric disorders, twin/singleton birth, location of birth, and maternal socioeconomic status.

For every 1 mg/L increase in maternal C-reactive protein, the risk of schizophrenia increased by 28%.

“This is the first time that this association has been demonstrated, indicating that an infection or increased inflammation during pregnancy could increase the risk of schizophrenia in the offspring,” said Dr. Brown, MD.

“Inflammation has been shown to alter brain development in previous studies, and schizophrenia is a neurodevelopmental disorder,” he said. “Thus, this study provides an important link between inflammation and schizophrenia and may help us to better understand the biological mechanisms that lead to this disorder. To the extent that the increased inflammation is due to infection, this work may suggest that approaches aimed at preventing infection may have the potential to reduce risk of schizophrenia.”

There are many other known causes of inflammation, including tissue injury and autoimmune disease, although the researchers did not examine these specific conditions in their study.

SOURCE: Otsuka Pharmaceutical Co., Ltd
July 14, 2014

Otsuka Pharmaceutical Co., Ltd. and H. Lundbeck A/S, today announced the submission of a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for brexpiprazole for the treatment of schizophrenia and as adjunctive treatment of major depressive disorder (MDD).

The clinical development program for brexpiprazole included more than 6,500 participants of whom more than 5,300 received brexpiprazole. The NDA is supported by seven completed Phase 2 or 3 clinical studies in the proposed indications. Following the submission the U.S. Food & Drug Administration (FDA) will determine if the NDA is sufficiently complete to allow for a substantive review of the data; a decision from the FDA on initiation of the substantive review is expected in September 2014.

Brexpiprazole is a novel investigational compound discovered by Otsuka and under co-development with Lundbeck. Brexpiprazole is a serotonin-dopamine activity modulator (SDAM) that acts as a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors.

The Sidewalk Psychiatrist (http://www.thesidewalkpsychiatrist.com) is a blog written by an experienced psychiatrist treating a variety of populations, from kids to adults. 

It is a casual but insightful read about psychiatry and pharmacology, especially psychopharmacology. His posts are concise, thought out and offer tips and tricks for other prescribers/providers.

SOURCE: Psychiatric Times
March 13, 2014 | Jeffrey J. Rakofsky, MD

Many of our patients want to incorporate nutritional supplements into their pharmacologic regimen. They view psychotropics with skepticism and prefer natural products, which are more consistent with their values and beliefs toward life and health. For some, supplements represent a seemingly safe augmentation strategy. Others view nutritional supplements as a “natural” treatment option and hope such agents will replace their psychotropic regimen.

With the multitude of nutritional products available to patients via the Internet and health-food stores, psychiatrists need to be prepared to respond to questions from patients about the value of these supplements. With so few FDA-approved treatment options in bipolar depression, bipolar patients, in particular, are likely to ask whether these products will help eliminate their painful and recurring depressive symptoms.

Along with my co-author, Boadie W. Dunlop, MD, I recently reviewed the efficacy data of nutritional supplements for the treatment of bipolar depression. From the PubMed and Ovid MEDLINE databases, I identified all randomized clinical trials of nutritional supplements in bipolar depressed patients that met the following inclusion criteria: the subject sample included adult bipolar (I, II, or NOS) depressed or euthymic patients; were randomized controlled trials; reported changes in depressive symptoms or depressive episode recurrences; and were written in English. Studies that enrolled both non-bipolar and bipolar patients were included only if they reported the results for the bipolar patients separately. Supplements were organized into 3 categories: essential nutrients/minerals, non-essential nutrients, and combinations of nutritional products. The study design, and efficacy and adverse event data for each study were evaluated.

What the evidence showed

Among essential nutrients/minerals, omega-3-fatty acids had the strongest evidence of efficacy for bipolar depression, although some studies failed to find positive effects from this supplement. The interpretation of results from omega-3-fatty acid trials is complicated by the varying doses and ratios of eicosapentaenoic acid and docosahexaenoic acid—the 2 forms of omega-3-fatty acids used in trials of this supplement.

Weak evidence supported the efficacy of vitamin C, whereas no data supported the usefulness of folic acid and choline. However, folic acid’s role in prevention of birth defects, particularly among bipolar patients, is of great importance—regardless of its usefulness for bipolar disorder symptoms.

Among the non-essential nutrients, the 2 studies of N-acetylcysteine produced unclear efficacy for treating acute depressive episodes relative to placebo. One study demonstrated its potential to improve depressive symptoms over time. The other, although nonsignificant, suggested it had a prophylactic effect against future depressive episodes.

Inositol is another nonessential nutrient for which the data were unclear. Although all but one of the studies of inositol failed to demonstrate efficacy, the negative studies were underpowered and indicated numerically positive effects. Cytidine was the least supported nonessential nutrient.

Combination supplements (ie, 2 or more supplements taken as a single pill) come in a variety of OTC products, but very few have been the focus of controlled, clinical evaluations. We found no evidence of efficacy for citicoline in uncomplicated bipolar depression, although it may have value for comorbid substance abuse among bipolar patients. Finally, the combination of omega-3-fatty acids and cytidine demonstrated no evidence of efficacy.

Our review did not support routine use of nutritional supplements in the treatment or prophylaxis of bipolar depression. However, study design limitations for both the positive and negative studies reduced the confidence with which our conclusions could be drawn. For example, many of the acute treatment studies had a long duration that may have allowed patients to experience a natural recovery from their episode, unrelated to the study treatment. This would diminish any drug-placebo difference and lead to false-negative outcomes. Sample sizes were often small, which could lead to both false-positive and false-negative efficacy assessments. Baseline mood symptom severity and/or episode were often not reported, thus introducing a potentially significant uncontrolled confounder of outcomes. Some studies included patients in any mood pole of bipolar disorder, making it unclear which phase of the illness was most affected by the study compound.

For some supplements, particularly the omega-3-fatty acids, the unique taste may have unblinded the participants or raters, leading to symptom reporting or scoring based on the expectation of improvements, rather than actual improvements. Changes to adjunctive psychotropic medication doses were permitted in some studies, which made it unclear whether a reported benefit or lack of benefit for a supplement was influenced by such medication changes. Finally, some studies included patients with very low symptom severity, which made it difficult to demonstrate the supplement’s potential benefit because of a floor effect on potential improvement.

Patients with bipolar disorder who seek alternative treatments in the form of nutritional supplements will likely be disappointed by these findings. However, supplements can be expensive, and they are usually not covered by health care insurance policies. In addition, these products may present unknown physical harms, because the FDA holds them to a different standard of safety than psychotropic medications. Finally, those who stop psychotropics, believing that supplements are superior and safer, can experience a worsening symptom course.

Given these risks, better-designed studies must be conducted to determine whether nutritional supplements will help bipolar depression before we encourage widespread use of individual supplements. Despite these inconclusive findings, psychiatrists must remain open to the possibility that with further studies, we may eventually identify minerals and supplements that will benefit bipolar patients. Remember, lithium—the cornerstone of bipolar treatment for several decades—is also a mineral.

REFERENCES

1. Benkert O, Graf-Morgenstern M, Hillert A, et al. Public opinion on psychotropic drugs: an analysis of the factors influencing acceptance or rejection. J Nerv Ment Dis. 1997;185:151-158.

2. Astin JA. Why patients use alternative medicine: results of a national study. JAMA. 1998;279:1548-1553.

3. Rakofsky JJ, Dunlop BW. Review of nutritional supplements for the treatment of bipolar depression [published online ahead of print December 18, 2013]. Depress Anxiety. doi: 10.1002/da.22220.

4. Green NS. Folic acid supplementation and prevention of birth defects. J Nutr. 2002;132(suppl 8):2356S-2360S.

5. US Food and Drug Administration. Q&A on dietary supplements. http://www.fda.gov/Food/Dietarysupplements/default.htm. Accessed February 24, 2014.

SOURCE: HealthDay News
May 12, 2014 | Kathleen Doheny 

Children taking medications to treat attention-deficit/hyperactivity disorder (ADHD) -- such as Adderall, Ritalin and Vyvanse -- are less likely to smoke, according to a new analysis.

Kids with ADHD who were treated with these so-called stimulant medications were about half as likely to smoke as children with this disorder who weren't treated with these medications, researchers found.

"We found an association between getting treated with stimulant medications and having a lower risk of smoking in adolescence and adulthood," said study researcher Erin Schoenfelder, clinical psychologist at Duke University School of Medicine in Durham, N.C.

The study, which was funded by the U.S. National Institute on Drug Abuse, is published online May 12 and in the June print issue of the journal Pediatrics.

About 11 percent of American children aged 4 to 17 have a diagnosis of ADHD, according to the U.S. Centers for Disease Control and Prevention (CDC). Children with ADHD can be impulsive, have trouble concentrating and may have other behavior problems. About 70 percent to 80 percent of children respond to stimulant medicine, according to the CDC. Behavior therapy can also help.

Experts have long known that children with ADHD have a higher risk of starting to smoke cigarettes. Teens with ADHD are two to three times more likely to smoke cigarettes than their friends who don't have the diagnosis, according to Schoenfelder, citing previous research. But, research on the effects of ADHD stimulant medicine on the risk of smoking has been conflicting.

To try to better answer the question of whether or not these medications could help prevent kids from smoking, the Duke researchers re-analyzed the results of 14 studies of cigarette smoking and ADHD treatments. The studies included more than 2,300 children with ADHD. About 1,400 of the kids were being treated with stimulant medications, according to the new analysis.

The studies were published between 1980 and 2013. The average follow-up time was about seven years. The researchers compared the teens treated with stimulants to those who weren't to see which group was more likely to smoke.

Overall, those on medications were about half as likely to smoke as those not on the medications, Schoenfelder said.

"Those who took their medication consistently and for a longer period of time had an even lower risk of smoking," she added.

The data she analyzed overwhelmingly showed that medications appear to decrease the risk of smoking, according to Schoenfelder.

Like all medications, ADHD medicines have side effects. This analysis showed a "slight effect" on growth, she said. However, that finding must be weighed against the many positive long-term benefits, she explained.

Schoenfelder pointed out that the researchers "can't say based on this study that the treatment caused the lower rate of smoking, but there is an association we found." However, association does not prove a cause-and-effect relationship.

One potential reason medication might have an effect is that both nicotine and the stimulant medications used to treat ADHD operate on the same pathways in the brain. They both improve the same processes that are disrupted in ADHD, according to Schoenfelder.

"Kids who have ADHD know that something is not quite right," said Dr. Trevor Resnick, chief of the department of neurology at Miami Children's Hospital, who commented on the study.

"They try to self-medicate," he explained, and "cigarettes would be an example of self-medication." As a result, children with ADHD have a much higher risk in general of turning to cigarettes, pot or illicit drugs, he said.

"What this study shows, similar to previous research, is that successful treatment of ADHD with stimulant medication decreases the risk of self-medication in these children," Resnick noted.

While stimulant medications do have several possible side effects, Resnick said, "most kids are able to tolerate" the medication.

SOURCE: DocGuide
June 2014 | Hung C, Liu C, Hsiao M, Yu N, Chu C

BACKGROUND 
Few studies have simultaneously compared the impacts of pharmacotherapy and mental diagnoses on metabolic syndrome (MetS) among psychiatric outpatients with mood and anxiety disorders. This study aimed to investigate the impacts of pharmacotherapy and mental diagnoses on MetS and the prevalence of MetS among these patients.

METHODS 
Two-hundred and twenty-nine outpatients (men/women = 85/144) were enrolled from 1147 outpatients with mood and anxiety disorders by systematic sampling. Psychiatric disorders and MetS were diagnosed using the Structured Clinical Interview for DSM-IV-TR and the new International Diabetics Federation definition, respectively. The numbers of antipsychotics, mood stabilizers, and antidepressants being taken were recorded. Logistic regression was used to investigate the impacts of pharmacotherapy and psychiatric diagnoses on MetS.

RESULTS 
Among 229 subjects, 51 (22.3%) fulfilled the criteria for MetS. The prevalence of MetS was highest in the bipolar I disorder (46.7%) patients, followed by bipolar II disorder (25.0%), major depressive disorder (22.0%), anxiety-only disorders (16.7%), and no mood and/or anxiety disorders (14.3%). The percentages of MetS among the five categories were correlated with those of the patients being treated with antipsychotics and mood stabilizers. Use of antipsychotics and/or mood stabilizers independently predicted a higher risk of MetS after controlling for demographic variables and psychiatric diagnoses. When adding body mass index (BMI) as an independent variable in the regression model, BMI became the most significant factor to predict MetS.

CONCLUSION 
BMI was found to be an important factor related to MetS. Pharmacotherapy might be one of underlying causes of elevated BMI. The interactions among MetS, BMI, pharmacotherapy, and psychiatric diagnoses might need further research.

SOURCE: JAMA Psychiatry
June 2014
Authors: Huhn M, Tardy M, Spineli L, Kissling W, Förstl H, Pitschel-Walz G, Leucht C, Samara M, Dold M, Davis J, Leucht S

There is debate about the effectiveness of psychiatric treatments and whether pharmacotherapy or psychotherapy should be primarily used. 

OBJECTIVES 
To perform a systematic overview on the efficacy of pharmacotherapies and psychotherapies for major psychiatric disorders and to compare the quality of pharmacotherapy and psychotherapy trials. 

EVIDENCE REVIEW 
We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Library (April 2012, with no time or language limit) for systematic reviews on pharmacotherapy or psychotherapy vs placebo, pharmacotherapy vs psychotherapy, and their combination vs either modality alone. Two reviewers independently selected the meta-analyses and extracted efficacy effect sizes. We assessed the quality of the individual trials included in the pharmacotherapy and psychotherapy meta-analyses with the Cochrane risk of bias tool. 

FINDINGS 
The search yielded 45 233 results. We included 61 meta-analyses on 21 psychiatric disorders, which contained 852 individual trials and 137 126 participants. The mean effect size of the meta-analyses was medium (mean, 0.50; 95% CI, 0.41-0.59). Effect sizes of psychotherapies vs placebo tended to be higher than those of medication, but direct comparisons, albeit usually based on few trials, did not reveal consistent differences. Individual pharmacotherapy trials were more likely to have large sample sizes, blinding, control groups, and intention-to-treat analyses. In contrast, psychotherapy trials had lower dropout rates and provided follow-up data. In psychotherapy studies, wait-list designs showed larger effects than did comparisons with placebo. 

CONCLUSIONS 
Many pharmacotherapies and psychotherapies are effective, but there is a lot of room for improvement. Because of the multiple differences in the methods used in pharmacotherapy and psychotherapy trials, indirect comparisons of their effect sizes compared with placebo or no treatment are problematic. Well-designed direct comparisons, which are scarce, need public funding. Because patients often benefit from both forms of therapy, research should also focus on how both modalities can be best combined to maximize synergy rather than debate the use of one treatment over the other.

SOURCE: New York Times
July 7, 2014 | Jan Hoffman

David Baldwin wasn’t sure how he had come across the other day in group therapy at the hospital, near the co-op apartment where he lives with his rescue cat, Zoey. He struggles with bipolar disorder, severe anxiety and depression. Like so many patients, he secretly wondered what his therapist thought of him.

But unlike those patients, Mr. Baldwin, 64, was able to find out, swiftly and privately. Pulling his black leather swivel chair to his desk, he logged onto a hospital website and eagerly perused his therapist’s session notes.

The clinical social worker, Stephen O’Neill, wrote that Mr. Baldwin’s self-consciousness about his disorder kept him isolated. Because he longed to connect with others, this was particularly self-defeating, Mr. O’Neill observed. But during the session, he had also discussed how he had helped out neighbors in his co-op.

“This seems greatly appreciated, and he noted his clear enjoyment in helping others,” Mr. O’Neill wrote. “This greatly assists his self-esteem.”

A smile animated Mr. Baldwin’s broad, amiable features. “I have a tough time recognizing that I’ve made progress,” he said. “So it’s nice to read this as a reminder.”

Mental health patients do not have the ready access to office visit notes that, increasingly, other patients enjoy. But Mr. Baldwin is among about 700 patients at Beth Israel Deaconess Medical Center who are participating in a novel experiment.

Within days of a session, they can read their therapists’ notes on their computers or smartphones. The hope is that this transparency will improve therapeutic trust and communication.

“We’re creating a revolution,” said Dr. Tom Delbanco, a professor of medicine at Harvard and a proponent of giving patients access to notes by therapists as well as by physicians. “Some people are aghast.”

The pilot project has raised questions in the mental health community. Which patients will benefit and which might be harmed? How will the notes alter a therapeutic relationship built on face-to-face exchanges? What will be the impact on confidentiality and privacy?

And the project presents difficult choices for those who argue for parity between medical and mental health patients. Should patients with schizophrenia, for example, who may stop taking their medication after reading that they are doing well, have the same access to treatment notes as those with irritable bowel syndrome?

But the lingering underlying question is, do patients really want to know what their therapists think? Dr. Kenneth Duckworth, who is the medical director of the National Alliance on Mental Illness, an advocacy group, said: “I’ve offered to share my notes with patients and they’ll say, ‘No, I’m good.’ But it’s a good concept that should be researched.”

The practice is so new that it is too early for a comprehensive evaluation. The Department of Veterans Affairs, which began making medical and mental health records available online last year, is only just beginning to study the effect on mental health patients.

Older studies from psychiatric wards where patients read charts with doctors found that the patients were confused or offended by the content. But as doctors helped interpret their notes, patients began participating more in their care and trusting their team.

Although Beth Israel therapists report that some patients have no interest in reading their notes, responses from a few have been positive and powerful.

Stacey Whiteman, 52, a former executive secretary in Needham with multiple sclerosis, faces growing cognitive as well as physical difficulties. The disease has shaken her self-image and relationships; her psychological health affects her willingness to manage the disease. She finds that her medical and mental health notes complement each other.

“Yes, the therapy notes can be hard to read, and sometimes I wonder, ‘Really, I said all of that?’ ” she said. “But there’s no question that reading this stuff just charges you back up to moving forward.”

While such a program may be feasible in larger systems like Beth Israel, a Harvard hospital, some solo practitioners fear it may require too much time and technological sophistication.

But Peggy Kriss, a psychologist in Newton, is an early adopter. For over a year she has maintained a website with private pages for patients on which she posts session notes, as well as articles, videos and meditations.

Toward the end of each session, she and the patient begin the note together defining the key points that have been raised.

Dr. Kriss said that for most of her patients, online notes have become the new normal. One described them to her as a security blanket between appointments.

Some write replies. “An O.C.D. patient told me I was spelling things wrong,” Dr. Kriss said. “So I said, ‘I’m just modeling anti-perfectionism for you.’ ”

The Beth Israel project grew out of OpenNotes, a program by Dr. Delbanco and his colleagues that made physicians’ notes accessible to 22,000 patients at three institutions. A 2011 study showed that patients responded positively and became more involved in their care.

More systems are adopting the model. At least three million patients now have swift access to office visit notes, including observations and recommendations.

But even those institutions have hesitated to share mental health notes. Critics have raised concerns about whether reading notes could prompt anxiety and even rejection of treatment. What will happen if the patient posts the notes on Facebook, inviting comment?

Proponents of access point out that such notes, which include extensive diagnostic reports, are already available to other doctors and to insurers.

Although patients have long had the right to their records, the process to obtain copies can be protracted. If a doctor thinks that reading notes would be harmful to the patient or others, they can be withheld.

Mindful of such pitfalls, the Beth Israel psychiatrists have offered notes initially to only 10 percent of patients. Clinical social workers are making notes more widely available, though some therapists have temporarily opted out. Nina Douglass, a social worker in the ob-gyn clinic, worries about patients with abusive partners. If the abuser insisted on reading the notes, the patient could be in danger.

“I can imagine that our work can be deepened and enhanced through people reading their notes,” Ms. Douglass said. “But one size doesn’t fit all.”

Mental health notes have very different readers: the therapist, who may use them as a memory prompt; other doctors treating the patient; insurers; and now the patient. Writing a note with necessary information for all can be daunting.

Mr. O’Neill, the social work manager, is pressing therapists to use straightforward descriptions. “I used ‘affect dysregulation,’ and a patient said, ‘What on earth is that? Are you saying I’m totally crazy?’ ” he said. “It just means they can get upset. So why not use the word ‘upset’?”

Some psychiatrists disagree.

“Diagnostic language is used among doctors to describe features of a mental illness,” said Dr. Brian K. Clinton, an assistant professor at Columbia University Medical Center who has written about sharing records. “I would be willing to discuss with a patient what I think. It’s a better way to communicate than a note I wrote for other doctors.”

But Dr. Michael W. Kahn, an assistant professor of psychiatry at Harvard Medical School who wrote about the project in JAMA, said that if the therapist explained the diagnosis, some patients might feel relieved, knowing their behavior fits a pattern that others also experience.

Dr. Glen O. Gabbard, a psychiatrist and professor at Baylor College of Medicine, said that opening notes to patients might have a chilling effect on doctors.

“A psychiatrist would be less likely to put down anything he is musing about as diagnostic possibilities or write about what he feels the patient is leaving out,” he said.

Mr. Baldwin’s longtime friends know about his harrowing battles with mental illness: The hospitalizations. The manic episodes. The depression. The anxiety so crippling that two years ago, at a Costco parking lot, he couldn’t get out of the car.

As he withdrew into his apartment, pints of ice cream, Zoey, and the telephone became his constant companions. During the worst sieges of anxiety, he would call a few friends three, four times a day.

That is the man they recall, he recounted in his freshly tidied apartment. Its décor is hopeful: a multicolored rug, violet curtains, a jaunty lime-green wall.

And so is Mr. Baldwin. He is trying to lose weight, maybe someday have a new man in his life.

He clicked open another therapy note.

Mr. Baldwin “is continuing to try to push himself to get out more and to be more socially connected even while his emotions tell him to do the opposite,” Mr. O’Neill wrote, adding that his patient is “clearly making good, and even courageous, efforts on a number of fronts.”

Mr. Baldwin, who celebrated his birthday recently with a museum lecture, movie and dinner, flushed with pride.

“I’m going to email this to my friends,” he said.

SOURCE: HealthDay News
June 17, 2014 | Robert Preidt

Children with anxiety problems actually have a bigger "fear center" in their brain, researchers report.

The study included 76 children aged 7 to 9, which is when anxiety-related traits and symptoms can first be reliably detected, according to the Stanford University School of Medicine researchers. The parents provided information about their youngsters' anxiety levels, and the children also underwent MRI scans of their brain structure and function.

The investigators focused on an area of the brain called the amygdala, which is a person's "fear center," and found that kids with high anxiety levels had a larger amygdala compared to children with low anxiety levels. This part of the brain, the researchers noted, had more connections to other brain regions involved in attention, emotion perception and regulation.

The researchers also developed a way to predict children's anxiety levels based on brain scan measurements of amygdala size and its level of connection to other brain areas, according to the study in the June issue of the journal Biological Psychiatry.

"It is a bit surprising that alterations to the structure and connectivity of the amygdala were so significant in children with higher levels of anxiety, given both the young age of the children and the fact that their anxiety levels were too low to be observed clinically," first author Dr. Shaozheng Qin said in a journal news release.

The study is an important advance in identifying young children at risk for anxiety disorders and improves understanding of how anxiety develops in people, according to Qin.

While the study found an association between reported levels of anxiety and the structure and connectivity of the amygdala in kids, it did not prove a cause-and-effect relationship.

SOURCE: Global Medical Education
Guest Commentary by Chittaranjan Andrade, MD

GME Research Review is a monthly newsletter where internationally recognized experts select, summarize, and provide a clinical commentary on the latest published research in psychiatry. Each summary has been derived from the relevant article’s abstract and the clinical commentary has been provided by our expert.

REVIEW INCLUDES:

• Negative Outcome of Charles Bonnet Syndrome
  
• Rate of Chiari I Malformation in Children of Mothers with Depression With and Without Prenatal SSRI Exposure
  
• Preventive Effects of Ramelteon on Delirium: A Randomized Placebo-controlled Trial
  
• Increased Risk of Acute Cardiovascular Events After Partner Bereavement: A Matched Cohort Study
  
• Preterm Birth and Antidepressant Medication Use During Pregnancy: A Systematic Review and Meta-analysis
  

Negative Outcome of Charles Bonnet Syndrome
Cox TM, Ffytche DH.
Br J Ophthalmol 2014

Objective
 The Charles Bonnet syndrome (CBS) describes the occurrence of visual hallucinations in persons with visual (typically, macular) impairment. It is generally believed that these hallucinations are non-distressing, and that the syndrome is uncommon, transient, and self-limiting. Most studies on CBS are based on small samples. This study described CBS in what is probably the largest study to date. 

Conclusion
The Charles Bonnet syndrome may be more common, less benign, and longer lasting than is commonly believed. 

Clinical Commentary
Given the low (31%) response rate, it is likely that persons with CBS, especially those with more severe and long-lasting CBS, self-selected themselves into the sample. The percentages reported in this study could therefore be suspect. Furthermore, given that the data were collected through a questionnaire (or a phone call, in some cases) and not through face-to-face clinical assessments, the data could also be suspect. Curiously, the authors did not discuss either limitation.

Rate of Chiari I Malformation in Children of Mothers with Depression With and Without Prenatal SSRI Exposure
Knickmeyer RC, Meltzer-Brody S, Woolson S, et al
Neuropsychopharmacology 2014

Objective
Selective serotonin reuptake inhibitors (SSRIs) have previously been associated with rare but specific congenital malformations after first trimester exposure during pregnancy. This magnetic resonance imaging (MRI) study suggests that SSRI exposure may also increase the risk of the Chiari I malformation (CIM), a condition in which the cerebellar tonsils extend significantly below the foramen magnum. 

Conclusion
Exposure to SSRIs during pregnancy is associated with a marked increase in the risk of MRI-diagnosed Chiari I malformation at 1 and 2 years of age. This risk is increased if SSRI exposure occurs at the time of conception, and if the duration of exposure is greater. This risk does not appear to be mediated by maternal depression. 

Clinical Commentary
It is interesting that a maternal family history of depression increased the SSRI-associated risk of CIM. Knickmeyer et al suggested that this may represent a double-hit situation where genetic (family history) and environmental (SSRI exposure) factors may interact to trigger an adverse outcome (CIM). In addition, underdevelopment of the posterior cranial fossa can crowd the developing hindbrain; CIM may be a consequence; the condition develops after birth. Whereas CIM is often asymptomatic, it may be associated with headache, disturbances of hearing or vision, lower cranial nerve disturbances, hydrocephalus, spinal cord syrinx, or other neurological conditions. A follow up of the CIM children in this study would educate readers about the clinical importance of the findings. Knickmeyer et al provided a competent explanation for and a responsible interpretation of their findings.

Preventive Effects of Ramelteon on Delirium: A Randomized Placebo-controlled Trial
Hatta K, Kishi Y, Wada K, et al
JAMA Psychiatry. 2014;71:397-403.

Objective
Medically ill inpatients, especially those who are elderly and those in intensive care units, are at increased risk of delirium. Medications such as antipsychotics but not cholinesterase inhibitors have been found effective in preventing delirium in elderly patients at risk. Encouraged by reports of benefit with melatonin 0.5 mg/night. This study examined whether the MT1 and MT2 melatonin receptor agonist ramelteon, an approved treatment for sleep-onset insomnia, offers benefits in this regard. 

Conclusions
Ramelteon (8 mg/night for 1 week) is associated with a substantial reduction in the risk of delirium in seriously medically ill inpatients. Onset of delirium is also approximately 1 day later in ramelteon-treated patients. 

Clinical Commentary
Ramelteon did not improve any sleep outcome; in fact, numerically (but not statistically) more ramelteon patients required emergency medication for insomnia. Therefore, improved sleep or mechanisms related thereto seems an unlikely explanation for the benefits observed with ramelteon. Perhaps modulation of melatonergic neurotransmission, or of hypothalamic activity, reduces the risk of delirium in elderly patients at risk. Melatonin and ramelteon are far better tolerated than antipsychotic drugs and are therefore more important as delirium preventive agents in elderly patients at risk. One wonders whether these drugs would also be effective in delirium prophylaxis in younger patients, post-surgical patients, and patients with alcohol or drug withdrawal states. 

Increased Risk of Acute Cardiovascular Events After Partner Bereavement: A Matched Cohort Study
Carey IM, Shah SM, DeWilde S, et al. 
JAMA Intern Med. 2014; 174: 598-605.

Objective
Death of a spouse is given the highest ranking (100 out of 100) on the Social Readjustment Rating Scale. Can the high emotional turmoil associated with partner bereavement result in adverse cardiovascular and other important health outcomes? If yes, what is the magnitude of the risk? This subject was addressed in this population-based matched cohort study conducted in the UK.

Results
The 30-day risk of fatal or non-fatal myocardial infarction or stroke was significantly higher in the bereaved group than in the nonbereaved group (0.16% vs 0.08%, respectively; IRR, 2.20; 95% CI, 1.52-3.15). This risk remained statistically significant but was substantially attenuated at 90 (0.38% vs 0.27%; IRR, 1.59) and 365 (1.28% vs 1.11%; IRR, 1.14) days. The risk of myocardial infarction and stroke was not significantly modified by age, sex, or preexisting cardiovascular disease at any time point (30, 90, and 365 days). The risk of myocardial infarction and stroke were each significantly elevated at 30 days (IRR, 2.14 and 2.40, respectively) and 90 days (IRR, 1.47 and 1.52, respectively), but not at 365 days (IRR, 1.20 and 1.02, respectively). The risks of non-myocardial infarction acute coronary syndrome and pulmonary embolism could not be assessed at 30 days because there were too few events. However, these risks were significantly increased at 90 but not at 365 days.

Clinical Commentary
The excess risk of fatal or non-fatal myocardial infarction or stroke was 0.08% in the first 30 days after partner bereavement; that is, 1 in 1,250. This statistic may be important at the population level but is perhaps not high at the individual level. The risk of acute myocardial infarction is elevated as early as a day after the experience of bereavement. A meta-analysis suggested that mortality after partner bereavement is higher in men than in women; however, this difference decreased with increasing age. Predictors of the risk of adverse outcomes after partner bereavement need to be identified. Whereas elegant biological mechanisms involving stress, cortisol, autonomic nervous system disturbances, changes in heart rate variability, and others may be validly proposed, it should also be remembered that bereaved persons, especially elderly bereaved persons, may neglect their own health care needs in matters such as compliance to current health instructions and attention to emerging medical symptoms.

Preterm Birth and Antidepressant Medication Use During Pregnancy: A Systematic Review and Meta-analysis
Huybrechts KF, Sanghani RS, Avorn J, et al
PLoS One. 2014; 9: e92778.  

Objective
Antidepressant drugs have been associated with an increased risk of preterm birth. However, the risk is small. For example, a recent meta-analysis of 15 studies reported that gestational age was 3.2 (95% CI, 1.8-4.5) days shorter in women who had received an antidepressant during pregnancy relative to controls who had not; there was little difference in analyses that were restricted to different sets of controls. Given that preterm birth is associated with increased neonatal morbidity and mortality, as well as with adverse long-term outcomes, these authors subjected the research in the field to a systematic review and meta-analysis.

Conclusions
Third but not first trimester antidepressant exposure is associated with an increased risk of preterm birth.

Clinical Commentary
Most of the studies in this meta-analysis adjusted risks for various confounding variables. However, no amount of adjustment, or even propensity matching, can alter the fact that illness characteristics are likely to be more severe in depressed women who take an antidepressant during pregnancy relative to depressed women who do not. Therefore, illness behavior, or genetic concomitants thereof (and not necessarily antidepressant use), may explain adverse pregnancy outcomes. This may be why antidepressant use was no longer associated with preterm birth in one study after depression severity was controlled for. Examples of illness behavior that is often not controlled for in such studies include nutrition, smoking, and alcohol and substance use or abuse. If illness behaviors increase adverse pregnancy outcomes, then antidepressant use might actually reduce the adverse pregnancy outcomes to the extent that antidepressants are able to reduce the adverse illness behaviors. This study provided a good discussion on the limitations of the literature in the field. For example, women may fill a prescription for an antidepressant drug but may not take a drug; or, they may take the drug irregularly; or, they may take the drug during part of the pregnancy but not during the whole pregnancy. For these and other reasons, it is hard to correctly classify antidepressant use during pregnancy, and hence interpretation of data becomes difficult.

SOURCE: MGH Center For Women's Mental Health
June 9, 2014

A recent study suggests that physical exercise during pregnancy may reduce depressive symptoms. This study from Spain included 184 healthy pregnant women (31.37 ± 3.62 years). Women randomized to the exercise group (EG) participated in a supervised exercise program consisting of three, 55- to 60-min sessions per week throughout pregnancy. A total of 167 pregnant women were analyzed; 90 in the exercise group and 77 in the control group. Significant differences were found between the two groups at the end of the study in terms of level of depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale (CES-D): 7.67 ± 6.30 in the exercise group vs. 11.34 ± 9.74 in the control group (p = .005). The percentage of women who were depressed was also lower in the exercise group (12.2%) as compared to the control group (24.7%).

 
Perales M, Refoyo I, Coteron J, Bacchi M, Barakat R. Exercise During Pregnancy Attenuates Prenatal Depression: A Randomized Controlled Trial. Eval Health Prof. 2014 May 28.