FDA Approves Asenapine for Acute Treatment of Schizophrenia and Manic or Mixed Episodes of Bipolar I Disorder With or Without Psychotic Features

The United States Food and Drug Administration approved asenapine (Saphris, Schering-Plough) for the acute treatment of schizophrenia in adults and manic or mixed episodes of bipolar I disorder with or without psychotic features in adults. Asenapine sublingual tablets are the first psychotropic to receive initial approval for both indications. The recommended starting and target dose of asenapine is 5 mg BID for acute schizophrenia and 10 mg BID for bipolar disorder. Dosage may be decreased to 5 mg BID in case of adverse events. No safety information is available for dosages >10 mg BID.

Over 3,000 patients participated in a series of trials for schizophrenia and bipolar disorder included in the drug application.

The most common adverse events include akathasia, oral hypoesthesia, and somnolence for schizophrenia. For patients with bipolar disorder adverse events include somnolence, dizziness, extrapyramidal symptoms other than akathisia, and weight increase.

For more information, please see the medication’s full prescribing information at www.saphris.com. – LS

FDA Approves Paliperidone palmitate for the Maintenance Treatment of Schizophrenia 

The US FDA approved paliperidone palmitate (Invega Sustenna, Janssen) for acute and maintenance treatment of schizophrenia in adults. The recommended starting dose of paliperidone palmitate is 234 mg on treatment day 1 and 156 mg one week later. These dosages are to be administered in the deltoid muscle. The monthly maintenance dose is 117 mg. The recommended dosage range (39–234) mg is based on individual patient tolerability and/or efficacy. Following the second dose, monthly maintenance doses can be administered in either the deltoid or gluteal muscle.

Approval was based on four acute symptom control studies and a longer maintenance study, which all compared paliperidone to placebo. Paliperidone palmitate proved to outweigh the positive and negative symptom scale total scores within the acute treatment trials. It effectively delayed typical schizophrenic relapse time compared to placebo within the longer-maintenance study. The final acute symptom control study was a randomized, multi-center, placebo-controlled parallel group study, where all patients received a dosage of 234 mg in the deltoid muscle on the first day. By day 8 and monthly onward, patients were also assigned to one of three possible fixed doses of paliperidone for 13 weeks.  

The most common adverse events were reactions at the injection site, sleepiness, dizziness, feeling of inner restlessness, and abnormal muscle movements, including tremor (shaking), shuffling, uncontrolled involuntary movements, and abnormal movements of the eye.

For more information, please see the medication’s full prescribing information at www.invegasustenna.com. – AC

Alcohol Consumption by Adolescents Associated with Co-Occurring Behavioral Problems

Although numerous studies have investigated the link between alcohol consumption and prevalence of mental health disorders as well as behavioral problems in the adolescent and young adult population, few have examined this association in a large-scale sample. Studies with small clinical samples have often found that alcohol consumption, particularly in excess, is associated with depression, conduct disorders, anxiety, and suicidal behavior in adolescents. In addition, few age- and gender-specific population studies have been conducted in youth alcohol consumption, although prior studies have shown that male and female adolescents and those of different ages often present with separate behavioral and mental health concerns.

Dr. Arve Strandheim at the Norwegian University of Science and Technology, and colleagues, sought to describe alcohol use in a large sample of teenagers and adolescents and its association with mental health and behavioral problems with a focus on age and gender. They evaluated the drinking behavior of 8,983 adolescents in Norway in order to determine if the presence of mental health and conduct disorders was due to alcohol consumption or other factors. All participants were 13–19 years of age and were gathered from the Young Nord-Trøndelag Health Study (HUNT), a population based, cross-sectional, self-report survey of adolescents on their physical and mental health as well as lifestyle patterns and socio-demographic factors that was conducted from 1995 to 1997.

High alcohol consumption was indicated as >10 episodes of lifetime intoxication, and participants’ drinking behavior was also measured in reported grams of alcohol consumed during a 2-week period. Mental health disorders were measured using the Symptom Check List, a five-item measurement of depression and anxiety, while behavioral problems were evaluated by an adjusted version of the 25-item Symptom Check List completed by the school.

Strandheim and colleagues found that, among those who completed the questionnaire, 43.3% reported never having been intoxicated and 28.9% reported >10 lifetime episodes of intoxication. The amount of intoxications increased as the participants aged. Examining gender differences, equal numbers of male and female adolescents reported no intoxications, while there was a small increase in the number of male adolescents who reported having >10 episodes of intoxication. A more concrete gender difference was found in male adolescents drank significantly higher volumes of alcohol than females. They also found that depression, anxiety, and attention problems increased with age and were more associated with female adolescents, while behavioral problems decreased with age and were more associated with males.

Regarding the association between drinking behavior and mental health and behavioral problems, they found that all evaluated mental health and behavioral problems were highly associated with increased alcohol consumption. Male and female adolescents who drank frequently were more likely to report conduct problems, while females who drank frequently also reported attention problems, depression, and anxiety.

The authors concluded that these results show that attention and conduct problems may play a role in the development of heavy alcohol use in adolescents. However, due to the nature of the Young HUNT study, causal relationships cannot be derived from these results. Nevertheless, clinicians should place additional emphasis on the drinking behavior of adolescents with attention and conduct problems as well as female patients with depression and anxiety. Further prospective and qualitative studies are also necessary to better understand the relationship between alcohol use and mental health and behavioral problems in adolescence.

Funding for this research was provided by the Central Norway Regional Health Authority and the County Council of Nord-Trøndelag. (Child Adolesc Psychiatry Ment Health. 2009;3(1):18). – CP

Surviving Cancer: When The Mind Cannot Remit

As cancer survival rates continue to rise, dealing with cancer-related mental health issues during remission is becoming an area of greater interest and clinical attention. An estimated 10.7 million Americans (including children) have received a diagnosis of cancer, according to 2005 data from the National Cancer Institute.

Karen E. Hoffman, MD, of Brigham and Women’s Hospital in Boston, and colleagues, evaluated the prevalence of serious psychological distress in survivors of adult-onset cancer ≥5 years after initial diagnosis. Using data from the 2002–2006 National Health Interview Survey, they compared 4,636 self-identified adult cancer survivors to 122,220 adult respondents with no previous cancer diagnosis. For survivors, the median age at diagnosis was 50 years of age, median age at interview was 66 years, and median time since diagnosis was 12 years. Serious psychological distress was defined as a K6 scale score of ≥13.

Cancer survivors had a significantly higher prevalence of psychological distress than those who had never received a cancer diagnosis (5.6% vs. 3%; P<.001). After adjustment for age, sex, relationship status, insurance status, and level of self-sufficiency, the adjusted odds ratio for psychological distress among survivors was 1.4. (95% CI, 1.2-1.7). Other factors associated with psychological distress among cancer survivors include younger age, unmarried status, less than high school education, no health insurance, more comorbidities, and inability to be self-sufficient in daily activities.

One-third of survivors with psychological distress reported seeing a mental health professional within the previous year, compared to ~9% of survivors and ~6% of those with no cancer history. According to the authors, general practitioners should be familiar with the propensity for distress in cancer survivors, especially in patients with more comorbidities and other expressed risk factors.

Funding for this research was provided by the Census Bureau. (Arch Gen Psychiatr. 2009;169(14):1274-1281). – LS

High Glutamate Levels in Brain with Depression, Low Cognitive Function

For the first time, researchers at the Joslin Diabetes Center in Syracuse, New York, and other establishments have found a substantial link between high glutamate levels within the brain and depression, as well as impaired cognitive function, in those with type 1 diabetes.

Glutamate, a neurotransmitter located within the brain, is produced from glucose, and shows higher levels of mild depression and demonstrates lower cognitive function on tests. Alan Jacoben, MD, at Harvard Medical School, and colleagues, demonstrated that the high levels of glutamate sometimes causes damage to neurons within diabetic patients. They also noted that the intolerance to glutamate levels is not just apparent in type 1 diabetes. Although prevalent in type 1 diabetes, but it can also be found in those with type 2 diabetes as well.

In data collected from ~123 people diagnosed with type 1 diabetes, proton magnetic resonance spectroscopy imaging was utilized to observe glutamate levels within the brain. Those diagnosed with type 1 diabetes also had varying degrees of lifetime glycemic control. In addition to diabetic patients studied, 38 subjects without diabetes were also included. The study, compiled in both North American and Korean research centers, mainly illustrated how those with type 1 diabetes had increased levels of glutamate in the prefrontal area of the brain.

According to their findings, concentrations of glutamate were 9% higher in subjects with diabetes. Performances on memory, executive function, and psychomotor speed tests were lower in the diabetes group. According to the study, depression affects up to 25% of people with type 1 diabetes. These findings of the effects of glutamate on the brain may lead to more research on diabetes interventions to improve the health of the brain, including new medications for both diabetes and depression.

Funding for this research was provided by the Korean Ministry of Science and Technology, the Korean Research Foundation, the National Alliance for Schizophrenia and Depression, and the National Institute of Health. (Arch Gen Psychiatry. 2009;66(8):878-887). – AC

Psychiatric dispatches is written by Amanda Cuomo, Carlos Perkins, Jr., and Lonnie Stoltzfoos.