Med Check

Children of patients with certain subtypes of bipolar disorder seem to be at increased risk for attention-deficit/hyperactivity disorder (ADHD) and other mental disorders. Aude Henin, Ph.D., and colleagues from the Massachusetts General Hospital and Harvard Medical School studied 102 clinically referred patients with bipolar disorder and their children (totaling 157) to identify patterns of mental illness in the second generation.

An early onset (at or before age 18) of bipolar disorder, comorbid substance use disorder, a history of disruptive behavior disorders in childhood, and comorbid multiple types of anxiety disorders in the bipolar parents were found to have a statistical association with increased risks of psychopathology in their children. Parental comorbid substance use disorder was significantly associated with their children's increased risks of substance use disorders, conduct disorder, and oppositional defiant disorder. The children's risk of ADHD was increased in parents who had an early onset of bipolar disorder, comorbid disruptive behavior disorders, and multiple anxiety disorders.

The study was supported by NARSAD, a nonprofit charitable organization that supports mental health research.

Methylphenidate hydrochloride extended-release tablets (oral osmotic [OROS] formulation) is found to be more effective than placebo in treating ADHD symptoms in adults, according to researchers, led by Sally Berry, M.D., Ph.D., at Johnson and Johnson, which makes the drug. Methylphenidate or placebo tablets were given to 229 ADHD patients aged 18 to 65 in this randomized, double-blind trial. The dosage of methylphenidate started at 36 mg/day and was titrated up to a maximum dose of 108 mg/day based on tolerability. Compared with the placebo group, patients taking methylphenidate saw a statistically significantly greater reduction in the Adult ADHD Investigator Symptom Rating Scale total score. The most common adverse events in the methylphenidate group were decreased appetite, headache, dry mouth, anxiety, nausea, increased blood pressure, and insomnia.

In an open-label, long-term follow-up study of the same drug formulation (average dose 67.7 mg/day), 358 adults were asked to take the drug for six months to a year. Five serious adverse events were reported, but none was deemed related to the drug. A mean weight loss of 1.6 kg and a mean heart rate increase of 3.3 beats per minute (bpm) were cited by the authors as major safety findings.

The studies were funded by McNeil Pediatrics.

Three hundred and twenty-six children between the ages of 6 and 12 with ADHD were followed for 12 months in an open-label safety study of Shire's methylphenidate patches (transdermal system). Robert Findling, M.D., director of the Division of Child and Adolescent Psychiatry at University Hospitals Case Medical Center and a professor of psychiatry and pediatrics at Case Western Reserve University, and colleagues reported the cardiovascular effects of the methylphenidate patches at doses of 10 mg/day (worn over a nine-hour period) to 30 mg /day. These children had participated in the company's previous studies of methylphenidate, so those who had experienced significant adverse effects might not have enrolled in this long-term study. At month 12, the mean change from baseline in diastolic blood pressure ranged from -0.9 to 2.3 mmHg, and the mean change in systolic blood pressure ranged from 2.1 to 5.1 mmHg.

The magnitude of blood pressure changes was not necessarily proportional to the dose. The mean change in pulse was -2.4 to 3.8 bpm. The electrocardiogram monitoring, the authors concluded, showed no clinically important trends in mean change from baseline to month 12. The reported cardiovascular adverse events included increased heart rate in three subjects, one with decreased blood pressure, and two with increased blood pressure; ECG reading abnormalities in eight subjects; and syncope in three subjects.

The study was funded by Shire.

A cross-sectional analysis of the data collected in the Course and Outcome of Bipolar Illness in Youth (COBY) study, conducted by Benjamin Goldstein, M.D., Ph.D., an assistant professor of psychiatry at Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, and colleagues indicates that approximately 26 percent of the 436 children with bipolar disorder enrolled in the study reported moderate to severe pain. Self-reported pain was measured on the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) depression rating scale, which excludes pain due to a diagnosable medical illness, at the study intake. The more severely ill appeared to experience more pain than others did. The factors significantly associated with pain were current depression, family history of bipolar disorder, lifetime physical and/or sexual abuse, and lifetime self-injurious behavior. The authors acknowledged that the causes and associations of pain in children with bipolar disorder are still poorly understood.

The COBY study was funded by the National Institute of Mental Health.

Antidepressants taken by women during pregnancy appear to be linked to elevated levels of nenuroendocrine hormones in their newborns, Sheila Marcus, M.D., an associate professor of psychiatry, and colleagues at the University of Michigan reported. Thirty-nine pregnant women seen at primary care and psychiatric clinics were recruited and categorized into three groups based on their depression and medication status: (1) those who had no current psychiatric disorders or a history of depression, (2) those who had a history of depression or anxiety and elevated Edinburgh Postnatal Depression Scale (EPDS) score of greater than 10 (that is, possible depression) but did not take antidepressants during pregnancy, and (3) those who had a history of major depression or anxiety and elevated EPDS score of greater than 10 and took antidepressants during pregnancy. Each group had 13 women.

Infants of the mothers who had taken antidepressants during pregnancy had a significant elevation in average adrenocorticotropic hormone (ACTH) level in cord blood compared with those in the other groups, who had not taken antidepressants. The average cortisol level in infant saliva was also higher in the medicated group, but the difference did not reach statistical significance. Women taking antidepressants experienced significantly higher frequency of birth complications, including preeclampsia, gestational diabetes, and premature rupture of membranes, than women with depression who had not taken antidepressants during pregnancy.

The authors acknowledged that women in the antidepressant-treated group had a higher Beck Depression Index score than those in the group with depression but who had not taken antidepressants, so that the difference in disease severity could have been a confounding factor for the outcomes. ▪