1. Methylphenidate in the treatment of female adolescents with cooccurrence of attention deficit/hyperactivity disorder and borderline personality disorder: a preliminary open-label trial.

Int Clin Psychopharmacol. 2008 Jul; 23(4):228-31

Golubchik P, Sever J, Zalsman G, Weizman A.

Child and Adolescent Outpatient Clinic, Geha Mental Health Center, Petah Tiqva, Israel. pgolubchik@clalit.org.il

Recent studies reported symptomatic overlap between attention deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD). Methylphenidate (MPH) is the most efficient treatment for ADHD. We assessed the efficacy and tolerability of MPH treatment in adolescent females who met the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for both disorders. Fourteen BPD/ADHD female adolescents aged 14-19 years were treated with MPH for 12 weeks, targeting ADHD, BPD symptoms, and aggressive behavior, as rated by ADHD-rating scale (ADHD-RS) and Clinical Global Impression-Severity (CGI-S) scale for BPD and aggressive behavior severity. A significant improvement was detected in both ADHD and BPD severity (baseline vs. end point, ADHD-RS: 33.1+/-4.8 vs. 17.6+/-5.2, P<0.001; BPD CGI-S: 4.6+/-0.8 vs. 3.4+/-0.8, P<0.0005, respectively) as well as in aggressive behavior (Aggression CGI-S: 3.5+/-1.3 vs. 1.8+/-0.5, P<0.001). MPH was well tolerated. MPH may be useful and well tolerated in treating some shared symptoms of ADHD and BPD among female adolescents. Controlled studies are needed to substantiate these findings.

2. Approved and investigational uses of modafinil : an evidence-based review.

Drugs. 2008;68(13):1803-39.

Kumar R.

Department of Family Medicine, University of Chicago, Chicago, Illinois, USA.

Modafinil is a wake-promoting agent that is pharmacologically different from other stimulants. It has been investigated in healthy volunteers, and in individuals with clinical disorders associated with excessive sleepiness, fatigue, impaired cognition and other symptoms. This review examines the use of modafinil in clinical practice based on the results of randomized, double-blind, placebo-controlled clinical trials available in the English language in the MEDLINE database. In sleep-deprived individuals, modafinil improves mood, fatigue, sleepiness and cognition to a similar extent as caffeine but has a longer duration of action. Evidence for improved cognition in non-sleep-deprived healthy volunteers is controversial.Modafinil improves excessive sleepiness and illness severity in all three disorders for which it has been approved by the US FDA, i.e. narcolepsy, shift-work sleep disorder and obstructive sleep apnoea with residual excessive sleepiness despite optimal use of continuous positive airway pressure (CPAP).

However, its effects on safety on the job and on morbidities associated with these disorders have not been ascertained. Continued use of CPAP in obstructive sleep apnoea is essential. Modafinil does not benefit cataplexy.In very small, short-term trials, modafinil improved excessive sleepiness in patients with myotonic dystrophy. It was efficacious in fairly large studies of attention deficit hyperactivity disorder (ADHD) in children and adolescents, and was as efficacious as methylphenidate in a small trial, but has not been approved by the FDA, in part because of its serious dermatological toxicity. In a trial of 21 non-concurrent subjects, with 2-week treatment periods, modafinil was as effective as dexamfetamine in adult ADHD. Modafinil was helpful for depressive symptoms in bipolar disorder in a trial that excluded patients with stimulant-induced mania. A single dose of modafinil may hasten recovery from general anaesthesia after day surgery. A single dose of modafinil improved the ability of emergency room physicians to attend didactic lectures after a night shift, but did not improve their ability to drive home and caused sleep disturbances subsequently.

Modafinil had a substantial placebo effect on outcomes such as fatigue, excessive sleepiness and depression in patients with traumatic brain injury, major depressive disorder, schizophrenia, post-polio fatigue and multiple sclerosis; however, it did not provide any benefit greater than placebo.Trials of modafinil for excessive sleepiness in Parkinson's disease, cocaine addiction and cognition in chronic fatigue syndrome provided inconsistent results; all studies had extremely small sample sizes. Modafinil cannot be recommended for these conditions until definitive data become available.Modafinil induces and inhibits several cytochrome P450 isoenzymes and has the potential for interacting with drugs from all classes. The modafinil dose should be reduced in the elderly and in patients with hepatic disease. Caution is needed in patients with severe renal insufficiency because of substantial increases in levels of modafinil acid. Common adverse events with modafinil include insomnia, headache, nausea, nervousness and hypertension. Decreased appetite, weight loss and serious dermatological have been reported with greater frequency in children and adolescents, probably due to the higher doses (based on bodyweight) used. Modafinil may have some abuse/addictive potential although no cases have been reported to date.

3. Disadvantaged Low-Birth-Weight Children More Likely to Have Attention Problems

Arch Gen Psychiatry 2008;65:1080-1086.

Marlene Busko

In a longitudinal study, low–birth-weight children had modestly increased levels of psychiatric problems such as aggression or anxiety throughout childhood.
However, those living in a disadvantaged inner-city community had a 3-fold higher risk for impulsivity and hyperactivity symptoms characteristic of attention-deficit/hyperactivity disorder (ADHD) compared with those living in a middle-class suburb.

"The differential effect of low birth weight on attention in urban children was unexpected, given that low–birth-weight effects for other outcomes such as cognitive abilities were uniform across the 2 communities," coauthor Naomi Breslau, PhD, from Michigan State University, in East Lansing, told Medscape Psychiatry.
"The results suggest a need for early identification of children with attention problems — even before the start of school — and a need to evaluate interventions to improve attention skills, since these contribute to children’s acquisition of academic skills and educational attainment — that is, whether they complete high school, enroll in college, and graduate," she added.

The study, with lead author Kipling M. Bohnert, also from Michigan State University, is published in the September issue of the Archives of General Psychiatry.

Improved Survival of Tiny Infants

Advances in neonatal medicine have increased the survival of low–birth-weight infants (2500 g or less), including very low–birth-weight infants (1500 g or less) and extremely low–birth-weight infants (1000 g or less), the authors write.

Previous studies have reported that these children have an increased risk for internalizing problems such as somatic complaints, anxiety, and depression; externalizing problems such as delinquent and aggressive behavior; and attention problems characteristic of ADHD.

The present study was based on data from low–birth-weight and normal-weight children born from 1983 through 1985 in 2 major hospitals in Detroit, Michigan. The children in the urban sample were primarily black and were more likely to have single mothers with less than a high school education.

When the children were age 6 years (n = 823) and age 11 years (n = 717), their behavior was evaluated by mothers using the Child Behavior Checklist and by teachers using the Teachers’ Report Form to determine the percentages of children with scores in the borderline or clinical assessment range.

The current study extended the previous studies to age 17 years and included 218 low–birth-weight urban children, 140 normal–birth-weight urban children, 181 low–birth-weight suburban children, and 159 normal–birth-weight suburban children.

Attention Problems Are a "Major Concern"

Among these 17-year-olds, the adjusted odds ratios (ORs) for having externalizing and internalizing problems were slightly higher in the low–birth-weight teens than in the normal-weight teens living in the same community (adjusted OR, 1.53 and 1.28 for externalizing and internalizing problems, respectively).

Among the teens living in the disadvantaged urban community, those with a low birth weight had an approximately 3-fold greater risk of having attention problems (adjusted OR, 2.78; 95% CI, 1.77 – 4.37; P = .001). The increased risk was greatest among teens whose birth weight was 1500 g or less.

In contrast, the teens living in the middle-class suburbs had no significant increased risk for attention problems associated with low birth weight.

The increased risk of having attention problems corresponding to those of ADHD that was seen in the disadvantaged, urban, low–birth-weight children raises a "major concern," since attention problems at the start of school predict lower academic achievement later on, the authors write.

These differences in low–birth-weight children living in advantaged vs disadvantaged communities "might reflect a beneficial influence of the enriched social environment afforded to children in suburban middle-class communities at home, at school, and in the neighborhood, [or] the urban disadvantaged environment might exacerbate the effect of prenatal adversity," they suggest.

4. Adults with ADHD Don't Reach Educational, Occupational Potentials

J Clin Psychiatry 2008; 69:1217-1222.

The results of a study published in the August issue of the Journal of Clinical Psychiatry suggest an association between attention-deficit/hyperactivity disorder and decreased educational and occupational attainment relative to what would be expected based on intellect.
"ADHD has been consistently associated with intellectual, educational, and employment deficits," lead author Dr. Joseph Biederman, of Massachusetts General Hospital, Boston, and colleagues write. To further examine the impact of these deficits, the research team conducted a case-control study from 1998 to 2003 that included 224 adults with ADHD.

The investigators used the Hollingshead socioeconomic status scale to assess educational and occupational status. Ordered logistic regression models were used to compute the expected educational and occupational levels of the subjects as a function of age, gender, and full-scale IQ.

The researchers found that subjects with ADHD attained significantly less education than predicted based on their IQ. In addition, based on their education level, ADHD patients were predicted to have significantly higher occupational levels than actually attained.

"Educational and occupational deficits in adults with ADHD are a consequence of ADHD and not IQ, and therefore represent under-attainments in these critical areas," Dr. Biederman said in an interview with Reuters Health. "Considering the critical importance of education and occupation for the individual in our society, these findings strongly support the importance of diagnosing and treating ADHD to avert these serious consequences."

Dr. Biederman and his colleagues plan to "continue evaluating various aspects of these deficits in the hope of developing appropriate preventive and early intervention strategies."

5. Special issues in the diagnosis and treatment of ADHD in adolescents.

Steinhoff KW.
Department of Pediatrics, University of California, Irvine School of Medicine, Irvine, CA.
Postgrad Med. 2008 Sep;120(3):60-8.

Attention-deficit/hyperactivity disorder (ADHD) is a common disorder among adolescents but can be a challenge to diagnose in this population for several reasons. Obvious symptoms of hyperactivity and impulsivity are displayed less frequently than in younger children. Direct observation by potential raters is more limited because adolescents spend less time with parents and usually have multiple teachers throughout the day. Also, adolescents often suffer from psychiatric comorbidities, which affect the presentation of ADHD and can confound the diagnosis. Similarly, impaired social skills and academic performance may result from this disorder or for other reasons. These difficulties underscore the importance of a careful and comprehensive assessment that includes parent-, teacher-, and self-reported measures of functioning in several environments, including school, home, and work.

Because ADHD is chronic and usually impairing in several domains (eg, social skills, academic performance, family relations, emotional health, driving), adequate treatment is essential. However, there are relatively few treatment studies in adolescents. Stimulant agents are well established as first-line medication treatment for both school-aged children and adults. Existing data support that this is also the case with adolescents. Specifically, both an extended-release formulation of methylphenidate, osmotic-release oral system (OROS(R) MPH; CONCERTA(R)) and a mixed amphetamine salts extended-release (MAS XR; Adderall(R) XR) have demonstrated efficacy and safety in reducing the core symptoms of ADHD in well-designed, multisite, placebo-controlled, double-blind trials. Additional research is needed to further refine diagnostic and assessment tools in the adolescent population.