FDA Approves Bupropion Extended-Release for Major Depressive Disorder
The United States Food and Drug Administration approved bupropion hydrochloride extended-release (Wellbutrin XL, GlaxoSmithKline) for the treatment of adult major depressive disorder (MDD) in September.
Bupropion XL should be initiated at a dosage of 150 mg/day in the morning, with an increase to 300 mg/day within 4 days. For patients who do not improve at 300 mg/day within 4 weeks, the dosage can be titrated to a maximum of 450 mg/day. Patients must wait 24 hours between each dosage.
Bupropion XL is associated with a dose-related risk of seizures. It should not be taken with any other formulations of bupropion, including sustained-release (SR) or immediate-release.
Bupropion XL has a lower risk of weight gain and sexual side effects than other forms of the drug. The adverse-event profile for bupropion XL is similar to that of bupropion SR and includes headache, dry mouth, nausea, insomnia, and sweating. —CN
Antipsychotic Use Linked to Increased Risk of Diabetes
Diabetes affects approximately 12 million Americans and has been found in two forms; type 1, common in juveniles, and type 2, mostly found in adults. Diabetes has been found to be associated with antipsychotic use in some patients. Case studies have suggested that some atypical antipsychotics may induce type 2 diabetes.
Dr. Francesca Cunningham, of the University of Illinois in Chicago, and colleagues, studied the risk of diabetes in patients taking antipsychotic medications for schizophrenia. They studied 19,878 patients, 5,981 of whom were taking olanzapine, 5,901 of whom were taking risperidone, and 977 of whom were taking quetiapine. Only 110 patients were taking clozapine, thus making it too small of a sample size to conduct a head-to-head comparison of that drug. They analyzed prescription data collected between October 1998 and September 2001. For study inclusion, patients had to be free of antipsychotics for 3 months prior to the study and had to initiate therapy due to the study. Patients with a history of diabetes were excluded from the study.
Cunningham and colleagues found an increased risk for diabetes in patients taking any of the three antipsychotics studied. For example, there was a 27% greater risk of developing diabetes in patients taking olanzapine, a 49% greater chance for diabetes in patients taking risperidone, and a 48% greater chance for diabetes in patients taking quetiapine.
Cunningham and colleagues also determined the hazard ratio by adjusting the patient population based on gender, race, marital status, diabetogenic agents, diabetic screening panels, and age (Table). The adjusted hazard ratio was found to be 1.50 for olanzapine, 1.47 for risperidone, and 1.54 for quetiapine.
A follow-up study is currently comparing the risk of diabetes among patients taking atypical antipsychotics. The study will enroll 3,000 patients from the initial study and conduct another medical chart review. —CN
(International Society for Pharmaco-epidemiology Meeting; August 2003; Philadelphia, PA)
OCD Symptoms May Be Common in New Parents
Obsessive distressing thoughts are common in both mothers and fathers after the birth of a baby, according to a new study surveying parents of newly born infants. While symptoms of obsessive-compulsive disorder (OCD) have been shown to be higher than expected in postpartum females, the overall prevalence these symptoms postpartum remains unknown. The current study examined the presence and phenomenology of obsessive intrusive thoughts, images, and impulses in a large sample including both male and female parents.
Jonathan S. Abramowitz, MD, and colleagues at the Mayo Clinic Department of Psychiatry and Psychology in Rochester, Minnesota, mailed 6-page surveys to 300 females who had given birth between December 2001 and April 2002. All women had experienced full-term uncomplicated deliveries and had no history of delusional disorders, schizophrenia, or bipolar disorder. An identical survey was mailed to the father of each infant. Participants were asked to provide up to three upsetting intrusive thoughts they had experienced in response to several demographic items. For example, for the item “burping the baby,” one might say “I sometimes think about what would happen if I hit her too hard.”
Severity of intrusive thoughts was assessed with the following four items from the Yale-Brown Obsessive Compulsive Scale: (A) time per day spent on intrusive thoughts (rated as 0=none, 1=≤1 hour, 2=1–3 hours, 3=3–8 hours, or 4=≥8 hours); (B) degree to which intrusive thoughts interfered with functioning socially or at work (rated as 0=none to 4=severe); (C) degree of distress from intrusive thoughts (rated as 0=none to 4=severe); and (D) degree of control over intrusive thoughts (rated as 0=completely to 4=not at all). Participants were also asked about their history of OCD and were assessed for depression using the Center for Epidemiological Studies Depression scale (CES-D).
Approximately 66% of survey completers (20%) reported intrusive unwanted thoughts. There was no significant difference in percentage of males versus females reporting such thoughts.
Seven categories of intrusive thoughts were derived: (1) suffocation or sudden infant death syndrome, eg, maybe the baby rolled over and cannot breathe; (2) accidents, eg, the neighbor’s dog may attack the baby; (3) ideas or urges of intentional harm, eg, will the baby be brain damaged if I throw her out the window?; (4) losing the infant, eg, someone may kidnap the baby at the grocery store; (5) severe illness, eg, the baby may have cerebral palsy; (6) inappropriate sexual thoughts, eg, a thought about the baby’s genitals; (7) contamination, eg, the baby may suffer microbiological contamination from a person or object (Table).
On average, disturbing thoughts lasted ≤1 hour/day and were mildly distressing, although such thoughts lasted longer and were more distressing for mothers than fathers. Both groups reported that the intrusions caused little functioning interference and that they were able to control the thoughts. CES-D scores were subclinical on average, but higher in women. There was a small to moderate association between severity of intrusive thoughts and depressive symptoms among mothers, but not fathers.
According to Abramowitz and colleagues, these results support the hypothesis that senseless, intrusive, unacceptable thoughts, ideas, urges, and images about infants are common among healthy parents of newborns. In addition, such thoughts are reported with similar prevalence among fathers and mothers. Furthermore, the obsessions resemble those observed in patients with OCD in that the thoughts often center around disastrous consequences and are considered senseless, excessive, and incongruent with the person’s beliefs.
A number of factors may contribute to development of intrusive obsessional thoughts, according to the researchers. While theories have blamed fluctuations in hormone levels during pregnancy and postpartum, the presence of similar obsessions in fathers weakens this theory. Rather, situational factors such as the stress of caring for a newborn may be responsible. In addition, sensitivity to external threat cues tend to play a role in obsessive thought; it is probable that one would be hypersensitive to cues of danger when first faced with the responsibility of caring for a helpless baby. This may also explain the increased frequency of distress reported by mothers, as they also reported spending more time with their infants than fathers. Occurrence of obsessional thoughts may also be more upsetting to mothers due to the pressure of being expected to be happy during the postpartum period.
The authors also point out the importance of knowing the difference between obsessional thoughts, which do not lead to violence, and psychotic thoughts, which may lead to harming a child. People with obsessional thoughts are disgusted and frightened by them, while those with psychotic thoughts view them as rational. For parents who mistakenly interpret their intrusive thoughts as indicators that they are evil people capable of harming their child, these thoughts will elicit further distress.
Abramowitz and colleagues suggest that parents who have difficulty controlling recurring thoughts of harm to their child should seek care from their primary care physician or psychiatrist who may be able to determine whether the thoughts are depressive, obsessional, or psychotic. —DH
(J Clin Psychol Med Settings. 2003; 3:157-164)
Study Finds Common Genetic Roots for Severe Psychoses
A recent study reported what may be the first hard evidence for a similar genetic origin between bipolar disorder and schizophrenia. Sabine Bahn, MD, of the University of Cambridge in the United Kingdom, and a multicentered team of colleagues, found that these major psychotic illnesses both showed dysfunction of key oligodendrocyte and myelination genes, including transcription factors that regulate these genes.
Oligodendrocytes are responsible for myelin development in brain cells; myelin sheaths, composed mostly of fats and proteins, function to insulate the nerve cells enabling them to conduct electric signals between the brain and other parts of the body. The similar expression changes observed in the brains of patients with bipolar disorder and schizophrenia, support the idea that the disorders share a common causative and pathophysiological etiology.
Bahn and colleagues collected prefrontal cortex tissue of 45 brains from the Stanley brain collection (Stanley Medical Research Institute, Bethesda, MD)—15 samples of schizophrenia, 15 of bipolar affective disorder, and 15 controls. Psychiatric diagnoses, using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, were made independently by two psychiatrists using medical records and telephone interviews with family members of the deceased. Gene-expression profiles of schizophrenia samples were compared with controls using indexing-based differential display polymerase chain reaction (PCR). Results were cross-validated with quantitative PCR, which was also used to determine expression profiles of 16 other oligodendrocyte and myelin genes in schizophrenia and bipolar disorder.
Similar dysfunction of key oligodendrocyte and myelin genes were observed in the brains of patients with schizophrenia and in those with bipolar disorder. The brains also showed a high degree of overlap in expression changes and several transcription factors known to coordinate myelin gene expression showed corresponding alterations. Overall, microarray analysis of the same genes correlated well.
Bahn and colleagues point out that although bipolar disorders and schizophrenia differ in presentation and clinical course, there is some overlap of symptoms and medications used for treatment of the disorders. The current findings suggest there may also be similar mechanisms involved in the disorders and that they may be more closely related than previously thought.
Bahn and colleagues also suggest that these results support those of other studies suggesting abnormalities in expression of lipid- and myelin-related genes in schizophrenia. These results surpass findings of other microarray investigations by showing similar expression changes in bipolar disorder, providing strong evidence that the disorders share a common genetic pathway.
Although the reason for the gene abnormalities remain unknown, the researchers suggest it may be related to infections of the central nervous system or other environmental issues. This is consistent with studies indicating that infections in early infancy may be a risk factor for schizophrenia and bipolar disorder. They posit that the ability to locate abnormalities in myelin may someday help physicians identify children likely to develop these mental disorders and provide treatment before symptoms surface.
Whether a reduction in oligodendrocyte number actually represents cellular dysfunction or whether it is simply a result of death has been debated. The authors note that the selective reduction observed in this study supports the latter view. They suggest that more refined expression studies are needed to confirm that abnormality is a result of dysfunction rather than death and to determine whether the changes are symbolic of a “sick” brain, are disease specific, or are secondary to another disease. —DH
Bowel Disease Associated With Emotional Problems In Children
More than one third of children with inflammatory bowel disease (IBD) suffer from psychological problems, including depression and anxiety. IBD is a group of chronic intestinal disorders with symptoms of abdominal pain, rectal bleeding, and/or diarrhea, resulting from inflammation of the bowel. The course of the disorder is often unpredictable, and treatment with medications can cause severe side effects, such as vomiting, rash, hair loss, pancreatitis, bone loss, and low white blood cell count.
Laura Mackner, MD, and colleagues at Ohio State University in Columbus, previously compared emotional health of 41 children who had been diagnosed with IBD at least 1 year prior to the study, with 27 healthy children. The researchers expected the results to indicate that the children had adjusted well to managing all aspects of the disease, but they were dismayed to find that many had psychological issues involving low self-esteem, negative body image, and lower emotional, social, and family functioning.
In an effort to further analyze the behavior, emotional, and social functioning of IBD children, Mackner and colleagues administered questionnaires to 50 children with IBD (ages 11–17) and their parents and teachers. Twenty-seven healthy children and their parents and teachers were used as controls. The researchers were specifically looking for a relationship between the emotional factors and severity of IBD, family functioning, and self-esteem. Children described themselves using a self-esteem and body image checklist; parents rated their child’s behavior socially and emotionally at home; and teachers were asked to describe the child’s behavior at school.
Parents of children with IBD were three times more likely to report that their child had significant and emotional problems compared to parents of healthy children. In addition, teachers of IBD children reported that these children had more attention problems and missed school 1.5 times more often than children without IBD. Social problems, such as being teased and withdrawn were reported by 17% of parents of the IBD group compared to none of those in the control group. Self-esteem and body image were not shown to differ between the groups.
Behavioral and emotional functioning was higher in IBD children who had stronger family relationships and higher self-esteem. However, positive relationships and self-esteem may not protect social functioning, which was shown to be more dependent on whether the IBD was active. Having to take medication during school hours or abide by a special diet differentiates the child from the rest of his or her peers and may cause teasing, which contributes to psychosocial stress.
Mackner and colleagues suggest that psychosocial interventions, along with medication when necessary, may help improve emotional functioning of children with IBD. They also suggest that children with IBD who show signs of trouble with school and social performance should be evaluated for emotional well-being. —DH
(American Psychological Association Annual Meeting; August 8, 2003; Toronto, Canada)
Stimulants Shown to Be Safe for Children With ADHD and Mania
The presence of mania in children with attention-deficit/hyperactivity disorder (ADHD) has made some physicians skeptical about prescribing stimulants due to the risk of increased side effects. However, research has found that such patients do not suffer increased side effects from methylphenidate.
Cathryn Galanter, MD, of Columbia University in New York City, conducted a placebo-controlled, double-blind study of 270 children 7–10 years of age who had participated in the Multimodal Treatment Study of ADHD. Following a lead-in stage, the children were administered methylphenidate titrated in three dosage levels or placebo for 4 weeks. Side effects in the children were determined by parents and teachers, who rated presence and severity of 10 side effects commonly associated with methylphenidate. The researchers constructed two proxies to distinguish children with ADHD and manic symptoms without bipolar disorder from those with ADHD only. The first proxy was based on the mania subsection of the Diagnostic Interview Schedule for Children (DISC), while the second was based on a response pattern on the Child Behavior Checklist (CBCL).
Manic symptoms were determined in 29 (10%) children according to the DISC proxy and 32 (11%) were diagnosed according to the CBCL. Seven children were shown to have manic symptoms according to both proxies. None of the children discontinued treatment due to adverse side effects during the titration period, although four were removed due to side effects during the lead-in phase. Children with mania and ADHD responded similarly to those without mania. They saw no difference between the groups in terms of irritability or other adverse side effects in response to methylphenidate.
Galanter and colleagues suggest that children with ADHD and manic symptoms may benefit from a carefully monitored methylphenidate trial. They plan to conduct studies investigating long-term response to stimulants in this population. —DH
(J Child Adolesc Psychopharmacol. 2003;2:123-136)
—Psychiatric Dispatches is compiled and written by Deborah Hughes and Christopher Naccari.