Suicidality, mood, psychomotor, and neurovegetative symptoms are stable across depressive episodes in bipolar disorder whereas the overall dimensional structure is not temporally stable, US researchers have discovered.

It has been suggested that depressive subtypes in bipolar disorder, characterized by groups of symptoms, have predictive or diagnostic value. However, this assumes that symptoms are stable across mood episodes, a hypothesis that has not been thoroughly investigated.

Roy Perlis, from Massachusetts General Hospital in Boston, and colleagues therefore studied 583 patients with bipolar I and II disorder from the Systematic Treatment Enhancement Program for Bipolar Disorder study who had two depressive episodes during 2 years of follow-up. Syndromal depressive mood episodes were determined using the DSM-IV criteria.

Of the participants, 66.2% had bipolar I disorder, 62.6% were female, 35.9% had a history of psychotic symptoms, 73.4% had a history of rapid cycling, and 41.2% had a history of suicide attempt. In total, 149 patients experienced a third depressive episode, at a median time to recurrence of 168 days.

The greatest stability between first and second depressive episodes was seen for neurovegetative symptoms, psychomotor symptoms, suicidal ideation, and depressed mood, while the least stable symptoms were loss of interest and fatigue.

Significant stability was also observed for the percentage of days irritable and days anxious, as well as for Clinical Global Impression scale scores and the count of DSM-IV mood symptoms. Similar findings were recorded for patients with three depressive episodes.

While a three-factor model including sleep, interest, and guilt had an excellent fit for data from the initial visit, a confirmatory model derived from first-episode data did not fit the second-episode data. Substantial differences in symptom correlations between first and second episodes also reduced the fit of a model in which all factor loadings were constrained to be equal across the two episodes.

The team concludes in the journal Bipolar Disorders: “We identified evidence of consistency of many symptoms between two episodes but with wide variation in the extent of correlation, and substantially less correlation when the episodes are separated by another depressive episode.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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• RISPERDAL(R) CONSTA(R) (Risperidone) Long-Acting Treatment Delayed The Time To Relapse In Patients With Bipolar I Disorder
• For Bipolar Depression, Surveyed Experts Indicate That Current And Emerging Therapies Have No Advantage Over Seroquel In Decreasing The Syptoms
• MTHFR gene not linked to bipolar disorder]]>
• If Bipolar Disorder Is Over-Diagnosed, What Are The Actual Diagnoses?

The clinically significant weight gain observed in bipolar disorder patients begins with the first manic episode, regardless of previous episodes, and may be due to the treatment required, say Canadian researchers.

Many studies have shown that bipolar disorder is associated with obesity, but these investigations have typically been retrospective or cross-sectional in design and focused on patients with long-term illnesses.

To determine the patterns of weight gain in early bipolar disorder, Lakshmi Yatham and colleagues from the University of British Columbia in Vancouver obtained weight gain data and laboratory metabolic measurements over a 12-month period from 47 bipolar disorder patients receiving maintenance therapy after their first manic episode and 24 age- and gender-matched healthy controls.

At baseline, there were no significant differences between patients and controls in terms of average body mass index (BMI), rates of overweight and obesity, and laboratory metabolic indices.

Over the first 6 months of follow-up, 46.8% of patients and 4.2% of controls gained ?7% over their baseline weight, at an average weight gain of 4.57 kg and 0.51 kg, respectively. However, rates of overweight and obesity did not differ significantly between patients and controls.

On logistic regression analysis, significant weight gain was associated with lower initial weight, male gender, and treatment with olanzapine and risperidone. Obese patients had significantly greater average serum triglyceride and fasting glucose levels than non-obese patients.

At 12 months, 19% of patients and 4% of controls gained ?15% over their baseline weight, and the average weight gain was 4.76 kg and 1.50 kg, respectively. Interestingly, the changes at 12 months were primarily due to changes over the first 6 months, as average weight change during the second 6 months was 0.19 kg for patients and 0.98 kg for controls, and 13% and 8.3%, respectively, gained ?7% over their 6-month body weight.

There were no significant associations between significant weight gain from 6??”12 months and any of the variables analyzed, the team notes in the Journal of Affective Disorders.

They write: “Given the long-term health consequences of overweight and obesity, these findings underscore the importance of considering weight and metabolic factors when making even the earliest treatment decisions for patients with bipolar disorder, and of frequently monitoring for and addressing weight gain.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

Free abstract

• Childhood ADHD impacts on clinical course of bipolar disorder
• FADS2 gene expression elevated in bipolar patients]]>
• What Rorschach Tests Really Tell Us

Bipolar disorder patients who have psychotic features have a worse prognosis and response to lithium monotherapy than patients without such features, the results of a Turkish study indicate.

It has previously been suggested that up to 50% of bipolar disorder patients in an acute manic episode have psychosis, with rates in child and adolescent patients higher than those seen in adult patients. However, the impact of psychotic symptoms on prognosis and clinical course has rarely been investigated.

I ?-zyildirim, from Ünye State Hospital in Ordu, and colleagues therefore studied 97 bipolar I disorder patients who had suffered from the condition for at least 4 years and had at least three mood episodes, comparing the clinical features and response to long-term prophylaxis between those with and without psychosis.

The results, published in the journal European Psychiatry, indicate that 43 patients were psychotic in all mood episodes, while 54 had never experienced psychotic symptoms.

There were no significant differences between the psychotic and non-psychotic groups in terms of age, gender distribution, age of onset, and cycling interval. A family history of bipolar disorder was significantly more common in the non-psychotic than psychotic group, at 29.6% versus 11.6%.

Non-psychotic patients were also significantly more likely to have a predominantly depressive episode type than psychotic patients, at 25.0% versus 5.0%, and were significantly less likely to having a predominantly manic/mixed episode type, at 68.8% versus 85.0%.

Psychotic patients were significantly more likely to have severe mood episodes and had significantly more hospitalizations than non-psychotic patients, at 100% versus 27.8% and 1.9 versus 1.4, respectively.

Psychotic patients were significantly less likely to have a response to lithium monotherapy and more likely to have a response to anticonvulsant plus antipsychoctic therapy than non-psychotic patients, at 43.3% versus 89.7% and 100% versus 55.6%, respectively.

The team concludes: “Determination of psychotic subtype might be predictive for the clinical course of illness and establishing the optimum prophylactic treatment.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

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The U.S. Food and Drug Administration (FDA) approved schizophrenia and manic or mixed episodes associated with bipolar I disorder in adolescents aged 13-17 years old.

The updated Zyprexa label states that clinicians should take into consideration the increased potential for weight gain and hyperlipidemia in adolescents compared to adults and the potential for long-term risks, which in many cases, may lead them to consider prescribing other drugs first in adolescents. Compared to patients from adult clinical trials, adolescents were also likely to experience increased sedation and greater increases in prolactin levels and hepatic transaminase (liver enzymes) levels. The recommended starting dose for adolescents is lower than that for adults.

An FDA Psychopharmacologic Drug Advisory Committee (PDAC) met in June and discussed the difficulties of diagnosing and treating these conditions in adolescents. The Zyprexa label provides additional guidance to physicians that medication therapy for pediatric schizophrenia or bipolar I disorder should be initiated only after a thorough diagnostic evaluation and careful consideration of the risks associated with medication treatment.

The updated Zyprexa label also highlights the need for a comprehensive treatment program in pediatric patients and recommends that Zyprexa be used as part of a “total treatment program for pediatric patients with schizophrenia and bipolar I disorder,” which may include psychological, educational and social interventions.

This approval follows a favorable vote regarding the safety and efficacy of Zyprexa from the FDA PDAC in June on Lilly’s supplemental New Drug Applications for these indications. The Committee examined findings from two pivotal clinical trials: one six-week trial in adolescents with schizophrenia and one three-week trial in adolescents with manic or mixed episodes associated with bipolar I disorder, as well as extensive Zyprexa safety data relevant to adolescents.

“There has been a recognized need in the mental health community for additional guidance on treating teens diagnosed with these serious mental illnesses,” said Cherri Miner, M.D., Lilly USA Neuroscience Senior Medical Director. “Customers have been asking for data from controlled studies in these populations, and now with this information added to our label, we can help physicians make informed treatment decisions.”

About Schizophrenia in Adolescents

Schizophrenia affects about 1 percent of Americans.(1) A substantial portion of first psychotic breaks for schizophrenia occur in adolescence. It has been estimated that 39 percent of males and 23 percent of females with schizophrenia experience onset of the disease before the age of 19.(2) Studies have suggested that early-onset schizophrenia is associated with worse long-term outcomes compared to onset of illness in adulthood.(3)

About Bipolar Disorder in Adolescents

Bipolar disorder affects approximately 5.7 million American adults, or about 2.6 percent of the U.S. population age 18 and older, in a given year.(4) It has an estimated prevalence of 0.1 percent to 2 percent among adolescents.(5) Lifetime prevalence of bipolar I disorder in community samples has varied from 0.4 percent to 1.6 percent.(6) It has been estimated that 20 percent of all patients with bipolar disorder experience their first episode during adolescence, with the peak age of onset for this group of patients occurring between 15 and 19 years of age.(7) Early onset of bipolar disorder is associated with greater severity of illness and more functional impairment.(8)

Safety Information for Zyprexa (olanzapine)

Zyprexa is indicated in adults in the United States for the treatment of schizophrenia, acute treatment of mixed and manic episodes of bipolar I disorder, and maintenance treatment of bipolar I disorder.

Zyprexa is indicated for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder in adolescents 13 to 17 years of age. When deciding among alternative treatments available for adolescents, clinicians should consider the increased potential for weight gain and hyperlipidemia compared to adults. Clinicians should consider the potential long-term risks when prescribing to adolescents, and in many cases this may lead clinicians to consider prescribing other drugs first in adolescents.

Olanzapine is not approved for the treatment of patients with dementia-related psychosis. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

In addition, compared to elderly patients with dementia-related psychosis taking a placebo, there was a significantly higher incidence of cerebrovascular adverse events (e.g. stroke, transient ischemic attack) in elderly patients with dementia-related psychosis treated with olanzapine.

The possibility of a suicide attempt is inherent in schizophrenia and bipolar I disorder. Close supervision of high-risk patient should accompany drug therapy.

As with all antipsychotic medications, a rare and potentially fatal condition known as Neuroleptic Malignant Syndrome (NMS) has been reported with olanzapine. If signs and symptoms appear, immediate discontinuation is recommended. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

Hyperglycemia, in some cases associated with ketoacidosis, coma, or death, has been reported in patients treated with atypical antipsychotics, including olanzapine. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics. Physicians should consider the risks and benefits when prescribing olanzapine to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level. Patients taking olanzapine should be monitored regularly for worsening of glucose control. Patients starting treatment with olanzapine should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, palyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment should undergo fasting blood glucose testing.

Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and follow-up lipid evaluations in patients using olanzapine, is advised. Clinically significant, and sometimes very high, elevations in triglyceride levels and modest mean elevations in total cholesterol have been observed with olanzapine use.

Potential consequences of weight gain should be considered prior to starting olanzapine. Patients receiving olanzapine should receive regular monitoring of weight.

Also, as with all antipsychotic treatment, prescribing should be consistent with the need to minimize Tardive Dyskinesia (TD). The risk of developing TD and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic increase. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

Olanzapine may induce orthostatic hypotension associated with dizziness, tachycardia, bradycardia, and in some patients, syncope, especially during the initial dose-titration period. Particular caution should be used in patients with known cardiovascular disease, cerebrovascular diseases, or those predisposed to hypotension.

Other potentially serious adverse events include decreased white blood cell count (leukopenia, neutropenia, agranulocytosis), seizures, elevated prolactin levels, cognitive and motor impairment, body temperature elevation, and trouble swallowing.

The recommended starting dose for adolescents is lower than that for adults. Compared to patients from adult clinical trials, adolescents were likely to gain more weight, experience increased sedation, and have greater increases in total cholesterol, triglycerides, LDL cholesterol, prolactin and hepatic transaminase levels. When deciding among the alternative treatments available for adolescents, clinicians should consider the increased potential for weight gain and hyperlipidemia compared to adults. Clinicians should consider the long-term risks when prescribing to adolescents, and in many cases this may lead them to consider prescribing other drugs first in adolescents. Medication treatment for adolescent schizophrenia and bipolar I disorder should be initiated only after a thorough diagnostic evaluation and careful consideration of the risks associated with medication treatment. Medication treatment for both adolescent schizophrenia and bipolar I disorder is indicated as part of a total treatment program that often includes psychological, educational and social interventions. Safety and effectiveness of olanzapine in patients <13 years of age have not been established.

The most common treatment-emergent adverse event associated with oral Zyprexa in placebo-controlled, short-term schizophrenia and bipolar mania trials in adults was somnolence. Other common events were dizziness, weight gain, personality disorder (COSTART term for nonaggressive objectionable behavior), constipation, akathisia, postural hypotension, dry mouth, asthenia, dyspepsia, increased appetite and tremor.

The most common treatment-emergent adverse events associated with oral olanzapine (vs placebo) in clinical trials of adolescents (13-17 years old) were sedation (44% vs 9%), weight increased (30% vs 6%), increased appetite (24% vs 6%), headache (17% vs 12%), fatigue (9% vs 4%), liver enzymes increased (8% vs 1%), dizziness (7% vs 2%), dry mouth (6% vs 0%), pain in extremity (5% vs 1%).

About Lilly

Lilly, a leading innovation-driven corporation, is developing a growing portfolio of pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers - through medicines and information - for some of the world’s most urgent medical needs.

Zyprexa® (olanzapine, Lilly)

P-LLY

This press release contains forward-looking statements about Zyprexa. These statements reflect management’s current beliefs; however, as with any pharmaceutical product there are risks and uncertainties in the process of research and development, regulatory review and commercialization. For further discussion of these and other risks and uncertainties, see Lilly’s filings with the United States Securities and Exchange Commission. Lilly undertakes no duty to update forward-looking statements.

References

(1) The National Institute of Mental Health. What is Schizophrenia

(2) Loranger, AW. (1984). Sex Difference in Age of Onset of Schizophrenia. Archives of General Psychiatry; 41:157-161.

(3) Fleischhaker, C. et al. (2005). Long-term Course of Adolescent Schizophrenia. Schizophrenia Bulletin; 31(3):769-780.

(4) Kessler RC, Chiu WT, Demler O, Walters EE. (2005). Prevalence, Severity, and Comorbidity of Twelve-month DSM-IV Disorders in the National Comorbidity Survey Replication (NCS-R). Archives of General Psychiatry, Jun; 62(6):617-27.

(5) Mauricio Tohen et al. (2007). Olanzapine versus Placebo in the Treatment of Adolescents with Bipolar Mania. American Journal of Psychiatry, 164: 1547-1556.

(6) Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, pg. 385.

(7) McClellan, J. and Werry, J. (1997). Practice Parameters for the Assessment and Treatment of Children and Adolescents with Bipolar Disorder. Journal of the American Academy of Child and Adolescent Psychiatry. 36(1):138-157.

(8) Axelson D et al. (2006). Phenomenology of children and adolescents with bipolar spectrum disorders. Archives of General Psychiatry; 63(10):1139-48.

Source: Eli Lilly and Company

View drug information on Zyprexa.

• Long-Term Tolerability And Safety Data Of Abilify(R) In Combination Treatment For Patients With Bipolar I Disorder

Study findings suggest that disrupted auditory attention is observed in bipolar disorder (BD) patients independent of their mood state, medication status, or history of psychotic features, but may be influenced by the presence of a comorbid anxiety disorder.

Previous studies have shown that BD patients show aberrations of event-related potential (ERP) measures of auditory processing elicited during “oddball” discrimination tasks, in which infrequent target tones presented within a series of frequent distracter tones must be identified.

“Aberrations in auditory ERPs may reflect a neurophysiologic marker, or endophenotype, for BD, but the effect of patients’ mood state, current medication usage, or history of other psychiatric disorders on these measures are not well understood,” explain Daniel Fridberg (Indiana University, Bloomington, USA) and co-authors.

The team therefore administered an auditory “oddball” discrimination task to elicit ERPs in 69 patients with type I BD, of whom 14 were unmedicated, and 52 healthy individuals with no history of psychiatric disorders. Patients were placed into subgroups based on whether they were euthymic or symptomatic, and amplitude and peak latency measures from N100, P200, N200, and P300 ERP components were compared across subgroups.

The P300 ERP component is believed to provide an index of selective attention and general cognitive efficiency, with the peak latency believed to represent stimulus evaluation speed independent of reaction time, and its amplitude representing neural activity underlying attention and memory process involved in updating stimulus representations.

N100, P200, and N200 ERP components precede the P300 in time and reflect earlier stages of information processing, the authors explain.

P300 amplitude to target tones was reduced in both the symptomatic and euthymic BD patient groups compared with controls. BD patients also had a prolongation in P300 latency compared with controls, at 408.3 versus 380.4 ms.

Furthermore, symptomatic and euthymic BD patient groups did not differ on P300 amplitude or latency, and also showed reduced P200 amplitude to frequent tones compared with controls.

Regression analysis showed that history of comorbid anxiety disorder diagnosis was associated with reduced N200 peak latency but increased P300 peak latency. No effects of medication status, history of psychotic features, or mood state on ERP measures in BD patients were observed.

Writing in the journal Bipolar Disorders, the team says that “the present study provides further support for auditory P300 amplitude as a candidate endophenotype for BD,” and “indicates that P300 latency may be sensitive to the presence of a comorbid anxiety disorder in BD patients.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

Free abstract

• Combined Data From Four Large-Scale Studies Demonstrate The Efficacy And Tolerability Of Seroquel In Bipolar Depression
• Mental Illness Was One Of The Costliest Conditions Between 1996 To 2006
• Communication Within The Brain Impaired By Genetic Variant With Possible Consequences Schizophrenia Or Manic Depression
• Stanford To Offer Bipolar Education Day On July 25

Self-reported concentration problems predict whether or not bipolar I disorder patients achieve stable employment, the results of a study indicate.

Previous studies have shown that cognitive deficits in bipolar disorder patients are associated with a decline in work performance, employment status, global functioning, and longer clinical course. However, many of these investigations have been hampered by methodological problems.

Andrew Gilbert, from the University of Pittsburgh School of Medicine in Pennsylvania, USA, and colleagues therefore studied 154 bipolar I disorder patients for 15??”43 months, gathering data on demographic characteristics and administering the Mood Spectrum Self-Report (MOOD-SR) questionnaire and Bipolar Disorder Visit Form.

The MOOD-SR was administered at baseline and at study termination, at which points employment was categorized as working ??” full-time, part-time, homemaker, or volunteer ??” or not working ??” leave of absence, disability, unemployed, or no longer volunteering. The patients were categorized clinically as good-stable, improving, worsening, or poor-stable.

In all, 46.6% of the patients were good-stable and employed at baseline and termination, 30.4% were poor-stable and not working at baseline and termination, 14.2% were improving, not working at baseline, and working at termination, and 8.8% were worsening, working at baseline, and not working at termination, the team reports in the Journal of Affective Disorders.

Regression analysis revealed that item 91 on the MOOD-SR, covering problems with concentration, education, and age, was significantly associated with employment.

Self-reported cognitive problems were significantly more common in the poor-stable than good-stable groups, at an odds ratio of 2.51. More well-educated patients were also significantly less likely to belong to the poor-stable than good-stable groups, at an odds ratio of 0.55. Physician-reported measures were not associated with employment.

The team concludes: “The ability to predict employment trajectory using a specific item from the MOOD-SR points to the sensitivity of this measure and may suggest that cognitive problems are more likely to predict employment trajectory if assessed in the context of specific limitations in functioning.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

Free abstract

• A receptor genes have selective influence on bipolar disorder phenotype]]>
• Schizophrenia-Linked Gene Controls The Birth Of New Neurons
• Combined Data From Four Large-Scale Studies Demonstrate The Efficacy And Tolerability Of Seroquel In Bipolar Depression

The dopaminergic system appears to play a central role in the pathophysiology of bipolar disorder and may point the way to novel treatments, the results of a review indicate.

A comprehensive pathophysiologic model of bipolar disorder is lacking, despite there being effective pharmacologic treatments for the disorder. Nevertheless, several brain regions and neuronal components of the behavioral and cognitive manifestations of bipolar disorder have been recently identified.

To extend knowledge of the role of dopamine in bipolar disorder, David Cousins (Newcastle University, UK) and colleagues conducted a review of behavioral, neurochemical, receptor, imaging, and genetic studies, as well as pharmacologic manipulation studies in comparison with other diseases.

The team writes in the journal Bipolar Disorders that dopaminergic pathways are associated with many areas implicated in the core symptoms of bipolar disorder and other associated conditions and, although mania and depression have been linked to increases and decreases in dopaminergic function, respectively, this model does not fit the clinical pattern.

The role of dopamine in bipolar disorder is supported by studies of pharmacologic interventions, with antimanic agents antagonizing dopaminergic activity and antidepressants commonly increasing such activity, as well as mania treatment leading to depression.

Acknowledging the limitations of such observations, the team says that the clinical manifestations of bipolar disorder have not yet been established as a unified process, and that several distinct processes may underlie the common clinical phenotype. Furthermore, comorbidities complicate the picture.

They also write that receptor occupancy changes in bipolar disorder psychosis point to individual pathway functions in bipolar disorder, despite imaging studies failing to identify consistent abnormalities.

The team concludes: “Dopaminergic mechanisms are likely to play a central role in our understanding of the pathophysiology of bipolar disorder and the development of new treatments.

“As the dopamine model of bipolar disorder continues to develop and is enriched by the findings from the broader field of dopamine neuroscience, a shift from a simple dichotomy of neurotransmitter activity seems inevitable.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

Free abstract

• Irritability Should Be Considered When Diagnosing Bipolar Disorder In Children

Despite government warnings about an increased risk of suicidal thoughts and actions while taking antiepileptic drugs, these medications do not appear to be associated with increased risk of suicide attempts in individuals with bipolar disorder, and may have a possible protective effect, according to a report in the December issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

Antiepileptic drugs are life-saving for those with seizure disorders and are also used to treat many other conditions, including mood disorders and nerve pain, the authors write as background information in the article. The 11 antiepileptic drugs include gabapentin, pregabalin, topiramate and carbamazepine. “On Jan. 31, 2008, the Food and Drug Administration issued an alert regarding increased risk of suicidal thoughts and behavior related to use of antiepileptic drugs,” the authors write. “On July 10, 2008, a Food and Drug Administration scientific advisory committee voted that, yes, there was a significant positive association between antiepileptic drugs and suicidality but voted against placing a black box warning on antiepileptic drugs for suicidality.”

Individuals with bipolar disorder - often treated with antiepileptic drugs - have a higher risk of attempted and completed suicide than the general population. “That makes this a population of interest in detecting the effect on suicide risk of antiepileptic drugs compared with a no-treatment control group,” the authors write. Robert D. Gibbons, Ph.D., of the University of Illinois at Chicago, and colleagues studied a cohort of 47,918 patients with bipolar disorder who had at least one year of data before and after their diagnosis in a national database of medical claims.

A total of 13,385 patients received one of 11 antiepileptic drugs and 25,432 received neither antiepileptic medications nor lithium. After treatment, those taking antiepileptic medication had similar rates of suicide attempts (13 per 1,000 patients per year) as those taking lithium (18 per 1,000 patients per year) or those who did not receive treatment (13 per 1,000 patients per year).

Among those taking antiepileptic drugs, the rate of suicide attempt was significantly lower after treatment (13 per 1,000 patients per year) than before treatment (72 per 1,000 patients per year). In patients who were not receiving treatment with another antiepileptic, an antidepressant or an antipsychotic medication, taking any antiepileptic mediation appeared protective against suicide attempts relative to no pharmacologic treatment (three per 1,000 suicide attempts per patient per year vs. 15 per 1,000 per patient per year).

“Our analysis also reveals that there is a selection effect, in that the pretreatment suicide attempt rate is five times higher than the rate in untreated patients,” the authors write. “If pretreatment suicide attempt rates reflect the severity of illness, it is the more severely impaired patients who receive treatment with an antiepileptic drug or lithium. Nevertheless, the post-treatment suicide attempt rate is significantly reduced relative to their elevated pretreatment levels to the level found at or below patients not receiving treatment. This finding suggests a possible protective effect of antiepileptic drug treatment on suicidality.”

Arch Gen Psychiatry.2009;66[12]:1354-1360.

Source
Archives of General Psychiatry

• FDA Advisory Committee Votes In Favor Of SAPHRIS(R) (asenapine) For Acute Bipolar I Disorder And Acute Schizophrenia
• Break-through Preventative Care Program For People Living With Bipolar Disorder

Two Brown University faculty members have received federal funding for innovative new neuroscience research projects focusing on brain development in infants and bipolar disorder in children.

Sean Deoni, assistant professor of engineering, plans to use his $2.5-million grant to study neurodevelopment throughout infancy and early childhood, from 2 months to age 5, using an MRI imaging technique at Brown he previously developed with colleagues.

Dr. Daniel Dickstein, assistant professor of psychiatry and human behavior at Alpert Medical School and head of the Pediatric Mood, Imaging and Neurodevelopment (Pedi-MIND) program at Bradley Hospital, has been awarded a $1.87-million grant to identify biological and behavioral markers that distinguish between development of full-blown and sub-syndromal bipolar disorder. Most of Dickstein’s research will take place at Bradley Hospital. The Pedi-Mind research program uses cutting-edge techniques including brain-imaging, behavorial tasks and genetic analyses to identify biological markers of psychological illness.

Both grants come through the National Institute of Mental Health’s (NIMH) BRAINS program and will span five years. Only seven BRAINS grants - Biobehavioral Research Awards for Innovative New Scientists - were awarded nationally in 2009, the program’s inaugural year.

Deoni and Dickstein are affiliated with the Brown Institute for Brain Science.

Deoni will study myelination, a process that is central to establishing efficient communication pathways throughout the brain. Myelination is the formation of the fatty myelin layer around brain neurons and fibers. Abnormal myelination can lead to disorders that affect walking, movement, communication, decision making and other functions. Scientists believe abnormal myelination can contribute to neurodevelopmental disorders including schizophrenia and developmental delay.

The idea of Deoni’s study is to investigate how myelin develops in the brain normally, in order to contrast with patients who face abnormal myelination. Deoni’s team will use neurobehavorial studies and MRI scans to gauge development of language, memory, fine and gross motor control and vision in children. Their goal is to understand which brain regions are responsible for each of those primary cognitive abilities, how they develop over time, and how deficits can give rise to conditions such as autism.

Dickstein will use his expertise in pediatric brain imaging and neurobehavioral data to assist in Deoni’s research program.

In turn, Deoni will use his expertise in white-matter networks to assist on Dickstein’s project, which will also include a team of experts from Bradley Hospital, Rhode Island Hospital, and Brown University. National experts from New York University, Yale and NIMH will also be involved.

In light of the rise in children and adolescents diagnosed with bipolar disorder during the last decade, Dickstein’s project will work in tandem with the COBY study (Course and Outcome of Bipolar Youth), which has been researching the development of bipolar disorder in children as they become young adults. The synergy between the two projects is designed to identify biological and behavioral markers that differentiate between full-blown and sub-syndromal bipolar disorder.

If successful, such markers could augment patients’ clinical history, leading to more specific diagnoses and treatment for children who may have biopolar disorder.

Sean Deoni, assistant professor of engineering, and Dr. Daniel Dickstein, assistant professor of psychiatry, have each received funding from the National Institute of Mental Health to study brain development in children with bipolar disorder. They will collaborate on each other’s projects.

Source:
Mark Hollmer
Brown University

• What Rorschach Tests Really Tell Us
• Brain Activity Determines Risk Or Resilience In Manic Depression
• GPR50 gene linked to affective disorder]]>

People who care for bipolar disorder (BD) patients with increasing suicidal ideation (SI) over time and depressive, rather than manic, symptoms are prone to suffering from depression and worsening health, show US researchers.

“Our study results may help to prospectively identify caregivers at risk for adverse health outcomes who may benefit from prevention-focused intervention,” say Cheryl Chessick (University of Colorado Denver School of Medicine) and co-authors.

For the study, the team evaluated 500 patients participating in the Systematic Treatment Enhancement Program for Bipolar Disorder ??” a multicenter study evaluating the course and outcome of patients with BD ??” and their primary caregivers (including 188 parental and 182 spousal) for up to 1 year.

Caregivers’ perceptions of their own physical health and depression were evaluated using the general health scale from the Medical Outcomes Study 36-item Short-Form Health Survey and the Center for Epidemiological Studies of Depression Scale, respectively.

After controlling for patient’s history of suicide attempts, education, baseline Global Assessment of Functioning scores, current alcohol or substance abuse, and living situation, higher SI scores at baseline and at 6 and 12 months were associated with lower caregiver health scores at all time points compared with patients who had lower SI scores at all times.

Furthermore, poorer caregiver health at 6 and 12 months was significantly associated with caring for patients who showed increased SI at 6 and/or 12 months compared with baseline. This association remained significant after controlling for confounding factors.

In contrast, patients’ depression scores at all time points were not significantly related to caregivers’ self-reported health. “Thus, SI appears to have contributed to caregivers’ health, whereas depression in the absence of SI did not,” remark the researchers.

Caregivers were more likely to have higher depression scores at all time points if they were caring for patients with higher SI at all follow-up points compared with caregivers of patients with lower SI, after controlling for confounding factors.

However, the increase in patients’ SI from baseline was not significantly associated with caregivers’ depression scores at 6 and 12 months after controlling for baseline caregivers’ depression and baseline patients’ SI.

Lastly, the researchers found that higher patient depression scores at all follow-up points were associated with higher caregiver depression scores after controlling for confounding factors.

Writing in the journal Bipolar Disorders, the team concludes: “Improving caregivers’ health may depend in some cases on fully stabilizing patients.”

They add: “Future research may be able to clarify why some caregivers are resilient even in the face of patients’ depression and SI.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

Free abstract

• 1A binding reductions in euthymic bipolar disorder patients]]>