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October 2005

Grossly Irresponsible Promotion of Topiramate (Topamax) for Bipolars by University of Toronto and Canadian Journal of Psychiatry: In a highly-biased, manufacturer-funded, open-label report of 16 weeks of topiramate added to the treatments of 109 bipolar patients treated by 17 different psychiatrists (80% depressed, only 3% manic and 8% hypomanic), by the end of the 16 weeks, depression and manic symptoms had decreased. Three of the four authors are employees of the manufacturer. Only the head of the Mood Psychopharmacology Unit at the University of Toronto, Dr. McIntyre, is not an employee, although the university received funding for this study.  The authors conclude with the totally unsupported claim that, "Adjunctive topiramate treatment can reduce the severity of manic and depressive symptoms, as well as reducing tremor and weight in outpatients with BD I or II." Incredibly, the study was approved by Health Canada and various "ethics" boards.  The authors do note that four [unpublished (i.e. suppressed), manufacturer-financed] placebo- and comparator-controlled trials conducted in patients with acute mania have failed to support the efficacy of topiramate as a monotherapy in bipolar disorder and are on file with the manufacturer, Johnson & Johnson. Open-label adjunctive topiramate in the treatment of unstable bipolar disorder. McIntyre RS, et al. University Health Network, Toronto, Ontario. . Can J Psychiatry. 2005 Jun;50(7):415-22. Ed: Shame on Health Canada and the so-called Canadian "ethics" committees.  This open trial could have served no purpose other than to falsely promote topiramate for bipolar disorder, which was the manufacturer's sole intent.  If the manufacturer really wanted to determine benefit, they would have funded yet another double-blind trial.  If open trials are truly needed before embarking on double-blind research, Health Canada and the ethics boards should prohibited publication of the results.  After all, Johnson and Johnson has prohibited publication of their own results of scientific, double-blind studies showing unfavorable outcomes, so there should be nothing wrong with the responsible governmental bodies prohibiting the publication of unscientific studies which do harm to the public welfare. For more, see Topiramate for Bipolars and Irresponsible Medicine.

Mahonia (Oregon Grape) May Help Psoriasis: In a clinical trial of 32 patients with mild to moderate bilateral psoriasis treated up to 6 months, one side of the body received Mahonia and the other standard psoriatic treatment (eg, Dovonex cream). The primary outcomes were patient ratings of the Mahonia-treated side alone and the comparison between treatments received on each side of their body. Eighty-four percent of patients rated the Mahonia-treated psoriasis as good to excellent response. When compared with standard treatment, 63% of patients rated Mahonia aquifolium equal to or better than the standard psoriatic treatment. A second similar study found similar results. Authors conclude that Mahonia aquifolium is a safe and effective treatment of patients with mild to moderate psoriasis. A Report on Three Recent Clinical Trials Using Mahonia aquifolium 10% Topical Cream and a Review of the Worldwide Clinical Experience With Mahonia aquifolium for the Treatment of Plaque Psoriasis. Gulliver WP, et al. University of Rochester. Am J Ther. 2005 September/October;12(5):398-406. Ed: I couldn't find the cream, both a liquid tincture is available for $7 for a 1 ounces bottle from iherb.com.  I had never heard of Mahonia. v

Teen Marijuana Addiction (Dependence) Not Unusual: A representative sample of 2446 young German adults ages 14-24 was followed up over a period of 4 years. 30% of the sample were cannabis users. Among all users, 35% met at least one dependence criterion: withdrawal (17%), tolerance (15%), loss of control (14%) and continued use despite a health problem (13%). Even without simultaneous use of other illicit drugs, 22% of low frequency users and 81% of high frequency users met at least one dependence criterion. The occurrence of a dependence syndrome or of specific dependence criteria could not be attributed to the use of other illicit drugs or to simultaneous nicotine and alcohol dependence. Dependence symptoms in young cannabis users? A prospective epidemiological study. Nocon A, et al. Max-Planck-Institute of Psychiatry, Munich, Germany. J Psychiatr Res. 2005 Sep 14. For more, see Marijuana.

Weekly Fish Meal Lowers Alzheimer's and Stroke Risk: In a study of 3718 people over age 64 and followed for 6 years with repeated testing, thos who ate one fish meal a week had a 10% slower decline in thinking than a control group; those eating two fish meals a week showed a 13% slower decline. Archive Neurol 10/10/05 epub. For more, see Diet and Dementia.

IQ Damaged and Thinking Dull from Smoking; Worse Than Alcohol!: In a 9-year follow-up study of 172 alcoholic and non-alcoholic men, researchers found, as expected, that alcoholism is associated with thinking problems and lower IQ, but their analysis also revealed that long-term smoking is too. The effect on memory, problem-solving and IQ was most pronounced among those who had smoked for years. Smoking was associated with diminished thinking ability even after alcohol and drug use were accounted for. Jennifer Glass, et al. University of Michigan. Drug and Alcohol Dependence 10/13/05. Many alcoholism-recovery programs don't emphasize quitting smoking, even though smoking can be a social and possibly chemical "cue" associated with alcohol consumption. Researchers at the University of California, San Francisco, found that alcoholics who smoke have lower brain volume than alcoholics who don't smoke. There is a growing body of evidence for a link between long-term smoking and thinking ability. The higher the pack-years and lifetime alcoholism severity scores, the lower the global cognitive proficiency scores and IQ. The impact of heavy lifetime smoking history was greater than the effect of lifetime drinking history. For more, see The Harm of Tobacco

Atypicals Slightly Better than Haldol for Cognitive Improvement Although Difference May be Due to Benztropine: In a 1-year DB study of 414 patients with schizophrenia and schizoaffective disorder, measurements of executive function, learning and memory, processing speed, attention/vigilance, verbal working memory, verbal fluency, motor function, and visuospatial ability found the greatest improvement for olanzapine and risperidone  (p<0.01), compared to haloperidol, although haloperidol also showed clear improvement (p=0.04 for haloperidol) and the difference was not clinically significant. One-year double-blind study of the neurocognitive efficacy of olanzapine, risperidone, and haloperidol in schizophrenia. Keefe RS, et al. Duke University. Schizophr Res. 2005 Sep 30.  Ed: Since many of the haloperidol patients were on benztropine (Cogentin) for side-effects and since this causes cognitive impairment, the entire difference may have been a side-effect of benztropine.  Amantidine can be used to treat the same side-effects without cognitive impairment, but few American psychiatrists are even aware of the use of amantidine for this indication. v

Retrospective Study Suggests Schizoaffective Disorder Often an Extension of Bipolar: In a retrospective study of at least a 5-year period for 61 schizoaffective, 57 bipolar I, and 55 schizophrenic outpatients, the schizoaffective disorder patients had a profile similar to the bipolar I patients but were significantly different from schizophrenic patients in educational level, marital status, occupation, drug and alcohol abuse episodes, presence of depressive, mixed and maniac episodes, family history of bipolar I and mood disorders, and use of medications. Only the age of onset, suicide attempts, and family history of suicide are not significantly different among the groups. The schizophrenic patients used antipsychotics for more days and the schizoaffective and bipolar I used more antidepressants and mood stabilizers. 37 (60.6%) schizoaffective patients had their diagnosis changed to bipolar disorder by their physician in different periods during the period studied. Demographic and clinical features of schizoaffective (schizobipolar) disorder-A 5-year retrospective study. Support for a bipolar spectrum disorder. Nardi AE, et al. Federal University of Rio de Janeiro. J Affect Disord. 2005 Sep 29. v

Poor Performance on Visuospatial Testing Predicts High Risk of Bipolar Disorder: Results on verbal, arithmetic, and visuospatial reasoning tests were obtained for 195,019 apparently healthy 19-20 year old male draftees into the Finnish Defense Forces. Follow-up 7.1 years later identified those developing bipolar disorder (N=100), schizophrenia (N=621), or other psychoses (N=527). There was a 34 times higher risk of developing bipolar disorder between the lowest and highest of nine categories of performance on visuospatial tested (OR=34.65) for bipolar disorder, 13.76 times higher for schizophrenia, and 4.28 times higher for other psychoses. In contrast, the higher the score for arithmetic reasoning, the greater the risk of bipolar disorder; a high score was associated with a more than 12-fold greater risk. Verbal test performance was not associated with higher risk for psychiatric disorder. Premorbid intellectual functioning in bipolar disorder and schizophrenia: results from a cohort study of male conscripts. Tiihonen J, et al. University of Kuopio, Finland. . Am J Psychiatry. 2005 Oct;162(10):1904-10. Ed: Finland must not diagnose Bipolar Disorder as often as American psychiatrists, since 100 out of 195,000 is many times smaller than what would be diagnosed in the U.S. where almost anyone with depression and irritability is called Bipolar. v

Schizophrenia Has High Rate of Diabetes, Hypertension, and Smoking: In a study of 689 adults in the Clinical Trials of Antipsychotic Treatment Effectiveness (CATIE) Schizophrenia Trial, the ten-year coronary heart disease risk was elevated in male (9.4% vs. 7.0%) and female (6.3% vs. 4.2%) schizophrenia patients compared to controls (p=0.0001). Schizophrenia patients had higher rates of smoking (68% vs. 35%), diabetes (13% vs. 3%), and hypertension (27% vs. 17%) and lower HDL cholesterol levels (43.7 vs. 49.3 mg/dl)(p<0.001). A comparison of ten-year cardiac risk estimates in schizophrenia patients from the CATIE study and matched controls. Goff DC, et al. MGH-Harvard. Schizophr Res. 2005 Sep 27. For more, see Schizophrenia and Diabetes.

Very Low Birth Weight Risk Factor for ADHD: In a study of 55 very low-birth-weight (</=1500 gm), 54 term small for gestational age (birth weight <10th centile) and 66 term control 14-15-year-olds (birth weight >/=10th centile), the very low-birth-weight group had more psychiatric symptoms and disorders (P < 0.001), especially ADHD, high frequency of ventricular dilatation, white matter reduction, thinning of corpus callosum, and gliosis (P < 0.01 vs controls). The ADHD score was significantly associated with white matter reduction and thinning of corpus callosum in this group. The term small for gestational age group had increased prevalence of psychiatric symptoms compared with controls, but not more frequent abnormalities on MRI. Low-birth-weight adolescents: psychiatric symptoms and cerebral MRI abnormalities. Indredavik MS, et al. Norwegian University of Science and Technology, Trondheim, Norway. Pediatr Neurol. 2005 Oct;33(4):259-66. For more, see ADHD Risk Factors

Tardive Dyskinesia Much Less with Atypicals But Still Very Uncommon with Traditionals: In the 3-year European Schizophrenia Outpatient Health Outcomes (SOHO) study, second-generation antipsychotics conferred a lower risk for tardive dyskinesia at 6 months than first-generation antipsychotics (0.9% vs. 3.8%, odds ratio [OR] = 0.29).Also, patients with tardive dyskinesia at baseline who were receiving second-generation antipsychotics were less likely than patients receiving first-generation antipsychotics to have tardive dyskinesia symptoms at 6 months (43.6% vs. 60.8%, OR = 0.50). Effects of Antipsychotic Treatment on Tardive Dyskinesia: A 6-Month Evaluation of Patients From the European Schizophrenia Outpatient Health Outcomes (SOHO) Study. Tenback DE, et al. Eli Lilly, Maastricht University, Institute of Psychiatry, London, U.K. J Clin Psychiatry. 2005 Sep;66(9):1130-1133. v

Clozapine (Clozaril) Appears to Increase Risk of Death: In a 10-year naturalistic study of 96 adults on clozapine, African American and Hispanic Americans had an markedly elevated risk of cardiovascular disease-related mortality (OR = 7.2, p = .09; OR = 11.3, p = .04, respectively) compared to European-American patients. The Kaplan-Meier estimate for new-onset diabetes mellitus was approximately 43%, and Hispanic American (OR = 4.3, p = .027) and African American (OR = 11.5, p = .0001) patients showed elevated risks of developing diabetes. Additionally, BMI, total cholesterol level, and serum triglyceride level modestly increased the odds ratio for the development of diabetes mellitus. The authors conclude, "These results support the hypothesis that clozapine-treated patients appear to be at risk for death from cardiovascular disease secondary to clozapine-associated medical disorders such as obesity, diabetes, hypertension, and hyperlipidemia." Clozapine, Diabetes Mellitus, Hyperlipidemia, and Cardiovascular Risks and Mortality: Results of a 10-Year Naturalistic Study. Henderson DC, et al. MGH-Harvard. J Clin Psychiatry. 2005 Sep;66(9):1116-1121. v

Patients Stayed on Geodon Better with Lower Costs: Medical and pharmacy claims data were used to compare persistence (days of therapy between first and last prescriptions); compliance (ratio of days of medication supplied to total days on therapy); and treatment costs in 1,810 adults with schizophrenia. Persistence was 31 days longer for patients receiving ziprasidone (228 days) than risperidone (193 days) or olanzapine (201 days). Compliance was significantly (P<.05) higher among patients receiving ziprasidone (87%) compared with other treatments (78%-80%). Ziprasidone patients had significantly larger decreases (-$6866) in mean annual psychiatric-related costs following therapy initiation than those on risperidone (-$3353; P = .0116) or olanzapine (-$4764; P = .0021). The primary driver of cost savings was reduced hospitalization after treatment initiation. Impact of atypical antipsychotics on outcomes of care in schizophrenia. Joyce AT, et al. PharMetrics, Watertown, Massachusetts 02472. Am J Manag Care. 2005 Sep;11(8 Suppl):S254-61. Am J Manag Care. 2005 Sep;11(8 Suppl):S254-61. v

Only 13% Schizophrenia Healthcare Costs in Hospital: Using nationally representative data over 2 years for 571,000 adults with schizophrenia living in the community,  there were $2.13 billion per year in direct medical expenses for schizophrenia with mean and median yearly per-patient expenses of $3726 and $1748, respectively. Inpatient care accounted for only 13% of costs, while ambulatory care and prescription drugs accounted for 75%. Medicaid incurred $1 billion spent on schizophrenia treatment. Mean per-person spending for schizophrenia patients with comorbidities ranged from $3913 per year for those with comorbid hypertension to $5618 per year for those with comorbid dyslipidemia. Mean annual total healthcare expenditures for patients with schizophrenia ranged from $5990 for those with no comorbid conditions to $12,292 for those with comorbid hypertension. Healthcare spending among community-dwelling adults with schizophrenia. McDonald M, et al. Pfizer, NY, NY. Am J Manag Care. 2005 Sep;11(8 Suppl):S242-7. v

Clozapine (Clozaril) Appears to Increase Risk of Death: In a 10-year naturalistic study of 96 adults on clozapine, African American and Hispanic Americans had an markedly elevated risk of cardiovascular disease-related mortality (OR = 7.2, p = .09; OR = 11.3, p = .04, respectively) compared to European-Americans. The Kaplan-Meier estimate for new-onset diabetes mellitus was approximately 43% of all patients with Hispanic American (OR = 4.3, p = .027) and African American (OR = 11.5, p = .0001) with the worst elevations. BMI, total cholesterol level, and serum triglyceride level modestly increased the odds ratio for the development of diabetes mellitus. The authors conclude, "These results support the hypothesis that clozapine-treated patients appear to be at risk for death from cardiovascular disease secondary to clozapine-associated medical disorders such as obesity, diabetes, hypertension, and hyperlipidemia." Clozapine, Diabetes Mellitus, Hyperlipidemia, and Cardiovascular Risks and Mortality: Results of a 10-Year Naturalistic Study. Henderson DC, et al. MGH-Harvard. J Clin Psychiatry. 2005 Sep;66(9):1116-1121. Ed: Olanzapine undoubtedly also increases the risk of death.

Olanzapine (Zyprexa) Disfavored for Ziprasidone (Geodon) and Aripiprazole (Abilify) Due to Side-effects: The main side-effects from atypicals are weight gain and metabolic effects, including disturbances in glucose metabolism and a risk of induced diabetes. However, the atypicals are not interchangeable: the risk of incurring these effects is high with clozapine and olanzapine, moderate with risperidone and quetiapine (but perhaps increasing at higher doses), and minimal with ziprasidone and aripiprazole. Atypical antipsychotics and the burden of disease. Simpson GM. LAC + USC Medical Center; Los Angeles. Am J Manag Care. 2005 Sep;11(8 Suppl):S235-41.

TD Higher with EPS and Akathesia: Baseline data on 1460 patients with schizophrenia as part of the Clinical Antipsychotic Trials of Intervention Effectiveness schizophrenia study found 212 with probable TD. These were older, had a longer duration of receiving antipsychotic medication, and were more likely to have been receiving a conventional antipsychotic and an anticholinergic agent. Diabetes mellitus (DM) and hypertension did not predict TD, whereas substance abuse did. TD subjects also had higher ratings of psychopathology, EPSE, and akathisia. Clinical correlates of tardive dyskinesia in schizophrenia: Baseline data from the CATIE schizophrenia trial. Miller DD, et al. University of Iowa. Schizophr Res. 2005 Sep 17.

Omega-3 Deprived Rats More Depressed and Aggressive: Male rat at weaning (21 days of age) were put of diets deficient or adequate in n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks. In the n-3 PUFA deprived compared with adequate rats, docosahexaenoic acid (DHA)(22:6n-3) in brain phospholipid was reduced by 36% and docosapentaenoic acid (DPA)(22:5n-6) was elevated by 90%, whereas brain phospholipid concentrations were unchanged. N-3 PUFA-deprived rats had a significantly increased (p = 0.03) score on the Porsolt Forced Swim test for depression, and increased blocking time (p = 0.03) and blocking number (p = 0.04) scores on the Isolation Induced Resident Intruder test for aggression. Large "effect sizes" (d > 0.8) were found on the depression score and blocking time score of the aggression test. Scores on the Open Field Test for locomotor activity did not differ significantly. Dietary N-3 polyunsaturated fatty acid deprivation in rats following weaning increases their behavioral depression and aggression test scores. Demar JC Jr, et al. J Lipid Res. 2005 Oct 6. Ed: Many human studies show omega-3 is important in preventing and treating depression. For more, see Omega-3 and Depression.

Mixed Depression and Hypomania Almost Entirely in Women: Mixed hypomania was defined at a given visit as a Young Mania Rating Scale score of 12 or higher and an Inventory of Depressive Symptomatology-Clinician-Rated Version score of 15 or higher. In 908 patients, 14,328 visits over 7 years found patients with bipolar I were significantly more likely to experience hypomania than those with bipolar II. Of all 1,044 visits by patients with hypomanic symptoms, 57% met criteria for mixed hypomania. The likelihood of depression was much greater for women during hypomania (P<.001) except at the most severe levels of hypomania or mania. When eliminating irritability and agitation factors, present in both depression and hypomania definitions, a mixed state effect persisted for women (P<.001) but not for men (P = .95). Mixed Hypomania in 908 Patients With Bipolar Disorder Evaluated Prospectively in the Stanley Foundation Bipolar Treatment Network: A Sex-Specific Phenomenon. Suppes T, et al. University of Texas Southwestern. Arch Gen Psychiatry. 2005 Oct;62(10):1089-1096. For more, see Bipolar Disorder.

Phenytoin Appears Mood Stabilizer for Both Mania and Depression in Small Studies: In a 5-week DB PC study of 39 manic patients of haloperidol+phenytoin vs. haloperidol+placebo, significantly more improvement occurred with phenytoin. In another DB crossover 6-month each study of 23 stable bipolar patients who had at least one episode per year in the previous 2 yr despite ongoing prophylaxis, 3 patients relapses on phenytoin and 9 on placebo [p =0.02]. In a 6-week DB study of phenytoin vs. fluoxetine in 33 patients with unipolar depression, there was no difference between fluoxetine and phenytoin. Phenytoin: an anti-bipolar anticonvulsant? Bersudsky Y. Ben Gurion University, Israel. Int J Neuropsychopharmacol. 2005 Oct 5;:1-6. For more, see New Anti-convulsants for Bipolars.

Lithium Prevents Suicides, Self-Harm, and Death Better than Others: In a comprehensive review of 32 studies of 1,389 patients were randomly assigned to receive lithium and 2,069 to receive other compounds, those on lithium were much less likely to die by suicide (2 vs. 11 suicides; odds ratio=0.26). The composite measure of suicide plus deliberate self-harm was also lower in patients who received lithium (odds ratio=0.21). There were fewer deaths overall in patients who received lithium (9 vs. 22 deaths; odds ratio=0.42). Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. Cipriani A, et al. University of Oxford, UK. . Am J Psychiatry. 2005 Oct;162(10):1805-19. For more, see Lithium.

Euphoria Not a Sign of Mania in Children: In a study, 86 children satisfying DSM-IV criteria for bipolar disorder with and without the proposed cardinal symptom of euphoria were compared in their bipolar symptom pattern, functioning and patterns of comorbidity. Severe irritability was the predominant abnormal mood rather than euphoria (94% vs. 51%). Grandiosity was not uniquely overrepresented in youth with mania, nor did the rate of grandiosity differ whether irritability or irritability and euphoria were the Criterion A mood symptom. Neither symptom profile, patterns of comorbidity nor measures of functioning differed related to the presence or absence of euphoria. These findings challenge the notion that euphoria represents a cardinal symptom of mania in children. Instead they support the clinical relevance of severe irritability as the most common presentation of mania in the young. How Cardinal are Cardinal Symptoms in Pediatric Bipolar Disorder? An Examination of Clinical Correlates. Wozniak J, et al. MGH-Harvard. Biol Psychiatry. 2005 Sep 27. Ed: Severe irritability also needs to be differentiated from learned anti-social behavior. The irritability should be both severe and something and comes and goes as the condition cycles and not in response to simple frustrations from the environment. For more, see Childhood Bipolar Disorder.

Metabolic Disorder, Obesity Very Common in Pennsylvania Bipolars; Attempt Suicide More Often: In a study of 171 patients recruited in the Bipolar Disorder Center for Pennsylvanians, 30% had metabolic syndrome, 49% abdominal obesity, 48% hypertriglyceridemia or were on a cholesterol-lowering medication, 23% low high-density lipoprotein cholesterol, 39% hypertension and 8% diabetes. Patients with the metabolic syndrome and patients with obesity  were more likely (p = 0.05 and p = 0.004, respectively) to report a lifetime history of suicide attempt/s. The prevalence of the metabolic syndrome in patients with bipolar disorder is alarmingly high. The authors strongly support the development and testing of interventions specifically designed for preventing and treating the metabolic syndrome and its components in patients with bipolar disorder. Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians. Fagiolini A, et al. University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh and Dubois Regional Medical Center. Bipolar Disord. 2005 Oct;7(5):424-30. . For more, see Other Studies on Bipolar.

Aripiprazole Appeared to Do Much Better for Mania than Haloperidol: In a 12-week aripiprazole manufacturer-funded DB study of 347 acute manic or mixed bipolar I patients, patients on aripiprazole were much more likely to have a full response to treatment that those taking haloperidol (50% vs. 28%; P < 0.001). However, at week 12, 51% of aripiprazole, but only 29% of haloperidol patients were still on their medication. Extrapyramidal adverse events were much more frequent with haloperidol than aripiprazole (63% v. 24%). Effectiveness of aripiprazole v. haloperidol in acute bipolar mania: double-blind, randomised, comparative 12-week trial. Vieta E, et al. University of Barcelona, Spain. Br J Psychiatry. 2005 Sep;187:235-42. Ed: Based on extensive research on manufacturer financed research, this study should be viewed with a great deal of caution.  One wonders how well the EPS side-effects were managed and whether psychiatrists were more quick to discontinue the study medication if EPS side-effects were present.  If this latter were true, it would definitely stack the deck in favor of the manufacturer's aripiprazole.  Also, many psychiatrists don't use the full range of superior treatments for EPS.  For example, very few use amantidine despite extensive research in its favor. For more, see Atypicals for Bipolar.

"What is a Bipolar Disorder?" Germans Guess the Melting of the Polar Ice Caps: In a telephone survey of 1006 randomly selected Germans, out of four options given, respondents were asked to select the one they considered to be correct. Most of the respondents (61%) believed that bipolar disorder is just another term for the melting of the polar ice caps, only 4.6 % associated it with mental illness. Results of a representative survey of the German population. Angermeyer MC et al. Universitat Leipzig, ermany. . Psychiatr Prax. 2005 Sep;32(6):289-91. Ed: I have repeatedly wished the ivory tower geniuses never changed from manic-depression. In any case, the Germans sure gave me a good laugh. v

Seroquel Patients Usually Undermedicated, But High Cost Eats Up Savings: Using a health plan database of patients with bipolar disorder or schizophrenia treated with quetiapine monotherapy for at least four consecutive months, commercially insured patients with schizophrenia (n = 581) or bipolar disorder (n = 2421) received quetiapine monotherapy at average daily doses of 237 mg and 147 mg, respectively. For schizophrenia, mental health charges decreased by $1.28 for each additional milligram of quetiapine (P = 0.1097). For bipolars, they decreased by $1.31 per additional milligram (P = 0.0484). For schizophrenia, hospitalizations were reduced by 0.4% for each additional milligram of quetiapine (P = 0.0189). Relationship between initial quetiapine dose and effectiveness as reflected in subsequent mental health service use among patients with schizophrenia or bipolar disorder. Gianfrancesco F, et al. Montgomery Village, MD. . Value Health. 2005 Jul-Aug;8(4):471-8. Ed: Unfortunately, Seroquel is so expensive at $.99 per mg per month, that increasing the dose is not cost-effective. Geodon is much more cost-effective and the preferred first-line choice. 

Mothers Eating Meat and Sugar in Pregnancy Increased Risk of Leukemia in Their Infants; Fish, Fruits, Vegetables Reduced the Risk: Because leukemia clone-specific chromosomal abnormalities are present at birth in children who later develop leukemia, the authors did a nationwide case-control study of acute lymphocytic leukemia (ALL) among children ages 12 to 59 months in Greece. Children (n=131) with ALL were matched to control children (n=131) hospitalized for minor conditions. Controlling for total energy intake and possible confounding factors, the risk of ALL in the offspring was 28% lower with increased maternal intake of fruits (OR, 0.72), 24% for increased vegetables (OR, 0.76), and 28% for increased fish and seafood (OR, 0.72), but 32% higher for maternal intake of sugars and syrups (OR, 1.32) and 25% higher for meat and meat products (OR, 1.25). Children of women who tend to consume during their pregnancies what is currently considered to be a healthy diet maybe at lower risk of ALL. Maternal diet and acute lymphoblastic leukemia in young children. Petridou E, et al. Athens University, Greece. . Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1935-9. For more, see Meat and Fats.

Fish Oil and Low Fat Diet Helped Multiple Sclerosis: In a 1-year DB PC study of 31 patients with relapsing-remitting MS, those on fish oil plus a low fat diet (15% fat) did better physically (P=0.050) and mentally (P=0.050) with reduced fatigue at 6 months (P=0.035) than those on olive oil capsules plus the AHA Step I diet (fat 30%). The relapse rate decreased in both groups but was slightly better for the fish oil-low fat group: -0.79 relapses/year (P=0.021) vs. -0.69 (P=0.044). Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. Weinstock-Guttman B, et al. State University of New York, Buffalo. Prostaglandins Leukot Essent Fatty Acids. 2005 Nov;73(5):397-404. Ed: There are many things that can to be to prevent and treat MS that few doctors ever tell their patients. For more, see Multiple Sclerosis.

Fatty Muscle Enzyme SCD-1 Plays Role in Obesity: Fat metabolism, fat storage, hunger, and obesity have a very complex system with many players. In a study comparing the severely obese and the lean, researchers found the fat-building enzyme stearoyl-CoA desaturase-1 (SCD-1) was three times more abundant in the muscle from the obese people.  SCD-1 slows down fat burning and promotes storage of fat droplets in the muscles.  When the researchers used genetic techniques to alter the cells of the lean individuals so they also had higher levels of the enzyme the cells began to store more fat. People may either inherit the SCD-1 genetic predisposition to obesity or develop it at some point in their life, possibly triggered by a poor diet. Exercise helps fight this type of obesity because regular physical activity encourages changes in the body to burn rather than lay down fat. Deborah Muoio et al. Cell Metabolism 10/12/05.

ENPP1 Gene Abnormalities Linked to Obesity and Type 2 Diabetes: Faulty versions of the gene ENPP1 disrupt the way the body stores energy and handles sugar by blocking the hormone insulin. Children with faulty versions were obese at as young as five years old. Researchers compared the genes of 1,225 children who were grossly obese or overweight at ages 5-11 with 1,205 normal weight children they found an obvious pattern - many of the obese children possessed culprit versions of ENPP1. When they looked at the adults in the families, they found a similar link between the ENPP1 variants and obesity, as well as between the gene variants and early warning signs of diabetes. ENPP1 was also linked to full-blown type 2 diabetes in the adults. However, genetic testing is of no value at the present time.  Exercising, eliminating sugar and animal fats (beef, pork, and the skin of chickens) from the diet were mentioned as important strategies. Philippe Froguel et al. Institut Pasteur  Nature Genetics 7/17/05. Ed: Many other genetic abnormalities have been linked to diabetes. However, a truly healthy diet, exercise, certain vitamins and minerals, and medication when necessary are still the only means of prevention and treatment. For more, see Obesity Genetics and Diabetes Risk Factors.

Three Different Types of Irritability Identified in ADHD Children: 274 ADHD children, 30 with co-morbid bipolar and 100 with co-morbid unipolar depression, were administered the Kiddie Schedule for Affective Disorders and Schizophrenia (Epidemiologic Version) structured diagnostic interview. Three measures of irritability were identified: oppositional defiant disorder (ODD)-type irritability, mad/cranky irritability, and super-angry/grouchy/cranky irritability. Oppositional defiant disorder-type irritability was very common in all ADHD subjects, was the least impairing, and did not increase the risk of mood disorder. Mad/cranky irritability was common in only ADHD children with a mood disorder, was more impairing than the ODD-type irritability, and was predictive of unipolar depression. Super-angry/grouchy/cranky irritability was common only in ADHD children with bipolar disorder, was the most impairing, and was predictive of both unipolar depression and bipolar disorder. Two percent of the subjects with ODD-type irritability only, 6% of subjects with mad/cranky irritability, and 46% of subjects with super-angry/grouchy/cranky irritability were diagnosed with bipolar disorder. Heterogeneity of Irritability in Attention-Deficit/Hyperactivity Disorder Subjects With and Without Mood Disorders. Mick E, et al. MGH-Harvard. Biol Psychiatry. 2005 Aug 5. v

Snoring Again Linked to ADHD in Children: In a study of 2147 children, 151 children with habitual snoring (HS) were compared to 302 controls. Children with ADHD were excluded. Of the remaining 96 habitual snorers and 190 control subjects (mean age: 9.4), HS had more symptoms of hyperactivity (Conners-ADHD index) (P: 0.033), attentional (P: 0.019), and conduct and oppositional defiant in subscales (P: 0.001) of Conners' Parent (Conners-P) and inattention hyperactivity scale (IHS)-Parents. A pooled score of Conners-P ADHD Index > 60 and IHS-Parent score > 1.25 showed considerable difference in HS when compared with controls (5.1% vs. 1.4%) (P < 0.0001). Daytime hyperactivity and excessive daytime sleepiness reported by parents correlated with scores of Conners-P and IHS-P (P < 0.01). Teachers' observations showed significant correlations with learning disability and the level of academic performance in HS (P < 0.01). Symptoms of inattention and hyperactivity in children with habitual snoring: evidence from a community-based study in Istanbul. Arman AR, et al. Marmara University, Istanbul, Turkey. Child Care Health Dev. 2005 Nov;31(6):707-17. For more, see ADHD Risk Factors and Causes.

Children with Psychiatric Difficulties at High Risk of Being Bullied: In a cross-sectional comparative study in 1984 and 1996, focusing on children's and their families in the Nordic countries, parents of 3000 randomly selected children ages 2-17 were surveyed each year. Parents reported bullying of their child in 15% of the cases, varying from 7% in Sweden to about 20% in Denmark and Finland. There was a small increase in bullying from 13.7% in 1984 to 16.4% in 1996. Bullying was somewhat more frequent in boys (OR: 1.4) and in children 2-6 and 7-12 years old (OR: 2.0 and 2.2 compared with older children). Children of single parents and of parents with low education had increased risks (OR: 1.4 and 1.4). Children with chronic conditions had higher risks for being bullied (OR: 2.3). In 1996 children with psychiatric/nervous problems and hyperactivity had high risks for being bullied (OR: 8.8 and 10.5) and for bullying others (3.9 and 3.5). Sweden had early focused on the problem and implemented a strong national policy before 1996, which may account for its much lower rate. After 1996 national anti-bullying policies were strengthened in the Nordic countries, most in Sweden and Norway. Parental reported bullying among Nordic children: a population-based study. Nordhagen R, et al. Norwegian Institute of Public Health, Oslo, Norway. Child Care Health Dev. 2005 Nov;31(6):693-701. v

Thomas E. Radecki, M.D., J.D.