Dec. #2 '05
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Cannabis-Induced Psychosis Often Leads to Schizophrenia: In a Danish study 535 patients with cannabis-induced psychosis with no previous history of psychosis were followed for at least 3 years. These were compared to people referred for schizophrenia-spectrum disorders for the first time, but who had no history of cannabis-induced psychosis. Schizophrenia-spectrum disorders were diagnosed in 44% of the cannabis-induced psychosis during follow-up. New psychotic episodes of any type were diagnosed in 77%. Male gender and young age were associated with increased risk. Development of schizophrenia-spectrum disorders was often delayed, and 47% of patients received a diagnosis more than a year after seeking treatment for a cannabis-induced psychosis. The patients developed schizophrenia at an earlier age than people in the comparison group (males, 24.6 v. 30.7 years, females, 28.9 v. 33.1 years).

The Diagnostic System Will Be Changed by Genetic Findings: The traditional dichotomous classification of the so-called "functional" psychoses form the basis of modern diagnostic practice in DSM-IV. However, genetic studies shows increasing evidence for an overlap in genetic susceptibility across the traditional classification categories--including association findings at DAOA(G72), DTNBP1 (dysbindin), COMT, BDNF, DISC1, and NRG1. For example, DISC1 and NRG1 may confer susceptibility to a form of illness with mixed features of schizophrenia and mania. Current findings highlight the need for alternative approaches to classification and conceptualization for psychiatric research rather than continuing to rely heavily on the traditional Kraepelinian dichotomy. Genes for Schizophrenia and Bipolar Disorder? Implications for Psychiatric Nosology. Craddock N, et al. Cardiff University. Schiz Bull 2005 Nov 30. v

Inhalant Abuse of Volatile Solvents: Solvent-induced psychosis is very similar in clinical presentation to standard schizophrenia.  Amotivational symptoms are somewhat more common, but delusions, hallucinations, emotional instability are all typical. Symptomatological structure of volatile solvent-induced psychosis: is "solvent psychosis" a discernible syndrome? Wada K, et al. Tokyo, Japan. Nihon Arukoru Yakubuzu Zasshi 2005 Oct;40(5):471-84. v

Ginkgo No Help in Mood in Normal Young and Old Adults: In a 12-week, DB PC study of ginkgo (120 mg per day) on 93 healthy older adults (ages 55-79) and 104 young adults (ages 18-43), longer-term memory assessed by associational learning tasks showed improvement with ginkgo in older adults (d = 0.52, p = 0.04). There was no statistically significant difference on a wide range of other cognitive abilities, executive function, attention and mood. For the young adult group no measure showed statistically significant effects of ginkgo enhancement. Ginkgo biloba: no robust effect on cognitive abilities or mood in healthy young or older adults. Burns NR, et al. University of Adelaide, Australia. Human Psychopharm 2005 Dec 5. Ed: This study has 6 times as many patient days as the one below. v

Vitamin D Reduced Falling in Elderly by 37%: In a 2-year, DB PC study of 149 elderly in hostels or nursing homes and with low normal (25-90) vitamin D levels, 665 falls occurred with vitamin D vs. 890 falls with placebo, a 27% decrease. The risk of fracture decreased 31% (OR 0.69). Excluding 85 subjects whose vitamin D compliance was not greater than 50%, revealed a significant 37% reduction in the incident rate ratio for falls with vitamin D treatment, 0.63. 8 people needed to be treated for one year to prevent a fall occurring. University of Western Australia, Perth, Australia. J Am Geriatr Soc. 2005 Nov;53(11):1881-8. For more, see Vitamin D.

Acetyl-L-Carnitine Helped Chronic Depression: In a 12-week DB PC study of 204 patients with dysthymia, long-lasting depression, acetyl-L-carnitine (ALCAR) 500 mg b.i.d. did as well as the atypical antipsychotic amisulpride 50 mg b.i.d. with patients in both groups showing considerable improvement. A double-blind, randomised, controlled clinical trial of acetyl-l-carnitine vs. amisulpride in the treatment of dysthymia. Zanardi R, et al. Vita-Salute University San Raffaele, Milan, Italy. Eur Neuropsychopharmacol 2005 Nov 25. Ed: Amisulpride has been shown better than placebo in at least 3 double-blind studies (Int Clin Psychopharm 2002 Dec) and better than sertraline and as good as several others. I, myself, have tried using acetyl-carnitine in a couple patients with very severe fatigue and moderate depression. For more, see The Carnitines.

Ziprasidone (Geodon) and Chlorpromazine (Thorazine) Did Equally Well: In a 12-week DB study of 306 patients with schizophrenia who had failed on three or more antipsychotics including 6-weeks of haloperidol just prior to the study, there was no overall difference between ziprasidone 80-160 mg/day and chlorpromazine 200-1200 mg/day.  Negative symptoms did improve more on ziprasidone, but improvements in BPRS total and core items and PANSS total scores were comparable at weeks 9 and 12. Ziprasidone was associated with a greater decrease in median prolactin levels and a lower incidence of clinically significant weight change. Neither agent caused any clinically important changes in QTc interval. Efficacy and tolerability of ziprasidone in patients with treatment-resistant schizophrenia. Kane JM, et al.  Albert Einstein College of Medicine and Pfizer. Int Clin Psychopharm 2006 Jan;21(1):21-28. v

A Major Cause of Alzheimer's Damage Detailed: In a study of the neurotoxicity caused by Alzheimer's apoE4 fragments using cultured mouse neuronal cells, of apoE4's 299 amino acids, fragments containing both the lipid- and receptor-binding regions, but lacking the C-terminal 27 amino acids (273-299), were found to be neurotoxic. The toxic fragments appear in the mitochondria, where they impaired membrane integrity and mitochondrial function. Robert W. Mahley, et al. UCSF. Proceedings of the National Academy of Science, December 20, 2005.

Cocaine Increases Risk of Parkinson's Disease: Exposure to cocaine alters the nerve bodies in the region of the brain called the substantia nigra (SNpc). These nerve make dopamine, a chemical lacking in Parkinson's Disease. Cocaine makes the SNpc in adults susceptible to further damage from environmental toxins that can cause Parkinson's disease. The findings also strongly suggest that women who abuse cocaine during pregnancies put their children at an increased risk for developing Parkinson's disease. Richard Smeyne, et al. St. Jude's. Neuroscience 12/05.

Genetics Major Cause of Living Longer: In a sib pair study in very old subjects for the purpose of mapping longevity loci, families with at least two long-living siblings (men aged 89 years or above; women aged 91 years or above), found that the standardised mortality ratios (SMRs) compared with the general Dutch population for all siblings of the long-living participants was 0.66. A similar survival benefit was also observed in the parents (SMR=0.76) and in the offspring of the long-living subjects (SMR=0.65). However, the SMR of the spouses of the long-living subjects was 0.95, on only slight better than average. The familial clustering of extended survival is unlikely to be caused by ascertainment bias, because in all analyses the long-living participants were excluded. Moreover, it is also unlikely to be caused by environmental factors, because the spouses of the long-living participants had a mortality risk comparable with the general Dutch population, whereas they share the same environment. Evidence of genetic enrichment for exceptional survival using a family approach: the Leiden Longevity Study. Schoenmaker M, et al. Leiden University, The Netherlands. European Journal of Human Genetics, 26 October 2005

Omega-3 Fatty Acids Low in Depression: In a study of 118 depressive patients, changes in fatty acid concentrations were found (deficits in omega3-fatty acids, in particular). Fatty acids were measured directly before and after experimentally induced stress and at admission, discharge and 3 months follow-up. Systolic and diastolic blood pressure, finger pulse amplitude, forehead temperature (FD) and the EMG activity of the musculus zygomaticus consistently correlated with concentrations of single unsaturated oleic (18:1n-9) and erucic acid (22:1) and saturated myristic (14:0) and lauric acid (12:0). The higher the concentration of the erucic acid at discharge the higher the depression score. High concentrations of palmitoleic acid and lauric acid were related to a low level of depression. Relationships between fatty acids and psychophysiological parameters in depressive inpatients under experimentally induced stress. Irmisch G, et al. Rostock University, Germany. Prostaglandins Leukot Essent Fatty Acids 2005 Dec 9.

Manganese Exposure in Welders Very Harmful, Causing Anxiety, Depression, Confusion: In a study of 62 welders with exposure to manganese and 46 matched controls, there was a high rate of symptoms and pronounced deficits in motor skills, visuomotor tracking speed and information processing, working memory, verbal skills (COWAT), delayed memory, and visuospatial skills in the welders. Odds ratios indicate highly elevated risk for neuropsychological and neurological symptomatology of manganism. Mood disturbances including anxiety, depression, confusion, and impaired vision showed very high odds ratios. Manganese exposure: Neuropsychological and neurological symptoms and effects in welders. Bowler RM, et al. San Francisco State University. Neurotoxicity 2005 Dec 9.

rTMS Helped Sequence Learning in Depressed: In a study of repetitive transcranial magnetic stimulation (rTMS) on sequence learning in depression, which may affect sequence learning and be amenable to normalization by rTMS, 19 patients with major depressive disorder (MDD) and 20 nondepressed controls were tested. MDD patients were examined before and following treatment with rTMS to the left dorsolateral prefrontal cortex in daily sessions of 1600 stimuli at 10 Hz and at an intensity of 110% of the motor threshold over a 2-week interval of time. MDD and nondepressed groups differed significantly with respect to baseline response speed. Following treatment, MDD patients had significantly improved mood, improved response speed, and improved procedural learning. These cognitive effects were greater in those patients who showed a significant improvement in depression. The Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) on Procedural Memory and Dysphoric Mood in Patients With Major Depressive Disorder. O'Connor MG, et al. Harvard. Cogn Behav Neurol 2005 Dec;18(4):223-227.

Traditional Mutual and Intergenerional Aid Linked to Less Depression: As the traditional culture declines so do these familiar roles, supports, and ways of coping. In a study of 1502 Chinese elders living in the People's Republic of China with a nine-item measure of traditional mutual aid and intergenerational exchange, there was a significant negative relationship between tradition and depression which suggests that adherence to tradition may have protective benefits. Relationship between adherence to tradition and depression in Chinese elders in China. Mjelde-Mossey LA, et al. Ohio State University, and University of Hong Kong. Aging Ment Health 2006 Jan;10(1):19-26. 

Sleep Apnea May Increase Psychiatric Illness: Using the Veterans Health Administration databases for more than 4 million veterans 118,105 were identified as having sleep apnea (3%). Mean age at diagnosis was 58. Psychiatric comorbid diagnoses in the sleep apnea group included depression (22%), anxiety (17%), posttraumatic stress disorder (12%), psychosis (5%), and bipolar disorders (3%). Compared with patients not diagnosed with sleep apnea, a significantly greater prevalence (P < .0001) was found for mood disorders, anxiety, posttraumatic stress disorder, psychosis, and dementia. Association of psychiatric disorders and sleep apnea in a large cohort. Sharafknaneh A, et al. Baylor College of Medicine, . . Sleep 2005 Nov 1;28(11):1405-11. For more, see Causes of Depression.

Carotid Thickening More Common: In a study of 14 elderly patients with late-onset major depressive disorder and 11 non-depressed controls, the carotid artery intima-medium thickness (IMT) was higher in the patient group vs the control group (1.26 vs 1.00; p < 0.03). There was a high correlation (r = 0.55, p < 0.05) between the carotid IMT and white matter hyperintensities among patients with late-onset major depressive disorder. The findings support the vascular depression hypothesis. Carotid intima-media thickness in late-onset major depressive disorder. Chen CS, et al. Kaohsiung, Taiwan. Int J Geriatr Psychiatry 2005 Dec 2;21(1):36-42.

Dementia and Mortality Higher After Late-Onset Depression: Late-onset depression (LOD) has a poor prognosis which may be worsened by the presence of cerebrovascular disease. In a 3-year follow-up of 50 patients with LOD and 35 healthy age matched controls, 7 participants had died (all from the depressed group) and six developed dementia, all but one from the depressed group. Poor outcome was predicted by lower High Density Lipoprotein (HDL), raised Erythrocyte Sedimentation Rate (ESR) and one test of immediate memory. Initial response to treatment was not associated with later outcome. Prognosis of late life depression: a three-year cohort study of outcome and potential predictors. Baldwin RC, et al. Manchester Royal Infirmary, UK. Int J Geriatr Psychiatry 2005 Dec 2;21(1):57-63. For more, see Geriatric Depression.

Citalopram No Increase in Major Birth Defects, But Close to Term May be Problem: 125 women who took citalopram at least in the first trimester, 54% of whom continued to take the drug throughout pregnancy were compared to matched controls. Fetal survival rates, mean birth weights, and duration of pregnancy were not statistically different. Infants whose mothers were exposed to citalopram in the first trimester had no increase in major malformations. There was a 320% increased risk (RR 4.2) in neonates exposed to citalopram close to term to be admitted to special-care nurseries as compared with the unexposed infants. Citalopram use in pregnancy: prospective comparative evaluation of pregnancy and fetal outcome. Sivojelezova A, et al. Hospital for Sick Children, Ontario, Canada. . Am J Obstet Gyne 2005 Dec;193(6):2004-9. v

Self-Help Materials No Added Benefit: In a 26-week randomized study of 96 adults with major depression seeing family practice doctors and given anti-depressants, Beck Depression Inventory (BDI) scores fell from 27.3 to 13.9 in the intention-to-treat analysis, individualized self-help materials increased knowledge about depression, but there were no between group differences in outcome. A randomized controlled trial of the use of self-help materials in addition to standard general practice treatment of depression compared to standard treatment alone. Salkovskis P, et al. King's College London, London, UK. Psychol Med 2005 Dec 7;:1-9. v

Depression Markedly Increased in Frequently Intoxicated Unemployed: Using the nationally representative 1996 Finnish Health Care Survey of 5993 adults ages 15-75 years, current unemployment was associated with major depressive episode (odds ratio, OR = 1.78) due entirely to long-term unemployment. Long-term unemployment with no frequent alcohol intoxication had a 72% higher risk of major depressive (OR = 1.72) and those with at least weekly alcohol intoxication had 1027% higher risk. Major depressive episode related to long unemployment and frequent alcohol intoxication. Hamalainen J, et al. Helsinki, Finland. Nord J Psychiatry 2005;59(6):486-91. v

Vytorin (Ezetimibe/Simvastin) Better than Increasing Atorvastatin (Lipitor): In a 6-week DB study of 435 hypercholesterolemic adults with coronary heart disease with high LDL cholesterol despite atorvastatin 10 mg/day, ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg did better than doubling the atorvastatin (ATV) dose. EZE/SIMVA 10/20 mg 32.8% decrease in bad cholesterol vs. 20.3% for atorvastatin; p </= 0.001). Apolipoprotein B (-23.4 vs. -14.7%) and HDL-C (1.8 vs. -0.4%) also favored switching to EZE/SIMVA 10/20 mg (p < 0.05). Lipid-altering efficacy of switching from atorvastatin 10 mg/day to ezetimibe/simvastatin 10/20 mg/day compared to doubling the dose of atorvastatin in hypercholesterolaemic patients with atherosclerosis or coronary heart disease. Barrios V, et al. Hospital Ramon y Cajal, Madrid, Spain. . Int J Clin Pract 2005 Dec;59(12):1377-86. For more, see Statins for Cholesterol.

Non-Narcotic NSAID Diclofenac Just as Good as Narcotic Tramadol for Migraines: In a DB study of 40 emergency room patients with severe migraine headaches, intramuscular (IM) tramadol 100 mg did no better than the non-narcotic IM diclofenac sodium 75 mg. Two-hour pain response rate was 80% for both tramadol and diclofenac groups. There were no statistically significant differences among groups in terms of 48-h pain response, rescue treatment, associated symptoms' response, headache recurrence and adverse event rates. Intramuscular tramadol vs. diclofenac sodium for the treatment of acute migraine attacks in emergency department: a prospective, randomised, double-blind study. Engindeniz Z, et al. Uludag University, Turkey, . J Headache Pain 2005 Jun;6(3):143-8. Ed: Numerous studies have shown that narcotics are not superior pain relievers. In my opinion, they should all be banned. Despite the lies of the pharmaceutical industry and their well-paid physicians, they often lead medical patients into a vicious circle of narcotic addiction. For more, see Opiates for Pain.

More Irresponsible Claims From Harvard and CNS Spectrum for Manufacturer of Adderall-XR: In an uncontrolled, unscientific report from Harvard, supposedly to "assess the long-term safety and effectiveness of mixed amphetamine salts extended release" (Adderall-XR) in ADHD adults combined subtype, the psychiatrists report on a 24-month, open-label extension of a very short 4-week, DB PC study of 223 adults given up to 60 mg/day. At monthly visits, supposedly, "efficacy" was assessed with the self-report ADHD Rating Scale IV (ADHD-RS-IV). Self-reported symptoms decreased by 7.2 points (P<.001). The title: "Long-term safety and effectiveness of mixed amphetamine salts extended release in adults with ADHD." Biederman J, et al. Harvard. CNS Spectrum 2005 Dec;10(12 Suppl 20):16-25. Ed: This is deceptive and unethical publishing.  An open trial of a highly subjective illness using self-reported symptoms while on an abuse-prone medication with a high street value cannot be called research.  Many patients are known to sell their medications while most enjoy taking them personally and don't want the crash.  If you were selling your medications, how would you make out those forms?  If a person were addicted to marijuana and could get free marijuana every month, how do you think that person would fill out self-report forms? Harvard reports that "ADHD symptoms significantly improved for all subjects." How likely is that in a real world?  Harvard, the home of Timothy Leary, has long been insensitive to the harm of controlled substances.  Open trials are worthless, misleading reports which should be banned.  They cannot prove cause-effect as claimed in the authors' title. Harvard and the CNS Spectrum should be ashamed. For more, see Irresponsible Medicine.

Highly Irresponsible Narcotic Researchers Promote Highly Addictive Narcotic for Mild, Brief Pain: In a DB PC study of 122 out-patients after knee arthroscopy, these doctors proved that 5 mg of the highly addictive narcotic oxymorphone (immediate release) up to once per hour was somewhat better than placebo for mild to moderate acute post-surgical pain. 29% of the patients had only mild pain with the remainder only moderate pain. None had severe pain.  Of placebo patients 52% did not ask for any other pain medication medication vs. 83% for oxymorphone. Less than half the patients (47%) rated oxymorphone IR "very good" or "excellent" for pain relief (47%) versus placebo (25%). Gimbel JS, Walker D, Ma T, Ahdieh H. Efficacy and safety of oxymorphone immediate release for the treatment of mild to moderate pain after ambulatory orthopedic surgery: results of a randomized, double-blind, placebo-controlled trial. Arch Phys Med Rehab 2005 Dec;86(12):2284-9. Ed: This is a highly unethical study in my opinion.  There is no non-narcotic comparison medication and the pain was at worst moderate and brief in duration.  To use a highly addictive medication in such a situation is simply immoral. Shame on the Archives of Physical Medicine and Rehabilitation for publishing this.  Gimbel in a wealthy orthopod who runs an independent research center in Phoenix. Three of his four published studies on PubMed involve narcotics and appear to have been funded by the manufacturers. I wonder what IRB approved this study?  Are there no DEA guidelines prohibiting the use of narcotics for mild and brief pain conditions?  Can narcotics now be prescribed like aspirin for a stubbed toe? Take one every hour until the pain goes away.

Vitamin D Helps the Lungs, Too: In a study of 14,091 patients, those with higher vitamin D levels in their blood had significantly better lung function. The difference between the two was more marked than that between smokers and those who had quit. The difference in performance between those with the highest and lowest concentrations of vitamin D was more marked that the difference between non-smokers and those who had given up. People with the highest concentration of vitamin D in their blood significantly outperformed others in FEV1 and FVC tests of speed and total amount able to be exhaled. It is unclear if increases in vitamin D through supplements or dietary intake will actually improve lung function in patients with chronic respiratory diseases. The researchers found vitamin D was higher in men than women, was inversely related to obesity levels, and declined with age. It was also lower in participants smoking more than 20 cigarettes a day compared with non-smokers. Vitamin D affects the repair and remodelling of lung tissue, which goes on throughout life. The effects of vitamin D can affect the growth of a wide variety of cell types.  Peter Black, et al. University of Auckland. Chest 12/05. Ed: Vitamin D is a very important vitamin.  Most of us don't get enough sunshine.  I recommend at least a 1000 IU capsule each day, which can be purchased for just 2 cents a day. For more, see The Many Benefits of Vitamin D.

Hemodialysis Anemia Helped Dramatically by Melatonin: Treatment of anemia in hemodialysis results in high ferritin and low transferrin saturation depstie IV iron supplementation because of iron trapping in the reticulaendothelial system. Melatonin reduces sytokines and prevents oxidative stress caused by iron and erythropoietin treatment. In 10 hemodialysis patients with ferritins of 981 and TASTs of 15.6%, oral lematonin 6 mg/d for 30 days markedly raised TASTs to 35.5% (p<0.0001), decreased ferritin to 752 ng/ml (p<0.05) and dramatically increased serum iron from 42.4 to 110 mgc/dL (p<0.0001). Hemotocrit and hemoglobin increased from 28.6/9.19 to 31.9/10.04 (p<0.05). Values fell back to baseline levels within 2 weeks of stopping melatonin. Neurology 2005 Dec;10:583-7. Ed: Melatonin is my candidate for the fountain of youth.  For more, see Melatonin.

Zinc Helps Interferon Treat Hepatitis B: In a DB study of 75 patients with intractable hepatitis C (type 1b) with more than 105 copies of virus/ml, zinc supplementation of interferon (IFN) therapy, ten million units of natural IFN-alpha was administered daily for 4 weeks followed by the same dose every other day for 20 weeks. In the IFN + Zn group, patients received an additional dose of 150 mg/day polaprezinc orally throughout the 24-week IFN course. Patients with higher levels of serum HCV (more than 5 x 105 copies/mL) had little response in both treatment groups. Patients with moderate amount of HCV (105 to 4.99 x 105/mL) showed high response rates in combination group (41% and 64%), better than IFN alone (18% and 18%). Zinc supplementation enhances the response to interferon therapy in patients with chronic hepatitis C. Takagi H, et al. Gunma University, Japan. . J Viral Hep 2001 Sep;8(5):367-71.

Polaprezinc Protects Rat Stomach Against Indomethacin: Polaprezinc is a chelate compound consisting of zinc and L-carnosine. It has been shown to prevent gastric mucosal injury. In a rat study on indomethacin (IND)-induced apoptosis in a rat gastric mucosal cell line, pretreatment with PZ suppressed caspase-3 activation and subsequent apoptosis in the cells exposed to 500 microM IND in a dose-dependent manner, and 50 microM PZ exhibited the maximum inhibitory effect. Among PZ subcomponents, zinc but not L-carnosine played a pivotal role in this antiapoptotic function. Protection by polaprezinc, an anti-ulcer drug, against indomethacin-induced apoptosis in rat gastric mucosal cells. Fuji Y, et al. Tottori University, Yonago, Japan. Japan J Pharmacol 2000 Sep;84(1):63-70.

Polaprezinc and Its Components Speed Healing of Acid-Induced Stomach Ulcers in Rats: In a study with diabetic rats given ulcers with hydrochloric acid, polaprezinc (>10 mg/kg) significantly aided healing as did ZnSO4/7H2O or a mixture of ZnSO4/7H2O and L-carnosine, but not by L-carnosine alone. Polaprezinc exerts a salutary effect on impaired healing of acute gastric lesions in diabetic rats. Korolkiewicz RP, et al.Kyoto Pharmaceutical University, Yamashina, Japan. Dig Dis Sci 2000 Jun;45(6):1200-9.




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