Valerian: Neither Valerian Nor Kava Helped Anxiety or Insomnia in Large Internet Study: It had to happen.  In the first internet-based, 4-week DB PC study of 391 adults with anxiety disorders from all across the U.S., neither those assigned to kava nor valerian did any better than placebo on tests for anxiety and insomnia. An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia. Jacobs BP, et al. University of California-San Francisco. Medicine (Baltimore). 2005 Jul;84(4):197-207. v

Vitamin E No Benefit on Mortality in Huge 10-Year U.S. DB Study: In a 10.1-year DB PC study of 39,876 healthy US women over age 44, those on 600 IU of natural-source vitamin E on alternate days had a nonsignificant 7% risk reduction (RR = 0.93; P = .26). There were no significant effects on the incidences of myocardial infarction (RR, 1.01) or stroke (RR, 0.98; P = .82), as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a significant 24% reduction (RR, 0.76; P = .03). There was no significant effect on the incidences of total cancer (RR, 1.01) or breast (RR, 1.005), lung (RR, 1.09), or colon cancers (RR, 1.00). Cancer deaths also did not differ significantly between groups. There was no significant effect of vitamin E on total mortality (RR, 1.04). Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. Lee IM, et al. Brigham and Women's Hospital-Harvard. JAMA. 2005 Jul 6;294(1):56-65. Ed: This study is so huge that it should lay to rest any possibility that taking vitamin E will help you live longer. I do not recommend taking vitamin E as a supplement. For more, see Vitamin E.

Low-Dose Aspirin No Benefit Against Cancer in Huge Study: In the 10.1-year Women's Health Study, a randomized DB PC 2 x 2 factorial trial of aspirin and vitamin E on 39,876 US women over age 44, a dose of 100 mg of aspirin (n=19 934) every other day had no effect on total cancer (RR = 1.01), breast cancer (RR, 0.98), colorectal cancer (RR, 0.97), or cancer of any other site, with the exception of lung cancer for which there was a trend toward reduction in risk (RR, 0.78; P = .08). There was also no reduction in cancer mortality either overall (RR, 0.95; P = .51) or by site, except for lung cancer mortality (n = 140; RR, 0.70; P = .04). No evidence of differential effects of aspirin by follow-up time or interaction with vitamin E was found. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. Cook NR, et al. Brigham and Women's Hospital- Harvard. JAMA. 2005 Jul 6;294(1):47-55. For more, see Cancer.

Vitamin D Increases Muscle Strength and Decreases Hip Fractures After Stroke: In a 2-year DB PC study of 96 elderly women with poststroke hemiplegia, those given 1,000 IU ergocalciferol daily had a 59% reduction in falls (p = 0.003). There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group. Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D(2) group during the 2-year study period (p = 0.049).  At baseline, serum 25-hydroxyvitamin D levels were in the deficient range (<10 ng/ml) in all patients; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and1,25-dihydroxyvitamin D levels. Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial. Sato Y, et al. Iizuka, Japan. Cerebrovasc Dis. 2005 Jul 27;20(3):187-192. Ed: This is just one of the many well-proven benefits of vitamin D.  Everyone should take 1000 IU per day and also go out in the sun daily. For more, see Vitamin D.

Topiramate Helped Depression in Preliminary Study: In a 10-week DB PC study of 64 women with recurrent major depressive disorder, those given topiramate had a a decrease in depression and anxiety scores on the HDRS (P=0.02), and all scales of STAXI (all P<0.001). Those on topiramate lost 9 pounds. Topiramate in treatment of depressive and anger symptoms in female depressive patients: A randomized, double-blind, placebo-controlled study. Nickel C, et al. Inntalklinik, Simbach/Inn, Germany. J Affect Disord. 2005 Aug;87(2-3):243-52. Ed: Topiramate is expensive and has a fairly high rate of side-effects. Much more research is needed before it is used to treat depression with so many better researched and less expensive medications available.

Neither Zyprexa Nor Risperdal Helped Psychotic Dementia in Elderly in Large Study: In a large 10-week DB PC study of patients with moderate-to-severe psychotic symptoms associated with dementia, those given olanzapine (N=204; 2.5 mg-10 mg/day), risperidone (N=196; 0.5 mg-2 mg/day) or placebo (N=94) had no significant treatment differences between groups after the 10 weeks. Overall discontinuation was olanzapine 16.2% vs. placebo 3.2% vs. risperidone 8.7%. Comparison of olanzapine and risperidone in the treatment of psychosis and associated behavioral disturbances in patients with dementia. Deberdt WG, et al. Brussels, Belgium. . Am J Geriatr Psychiatry. 2005 Aug;13(8):722-30. Ed: Since Zyprexa is associated with a higher mortality rate in the elderly, since it is of marginal benefit, if any, it doesn't seem like it should be used. v

Melatonin Helps Parkinson Patients Sleep: In a 2-week per treatment DB PC crossover study of 40 Parkinson's patients with 1-week washouts, a significant improvement in total nighttime sleep time occurred only with the 50 mg melatonin compared to placebo, not with the 5 mg. However, there was significant improvement in subjective sleep disturbance, sleep quantity, and daytime sleepiness during the 5 mg melatonin treatment compared to placebo. Melatonin for sleep disturbances in Parkinson's disease. Dowling GA, et al. University of California, San Francisco. Sleep Med. 2005 Aug 3. Ed: I like melatonin for sleep and also for the brain, especially after age 50. For more, see Melatonin.

Trazodone Just as Good as Paxil for Depression: In a 6-week DB PC study of 108 adults with major depression, trazodone prolonged release 150-450 mg/day did just as well as paroxetine 20-40 mg/day. There were no significant differences between the groups at endpoint in efficacy measures, and in percentage of responders (> 85%) or patients in remission (> 65%). Sleep disorders (HAM-D subset) were significantly less evident for patients in the trazodone group at the end of the study (p < 0.05). Adverse drug reactions were reported by 35% of trazodone-treated patients (mainly of the nervous system) and 26% of paroxetine-treated patients (mainly gastrointestinal), although none was considered to be serious. A comparative, randomised, double-blind study of trazodone prolonged-release and paroxetine in the treatment of patients with major depressive disorder. Kasper S, et al. Medical University, Vienna, Austria. Curr Med Res Opin. 2005 Aug;21(8):1139-46. Ed: The so-called SSRI magic bullet for depression has been disproven for the umpteenth time. Don't trust pharmaceutical companies! For more, see Depression.

Daily Teriparatide Injections Helped Osteoporosis Back Pain: In a 14 DB PC study of 146 women with back pain due to osteoporosis with 30 months follow-up, women who daily self-injected teriparatide 40 microg did better than those on daily oral alendronate 10 mg with a 73% reduced risk for any back pain (relative risk 0.27) and 81% reduced risk of moderate or severe back pain (relative risk 0.19) vs. alendronate. Longterm reduction of back pain risk in women with osteoporosis treated with teriparatide compared with alendronate. Miller PD, et al. Lilly Research Laboratories, Indianapolis, Indiana, USA. J Rheumatol. 2005 Aug;32(8):1556-62. Ed: This is a highly expensive treatment, costing thousands of dollars each month.  The results are good, but whether using all of my other recommended interventions for osteoporosis would change the results of this study, I don't know. Teriparatide stimulate new bone construction. For more, see Osteoporosis.

Brain: Orbitofrontal Cortex Sometimes Damaged: The orbitofrontal cortex is involved in the monitoring of reward and in judgement. Lesion studies and functional neuroimaging investigations implicate this region in affective disorders, and altered neuronal and glial cell composition have been observed in this region in patients with major depressive disorder (MDD). In a study of 60 postmortem brains from patients with bipolar disorder (BPD), schizophrenia, MDD, and controls, researchers found a neuronal size reduction in BPD in layer 1 (21%, p=0.007) and a trend for a reduction in layer 5 (20%, p=0.05). There was a significant interaction effect of brain hemisphere and group on neuronal size in layer 3 (p=0.001), with evidence for reduced layer 3 neuronal sizes in MDD (30%, p<0.001). There were no group differences in glial cell size nor for differences in glial or neuronal density. There was no evidence for neuronal or glial pathology in this region in schizophrenia. Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia. Cotter D, et al. Dublin, Ireland. Bipolar Disord. 2005 Aug;7(4):358-69. For more see Bipolar Disorder and Causes of Depression.

Everybody's Bipolar: In a report from San Diego and Italy, 563 consecutive private outpatients with a DSM-IV-diagnosed major depressive episode (MDE) were evaluated using a modified SCID-CV, a duration of hypomania >/=2 days (rather than the 4-day floor cutoff recommended), did not follow the SCID-CV's stem (mood) skip-out instruction, focused more on past history of overactive behavior rather than mood change, and assessed hypomanic features both outside and during index MDE. Bipolar-II was diagnosed in 56.8% of patients. Compared with MDD, BPII had a significantly earlier index age and age at onset of first MDE and higher rates of atypical features, depressive recurrences, hypomanic symptoms during MDE, trait mood lability, and bipolar family history (p = .0000 for all variables). Optimizing the Detection of Bipolar II Disorder in Outpatient Private Practice: Toward a Systematization of Clinical Diagnostic Wisdom. Akiskal HS, Benazzi F.  University of California, San Diego, and National Health Service, Forli, Italy. J Clin Psychiatry. 2005 Jul;66(7):914-921. Ed: I strongly disagree with the trend of diagnosing the majority of depressed patients as bipolar.  What it does is deprive many patients of vigorous treatment for depression as many psychiatrists obsess about avoiding mania.  It also means that many patients will be also given divalproex, lamotrigine, or an atypical anti-psychotic and that for most of them this is unnecessary. Even true bipolars suffer from depression three times as long as they have mania and the depression is much more painful. Many psychiatrists undertreat the depression.  Bipolars are much more likely to kill themselves while depressed than while manic. Drug companies love studies like this, since most anti-depressants have lost their patent protection, while popular anti-manic treatments are still covered. This is a dangerous direction for psychiatry to go. For more, see Bipolar Disorder.

Irresponsible Claims From Harvard and Canadian Journal of Psychiatry: The authors claim that their tiny, open-label, uncontrolled, mixed diagnosis, 16-week study "assess(es) the antidepressant efficacy and tolerability of adjunctive ropinirole in 10 outpatients (7 MDD, 3 Bipolar) with treatment-resistant depression." The report on giving the Parkinson's drug ropinirole 0.25 to 1.5 mg daily added to tricyclic antidepressants or selective serotonin reuptake inhibitors found that MADRS depression scores decreased from 29.6 at baseline to 16.9 at endpoint (P < 0.02). The Harvard psychiatrists wrongfully claim that 4 of 10 (40%) patients "responded to the medication." They only know that four patients got better while on the medication. They also wrongfully claim that their poorly designed study "suggest(s) that, in selected cases of TRD, ropinirole augmentation of antidepressants is effective." Ropinirole in treatment-resistant depression: a 16-week pilot study. Cassano P, et al. Harvard-Massachusetts General. . Can J Psychiatry. 2005 May;50(6):357-60. Ed: The researchers did get informed consent and were monitored by an IRB. However, an uncontrolled, open-label study can never be used to determine possible efficacy in the treatment of depression.  Maybe, ropinirole will someday be found useful.  But, such open label, preliminary investigations should never be published and, if published, should emphasize that they cannot evaluate efficacy.  Open-label studies have repeatedly misled thousands of American psychiatrists to give patients medications before they have ever been correctly tested for efficacy only later to find out that the medications were worthless for what the doctor was trying to treat.  For more, see Open Trial Claims.

Suicide Higher in Shorter Men: Previous studies have found associations between poor fetal and infant growth and the risk of suicide. In a record linkage study of the birth, conscription, mortality, family, and census register data of 1,299,177 Swedish men followed from age 18 to a maximum of age 49, there were 3,075 suicides over an average follow-up period of 15 years. There was a strong inverse association between height and suicide risk. In fully adjusted models, a 5-cm increase in height was associated with a 9% decrease in suicide risk. Strong inverse association between height and suicide in a large cohort of Swedish men: evidence of early life origins of suicidal behavior? Magnusson PK, et al. Am J Psychiatry 7/2005;162:1373-5. v

Alzheimer's Has Decreased MEOX2 Which Helps Form Blood Supply to Brain Tissue: In a study of endothelial cells from the lining of blood vessels in the brain, taken from autopsy samples from people with Alzheimer's, researchers found that expression of MEOX2, or mesenchyme homeobox 2, also known as GAX, was low in the cells of those with Alzheimer's. When there are low levels of MEOX2 expression, the affected cells cannot form any form of blood supply system, and so die. It also increased the level of a protein that removes amyloid beta peptide, the toxin that builds up in brain tissue in Alzheimer's disease. Restoration of the gene expression level in the human brain cells was found to stimulate the formation of new blood vessels. In further studies, one copy of the gene was deleted in mice, creating damage similar to that seen in the brains of people with Alzheimer's. Berislav Zlokovic, et al. University of Rochester. Nature Medicine 8/21/05.

Most Mild Alzheimer's Patients Showed Safety Deficits on Task-Switching Driving Test: In a study of 33 mild Alzheimer patients (average MMSE 26.1 (3.0)) and 167 controls, the patients did just as well on a straight driving test, but when asked to identify roadsigns and restaurants on a one mile commercial stretch, they identified one third fewer landmarks and committed three times as many at-fault safety errors, such as failing to notice a large speed limit sign, suggesting difficulty in task switching between driving and observing (p<0.0001). Some Alzheimer patients (24%) performed well, so assessing fitness to drive should include controlled cognitive challenges while driving. Driver landmark and traffic sign identification in early Alzheimer’s disease. E Y Uc, et al. J Neurol Neurosurg Psychiatry 2005;76: 764-8

Folate Helps Prevent Alzheimer's: From the Baltimore Longitudinal Study of Aging, 579 over 59 without Alzheimer's disease were followed for nine years.  Foods rich in folate include oranges, bananas, leafy green vegetables, asparagus, broccoli, liver, and many types of beans and peas, as well as fortified bread. During follow-up, 57 developed Alzheimer's disease. Those with a higher dietary intake of folate had a 60% lower rate of the disease compared to the lowest quartile. Older adults whose total folate intake (diet and supplement) equaled or exceeded the 400 microgram RDA reduced their chances of developing Alzheimer's disease by 55 percent. No association was seen between intakes of vitamin C, carotenoids, or vitamin B-12. Vitamin E and B-6 had no effect when controlling for folate. Maria Corrada, et al. University of California, Irvine. WebMD 8/15/05. For more, see Alzheimer's.

Suicide Attempters Helped by Cognitive Therapy: In an 18-month random assignment study of 120 adults who recently attempted suicide, those assigned to 10 sessions of cognitive therapy had a 49% lower rate of reattempting suicide than those assigned to enhanced standard care. 13 participants (24.1%) in the cognitive therapy group and 23 participants (41.6%) in the usual care group made at least 1 subsequent suicide attempt (asymptotic z score, 1.97; P = .049)(hazard ratio, 0.51). The severity of self-reported depression was significantly lower for the cognitive therapy group than for the usual care group at 6 months (P= .02), 12 months (P = .009), and 18 months (P = .046). Gregory K. Brown, et al. University of Pennsylvania. JAMA. 2005;294:563-570. For more, see Suicide.

Even Heat-Treated Lactobacillus Can Help Child Allergic Rhinitis: Live Lactobacillus paracasi 33 (LP33) may effectively improve the quality of life for children with perennial allergic rhinitis. It has been demonstrated that heat-killed lactic acid bacteria (LAB) suppress specific immunoglobulin E synthesis and stimulate interleukin-12 production in animals. In a 30-day DB PC study of 90 patients with allergic rhinitis induced by house-dust-mite, groups A and B received two capsules per day of live or heat-killed LAB (5 x 10(9) colony-forming units/capsule), while those in Group C received placebo capsules. Groups A and B rhinoconjunctivitis-related quality of life improved, as compared with the placebo group, in terms of both frequency (9.47, 6.30, vs. -3.47; p < 0.0001) and level of bother (5.91, 6.04, vs. -2.80; p = 0.004). The efficacy and safety of heat-killed Lactobacillus paracasei for treatment of perennial allergic rhinitis induced by house-dust mite. Peng GC, et al. China Medical University Hospital, Taichung, Taiwan, ROC. Pediatr Allergy Immunol. 2005 Aug;16(5):433-8. For more, see Allergic Rhinitis and Yogurt for Allergies.

Circumcision Markedly Reduces Risk of AIDS: In a 21-month random assignment study of 3000 men ages 18-24 in South Africa, all the men in the trial received intensive counselling on avoiding infection with HIV during heterosexual sex at the beginning of the trial and at 3-month, 12-month, and 21-month follow-ups. They were given free condoms. Men in the circumcised group reported slightly more sexual contacts than the uncircumcised men (7.6 contacts in the first 9 months of the trial compared to 6 contacts in the uncircumcised group) but had fewer cases of HIV infection. Eighteen men in the circumcised group and 51 in the uncircumcised group became infected. The trial was stopped early and circumcision offered to all participants.Bertran Auvert, et al. University of Versailles.(Science 2005;309:860). For more, see Circumcision.

Balsamodendrom Mukul Helped Hypertensives in Small Study: In a 6-week DB PC study of 57 newly diagnosed hypertensives, those taking Balsamodendron mukul (an extract of the gum of a small tree) 1.5 g/d did better than placebo with levels of systolic blood pressure, diastolic blood pressure, plasma total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglycerides, free fatty acids, and phospholipid levels were significantly reduced, and high-density lipoprotein cholesterol levels were significantly elevated. Combined therapy with B. mukul and nifedipine was more beneficial than the treatment with B. mukul alone. Single- or double-blind treatment With Balsamodendron mukul and nifedipine in hypertensive patients. Panneerselvam J, et al. Annamalai University, India. J Clin Hypertens (Greenwich). 2005 Jun;7(6):340-5. Ed: I never heard of this one. The report is sketchy and very preliminary. For more, see Non-Medical Treatments of Hypertension.

Lamotrigine May Have Helped Anger in Borderlines: Anger and aggression are typical in borderline patients. In an 8-week DB PC study of 27 female borderlines, those taking lamotrigine had a significant (p < 0.01) change on four STAXI scales (State-Anger, Trait-Anger, Anger-Out, Anger-Control) but not the Anger-In scale, where a difference of only 8.5% (p < 0.2) was found. Lamotrigine treatment of aggression in female borderline-patients: a randomized, double-blind, placebo-controlled study. Tritt K, et al. University Clinic, Regensburg, Germany. J Psychopharmacol. 2005 May;19(3):287-91. For more, see Borderlines and Aggression. 

Videogame Violence Causes Real World Violence: This updated meta-analysis reveals that exposure to violent video games is significantly linked to increases in aggressive behaviour, aggressive cognition, aggressive affect, and cardiovascular arousal, and to decreases in helping behaviour. Experimental studies reveal this linkage to be causal. Correlational studies reveal a linkage to serious, real-world types of aggression. Methodologically weaker studies yielded smaller effect sizes than methodologically stronger studies, suggesting that previous meta-analytic studies of violent video games underestimate the true magnitude of observed deleterious effects on behaviour, cognition, and affect. An update on the effects of playing violent video games. Anderson CA. Iowa State University. . J Adolesc. 2004 Feb;27(1):113-22. For more, see TV and Entertainment Violence. 

Depression More Than Triples Rate of Disability in Dementia: In a community-based group of 216 elderly people with low-to-moderate education level, very early dementia alone was strongly associated with functional disability, and this association tripled in subjects with both very early dementia and symptoms of depression, i.e., for very early dementia an 11-fold higher risk for disability, for very early dementia and depression a 37-fold higher risk for functional dependence. Diana De Ronchi, et al. Univ. of Bologna, Italy. . Am J Geriatr Psychiatry. 2005 Aug;13(8):672-85

White Matter Lesions Increased with Depression and Subjective Memory Complaints: Subjective memory complaints (SMC) and cerebral white-matter lesions (WML) are very prevalent among elderly. In a cross-sectional study of 60 elderly without dementia, but given an MRI, the best correlate of SMC was the severity of depressive symptoms, although SMC and WML were strongly correlated. Objective cognitive performance was not significantly associated with SMC after adjusting for WML and mood. The presence of a history of late-onset depression was a strong correlate of WML severity, even after adjusting for age, gender, and education. Subjective memory complaints, white-matter lesions, depressive symptoms, and cognition in elderly patients. Minetts TS, et al. Sao Paulo Federal University, Brazil. . Am J Geriatr Psychiatry. 2005 Aug;13(8):665-71. For more, see Dementia.

Light Drinking, Especially Wine, Associated with Less Dementia: In a 2-year follow-up study of elderly people from six communities in Chongqing, China, after adjusting for age, sex, educational level and cigarette smoking, light-to-moderate drinking was associated with a significantly lower risk of dementia compared with non-drinking. Excessive drinking was related to a higher risk of dementia. The effect of light-to-moderate drinking seemed most prominent among vascular dementia: 0.63 for Alzheimer's disease, 0.31 for vascular dementia and 0.45 for other dementia. A light-to-moderate intake of beer was associated with a significantly higher risk of dementia than a non-drinker of beer. For wine, a significantly lower risk of dementia existed for a light-to-moderate drinker. A 2-year follow-up study of alcohol consumption and risk of dementia. Deng J, et al. Third Military Medical University, Chongqing, China. Clin Neurol Neurosurg. 2005 Aug 3. Ed: This is similar to other studies. If you drink, I recommend a maximum of 4 ounces of red wine per day. For more, see Alcohol and Dementia.

Paroxetine (Paxil) Caused Increased Suicide Attempts in Large Study: In a DB PC study of 916 adults on paroxetine, seven attempted to take their own life vs. one of 550 patients on placebo. Their conclusions are published in the journal Dr Ivar Aursnes, et al. University of Oslo. BMC Medicine 8/21/05. Ed: Paroxetine is the only short-acting SSRI anti-depressant and has long had a serious problem with drug withdrawal symptoms, even between regular doses. v

Insomniac Elderly More Likely to Become Depressed: In a 1-year follow-up study of 147 men and women over the age of 60 with no history of mental illness, 34 had persistent insomnia, 47 less persistent "indeterminate insomnia," while 66 had no sleep troubles. During the year, 12 developed depression: 6 with persistent insomnia, 4 had indeterminate insomnia and 2 no trouble sleeping. Elderly patients with persistent insomnia were six times more likely to experience serious new-onset depression than individuals who sleep easily. Ten of the 12 depressed patients were women, and all the patients who became depressed while suffering from a persistent form of insomnia were female. Perlis said its unclear why elderly women might be at especially high risk for the insomnia-depression connection. Perlis, M, et al. University of Rochester, J Behavioral Sleep Medicine late 2005. Another study by Perlis of 1,221 elderly treated for depression, those with insomnia were 12 times more likely to still be depressed 6 months later and 10 times more likely to be depressed 1 year later. Ed: This may be a lack of serotonin, which is converted into melatonin to aid sleep. A lack of melatonin causes insomnia, while depression is often caused by a lack of serotonin effect. 5-HTP, a serotonin precursor, has been used for depression. I would hypothesize that it is better for depression with insomnia than depression without insomnia and that it might prevent depression in elderly with insomnia. For more, see Causes of Depression and Insomnia.

Texas Department of State Health Services, Canada Strongly Influenced by Pharmaceutical Industry: The pharmaceutical industry has been pouring money into Texas psychiatric departments. This may influence their psychiatrists and thereby influence the State Health Services Treatment Guidelines (J Clin Psychiatry Aug '05) to promote their drugs.  Lamotrigine is recommended as the first line treatment for Bipolar I depression despite the fact that it has never once been compared to the much less expensive standard anti-depressants and despite the fact that most BD1 patients are already on an antimanic agent. In fact the largest study found lamotrigine no better than placebo for bipolar, depressed patients.  Texas also strongly favor the two most expensive atypical antipsychotics, olanzapine (Zyprexa) and quetiapine (Seroquel), despite the fact that both are fattening and cause more diabetes than the much less expensive once-a-day ziprasidone (Geodon).  They also promote divalproex (Depakote) as a first line treatment for manic episodes despite its very high suicide rate compared to lithium.  Texas makes no mention of folate or omega-3 fatty acids despite their benign nature and, at least in the case of folate, proven efficacy.  Surprisingly, Texas still promotes the expensive topiramate (Topamax) for mania despite multiple, unpublished, double-blind studies proving that it is worthless.  For unknown reasons, Texas doesn't like aripiprazole despite its lack of weight gain vs. depakote and olanzapine which cause huge amounts of weight gain.  Since more and more psychiatrists are calling everyone bipolar, lamotrigine will be used far in excess of what its skimpy research would suggest sensible. Canadian CANMAT guidelines put anti-depressants paired with an anti-manic agent as a first line treatment (Bipolar Disord. 2005;7 Suppl 3:5-69.). However, the CANMAT also mentions lamotrigine as a first line treatment, although CANMAT is heavily influence by the University of British Columbia which received industry funding for a huge lamotrigine study, which interestingly found lamotrigine worthless for preventing bipolar depression! UBC psychiatrists warn against the induction of mania by anti-depressants. However, the rate of mania induction by anti-depressants like bupropion are very small and I think that there is a serious risk in over reliance on anti-manic therapies in Bipolar treatment. The APA in 2002 was influenced against anti-depressants on dubious data. 

Junk Science from the Journal of Affective Disorder: Psychiatrists from the University of Alcala in Spain make the wild claim that there retrospective chart review of just 34 charts of bipolar outpatients treated with lamotrigine as a sole or add-on treatment is able to "evaluate the effectiveness and safety of lamotrigine in bipolar spectrum patients." Clinic notes were used to score the Clinical Global Impression for Bipolar Disorders (CGI-BP-M) scale and to identify manic, hypomanic mixed or depressive relapses. Treatment duration ranged very widely from 6-96 weeks. While only 47% had their depression lift and only 32% remained not depressed in follow-up, they not only just to the conclusion that "lamotrigine was safe and effective" but also that the "effectiveness of lamotrigine was greater for those patients diagnosed with bipolar spectrum disorders other than bipolar I." Lamotrigine for the treatment of bipolar spectrum disorder: a chart review. Montes JM, et al. Universidad de Alcala, Madrid, Spain. . J Affect Disord. 2005 May;86(1):69-73. Ed: Shame on the Journal of Affective Disorder for publishing such dishonest and wild claims of effectiveness.  Such open retrospective chart reviews are even worse that open studies which have already been repeatly shown to be virtually worthless and extremely misleading. I encourage you to email the editors of the journal, Hagop S. Akiskal of the University of California, San Diego, and protest this promotion of junk science. . and Cornelius Katona at the University of Kent in the UK.  (The University of Kent emailed to note that the study had been accepted by Akiskal in the U.S.

More Junk Science from the Journal of Affective Disorder: Psychiatrists at the University of Tennessee treated 24 women with cyclothymic temperament and refractory depression with lamotrigine in a totally uncontrolled study. Eighteen (75%) met DSM-IV criteria for bipolar II disorder. In two thirds of the cases, lamotrigine was add-on therapy to an antidepressant. The only measure of response to therapy was the DSM-IV Global Assessment of Functioning (GAF). The authors claim that 16 (70%) had sustained "responses" instead of sustained improvement, suggesting that all 16 were helped by lamotrigine and that their study was proof of effectiveness. They state, "Robust, sustained responses to lamotrigine monotherapy were seen in 4 patients (17%)," and 12 had a remission of their depression for at least 12 months. Only "seven patients (30%) received no apparent benefit from lamotrigine." They conclude, "Lamotrigine induced prolonged illness remissions in a substantial number of female patients whose symptoms were both complex and refractory." Sustained remission with lamotrigine augmentation or monotherapy in female resistant depressives with mixed cyclothymic-dysthymic temperament. Manning JS, et al. University of Tennessee-Memphis. . J Affect Disord. 2005 Feb;84(2-3):259-66.

FDA Approving Meds on Skimpy Data: The FDA under President Bush has approved many psychiatric medications for very dubious indications, based on very borderline data.  Lamotrigine has been approved for maintenance of bipolar disorder despite the fact that it has never been compared to anti-depressants and is worthless in preventing mania.  In fact, one recent very large study found it worthless for bipolar depressed patients.  It only helped the less common bipolar manic patients avoid becoming depressed.  The FDA has approved clozapine for suicide prevention in schizophrenia based on a study showing a small decrease in suicidal attempts, but no actual decrease in successful suicides which were non-significantly higher in the clozapine group.  Olanzapine with fluoxetine has been approved for acute bipolar depression based only on a placebo study showing slight benefit.  Of course, olanzapine causes huge weight gain in many patients and diabetes and early death in a smaller number.  The FDA has approved the "date-rape" drug and other insanely addictive drugs like Oxycontin with absolutely no need for their presence on the market.  Clearly, the FDA is too friendly with the pharmaceutical industry and patients suffer.

Wall Street biotech insider gets No. 2 job at the FDA: August 24, 2005: By Alicia Mundy, Seattle Times Washington bureau: Only a month ago, Dr. Scott Gottlieb was a Wall Street insider, promoting hot biotech stocks to investors. Now Gottlieb holds the No. 2 job at the Food and Drug Administration (FDA), the federal agency that approves new drugs, oversees their safety and affects the fortunes of companies he once touted. Wall Street likes the appointment of Gottlieb, 33, who believes in faster drug approval and fewer news-release warnings to the public about potential side effects of drugs. But some medical experts are shocked by his July 29 appointment, coming at a time when the public is increasingly concerned about the safety of popular medicines. In addition, the federal government has just begun scrutinizing the growing financial ties between Wall Street firms and doctors researching new drugs. Gottlieb's new job "further impedes the independence of the FDA," said Dr. Jerome Kassirer, former editor of The New England Journal of Medicine. "Gottlieb has an orientation which belies the goal of the FDA." "I've never heard of anything like this," said Merrill Goozner, a director at the liberal Center for Science in the Public Interest. "If he's had dealings regarding companies whose products are up for review at the agency, it strikes me as a potential conflict of interest. You want a barrier between the regulated and the regulators. It's fundamental," Goozner said.

TBP/SCA17 Trinucleotide Repeats More Common in Schizophrenia: Trinucleotide repeat (TNR)-containing TBP/SCA17 genes were found more often 100 unrelated schizophrenia patients than in 124 controls without evident neurodegenerative or psychiatric disorders (P=0.0149), with an increased frequency of 36 repeats in the patients and two patients carrying 45 TNR expansions were identified. TBP/SCA17 is the TATA box binding protein gene mapped to chromosome 6q27. TNR expansions of the TBP/SCA17 gene may contribute to the genetic risk of schizophrenia in a small percentage of cases. Expanded trinucleotide repeats in the TBP/SCA17 gene mapped to chromosome 6q27 are associated with schizophrenia. Lee-Chen GJ, et al. National Taiwan Normal University. Schizophr Res. 2005 Jul 28

Myelin-Associated Glycoprotein Gene Polymorphisms Linked to Schizophrenia: Results of gene expression microarray and quantitative PCR studies have suggested abnormalities in the expression of myelin-related genes including myelin-associated glycoprotein (MAG) in schizophrenic patients. Research provides strong evidence for oligodendrocyte dysfunction in schizophrenics. In this study of four single nucleotide polymorphisms (SNPs), rs2301600, rs3746248, rs720309 and rs720308, of this gene in Chinese schizophrenic patients (n=470) and healthy controls (n=470). The distribution of rs720309 T/A genotypes showed a strong association with schizophrenia (P=0.0008). A haplotype constructed of rs720309-rs720308 also revealed a significant association with schizophrenia (P=0.0084). Polymorphisms of myelin-associated glycoprotein gene are associated with schizophrenia in the Chinese Han population. Wan C, et al. Center for Human and Animal Genetics, Beijing, China; Shanghai Jiao Tong University. Neurosci Lett. 2005 Jul 19 

Folate MTHFR Gene T677T, A1298A, C677C, C1298C Polymorphisms Increase Risk: The researchers previously found an association between the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C polymorphisms and schizophrenia in patients from Bakirkoy, Turkey [Sazci, A., et al. Mol. Brain Res. 117, 104-107]. To confirm this, they analyzed the genotypes of MTHFR677 and MTHFR1298 of 297 schizophrenic patients and 341 healthy controls from Erenkoy, Turkey.  The T677T genotype was overrepresented in the total schizophrenic patients (OR=1.94; P=0.014). Similarly, the T677T/A1298A compound genotype was the most significant one in the total schizophrenic patients (OR=2.40; P=0.003). The C1298C genotype was overrepresented in the total schizophrenic patients (OR=1.71; P=0.042). Likewise, the C677C/C1298C compound genotype was significant in the total schizophrenic patients (OR=1.69; P=0.055). The T677T genotype and T677T/A1298A compound genotype were significantly overrepresented (OR=2.18; P=0.029; OR=2.75; P=0.012) in men schizophrenic patients, but not women. Association of the C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene with schizophrenia: Association is significant in men but not in women. Sazci A, et al. University of Kocaeli, Kocaeli, Turkey. Prog Neuropsychopharmacol Biol Psychiatry. 2005 Aug 2. For more, see Schizophenia Genetics.

Neuregulin-1 Polymorphisms Linked to Late Onset Alzheimer's with Psychosis: Probands with late onset Alzheimer's disease (LOAD) exhibit positive symptoms of psychosis, 30-60% of the time. Positive symptoms of psychosis have been shown to appear prior to the onset of dementia to be accompanied by greater cognitive deficits, and to predict a more rapid decline. A study of the distribution of AD with psychosis (ADP) in families from the NIMH Alzheimer's Disease Genetic Initiative sample indicates that the trait is heritable, and linkage studies of multiplex ADP families have found suggestive peaks on 2p, 6q, 8p, and 21q. A genome scan of idiopathic psychosis, schizophrenia, in the Icelandic population identified a risk haplotype within the 5' region of neuregulin-1 (NRG1) on 8p12. Associations with NRG1 SNPs have also been found in other schizophrenia populations from Scotland, Ireland, and China. Here, researchers found a significant linkage peak for ADP on 8p12 in the NIMH AD dataset, encompassing the NRG1 region. The NRG1 SNP (single nucleotide polymorphism), rs392499, was linked with ADP, P = 0.008. This same SNP is part of a 3-SNP haplotype preferentially transmitted to individuals with this phenotype. NRG1 plays a role in increasing the genetic risk to positive symptoms of psychosis in a proportion of LOAD families. Neuregulin-1 polymorphism in late onset Alzheimer's disease families with psychoses. Go RC, et al. University of Alabama, Birmingham, Alabama. Am J Med Genet B Neuropsychiatr Genet. 2005 Aug 4. v

Ziprasidone (Geodon) Did as Well as Olanzapine (Zyprexa) for Schizophrenia: In a 6-month DB flexible dosage continuation study of schizophrenic or schizoaffective patients who had responded, comparable improvements in BPRS and CGI severity scores were seen with both olanzapine and ziprasidone. Olanzapine increased weight, total cholesterol, low-density lipoprotein cholesterol, and fasting insulin. Mean QTc values at endpoint were 407.1 msec (baseline mean=406.0 msec) and 394.4 msec (baseline mean=399.7 msec) for ziprasidone and olanzapine, respectively. No patient had a QTc interval >/=500 msec. Six-month, blinded, multicenter continuation study of ziprasidone versus olanzapine in schizophrenia. Simpson GM, et al. University of Southern California. . Am J Psychiatry. 2005 Aug;162(8):1535-8. Ed: Geodon is just as good, much less expensive with once-a-day dosing, and causes no weight gain. Why would anyone use Zyprexa as a first line drug? For more, see Geodon.

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

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