Emotional Deficits Don't Improve: In a study of 13 first episode schizophrenics, deficits in emotion perception were present at illness onset of schizophrenia and showed minimal response to effective antipsychotic treatment. Effects of antipsychotic treatment on emotion perception deficits in first-episode schizophrenia. Herbener ES, et al. University of Illinois at Chicago. . Am J Psychiatry. 2005 Sep;162(9):1746-8. For more, see Schizophrenia.

Glycine Low; Homocysteine High in Schizophrenia: Altered glycine and homocysteine levels may contribute to N-methyl-d-aspartate receptor dysfunction in schizophrenia. Plasma levels of amino acids in 94 patients with schizophrenia were compared with those in 34 age- and sex-matched normal subjects. Glycine levels and glycine-serine ratios were lower and homocysteine levels were higher in patients than in controls. Low glycine levels correlated with a greater number of negative symptoms. The glycine-serine ratios of normal subjects and patients being treated with clozapine did not differ significantly. Relation of plasma glycine, serine, and homocysteine levels to schizophrenia symptoms and medication type. Neeman G, et al. Jerusalem, Israel. . Am J Psychiatry. 2005 Sep;162(9):1738-40. For more, see Glycine for Schizophrenia.

Folate Low in Pregnancy May Increase Schizophrenia: Many different lines of research support the hypothesis that schizophrenia is a disorder of development with etiological factors implicated as early as the second trimester in utero. A research review by the authors supports the hypothesis that maternal low folate and high homocysteine levels may provide a potential teratogenic mechanism that increases the risk for developing schizophrenia. Do maternal folate and homocysteine levels play a role in neurodevelopmental processes that increase risk for schizophrenia? Picker JE, Coyle JT. Harvard-McLean. Harv Rev Psychiatry. 2005 Jul-Aug;13(4):197-205. 

Vitamin C Helped Schizophrenics: In an 8-week DB PC crossover study of 40 schizophrenic patients, increased serum MDA and decreased plasma ascorbic acid levels were found in schizophrenic patients. These levels were reversed significantly after treatment with vitamin C along with atypical antipsychotics compared to placebo with atypical antipsychotics. BPRS change scores at 8 weeks improved statistically significant with vitamin C as compared to placebo. Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia. Dakhale GN, et al. Government Medical College, Nagpur, India. Psychopharmacology (Berl). 2005 Aug 13;:1-5. Ed: One study isn't proof, but vitamin C is inexpensive, safe, and a good supplement for everyone.  I recommend 500-1000 mg/day. For more, see Vitamins in Schizophrenia.

Yale Psychiatrist Protests Pharmaceutical Industry's Pushing of Psychiatric Medications: The rapid growth in sales of psychotropic medications during the late 1980s and 1990s, reaching $20 billion/year, including the increased use of seritonin reuptake inhibitors for depression, and atypical antipsychotics for schizophrenia (and stimulants for children and adults). Recently, some of the therapeutic claims for these medications have been challenged, and under-appreciated risks have turned out to be significant liabilities. Drug manufacturers increasingly dominate clinical trials research and evidence suggests that study designs and data presentations have been slanted to show products in a favorable light while unfavorable data were suppressed. The extensive financial ties between the pharmaceutical industry and academic researchers, professional associations, and consumer groups has discouraged expression of critical views. The narrow legal mandate of the FDA to evaluate the safety and efficacy of new drugs only in comparison to placebo (rather than in comparison to other treatments) has limited its contribution. In the absence of reliable, impartial research on the risk and benefits of psychotropic medications, both before and after they are brought to market, pharmacy benefits management cannot achieve its goal of maximizing health care benefits per dollar spent. Further institutional support is needed for independent research, either conducted or funded by the federal government. The growth of psychopharmacology in the 1990s: Evidence-based practice or irrational exuberance. Rosenheck R. Yale Medical School. Int J Law Psychiatry. 2005 Aug 25. Ed: Add to this the pushing of drugs in direct to consumer advertising, the widespread bribing of policians and political parties by the drug pushers, and the conflict of interest of psychiatrists who make money by prescribing drugs. Even add school teachers who would rather have their students drugged on stimulants so they will sit in their chairs rather than change the way the classrooms are run by eliminating "open classroom" features.  In my experience, most patients who come to me are being overmedicated.  It's even worse with children. For more, see The Corruption of Psychiatry.

Short Babies at Risk for Schizophrenia: In a huge study of 719,476 Swedes from the age of 16 with 9.9 years of follow-up, there were 736 cases of schizophrenia. There was little evidence of an association between birthweight and schizophrenia (hazard ratio per kg increase in birthweight: 0.90); the HR in babies weighing <2.5 kg compared to 3.5-4.0 kg was 1.29. However, short babies were at an increased risk with 47% less schizophrenia for every 4 extra inches in length (HR per 10 cm increase in birth length: 0.53). In males, low body mass index and short height at age 18 were associated with increased risk. There is some evidence that patterns of risk in relation to fetal growth differ depending on post-natal growth patterns: the increased risk associated with low body mass index was restricted to long babies who became light adults. Cohort study of 720,000 Swedish men and women. Gunnell D, et al. Bristol, UK. Schizophr Res. 2005 Aug 24. Ed: This connection could be in part due to a vitamin D deficiency, since vitamin D supplementation in pregnancy or infancy dramatically lowers the risk of schizophrenia and vitamin D supplementation plays a role in bone formation and calcium absorption. For more, see Schizophrenia Risk Factors.

Vagal Nerve Stimulation for Depression Not Very Helpful: In a 10-week, randomized, masked trial comparing adjunctive VNS with sham treatment in 235 outpatients with nonpsychotic major depressive disorder (n = 210) or nonpsychotic, depressed phase, bipolar disorder (n = 25) who had not responded adequately to between two and six research-qualified medication trials, medications were kept stable. At 10-weeks, HRSD(24) depression score response rates were 15.2% for the active (n = 112) and 10.0% for the sham (n = 110) groups (p = .251, last observation carried forward [LOCF]). Response rates with a secondary outcome, the Inventory of Depressive Symptomatology - Self-Report (IDS-SR(30)), were 17.0% (active) and 7.3% (sham) (p = .032, LOCF). VNS was well tolerated; 1% left the study because of adverse events. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Rush AJ, et al.  University of Texas Southwestern Medical Center, Dallas. . Biol Psychiatry. 2005 Sep 1;58(5):347-54. v

Exercise Lowers Colon Cancer in Men: As part of a 4-year DB PC study of 930 patients with one or more recently resected colorectal adenoma, researchers found no association between measures of physical activity or BMI and tubular adenomas or hyperplastic polyps. However, among men, there were strong inverse associations between physical activity and advanced neoplastic polyps. Compared with men whose total daily energy expenditure was in the lowest tertile, those in the highest tertile had a risk ratio of 0.35; there was no similar reduction observed among women. The association of physical activity and body mass index with the risk of large bowel polyps. Wallace K, et al. .. Cancer Epidemiol Biomarkers Prev. 2005 Sep;14(9):2082-6. v

Perphenazine (Trilafon) Does Just as Well as Atypical Anti-Psychotics in Huge Study: In a huge 18-month DB PC study of 1493 patients with schizophrenia at 57 U.S. sites, patients received either olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the FDA. Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. The efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine, while a little more effective, was associated with greater weight gain and increases in measures of glucose and lipid metabolism. Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia. Lieberman JA, et al. N Engl J Med. 2005 Sep 19. v

Junk Psychiatry from the Journal of Psychopharmacology: In yet another misleading open trial, Italian psychiatrists used  mirtazapine on 44 adults with generalized anxiety disorder.  The claimed that they were studying the efficacy of mirtazapine, despite the fact that it is impossible to study efficacy with open trials in psychiatric disorders due to the extreme amount of bias that creeps into the large majority of studies. They claimed to have found a very high "response rate" in patients on mirtazapine, suggesting that these patients were responding to mirtazazepine and that in some way they had shown that mirtazazepine was effective. They claimed that their study "supports the notion that mirtazapine is an efficacious," which is absolutely untrue. Of course, virtually every anti-depressant ever researched for generalized anxiety disorder in double-blind research helps, but this is no excuse for publishing a worthless report.  With the horrendous record of open trials misleading thousands of psychiatrists in the recent past in the gabapentin and topiramate bipolar scandals, you would think that academic journals would stop their slavish publishing of phony open trials.  It is extremely likely that this study was financed by the manufacturer and that the journal receives advertising income from the manufacturer. Mirtazapine treatment of Generalized Anxiety Disorder: a fixed dose, open label study. Gambi F, et al. University 'G. D'Annunzio' of Chieti, Italy. . J Psychopharmacol. 2005 Sep;19(5):483-487.  For more, see Open Trials under Irresponsible Medicine.

Venlafaxine (Effexor) and Fluoxetine (Prozac) Only a Little Better than Placebo: In a 6-week DB PC study of 308 outpatients with depression, venlafaxine-immediate release (75-225mg/day; n=102) did a little better than fluoxetine (20-60mg/day; n=104), which did a little better than placebo (n=102). Remission (defined as HAM-D7) rates were 32%, 28%, and 22% for venlafaxine, fluoxetine, and placebo. Few differences between the active treatments attained statistical significance. Side-effects were somewhat less with fluoxetine. A double-blind, placebo-controlled comparison of venlafaxine and fluoxetine treatment in depressed outpatients. Nemeroff CB, Thase ME. Emory University. J Psychiatr Res. 2005 Sep 12. v

Fluvoxamine Helped Elderly Depressed Better than Sertraline: In a 7-week DB study of 93 hospitalized depressed adults over age 59 with major depression, sertraline (150 mg daily) did not do as well as fluvoxamine (200 mg daily) with 56% improving while on sertraline vs.72% on fluvoxamine (P = 0.007). Since there was no placebo control group, one cannot conclude that sertraline was of any value. Sertraline Versus Fluvoxamine in the Treatment of Elderly Patients With Major Depression: A Double-blind, Randomized Trial. Rossini D, et al. University of Bologna, Italy. J Clin Psychopharmacol. 2005 Oct;25(5):471-475. v

First Generation Anti-Psychotics Slightly Safer Than Second for Stroke, Especially Safer than Risperdal: Using the regional database of prescriptions reimbursed by the National Health Service of all patients aged 65 or older who received antipsychotic prescriptions during 2001, strokes occurred in 3.31% of elderly exclusively exposed to SGAs and 2.37% exposed to first-generation antipsychotics. Only risperidone showed a significant risk of 43% (OR = 1.43). Second-Generation Antipsychotics and Risk of Cerebrovascular Accidents in the Elderly. Percudani M, et al. University of Verona, Italy. J Clin Psychopharmacol. 2005 Oct;25(5):468-470. For more, see Strokes and Antipsychotics.

Aspirin+Paracetamol+Caffeine Better than Individual Components: In a huge 1743-patient DB PC study, two tablets of the fixed combination of 250 mg acetylsalicylic acid (ASA) + 200 mg paracetamol + 50 mg caffeine did better than two tablets of 250 mg ASA + 200 mg paracetamol, two tablets of 500 mg ASA, two tablets of 500 mg paracetamol, two tablets of 50 mg caffeine, or placebo in patients who were used to treating their episodic tension-type headache or migraine attacks with non-prescription analgesics. For 'time to 50% pain relief', the fixed combination of ASA, paracetamol and caffeine was superior to the combination without caffeine (P = 0.0181), the mono-substances ASA (P = 0.0398), paracetamol (P = 0.0016), caffeine (P < 0.0001) and placebo (P < 0.0001). All active treatments except caffeine differed significantly (P < 0.0001) from placebo. The fixed combination of acetylsalicylic acid, paracetamol and caffeine is more effective than single substances and dual combination for the treatment of headache: a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study. Diener H, et al. University of Essen, Germany. Cephalalgia. 2005 Oct;25(10):776-87. v

St. John's Wort Found Effective Once Again: In a 12-week DB PC study of St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo with 135 adults with major depression, the HAMD-17 depression scores dropped the most in the St John's wort group ( 10.2 vs. 12.6 placebo and 13.3 fluoxetine). There was also a trend toward higher rates of remission (HAMD-17 <8) in the St John's wort group (38%) compared with the fluoxetine group (30%) and the placebo group (21%). A Double-blind, Randomized Trial of St John's Wort, Fluoxetine, and Placebo in Major Depressive Disorder. Fava M, et al. MGH-Harvard. J Clin Psychopharmacol. 2005 Oct;25(5):441-447. For more, see St. John's Wort for Depression.

Opioid Pain Relievers No Value for Pain is Depressed, Anxious, Neurotic: Comprised mainly of depression, anxiety, and high neuroticism, psychopathology diminishes the effectiveness of many chronic pain treatments. In a DB PC crossover study of discogenic low back pain in 60 patients not on opioids, a single IV dose of morphine's pain reduction minus placebo pain reduction revealed a 59% total pain relief in the low depression-anxiety-neurotic group vs. 21% in the high group, P=.0001. High levels of psychopathology have markedly diminished opioid analgesia in patients with discogenic low back pain. The association between negative affect and opioid analgesia in patients with discogenic low back pain. Wasan AD, et al. Brigham and Women's-Harvard. Ed: The doping of America by pain doctors is intense.  In rural Pennsylvania, huge amounts of easily obtained narcotic pills are being abused by pain patients hooked by their doctors and incredible numbers of young people are becoming narcotic addicts when they obtain these pills on the street to get high at parties. An 80 mg oxycontin pill costs $7 at the pharmacy and sells for $60 on the street.  Thus, a patient selling his month's prescription on the street can make over $3,000 a month in profit from just 60 pills.  Imagine the temptation to sell one's pills when you are trying to exist on a total of $600 per month disability or less.  One of my patients reported being followed by pushers out of the department store where she worked when they overheard that she had back pain. For more, see Pain.

Orthostatic Hypotension Remedy: In a large, but low quality retrospective study of 399 patients with orthostatic hypotension by the manufacturer of Korodin Herz-Kreislauf-Tropfen, a herbal drug containing D-camphor (CAS 76-22-2; 2.5 %) and a liquid extract of fresh hawthorn berries (97.3%), which has been used since many years for the treatment of orthostatic hypotension, the adjusted odds ratio for improvement was 5.6, the adjusted mean increase of the systolic blood pressure the 2-fold compared to the control group of 91 patients threated with other remedies. The difference was highly significant and did not depend on age or initial blood pressure. In the test group two adverse events were observed which had no relation to the medication. Efficacy and safety of a herbal drug containing hawthorn berries and D-camphor in hypotension and orthostatic circulatory disorders/results of a retrospective epidemiologic cohort study. Hempel B, et al. Robugen GmbH Pharmazeutische Fabrik, Esslingen-Zell. Arzneimittelforschung. 2005;55(8):443-50. Ed: While the hawthorn is available, I found no such combination available except in Germany.  Also, increasing systolic blood pressure doesn't sound good. v

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

modern-psychiatry.com