Dec. '05
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COMT Dopamine Gene Variant Increases Risk of Schizophrenia: Many different genetic abnormalities can cause schizophrenia. In a new study by Allan Reiss et al of Stanford University, children who possess one copy of an abnormal gene variant for the COMT gene on chromosome 22 are much more likely to develop schizophrenia. This deletion of one copy of the normally available two healthy genes occurs in 1 of 4,000 births. 30% of 24 children followed eventually developed schizophrenia. These children were also prone to heart disease, cleft palate, and learning disorders. The COMT gene produces a protein that breaks down dopamine. It has two normal variant, one stronger at breaking down dopamine than the other. Children with one abnormal variant and the normal weak variant were the most affected with greater shrinkage of the prefrontal brain. The defect means that these individuals have too much dopamine. Nature Neuroscience 11/05. For more, see Genetics in Schizophrenia.

Anti-Depressants Don't Increase Risk of Bipolar Mania: Previous research showed that bipolar-1 patients on medicine to block mania were at no increased risk of developing mania if given an anti-depressant as well.  These patients actually did better, since depression is the major difficulty in bipolar illness, occurring four times more often than mania. New research, presented by Christine Truman at the New Clinical Drug Evaluation Unit sponsored by NIMH found that the rate of switches into mania during 511 episodes of major depression in 125 patients with bipolar II disorders occurred no more often in the eight weeks after treatment with anti-depressants compared to the eight weeks before the onset of the major depressive episode.  Also, there was no difference in the 186 major depressive episodes treated with anti-depressants vs. the 325 episodes treated without anti-depressants. Clin Psych News 11-0/5 p. 28. For more, see Bipolar Depression

Two Different Gene Variants Linked to Dyslexia: Two chromosome-6 genes which aid the neuronal migration in the developing brain, when abnormal, can each cause dyslexia according to four recent studies. Jeffrey Gruen et al of Yale studies 536 parents and siblings in 153 families with at least one dyslexic and found only those with an abnormal variant of the DCDC2 gene had dyslexia. Proceedings of the Natl Acad Sci 11/05. Juha Kere of the Karolinska Institute in Stockholm found similar results in 111 German families. Amer J Human Genetics 11/05. Two English studies found instead abnormalities in the KIAA0319 gene. Julie Williams of Cardiff University studied 233 dyslexics and 273 normals (Amer J Human Genetics) while a similar University of Oxford study by Anthony Monaco confirmed those results. v

Avonex Not Cost-Effective in MS; Very Slight Benefit: Interferon beta-Ia (Avonex) 30 microg, intramuscular (i.m.), once weekly is somewhat effective in delaying clinically definite multiple sclerosis (CDMS) following a single demyelinating event (SDE). The incremental cost of Avonex per quality-adjusted monosymptomatic life years gained was $227586 and $189286 from Ministry of Health and societal perspectives, respectively. Economic evaluation of Avonex (interferon beta-Ia) in patients following a single demyelinating event. Iskedjian M, et al. PharmIdeas Research and Consulting Inc., Oakville, Ontario, Canada. . Mult Scler. 2005 Oct;11(5):542-51.

Depression and Other Psychiatric Difficulty Much Higher in MS: In a controlled epidemiological study of 50 outpatients with clinically definite relapsing-remitting MS and 50 healthy matched controls, MS patients reported a 217% higher prevalence of psychiatric disorders with 46% suffering from major depressive disorder. The risk of suffering from any non-mood psychiatric disorder was also higher in MS patients than in controls (odds ratio 2.67). Risk factors for depression were female sex and severity of disability, but not therapy with interferon beta or longer duration of illness. Psychiatric disorders and depression in multiple sclerosis outpatients: impact of disability and interferon beta therapy. Galeazzi GM, et al. University of Modena and Reggio Emilia, Italy. . Neurol Sci. 2005 Oct;26(4):255-62.

Suicide Increased 112% in MS: In a linkage study using the Danish Multiple Sclerosis Registry and the Cause of Death Registry of all 10,174 persons with multiple sclerosis from 1953 to 1996 with follow up to January 1999, 115 adults had taken their own lives, whereas the expected number of suicides was only 54.2. The increased risk was particularly high during the first year after diagnosis (SMR = 3.15). The excess suicide risk has not declined since 1953. Suicide among Danes with multiple sclerosis. Bronnum-Hansen H, et al. Copenhagen K, Denmark. .  J Neurol Neurosurg Psychiatry. 2005 Oct;76(10):1457-9.

Vitamin K Helped Prevent Animal Model of MS: Vitamin K(2) is widely used for hypoprothrombinemia and osteoporosis in Japan. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), VK2 helped although it was not effective when given after the onset. Inflammatory cellular infiltration and the expression of both MHC class II and inducible nitric oxide synthase (iNOS) were reduced in the spinal cords of VK2-treated rats with EAE. The inhibitory effect of VK2 on the iNOS expression in glial cells was also observed in vitro. Considering the long use of VK2  is without noticeable untoward effects, it may be applicable to the patients with MS. Vitamin K(2) ameliorates experimental autoimmune encephalomyelitis in Lewis rats. Moriya M, et al. Osaka University, Japan. J Neuroimmunol. 2005 Sep 5

Relatives of MS Patients At Risk: Using a nationwide registers, the risks of MS in a population-based cohort of 19,615 first-degree relatives of 8,205 Danish MS patients followed for 30 years, first-degree relatives had a 610% increased risk of MS (n = 90) compared with the background population. The familial excess lifetime risk was found to be 2.5%. This percentage should be added to a sporadic absolute risk in the general population of 0.5% in women and 0.3% for men. Spouses of MS patients did not experience an increased risk of MS, suggesting no major role for environmental factors acting in adulthood. Familial risk of multiple sclerosis: a nationwide cohort study. Nielsen NM, et al. Copenhagen, Denmark. Am J Epidemiol. 2005 Oct 15;162(8):774-8.

Vitamin D Might Help MS More Than Avonex: 15 patients with relapsing-remitting MS and at least one clinical relapse within the previous 12 months received oral calcitriol (target dose: 2.5 microg/d) for 48 weeks. Dietary calcium was restricted to 800 mg/d. The on-study exacerbation rate (27%) was less than baseline. Four patients experienced five clinical relapses but only one patient worsened by >1 EDSS point. Brain MRI revealed enhancing lesions in five patients at baseline (33%) and in four (29%) at both 24 and 48 weeks. A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. Wingerchuk DM, et al. Mayo Clinic, Scottsdale, Arizona. . J Neurol Neurosurg Psychiatry. 2005 Sep;76(9):1294-6. For more, see Multiple Sclerosis.

Osteoporosis More Common in Depressed Anorexics: Forty-five Polish anorexic girls aged 13-23 yr, matched by age, the 14 with comorbid depression had lower BMD than those with AN alone (LS Z-scores, -2.6 vs. -1.7; P = 0.02). Quantitative assessment of depression correlated independently with total body BMD (r = -0.4; P < 0.05) and LS BMD (r = -0.6; P < 0.001). Depression in anorexia nervosa: a risk factor for osteoporosis. Konstantynowicz J, et al. University Children's Hospital, Bialystok, Poland . J Clin Endocrinol Metab. 2005 Sep;90(9):5382-5.

Peptide YY May Play Role in Anorexia: PYY is an intestinally derived anorexigen that acts via the Y2 receptor, and Y2 receptor deletion in rodents increases bone formation. Known regulators of bone turnover such as growth hormone (GH), cortisol and estrogen explain only a fraction of the variability in bone turnover marker levels. In 23 AN girls and 21 healthy adolescents 12-18 yr old, AN girls had higher PYY levels compared with controls (17.8 vs. 4.8 pg/ml, P < 0.0001). Predictors of log PYY were nutritional markers including BMI (r = -0.62, P < 0.0001), fat mass (r = -0.55, P = 0.0003) and REE (r -0.51, P = 0.0006), and hormones including GH (r = 0.38, P = 0.004) and T3 (r = -0.59, P = 0.0001). BMI, fat mass, REE, GH and T3 explained 68% of the variability of log PYY. Log PYY predicted % calories from fat (r = -0.56, P = 0.0002), and independently predicted osteocalcin (r = -0.45, P = 0.003), bone specific alkaline phosphatase (r = -0.46, P = 0.003), N-telopeptide/creatinine (r = -0.55, P = 0.0003) and deoxypyridinoline/creatinine (r = -0.52, P = 0.001) on regression modeling. Elevated PYY may contribute to reduced intake and decreased bone turnover in AN. Elevated Peptide YY Levels in Adolescent Girls with Anorexia Nervosa. Misra M, et al. MGH-Harvard. J Clin Endocrinol Metab. 2005 Nov 8. For more, see Anorexia.

Rip-Off Modified Fish Oil "Drug:" The drug manufacturer Reliant is now selling ethyl DHA and EPA as an expensive medication (Omacor) costing $131 per month for four capsules (Med Letter 11/7/05).  One capsule per day reduced mortality by 41% in victims of recent heart attacks.  However, there is absolutely no research showing the ethyl DHA and EPA is superior to the regular DHA and EPA found in unmodified fish oil, which costs only $5 per month for four capsules (Wal-Mart 12/05).  It is simply another raid by drug manufacturers on the American consumer with the willing assistance of the Bush administration. For more, see Fish for Coronary Heart Disease.

Perivascular Space Enlargement Increased with Worse Mental Ability: The abnormal channels are known as enlarged perivascular spaces, rare in young, healthy adults, are very common in older people, and in conditions such as diabetes, Parkinson's disease, and high blood pressure. The enlarged perivascular spaces might be an indicator of overall brain shrinkage, or they might reflect specific damage to brain tissue around blood vessels. In 100 healthy elderly males, more enlarged perivascular spaces was linked to worse mental ability. Joanna Wardlaw et al, Edinburgh University. J Neurol NeuroSurg Psychiatry 12/05. For more, see Risk Factors for Alzheimer's.

Calcium Linked to Lower Diabetes Risk: Data from 10,066 women over age 44 in the Women's Health Study who were free of cardiovascular disease, cancer, or diabetes and who never used postmenopausal hormones compared different dietary intake levels of calcium and vitamin D. In age- and calorie-adjusted analyses, higher intakes of total, dietary, and supplemental calcium were significantly and inversely associated with the prevalence of metabolic syndrome. After further adjusting for smoking status, exercise, alcohol intake, multivitamin use, and parental history of myocardial infarction before age 60 years, the ORs of having the metabolic syndrome for increasing quintiles of total calcium intake were 1.00 (reference), 0.82, 0.84, 0.70, and 0.64 (P<0.0001). This association was not appreciably altered by additional adjustment for other dietary factors or total vitamin D intake. Neither total (P = 0.13) nor supplemental (P = 0.45) vitamin D was significantly associated with metabolic syndrome. Strong relations between intakes of dairy products and metabolic syndrome were observed. After adjustment for lifestyle and dietary factors, the multivariable ORs comparing highest with lowest intake categories were 0.66 (P <0.0001) for total dairy products and 0.85 (P = 0.05) for total milk intake. Dietary Calcium, Vitamin D, and the Prevalence of Metabolic Syndrome in Middle-Aged and Older U.S. Women. Liu S, et al. Harvard. . Diabetes Care 2005 Dec;28(12):2926-2932. Ed: Vitamin D supplements are hard to find. Few women in this study took my recommended 1000 IU a day. From, this dose costs only 2 cents a day. 

Vitamin D: Low in New Cases of Diabetes Type 1: Supplementation Advocated: An epidemiological retrospective study and a recent prospective study from Finland have both concluded that vitamin D (3) supplementation at birth protects individuals from type 1 diabetes later in life. Moreover, it is thought that vitamin D (3) supplementation, in particular its activated form, 1,25-dihydroxyvitamin D (3) [1,25-(OH) (2)D (3)], may act as an immunomodulator, facilitating the shift from a Th1 to a Th2 immune response. In a study of 88 newly diagnosed patients with type 1 diabetes and 57 matched controls, levels of both 25OHD (3) and 1,25-(OH) (2)D (3) were significantly lower in patients compared to controls (p < 0.01 and p < 0.03). Vitamin D (3) may be an important pathogenic factor in type 1 diabetes independent of geographical latitude, and that its supplementation should be considered not only at birth, but also at diagnosis of type 1 diabetes with the aim of favouring a Th2 immune response and protecting residual beta cells from further destruction. Low Levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in Patients with Newly Diagnosed Type 1 Diabetes. Pozzilli P, et al. University Campus Bio Medico. Horm Metab Res 2005 Nov;37(11):680-3. For more, see Risk Factors for Diabetes.

Gingivitis: Higher Vitamin D Helps a Little: In 6700 never smokers ages 13-90 from the third National Health and Nutrition Examination Survey, when adjusted for subject- and site-specific covariates included age, sex, race-ethnicity, income, body mass index, diabetes, use of oral contraceptives and hormone replacement therapy among women, intake of vitamin C, missing teeth, full crown coverage, presence of calculus, frequency of dental visits, and dental examiner and survey phase, compared to those in the lowest 25(OH)D quintile, the highest 25(OH)D quintile were 20% less likely to bleed on gingival probing (P< 0.001). The association appeared to be linear over the entire 25(OH)D range, was consistent across racial or ethnic groups, and was similar among men and women as well as among users and nonusers of vitamin and mineral supplements. Association between serum concentrations of 25-hydroxyvitamin D and gingival inflammation. Dietrich T, et al. Boston University. . Am J Clin Nutr 2005 Sep;82(3):575-80. Ed: Vitamin D is great.  Everyone should take at least 1000 IU per day, which costs $0.02/day from For more, see Dental.

Pomegranate Juice Helped Mice: Richard Hartman et al of Loma Linda University found that feeding mice who were genetically prone to develop an Alzheimer's-like disease the equivalent of 1-2 cups per day of pomegranate juice from young adulthood reduced the build up of beta-amyloid plaques in their brains. The mice did much better in maze and other tests than mice given sugar-water supplements. Antioxidants were thought to be preventing the damage. Sci News 2/3/05. Ed: I like purple grape juice. It's a lot cheaper. For more, see Diet and Alzheimer's.

Head Trauma Linked to Increased ADHD: In a 1-year follow-up of 103 children ages 3-14 with closed head trauma, 15% developed secondary ADHD. Some showed personality changes. Max JE, et al. UC, San Diego. J Am Acad Child Adolesc Psychiatry 2005;44-1041-9. For more, see Causes of ADHD.

DNA Damage Caused by Methylphenidate; May Cause Cancer!:  In 12 children on methylphenidate, peripheral blood lymphocytes were obtained before and three months after starting the drug. In all participants, treatment caused a significant 3, 4.3 and 2.4-fold increase in chromosome aberrations, sister chromatid exchanges and micronuclei frequencies, respectively (P=0.000 in all cases). There is a well-documented relationship between elevated frequencies of chromosome aberrations and increased cancer risk. Cytogenetic effects in children treated with methylphenidate. El-Zein RA, et al. University of Texas M.D. Anderson Cancer Center. Cancer Lett 2005 Dec 18;230(2):284-91.

Tonsillectomy Helped ADHD: In a prospective study of 52 children, ages 2.5-18 with obstructive sleep apnea syndrome (OSAS), adenotonsillectomy was perfomred if the results of polysomnography showed an obstructive apnea/hypopnea index (AHI) of 5 or greater. Preoperative Behavior Assessment System for Children (BASC) t scores for all behavioral scales and composites averaged greater than 50. After surgery, improvement occurred in aggression, atypicality, depression, hyperactivity, and somatization (p </= .001). Age, ethnicity, parental education, parental income, severity of OSAS, sex, and AHI were not correlated with changes in scores. Child behavior after adenotonsillectomy for obstructive sleep apnea syndrome. Mitchell RB, et al. University of New Mexico. Ed: This is exciting. Two studies has shown that snoring problems often predate ADHD. Perhaps, CPAP may also help for a much lower cost. Perhaps melatonin might decrease OSAS damage, as it does for many types of brain damage in animal studies. For more, see ADHD Treatment.

Clonidine Not as Good as Suboxone for Teens: In a 28-day DB study of 36 teens ages 13-18 with opioid dependence, 72% of Suboxone, but only 39% of clonidine patients stayed in treatment. In addition, 61% of Suboxone but only 5% of clonidine patients participated in a naltrexone phoas requiring 3 negative urines within one week. Marsch LA, et al. Univ Vermont. Arch Gen Psychiatry 2005;62:1157-64. For more, see Suboxone.

Irritable Bowel Syndrome Helped by Melatonin: In a DB PC crossover study of 17 females with IBS with 8 weeks each of either melatonin or placebo and a four week washout in between melatonin 3 mg a night led to IBS scores improving (3.9) better than with placebo (1.3, P = 0.037). Those achieving mild-to-excellent improvement in IBS symptoms were melatonin 88% vs. placebo 47%, (P = 0.04). The changes in mean sleep, anxiety, and depression scores were similar with either melatonin or placebo. Melatonin improves bowel symptoms in female patients with irritable bowel syndrome: a double-blind placebo-controlled study. Lu WZ, et al.  National University of  Singapore . Aliment Pharmacol Ther. 2005 Nov 15;22(10):927-34. For more, see Other Benefits of Melatonin.

Vitamin D Reduced Falling in Elderly: In a 2-year DB PC study of 625 residents (mean age 83.4) with serum 25-hydroxyvitamin D levels between 25 and 90 nmol/L, i.e. not deficient, vitamin D supplementation (ergocalciferol, initially 10,000 IU given once weekly and then 1,000 IU daily) or placebo for 2 years. All received 600 mg of calcium daily as calcium carbonate. In intention-to-treat analysis, the incident rate ratio for falling was 0.73 with vitamin D was significant. The odds ratio for ever falling was 0.82 and for ever fracturing was 0.69, both just short of significance. Those who took at least half the prescribed capsules (n=540), had an incident rate ratio for falls of 0.63, a significant odds ratio (OR) for ever falling of 0.), and an OR for ever fracturing of 0.68. Should older people in residential care receive vitamin d to prevent falls? Results of a randomized trial. Flicker L, et al. University of  Western Australia, Perth, Australia. J Am Geriatr Soc. 2005 Nov;53(11):1881-8. For more, see Vitamin D.

Helped Normals in DB: Omega-3 Help Mood and Attention in Normal Adults: In a 35-day DB PC study of healthy adults, the mood profile was improved after Omega-3 with increased vigor and reduced anger, anxiety and depression states. This was associated with an effect on reactivity with a reduction of reaction time. The latency of EMG activation was concomitantly. Omega-3 supplementation is associated with an improvement of attentional and physiological functions, particularly those involving complex cortical processing. Cognitive and physiological effects of Omega-3 polyunsaturated fatty acid supplementation in healthy subjects. Fontani G, et al.  University of Siena, Italy. Eur J Clin Invest 2005; 35 (11): 691-699. For more, see Omega-3 and Fish Oil for Depression.

Duloxetine (Cymbalta) Withdrawal Side-Effect: In a pooled analysis of 6 short-term treatment studies, in which treatment was stopped abruptly, reported problems were 44.3% and 22.9% of duloxetine- and placebo-treated patients (p<0.05). The abrupt discontinuation of duloxetine compared with placebo caused dizziness (12.4%), nausea (5.9%), headache (5.3%), paresthesia (2.9%), vomiting (2.4%), irritability (2.4%), and nightmares (2.0%). The majority of these (65.0%) resolved within 7 days. More occurred with high dose 120 mg/day. Extended treatment with duloxetine beyond 8-9 weeks did not appear to be associated with an increased incidence or severity of DEAEs. Symptoms following abrupt discontinuation of duloxetine treatment in patients with major depressive disorder. Perahia DG, et al. Lilly Co. Gordon Hospital London, UK. J Affect Disord. 2005 Oct 30. Ed: These withdrawal effects may not be more than average for anti-depressants, which should be gradually withdrawn over a couple weeks at least. For more, see Cymbalta.

Fish Oil Reduced Arrhythmias in Defibrillator Patients: In a 12-month DB PC study of 402 patients with implanted cardioverter/defibrillators (ICDs), the noncompliance rate was high (35% in both groups). The fish oil supplement showed a trend toward a prolonged time to the first ICD event (VT or VF) or of death from any cause (risk reduction of 28%; P=0.057). When therapies for probable episodes of VT or VF were included, the risk reduction became significant at 31%; P=0.033. For those who stayed on protocol for at least 11 months, the antiarrhythmic benefit of fish oil was improved for those with confirmed events (risk reduction of 38%; P=0.034). Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake. Leaf A, et al. Harvard. . Circulation. 2005 Nov 1;112(18):2762-8. For more, see Fish Oil for the Heart.

Leucine Helped Power in Endurance Canoeists: Branched chain amino acids (BCAA), particularly leucine, might help endurance and strength/power performance. In a 6-week DB PC study of 13 competitive outrigger canoeists, L-leucine (45 mg/kg resulted in significantly increased power [6.7 v. 6.0 work/kg]. Rowing time significantly increased [77.6-88.3 min] and average RPE significantly decreased [14.5-12.9] with leucine supplementation while these variables were unchanged with the placebo. Leucine supplementation had no effect on the plasma tryptophan to BCAA ratio, HR or anthropometric variables. Six weeks' dietary leucine supplementation significantly improved endurance performance and upper body power in outrigger canoeists without significant change in the plasma ratio of tryptophan to BCAA. Effects of dietary leucine supplementation on exercise performance. Crowe MJ, et al. James Cook University, Australia, .. Eur J Appl Physiol. 2005 Oct 29;:1-9 v

Oct. 05 ADHD Review: Dopamine D4 and D5 Receptor, Dopamine and Serotonin Transporter and Synaptosomal Protein Gene Polymorphisms:  ADHD is highly heritable. Meta-analyses or pooled data analyses support association between ADHD and polymorphisms in DRD4, DRD5 and SLC6A3 which encode dopamine D4 and D5 receptors and the dopamine transporter, respectively. A weaker body of evidence also supports associations with SNAP-25 (synaptosomal-associated protein, 25 kDa) and SLC6A4 (serotonin transporter). The genetics of attention deficit hyperactivity disorder. Thapar A, et al. Cardiff University, UK . Hum Mol Genet 2005 Oct 15;14 Spec No. 2:R275-82. Ed: There may be dozens of different polymorphisms with each of the affected genes. Some of these may be harmless, and others harmful to varying degrees. For more, see ADHD Genetics.

Blood Pressure Meds Cut Headaches 33%: In a meta-analysis the 94 DB studies of 2-14 weeks including 23,599 adults of thiazides, {beta} blockers, angiotensin converting enzyme inhibitors, or angiotensin II receptor antagonists for hypertension, active treatment lowered systolic and diastolic blood pressures by 9.4 and 5.5 mm Hg compared to placebo. Those on the antihypertensive drugs were a third less likely to report headache than on placebo (8% v 12%; odds ratio 0.67, P < 0.001). {beta} blockers were better at preventing headache than the other types of drug (odds ratio 0.47). Prevalence of headache went down by an extra 13% (relative to placebo) for every extra 5 mm Hg reduction in diastolic blood pressure.  Law et al. Headaches and the treatment of blood pressure: results from a meta-analysis of 94 randomized placebo controlled trials with 24 000 participants. Circulation 2005;112: 2301-6. For more, see Headaches.

Car Crashes Tripled for Driver's When High: A French nationwide study of over 10,000 fatal accidents for which blood levels were available has found that 3% of driver's were high on marijuana and that they were 3 times more likely to be involved in an auto accident while high after controlling for alcohol consumption compared to drivers without drugs or alcohol in their system. Alcohol was still several times more dangerous, causing 29% of all fatal car crashes. Cannabis intoxication and fatal road crashes in France: population based case-control study. Bernard Laumon, et al. Brit Med J 2005;331:1371 (10 December). For more, see Marijuana.

Lexapro Said to Help Social Anxiety Disorder in Bogus Study: In a poorly designed DB PC study, intentionally designed to make Lexapro look good, 371 patients with a primary diagnosis of social anxiety disorder who had received 12 weeks of Lexapro in an open-label trial, were then assigned to either stay of Lexapro 10-20 mg/day or to have the medicine abruptly withdrawn and given look-alike placebos. The risk of relapse was 180% higher for placebo than for Lexapro (p < .001), resulting in fewer Lexapro relapses (22% vs. 50%). A 24-week randomized, double-blind, placebo-controlled study of escitalopram for the prevention of generalized social anxiety disorder. Montgomery SA, et al. Imperial College, London, U.K. and others. J Clin Psychiatry. 2005 Oct;66(10):1270-8. Ed: This study must have been designed by the manufacturer. Lexapro has a 26% side-effect discontinuation rate according to the manufacturer’s insert in the PDR. This study avoids those cases.  It also avoids those who didn’t improve while on Lexapro. These two groups totaled 34% in this study which started with 517 patients, 149 of whom had side-effects or failed to improve while on Lexapro. It also subjects patients to abrupt withdrawal, which is known to have a harmful effect with many antidepressants.  Thus, an additional unknown percentage of the placebo relapses is almost certainly due to drug withdrawal. Only a drug dealer and his accomplices could like this study design. For more, see Social Anxiety Disorder.

Atypical Anti-Psychotic Inferior to Fluoxetine or Nortriptyline for SSRI and Nortriptyline Failures: In an 8 week DB study of 500 patients, who had failed to respond to an SSRI and then also failed to respond to a trial of nortriptyline during an open-label lead-in phase, these patients were randomly assigned to 1 of 4 treatment groups: olanzapine (6-12 mg/day) plus fluoxetine (25-50 mg/day) combination, olanzapine alone, fluoxetine, or nortriptyline (25-175 mg/day). MADRS depression scores decreased by 8.7 points from baseline (28.5) for the olanzapine/fluoxetine combination, 7.0 points for olanzapine alone (p = .08), 8.5 for fluoxetine alone (p = .84), and 7.5 for nortriptyline (p = .30), with no significant differences among the therapies. A post hoc analysis of a subgroup of patients who had an SSRI treatment failure during their current MDD episode (N = 314) revealed that the olanzapine/fluoxetine combination group had a significantly (p = .005) greater decrease in MADRS scores than the olanzapine group. Olanzapine/Fluoxetine Combination for Treatment-Resistant Depression: A Controlled Study of SSRI and Nortriptyline Resistance. Shelton RC, et al. Vanderbilt University and Lilly Drug Company. J Clin Psychiatry. 2005 Oct;66(10):1289-97. Ed: It appears that atypical anti-psychotics are a waste of money in treating treatment resistant depression, even when compared to using the medication with which the patients had been resistant.  Switching to bupropion, an MAO inhibitor or adding lithium, l-thyroxine, and/or folic acid might all have done better. For more, see Atypicals for Depression