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Collaborative Care of Elderly Depression Helped: In a very large 12-month random-assignment study of 1801 elderly over age 59 (average 71)with Major Depressive Disorder, those randomized to the Improving Mood: Promoting Access to Collaborative Treatment (IMPACT) intervention compared to a control group receiving usual care experienced significantly better physical functioning at 1 year than usual-care patients. Intervention patients were also less likely to rate their health as fair or poor (37.3% vs 52.4%, P<.001). Combining both study groups, patients whose depression improved were more likely to experience improvement in physical functioning. Treatment of depression improves physical functioning in older adults. Callahan CM, Kroenke K, et al. Indiana University Center for Aging Research. J Am Geriatr Soc. 2005 Mar;53(3):367-73. For more, see Geriatric Depression. Prozac Increases Norepinephrine, Epinephrine, and Dopamine: In a study of 12 patients treated with fluoxetine for 40 days compared to 40 healthy controls, plasma norepinephrine, epinephrine and dopamine levels significantly increased after acute and chronic treatment (p < 0.001), reaching the highest concentrations on the last day. Blardi et al. University of Siena. Neuropsychobiology. 2005;51(2):72-6. v Headaches Common in Depression: In a study of 34 men and 117 women suffering from a Major Depressive Disorder, 48% reported a history of migraine and 21% reported chronic daily headaches (CHD) during this episode. Higher HAMD depression scores, female gender, and chronic depression were independently associated with migraine or CDH. Risk factors associated with migraine or chronic daily headache in out-patients with major depressive disorder. Hung CI, Wang SJ, et al. Chang Gung University, Taiwan. Acta Psychiatr Scand. 2005 Apr;111(4):310-5. For more, see Depression. Depressed with Substance Abuse More Impaired and More Suicidal: If a study of 1484 adults with a major depressive disorder, 28% reported a current substance abuse disorder. These were more likely to be men (P < .0001), to be either divorced or never married (P = .018), to have a younger age of onset of depression (P = .014), and to have a higher rate of previous suicide attempts (P = .014). They also reported greater functional impairment due to their illness (P = .0111). The presence of SUD symptoms did not alter the overall depressive symptom pattern of presentation, except that the dual-diagnosed patients had higher levels of hypersomnia (P = .006), anxious mood (P = .047), and suicidal ideation (P = .036). Substance use disorder comorbidity in major depressive disorder: an exploratory analysis of the Sequenced Treatment Alternatives to Relieve Depression cohort. Davis LL, Rush JA, et al. VA Medical Center, Tuscaloosa, AL. Compr Psychiatry. 2005 Mar-Apr;46(2):81-9. v Folic Acid and B-12 for Depression Urged: Both low folate and low vitamin B12 have been found in studies of depressive patients. An association between depression and low levels of the two vitamins is found in studies of the general population. Low plasma or serum folate has also been found in patients with recurrent mood disorders treated by lithium. A link between depression and low folate has similarly been found in patients with alcoholism. Hong Kong and Taiwan populations with traditional Chinese diets (rich in folate), including patients with major depression, have high serum folate concentrations. However, these countries have very low life time rates of major depression. Low folate levels are linked to a poor response to antidepressants, and treatment with folic acid improves response to antidepressants. High vitamin B12 status may be associated with better treatment outcome. Folate and vitamin B12 are major determinants of one-carbon metabolism, in which S-adenosylmethionine (SAM) is formed. SAM donates methyl groups that are crucial for neurological function. Increased plasma homocysteine is a functional marker of both folate and vitamin B12 deficiency. Increased homocysteine levels are found in depressive patients. In a large population study from Norway increased plasma homocysteine was associated with increased risk of depression but not anxiety. There is substantial evidence of a common decrease in serum/red blood cell folate, serum vitamin B12 and an increase in plasma homocysteine in depression. Furthermore, the MTHFR C677T polymorphism that impairs the homocysteine metabolism is overrepresented among depressive patients. The authors suggest that folic acid (800 microg daily) and vitamin B12 (1 mg daily) should be tried to improve treatment outcome in depression. Treatment of depression: time to consider folic acid and vitamin B12. Coppen A, Bolander-Gouaille C. Epsom, Surrey, UK. J Psychopharmacol. 2005 Jan;19(1):59-65. Ed: I agree with the authors. For more, see Folate for Depression. Harvard, Pittsburgh Push Modafinil (Provigil) for Drug Company Despite Study Documenting Very Little Benefit: In a multicenter 8-week DB PC study of 311 patients with major depression and only partial responses to SSRI therapy after at least 8 weeks, half were given the expensive brandname stimulant modafinil 200 mg/day, an "orphan" drug approved only for the treatment of narcolepsy. There was no significant improvement in 31-item or 17-item HAM-D depression scores, Epworth Sleepiness scores, Fatigue Severity scores, Brief Fatigue Inventory scores, or MADRS depression scores. More side-effects occurred with modafinil (nausea and jitteriness). The only significant finding favoring modafinil and only at final visit, modafinil improved patients' overall clinical condition compared with placebo on the basis of Clinical Global Impressions-Improvement scores (p = .02). The authors claim, that based on their study, "these findings suggest that modafinil is a well-tolerated and potentially effective augmenting agent for SSRI partial responders with fatigue and sleepiness." A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. Fava M, Thase ME, DeBattista C. MGH-Harvard and University of Pittsburgh. Ed: The company manufacturing modanifil has a long history of funding very brief, even single dose studies, to irresponsibly push its drug. This study actually has a good research design and found nothing. The CGI is the most unreliable of all research measures. It could easily be influenced just by the fact that patients like the little amphetamine like surge you get after taking modafinil. That doesn't mean its good for you. Harvard and the University of Pittsburgh have long histories of cranking out studies for drug companies. For more, see Modanifil and Irresponsible Medicine. Aspirin with Statins and Beta-Blockers Appear
Best for Reducing Heart Mortality in English Study: In a study of 13 029
patients with a first diagnosis of ischaemic heart disease, 2266
cases were matched to 9064 controls. Drug combinations associated with
the greatest reduction in all cause mortality were statins, aspirin,
and Having a Gun at Work for Protection Dramatically Increases the Risk of Death: Workers in 315 North Carolina gas convenience stores, grocery stores, and other locations who take weapons with them to work are three to seven times as likely to be murdered at work than workers in equivalent jobs in which weapons are prohibited, a study has found. 3% of Americans Follow Basic Health Recommendations: A study of national data has shown that only 3% of Americans followed all four of the recommended rules: no smoking (76%), maintain a normal weight (40%), eat at least 5 servings of vegetables and fruit a day (23%), and get 30 minutes of moderate to severe exercise (22%)(the exercise was often part of normal living, e.g. housecleaning, gardening, sports, walking, etc). Women, older people, European-Americans, better educated people, people in good health, and wealthier people did a little bit better in following the rules. Younger people were slightly better at maintaining a body mass index of 25 or less (Matthew Reeves, et al. Michigan State University. Archives of Internal Medicine 2005;165:854-7). For more, see Recommendations for Healthy Living. Danes, Sweded, and Swiss Feel Most Healthy: In a
study of over 22,000 Europeans over age 50, those in northern Europe are more
likely to consider themselves in good health than those in the south. According
to their subjective assessment, nearly 50% of Danish respondents and more than
40% of Swedes and Swiss consider themselves to be in very good or excellent
health. The least healthy, in their own view, are the French, German, Italian,
and Spanish, with only some 20% saying that they are in very good or excellent
health. In comparing healthcare expenditure with life expectancy, France,
Sweden, and Switzerland are examples where both are high. In the United Kingdom,
Greece, Austria, and Belgium both are low. Italy and Spain spend a smaller share
of gross domestic product on health, but have above average life expectancy. The
reverse is true of the Netherlands, Germany, and Denmark. The survey found a
strong relationship between socioeconomic status and income, on one hand, and
physical and mental health on the other. People with low education levels tended
to be 70% more likely to be physically inactive and 50% more obese. BMJ 2005;330:1044 (7 May)
Low Folate, not Low B-12, Slowed Depression Improvement on Fluoxetine
(Prozac): In a study of 110 adults with Major Depression who responded
to an 8-week trial of fluoxetine, patients with initial low folate levels
(</=2.5 ng/ml) were much more likely to experience a later onset of clinical
improvement than patients with normal levels (p=0.0028). The delayed improvement
average 1 1/2 weeks. B12 and homocysteine level status did not predict time to
clinical improvement (p>0.05). The relationship between serum folate, vitamin
B12, and homocysteine levels in major depressive disorder and the timing of
improvement with fluoxetine. Papakostas GI, Petersen T, et al. MGH-Harvard. Int
J Neuropsychopharmacol. 2005 May 9;:1-6. For much more, see Folate
and Depression. Bright Light Helped Non-Seasonal Depression: In a 5-week DB PC
study of 102 patients with non-seasonal Major Depression and all treated with
sertraline (Zoloft), those also treated with white very bright light (10.000 lx,
1 h/day) did significantly better on all measures of depression and anxiety
compared to those treated with red dim light (50 lx, 30 min/day). Martiny K,
Lunde M, et al. Hilleroed, Denmark. Adjunctive bright light in non-seasonal
major depression: results from patient-reported symptom and well-being scales. Acta
Psychiatr Scand 2005: 111: 453-459. For more, see Bright
Light for Depression. No Benefit for St. John or Sertraline in DB Partially Explained: 340
patients with Major Depression in a DB PC study of hypericum
900-1500 mg/day vs. sertraline 50-100 mg/day vs. placebo for 8 weeks with 18 added weeks for
responders found no benefit for either treatment. Effect of Hypericum perforatum (St John's wort) in major depressive
disorder: a randomized controlled trial. Hypericum Depression Trial Study Group.
JAMA 2002 Apr 10;287(14):1807-14. Ed: This was a "failed
study." Obviously, sertraline usually does better than placebo, but not in
every study. The same is true of St. John's wort. A test of blood
samples well after the study was over found that 16% of the people on placebo
actually had hypericum in their blood, suggesting that they had purchased it on
their own and were taking it despite being involved in the study. Of the
people who were supposed to be taking hypericum, 17% had none in their blood
test, suggesting that they were not taking it. All of the sertraline
patients had some sertraline in their blood. The St. John's may have helped some
of the placebo patients and those who were supposed to be taking St. John's but
didn't may not have done as well as they would have. Such patient
non-compliance increases the risk of a failed study. J
Clin Psychopharmacol. 2005 Jun;25(3):243-249. For more, see St.
John's Wort for Depression. Alcoholism Rampant in Canada; One-Third Depressed Had Alcoholism: In
a national representative sample of Canada in 2000/01, 20% of current drinkers
age 18 or older were a regular heavy drinker, an increase of 2% in four years
(p<0.001)( 29% of male and 11% of female drinkers were heavy drinkers).
Alcohol dependence, however, was nearly equal: 11.6% of male drinkers and 11.1%
of female. Among persons who have experienced a depressive episode in the year
prior to their 2000/01 interview, the prevalence of alcohol dependence was 32%
while it was just 9.5% for persons without depression. Those suffering a
depression were 260% more likely to be classified as alcohol dependent. Perceived
stress was the only factor that was consistently associated with comorbidity
among both men and women. Alcohol dependence and depression among heavy drinkers
in Canada. Lukassen J, Beaudet MP. Canadian Centre for Justice Statistics,
Ottawa, Canada. Depression Increased Heart Disease by 50%: In a nested
case-referent study within the Prospective Epidemiological Study of Myocardial
Infarction (PRIME) study of healthy middle-aged men from Belfast and France, the
baseline plasma sample from 335 future cases (angina pectoris, nonfatal
myocardial infarction, coronary death) and 670 controls were compared. After
controlling for known risk factors, depression increased the risk of future
heart disease by 50%. Contributions of Depressive Mood and Circulating
Inflammatory Markers to Coronary Heart Disease in Healthy European Men. The
Prospective Epidemiological Study of Myocardial Infarction (PRIME). Empana JP,
Sykes DH, et al. Villejuif, France. Circulation.
2005 May 2 Serotonin Transporter Gene Abnormality Makes Individuals More Depressed
from Mild Stress: In a study of 549 adult twins, individuals with 2
short alleles (SS) at the 5-HTT locus were more sensitive to the depressing
effects of stress than were those with 1 or 2 long (SL or LL) alleles. When
level of stress was examined, SS twins sometimes became depressed with two
common low-threat events while these had little impact on SL and LL genotypes.
The 5-HTT genotype did not modify the effects of stress on risk for generalized
anxiety syndrome. The interaction of stressful life events and a serotonin
transporter polymorphism in the prediction of episodes of major depression: a
replication. Kendler KS, Kuhn JW, et al. Medical College of Virginia, Richmond. Arch
Gen Psychiatry. 2005 May;62(5):529-35. Medication Helped Depression Psychotherapy Failures and Vice-Versa: In
a 12-week randomized crossover study of 140 outpatients with chronic major
depression, the rates of response and remission after 12 weeks of nefazodone (Serzone)
100-600 mg/d vs. cognitive-behavioral psychotherapy (CBP) were the same. Both
the switch from nefazodone to CBP and the switch from from CBP to nefazodone
resulted in clinically and statistically significant improvements in symptoms.
Neither the rates of response nor the rates of remission were significantly
different when the groups of completers were compared. However, the switch to
CBASP following nefazodone therapy was associated with fewer dropouts due to
side-effects, which may explain the higher intent-to-treat response rate among
those crossed over to CBP (57% vs 42%). Chronic Depression: Medication (Nefazodone)
or Psychotherapy (CBP) Is Effective When the Other Is Not. Schatzberg AF, Rush
AJ, et al. Stanford University. Arch
Gen Psychiatry. 2005 May;62(5):513-20. For more, see Serzone
and Psychotherapy. Ed: Serzone
is not my favorite, but the manufacturer apparently funded this 14-center study
including Stanford, Texas, and Harvard. It's sad to see the big name
universities constantly lining up with the brand-name drug manufacturers in
order to get the money. Breakpoint Cluster Gene Abnormalities Linked to Bipolar and Major
Depression: The breakpoint cluster region (BCR) gene is located on
chromosome 22q11, one of the most significant susceptibility loci in bipolar
disorder linkage studies. The BCR gene encodes a Rho GTPase activating protein,
which play important roles in neurite growth and axonal guidance. In a study of
Japanese patients with bipolar disorder (n = 171), major depressive disorder (n
= 329) and controls (n = 351) testing eleven single nucleotide polymorphisms (SNPs),
including a missense one (A2387G; N796S), in the genomic region of BCR, allelic
associations with bipolar disorder were observed for three SNPs, and
associations with bipolar II disorder were observed in ten SNPs including N796S
SNP (bipolar disorder, p = .0054; bipolar II disorder p = .0014). There was an
association with major depression in six SNPs. S796 allele carriers were 210%
more common in bipolar II patients (p = .0046). Furthermore, we found a stronger
evidence for association with bipolar II disorder in a multi-marker haplotype
analysis (p = .0002). The Breakpoint Cluster Region Gene on Chromosome 22q11 is
Associated with Bipolar Disorder. Hashimoto R, Okada T, et al. National Center
of Neurology and Psychiatry, Kodaira. Biol
Psychiatry. 2005 May 15;57(10):1097-102. v One Wolfram Gene Abnormal Increased Risk of Depression Hospitalization
600%: Heterozygous carriers of wolframin mutations are relatively
frequent in the population. Members of 25 Wolfram Syndrome families were tested.
Eleven had psychiatric hospitalizations and were genotyped through mutation
analysis. Eight carried the wolframin mutation transmitted in their family
(one-sided P=0.0022). All had been hospitalized for a major depression.
The relative risk of psychiatric hospitalization for depression was increased
610% for carriers of a single wolframin mutation compared to noncarriers.
Wolframin mutations and hospitalization for psychiatric illness. Swift M, Swift
RG. Disease Insight Research Foundation, Ardsley, NY, USA. Molecular
Psychiatry 26 April 2005. For more, see The
Genetics of Depression. rTMS Again as Good as ECT for Depression with Improved Memory and
Thinking Instead of Deteriorated: In a randomized study of 30 patients
with treatment-refractory non-psychotic major depression, an average of ten
treatments with either unilateral ECT or left prefrontal rTMS (repeated
Transcranial Magnetic Stimulation) were given. Treatment response was 46% for
ECT and 44% for rTMS showing a reduction of 50% or more in HAM-D depression
scores. In patients treated with rTMS, cognitive performance remained constant
or improved and memory complaints became fewer, whereas in the ECT group memory
recall deficits appeared and memory complaints remained. Distinctive
neurocognitive effects of repetitive transcranial magnetic stimulation and
electroconvulsive therapy in major depression. Schulze-Rauschenbach SC, et al.
University of Bonn, Germany. Br
J Psychiatry. 2005 May;186:410-6. For more, see rTMS
amd ECT. African-Americans More Depression: In a study of 4,275
community-dwelling persons over age 64 (62% African-Americans),
African-Americans reported approximately 60% more symptoms than
European-Americans (p<.001). The differences were larger for men than for
women. After controlling for age, sex, time, education, income, and related
interaction terms, the ethnic difference was reduced by almost half but remained
strong and increased slightly over time. Black-white differences in depressive
symptoms among older adults over time. Skarupski KA, Mendes de Leon CF, et al.
Rush Institute for Healthy Aging, Chicago. J
Gerontol B Psychol Sci Soc Sci. 2005 May;60(3):P136-42. Vitamin D 800 IU Necessary for Bone Benefit: In a review of DB
PC studies of oral vitamin D with or without calcium vs calcium supplementation
or placebo in adults over 59, five RCTs for hip fracture (n = 9294) and 7 RCTs
for nonvertebral fracture risk (n = 9820) met inclusion criteria. All used
cholecalciferol. A vitamin D dose of 700 to 800 IU/d reduced the relative risk
(RR) of hip fracture by 26% (3 RCTs with 5572 persons; pooled RR, 0.74) and any
nonvertebral fracture by 23% (5 RCTs with 6098 persons; pooled RR, 0.77) vs
calcium or placebo. No significant benefit was observed for RCTs with 400 IU/d
vitamin D (2 RCTs with 3722 persons; pooled RR for hip fracture, 1.15; and
pooled RR for any nonvertebral fracture, 1.03). An oral vitamin D dose of 400 IU/d
is not sufficient for fracture prevention. Fracture prevention with vitamin D
supplementation: a meta-analysis of randomized controlled trials.
Bischoff-Ferrari HA, Willett WC, et al. Harvard. JAMA.
2005 May 11;293(18):2257-64.
Calcium, Dairy Increase Prostate Cancer Risk: In a 10-year
prospective study of 3612 men in the first National Health and Nutrition
Examination Epidemiologic Follow-up Study, 131 prostate cancer cases developed.
Compared with men in the lowest third for dairy food intake, men in the highest
third had a 120% higher risk (RR = 2.2; P = 0.05). Low-fat milk was associated
with 50% increased risk, but whole milk was not. Dietary calcium was also
strongly associated with 120% increased risk (RR = 2.2; trend P = 0.001). After
adjustment for calcium intake, neither vitamin D nor phosphorus was clearly
associated with risk. Dairy, calcium, and vitamin D intakes and prostate cancer
risk in the National Health and Nutrition Examination Epidemiologic Follow-up
Study cohort. Tseng M, Breslow RA, et al. Philadelphia, PA. Am
J Clin Nutr. 2005 May;81(5):1147-54. For more, see Prostate
Cancer. Low Vitamin D Linked to Obesity: In the Longitudinal Aging Study Amsterdam of 453 adults over age 64, researchers found, that higher BMI, waist circumference, and sum of skinfolds were statistically significantly associated with lower vitamin D (25-OH-D) (all P < 0.05), and with higher parathyroid hormone (PTH) (all P < 0.05). The percentage of total body fat was more strongly associated with 25-OH-D and PTH (both P < 0.001) as compared with anthropometric measures. Adiposity in relation to vitamin D status and parathyroid hormone levels a population-based study in older men and women. Snijder MB, van Dam RM, et al. VU University Medical Center, Amsterdam, The Netherlands. J Clin Endocrinol Metab. 2005 Apr 26 Irritable Bowel Helps by Melatonin: In a 2-week
DB PC study of 40 Irritable Bowel Syndrome adults with sleep disturbances,
melatonin 3 mg at before bedtime significantly decreased mean abdominal pain
score (2.35 vs 0.70, p<0.001), and increased mean rectal pain threshold (24.8
vs 33.7 mmHg, p<0.01). Bloating, stool type, stool frequency, anxiety and
depression scores did not significantly differ. Melatonin did not influence
sleep including total sleep time, sleep latency, sleep efficiency, sleep onset
latency, arousals, duration of stage 1-4, REM sleep and REM onset latency.
Melatonin improves abdominal pain in irritable bowel syndrome patients who have
sleep disturbances: a randomised double blind placebo controlled study. Song GH,
Leng PH, et al. National University of Singapore. Gut.
2005 May 24. For more, see Irritable Bowel
Syndrome. Qigong No Advantage Over Conventional Exercise for Hypertension, Depression: Qigong is a traditional Chinese exercise consisting of breathing and gentle movements. In a 16-week, randomized study of 88 patients with mild essential hypertension, blood pressure decreased significantly from 146.3/93.0 mmHg at baseline to 135.5/87.1 mmHg with qigong vs. from 140.9/93.1 mmHg to 129.7/86.0 mmHg with conventional exercise. Heart rate, weight, BMI, waist circumference, total cholesterol, renin and 24 h urinary albumin excretion significantly decreased in both groups after 16 weeks. General health, bodily pain, social functioning and depression also improved in both groups. No significant differences between qigong and conventional exercise were found. Randomised controlled trial of qigong in the treatment of mild essential hypertension. Cheung BM, Lo JL, et al. University of Hong Kong. Journal of Human Hypertension 19 May 2005. For more, see Exercise and Depression. Damiana Anti-Anxiety Effect in Mice: Turnera aphrodisiaca Ward (Damiana) has been traditionally used for the treatment of anxiety neurosis, and as an aphrodisiac. Tinctures (85% ethanol extracts) have also been used for the treatment of central nervous system disorders. Three different dried tinctures of T. aphrodisiaca were used in mice to measure anti-anxiety effects at 50, 75, 100, 125 or 150 mg/kg in an elevated plus maze apparatus. They had significant anxiolytic activity at 50 mg/kg (NLK), 75 mg/kg (DWSG) and 125 mg/kg (SBL), respectively, with reference to control as well as standard (diazepam, 2 mg/kg p.o.). Anti-anxiety Activity Studies on Homoeopathic Formulations of Turnera aphrodisiaca Ward. Kumar S, Sharma A. Evid Based Complement Alternat Med. 2005 Mar;2(1):117-119. Ed: No published research except the above study is available for damiana for anxiety (Pubmed 5/28/05). It is widely sold for sexual enhancement, but only one single study is available in which damiana was part of an apparently effective concoction for women with sexual problems. Smaller Amygdala Gray Matter in Pediatric Anxiety: In an MRI study, reductions in left amygdala gray matter volume were found for pediatric patients with anxiety disorders. Selective reduction in amygdala volume in pediatric anxiety disorders: a voxel-based morphometry investigation. Milham MP, Nugent AC, et al. University of Illinois, Urbana. Biol Psychiatry. 2005 May 1;57(9):961-6. Vegetarian or Health Conscious Diets and Exercise Markedly Increase Longevity: In a 21-year follow-up of 1,225 vegetarians and 679 health-conscious persons in Germany, standardized mortality ratios for all-cause mortality was well below 100: 59 [95% confidence interval, 54-64], predominantly due to a deficit of deaths from circulatory diseases. Vegetarian compared with nonvegetarian diet had no effect on overall mortality [RR 1.10], whereas moderate and high physical activity significantly reduced risk of death (RR 0.62), adjusted for age, sex, smoking, alcohol intake, body mass index, and educational level. Vegetarian diet was associated with a reduced RR of 0.70 (95% CI, 0.41-1.18) for ischemic heart disease, which could partly be related to avoidance of meat. Lifestyle determinants and mortality in German vegetarians and health-conscious persons: results of a 21-year follow-up. Chang-Claude J, Hermann S, et al. German Cancer Research Center, Heidelberg, Germany. Cancer Epidemiol Biomarkers Prev. 2005 Apr;14(4):963-8. For more, see Longevity. 33
Thomas E. Radecki, M.D., J.D. www.modern-psychiatry.com
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