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Double-blind, controlled trial of inositol treatment of depression.
Levine J, Barak Y, Gonzalves M, Szor H, Elizur A, Kofman O, Belmaker RH.
Yehuda Abarbanel Mental Health Center, Bat Yam, Israel.
Am J Psychiatry 1995 May;152(5):792-4
OBJECTIVE: CSF levels of inositol have been reported to be lower than normal in depressed subjects. The authors administered inositol to depressed patients in a double-blind, controlled trial. METHOD: Under double-blind conditions, 12 g/day of inositol (N = 13) or placebo (N = 15) was administered to depressed patients for 4 weeks. RESULTS: The overall improvement in scores on the Hamilton Depression Rating Scale was significantly greater for inositol than for placebo at week 4. No changes were noted in hematology or in kidney or liver function. CONCLUSIONS: This may be the first use of the precursor strategy for a second messenger rather than a neurotransmitter in treating depression. Although inositol had a significant antidepressant effect in this study, replication is crucial.
Follow-up and relapse analysis of an inositol study of depression.
Levine J, Barak Y, Kofman O, Belmaker RH.
Abarbanel Mental Health Center, Bat Yam, Israel.
Isr J Psychiatry Relat Sci 1995;32(1):14-21
A recent controlled double-blind study of 28 patients treated with 12 gm daily of inositol or placebo revealed significant antidepressant effect for this second messenger precursor. Patients were followed-up by interview and Hamilton Depression Scale 10-12 months after the end of the study. Half of the patients who had responded well to inositol relapsed rapidly after inositol discontinuation whereas none of those who responded to placebo relapsed rapidly after placebo cessation. Klein suggested that true drug responders to tricyclic antidepressants respond slowly and gradually whereas placebo responders improve early in an abrupt fashion. However, in the recent study both inositol and placebo responders improved at similar rates. Hamilton Depression Scale Scores 10-12 months after completion of the study were not significantly different between those who had responded and those who had not responded to inositol or to placebo.
St John's wort for depression--an overview and meta-analysis of randomised clinical trials.
Linde K, Ramirez G, Mulrow CD, Pauls A, Weidenhammer W, Melchart D.
Projekt Munchener Modell, Ludwig-Maximilians-Universitat, Munich, Germany.
BMJ 1996 Aug 3;313(7052):253-8
OBJECTIVE--To investigate if extracts of Hypericum perforatum (St John's wort) are more effective than placebo in the treatment of depression, are as effective as standard antidepressive treatment, and have fewer side effects than standard antidepressant drugs. DESIGN-Systematic review and meta-analysis of trials revealed by searches. TRIALS--23 randomised trials including a total of 1757 outpatients with mainly mild or moderately severe depressive disorders: 15 (14 testing single preparations and one a combination with other plant extracts) were placebo controlled, and eight (six testing single preparations and two combinations) compared hypericum with another drug treatment. MAIN OUTCOME MEASURES--A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group), and numbers of patients reporting and dropping out for side effects. RESULTS--Hypericum extracts were significantly superior to placebo (ratio = 2.67; 95% confidence interval 1.78 to 4.01) and similarly effective as standard antidepressants (single preparations 1.10; 0.93 to 1.31, combinations 1.52; 0.78 to 2.94). There were two (0.8%) drop outs for side effects with hypericum and seven (3.0%) with standard antidepressant drugs. Side effects occurred in 50 (19.8%) patients on hypericum and 84 (52.8%) patients on standard antidepressants. CONCLUSION--There is evidence that extracts of hypericum are more effective than placebo for the treatment of mild to moderately severe depressive disorders. Further studies comparing extracts with standard antidepressants in well defined groups of patients and comparing different extracts and doses are needed.
Can winter depression be prevented by Ginkgo biloba extract? A placebo-controlled trial.
Lingaerde O, Foreland AR, Magnusson A.
Department of Research and Education, Aker Hospital, Oslo, Norway.
Acta Psychiatr Scand 1999 Jul;100(1):62-6
OBJECTIVE: The aim was to test the hypothesis that the Ginkgo biloba extract PN246, in tablet form (brand name Bio-Biloba), may prevent the symptoms of winter depression (WD) in patients with seasonal affective disorder (SAD). METHOD: A total of 27 SAD patients were randomized to receive double-blind placebo or Bio-Biloba for 10 weeks or until they developed symptoms of WD, starting in a symptom-free phase about 1 month before expected WD symptoms. An extended Montgomery-Asberg Depression Rating Scale was completed before and immediately after termination of medication. The patients also self-rated some key symptoms on a visual analogue scale every 2 weeks during the trial. RESULTS: There were no significant differences between the treatment groups in the number of patients who developed treatment-requiring WD, or in the development of single key symptoms during the trial. CONCLUSION: We did not find that Ginkgo biloba was able to prevent the development of the symptoms of winter depression.
How does stress affect you? An overview of stress, immunity, depression and disease.
Maddock C, Pariante CM.
Maudsley Hospital, London SE5 8AZ, UK.
Epidemiol Psichiatr Soc 2001 Jul-Sep;10(3):153-62
OBJECTIVE: Stress is a term that has become synonymous with modern life. This review aims to appraise the evidence linking stress with disease with particular reference to the major causes of morbidity and mortality in the Western World, cardiovascular disease, cancer, and depression. Changes in immune parameters in stressful situations were reviewed as a possible pathophysiological mechanism for such effects.
METHOD: A Medline search was carried out for the period 1996-2000 to identify recent findings in this field using the terms "stress", "disease", "immune system". Relevant references that were found in all identified publications were also followed up.
RESULTS: There is evidence to link stress with the onset of major depression and with a poorer prognosis in cardiovascular disease and cancer. Few small studies suggest that stress management strategies may help to improve survival. Chronic stress appears to result in suppression of the immune response, whereas immune activation and suppression have been associated with acute stress. Inflammatory cytokines, soluble mediators of the immune response, can result in symptoms of depression.
CONCLUSION: Further prospective epidemiologically based studies are needed to clarify the role of stress on disease onset, course, and prognosis. Stress management strategies, aimed at prolonging survival in patients with cardiovascular disease, cancer, and possibly other chronic illnesses, are an exciting area of further research. Immune system changes may account for the relationship between stress and disease. We propose the "stress, cytokine, depression" model as a biological pathway to explain the link between stressful life events and depression.
Effect of St. John's wort (Hypericum perforatum) on cytochrome P-450 2D6 and 3A4 activity in healthy volunteers.
Markowitz JS, DeVane CL, Boulton DW, Carson SW, Nahas Z, Risch SC.
Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston
29425, USA. markowij@musc.edu
Life Sci 2000 Jan 21;66(9):PL133-9
The effects of the herb St. John's wort (Hypericum perforatum), a purported antidepressant, on the activity of cytochrome P-450 (CYP) 2D6 and 3A4 was assessed in seven normal volunteers. Probe substrates dextromethorphan (2D6 activity) and alprazolam (3A4 activity) were administered orally with and without the co-administration of St. John's wort. Urinary concentrations of dextromethorphan and dextrorphan were quantified and dextromethorphan metabolic ratios (DMRs) determined. Plasma samples were collected (0-60 hrs) for alprazolam pharmacokinetic analysis sufficient to estimate tmax, Cmax, t 1/2, and AUC. Validated HPLC methods were used to quantify all compounds of interest. No statistically significant differences were found in any estimated pharmacokinetic parameter for alprazolam or DMRs. These results suggest that St. John's wort, when taken at recommended doses for depression, is unlikely to inhibit CYP 2D6 or CYP 3A4 activity.
Comparing aerobic with nonaerobic forms of exercise in the treatment of clinical depression: a randomized trial.
Martinsen EW, Hoffart A, Solberg O.
Modum Bads Nervesanatorium, Forde, Norway.
Compr Psychiatry 1989 Jul-Aug;30(4):324-31
We compared aerobic with nonaerobic forms of exercise in the treatment of clinical depression. Ninety-nine inpatients, who met the DMS-III-R criteria for major depression, dysthymic disorder, or depressive disorder not otherwise specified (NOS), took part in the study. They were randomly assigned to two different physical training conditions, aerobic and nonaerobic. In both conditions, one hour of training was performed three times a week for a period of 8 weeks. There was a significant increase in maximum oxygen uptake (VO2 max) in the aerobic group; there was no change in the nonaerobic group regarding this variable. Depression scores in both groups were significantly reduced during the study, but there was no significant difference between the groups. The correlation between increase in physical fitness and reduction in depression scores was low. The study indicates that the antidepressive effects associated with exercises are not restricted to aerobic forms of training.
EGG phosphatidylcholine combined with vitamin B12 improved memory impairment following lesioning of nucleus basalis in rats.
Masuda Y, Kokubu T, Yamashita M, Ikeda H, Inoue S.
Q.P. Corporation, Department of Neuropsychiatry, Kochi Medical School, Tokyo, Japan.
Life Sci 1998;62(9):813-22
We investigated the effects of egg phosphatidylcholine (PC) combined with vitamin B12 on memory in the Morris water maze task, and on choline and acetylcholine (ACh) concentrations in the brain of rats. Animals with nucleus basalis Magnocellularis (NBM) lesion received intragastric administration of egg PC or vitamin B12, or both for 18 days. Memory acquisition and retention were remarkably impaired in NBM lesioned rats compared with in sham-operated control. NBM lesioned group had lower choline and ACh concentrations than control group in the frontal cortex. High dose of egg PC alone significantly increased choline concentration, but did not change ACh concentration in the frontal cortex. High dose of vitamin B12 alone did not change choline and ACh concentrations in the brain. Either egg PC or vitamin B12 did not improve memory acquisition and retention. However, low dose of egg PC combined with vitamin B12 significantly increased ACh concentration and improved memory acquisition and retention in the NBM lesioned rats. We concluded that egg PC combined with vitamin B12 improved the memory impairment of NBM lesioned rats through the action on the cholinergic neurons.
Use of neurotransmitter precursors for treatment of depression.
Meyers, S.
Altern. Med. Rev. 2000 Feb; 5(1): 64-71 (spmeyers@lbl.gov;http://www.thorne.com/altmedrev/.fulltext/5/1/64.html).
Fatal malignant hyperthermia as a result of ingestion of tranylcypromine (Parnate) combined with white wine and cheese.
Mirchandani H, Reich LE.
J Forensic Sci 1985 Jan;30(1):217-20
Fatal malignant hyperthermia occurred in a patient who was taking tranylcypromine (Parnate) and ingested wine and cheese. The case findings are presented along with a review of the literature concerning adverse interactions between monoamine oxidase (MAO) inhibitors and certain foods and beverages. Hyperthermia and its possible causative mechanisms and treatments are discussed. The facts suggest that the complicated dietary restrictions attending the use of MAO inhibitors and the possibility of severe and even catastrophic reactions resulting from violations of these restrictions make the use of these drugs fraught with danger and therefore not a first choice for the treatment of depression.
Direct effects of estrogens on the endocrine function of the mammalian testis.
Moger WH.
Can J Physiol Pharmacol 1980 Sep;58(9):1011-22
This article reviews literature relevant to the view that estradiol (E2) synthesized in the testis acts locally to modify testosterone secretion. Despite a lack of convincing evidence from in vitro experiments, in vivo experiments with intact and hypophysectomized animals have demonstrated that estrogens can inhibit testosterone secretion by acting directly on the testis. Reduced testosterone production in estrogen-treated animals probably results from reduced 17 alpha-hydroxylase and (or) C17-C20 lyase activity. Estrogen-inhibited steroidogenesis may result from estrogen binding to high affinity--low capacity estrogen receptors. Besides being an estrogen target tissue, the testis produces E2; the cellular site of testicular E2 synthesis remains controversial. Recent studies indicate that E2 is synthesized primarily in the Sertoli cells of neonatal rats and in the Leydig cells of older rats. Follicle-stimulating hormone and human chorionic gonadotropin (hCG) increase testicular aromatase activity and E2 concentrations in neonatal and older rats, respectively. An increase in testicular E2 concentrations, following hCG administration, may be one mechanism by which testosterone synthesis becomes desensitized to subsequent hCG stimulation. However, whether gonadotropin-stimulated testicular E2 synthesis is part of a physiologically relevant "short" feedback loop that participates in the regulation of testosterone synthesis remains to be determined.
Evaluation of the relative potency of individual competing amino acids to tryptophan transport in endogenously depressed patients.
Moller, Svend E.
Psychiatry Research 3(2):141-150, 1980
The relative potency of the individual amino acids as competitive inhibitors of tryptophan transport into the human brain was evaluated retrospectively; the combination of competitors that yields the highest predictive value of the plasma tryptophan ratio for the course of treatment of depressed patients with L-tryptophan was also examined. Phenylalanine consistently reduced, and isoleucine slightly reduced the predictive value of the plasma tryptophan ratio. The ratio of tryptophan to the sum of valine, leucine, and tyrosine was identified as most predictive for the therapeutic response to tryptophan. L-tryptophan responders showed a normal plasma total tryptophan concentration as did the nonresponders, whereas the concentration of the three competitors was significantly elevated. It is concluded that while the plasma ratio of tryptophan to the sum of valine, leucine, and tyrosine is a useful predictor of the course of depressives on L-tryptophan, it does not definitely separate out the L-tryptophan responders from the control subjects.
Relationship between plasma ratio of tryptophan to competing amino acids and the response to L-tryptophan treatment in endogenously depressed patients.
Moller SE, Kirk L, Honore P.
J Affect Disord 1980 Mar;2(1):47-59
The ratio of the plasma of total tryptophan to those amino acids that compete with tryptophan during transport into the brain was determined in 60 control subjects and 87 patients suffering from endogenous depression, all females. The plasma ratio in the control subjects showed a significant negative correlation with age. There was no significant difference in the distribution of the biochemical data between the control subjects and the depressed patients. There was a significant higher proportion of bipolar depressed subjects compared to unipolar depressives and patients of uncertain polarity who showed a plasma ratio in the lower normal range. Thirty-two patients were subsequently treated with L-tryptophan. In the patients who showed a particularly low plasma ratio of tryptophan to competing amino acids a remission frequency of 80% was observed on day 14. The efficacy of L-tryptophan in the patients who showed a plasma ratio within the upper normal range was extremely poor. The results suggest that the ratio in the plasma of tryptophan to competing amino acids is a useful predictor of the course of treatment of depressed subjects with L-tryptophan.
St. John's wort induces hepatic drug metabolism through activation ofthe pregnane X receptor.
Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM,
Collins JL, Kliewer SA.
Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, 5
Moore Drive, Research Triangle Park, NC 27709, USA.
Proc Natl Acad Sci U S A 2000 Jun 20;97(13):7500-2
St. John's wort (Hypericum perforatum) is an herbal remedy used widely for the treatment of depression. Recent clinical studies demonstrate that hypericum extracts increase the metabolism of various drugs, including combined oral contraceptives, cyclosporin, and indinavir. In this report, we show that hyperforin, a constituent of St. John's wort with antidepressant activity, is a potent ligand (K(i) = 27 nM) for the pregnane X receptor, an orphan nuclear receptor that regulates expression of the cytochrome P450 (CYP) 3A4 monooxygenase. Treatment of primary human hepatocytes with hypericum extracts or hyperforin results in a marked induction of CYP3A4 expression. Because CYP3A4 is involved in the oxidative metabolism of >50% of all drugs, our findings provide a molecular mechanism for the interaction of St. John's wort with drugs and suggest that hypericum extracts are likely to interact with many more drugs than previously had been realized.
The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women.
Morales AJ, Haubrich RH, Hwang JY, Asakura H, Yen SS.
Department of Reproductive Medicine, School of Medicine, University of California San Diego, La Jolla, USA.
Clin Endocrinol (Oxf) 1998 Oct;49(4):421-32
OBJECTIVE: The biological role of the adrenal sex steroid precursors--DHEA and DHEA sulphate (DS) and their decline with ageing remains undefined. We observed previously that administration of a 50 daily dose of DHEA for 3 months to age-advanced men and women resulted in an elevation (10%) of serum levels of insulin-like growth factor-I (IGF-I) accompanied by improvement of self-reported physical and psychological well-being. These findings led us to assess the effect of a larger dose (100 mg) of DHEA for a longer duration (6 months) on circulating sex steroids, body composition (DEXA) and muscle strength (MedX).
SUBJECTS AND DESIGN: Healthy non-obese age-advanced (50-65 yrs of age) men (n = 9) and women (n = 10) were randomized into a double-blind placebo-controlled cross-over trial. Sixteen subjects completed the one-year study of six months of placebo and six months of 100 mg oral DHEA daily.
MEASUREMENTS: Fasting early morning blood samples were obtained. Serum DHEA, DS, sex steroids, IGF-I, IGFBP-1, IGFBP-3, growth hormone binding protein (GHBP) levels and lipid profiles as well as body composition (by DEXA) and muscle strength (by MedX testing) were measured at baseline and after each treatment.
RESULTS: Basal serum levels of DHEA, DS, androsternedione (A), testosterone (T) and dihydrotestosterone (DHT) were at or below the lower range of young adult levels. In both sexes, a 100 mg daily dose of DHEA restored serum DHEA levels to those of young adults and serum DS to levels at or slightly above the young adult range. Serum cortisol levels were unaltered, consequently the DS/cortisol ratio was increased to pubertal (10:1) levels. In women, but not in men, serum A, T and DHT were increased to levels above gender-specific young adult ranges. Basal SHBG levels were in the normal range for men and elevated in women, of whom 7 of 8 were on oestrogen replacement therapy. While on DHEA, serum SHBG levels declined with a greater (P < 0.02) response in women (-40 +/- 8%; P = 0.002) than in men (-5 +/- 4%; P = 0.02). Relative to baseline, DHEA administration resulted in an elevation of serum IGF-I levels in men (16 +/- 6%, P = 0.04) and in women (31 +/- 12%, P = 0.02). Serum levels of IGFBP-1 and IGFBP-3 were unaltered but GHBP levels declined in women (28 +/- 6%; P = 0.02) not in men. In men, but not in women, fat body mass decreased 1.0 +/- 0.4 kg (6.1 +/- 2.6%, P = 0.02) and knee muscle strength 15.0 +/- 3.3% (P = 0.02) as well as lumbar back strength 13.9 +/- 5.4% (P = 0.01) increased. In women, but not in men, an increase in total body mass of 1.4 +/- 0.4 kg (2.1 +/- 0.7%; P = 0.02) was noted. Neither gender had changes in basal metabolic rate, bone mineral density, urinary pyridinoline cross-links, fasting insulin, glucose, cortisol levels or lipid profiles. No significant adverse effects were observed.
CONCLUSIONS: A daily oral 100 mg dose of DHEA for 6 months resulted in elevation of circulating DHEA and DS concentrations and the DS/cortisol ratio. Biotransformation to potent androgens near and slightly above the range of their younger counterparts occurred in women with no detectable change in men. Given this hormonal milieu, an increase in serum IGF-I levels was observed in both genders but dimorphic responses
were evident in fat body mass and muscle strength in favour of men. These differences in
response to DHEA administration may reflect a gender specific response to DHEA and/or the presence of confounding factor(s) in women such as oestrogen replacement therapy.
Tryptophan depletion and risk of depression relapse: a prospective study of tryptophan depletion as a potential predictor of depressive episodes.
Moreno FA, Heninger GR, McGahuey CA, Delgado PL.
Department of Psychiatry, College of Medicine, The University of Arizona Health Sciences Center, Tucson 85724, USA.
Biol Psychiatry 2000 Aug 15;48(4):327-9
BACKGROUND: This study investigated the relationship between depressive symptom
response during tryptophan depletion and future depressive episodes. METHODS: Twelve subjects with prior major depressive episodes in remission and medication-free for > or =3 months (patients), and 12 matched healthy (control) subjects received two tryptophan depletion tests 1 week apart. During follow-up the Hamilton Depression Rating Scale was administered weekly for 1 month, monthly for 3 months, and once at 6 and 12 months. RESULTS: With results from both tests, tryptophan depletion has a sensitivity of 78%, specificity of 80%, positive predictive value of 70%, and negative predictive value of 86% to identify future depressive episodes. Survival analysis shows that mood response to tryptophan depletion reliably predicts major depressive episodes during the follow-up year (r =.2725, p =.014). CONCLUSIONS: Tryptophan depletion may be clinically useful in identifying individuals at risk for future major depressive episodes.
Cognitive behavior therapy, relaxation training, and tricyclic antidepressant medication in the treatment of depression.
Murphy GE, Carney RM, Knesevich MA, Wetzel RD, Whitworth P.
Washington University in St. Louis School of Medicine, St. Louis, Missouri 63110, USA.
Psychol Rep 1995 Oct;77(2):403-20
Outcomes of seven treatment trials comparing cognitive behavioral therapy to treatment with tricyclic antidepressant medication in major depressive disorder have been quite similar to one another. This led us to question whether treatment outcome in time-limited studies reflected a unique effect of cognitive behavioral therapy. To test the uniqueness hypothesis, relaxation training, a nonpharmacologic, noncognitive treatment, was chosen as a comparison for cognitive behavioral therapy as well as drug therapy. Treatment duration was 16 weeks. The sample of 37 patients treated for major depressive disorder was less depressed than those previously studied. For both cognitive behavioral therapy and relaxation training, outcome of depression was superior to that of tricyclic antidepressant medication by endpoint analysis. The posttreatment scores on the Beck Depression Inventory of 82% of the group receiving cognitive behavioral therapy improved to a Beck Depression Inventory score < or = 9 which was not significantly greater than that for the group receiving relaxation training (73%), so a unique effect was not demonstrated for cognitive behavioral therapy. The outcome for tricyclic antidepressant medication (29% improved to criteria) was significantly worse than that for cognitive behavioral therapy. The patient's pretreatment initial expectancy was not predictive.
One-Year Prevalence of Depressive Disorders Among Adults 18 and Over in the U.S.: NIMH ECA Prospective Data.
Narrow, W.E.
Population estimates based on U.S. Census estimated residential population age 18 and over on July 1, 1998 (unpublished data).
Women's Bodies, Women's Wisdom 1994.
Northup, C.
New York, NY: Bantam Books.
Physical activity and mental health: current concepts.
Paluska SA, Schwenk TL.
Rex Sports Medicine Institute, Cary, North Carolina, USA. scott.paluska@rexhealth.com
Sports Med 2000 Mar;29(3):167-80
Physical activity may play an important role in the management of mild-to-moderate mental health diseases, especially depression and anxiety. Although people with depression tend to be less physically active than non-depressed individuals, increased aerobic exercise or strength training has been shown to reduce depressive symptoms significantly. However, habitual physical activity has not been shown to prevent the onset of depression. Anxiety symptoms and panic disorder also improve with regular exercise, and beneficial effects appear to equal meditation or relaxation. In general, acute anxiety responds better to exercise than chronic anxiety. Studies of older adults and adolescents with depression or anxiety have been limited, but physical activity appears beneficial to these populations as well. Excessive physical activity may lead to overtraining and generate psychological symptoms that mimic depression. Several differing psychological and physiological mechanisms have been proposed to explain the effect of physical activity on mental health disorders. Well controlled studies are needed to clarify the mental health benefits of exercise among various populations and to address directly processes underlying the benefits of exercise on mental health.
Total Wellness 1996.
Pizzorno, J.
Rocklin, CA: Prima.
Testosterone therapy for human immunodeficiency virus-positive men with and without hypogonadism.
Rabkin JG, Wagner GJ, Rabkin R.
New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York 10032, USA. jgr1@columbia.edu
J Clin Psychopharmacol 1999 Feb;19(1):19-27
This study was designed to evaluate the safety and effectiveness of testosterone therapy for clinical symptoms of hypogonadism (low libido, low mood, low energy, loss of appetite/weight) in human immunodeficiency virus-positive men with CD4 cell counts less than 400 cells/mm3 and deficient or low normal serum testosterone levels. The trial consisted of 8 weeks of open treatment with 400 mg of intramuscular testosterone cypionate biweekly. Responders were maintained at this dosage for another 4 weeks and then were randomized in a double-blind, placebo-controlled, 6-week discontinuation trial. Of the 112 men who completed at least 8 weeks of treatment, 102 (91%) were rated as responders on a global assessment of sexual desire/function. Of the 34 study completers with major depressive disorder and/or dysthymia, 79% reported significant improvement in mood at week 8. Average weight change was a gain of 3.7 pounds, with 45% gaining more than 5 pounds. Eighty-four men entered and 77 completed the double-blind phase; of these, 78% of completers randomized to testosterone and 13% randomized to placebo maintained their response. No significant medical or immunologic adverse effects were identified. Testosterone therapy was well tolerated and effective in ameliorating symptoms of clinical hypogonadism, and equally so for men with and without testosterone deficiency. For patients with major depression and/or dysthymia, improvement was equal to that achieved with standard antidepressants.
The neuroimmunology of stress and depression.
Raison CL, Miller AH.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine,
Atlanta, GA 30335, USA. craison@emory.edu
Semin Clin Neuropsychiatry 2001 Oct;6(4):277-94
This article reviews evidence that shows a bidirectional relationship between the brain and the immune system. As a result of this relationship, mental factors such as stress and depression have been shown to affect immune system functioning, with both immunosuppression and immune activation being reported. Stress and depression also have been associated with worse outcomes in immune-related disorders including cancer and infectious diseases suggesting that stress/depression effects on the immune system are clinically relevant to disease expression. Conversely, several lines of evidence suggest that immune system activation such as during infectious diseases, cancer, and autoimmune disorders is associated with the development of behavioral symptoms similar to those seen in the context of chronic stress or major depression. These findings implicate a role for the immune system in the cause of behavioral disorders in a wide range of medical illnesses. Finally, a paradigm is proposed in which abnormal functioning of either the hypothalamic-pituitary-adrenal (HPA) axis or the inflammatory response system disrupts feedback regulation of both neuroendocrine and immune systems contributing to the development of neuropsychiatric and immunologic disorders. Copyright 2001 by W.B. Saunders Company
[Neuropsychic effects of dehydroepiandrosterone]. [Article in French]
Rigaud AS, Pellerin J.
Service de Medecine Interne et de Gerontologie, Hopital Broca, CHU Cochin Port-Royal, Universite Rene-Descartes - Paris-V, 54-56, rue Pascal, 75013 Paris.
Ann Med Interne (Paris) 2001 Apr;152 Suppl 3:43-9
Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEA-S) are secreted primarily by the adrenal glands. DHEA could also be a neuroactive steroidal hormone. Because basal levels of DHEA and DHEA-S in humans decrease significantly with age, these hormones have been assumed to be involved in the aging process and in a number of pathologies which develop with aging: immunosenescence, increased mortality, increased incidence of cancer, osteoporosis and cardiovascular diseases. However, its role is still unknown. In humans, cross sectional and longitudinal studies have shown that DHEA might be associated with global measures of well-being and functioning, but positive effects on measures of memory and attention could not be found. Studies investigating DHEA and DHEA-S levels in dementia have produced controversial results. Short-term experimental studies have not shown significant improvement in global measures of well-being and functioning in healthy subjects but have revealed preliminary evidence for mood enhancing and antidepressant effects of DHEA. There is no evidence that DHEA could induce addiction in human beings.
The benefit from whole body acupuncture in major depression.
Roschke J, Wolf C, Muller MJ, Wagner P, Mann K, Grozinger M, Bech S.
Department of Psychiatry, University of Mainz, Untere Zahlbacher Str. 8, 55101, Mainz,
Germany. roeschke@goofy.zdv.uni-mainz.de
J Affect Disord 2000 Jan-Mar;57(1-3):73-81
BACKGROUND: In a single-blind placebo-controlled study design we investigated the
efficacy of acupuncture additionally applied to drug treatment in major depression.
METHODS: We randomly included 70 inpatients with a major depressive episode in three different treatment groups: verum acupuncture, placebo acupuncture and a control group All three groups were pharmacologically treated with the antidepressant mianserin. The verum group received acupuncture at specific points considered effective in the treatment of depression. The placebo group was treated with acupuncture at non-specific locations and the control group received pharmacological treatment plus clinical management. Acupuncture was applied three times a week over a period of 4 weeks. Psychopathology was rated by judges blind to verum/placebo conditions twice a week over 8 weeks. RESULTS: Patients who experienced acupuncture improved slightly more than patients treated with mianserin alone. CONCLUSIONS: Additionally applied acupuncture improved the course of depression more than pharmacological treatment with mianserin alone. However, we could not detect any differences between placebo and verum acupuncture.
Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women.
Salmaggi P, Bressa GM, Nicchia G, Coniglio M, La Greca P, Le Grazie C.
Obstetrics and Gynecology Department, University La Sapienza School of Medicine,
Rome, Italy.
Psychother Psychosom 1993;59(1):34-40
S-adenosyl-L-methionine (SAMe) is a naturally occurring substance which is a major source of methyl groups in the brain and has been found in previous studies to be an effective antidepressant. The aim of this study was to assess the efficacy of oral SAMe in the treatment of depressed postmenopausal women in a 30-day double-blind placebo-controlled randomized trial. During the course of the study, 80 women, between the ages of 45 and 59, who were diagnosed as having DSM-III-R major depressive disorder or dysthymia between 6 and 36 months following either natural menopause or hysterectomy, underwent 1 week of single-blind placebo washout, followed by 30 days of double-blind treatment with either SAMe 1,600 mg/day or placebo. There was a significantly greater improvement in depressive symptoms in the group treated with SAMe compared to the placebo group from day 10 of the study. Side effects were mild and transient.
Smart Fats 1997.
Schmidt, M.A.
Berkeley, CA: North Atlantic Books/Frog.
Plasma vitamin C concentrations in patients in a psychiatric hospital.
Schorah CJ, Morgan DB, Hullin RP.
Hum Nutr Clin Nutr 1983 Dec;37(6):447-52
Plasma vitamin C was measured in 885 patients in a psychiatric hospital and in 110 healthy controls. The average value was lower in the patients (0.51 mg/100 ml) than in the controls (0.87 mg/100 ml). Length of stay in hospital had little effect on plasma vitamin C in the patients, but the values were marginally lower in males, females on iron therapy and in those with senile dementia. In the patients, many of whom had been offered a similar diet for several years, age was not associated with a change in plasma vitamin C and this suggests that changes in vitamin C with age that have been reported reflect differences in intake. Few patients had values as low as those found in clinical scurvy (less than 0.1 mg/100 ml), but many (32 per cent) had concentrations below the threshold (0.35 mg/100 ml) at which some detrimental effects on health have been reported.
Equivalence of St John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression.
Schrader E. Praxis Klinische Arzneimittelforschung, Pohlheim, Germany.
Int Clin Psychopharmacol 2000 Mar;15(2):61-8
Treatment with St John's wort extract tablets (hypericum Ze 117) and the commonly used slow serotonin reuptake inhibitor (SSRI) fluoxetine was compared in patients with mild-moderate depression with entry Hamilton Depression Scale (HAM-D) (21-item) in the range 16-24, in a randomized, double-blind, parallel group comparison in 240 subjects; fluoxetine: 114 (48%), hypericum: 126 (52%). After 6 weeks' treatment, mean HAM-D at endpoint decreased to 11.54 on hypericum and to 12.20 on fluoxetine (P < 0.09), while mean Clinical Global Impression (CGI) item I (severity) was significantly (P < 0.03) superior on hypericum, as was the responder rate (P = 0.005). Hypericum safety was substantially superior to fluoxetine, with the incidence of adverse events being 23% on fluoxetine and 8% on hypericum. The commonest events on fluoxetine were agitation (8%), GI disturbances (6%), retching (4%), dizziness (4%), tiredness, anxiety/nervousness and erectile dysfunction (3% each), while on hypericum only GI disturbances (5%) had an incidence greater than 2%. We concluded that hypericum and fluoxetine are equipotent with respect to all main parameters used to investigate antidepressants in this population. Although hypericum may be superior in improving the responder rate, the main difference between the two treatments is safety. Hypericum was superior to fluoxetine in overall incidence of side-effects, number of patients with side-effects and the type of side-effect reported.
Depressive episode primarily unresponsive to therapy in elderly patients: efficacy of Gingko biloba extract (EGb 761) in combination with antidepressants.
Schubert, H., Halama, P.
Geriatr. Forsch. 1993; 3: 45-53.
No abstract available.
Testosterone, gonadotropin, and cortisol secretion in male patients with major depression.
Schweiger U, Deuschle M, Weber B, Korner A, Lammers CH, Schmider J, Gotthardt U, Heuser I.
Max-Planck-Institute of Psychiatry, Clinical Institute, Munich, Germany.
schweiger.u@psychiatry.mu-Luebeck.de
Psychosom Med 1999 May-Jun;61(3):292-6
OBJECTIVE: Previous studies of sex hormone concentrations in depression yielded
inconsistent results. However, the activation of the hypothalamic-pituitary-adrenal system seen in depression may negatively affect gonadal function at every level of regulation. The objective of this study was to explore whether major depressive episodes are indeed associated with an alteration of gonadal function. METHODS: Testosterone, pulsatile LH secretion, FSH, and cortisol were assessed using frequent sampling during a 24-hour period in 15 male inpatients with major depression of moderate to high severity and in 22 healthy comparison subjects (age range 22-85 years). RESULTS: An analysis of covariance model showed that after adjustment for age only, daytime testosterone (p < .01), nighttime testosterone (p < .05), and 24-hour mean testosterone secretion (p < .01) were significantly lower in the depressed male inpatients. There was also a trend for a decreased LH pulse frequency in the depressed patients (p < .08). CONCLUSIONS: Gonadal function may be disturbed in men with a depressive episode of moderate to high severity.
The effect of aerobic exercise on self-esteem and depressive and anxiety symptoms among breast cancer survivors.
Segar ML, Katch VL, Roth RS, Garcia AW, Portner TI, Glickman SG, Haslanger S, Wilkins EG.
Division of Kinesiology, School of Public Health, University of Michigan, Ann Arbor, USA.
Oncol Nurs Forum 1998 Jan-Feb;25(1):107-13
PURPOSE/OBJECTIVES: To evaluate the effects of 10 weeks of aerobic exercise on depressive and anxiety symptoms and self-esteem of breast cancer survivors.
DESIGN: Experimental, crossover. SETTING: Midwestern university town. SAMPLE: Twenty-four breast cancer survivors (mean time following surgery 41.8 months; ranging from 1 to 99 months) recruited via mail and cancer support groups. The mean age of the sample was 48.9 years. METHODS: Subjects were assigned randomly into exercise (EX), exercise-plus-behavior modification (EX + BM), and control groups. EX and EX + BM groups exercised aerobically four days/week at > or = 60% of age-predicted maximum heart rate for 10 weeks. Data were collected pretest, post-test, and crossover (12 weeks following post-test). Because pretest or post-test scores showed no statistical differences between EX and EX + BM groups, data were combined to form one group. MAIN RESEARCH VARIABLES: Aerobic exercise (four days/ week; 30-40 minutes/session), depression, (Beck Depression inventory), anxiety (Speilberger State-Trait Anxiety Inventory), and self-esteem (Rosenberg Self-Esteem Inventory). FINDINGS: Pre- to post-test analyses revealed that women who exercised had significantly less depression and state and trait anxiety over time compared to controls. After the crossover, the control group demonstrated comparable improvements in both depressive and state anxiety scores. Self-esteem did not change significantly. Subjects who received exercise recommendations from their physicians exercised significantly more than subjects who received no recommendation. CONCLUSIONS: Mild to moderate aerobic exercise may be of therapeutic value to breast cancer survivors with respect to depressive and anxiety symptoms but not to self-esteem. A physician's recommendation to exercise appears to be an important factor in a patient's exercise adherence. IMPLICATIONS FOR NURSING PRACTICE: To Improve depressive and anxiety symptoms following breast cancer surgery, healthcare professionals should consider recommending mild to moderate exercise.
Testosterone and depression in aging men.
Seidman SN, Walsh BT.
Department of Psychiatry, College of Physicians and Surgeons of Columbia University,
New York, NY 10032, USA.
Am J Geriatr Psychiatry 1999 Winter;7(1):18-33
In men, testosterone secretion affects neurobehavioral functions such as sexual arousal, aggression, emotional tone, and cognition. Beginning at approximately age 50, men secrete progressively lower amounts of testosterone; about 20% of men over age 60 have lower-than-normal levels. The psychiatric sequelae are poorly understood, yet there is evidence of an association with depressive symptoms. The authors reviewed 1) the physiology of the hypothalamic-pituitary-gonadal axis and its changes with age in men; and 2) the evidence linking testosterone level and major depression in men. Data on this relationship are derived from two types of studies: observational studies comparing testosterone levels and secretory patterns in depressed and non-depressed men, and treatment studies using exogenous androgens for male depression. The data suggest that some depressed older men may have state-dependent low testosterone levels and that some depressed men may improve with androgen treatment.
Course of depressive symptoms over follow-up. Findings from the NationalInstitute of Mental Health Treatment of Depression Collaborative Research Program.
Shea MT, Elkin I, Imber SD, Sotsky SM, Watkins JT, Collins JF, Pilkonis PA,
Beckham E, Glass DR, Dolan RT, et al.
Department of Psychiatry and Human Behavior, Brown University, Providence, RI02906.
Arch Gen Psychiatry 1992 Oct;49(10):782-7
We studied the course of depressive symptoms during an 18-month naturalistic follow-up period for outpatients with Major Depressive Disorder treated in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. The treatment phase consisted of 16 weeks of randomly assigned treatment with the following: cognitive behavior therapy, interpersonal therapy, imipramine hydrochloride plus clinical management (CM), or placebo plus CM. Follow-up assessments were conducted at 6, 12, and 18 months after treatment. Of all patients entering treatment and having follow-up data, the percent who recovered (8 weeks of minimal or no symptoms following the end of treatment) and remained well during follow-up (no Major Depressive Disorder relapse) did not differ significantly among the four treatments: 30% (14/46) for those in the cognitive behavior therapy group, 26% (14/53) for those in the interpersonal therapy group, 19% (9/48) for those in the imipramine plus CM group, and 20% (10/51) for those in the placebo plus CM group. Among patients who had recovered, rates of Major Depressive Disorder relapse were 36% (8/22) for those in the cognitive behavior therapy group, 33% (7/21) for those in the interpersonal therapy group, 50% (9/18) for those in the imipramine plus CM group, and 33% (5/15) for those in the placebo plus CM group. The major finding of this study is that 16 weeks of these specific forms of treatment is insufficient for most patients to achieve full recovery and lasting remission. Future research should be directed at improving success rates of initial and maintenance treatments for depression.
Meditation as an adjunct to a happiness enhancement program.
Smith WP, Compton WC, West WB.
Department of Psychology, Middle Tennessee State University, Murfreesboro 37132, USA.
J Clin Psychol 1995 Mar;51(2):269-73
This study investigated the impact that meditation has on Fordyce's (1977, 1983) Personal Happiness Enhancement Program (PHEP). Experimental subjects were divided into two groups, both of which received instruction on the PHEP. Subjects in one experimental group were taught a meditation exercise in addition to the PHEP. A control group received no instruction. The Happiness Measure, Psychap Inventory, Beck Depression Inventory, and State-Trait Anxiety Scale were dependent measures. The three (groups) x two (pre-post) mixed ANOVAs with Student Newman-Keuls found that the meditation plus PHEP group significantly improved on all dependent measures over both the PHEP only group and the control group. The PHEP only group improved significantly over the control group on all measures except state anxiety.
Omega 3 fatty acids in bipolar disorder: a preliminary double-blind, placebo-controlled trial.
Stoll AL, Severus WE, Freeman MP, Rueter S, Zboyan HA, Diamond E, Cress KK, Marangell LB.
Brigham and Women's Hospital, Department of Psychiatry, Harvard Medical School, Boston, Mass, USA. alstoll@mclean.harvard.edu
Arch Gen Psychiatry 1999 May;56(5):407-12
BACKGROUND: Omega3 fatty acids may inhibit neuronal signal transduction pathways in a manner similar to that of lithium carbonate and valproate, 2 effective treatments for bipolar disorder. The present study was performed to examine whether omega3 fatty acids also exhibit mood-stabilizing properties in bipolar disorder. METHODS: A 4-month, double-blind, placebo-controlled study, comparing omega3 fatty acids (9.6 g/d) vs placebo (olive oil), in addition to usual treatment, in 30 patients with bipolar disorder. RESULTS: A Kaplan-Meier survival analysis of the cohort found that the omega3 fatty acid patient group had a significantly longer period of remission than the placebo group (P = .002; Mantel-Cox). In addition, for nearly every other outcome measure, the omega3 fatty acid group performed better than the placebo group. CONCLUSION: Omega3 fatty acids were well tolerated and improved the short-term course of illness in this preliminary study of patients with bipolar disorder.
Diet and monoamine oxidase inhibitors: a re-examination.
Sullivan EA, Shulman KI.
Can J Psychiatry 1984 Dec;29(8):707-11
Monoamine oxidase inhibitors (MAOIs) are attracting renewed attention as effective antidepressants for refractory depressions, particularly among the elderly. However, widespread fears concerning the interactions of MAOIs with tyramine-containing foods have led to the development of long and complicated diets. These diets have served as an obstacle to the ready use of MAOIs, yet very little systematic or critical review of the basis for food restriction has been undertaken. An international survey of MAOI diets was conducted and from the diets collected, foods were categorized according to frequency of restriction on the diet lists. On the basis of this survey and a critical review of the literature it was determined that only four foods clearly warrant absolute prohibition: aged cheese, pickled fish (herring), concentrated yeast extracts and broad bean pods. While there is insufficient evidence to prohibit alcohol completely (even chianti wine) true moderation must apply. It is suggested that a radically simplified diet should be investigated on a prospective basis.
Double-blind randomized controlled study of the efficacy and tolerability of two reversible monoamine oxidase A inhibitors, pirlindole and moclobemide, in the treatment of depression.
Tanghe A, Geerts S, Van Dorpe J, Brichard B, Bruhwyler J, Geczy J.
Groepspraktijk voor Psychotherapie, Biologische Psychiatrie en co-Therapie,
Bruges, Belgium.
Acta Psychiatr Scand 1997 Aug;96(2):134-41
The aim of this double-blind randomized study was to compare the efficacy and the tolerability of moclobemide (300-600 mg daily) and pirlindole (150-300 mg daily), two reversible inhibitors of MAO-A (RIMAs), in the treatment of depression. In total 116 patients were included in the trial, 111 patients (52 patients on pirlindole and 59 patients on moclobemide) were evaluable for efficacy and safety, and 77 patients completed the whole study (42 days of administration). Both treatments produced highly significant improvements in the Hamilton Depression Rating Scale (HDRS) score, the Hamilton Anxiety Rating Scale (HARS) score and the Montgomery-Asberg Rating Scale MADRS) score from day 7 to day 42. The pattern of development of the three scores in the two groups did not differ significantly. After 42 days of treatment, an improvement of > or = 50% in the HDRS score was noted in 80% and 67% of patients in the pirlindole and moclobemide groups, respectively. A total of 30 (58%) patients on pirlindole and 33 (56%) patients on moclobemide experienced side-effects that were considered to be possibly or probably related to the medication. The differences between the two drugs were non-significant for all types of side-effect, with the exception of dry mouth and tachycardia, which were significantly more frequent with moclobemide.
Treatment of men with major depression: a comparison of sequential cohorts treated with either cognitive-behavioral therapy or newer generation antidepressants.
Thase ME, Friedman ES, Fasiczka AL, Berman SR, Frank E, Nofzinger EA,
Reynolds CF 3rd.
Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh School of Medicine, PA 15213, USA.
J Clin Psychiatry 2000 Jul;61(7):466-72
OBJECTIVE: This report compares response to cognitive-behavioral therapy (CBT) and pharmacotherapy in sequential cohorts of men with DSM-III-R major depression. METHOD: Patients were enrolled in consecutive standardized 16-week treatment protocols conducted in the same research clinic. The first group (N = 52) was treated with Beck's model of CBT, whereas the second group (N = 23) received randomized but open-label treatment with either fluoxetine (N = 10) or bupropion (N = 13). Crossover to the alternate medication was permitted after 8 weeks of treatment for antidepressant nonresponders. The patient groups were well matched prior to treatment. Outcomes
included remission and nonresponse rates, as well as both independent clinical evaluations and self-reported measures of depressive symptoms. RESULTS: Despite limited statistical power to detect differences between treatments, depressed men treated with pharmacotherapy had significantly greater improvements on 4 of 6 continuous dependent measures and a significantly lower rate of nonresponse (i.e., 13% vs. 46%). The difference favoring pharmacotherapy was late-emerging and partially explained by crossing over nonresponders to the alternate medication. The advantage of pharmacotherapy over CBT also tended to be larger among the subgroup of patients with chronic depression. CONCLUSION: Results of prior research comparing pharmacotherapy and CBT may have been influenced by the composition of study groups, particularly the gender composition, the choice of antidepressant comparators, or an interaction of these factors. Prospective studies utilizing flexible dosing of modern antidepressants and, if necessary, sequential trials of dissimilar medications are needed to confirm these findings.
Effect of Korean red ginseng on psychological functions in patients with severe climacteric syndromes.
Tode T, Kikuchi Y, Hirata J, Kita T, Nakata H, Nagata I.
Department of Obstetrics and Gynecology, National Defense Medical College,
Tokorozawa, Saitama, Japan. qw104765@nifty.ne.jp
Int J Gynaecol Obstet 1999 Dec;67(3):169-74
OBJECTIVE: To evaluate the degree of psychological dysfunction and levels of stress hormones in postmenopausal women with climacteric syndromes and effect of Korean red ginseng (RG) on them. METHODS: ACTH, cortisol and DHEA-S in peripheral blood from 12 postmenopausal women with climacteric syndromes or 8 postmenopausal women
without any climacteric syndrome were measured before and 30 days after treatment with daily oral administration of 6 g RG. Blood samples were collected in the early morning on the bed-rest. In postmenopausal women with climacteric syndromes such as fatigue, insomnia and depression, psychological tests using the Cornell Medical Index (CMI) and the State-Trait Anxiety Inventory (STAI) were performed before and 30 days after treatment with RG. RESULTS: CMI score as well as anxiety (A)-state in STAI score in postmenopausal women with climacteric syndromes was significantly higher than that without climacteric syndrome, while DHEA-S levels in postmenopausal women with
climacteric syndromes were about a half of those without climacteric syndrome. Consequently, cortisol/DHEA-S (C/D) ratio was significantly higher in postmenopausal women with climacteric syndromes than in those without climacteric syndrome. When postmenopausal women with climacteric syndromes were treated with daily oral administration of 6 g RG for 30 days, CMI and STAI A-state scores decreased within normal range. Although the decreased DHEA-S levels were not restored to the levels in postmenopausal women without climacteric syndrome, the C/D ratio decreased significantly after treatment with RG. CONCLUSIONS: Improvement of CMI and STAI scores in postmenopausal women suffering climacteric syndromes, particularly fatigue, insomnia and depression, by RG seemed to be brought about in part by effects of RG on stress-related hormones as shown by a decrease in C/D ratio.
Clinical correlations of one-carbon metabolism abnormalities.
Tolbert LC, Monti JA, Walter-Ryan W, Alarcon RD, Bahar B, Keriotis JT, Allison
JG, Cates A, Antun F, Smythies JR.
Department of Psychiatry, University of Alabama, Birmingham.
Prog Neuropsychopharmacol Biol Psychiatry 1988;12(4):491-502
1. Ninety psychiatric inpatients with a DSM III diagnosis of schizophrenia, mania, or major depression were studied. 2. Upon admission/transfer to the Clinical Studies Unit, and prior to discharge, measurements of symptom severity (BPRS, Ham-D, Young's Mania Scale) and blood samples were obtained. 3. Erythrocytes from these paired (admission and discharge) blood samples were assayed for methionine adenosyltransferase (MAT) activity and phosphatidylcholine (PC) content. 4. Comparisons were made between the changes in MAT Vmax, or % PC, and changes in symptom severity. 5. For the majority of the patients (79.3% of the schizophrenics; 84.6% of the depressives; and 93.8% of the manics), clinical improvement was associated with a "normalization" of enzyme activity. The association between changes in % PC and clinical response did not achieve significant correlation.
Pharmacology. How the body's "garbage disposal" may inactivate drugs.
Vogel, G.
Science 2001 Jan 5; 291(5501): 35-7.
No abstract available.
Efficacy and tolerability of St. John's wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10.
Vorbach EU, Arnoldt KH, Hubner WD.
Department of Psychiatry and Psychotherapy, Ev. Krankenhaus Elisabethenstift, Darmstadt, Germany.
Pharmacopsychiatry 1997 Sep;30 Suppl 2:81-5
The special extract of St. John's wort, LI 160, exhibited a superior antidepressant efficacy compared to placebo in several controlled trials. Two further trials demonstrated a similar reduction of depressive symptomatology under LI 160 compared to tricyclics. All these trials were performed in mildly to moderately depressed patients. The present investigation was a randomized, controlled, multicentre, 6-week trial comparing 1800 mg LI 160/die to 150 mg imipramine/die in severely depressed patients according to ICD-10. The main efficacy parameter, a reduction of the total score of the Hamilton Depression Scale, proved both treatment regimens very effective at the end of the 6 week treatment period (mean values 25.3 to 14.5 in the LI 160 group and 26.1 to 13.6 in the imipramine group), but not statistically equivalent within a a-priori defined 25% interval of deviation. The analysis of subgroups with more than a 33% and 50% reduction of the HAMD total score justified the assumption of equivalence within a 25% deviation interval. This view was also supported by the global efficacy ratings from patients and investigators. Regarding adverse events, the nonrejection of the nonequivalence hypothesis denotes a superiority of the herbal antidepressant. These main result indicate that LI 160 might be a treatment alternative to the synthetic tricyclic antidepressant imipramine in the majority of severe forms of depressions. However, more studies of this type must be performed before a stronger recommendation can be made.
Patient compliance with MAO inhibitor therapy.
Walker JI, Davidson J, Zung WW.
J Clin Psychiatry 1984 Jul;45(7 Pt 2):78-80
Exaggerated fears of monoamine oxidase inhibitors (MAOIs) and of their interactions with foods often restrict their use. A review of the literature reveals seven food items most likely to produce a hypertensive crisis in combination with MAOI administration: aged cheeses, smoked or pickled fish, beef or chicken liver, dry fermented sausage, pods of broad beans, brewer's yeast products, and certain alcoholic beverages. Improved understanding of the dietary restrictions, benefits, and mechanism of action of the MAOIs can enhance cooperation with the prescribed treatment program.
Caring for Depression 1996.
Wells, K.B., Sturm, R. et al.
Cambridge, MA: Harvard University Press.
Effects of a standardized ginseng extract on quality of life and physiological parameters in symptomatic postmenopausal women: a double-blind, placebo-controlled trial. Swedish Alternative Medicine Group.
Wiklund IK, Mattsson LA, Lindgren R, Limoni C.
Department of Health and Primary Health Care, University of Bergen, Norway.
ingela.wiklund@astrazeneca.com
Int J Clin Pharmacol Res 1999;19(3):89-99
A randomized, multicenter, double-blind, parallel group study was performed to assess the effects of a standardized ginseng extract compared with those of a placebo on quality of life (QoL) and on physiological parameters in symptomatic postmenopausal women. Validated questionnaires [Psychological General Well-Being (PGWB) index, Women's Health Questionnaire (WHQ)] and Visual Analogue (VA) scales were used to assess the effects of the extract on QoL at baseline and after 16 weeks' treatment with either the ginseng extract or placebo. To assess the efficacy of ginseng on postmenopausal symptoms, physiological parameters [follicle-stimulating hormone (FSH) and estradiol levels, endometrial thickness, maturity index and vaginal pH] were recorded at the same time points. Of the 384 randomized patients (mean age 53.5 +/- 4.0 years), the questionnaires were completed by 193 women treated with ginseng and 191 treated with placebo. With regard to the primary endpoint (total score of the PGWB index) the extract showed only a tendency for a slightly better overall symptomatic relief (p < 0.1). Exploratory analysis of PGWB subsets, however, reported p-values < 0.05 for depression, well-being and health subscales in favor of ginseng compared with placebo. No statistically significant effects were seen for the WHQ and the VA scales or the physiological parameters, including vasomotor symptoms (hot flushes). The positive effects of ginseng on health-related QoL in menopausal women should be further investigated. This study shows, however, that the beneficial effects of ginseng are most likely not mediated by hormone replacement-like effects, as physiological parameters such as FSH and estradiol levels, endometrial thickness, maturity index and vaginal pH were not affected by the treatment.
Comparison of St John's wort and imipramine for treating depression: randomised controlled trial.
Woelk H.
Klinik fur Psychiatrie und Psychotherapie, Akademisches Lehrkrankenhaus der Universitat Giessen, Licher Strasse 106, D-35394 Giessen, Germany.
BMJ 2000 Sep 2;321(7260):536-9
OBJECTIVES: To compare the efficacy and tolerability of Hypericum perforatum (St John's wort extract) with imipramine in patients with mild to moderate depression. DESIGN: Randomised, multicentre, double blind, parallel group trial. SETTING: 40 outpatient clinics in Germany. Participants: 324 outpatients with mild to moderate depression. INTERVENTION: 75 mg imipramine twice daily or 250 mg hypericum extract ZE 117 twice daily for 6 weeks. MAIN OUTCOME MEASURES: Hamilton depression rating scale, clinical global impression scale, and patient's global impression scale. RESULTS: Among the 157 participants taking hypericum mean scores on the Hamilton depression scale decreased from 22.4 at baseline to 12.00 at end point; among the 167 participants taking imipramine they fell from 22.1 to 12.75. Mean clinical global impression scores at end point were 2.22 out of 7 for the hypericum group and 2.42 for the imipramine group. On the 7 point self assessments of global improvement completed by participants (score of 1 indicating "very much improved" and 7 indicating "very much deteriorated") mean scores were 2.44 in the hypericum group and 2.60 in the imipramine group. None of the differences between treatment groups were significant. However, the mean score on the anxiety-somatisation subscale of the Hamilton scale (3.79 in the hypericum group and 4.26 in the imipramine group) indicated a significant advantage for hypericum relative to imipramine. Mean scores on the 5 point scale used by participants to assess tolerability (score of 1 indicating excellent tolerability and 5 indicating very poor tolerability) were better for hypericum (1.67) than imipramine (2.35). Adverse events occurred in 62/157 (39%) participants taking hypericum and in 105/167 (63%) taking imipramine. 4 (3%) participants taking hypericum withdrew because of adverse events compared with 26 (16%) taking imipramine. CONCLUSIONS: This Hypericum perforatum extract is therapeutically equivalent to imipramine in treating mild to moderate depression, but patients tolerate hypericum better.
Dehydroepiandrosterone (DHEA) treatment of depression.
Wolkowitz OM; Reus VI; Roberts E; Manfredi F; Chan T; Raum WJ; Ormiston S ;
Johnson R; Canick J; Brizendine L; Weingartner H
Department of Psychiatry, University of California, San Francisco, School of Medicine
94143-0984, USA.
Biol Psychiatry (United States) Feb 1 1997, 41 (3) p311-8
Dehydroepiandrosterone (DHEA) and its sulfate, DHEA-S, are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects. In this study, six middle-aged and elderly patients with major depression and low basalplasma DHEA f1p4or DHEA-S levels were openly administered DHEA (30-90 mg/d x 4weeks) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals. Depression ratings, as well as aspects of memory performance significantly improved. One treatment-resistant patient received extended treatment with DHEA for 6 months: her depression ratings improved 48-72% and her semantic memory performance improved 63%. These measures returned to baseline after treatment ended. In both studies, improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels. These preliminary data suggest DHEA may haveantidepressant and promemory effects and should encourage double-blind trials indepressed patients.
Double-blind treatment of major depression with dehydroepiandrosterone.
Wolkowitz OM, Reus VI, Keebler A, Nelson N, Friedland M, Brizendine L, Roberts E
Department of Psychiatry, University of California Medical Center, San Francisco, USA.
owenw@itsa.ucsf.edu
Am J Psychiatry 1999 Apr;156(4):646-9
OBJECTIVE: This study was designed to assess possible antidepressant effects of dehydroepiandrosterone (DHEA), an abundant adrenocortical hormone in humans.
METHOD: Twenty-two patients with major depression, either medication-free or on stabilized antidepressant regimens, received either DHEA (maximum dose = 90 mg/day) or placebo for 6 weeks in a double-blind manner and were rated at baseline and at the end of the 6 weeks with the Hamilton Depression Rating Scale. Patients previously stabilized with antidepressants had the study medication added to that regimen; others received DHEA or placebo alone.|
RESULTS: DHEA was associated with a significantly greater decrease in Hamilton depression scale ratings than was placebo. Five of the 11 patients treated with DHEA, compared with none of the 11 given placebo, showed a 50% decrease or greater in depressive symptoms.
CONCLUSIONS: These results suggest that DHEA treatment may have significant antidepressant effects in some patients with major depression. Further, larger-scale trials are warranted.
Maximize Your Vitality & Potency 1998.
Wright, J.
Petaluma, CA: Smart Publications.
Replacement of DHEA in aging men and women. Potential remedial effects.
Yen SS, Morales AJ, Khorram O.
Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093, USA.
Ann N Y Acad Sci (UNITED STATES) Dec 29 1995, 774 p128-42
DHEA in appropriate replacement doses appears to have remedial effects with respect to its ability to induce an anabolic growth factor, increase muscle strength and lean body mass, activate immune function, and enhance quality of life in aging men and women, with no significant adverse effects. Further studies are needed to confirm and extend our current results, particularly the gender differences.
The use of diet and dietary components in the study of factors controllingaffect in humans: a review.
Young SN.
Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
J Psychiatry Neurosci 1993 Nov;18(5):235-44
Although one of the first biological treatments of a major psychiatric disorder was the dietary treatment of pellagra, the use of diet and dietary components in the study of psychopathology has not aroused much interest. This article reviews three areas in which the dietary approach has provided interesting information. The tryptophan depletion strategy uses a mixture of amino acids devoid of tryptophan to lower brain tryptophan in order to study the symptoms that can be elicited. One effect of tryptophan depletion is a lowering of mood, the magnitude of which seems to depend on the baseline state of the subject. Therefore, recovered depressed patients often undergo an acute relapse, while normal subjects show more moderate changes of mood. Totally euthymic subjects show no lowering of mood, but subjects with high normal depression scale scores or subjects with a family history of depression show a moderate lowering of mood. These data indicate that low serotonin levels alone cannot cause depression. However, serotonin does have a direct effect on mood, and low levels of serotonin contribute to the etiology of depression in some depressed patients. Folic acid deficiency causes a lowering of brain serotonin in rats, and of cerebrospinal fluid 5-hydroxyindoleacetic acid in humans. There is a high incidence of folate deficiency in depression, and there are indications in the literature that some depressed patients who are folate deficient respond to folate administration. Folate deficiency is known to lower levels of S-adenosylmethionine, and S-adenosylmethionine is an antidepressant that raises brain serotonin levels. These data suggest that low levels of serotonin in some depressed patients may be a secondary consequence of low levels of S-adenosylmethionine. They also suggest that the dietary intake and psychopharmacological action of methionine, the precursor of S-adenosylmethionine, should be studied in patients with depression. Normal meals have definite effects on mood and performance in humans. The composition of the meal, in terms of protein and carbohydrate content, can influence these behaviors. Because protein and carbohydrate meals can influence brain serotonin in rats, these effects in humans have usually been interpreted in terms of altered serotonin functioning. However, the current balance of evidence is against the involvement of serotonin in the acute effects of protein and carbohydrate meals in humans. The underlying mechanisms involved are unknown, but there are a variety of possibilities.(ABSTRACT TRUNCATED AT 400 WORDS)
Folic acid and psychopathology.
Young SN, Ghadirian AM.
Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Prog Neuropsychopharmacol Biol Psychiatry 1989;13(6):841-63
1. The incidence of folic acid deficiency is high in patients with various psychiatric isorders including depression, dementia and schizophrenia. 2. In epileptics on anticonvulsants, folate deficiency often occurs because anticonvulsants inhibit folate absorption. In these patients folate deficiency is often associated with psychiatric symptoms. 3. In medical patients psychiatric symptoms occur more frequently, and in psychiatric patients symptoms are more severe, in those with folate deficiency than in those with normal levels. 4. Many open studies have demonstrated therapeutic effects of folate administration on psychiatric symptoms in folate deficient patients. 5. Several placebo-controlled studies have not demonstrated therapeutic effects, possibly because the doses they used (15-20 mg/day) are known to be toxic and to cause mental symptoms. 6. Two placebo-controlled studies have demonstrated beneficial effects of folic acid administration, one in patients with a syndrome of psychiatric and neuropsychological changes associated with folate deficiency and the other in patients on long-term lithium therapy. In the latter study the dose was only 0.2 mg/day. 7. Folic acid deficiency is known to lower brain S-adenosylmethionine and 5-hydroxytryptamine. S-Adenosylmethionine, which has antidepressant properties, raises brain 5-hydroxytryptamine. Thus, depression associated with folate deficiency is probably related to low brain 5HT. 8. S-Adenosylmethionine is involved in many methylation reactions, including methylation of membrane phospholipids, which influences membrane properties. This may explain the wide variety of symptoms associated with folate deficiency. 9. Because the costs and risks associated with low doses of folic acid (up to 0.5 mg/day) are small, folic acid should be given as an adjunct in the treatment of patients with unipolar or bipolar affective disorders and anorexia, epileptics on anticonvulsants, geriatric patients with mental symptoms and patients with gastrointestinal disorders who exhibit psychiatric symptoms. 10. Although the majority of the patients listed above will probably not be helped by folic acid therapy, a significant minority are likely to have folate-responsive symptoms.
Relationship between dopamine-stimulated phospholipid methylation and the single-carbon folate pathway.
Zhao R, Chen Y, Tan W, Waly M, Sharma A, Stover P, Rosowsky A, Malewicz B, Deth RC.
Department of Pharmaceutical Sciences, Northeastern University, Boston,
Massachusetts 02115, USA.
J Neurochem 2001 Aug;78(4):788-96
In a previous study we demonstrated the ability of dopamine (DA) to stimulate phospholipid methylation (PLM) via a novel mechanism involving the D4 dopamine receptor (D4R) in which single-carbon folates appeared to be the primary source of methyl groups. To further understand the relationship between D4R-mediated PLM and folate metabolism, we examined the effect of several folate pathway interventions on the level of basal and DA-stimulated incorporation of [14C]-labeled formate into phospholipids in cultured SH-SY5Y neuroblastoma cells. These interventions included: (i) Overexpression of methenyltetrahydrofolate synthetase (MTHFS). (ii) Treatment with 5-formylTHF. (iii) Treatment with the MTHFS inhibitor 5-formyltetrahydrohomofolic acid (5-formylTHHF). (iv) Growth in nucleoside-free media. 31P-NMR was also used to follow DA-induced changes in cell phospholipid composition. MTHFS overexpression and 5-formylTHHF treatment, both of which lower 5-methylTHF levels, each reduced basal PLM and its stimulation by DA. In contrast, 5-formylTHF, which increases 5-methylTHF, caused a dose-dependent increase in both basal and DA-stimulated PLM. Growth in nucleoside-free media caused time-dependent changes in PLM, which were due to the absence of purine nucleosides. While basal PLM was maintained at a reduced level, DA-stimulated PLM was initially increased followed by a later decrease. Together, these findings indicate a close functional relationship between single-carbon folate metabolism and DA-stimulated PLM, consistent with a role for 5-methylTHF as the methyl donor for the D4R-mediated process.
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