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[Low concentration level of total serum cholesterol as a risk factor for suicidal and aggressive behavior] [Article in Polish]
Ainiyet J, Rybakowski J. Kliniki Psychiatrii Doroslych AM w Poznaniu.
Psychiatr Pol 1996 May-Jun;30(3):499-509
The data have been presented for possible association between low total serum cholesterol concentration and the increased risk of suicidal and aggressive behavior. The analysis of results from some long-term epidemiological studies shows an excess of suicides and violent death cases among persons with low baseline total serum cholesterol level and in those in whom this level was lowered by means of pharmacotherapy or dieting. In patients hospitalized on psychiatric wards, having low total serum cholesterol concentration, a higher intensity of suicidal thoughts and tendencies was found. Such relationship was most evident in patients with depression. In some populations, an association between low total cholesterol level and the tendency to aggressive behavior was also found. Higher intensity of aggression was also observed in animals receiving low-cholesterol diet. A hypothesis was discussed, postulating the connection between low cholesterol level and lower activity of central serotonergic structures responsible for the inhibition of impulsive behavior.
Nutrition and depression: the role of folate.
Alpert JE, Fava M. Department of Psychiatry, Harvard Medical School, Boston, MA 02114, USA.
Nutr Rev 1997 May;55(5):145-9
A relationship between folate and neuropsychiatric disorders has been inferred from clinical observation and from the enhanced understanding of the role of folate in critical brain metabolic pathways. Depressive symptoms are the most common neuropsychiatric manifestation of folate deficiency. Conversely, borderline low or deficient serum or red blood cell folate levels have been detected in 15-38% of adults diagnosed with depressive disorders. Recently, low folate levels have been linked to poorer antidepressant response to selective serotonin reuptake inhibitors. Factors contributing to low serum folate levels among depressed patients as well as the circumstances under which folate and its derivatives may have a role in antidepressant pharmacotherapy must be further clarified.
Androderm Testosterone Transdermal System.
U.S. Prescribing Information 1997.
Philadelphia, PA: Smith Kline Beecham.
HerbalGram
Anon.
2000; 50: 20.
Exercise treatment for major depression: maintenance of therapeutic benefit at 10 months.
Babyak M, Blumenthal JA, Herman S, Khatri P, Doraiswamy M, Moore K, Craighead WE, Baldewicz TT, Krishnan KR. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
Psychosom Med 2000 Sep-Oct;62(5):633-8
OBJECTIVE: The purpose of this study was to assess the status of 156 adult volunteers with major depressive disorder (MDD) 6 months after completion of a study in which they were randomly assigned to a 4-month course of aerobic exercise, sertraline therapy, or a combination of exercise and sertraline. METHODS: The presence and severity of depression were assessed by clinical interview using the Diagnostic Interview Schedule and the Hamilton Rating Scale for Depression (HRSD) and by self-report using the Beck Depression Inventory. Assessments were performed at baseline, after 4 months of treatment, and 6 months after treatment was concluded (ie, after 10 months). RESULTS: After 4 months patients in all three groups exhibited significant improvement; the proportion of remitted participants (ie, those who no longer met diagnostic criteria for MDD and had an HRSD score < 8) was comparable across the three treatment conditions. After 10 months, however, remitted subjects in the exercise group had significantly lower relapse rates (p = .01) than subjects in the medication group. Exercising on one's own during the follow-up period was associated with a reduced probability of depression diagnosis at the end of that period (odds ratio = 0.49, p = .0009). CONCLUSIONS: Among individuals with MDD, exercise therapy is feasible and is associated with significant therapeutic benefit, especially if exercise is continued over time.
Changes in the pituitary-testicular system with age.
Baker HW, Burger HG, de Kretser DM, Hudson B, O'Connor S, Wang C, Mirovics A, Court J, Dunlop M, Rennie GC
Clin Endocrinol (Oxf) 1976 Jul;5(4):349-72
In order to provide a comprehensive account of pituitary-testicular function in man, 466 subjects, ranging in age from 2 to 101 years, were studied to examine blood levels of the pituitary gonadotrophins (LH and FSH), the sex steroids testosterone and oestradiol, the binding capacity of the sex hormone binding globulin (SHBG), the free testosterone and oestradiol fractions, and the transfer constant for the peripheral conversion of testosterone to oestradiol. The results were compared with clinical indices of testicular size, sexual function and secondary sex hair distribution. Serum LH and FSH were low before puberty, increased in pubertal adolescents to levels somewhat above those of adults and subsequently increased progressively over the age of 40 years. Testosterone levels fell slowly after the age of 40, while there was a slight rise in plasma oestradiol with increasing age. FSH and testosterone showed small seasonal variations in young adult men, the lowest values being seen in winter. SHBG binding capacity was high in two prepubertal boys, fell in adult men, but increased in old age. Free testosterone and oestradiol levels fell in old age. The metabolic clearance rates (MCR) of testosterone and oestradiol also fell in old age, while the conversion of testosterone to oestradiol was increased. Many correlations were observed between various hormonal and clincial measurements. The evidence is consistent with a primary decrease in testicular function over the age of 40 years.
Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study.
Barrett-Connor E, Von Muhlen DG, Kritz-Silverstein D. Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, La Jolla 92093-0607, USA.
J Clin Endocrinol Metab 1999 Feb;84(2):573-7
A cross-sectional population-based study examined the association between endogenous sex hormones and depressed mood in community-dwelling older men. Participants included 856 men, ages 50-89 yr, who attended a clinic visit between 1984-87. Total and bioavailable testosterone, total and bioavailable estradiol, and dihydrotestosterone levels were measured by radioimmunoassay in an endocrinology research laboratory. Depressed mood was assessed with the Beck Depression Inventory (BDI). Levels of bioavailable testosterone and bioavailable estradiol decreased with age, but total testosterone, dihydrotestosterone, and total estradiol did not. BDI scores increased with age. Low bioavailable testosterone levels and high BDI scores were associated with weight loss and lack of physical activity, but not with cigarette smoking or alcohol intake. By linear regression or quartile analysis the BDI score was significantly and inversely associated with bioavailable testosterone (both Ps = 0.007), independent of age, weight change, and physical activity; similar associations were seen for dihydrotestosterone (P = 0.048 and P = 0.09, respectively). Bioavailable testosterone levels were 17% lower for the 25 men with categorically defined depression than levels observed in all other men (P = 0.01). Neither total nor bioavailable estradiol was associated with depressed mood. These results suggest that testosterone treatment might improve depressed mood in older men who have low levels of bioavailable testosterone. A clinical trial is necessary to test this hypothesis.
Brief communication. Vitamin B1, B2, and B6 augmentation of tricyclic antidepressant treatment in geriatric depression with cognitive dysfunction.
Bell IR, Edman JS, Morrow FD, Marby DW, Perrone G, Kayne HL, Greenwald M, Cole JO. Department of Psychiatry, Harvard Medical School.
J Am Coll Nutr 1992 Apr;11(2):159-63
This was a 4-week randomized placebo-controlled double-blind study to assess augmentation of open tricyclic antidepressant treatment with 10 mg each of vitamins B1, B2, and B6 in 14 geriatric inpatients with depression. The active vitamin group demonstrated significantly better B2 and B6 status on enzyme activity coefficients and trends toward greater improvement in scores on ratings of depression and congnitive function, as well as in serum nortriptyline levels compared with placebo-treated subjects (Ss). Without specific supplementation, B12 levels increased in Ss receiving B1/B2/B6 and decreased in placebo Ss. These findings offer preliminary support for further investigation of B complex vitamin augmentation in the treatment of geriatric depression.
Mood alteration with yoga and swimming: aerobic exercise may not be necessary.
Berger BG, Owen DR. Department of Physical Education, Brooklyn College, City University of New York 11210.
Percept Mot Skills 1992 Dec;75(3 Pt 2):1331-43
The mood benefits of Hatha yoga and swimming, two activities that differ greatly in aerobic training benefits, were examined. College students (N = 87) in two swimming classes, a yoga class, and a lecture-control class completed mood and personality inventories before and after class on three occasions. A multivariate analysis of variance indicated that both yoga participants (n = 22) and swimmers (n = 37) reported greater decreases in scores on Anget, Confusion, Tension, and Depression than did the control students (n = 28). The consistent mood benefits of yoga supported our earlier observation that the exercise need not be aerobic to be associated with mood enhancement. However, underlying and causal mechanisms remain uncertain. Among the men, the acute decreases in Tension, Fatigue, and Anger after yoga were significantly greater than those after swimming. Yoga may be even more beneficial than swimming for men who personally select to participate. The women reported fairly similar mood benefits after swimming and yoga. It seems that aerobic exercise may not be necessary to facilitate the mood benefits. Also, students with greater mood changes attended class more regularly than those who reported fewer psychological benefits. Maximizing the immediate psychological benefits of exercise might be one way to encourage adults to be physically active.
Familial gynecomastia with increased extraglandular aromatization of plasma carbon19-steroids.
Berkovitz GD, Guerami A, Brown TR, MacDonald PC, Migeon CJ
J Clin Invest 1985 Jun;75(6):1763-9
We evaluated a family in which gynecomastia occurred in five males in two generations. In each affected subject, gynecomastia and male sexual maturation began at an early age. The ratio of the concentration of plasma estradiol-17 beta to that of plasma testosterone was elevated in each affected subject. In the three siblings with gynecomastia, the transfer constant of conversion of androstenedione to estrone (i.e., the fraction of plasma androstenedione that was converted to estrone as measured in the urine) was 10 times that of normal persons. The transfer constant of conversion of testosterone to estradiol-17 beta in the one subject studied also was 8-10 times that of normal men, whereas the transfer constants of conversion of estrone to estradiol-17 beta and of estradiol-17 beta to estrone were normal. Despite the elevation in extraglandular aromatase activity, there was a normal response of the hypothalamic-pituitary axis to provocative stimuli. This is the second documentation of gynecomastia that is associated with increased extraglandular aromatase activity, and the first time that the defect was found to be familial with a probable X-linked (or autosomal dominant, sex limited) mode of inheritance.
Efficacy of S-adenosyl-L-methionine in speeding the onset of action of imipramine
Berlanga C, Ortega-Soto HA, Ontiveros M, Senties H Special Studies Clinic, Mexican Institute of Psychiatry, Tlalpan. Psychiatry Res 1992 Dec;44(3):257-62
A double-blind clinical trial was carried out to evaluate the efficacy of S-adenosyl-L-methionine (SAMe) in speeding the onset of action of imipramine (IMI). SAMe is a naturally occurring substance that has been shown to possess antidepressant activity with a rapid mode of onset and minimal side effects. Sixty-three outpatients with moderate to severe depression were included in the study. After an initial 1-week placebo period, only 40 patients entered the active treatment phase. During the first 2 weeks of the trial, half of these patients received 200 mg/day of SAMe intramuscularly, while the other half received placebo. Simultaneously, oral IMI was administered to all patients at a fixed dose of 150 mg/day. The onset of clinical response was determined by evaluating patients every second day. By the end of week 2, the parenteral treatment was suppressed and IMI was adjusted according to individual needs. Depressive symptoms decreased earlier in the patients who were receiving the SAMe-IMI combination than in those who were receiving the placebo-IMI combination.
5-Hydroxytryptophan: a clinically-effective serotonin precursor.
Birdsall TC. 73541.2166@compuserve.com
Altern Med Rev 1998 Aug;3(4):271-80
5-Hydroxytryptophan (5-HTP) is the intermediate metabolite of the essential amino acid L-tryptophan (LT) in the biosynthesis of serotonin. Intestinal absorption of 5-HTP does not require the presence of a transport molecule, and is not affected by the presence of other amino acids; therefore it may be taken with meals without reducing its effectiveness. Unlike LT, 5-HTP cannot be shunted into niacin or protein production. Therapeutic use of 5-HTP bypasses the conversion of LT into 5-HTP by the enzyme tryptophan hydroxylase, which is the rate-limiting step in the synthesis of serotonin. 5-HTP is well absorbed from an oral dose, with about 70 percent ending up in the bloodstream. It easily crosses the blood-brain barrier and effectively increases central nervous system (CNS) synthesis of serotonin. In the CNS, serotonin levels have been implicated in the regulation of sleep, depression, anxiety, aggression, appetite, temperature, sexual behaviour, and pain sensation. Therapeutic administration of 5-HTP has been shown to be effective in treating a wide variety of conditions, including depression, fibromyalgia, binge eating associated with obesity, chronic headaches, and insomnia.
L-deprenyl plus L-phenylalanine in the treatment of depression.
Birkmayer W, Riederer P, Linauer W, Knoll J.
J Neural Transm 1984;59(1):81-7
The antidepressive efficacy of 1-deprenyl (5-10 mg daily) plus 1-phenylalanine (250 mg/day) has been evaluated in 155 unipolar depressed patients. Both oral and intravenous administration showed beneficial effects in 90% of outpatients and 80.5% of inpatients. It is concluded that this combined treatment has a potent antidepressive action based on the accumulation of 1-phenylethylamine in the brain.
Dehydroepiandrosterone treatment of midlife dysthymia.
Bloch M, Schmidt PJ, Danaceau MA, Adams LF, Rubinow DR. Behavioral Endocrinology Branch, National Institute of Mental Health, Bethesda, MD 20892-1276, USA.
Biol Psychiatry 1999 Jun 15;45(12):1533-41
BACKGROUND: This study evaluated the efficacy of the adrenal androgen, dehydroepiandrosterone, in the treatment of midlife-onset dysthymia.
METHODS: A double-blind, randomized crossover treatment study was performed as follows: 3 weeks on 90 mg dehydroepiandrosterone, 3 weeks on 450 mg dehydroepiandrosterone, and 6 weeks on placebo. Outcome measures consisted of the following. Cross-sectional self-ratings included the Beck Depression Inventory, and visual analogue symptom scales. Cross-sectional objective ratings included the Hamilton Depression Rating Scale, the Cornell Dysthymia Scale and a cognitive test battery. Seventeen men and women aged 45 to 63 years with midlife-onset dysthymia participated in this study. Response to dehydroepiandrosterone or placebo was defined as a 50% reduction from baseline in either the Hamilton Depression Rating Scale or the Beck Depression Inventory.
RESULTS: In 15 patients who completed the study, a robust effect of dehydroepiandrosterone on mood was observed compared with placebo. Sixty percent of the patients responded to dehydroepiandrosterone at the end of the 6-week treatment period compared with 20% on placebo. A significant response was seen after 3 weeks of treatment on 90 mg per day. The symptoms that improved most significantly were anhedonia, loss of energy, lack of motivation, emotional "numbness," sadness, inability to cope, and worry. Dehydroepiandrosterone showed no specific effects on cognitive function or sleep disturbance, although a type II error could not be ruled out.
CONCLUSIONS: This pilot study suggests that dehydroepiandrosterone is an effective treatment for midlife-onset dysthymia.
Effects of exercise training on older patients with major depression.
Blumenthal JA, Babyak MA, Moore KA, Craighead WE, Herman S, Khatri P, Waugh R, Napolitano MA, Forman LM, Appelbaum M, Doraiswamy PM, Krishnan KR. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. blume003@mc.duke.edu
Arch Intern Med 1999 Oct 25;159(19):2349-56
BACKGROUND: Previous observational and interventional studies have suggested that regular physical exercise may be associated with reduced symptoms of depression. However, the extent to which exercise training may reduce depressive symptoms in older patients with major depressive disorder (MDD) has not been systematically evaluated.
OBJECTIVE: To assess the effectiveness of an aerobic exercise program compared with standard medication (ie, antidepressants) for treatment of MDD in older patients, we conducted a 16-week randomized controlled trial.
METHODS: One hundred fifty-six men and women with MDD (age, < or = 50 years) were assigned randomly to a program of aerobic exercise, antidepressants (sertraline hydrochloride), or combined exercise and medication. Subjects underwent comprehensive evaluations of depression, including the presence and severity of MDD using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) scores before and after treatment. Secondary outcome measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions.
RESULTS: After 16 weeks of treatment, the groups did not differ statistically on HAM-D or BDI scores (P = .67); adjustment for baseline levels of depression yielded an essentially identical result. Growth curve models revealed that all groups exhibited statistically and clinically significant reductions on HAM-D and BDI scores. However, patients receiving medication alone exhibited the fastest initial response; among patients receiving ombination therapy, those with less severe depressive symptoms initially showed a more rapid response than those with initially more severe depressive symptoms.
CONCLUSIONS: An exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons. Although antidepressants may facilitate a more rapid initial therapeutic response than exercise, after 16 weeks of treatment exercise was equally effective in reducing depression among patients with MDD.
The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders
Bottiglieri T, Hyland K, Reynolds EH Metabolic Disease Center, Baylor Research Institute, Dallas, Texas.
Drugs 1994 Aug;48(2):137-52
This review focuses on the biochemical and clinical aspects of methylation in neuropsychiatric disorders and the clinical potential of their treatment with ademetionine (S-adenosylmethionine; SAMe). SAMe is required in numerous transmethylation reactions involving nucleic acids, proteins, phospholipids, amines and other neurotransmitters. The synthesis of SAMe is intimately linked with folate and vitamin B12 (cyanocobalamin) metabolism, and deficiencies of both these vitamins have been found to reduce CNS SAMe concentrations. Both folate and vitamin B12 deficiency may cause similar neurological and psychiatric disturbances including depression, dementia, myelopathy and peripheral neuropathy. SAMe has a variety of pharmacological effects in the CNS, especially on monoamine neurotransmitter metabolism and receptor systems. SAMe has antidepressant properties, and preliminary studies indicate that it may improve cognitive function in patients with dementia. Treatment with methyl donors (betaine, methionine and SAMe) is associated with remyelination in patients with inborn errors of folate and C-1 (one-carbon) metabolism. These studies support a current theory that impaired methylation may occur by different mechanisms in several neurological and psychiatric disorders.
Homocysteine, folate, methylation, and monoamine metabolism in depression.
Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH. Department of Neurology, King's College Hospital, London, UK.
J Neurol Neurosurg Psychiatry 2000 Aug;69(2):228-32
OBJECTIVES: Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, difficulties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression.
METHODS: In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes.
RESULTS: Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls.
CONCLUSIONS: Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement.
Comparison of an extract of hypericum (LI 160) and sertraline in the treatment of depression: a double-blind, randomized pilot study.
Brenner R, Azbel V, Madhusoodanan S, Pawlowska M. St. John's Episcopal Hospital, Far Rockaway, New York 11691, USA.
Clin Ther 2000 Apr;22(4):411-9
BACKGROUND: Hypericum (St. John's wort) has been shown to be as efficacious and well tolerated as standard antidepressants in the treatment of depression but has not been compared with selective serotonin reuptake inhibitors (SSRIs).
OBJECTIVE: This study compared hypericum and the SSRI sertraline in the treatment of depression.
METHODS: In a double-blind, randomized study conducted in a community hospital, 30 male and female outpatients (19 women, 11 men; mean age, 45.5 years) with mild to moderate depression received 600 mg/d of a standardized extract of hypericum (LI 160) or 50 mg/d sertraline for I week, followed by hypericum 900 mg/d or sertraline 75 mg/d for 6 weeks.
RESULTS: The severity of symptoms, as assessed by scores on the Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impression scale, was significantly reduced in both treatment groups (< 0.01). Clinical response (defined as a < or =50% reduction in HAM-D scores) was noted in 47% of patients receiving hypericum and 40% of those receiving sertraline. The difference was not statistically significant. Both agents were well tolerated. A post hoc power analysis indicated that failure to reach statistical significance between treatments resulted primarily from an absence of clinical differences rather than the small sample size.
CONCLUSION: The hypericum extract was at least as effective as sertraline in the treatment of mild to moderate depression in a small group of outpatients.
S-adenosyl-l-methionine (SAMe) as antidepressant: Meta-analysis of clinical studies
Bressa GM Department of Psychiatry, University Cattolica Sacro Cuore School of Medicine, Rome, Italy.
Acta Neurol Scand Suppl 1994;154:7-14
Introduction - S-adenosyl-l-methionine (SAMe) is a naturally-occurring substance which is a major source of methyl groups in the brain. Material and methods - We conducted a meta-analysis of the studies on SAMe to assess the efficacy of this compound in the treatment of depression compared with placebo and standard tricyclic antidepressants. Results - Our meta-analysis showed a greater response rate with SAMe when compared with placebo, with a global effect size ranging from 27% to 38% depending on the definition of response, and an antidepressant effect comparable with that of standard tricyclic antidepressants. Conclusion - The efficacy of SAMe in treating depressive syndromes and disorders is superior with that of placebo and comparable to that of standard tricyclic antidepressants. Since SAMe is a naturally occurring compound with relatively few side-effects, it is a potentially important treatment for depression.
[Effect of pyridoxine on the psychopathology and pathochemistry of involutional depressions] [Article in Russian]
Bukreev VI.
Zh Nevropatol Psikhiatr Im S S Korsakova 1978;78(3):402-8
In agreement with the catecholamine hypotheses of affective disorders the main role in the pathogenesis of depressive states is allocated to the central "noradrenergic insufficiency". The author thinks it feasible to use pyridoxine (vit. B6) in the treatment of depressive states, inasmuch as it is involved in the process of catecholamine synthesis as a cofactor of DOPA-decarboxylase. The author examined 48 patients among which 31 were with involutional melancholia and 17 with manic-depressive psychoses, manifesting after 40 years. Along with a positive therapeutical effect there was an increase in the noradrenaline excretion and a drop in the relative adrenaline content.
Neuropsychiatric disorders associated with nutritional deficiencies. Incidence and therapeutic implications
Carney M.W.P. Hill House, Mount Park Road,Harrow-on-the-Hill, Middlesex HA13JY United Kingdom
CNS Drugs ( CNS DRUGS ) (New Zealand) 1995, 3/4 (279-290) Deficiencies of various vitamins are associated with a variety of neuropsychiatric manifestations. Depression is a feature of deficiencies of folic acid, vitamin B 2 (riboflavin) and vitamin B 6 (pyridoxine), while vitamin B 1 (thiamine) deficiency is associated with several psychosyndromes including alcoholism and schizophrenia. Data from recent studies of vitamin deficiency reveal that gross manifestations such as beri-beri (characteristics include Wernicke's encephalopathy and Korsakoff's syndrome) and pellagra (characteristics include fatigue, insomnia and encephalopathy) are now relatively rare in the Western world. However, milder and subclinical syndromes are still common. For example, the prevalence of low levels of vitamin B 12 (cyanocobalamin) is has been estimated to be 5.8 to 26.1% in psychiatric patients, while that of folic acid is higher at 15 to 51% (derived from various studies). Despite these apparent associations, whether deficiencies of vitamins are causal in neuropsychiatric disorders or a result of them is difficult to determine. For example, there is little direct evidence of a causal role for folic acid in neuropsychiatric disorders, except in the rare in-born errors of metabolism that present with neuropsychiatric abnormalities. It is known that folic acid deficiency is associated with the use of many therapeutic drugs, concomitant physical illnesses and chronicity of psychiatric illness. However, retrospective studies of the effects of folic acid replacement therapy in deficient patients, employing clinical and social outcome criteria, have shown an improvement in psychiatric symptoms over a period of 6 to 12 months in most patients. Controlled studies of folic acid replacement therapy are also encouraging. In 1 double-blind, placebo-controlled add-on trial involving patients with endogenous depression and schizophrenia, the majority of folic acid treated patients improved compared with placebo recipients. The situation with regard to a causal role for other vitamins in neuropsychiatric disorders is even less clear. Obviously, more data are needed in this area to assist clinicians in determining the aetiology of episodes of depression and other neuropsychiatric disorders and, ultimately, their treatment.
Red cell folate concentrations in psychiatric patients
Carney M.W.P.; Chary T.K.N.; Laundy M.; Bottiglieri T.; Chanarin I.; Reynolds E.H.; Toone B. Department of Psychiatry, Clinical Research Centre, Northwick Park Hospital, Watford Road,Harrow HA1 3UJ United Kingdom
Journal of Affective Disorders ( J. AFFECT. DISORD. ) (Netherlands) 1990, 19/3 (207-213) Red cell folate and vitamin B12 estimations were performed on 243 successively admitted in-patients at a District General Hospital Psychiatric Unit and 42 out-patients (29 attending a lithium clinic). Patients were classified into five diagnostic groups. The mean ages of the manic and schizophrenic patients were lower than of the depressed or euthymic patients but age was not correlated with red cell folate or serum B12 levels in any group. There were 89 (31%) patients with red cell folate below 200 ng/ml and 35 (12%) with concentrations below 150 ng/ml. Significantly more of these low-folate patients were in-patients than outpatients. The mean red cell folate in the depressed patients was significantly lower than in the euthymic, manic and schizophrenic groups. Alcoholics had a similar mean red cell folate to depressed patients which was not quite significantly lower than the other groups. The mean serum B12 level in the alcoholics was, however, significantly raised. There were no significant differences in red cell folate or serum B12 between lithium-treated and untreated euthymic patients. The highest proportions of values below 200 ng/ml and 150 ng/ml were found in depressed and alcoholic patients. Endogenous depressives had the highest percentage of values below 150 ng/ml (folate-deficient) of all psychiatric groups and alcoholic patients. The significance of these findings is discussed.
S-Adenosylmethionine treatment of depression in patients with Parkinson's disease: a double-blind, crossover study versus placebo.
Carrieri, P.B. et al.
Curr. Ther. Res. 1990; 48: 154-60.
No abstract available.
St. John's Wort: Nature's Blues Buster 1998.
Cass, H.
East Rutherford, NJ: Avery.
A controlled clinical trial of L-tryptophan in acute mania.
Chouinard G, Young SN, Annable L.
Biol Psychiatry 1985 May;20(5):546-57
In a 2-week study, 24 newly admitted manic patients were treated for 1 week with L-tryptophan (12 g/day); during the second week, half the patients, chosen at random, continued to receive tryptophan, while placebo was substituted in the other half under double-blind conditions. In the open phase of the study, there was a clinically and statistically (p less than 0.001) significant reduction in manic symptom scores, with little need for haloperidol prn. Patients who continued to be treated with tryptophan showed no significant change in mean scores during the second week, but those who were switched to placebo tended (p less than 0.10) to show an increase in the mean scores for manic symptoms. There was a significant (p less than 0.05) increase in the geometric mean of morning fasting total and free plasma tryptophan concentrations in men, but not in women. These results suggest that increasing the synthesis of 5-hydroxytryptamine has some therapeutic effect in mania.
Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial.
Coppen A, Bailey J. MRC Neuropsychiatry Laboratory, West Park Hospital, KT19 8PB, Surrey, Epsom, UK.
J Affect Disord 2000 Nov;60(2):121-30
BACKGROUND: A consistent finding in major depression has been a low plasma and red cell folate which has also been linked to poor response to antidepressants. The present investigation was designed to investigate whether the co-administration of folic acid would enhance the antidepressant action of fluoxetine.
METHODS: 127 patients were randomly assigned to receive either 500 microg folic acid or an identical looking placebo in addition to 20 mg fluoxetine daily. All patients met the DSM-III-R criteria for major depression and had a baseline Hamilton Rating Scale (17 item version) score for depression of 20 or more. Baseline and 10-week estimations of plasma folate and homocysteine were carried out.
RESULTS: Patients receiving folate showed a significant increase in plasma folate.This was less in men than in women. Plasma homocysteine was significantly decreased in women by 20.6%, but there was no significant change in men. Overall there was a significantly greater improvement in the fluoxetine plus folic acid group. This was confined to women where the mean Hamilton Rating Scale score on completion was 6.8 (S.D. 4. 1) in the fluoxetine plus folate group, as compared to 11.7 (S.D. 6. 7) in the fluoxetine plus placebo group (< 0.001).A percentage of 93. 9 of women, who received the folic acid supplement, showed a good response (< 50% reduction in score) as compared to 61.1% of women who received placebo supplement (< 0.005). Eight (12.9%) patients in the fluoxetine plus folic acid group reported symptoms possibly or probably related to medication, whereas in the fluoxetine plus placebo group 19 (29.7%) patients reported such symptoms (< 0.05).
LIMITATIONS AND CONCLUSIONS: Folic acid is a simple method of greatly improving the antidepressant action of fluoxetine and probably other antidepressants. Folic acid should be given in doses sufficient to decrease plasma homocysteine. Men require a higher dose of folic acid to achieve this than women, but more work is required to ascertain the optimum dose of folic acid.
S-Adenosyl-Methionine improves depression in patients with Parkinson's disease in an open-label clinical trial.
Di Rocco A, Rogers JD, Brown R, Werner P, Bottiglieri T.
Department of Neurology, Beth Israel Medical Center-Albert Einstein College of Medicine, New York, NY 10003, USA.
Mov Disord 2000 Nov;15(6):1225-9
We report a pilot study of S-adenosyl-methionine (SAM) in 13 depressed patients with Parkinson's disease. All patients had been previously treated with other antidepressant agents and had no significant benefit or had intolerable side effects. SAM was administered in doses of 800 to 3600 mg per day for a period of 10 weeks. Eleven patients completed the study, and 10 had at least a 50% improvement on the 17-point Hamilton Depression Scale (HDS). One patient did not improve. Two patients prematurely terminated participation in the study because of increased anxiety. One patient experienced mild nausea, and another two patients developed mild diarrhea, which resolved spontaneously. The mean HDS score before treatment was 27.09 +/- 6.04 (mean +/- standard deviation) and was 9.55 +/- 7.29 after SAM treatment (< 0.0001). Although uncontrolled and preliminary, this study suggests that SAM is well tolerated and may be a safe and effective alternative to the antidepressant agents currently used in patients with Parkinson's disease.
Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients.
Edwards R, Peet M, Shay J, Horrobin D. University Department of Psychiatry, University of Sheffield, UK.
J Affect Disord 1998 Mar;48(2-3):149-55
BACKGROUND: There is a hypothesis that lack of n-3 polyunsaturated fatty acids (PUFAs) is of aetiological importance in depression. Docosahexaenoic acid, a member of the n-3 PUFA family, is a crucial component of synaptic cell membranes. The aim of this study was to measure RBC membrane fatty acids in a group of depressed patients relative to a well matched healthy control group. METHOD: Red blood cell (RBC) membrane levels, and dietary PUFA intake were measured in 10 depressed patients and 14 matched healthy control subjects. RESULTS: There was a significant depletion of RBC membrane n-3 PUFAs in the depressed subjects which was not due to reduced calorie intake. Severity of depression correlated negatively with RBC membrane levels and with dietary intake of n-3 PUFAs. CONCLUSION: Lower RBC membrane n-3 PUFAs are associated with the severity of depression. LIMITATIONS: Although patient numbers were small, confounding factors were well controlled for and the results were highly significant. Results of the dietary data would tend to be weakened due to the limitations associated with dietary assessment. CLINICAL RELEVANCE: The findings raise the possibility that depressive symptoms may be alleviated by n-3 PUFA supplementation.
[Acupuncture in patients with minor depressive episodes and generalized anxiety. Results of an experimental study] [Article in German]
Eich H, Agelink MW, Lehmann E, Lemmer W, Klieser E. Klinik fur Psychiatrie und Psychotherapie, am Evangelischen Krankenhaus Gelsenkirchen Universitatsklinik der Ruhr-Universitat Bochum.
Fortschr Neurol Psychiatr 2000 Mar;68(3):137-44
In a placebo-controlled, randomized, modified double-blind study we investigated the effects of body needle acupuncture (n = 10) in 43 patients with minor depression (ICD 10 F32.0, F32.1) and 13 patients with generalized anxiety disorders (ICD10 F41.1). The severity of the disease was assessed by the Clinical Global Impression Scale (CGI). Treatment response was defined as a significant improvement in CGI. An intent-to-treat analysis was performed to compare treatment responses between verum- and placebo acupuncture. After completing an total of 10 acupuncture sessions the verum acupuncture group (n = 28) showed a significantly larger clinical improvement compared to the placebo group (Mann-Whitney test, < 0.05). There were significantly more responders in the verum-compared to the placebo group (60.7% vs. 21.4%; chi-square test, < 0.01). In contrast, no differences in the response rates were evident just after 5 acupuncture sessions. A multivariate analysis with the independent factor acupuncture (verum vs. placebo) and the results of the results of the additional rating scales (total score of HAMA, HAMD, Bf-S, BL) as dependent variables (ANOVA, 1:54 D.F.) revealed a clear trend towards lower HAMA scores in the verum group after completing 10 acupunctures (F3.29, p = 0.075). This corresponds well to the high response rate of 85.7% in patients with generalized anxiety disorders, in whom verum acupuncture was applied. Our results indicate that needle acupuncture (Du.20, Ex.6, He.7, Pe.6, Bl.62) leads to a significant clinical improvement as well as to a remarkable reduction in anxiety symptoms in patients with minor depression or with generalized anxiety disorders. The total sum of acupuncture sessions and the specific location of acupuncture needle insertions might be important factors for bringing about therapeutic success.
A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression.
Emslie GJ, Rush AJ, Weinberg WA, Kowatch RA, Hughes CW, Carmody T, Rintelmann J. Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, USA.
Arch Gen Psychiatry 1997 Nov;54(11):1031-7
BACKGROUND: Depression is a major cause of morbidity and mortality in children and adolescents. To date, randomized, controlled, double-blind trials of antidepressants (largely tricyclic agents) have yet to reveal that any antidepressant is more effective than placebo. This article is of a randomized, double-blind, placebo-controlled trial of fluoxetine in children and adolescents with depression. METHODS: Ninety-six child and adolescent outpatients (aged 7-17 years) with nonpsychotic major depressive disorder were randomized (stratified for age and sex) to 20 mg of fluoxetine or placebo and seen weekly for 8 consecutive weeks. Randomization was preceded by 3 evaluation visits that included structured diagnostic interviews during 2 weeks, followed 1 week later by a 1-week, single-blind placebo run-in. Primary outcome measurements were the global improvement of the Clinical Global Impressions scale and the Children's Depression Rating Scale--Revised, a measure of the severity depressive symptoms. RESULTS: Of the 96 patients, 48 were randomized to fluoxetine treatment and 48 to placebo. Using the intent to treat sample, 27 (56%) of those receiving fluoxetine and 16 (33%) receiving placebo were rated "much" or "very much" improved on the Clinical Global Impressions scale at study exit (chi 2 = 5.1, df = 1, P = .02). Significant differences were also noted in weekly ratings of the Children's Depression Rating Scale--Revised after 5 weeks of treatment (using last observation carried forward). Equivalent response rates were found for patients aged 12 years and younger (n = 48) and those aged 13 years and older (n = 48). However, complete symptom remission (Children's Depression Rating Scale--Revised < or = 28) occurred in only 31% of the fluoxetine-treated patients and 23% of the placebo patients. CONCLUSION: Fluoxetine was superior to placebo in the acute phase treatment of major depressive disorder in child and adolescent outpatients with severe, persistent depression. Complete remission of symptoms was rare.
Massage therapy effects.
Field TM. Touch Research Institute, University of Miami School of Medicine, FL 33101, USA.
Am Psychol 1998 Dec;53(12):1270-81
Massage therapy is older than recorded time, and rubbing was the primary form of medicine until the pharmaceutical revolution of the 1940s. Popularized again as part of the alternative medicine movement, massage therapy has recently received empirical support for facilitating growth, reducing pain, increasing alertness, diminishing depression, and enhancing immune function. In this article studies are reviewed that document these effects, and models are proposed for potential underlying mechanisms.
Comparison of regimens containing oral micronized progesterone or medroxyprogesterone acetate on quality of life in postmenopausal women: a cross-sectional survey.
Fitzpatrick LA, Pace C, Wiita B. Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
J Womens Health Gend Based Med 2000 May;9(4):381-7
A cross-sectional survey was conducted to examine quality of life (QOL) related to physiological, somatic, and vasomotor effects of changing progestogen treatment from medroxyprogesterone acetate (MPA) to micronized progesterone in postmenopausal women. Eligible women (n = 176) were currently using hormone replacement therapy (HRT) containing micronized progesterone for 1-6 months and had previously received HRT containing MPA. QOL was assessed via telephone interview using the Greene Climacteric Scale and the Women's Health Questionnaire. When compared with the MPA-containing regimen, women using micronized progesterone-containing HRT experienced significant improvement in vasomotor symptoms, somatic complaints, and anxiety and depressive symptoms. Women reported improved perceptions of their patterns of vaginal bleeding and control of menopausal symptoms while on the micronized progesterone-containing regimen. Approximately 80% of women reported overall satisfaction with the micronized progesterone-containing regimen. A micronized progesterone-containing HRT regimen offers the potential for improved QOL as measured by improvement of menopause-associated symptoms.
Effect of vitamin B complex on neurotransmission and neurite outgrowth.
Fujii A, Matsumoto H, Yamamoto H. Department of Pharmacology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
Gen Pharmacol 1996 Sep;27(6):995-1000
1. The effect of vitamin B complex (vitamin B1, B6 and B12) was studied on nerve conduction velocity in acrylamide-neuropathy rats maintained on refined semisynthetic complete vitamin and vitamin B-deficient diets in vivo and on neurite outgrowth in vitro using cells obtained from dorsal root ganglions of mice. 2. Acrylamide neuropathy was clearer in the group maintained on a refined semisynthetic vitamin B-deficient diet than in those on a refined semisynthetic complete vitamin diet. The neurotoxicity was lowest in the group given vitamin B complex prophylactic-therapeutically, next higher following therapeutic administration and last with no vitamin B complex administration in both groups maintained on a refined semisynthetic vitamin B-deficient diet and a refined semisynthetic complete vitamin diet. 3. The nerve conduction velocity tended to decrease by treatment with acrylamide. The decrement of nerve conduction velocity was partially inhibited by vitamin B complex. No significant difference was found in the groups treated with acrylamide and given vitamin B complex prophylactic-therapeutically and the control (no acrylamide treatment) in the group maintained on a refined semisynthetic vitamin B-deficient diet. 4. The greatest neurite outgrowth was found in the group treated with vitamins B1, B6 and B12-enriched medium, followed by the group of vitamin B12-enriched and vitamin B1-enriched media. All groups treated with a vitamin B-enriched medium had significantly greater (< 0.01) outgrowth than the controls.
The making of a user friendly MAOI diet.
Gardner DM, Shulman KI, Walker SE, Tailor SA. Department of Pharmacy, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada.
J Clin Psychiatry 1996 Mar;57(3):99-104
BACKGROUND: Many monoamine oxidase inhibitor (MAOI) diets are considered to be excessively restrictive and founded on poor scientific evidence. We present a safe and practical MAOI diet based on the related clinical and analytic data. METHOD: We used a critical review of the literature and our own tyramine assay results to categorize foods to be restricted absolutely, taken in moderation only, or unrestricted. RESULTS: We recommend that users avoid aged cheese; aged or cured meats (e.g., air-dried sausage); any potentially spoiled meat, poultry, or fish; broad (fava) bean pods; Marmite concentrated yeast extract; sauerkraut; soy sauce and soy bean condiments; and tap beer. Wine and domestic bottled or canned beer are considered safe when consumed in moderation. Other foods not mentioned are considered unrestricted. CONCLUSION: The concerns about perpetuating an overly restrictive MAOI diet include the avoidance by prescribers of a potentially useful treatment option, excessive limitations on lifestyle for patients, and increased risk to patients secondary to noncompliance with the diet. We propose an MAOI diet that has a solid scientific and clinical basis and that is, above all, practical.
St John's wort for depression: a systematic review.
Gaster B, Holroyd J. Department of Medicine, University of Washington, Seattle, USA. barakg@u.washington.edu
Arch Intern Med 2000 Jan 24;160(2):152-6
To address whether St John's wort is useful for the treatment of depression we attempted to retrieve all English-language articles with data on the efficacy, safety, and availability of St John's wort. Randomized, controlled, double-blind trials were selected and assessed for methodological quality using a standardized checklist, and data on pharmacology, cost, regulation, and safety were extracted. Eight studies were identified, found to be of generally good methodological quality, and determined to provide a modest amount of data to suggest that St John's wort is more effective than placebo in the treatment of mild to moderate depression. The absolute increased response rate with the use of St John's wort ranged from 23% to 55% higher than with placebo, but ranged from 6% to 18% lower compared with tricyclic antidepressants. More data are required to assess both its use in severe depression and its efficacy compared with other antidepressants. Rates of side effects were low. As a dietary supplement, St John's wort is currently largely unregulated, but the Food and Drug Administration is reviewing plans to tighten its regulatory oversight.
St. John's Wort extract: efficacy for menopausal symptoms of psychological origin.
Grube B, Walper A, Wheatley D. Lichtwer Pharma AG, Berlin, Germany.
Adv Ther 1999 Jul-Aug;16(4):177-86
Herbal remedies such as St. John's Wort preparations can be used successfully to relieve the psychological and vegetative symptoms of menopause. This drug-monitoring study investigated 12 weeks of treatment with St. John's Wort, one tablet three times daily (900 mg Hypericum, Kira), in 111 women from a general medical practice. The patients, who were between 43 and 65 years old, had climacteric symptoms characteristic of the pre- and postmenopausal state. Treatment outcome was evaluated by the Menopause Rating Scale, a self-designed questionnaire for assessing sexuality, and the Clinical Global Impression scale. The incidence and severity of typical psychological, psychosomatic, and vasomotor symptoms were recorded at baseline and after 5, 8, and 12 weeks of treatment. Substantial improvement in psychological and psychosomatic symptoms was observed. Climacteric complaints diminished or disappeared completely in the majority of women (76.4% by patient evaluation and 79.2% by physician evaluation). Of note, sexual well-being also improved after treatment with St. John's Wort extract.
Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine.
Harrer G, Schmidt U, Kuhn U, Biller A. Institut fur Forensische Psychiatrie der Universitat Salzburg, Germany.
Arzneimittelforschung 1999 Apr;49(4):289-96
In a randomised double-blind comparative trial, the antidepressant efficacy of a daily dose of 800 mg of the St. John's wort extract LoHyp-57 (dry extract of St. John's wort, drug extrakt ratio 5-7:1, solvent, ethanol 60% [w/w]) was shown to be equivalent to that of 20 mg fluoxetine (CAS 54910-89-3) in elderly patients with mild or moderate depressive episodes according to ICD 10 (International Statistical Classification of Diseases and Related Health Problems). Treatment was given for six weeks. 149 out-patients (129 females and 20 males) were included in the intention-to-treat analysis. 72 of these patients were assigned to the ICD 10 diagnostic criterion F32.0 (mild depressive episode), while 77 patients were suffering from moderate depressive episodes, corresponding to F32.1. The principal target criterion was the patient's global score on the HAMILTON Depression Scale (items 1-17). During the six-week course of treatment with LoHyp-57, the HAMILTON global score fell from 16.60 points at entry to 7.91 points, and in the fluoxetine sample it fell from 17.18 to 8.11 points. In the group of patients with mild depressive episodes, the score showed a mean fall from 14.21 to 6.21 points on LoHyp-57, and from 15.21 to 7.46 points on fluoxetine. In patients with moderate depressive episodes, the score showed a mean fall from 18.73 to 9.43 points on LoHyp-57 and from 19.10 to 8.75 points on fluoxetine. The efficacy of both medications was found to be equivalent both in mild and moderate depressive episodes. Both treatment groups showed adverse drug reactions (ADRs). Twelve ADRs with a possible relationship to the study medication were reported during treatment with LoHyp-57. Six patients were prematurely withdrawn from treatment with the study medication for this reason. On fluoxetine 17 ADRs occurred with a possible relationship to the study medication. These led to abandonment of treatment and therefore premature withdrawal from the study in 8 cases.
Group exercise reduces depression in obese women without weight loss.
Hayward LM, Sullivan AC, Libonati JR. Department of Physical Therapy, Bouve College of Health Sciences, Northeastern University, Boston, MA, USA. lhayward@lynx.neu.edu
Percept Mot Skills 2000 Feb;90(1):204-8
Given participation in a 6-mo. exercise and relaxation training 8 obese women showed significant change in scores on the Beck Depression Inventory over the 6-mo. interval, but not on Body Mass Index or Medical Outcome Study Short-Form-36.
Dietary polyunsaturated fatty acids and depression: when cholesterol does not satisfy.
Hibbeln JR, Salem N Jr. Laboratory of Membrane Biophysics and Biochemistry, DICBR, National Institute of Alcohol Abuse and Alcoholism, Rockville, MD 20852, USA.
Am J Clin Nutr 1995 Jul;62(1):1-9
Recent studies have both offered and contested the proposition that lowering plasma cholesterol by diet and medications increases suicide, homicide, and depression. Significant confounding factors include the quantity and distribution of dietary n-6 and n-3 polyunsaturated essential fatty acids that influence serum lipids and alter the biophysical and biochemical properties of cell membranes. Epidemiological studies in various countries and in the United States in the last century suggest that decreased n-3 fatty acid consumption correlates with increasing rates of depression. This is consistent with a well-established positive correlation between depression and coronary artery disease. Long-chain n-3 polyunsaturate deficiency may also contribute to depressive symptoms in alcoholism, multiple sclerosis, and post-partum depression. We postulate that adequate long-chain polyunsaturated fatty acids, particularly docosahexaenoic acid, may reduce the development of depression just as n-3 polyunsaturated fatty acids may reduce coronary artery disease.
Clinical and subclinical hypothyroidism in patients with chronic and treatment-resistant depression.
Hickie I, Bennett B, Mitchell P, Wilhelm K, Orlay W. School of Psychiatry, University of New South Wales, Academic Department of Psychiatry, St George Hospital and Community Service, Kogarah, Australia.
Aust N Z J Psychiatry 1996 Apr;30(2):246-52
OBJECTIVE: To investigate the relationship between hypothyroidism and treatment-resistant depression (TRD). METHOD: A retrospective case audit of 93 inpatients of a specialist Mood Disorders Unit. Patients referred with TRD were sub-classified into 'adequate' or 'inadequate' prior treatment groups on the basis of pre-established criteria, and compared with a 'non-TRD' control sample. Grades I (clinical) and II (subclinical) hypothyroidism were determined by review of relevant thyroid indices. RESULTS: Patients had chronic depressive disorders (sub-group means of 57.5-82.2 weeks of illness). Of those patients referred with TRD, 22% (10/46) had evidence of clinical or subclinical hypothyroidism compared with 2% (1/47) of the non-TRD patients (< 0.01). A gradient in the rates of grade I hypothyroidism was observed with the adequately-treated TRD patients having the highest rate (13%), the inadequately-treated TRD patients having an intermediate rate (7%), and the non-TRD patients having the lowest rate (2%). Consistent with this view, the inadequately-treated TRD group had the highest rate of grade II hypothyroidism (p = 0.01) and tended to have higher thyroid stimulating hormone (TSH) values (p = 0.06). Differences in the rates of hypothyroidism could not be accounted for by differences in age or prior exposure to lithium and/or carbamazepine. Duration of the depressive episode was negatively correlated with both the free thyroxine indices (r = -0.25, < 0.05) and TSH levels (r = -0.32, < 0.01). CONCLUSIONS: This study suggests that relative hypothyroidism may play a role in the development of some treatment-resistant depressive disorders.
The use of androgens in menopause.
Hoeger KM, Guzick DS. University of Rochester, Department of Obstetrics & Gynecology, NY 14642-8668, USA.
Clin Obstet Gynecol 1999 Dec;42(4):883-94
Recent increase in the potential role for androgen supplementation in the menopause, as well as the availability of nontraditional, over-the-counter food supplements containing DHEA, currently touted for postmenopausal health, have raised the need for clinicians to have a working knowledge of both potential benefits and risks of androgen replacement as a supplement to traditional hormone replacement therapy. There is compelling evidence that androgen levels are reduced after bilateral oophorectomy. The degree of androgen reduction after natural menopause may be less, and the onset of this decrease more gradual in this population. A decrease in androgen levels has been proposed as one etiology for decreased libido, and there is some evidence to support androgen use in oophorectomized women suffering from diminished libido. Such evidence is mixed, however, in naturally menopausal women. Androgen replacement may provide additional relief of menopausal symptoms in some patients, but this evidence is also inconsistent. Initial studies seem to support a perceived enhancement in psychological well-being, but confirmatory, long-term studies are still needed. Available evidence suggests a positive impact on bone density with the use of some androgen preparations, but no consistent benefit from DHEA has been demonstrated. Although androgen therapy can induce decreases in HDL cholesterol levels, the clinical impact of this is not yet known. Currently, there is little support for the routine use of androgen supplementation in the menopause. Additionally, a number of adverse events may be associated with androgen use. Careful patient selection, with comprehensive evaluation to sort out other possible medical or psychological conditions, should be undertaken before the initiation of androgen replacement. Currently available preparations are limited in number and flexibility in dosing, but there is ongoing effort to develop new delivery systems and therapeutics so that options available in the future may allow for enhanced availability and efficacy.
Decreased cerebral 5-HT1A receptors during ageing: reversal by Ginkgo biloba extract (EGb 761).
Huguet F, Drieu K, Piriou A. Institut des Xenobiotiques, Faculte de Medecine et de Pharmacie, Poitiers, France.
J Pharm Pharmacol 1994 Apr;46(4):316-8
Investigation of [3H]8-hydroxy-2(di-n-propylamino)tetralin binding to 5-HT1A receptors in cerebral cortex membranes of Wistar rats showed that the maximal number of binding sites (Bmax) was reduced significantly (22%) in aged (24-month-old) as compared with young (4-month-old) animals. Chronic treatment with Ginkgo biloba extract did not alter binding in young rats but increased binding density significantly (33%) in aged rats. These results confirm previously described age-related 5-hydroxytryptaminergic alterations. Together with data in the literature, they also suggest a restorative effect in aged rats, associated with decreased receptor density resulting from the protective action of Ginkgo biloba extract treatment on neuronal membrane.
Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison's disease in a randomized, double blind trial.
Hunt PJ, Gurnell EM, Huppert FA, Richards C, Prevost AT, Wass JA, Herbert J, Chatterjee VK. Department of Endocrinology, University of Oxford, Radcliffe Infirmary, Oxford, United Kingdom.
J Clin Endocrinol Metab 2000 Dec;85(12):4650-6
Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) are adrenal precursors of steroid biosynthesis and centrally acting neurosteroids. Glucocorticoid and ineralocorticoid deficiencies in Addison's disease require life-long hormone replacement, but the associated failure of DHEA synthesis is not corrected. We conducted a randomized, double blind study in which 39 patients with Addison's disease received either 50 mg oral DHEA daily for 12 weeks, followed by a 4-week washout period, then 12 weeks of placebo, or vice versa. After DHEA treatment, levels of DHEAS and Delta(4)-androstenedione rose from subnormal to within the adult physiological range. Total testosterone increased from subnormal to low normal with a fall in serum sex hormone-binding globulin in females, but with no change in either parameter in males. In both sexes, psychological assessment showed significant enhancement of self-esteem with a tendency for improved overall well-being. Mood and fatigue also improved significantly, with benefit being evident in the evenings. No effects on cognitive or sexual function, body composition, lipids, or bone mineral density were observed. Our results indicate that DHEA replacement corrects this steroid deficiency effectively and improves some aspects of psychological function. Beneficial effects in males, independent of circulating testosterone levels, suggest that it may act directly on the central nervous system rather than by augmenting peripheral androgen biosynthesis. These positive effects, in the absence of significant adverse events, suggest a role for DHEA replacement therapy in the treatment of Addison's disease.
Effect of acute and chronic administration of dehydroepiandrosterone on (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced wet dog shaking behavior in rats.
Inagaki M, Kagaya A, Takebayashi M, Horiguchi J, Yamawaki S. Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan.
J Neural Transm 1999;106(1):23-33
It has been reported that dehydroepiandrosterone (DHEA) or dehydroepiandrosterone sulfate (DHEA-S) is associated with affective disorders and that pathology of affective disorders are related with dysfunction of serotonin(5-HT)-2A receptor-mediated responses. In this study, we investigated the effect of DHEA on (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI), 5-HT-2A receptor agonist, -induced wet dog shaking behavior (WDS) in rats. Acute treatment with DHEA inhibited the DOI-induced WDSs dose dependently. This inhibition was recovered by opioid receptor antagonist, naltrexone. 5-HT-2A receptor-mediated WDSs were desensitized after chronic treatment with DOI, however chronic treatment with DHEA had no effect on this desensitization. Chronic treatment with DHEA had no facilitating effect of chronic dexamethasone treatment on DOI-induced WDSs. These findings may lead the possibility that DHEA has the inhibitory effect of 5-HT-2A mediated signaling pathway via non-genomic action.
Antidepressant efficacy of Sudarshan Kriya Yoga (SKY) in melancholia: a randomized comparison with electroconvulsive therapy (ECT) and imipramine.
Janakiramaiah N, Gangadhar BN, Naga Venkatesha Murthy PJ, Harish MG, Subbakrishna DK, Vedamurthachar A. Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
J Affect Disord 2000 Jan-Mar;57(1-3):255-9
BACKGROUND: Sudarshan Kriya Yoga (SKY) is a procedure that involves essentially rhythmic hyperventilation at different rates of breathing. The antidepressant efficacy of SKY was demonstrated in dysthymia in a prospective, open clinical trial. This study compared the relative antidepressant efficacy of SKY in melancholia with two of the current standard treatments, electroconvulsive therapy (ECT) and imipramine (IMN). METHODS: Consenting, untreated melancholic depressives (n=45) were hospitalized and randomized equally into three treatment groups. They were assessed at recruitment and weekly thereafter for four weeks. RESULTS: Significant reductions in the total scores on Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HRSD) occurred on successive occasions in all three groups. The groups, however, did not differ. Significant interaction between the groups and occasion of assessment occurred. At week three, the SKY group had higher scores than the ECT group but was not different from the IMN group. Remission (total HRSD score of seven or less) rates at the end of the trial were 93, 73 and 67% in the ECT, IMN and SKY groups, respectively. No clinically significant side effects were observed. DISCUSSION: Within the limitations of the design (lack of double blind conditions), it can be concluded that, although inferior to ECT, SKY can be a potential alternative to drugs in melancholia as a first line treatment.
Treatment of seasonal affective disorder (SAD) with hypericum extract.
Kasper S. Department of General Psychiatry, University of Vienna, Austria.
Pharmacopsychiatry 1997 Sep;30 Suppl 2:89-93
Seasonal affective disorder (SAD) is a subgroup of major depression and characterized by a regular occurrence of symptoms in autumn/winter and full remission or hypomania in spring/summer. Light therapy (LT) and recently pharmacotherapy with specific antidepressants have been shown to be beneficial. Within the array of pharmacotherapy hypericum extract has also been found to be effective in a single-blind study (Martinez et al., 1994). In this 4 weeks treatment study 900 mg of hypericum was associated with a significant reduction in the total score of the Hamilton Depression Rating Scale. There was no significant difference when bright light therapy was combined with hypericum, compared to the situation without bright light therapy. Overall, hypericum was well tolerated and therefore the data suggest that pharmacological treatment with hypericum may be an efficient therapy in patients with SAD, which needs to be substantiated in further controlled studies.
A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression.
Keller MB, McCullough JP, Klein DN, Arnow B, Dunner DL, Gelenberg AJ, Markowitz JC, Nemeroff CB, Russell JM, Thase ME, Trivedi MH, Zajecka J. Department of Psychiatry, Brown University, Providence, RI 02906, USA.
N Engl J Med 2000 May 18;342(20):1462-70
BACKGROUND: Patients with chronic forms of major depression are difficult to treat, and the relative efficacy of medications and psychotherapy is uncertain.
METHODS: We randomly assigned 681 adults with a chronic nonpsychotic major depressive disorder to 12 weeks of outpatient treatment with nefazodone (maximal dose, 600 mg per day), the cognitive behavioral-analysis system of psychotherapy (16 to 20 sessions), or both. At base line, all patients had scores of at least 20 on the 24-item Hamilton Rating Scale for Depression (indicating clinically significant depression). Remission was defined as a score of 8 or less at weeks 10 and 12. For patients who did not have remission, a satisfactory response was defined as a reduction in the score by at least 50 percent from base line and a score of 15 or less. Raters were unaware of the patients' treatment assignments.
RESULTS: Of the 681 patients, 662 attended at least one treatment session and were included in the analysis of response. The overall rate of response (both remission and satisfactory response) was 48 percent in both the nefazodone group and in the psychotherapy group, as compared with 73 percent in the combined-treatment group. (< 0.001 for both comparisons). Among the 519 subjects who completed the study, the rates of response were 55 percent in the nefazodone group and 52 percent in the psychotherapy group, as compared with 85 percent in the combined-treatment group (< 0.001 for both comparisons). The rates of withdrawal were similar in the three groups. Adverse events in the nefazodone group were consistent with the known side effects of the drug (e.g., headache, somnolence, dry mouth, nausea, and dizziness).
CONCLUSIONS: Although about half of patients with chronic forms of major depression have a response to short-term treatment with either nefazodone or a cognitive behavioral-analysis system of psychotherapy, the combination of the two is significantly more efficacious than either treatment alone.
Folates: supplemental forms and therapeutic applications.
Kelly GS. gregnd@worldnet.att.net
Altern Med Rev 1998 Jun;3(3):208-20
Folates function as a single carbon donor in the synthesis of serine from glycine, in the synthesis of nucleotides form purine precursors, indirectly in the synthesis of transfer RNA, and as a methyl donor to create methylcobalamin, which is used in the re-methylation of homocysteine to methionine. Oral folates are generally available in two supplemental forms, folic and folinic acid. Administration of folinic acid bypasses the deconjugation and reduction steps required for folic acid. Folinic acid also appears to be a more metabolically active form of folate, capable of boosting levels of the coenzyme forms of the vitamin in circumstances where folic acid has little to no effect. Therapeutically, folic acid can reduce homocysteine levels and the occurrence of neural tube defects, might play a role in preventing cervical dysplasia and protecting against neoplasia in ulcerative colitis, appears to be a rational aspect of a nutritional protocol to treat vitiligo, and can increase the resistance of the gingiva to local irritants, leading to a reduction in inflammation. Reports also indicate that neuropsychiatric diseases secondary to folate deficiency might include dementia, schizophrenia-like syndromes, insomnia, irritability, forgetfulness, endogenous depression, organic psychosis, peripheral neuropathy, myelopathy, and restless legs syndrome.
Vitamin D3 enhances mood in healthy subjects during winter.
Lansdowne AT, Provost SC. Department of Psychology, The University of Newcastle, Callaghan NSW, Australia.
Psychopharmacology (Berl) 1998 Feb;135(4):319-23
Mood changes synchronised to the seasons exist on a continuum between individuals, with anxiety and depression increasing during the winter months. An extreme form of seasonality is manifested as the clinical syndrome of seasonal affective disorder (SAD) with carbohydrate craving, hypersomnia, lethargy, and changes in circadian rhythms also evident. It has been suggested that seasonality and the symptoms of SAD may be due to changing levels of vitamin D3, the hormone of sunlight, leading to changes in brain serotonin. Forty-four healthy subjects were given 400 IU, 800 IU, or no vitamin D3 for 5 days during late winter in a random double-blind study. Results on a self-report measure showed that vitamin D3 significantly enhanced positive affect and there was some evidence of a reduction in negative affect. Results are discussed in terms of their implications for seasonality, SAD, serotonin, food preference, sleep, and circadian rhythms.
Controlled trials of inositol in psychiatry.
Levine J. Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.
Eur Neuropsychopharmacol 1997 May;7(2):147-55
Inositol is a simple polyol precursor in a second messenger system important in the brain. Cerebrospinal fluid inositol has been reported as decreased in depression. A double-blind controlled trial of 12 g daily of inositol in 28 depressed patients for four weeks was performed. Significant overall benefit for inositol compared to placebo was found at week 4 on the Hamilton Depression Scale. No changes were noted in hematology, kidney or liver function. Since many antidepressants are effective in panic disorder, twenty-one patients with panic disorder with or without agoraphobia completed a double-blind, placebo-controlled, four week, random-assignment crossover treatment trial of inositol 12 g per day. Frequency and severity of panic attacks and severity of agoraphobia declined significantly with inositol compared to placebo. Side-effects were minimal. Since serotonin re-uptake inhibitors benefit obsessive compulsive disorder (OCD) and inositol is reported to reverse desensitization of serotonin receptors, thirteen patients with OCD completed a double-blind controlled crossover trial of 18 g inositol or placebo for six weeks each. Inositol significantly reduced scores of OCD symptoms compared with placebo. A controlled double-blind crossover trial of 12 g daily of inositol for a month in twelve anergic schizophrenic patients, did not show any beneficial effects. A double-blind controlled crossover trial of 6 g of inositol daily vs. glucose for one month each was carried out in eleven Alzheimer patients, with on clearly significant therapeutic effects. Antidepressant drugs have been reported to improve attention deficit disorder (ADDH) with hyperactivity symptomatology. We studied oral inositol in children with ADDH in a double-blind, crossover, placebo-controlled manner. Eleven children, mean age 8.9 +/- 3.6 years were enrolled in an eight week trial of inositol or placebo at a dose of 200 mg/kg body weight. Results show a trend for aggravation of the syndrome with myo-inositol as compared to placebo. Recent studies suggest that serotonin re-uptake inhibitors are helpful in at least some symptoms of autism. However a controlled double-blind crossover trial of inositol 200 mg/kg per day showed no benefit in nine children with autism. Cholinergic agonists have been reported to ameliorate electroconvulsive therapy (ECT)-induced memory impairment. Inositol metabolism is involved in the second messenger system for several muscarinic cholinergic receptors. Inositol 6 g daily was given in a crossover-double-blind manner for five days before the fifth or sixth ECT to a series of twelve patients, without effect. These results suggest that inositol has therapeutic effects in the spectrum of illness responsive to serotonin selective re-uptake inhibitors, including depression, panic and OCD, and is not beneficial in schizophrenia, Alzheimer's ADDH, autism or ECT-induced cognitive impairment. |