Posted by Hombre on April 28, 2010, at 3:59:05 [reposted on May 4, 2010, at 0:04:49 | original URL]
It's too early to tell for sure, but I seem to be having a good response to magnesium supplementation in addition to my meds. Here are some interesting journal articles I've pulled from Pubmed that might explain magnesium's role in depression.
J Neural Transm. 2007 Sep;114(9):1129-34. Epub 2007 Apr 20.
Modulation of antidepressant-like activity of magnesium by serotonergic system.Poleszak E.
Department of Pharmacology and Pharmacodynamics, Skubiszewski Medical University of Lublin, Lublin, Poland. ewa.poleszak@am.lublin.pl
AbstractThe influence of magnesium on the action of antidepressants drugs with different pharmacological profiles citalopram, reboxetine and tianeptine, was investigated in the forced swim test (FST) in mice. Magnesium (10 mg Mg/kg) given with reboxetine (2.5 mg/kg) did not change the behavior of animals in the FST. A synergistic effect was seen when magnesium (10 mg Mg/kg) was given jointly with citalopram (15 mg/kg) or tianeptine (20 mg/kg) in the FST, without accompanying changes in locomotor activity. Moreover, the antidepressant-like effect of magnesium (30 mg Mg/kg) was significantly reduced by pretreatment of mice with an inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA, 200 mg/kg). Thus, the antidepressant-like action of magnesium in the FST seems to involve an interaction with serotonergic system.
Neuropharmacology. 2004 Dec;47(8):1189-97.
Magnesium-deficient diet alters depression- and anxiety-related behavior in mice--influence of desipramine and Hypericum perforatum extract.Singewald N, Sinner C, Hetzenauer A, Sartori SB, Murck H.
Department of Pharmacology and Toxicology, Institute of Pharmacy and CMBI, Leopold-Franzens-University of Innsbruck, Peter-Mayr-Str. 1, A-6020 Innsbruck, Austria. nicolas.singewald@uibk.ac.at
AbstractA relation between magnesium (Mg) status and mood disorders has been suggested, but evidence remains inconsistent. Therefore, we examined in mice whether Mg-depletion would alter behavior evaluated in established animal models of depression and anxiety and whether these effects would be sensitive to antidepressants. Compared to control mice fed with normal diet, mice receiving a low Mg diet (10% of daily requirement) for several weeks displayed increased immobility time in the forced swim test, indicating enhanced depression-like behavior. In addition, the partial Mg-depletion increased anxiety-related behavior in the light/dark and open field test, while locomotor activity or motor coordination was not influenced. Chronic oral administration of desipramine (30 mg/kg/day), or Hypericum extract LI160 (Hyp, 380 mg/kg/day) prevented the "pro-depression-like" forced swim behavior in Mg-depleted mice. Furthermore, the increase in anxiety-related behavior of Mg-depleted mice was abolished in both the open field and light dark test by Hyp. Taken together, we report that Mg-depletion leads to enhanced depression- and anxiety-related behavior in mice, which was further validated by the reversibility of the behavioral changes by known antidepressant and anxiolytic substances. Further, the utility of Mg-depletion as a new screening model for clinically active antidepressant and anxiolytic drugs is suggested.
Magnes Res. 2009 Sep;22(3):163S-166S.
Magnesium in major depression.Nechifor M.
Department of Pharmacology, Gr. T. Popa University of Medicine and Pharmacology, Universitatii 16, Iasi, Romania. nechifor@umfiasi.ro
AbstractThere are contradictory data regarding the levels of magnesium in patients with major depression (MD) and how antidepressants influence their concentration. Our results show erythrocyte magnesium in patients with MD (44.39 /- 2.7 mg/L vs. 59.1 /- 3.2 mg/L in control group, p < 0.05) and only in patients with severe MD (Hamilton score > 23) was a moderate decrease in plasmatic magnesium observed (17.7 /- 1.5 mg/L vs. 22.9 /- 3.3 mg/L in control group). Therapy with antidepressants from different groups and with different mechanisms of action, such as amytriptiline (25 mg x 3/day per os, 4 weeks) and sertraline (50 mg x 3/day per os, 4 weeks) leads to a significant increase of magnesium concentration in erythrocytes (57.6 /- 4.5 mg/L after amytriptiline, respectively 56.9 /- 3.2 mg/L after sertraline, p < 0.05 vs. before therapy). At the same time, in patients with MD, plasmatic levels of zinc were significantly decreased before therapy and increased after treatment with amytriptiline and sertraline (0.68 /- 0.09 mg/L before treatment vs. 0.9 /- 0.07 after amytriptiline). There is a positive correlation between concentrations of magnesium in erythrocytes and the clinical evolution of patients with MD. We consider that increasing intracellular concentration is a component of the antidepressant mechanism of sertraline and amytriptiline and maybe of other antidepressants. Anhedonia and autolytic tendencies are important elements of MD symptomatology. We tested the influence of MgCl2 0.2 mM/kg/day on a reward system using conditioned place preference (Panlab) in rats. Our data show a moderate stimulation of the reward system by magnesium (290.6 /- 27 s time spent in a conditioned compartment before magnesium treatment and 363.3 /- 16 s after magnesium treatment) that reflects a stimulation of the reward system (RS). We consider that a magnesium-induced stimulation of the RS is an important issue for treating anhedonia in patients with MD. An increase of intracellular magnesium may be part of the mechanism of action of antidepressants.
Biol Trace Elem Res. 2010 Feb;133(2):153-61. Epub 2009 Jun 19.
Associations of serum Ca and Mg levels with mental health in adult women without psychiatric disorders.Jung KI, Ock SM, Chung JH, Song CH.
Department of Psychiatry, St. Paul's Hospital, The Catholic University of Korea, 620-56 Cheonnong-dongm, Dongdaemun-gu, 130-709, Seoul, Korea.
AbstractSeveral lines of evidence from previous studies suggest that Calcium (Ca) and Magnesium (Mg) may be involved in intracellular and interneuronal processes associated with affective disorders. However, there have been inconsistent results on the effect of Ca and Mg on depressive mood disorder. This cross-sectional study was conducted to determine whether serum Ca and Mg levels, as well as serum Ca/Mg ratio, are associated with mental health in relatively healthy, adult women without psychiatric disorders. One hundred and twelve adult women were recruited from the outpatient clinic in a university hospital setting. Serum Ca and Mg levels were measured and indicators of mental health such as depression, anxiety, and stress were evaluated using two validated questionnaires; the Hospital Anxiety Depression Scale and the Modified Brief Encounter Psychosocial Instrument Stress Scale. After categorizing the serum Ca and Mg levels, and the Ca/Mg ratio into tertiles, the mean scores on each mental health scale were compared using analysis of covariance. The risk of depressive mood disorder according to the tertiles of serum Mg level and serum Ca/Mg ratio was assessed using logistic regression analysis. Women in the middle tertile of serum Ca/Mg ratio had significantly lower scores on depression and stress scales (p = 0.004 and p = 0.007, respectively) and a lower odds ratio (OR) for the risk of depressive mood disorder (OR = 0.31, CI(95%) 0.10-0.93) than those in the highest tertile. The OR for the risk of depressive mood disorder was higher in women in the lowest tertile of serum Mg than in those in the highest tertile (OR = 3.92, CI(95%) 1.11-13.83). Serum Mg level and serum Ca/Mg ratio may be involved in the mechanism for the progression of depressive mood or stress perception in relatively healthy, adult women.
Magnes Res. 2008 Dec;21(4):218-23.
Efficacy and safety of oral magnesium supplementation in the treatment of depression in the elderly with type 2 diabetes: a randomized, equivalent trial.Barragán-Rodríguez L, Rodríguez-Morán M, Guerrero-Romero F.
FACP, Siqueiros 225 esq/Castańeda, 34000 Durango, Dgo., Mexico.
AbstractTo evaluate the efficacy and safety of oral magnesium supplementation, with magnesium chloride (MgCl2), in the treatment of newly diagnosed depression in the elderly with type 2 diabetes and hypomagnesemia. Twenty-three elderly patients with type 2 diabetes and hypomagnesemia were enrolled and randomly allocated to receive either 50 mL of MgCl2 5% solution equivalent to 450 mg of elemental magnesium or Imipramine 50 mg daily during 12 weeks. Widowhood or divorce in the last six months, alcoholism, degenerative illnesses of the nervous central system, recent diagnosis of diabetes, previous or current treatment with antidepressants, chronic diarrhea, use of diuretics, and reduced renal function were exclusion criteria. Hypomagnesemia was defined by serum magnesium levels < 1.8 mg/dL and depression by Yasavage and Brink score > or = 11 points. The primary trial end point was the improvement of depression symptoms. At baseline, there were no differences by age (69 /- 5.9 and 66.4 /- 6.1 years, p = 0.39), duration of diabetes (11.8 /- 7.9 and 8.6 /- 5.7 years, p = 0.33), serum magnesium levels (1.3 /- 0.04 and 1.4 /- 0.04 mg/dL, p = 0.09), and Yasavage and Brink Score (17.9 /- 3.9 and 16.1 /- 4.5 point, p = 0.34) in the groups with MgCl2 and imipramine, respectively. At end of follow-up, there were no significant differences in the Yasavage and Brink score (11.4 /- 3.8 and 10.9 /- 4.3, p = 0.27) between the groups in study; whereas serum magnesium levels were significantly higher in the group with MgCl2 (2.1 /- 0.08 mg/dL) than in the subjects with imipramine (1.5 /- 0.07 mg/dL), p < 0.0005. In conclusion, MgCl2 is as effective in the treatment of depressed elderly type 2 diabetics with hypomagnesemia as imipramine 50 mg daily.
Aust N Z J Psychiatry. 2009 Jan;43(1):45-52.
Association between magnesium intake and depression and anxiety in community-dwelling adults: the Hordaland Health Study.Jacka FN, Overland S, Stewart R, Tell GS, Bjelland I, Mykletun A.
University of Melbourne, Department of Clinical and Biomedical Sciences: Barwon Health, Vic., Australia. felice@barwonhealth.org.au
Comment in:
* Aust N Z J Psychiatry. 2009 Jun;43(6):580.
Abstract
OBJECTIVE: Systemic inflammation is associated with both the dietary intake of magnesium, and depression. Limited experimental and clinical data suggest an association between magnesium and depression. Thus, there are reasons to consider dietary magnesium as a variable of interest in depressive disorders. The aim of the present study was to examine the association between magnesium intake and depression and anxiety in a large sample of community-dwelling men and women. This sample consisted of 5708 individuals aged 46-49 or 70-74 years who participated in the Hordaland Health Study in Western Norway. METHODS: Symptoms of depression and anxiety were self-reported using the Hospital Anxiety and Depression Scale, and magnesium intake was assessed using a comprehensive food frequency questionnaire. RESULTS: There was an inverse association between standardized energy-adjusted magnesium intake and standardized depression scores that was not confounded by age, gender, body habitus or blood pressure (beta=-0.16, 95% confidence interval (CI)=-0.22 to -0.11). The association was attenuated after adjustment for socioeconomic and lifestyle variables, but remained statistically significant (beta=-0.11, 95%CI=-0.16 to -0.05). Standardized magnesium intake was also related to case-level depression (odds ratio (OR)=0.70, 95%CI=0.56-0.88), although the association was attenuated when adjusted for socioeconomic and lifestyle factors (OR=0.86, 95%CI=0.69-1.08). The inverse relationship between magnesium intake and score and case-level anxiety was weaker and not statistically significant in the fully adjusted models. CONCLUSION: The hypothesis that magnesium intake is related to depression in the community is supported by the present findings. These findings may have public health and treatment implications.
Pharmacol Rep. 2008 Sep-Oct;60(5):588-9.
Antidepressant activity of zinc and magnesium in view of the current hypotheses of antidepressant action.Szewczyk B, Poleszak E, Sowa-Kućma M, Siwek M, Dudek D, Ryszewska-Pokraśniewicz B, Radziwoń-Zaleska M, Opoka W, Czekaj J, Pilc A, Nowak G.
Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. szewczyk@if-pan.krakow.pl
AbstractThe clinical efficacy of current antidepressant therapies is unsatisfactory; antidepressants induce a variety of unwanted effects, and, moreover, their therapeutic mechanism is not clearly understood. Thus, a search for better and safer agents is continuously in progress. Recently, studies have demonstrated that zinc and magnesium possess antidepressant properties. Zinc and magnesium exhibit antidepressant-like activity in a variety of tests and models in laboratory animals. They are active in forced swim and tail suspension tests in mice and rats, and, furthermore, they enhance the activity of conventional antidepressants (e.g., imipramine and citalopram). Zinc demonstrates activity in the olfactory bulbectomy, chronic mild and chronic unpredictable stress models in rats, while magnesium is active in stress-induced depression-like behavior in mice. Clinical studies demonstrate that the efficacy of pharmacotherapy is enhanced by supplementation with zinc and magnesium. The antidepressant mechanisms of zinc and magnesium are discussed in the context of glutamate, brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase-3 (GSK-3) hypotheses. All the available data indicate the importance of zinc and magnesium homeostasis in the psychopathology and therapy of affective disorders.
Magnes Res. 2008 Jun;21(2):97-100.
Interactions between magnesium and psychotropic drugs.Nechifor M.
Department of Pharmacology, University of Medicine and Pharmacy Gr. T. Popa, Iasi, Romania. mnechif@yahoo.com
AbstractPsychotropic drugs (antidepressants, antimanic drugs, antipsychotics, analgesic opioids, and others) are among the most frequently used medicines. Between these drugs and magnesium there are pharmacokinetic and pharmacodynamic interactions. Erythrocyte magnesium is decreased in patients with severe major depression (MD) vs normal subjects (44 /- 2.7 mg/L in MD group vs 59.1 /- 3.2 mg/L in control group, p < 0.01). Therapy with sertraline, 150 mg/day p.o. -21 days or with amitryptiline 3 x 25 mg/day p.o. 28 days increases significantly erythrocyte concentration of magnesium (56.9 /- 5.22 mg/L after sertraline vs 44 /- 2.7 mg/L before sertraline, p < 0.01). In patients with acute paranoid schizophrenia, erythrocyte magnesium concentration is decreased vs healthy subjects. Haloperidol, 8 mg/day, p.o. for 21 days or risperidone, 6 mg/day p.o. for 21 days have increased significantly erythrocyte magnesium concentration (46.21 /- 3.1 mg/L before haloperidol and 54.6 /- 2.7 mg/L after haloperidol, p < 0.05). Antimanic drugs (mood stabilizers) as carbamazepine, 600 mg/day, p.o., 4 weeks and sodium valproate, 900 mg/day p.o., 4 weeks, increased significantly magnesium in patients with bipolar disorder type I. Increased magnesium status positively correlated with enhancement of the clinical state. The existent data sustain the idea that an increase of erythrocyte magnesium is involved in the mechanism of action of some psychotropic drugs. Magnesium supply decreased the intensity of morphine-induced physical drug dependence. In heroin addicts, the plasma magnesium concentration is decreased.
Neuron. 2010 Jan 28;65(2):165-77.
Enhancement of learning and memory by elevating brain magnesium.Slutsky I, Abumaria N, Wu LJ, Huang C, Zhang L, Li B, Zhao X, Govindarajan A, Zhao MG, Zhuo M, Tonegawa S, Liu G.
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Comment in:
* Neuron. 2010 Jan 28;65(2):143-4.
Abstract
Learning and memory are fundamental brain functions affected by dietary and environmental factors. Here, we show that increasing brain magnesium using a newly developed magnesium compound (magnesium-L-threonate, MgT) leads to the enhancement of learning abilities, working memory, and short- and long-term memory in rats. The pattern completion ability was also improved in aged rats. MgT-treated rats had higher density of synaptophysin-/synaptobrevin-positive puncta in DG and CA1 subregions of hippocampus that were correlated with memory improvement. Functionally, magnesium increased the number of functional presynaptic release sites, while it reduced their release probability. The resultant synaptic reconfiguration enabled selective enhancement of synaptic transmission for burst inputs. Coupled with concurrent upregulation of NR2B-containing NMDA receptors and its downstream signaling, synaptic plasticity induced by correlated inputs was enhanced. Our findings suggest that an increase in brain magnesium enhances both short-term synaptic facilitation and long-term potentiation and improves learning and memory functions. Copyright 2010 Elsevier Inc. All rights reserved.
Pak J Biol Sci. 2009 May 15;12(10):798-803.
Development of morphine induced tolerance and withdrawal symptoms is attenuated by lamotrigine and magnesium sulfate in mice.Habibi-Asl B, Hassanzadeh K, Vafai H, Mohammadi S.
Department of Pharmacology and Toxicology, School of Pharmacy, Tabriz University (Medical Sciences), Tabriz, Iran.
AbstractThe goal of this study was to evaluate the effects of lamotrigine and magnesium sulfate on morphine induced tolerance and withdrawal symptoms in mice. Different groups of mice were received morphine (30 mg kg(-1), s.c.) or morphine (30 mg kg(-1), s.c.) lamotrigine (10, 20, 30 or 40 mg kg(-1), i.p.) or morphine (30 mg kg(-1), s.c.) magnesium sulfate (20, 40 or 60 mg kg(-1), i.p.) or morphine (30 mg kg(-1), s.c.) [lamotrigine (10 mg kg(-1), i.p.) magnesium sulfate (20mg kg(-1), i.p.)] daily for 4 days. Tolerance was assessed using hot plate after administration of a test dose of morphine (9 mg kg(-1), i.p.) on fifth day. Withdrawal zsymptoms (Jumping and Rearing) were assessed by administration of naloxone (5 mg kg(-1), i.p.) 2 h after the last dose of morphine in fourth day. It was found that administration of lamotrigine or magnesium sulfate or their combination decreased the morphine induced tolerance and withdrawal symptoms. From these results it is concluded that lamotrigine and magnesium sulfate alone or in combination could prevent the development of morphine tolerance and withdrawal symptoms. Glutamate release inhibitory effect of lamotrigine and its possible mechanism and property of magnesium, blocking the N-Methyl-D-Aspartate (NMDA) receptor calcium channel, is probably its mechanism on preventing morphine induced tolerance and dependence.
Pharmacol Rep. 2008 Jul-Aug;60(4):483-9.
Benzodiazepine/GABA(A) receptors are involved in magnesium-induced anxiolytic-like behavior in mice.Poleszak E.
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Staszica 4, PL 20-081 Lublin, Poland. ewa.poleszak@am.lublin.pl
AbstractBehavioral studies have suggested an involvement of the glutamate pathway in the mechanism of action of anxiolytic drugs, including the NMDA receptor complex. It was shown that magnesium, an NMDA receptor inhibitor, exhibited anxiolytic-like activity in the elevated plus-maze test in mice. The purpose of the present study was to examine interaction between magnesium and benzodiazepine/GABA(A) receptors in producing anxiolytic-like activity. We examined behavior of mice treated with magnesium and benzodiazepine/GABA(A) receptor ligands, in the elevated plus maze. The anxiolytic-like effect of magnesium (20 mg/kg) was antagonized by flumazenil (10 mg/kg) (benzodiazepine receptor antagonist) while combined treatment with the non-effective doses of magnesium (10 mg/kg) and benzodiazepines (diazepam (0.5 mg/kg) or chlordiazepoxide (2 mg/kg)) produced synergistic interaction (increased time in open arms and number of open arm entries) in this test. The obtained data indicate that benzodiazepine receptors are involved in the anxiolytic-like effects of magnesium.
Neuropharmacology. 2004 Dec;47(8):1189-97.
Magnesium-deficient diet alters depression- and anxiety-related behavior in mice--influence of desipramine and Hypericum perforatum extract.Singewald N, Sinner C, Hetzenauer A, Sartori SB, Murck H.
Department of Pharmacology and Toxicology, Institute of Pharmacy and CMBI, Leopold-Franzens-University of Innsbruck, Peter-Mayr-Str. 1, A-6020 Innsbruck, Austria. nicolas.singewald@uibk.ac.at
AbstractA relation between magnesium (Mg) status and mood disorders has been suggested, but evidence remains inconsistent. Therefore, we examined in mice whether Mg-depletion would alter behavior evaluated in established animal models of depression and anxiety and whether these effects would be sensitive to antidepressants. Compared to control mice fed with normal diet, mice receiving a low Mg diet (10% of daily requirement) for several weeks displayed increased immobility time in the forced swim test, indicating enhanced depression-like behavior. In addition, the partial Mg-depletion increased anxiety-related behavior in the light/dark and open field test, while locomotor activity or motor coordination was not influenced. Chronic oral administration of desipramine (30 mg/kg/day), or Hypericum extract LI160 (Hyp, 380 mg/kg/day) prevented the "pro-depression-like" forced swim behavior in Mg-depleted mice. Furthermore, the increase in anxiety-related behavior of Mg-depleted mice was abolished in both the open field and light dark test by Hyp. Taken together, we report that Mg-depletion leads to enhanced depression- and anxiety-related behavior in mice, which was further validated by the reversibility of the behavioral changes by known antidepressant and anxiolytic substances. Further, the utility of Mg-depletion as a new screening model for clinically active antidepressant and anxiolytic drugs is suggested.
J Am Coll Nutr. 2004 Oct;23(5):529S-533S.
Magnesium attenuates post-traumatic depression/anxiety following diffuse traumatic brain injury in rats.Fromm L, Heath DL, Vink R, Nimmo AJ.
Department of Pathology, University of Adelaide, Adelaide, SA, Australia.
AbstractOBJECTIVE: Magnesium (Mg) declines after traumatic brain injury (TBI), a decline believed associated with ensuing neuronal cell death and subsequent functional impairment. While Mg's effects on motor and cognitive deficits following TBI have been well studied, few studies have addressed post-traumatic depression as an outcome parameter, despite its being a major clinical problem with an incidence of between 6 and 77%. We investigated the incidence of post-traumatic depression/anxiety in an animal model of diffuse TBI, and explored the use of magnesium sulfate (MgSO(4)) as an interventional treatment. METHODS: Diffuse TBI was induced in 32 anesthetized, adult, male Sprague-Dawley rats, using the 2 m impact-acceleration model of injury. At 30 min after injury, half of the rats received 250 micromol/kg i.v. MgSO(4); the other half served as non-treated controls. Before and for 6 weeks after injury, the open-field, spontaneous activity test was used to determine post-traumatic depression/anxiety relative to pre-injury. In this test, animals are placed in a 1-meter square box with 100 squares marked on the base. The number of squares entered in a 5-min period is recorded. Incidence of post-traumatic depression/anxiety was defined as the number of animals demonstrating a reduction in spontaneous activity to less than 100 squares in 5 min. Prior to injury, rats typically entered a mean of 201 /- 12 (SEM) squares over a 5 min observation period. RESULTS: At 1 week after injury, non-treated animals had a mean core of 62 /- 13. The incidence of post-traumatic depression/anxiety in these animals was 61%, which is similar to that observed clinically. In contrast, animals treated with MgSO(4) had a mean activity score of 144 /- 23 at 1 week after TBI and an incidence of depression/anxiety of less than 30%. The significant difference between groups persisted for the entire 6-week observation period. CONCLUSIONS: The improvement in post-traumatic depression/anxiety conferred by Mg adds further weight to available evidence of Mg's benefit as a neuroprotective agent after TBI.
poster:Hombre
thread:946186
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