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Interactions Between Magnesium and Psychotropic Drugs
Interactions Between Magnesium and Psychotropic Drugs
Psychotropic drugs represent some of the most both directions. Data available about all these inter-
important and frequently used drug categories. actions are, on the other hand, non-concordant.
There are several psychotropic groups such as: anxi- Our research was aimed to determine variations in
olitics, antidepressives, antipsychotics, hypomania- magnesium and other bivalent cations in patients
cals, etc. with major depression and the effects of some anti-
Magnesium has complex actions at the central ner- depressives on serum and tissue magnesium levels.
vous system (CNS) level. Both pharmacodynamic Research was performed on a 76 adult patients of
and pharmacokinetic interactions have been noticed both sexes (primarily women). Pregnant women,
doi: 10.1684/mrh.2008.0131
between plasma/tissue magnesium concentration alcoholics, patients with kidney or liver failure or
and psychotropic drug actions. Interactions are in those receiving medical drugs containing cations or
diuretics were not included in the study. Depression
severity was determined using the Hamilton rating
scale of depression. Only patients with medium or
Presented at the European Meeting on Magnesium, EuroMag, severe major depression (MD) were included in the
Paris, May 15-17, 2008. study (Hamilton score 17 or over). Determinations of
97
M. NECHIFOR
plasmatic and erythrocyte magnesium and copper, and after 30 days of therapy. Patients received, in a
zinc, iron and manganese levels in plasma were per- randomised manner, haloperidol 8 mg/day, for
formed before starting antidepressive therapy and 21 days or risperidone (Rispolept®, Janssen Cilag),
after 28 days of treatment. Some of the patients 6 mg/day for 21 days. Serum and erythrocyte magne-
received sertraline (Zoloft®, Pfizer, 150 mg/day per sium levels were also determined in a group of
os at least for 28 days) while the other group received healthy people, with the same sex and age distribu-
amitriptiline 3 x 25 mg/day per os at least for 28 days. tion pattern as the studied groups. Previous studies
Our data show that the erythrocyte magnesium showed no statistically significant differences
level was significantly decreased in the group with between serum magnesium levels in patients with
MD (44 ± 2.7 mg/L in MD group vs 59.1 ± 3.2 mg/L in schizophrenia vs controls [9, 10]. On the other hand,
control group, p < 0.01). In both sertraline and amit- there is a significant decrease in magnesium ery-
ryptiline groups, the erythrocyte magnesium level throcyte levels (59.2 ± 4.1 mg/L in control vs
increased (57.6 ± 4.5 mg/L in amytryptiline group 46.21 ± 3.1 mg/L in schizophrenic patients, p < 0.05).
and 56.9 ± 5.22 mg/L in sertraline group, p < 0.01 vs After 3 weeks of antipsychotic treatment, in both
before treatment) [1]. The magnesium plasma level haloperidol and risperidone treated patients, the
was significantly lower vs. controls only in the severe magnesium erythrocyte concentrations expressed a
MD group (Hamilton score > 23) (17.8 ± 2.2 mg/mL significant increase (up to 54.6 mg/L in haloperidol
vs 22.9 ± 1.9 mg/mL in healthy controls, p < 0.05) [1]. treated patients and up to 52.8 mg/L in the risperidone
Meanwhile, the plasma copper concentration was treated group, p < 0.05 vs before treatment levels).
found to be significantly increased in MD patients Together with a significant increase in magnesium
(0.86 ± 0.05 mg/L vs 0.63 ± 0.01 mg/L in control erythrocyte levels, we also demonstrated a signifi-
group). The zinc plasma level was decreased in the cant decrease in serum copper levels in both risperi-
MD group [2, 3]. done and haloperidol treated groups (0.8 ± 0.15 mg/L
Also, we could establish a positive correlation before treatment vs 0.62 ± 0.08 mg/L after risperi-
between an increase in the erythrocyte and plasma done treatment, p < 0.01) [9].
magnesium concentrations and the patient’s clinical Bipolar disorder (BD) (also called maniac-
state. No changes in serum calcium concentration depressive psychosis) is included in the group of
after sertraline or amytryptiline treatment could be affective psychosis. BD is a heterogeneous disease
established [4]. Our research showed partially con- with many clinical aspects. There is more than one
cordant results with these of Schlegel-Zawadzka form of BD. Data existing about changes in plasmatic
et al. [5], who observed a significant increase in zinc and cellular levels of magnesium are contradictory. It
serum levels after amytriptiline therapy in an experi- is possible that the heterogeneity of data about mag-
mental model of depression in rats. Also, our results nesium in patients with BD results from studies on
are concordant with Levine et al. [6], who reported a different types of BD.
significant increase in the Ca/Mg ratio in cerebrospi- The number of drugs used in the therapy of this
nal fluid (CSF) and in serum in patient with MD disease has markedly increased from lithium salts to
before beginning any treatment. new mood stabilizers (such as sodium valproate,
Schizophrenia is considered the most severe psy- lamotrigine, carbamazepine, etc) [11]. There is a
chosis. Our data, referring to intra- and extra-cellular competition between Li+ and Mg2+ for some intra-
magnesium concentrations in patients diagnosed neuronal binding sites [12]. Administration of lithium
with schizophrenia, are relatively contradictory. salts increases intracellular concentration of magne-
Some authors found increased levels of magnesium sium. We searched for the influence of carbam-
in CSF and serum [7, 8]. We studied serum and eryth- azepine (600 mg/day per os for 4 weeks) and sodium
rocyte magnesium concentrations in a group of 56 valproate (Orfiril®, Desitin Arzneimittel GmbH; 900
adult patients (32 women and 24 men) with paranoid mg/day per os for 4 weeks) in patients with BD admit-
schizophrenia (DSM IV) admitted with psychiatric ted in an acute manic episode, without previous
attacks to the clinical psychiatric hospital in Socola therapy. Both carbamazepine and sodium valproate
Iaşi (Romania) and who received antipsychotic treat- in the above mentioned doses significantly increased
ment before hospitalisation. Patients with chronic concentrations of intracellular magnesium after 4
renal failure, cardiac failure, chronic ethanol intake, weeks (initial Mg concentration 45.01 ± 1.87 mg/L vs
malabsorption syndromes, and patients treated with 52 ± 0.9 mg/L after sodium valproate, p < 0.05) [13].
diuretics or magnesium containing drugs were not Total magnesium concentrations in erythrocytes in
included in the study. Plasma and erythrocyte magne- BD patients during the acute episode were signifi-
sium concentrations were determined on admittance cantly decreased vs control group (45.01 ± 1.87 mg/L
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MAGNESIUM AND PSYCHOTROPIC DRUGS
in BD group vs 59.15 ± 2 mg/L in control group, naloxone (1 mg/kg i.p.) and symptoms were fol-
p < 0.01) [14]. Increasing intracellular brain levels of lowed. Our results [15] show a significant decrease in
magnesium determines a decreasing glutamate- the intensity of withdrawal syndromes (especially
induced activation of NMDA receptors and conse- grooming, locomotor activity, aggressive postures)
quently alleviates maniac psychomotor hyperactivity in the group that received magnesium during
(figure 1). Because psychotropic drugs with differ- morphine-induced dependence. We consider that
ent chemical structures and different mechanisms of this indicates that magnesium decreased the inten-
action increase magnesium concentrations in the sity of morphine-induced dependence. It is not a
erythrocytes of BP patients, we consider this direct action of magnesium during the withdrawal
increase an important element in mechanism of syndrome, magnesium intake ceasing before the
action of mood stabilizers in BD. naloxon administration. Our results correlate with
There are interactions between magnesium and data showing that the plasmatic level of magnesium
opiate analgesics. We searched for the influence of is decreased in heroin addicted patients [16, 17]. We
magnesium in morphine-induced experimental drug consider that magnesium may modulate the intensity
dependence in rat. We administrated morphine for of psychotropic drug -induced dependence.
11 days in a group of rats in progressively increased We consider that magnesium-psychotropic drug
doses (5 mg/kg/day s.c. on the first day to interactions play an important role in the pharmaco-
90 mg/kg/day s.c. on the eleven day). A second group dynamic effects of this group of drugs, although the
received morphine (as the first group) and magne- proven number of psychotropic drugs that influence
sium acexamate (MgAcx) 0.5 mEq/kg i.p. daily, 1 h plasmatic and intracellular magnesium level is rela-
before the morphine for 11 days. Withdrawal tively limited. This effect might play a role in their
syndromes were induced after the 11th day with therapeutic effect.
Sodium
Lithium salts Carbamazepine valproate
INCREASE+ +
+
Partially block the
Ca2+ channel
Mg2+ coupled with
NMDA receptor
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M. NECHIFOR
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