lithium-chloride and Acute-Disease

To evaluate the efficacy of lithium in the treatment of acute mania.. Systematic overview of the literature and meta-analysis of randomised controlled trials. Estimation of (i) the differences in the reduction in mania severity scores, and (ii) the ratio and difference in improvement response rates.. A total of 658 patients from 12 trials were included. Treatment periods ranged from 3 to 4 weeks. The response rate ratio for lithium against placebo was 1.95 (95%CI 1.17-3.23). The mean number needed to treat was five (95%CI 3-20). Patients were twice as likely to obtain remission with lithium than with chlorpromazine (rate ratio = 1.96, 95%CI 1.02-3.77). The mean number needed to treat was four (95%CI 3-9). Neither carbamazepine nor valproate was more effective than lithium. The response rate ratios were 1.01 (95%CI 0.54-1.88) for lithium compared to carbamazepine and 1.22 (95%CI 0.91-1.64) for lithium against valproate. Haloperidol was no better than lithium on the basis of improvement based on assessment of global severity. The differences in effects between lithium and risperidone were -2.79 (95%CI -4.22 to -1.36) in favour of risperidone with respect to symptom severity improvement and -0.76 (95%CI -1.11 to -0.41) on the basis of reduction in global severity of disease. Symptom and global severity was as well controlled with lithium as with verapamil. Lithium caused more side-effects than placebo and verapamil, but no more than carbamazepine or valproate.. The clinical trial evidence suggests that lithium should remain the first line treatment for acute mania.

Topics: Acute Disease; Adolescent; Adult; Aged; Antimanic Agents; Bipolar Disorder; Female; Humans; Lithium Chloride; Male; Middle Aged; Severity of Illness Index; Treatment Outcome

There are no published placebo-controlled studies of any agent in the treatment of acute mania in children or adolescents. This is the first placebo-controlled study of lithium's efficacy in the treatment of acute mania in adolescents.. In this discontinuation study, participants received open treatment with lithium at therapeutic serum levels (mean 0.99 mEq/L) for at least 4 weeks. Responders were randomly assigned to continue or discontinue lithium during a 2-week double-blind, placebo-controlled phase. This study had 80% power to detect a 40% difference in exacerbation rates between groups (10% on lithium versus 50% on placebo).. Twenty-three of 40 protocol participants (57.5%) experienced a clinically significant symptom exacerbation during the 2-week double-blind phase. However, the slightly lower exacerbation rate in the group maintained on lithium (10/19 or 52.6%) versus the group switched to placebo (13/21 or 61.9%) did not reach statistical significance.. This study does not support a large effect for lithium continuation treatment of adolescents with acute mania, mostly due to the unexpectedly high rate of exacerbations in the group that continued on lithium. Further studies are warranted to clarify whether acute mania in adolescents is lithium responsive.

Topics: Acute Disease; Adolescent; Aggression; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Brief Psychiatric Rating Scale; Comorbidity; Disease Progression; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium Chloride; Male; Psychotic Disorders; Recurrence; Risperidone; Treatment Outcome

Three separate lithium chloride doses, calculated according to body weight, and a placebo were administered under double-blind conditions to 68 manic inpatients. The relationship of lithium chloride treatment dose to steady-state serum lithium levels (day 7 to 10 of treatment) and clinical response were examined. High (0.72 mEq/kg/day) and medium (0.5 mEq/kg/day) lithium chloride doses were more efficacious than placebo (P<.001 and P<.05, respectively), as determined by decrements in global mania ratings (day 7 to 10 of treatment). A low dose (0.24 mEq/kg/day) was not found to be more efficacious than placebo. The proportion of patients with improved manic ratings increased markedly as a function of increased steady-state serum lithium level(chi-squared for trend in proportions, 17.91; P<.001).

Topics: Acute Disease; Adolescent; Adult; Aged; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Body Weight; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lithium Chloride; Male; Middle Aged; Patient Dropouts; Placebos; Psychiatric Status Rating Scales; Treatment Outcome

The antiapoptotic protein Bcl-xL is involved in development of neurobiological resilience to stress; hence, the possibility of use of psychotropic drugs to increase its expression in brain in response to stress is of considerable interest. Lithium is a neurotropic drug widely used in psychiatry. In work, we studied effects of lithium administration (for 2 or 7 days) on the expression of Bcl-xL mRNA and protein in the hippocampi and cortices of rats subjected to stress that induced depression-like behavior in the animals. In contrast to the brain-derived neurotrophic factor (BDNF), whose expression decreased in the hippocampus in response to acute stress, stress increased the level of Bcl-xL mRNA in the hippocampus, but decreased it in the frontal cortex. Treatment of stressed animals with lithium for 2 or 7 days increased Bcl-xL protein levels 1.5-fold in the hippocampus, but it decreased them in the cortex. Therefore, Bcl-xL expression in the brain can be modulated by both stress and psychotropic drugs, and the effects of these factors are brain region-specific: both stress exposure and lithium administration activated Bcl-xL expression in the hippocampus and suppressed it in the frontal cortex. The activation of Bcl-xL expression in the hippocampus by lithium, demonstrated for the first time in this study, suggests an important role of this protein in the therapeutic effects of lithium in the treatment of stress-induced psychoemotional disorders.

Topics: Acute Disease; Animals; bcl-X Protein; Frontal Lobe; Gene Expression Regulation; Hippocampus; Lithium; Lithium Chloride; Male; Rats; Rats, Wistar; Stress, Psychological

Lithium continues to be the treatment of choice for bipolar disorder. Acute lithium poisoning is a potentially serious event. We present a retrospective observational significative study of episodes of acute lithium poisoning during a 52- month period. Poisoning was defined by a blood lithium concentration of 1.5 mEq/L or higher. We analyzed treatment and epidemiologic and clinical characteristics of 70 episodes were identified (incidence density among treated patients, 1.76 per 100 patient-years). The most frequent cause of lithium poisoning was a concurrent medical condition (46%). Most poisonings were mild (74.2%), but neurologic involvement was identified in 40.3%. Electrocardiographic abnormalities were found in 8 cases. Acute renal failure, found in 23 patients (37.1%), was mild in most cases, although 11 patients required hemodialysis. We concluded that acute lithium poisoning is an uncommon complication, but risk needs to be lowered. Patients should be warned to avoid dosage errors and to take special care during concurrent illnesses and while taking other medications.. El litio sigue siendo el tratamiento de elección en el trastorno bipolar. La intoxicación aguda por litio (IAL) es un cuadro potencialmente grave. Se presenta un estudio observacional, retrospectivo de las IAL observadas durante un periodo de 52 meses. Se definió como IAL cuando se registró una concentración de litio en sangre 1,5 mEq/L. Se analizaron sus características clínicas, epidemiológicas y su tratamiento de 70 episodios de IAL (densidad de incidencia: 1,76 IAL por cada 100 pacientes tratados-año). La causa más frecuente de IAL fue un proceso patológico intercurrente (46%). La mayoría fueron de carácter leve (74,2 %), con sintomatología neurológica en el 40,3%. En 8 IAL hubo alteraciones electrocardiográficas, 23 IAL (37,1%) se asociaron con fracaso renal agudo, la mayoría de carácter leve y 11 precisaron hemodiálisis. Se concluye que la IAL es una complicación infrecuente, pero es necesario disminuir su riesgo advirtiendo al paciente ante la existencia de procesos intercurrentes, errores en la posología o polimedicación.

Topics: Acute Disease; Acute Kidney Injury; Aged; Antidepressive Agents; Bipolar Disorder; Comorbidity; Female; Humans; Lithium Chloride; Male; Middle Aged; Nervous System Diseases; Poisoning; Renal Dialysis; Retrospective Studies

Exogenous expression of the transcription factor Scl (Tal1) in WEHI-3B D+ myelomonocytic leukemia cells interferes with their capacity to respond to all-trans retinoic acid (ATRA) induced differentiation; combination of ATRA with LiCl, however, circumvents the inhibition of differentiation produced by Scl. To gain information on the possible involvement of this transcription factor in the non-responsiveness of acute myelocytic leukemia (AML) patients to ATRA, we compared the endogenous expression levels of Scl and its transcription complex partners [i.e., Rbtn1 (LMO1), Rbtn2 (LMO2), Ldb1, and GATA family proteins] in leukemic blast cells from patients with AML and acute promyelocytic leukemia (APL), and determined the effects of lithium chloride alone or in combination with ATRA on the capacity of blast cells to differentiate during short-term ex vivo culture. Levels of Scl, Rbtn2, GATA1, and Ldb1 expression were comparable in AML and APL blasts, while the levels of expression of Rbtn1, GATA2, and GATA3 were absent or markedly lower in APL cells. Differentiation markers (cell surface myeloid antigens CD11b, CD15, CD14, and CD33) were also analyzed in blast cells. ATRA produced changes in at least one surface antigen differentiation marker in 89% of patient blasts, while LiCl caused such changes in 72% of the leukemic cells of patients. The combination of LiCl and ATRA induced the differentiation of leukemic blasts from 94% of patients. Although the expression of the transcription factors did not act as individual predictors of responsiveness or non-responsiveness to the inducers of differentiation, ATRA or ATRA plus LiCl, the addition of LiCl to ATRA increased the differentiation response over that of ATRA alone in a number of leukemic samples. These findings suggest that the combination of LiCl and ATRA may produce some clinical benefit in the treatment of the myeloid leukemias.

Topics: Acute Disease; Adult; Aged; Base Sequence; Basic Helix-Loop-Helix Transcription Factors; Bone Marrow Cells; Cell Differentiation; DNA Primers; DNA-Binding Proteins; Female; Flow Cytometry; Humans; Leukemia, Myeloid; Lithium Chloride; Male; Middle Aged; Proto-Oncogene Proteins; T-Cell Acute Lymphocytic Leukemia Protein 1; Transcription Factors; Tretinoin

Animals made ill by intraperitoneal injection with toxins, such as lithium chloride (LiCl) or lipopolysaccharides (LPS), or presented with cues associated with LiCl become hyperalgesic [Pain 56 (1994) 227]. The descending pronociceptive neurocircuitry and spinal pharmacology that underlie these effects bear the same features as those that mediate analgesic tolerance to morphine [Neurosci. Biobehav. Rev. 23 (1999) 1059]. Thus, we examined whether LiCl, LPS or cues paired with LiCl could reduce morphine analgesia. Morphine analgesia in the tail flick test was reduced 24 h but not 7 days following injection with LiCl, and 24 h following injection with LPS. In addition, morphine analgesia was reduced in the hot plate test 40 min and 24 h following LiCl. Furthermore, these effects occurred in the absence of detectable hyperalgesia indicating that illness-induced tolerance was not the result of an increase in pain sensitivity offsetting analgesia. Finally, rats tested in a context associated with LiCl demonstrated less morphine analgesia than rats tested in a context not associated with LiCl or rats naive to LiCl suggesting that illness activates descending mechanisms that antagonize analgesia rather than simply desensitizing opioid receptors. Thus, in addition to provoking hyperalgesia, illness-inducing agents also activate endogenous antianalgesic mechanisms.

Topics: Acute Disease; Analgesia; Analgesics, Opioid; Animals; Conditioning, Psychological; Cues; Disease; Hyperalgesia; Lipopolysaccharides; Lithium Chloride; Male; Morphine; Neuroimmunomodulation; Pain; Pain Measurement; Pain Threshold; Rats; Rats, Wistar

Lithium is an established mood stabilizer and neuroprotective agent frequently used in the treatment of bipolar disorder and as an adjuvant in drug-resistant unipolar depression. The mechanisms underlying both the therapeutic efficacy of lithium and the exacerbation of symptoms following rapid withdrawal are not understood. From previous studies showing antidepressant and neuroprotective activities of thyrotropin releasing hormone (TRH) and TRH-related neuropeptides we hypothesized that lithium may have substantial effects on the expression and secretion of these peptides and/or their receptors in various rat brain regions involved in the regulation of mood. Chronic lithium effect on TRH receptor binding studies: The effect of 1 and 2 weeks of dietary lithium on [(3)H]3-Me-His-TRH binding to plasma membranes of nucleus accumbens, amygdala and pituitary of young adult male Wistar and the endogenously 'depressed' Wistar Kyoto (WKY) rats was measured by the method of Burt and Taylor [Burt, D.R., Taylor, R.L., Endocrinology 106 (1980) 1416-1423]. Acute, chronic and withdrawal effect of lithium on TRH and TRH-like peptide levels in young, adult male Sprague-Dawley rats: Rats were divided into four lithium treatment groups. Control animals received a standard laboratory rodent chow. The acute group received a single i.p. injection of 1.5 milli-equivalents of LiCl 2 h prior to killing. The chronic and withdrawal groups received standard rodent chow containing 1.7 g/kg LiCl for 2 weeks. Withdrawal rats were returned to standard chow 48 h prior to killing while the chronic animals continued on the LiCl diet. TRH, TRH-Gly (pGlu-His-Pro-Gly, a TRH precursor), EEP (pGlu-Glu-Pro-NH(2), a TRH-like peptide with antidepressant activity) and Ps4 (a prepro-TRH-derived TRH-enhancing decapeptide) immunoreactivity (IR) were measured in 13 brain regions. The remaining samples were pooled and fractionated by high-pressure liquid chromatography followed by EEP radioimmunoassay. Chronic lithium treatment increased [(3)H]3Me-TRH binding in the nucleus accumbens and amygdala about two-fold in both Wistar and WKY rats but no change was observed in pituitary binding. The most widespread changes in TRH and TRH-related peptide levels were observed in the withdrawal group compared to the controls. The direction of change for the total IR was consistent for all TRH-IR and TRH-related peptide-IR within a given tissue. For example, withdrawal increased all peptide levels in the pyriform co

Topics: Acute Disease; Animals; Brain; Chromatography, High Pressure Liquid; Drug Administration Schedule; Lithium Chloride; Male; Neuropeptides; Protein Binding; Protein Precursors; Pyrrolidonecarboxylic Acid; Rats; Rats, Inbred WKY; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Thyrotropin-Releasing Hormone; Substance Withdrawal Syndrome; Thyrotropin-Releasing Hormone

Topics: Acute Disease; Heart Septal Defects, Atrial; Humans; Indicator Dilution Techniques; Lithium Chloride