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1
Tournier, M., A. Cougnard, B. Bégaud, A. Thiébaut, and H. Verdoux. "The Metabolic Impact of the Antipsychotic Drugs in Patients with Bipolar Disorder." European Psychiatry 24, S1 (January 2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)70490-0.
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Objective:To assess the metabolic impact of adding an antipsychotic to a mood stabilizer or switching a mood stabilizer to an antipsychotic in patients with bipolar disorder.Methods:A retrospective fixed cohort study was conducted through the claims database of the French health care program for the self-employed workers. The study population consisted of 3.172 patients age 18 and over who were exposed to mood stabilizers (i.e. lithium, valproate) a 3 month-period in 2004 without dispensing of non-sedative antipsychotic, antidiabetic or lipid-lowering drugs. The outcome was the occurrence of a metabolic incident over the follow-up period, using the dispensing of an antidiabetic drug as a marker of diabetes and the dispensing of a lipid-lowering drug as a marker of hypercholesterolemia or hypertriglyceridemia. A Cox proportional hazard model was used to assess the metabolic impact of the antipsychotics; using mood stabilizers as a reference. Antipsychotic exposition was stratified in «current» and «recent» (discontinued for less than 6 months) at the time of the metabolic incident.Results:196 patients (6.2%) received a first-generation antipsychotic, 352 (11.1%) a second-generation antipsychotic, 565 (17.8%) a sedative antipsychotic and 367 patients (11.6%) presented with a metabolic incident over the study period. The recent dispensing of a second-generation antipsychotic was associated with the occurrence of a metabolic incident [HR 2.1 (95%CI 1.2-3.7) p=0.006], while current dispensing or dispensing of first-generation antipsychotics were not.Conclusion:Second-generation antipsychotics have a metabolic impact compared to classic mood stabilizers in patients with bipolar disorder.
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Kahn, David, and Rebecca Chaplan. "The “Good Enough” Mood Stabilizer: A Review of the Clinical Evidence." CNS Spectrums 7, no. 3 (March 2002): 227–37. http://dx.doi.org/10.1017/s1092852900017594.
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ABSTRACTA growing family of medications is used for mood stabilization in bipolar disorder. These medications fall into two broad categories according to likely mechanisms of action. Within the categories, specific drugs may vary in their efficacy for different phases of the disorder. The first category, including lithium, anticonvulsants, and some novel treatments, appears to have mechanisms related to intracellular second messengers. These medications have more pronounced antimanic than antidepressant effects, except for lamotrigine, which has antidepressant effects without precipitating mania. The second group of mood stabilizers is the atypical antipsychotics, which act through dopamine and other monoamines. Olanzapine and in all likelihood other drugs in the class possess marked, acute antimanic properties and possible antidepressant properties, but require further study before they can be used as routine options in long-term care. It is clear that the advent of multiple mood stabilizer candidates has not yet led to a single ideal therapy for bipolar disorder, but rather to options that can be flexibly tailored to the lifetime needs of individual patients, in sequences or combinations, and perhaps in conjunction with other classes of psychotropics.
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Williams, R., W. J. Ryves, E. C. Dalton, B. Eickholt, G. Shaltiel, G. Agam, and A. J. Harwood. "A molecular cell biology of lithium." Biochemical Society Transactions 32, no. 5 (October 26, 2004): 799–802. http://dx.doi.org/10.1042/bst0320799.
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Lithium (Li+), a mood stabilizer, has profound effects on cultured neurons, offering an opportunity to investigate its cellular biological effects. Here we consider the effect of Li+ and other psychotropic drugs on growth cone morphology and chemotaxis. Li+ inhibits GSK-3 (glycogen synthase kinase-3) at a therapeutically relevant concentration. Treated cells show a number of features that arise due to GSK-3 inhibition, such as altered microtubule dynamics, axonal branching and loss of semaphorin 3A-mediated growth cone collapse. Li+ also causes growth cones to spread; however, a similar effect is seen with two other mood stabilizers, valproic acid and carbamazepine, but without changes in microtubules or axon branching. This common effect of mood stabilizers is mediated by changes in inositol phosphate signalling, not GSK-3 activity. Given the presence of neurogenesis in the adult brain, we speculate that changes in growth cone behaviour could also occur during treatment of mental disorders.
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Dubovsky, Steven L., and Amelia N. Dubovsky. "Maintenance Treatment of Bipolar Disorder with Ziprasidone in Adjunctive Use with Lithium or Valproate." Clinical Medicine Insights: Therapeutics 4 (January 2012): CMT.S7369. http://dx.doi.org/10.4137/cmt.s7369.
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Ziprasidone is a second generation (“atypical”) antipsychotic drug that has been used alone and as an adjunct to standard mood stabilizers to reduce recurrence rates in bipolar disorder. Approval of ziprasidone as an adjunct to lithium or valproate in 2009 was based on an industry sponsored study of 584 outpatients with a current or recent manic episode; 240 of these subjects were randomized to adjunctive ziprasidone or placebo and 138 completed a six month trial. Patients enrolled in maintenance studies did not have refractory mood disorders, comorbid conditions or risk of dangerousness. Maintenance ziprasidone augmentation is an option for patients who do not respond to a single mood stabilizer rapidly, and possibly for those with residual psychotic symptoms, but there are insufficient data to prefer this approach to combinations of mood stabilizers or augmentation with other agents. Ziprasidone is generally well tolerated, with less sedation and weight gain than many other antipsychotic drugs; it should be taken with food. Primary interactions of concern are with other serotonergic medications, MAO inhibitors, and other medications that prolong the QT interval.
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Del’Guidice, Thomas, Camille Latapy, Antonio Rampino, Jivan Khlghatyan, Morgane Lemasson, Barbara Gelao, Tiziana Quarto, et al. "FXR1P is a GSK3β substrate regulating mood and emotion processing." Proceedings of the National Academy of Sciences 112, no. 33 (August 3, 2015): E4610—E4619. http://dx.doi.org/10.1073/pnas.1506491112.
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Inhibition of glycogen synthase kinase 3β (GSK3β) is a shared action believed to be involved in the regulation of behavior by psychoactive drugs such as antipsychotics and mood stabilizers. However, little is known about the identity of the substrates through which GSK3β affects behavior. We identified fragile X mental retardation-related protein 1 (FXR1P), a RNA binding protein associated to genetic risk for schizophrenia, as a substrate for GSK3β. Phosphorylation of FXR1P by GSK3β is facilitated by prior phosphorylation by ERK2 and leads to its down-regulation. In contrast, behaviorally effective chronic mood stabilizer treatments in mice inhibit GSK3β and increase FXR1P levels. In line with this, overexpression of FXR1P in the mouse prefrontal cortex also leads to comparable mood-related responses. Furthermore, functional genetic polymorphisms affecting either FXR1P or GSK3β gene expression interact to regulate emotional brain responsiveness and stability in humans. These observations uncovered a GSK3β/FXR1P signaling pathway that contributes to regulating mood and emotion processing. Regulation of FXR1P by GSK3β also provides a mechanistic framework that may explain how inhibition of GSK3β can contribute to the regulation of mood by psychoactive drugs in mental illnesses such as bipolar disorder. Moreover, this pathway could potentially be implicated in other biological functions, such as inflammation and cell proliferation, in which FXR1P and GSK3 are known to play a role.
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Balasubramanian, Diana, John F. Pearson, and Martin A. Kennedy. "Gene expression effects of lithium and valproic acid in a serotonergic cell line." Physiological Genomics 51, no. 2 (February 1, 2019): 43–50. http://dx.doi.org/10.1152/physiolgenomics.00069.2018.
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Valproic acid (VPA) and lithium are widely used in the treatment of bipolar disorder. However, the underlying mechanism of action of these drugs is not clearly understood. We used RNA-Seq analysis to examine the global profile of gene expression in a rat serotonergic cell line (RN46A) after exposure to these two mood stabilizer drugs. Numerous genes were differentially regulated in response to VPA (log2 fold change ≥ 1.0; i.e., odds ratio of ≥2, at false discovery rate <5%), but only two genes ( Dynlrb2 and Cdyl2) showed significant differential regulation after exposure of the cells to lithium, with the same analysis criteria. Both of these genes were also regulated by VPA. Many of the differentially expressed genes had functions of potential relevance to mood disorders or their treatment, such as several serpin family genes (including neuroserpin), Nts (neurotensin), Maob (monoamine oxidase B), and Ap2b1, which is important for synaptic vesicle function. Pathway analysis revealed significant enrichment of Gene Ontology terms such as extracellular matrix remodeling, cell adhesion, and chemotaxis. This study in a cell line derived from the raphe nucleus has identified a range of genes and pathways that provide novel insights into potential therapeutic actions of the commonly used mood stabilizer drugs.
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Walder, Alice, and Pierre Baumann. "Mood Stabilizer Therapy and Pravastatin: Higher Risk for Adverse Skin Reactions?" Acta Medica (Hradec Kralove, Czech Republic) 52, no. 1 (2009): 15–18. http://dx.doi.org/10.14712/18059694.2016.101.
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We report on a serious side effect in a severely depressed 55-year-old woman, who presented an erythematous pigmented skin rash on the whole body under combination treatment with antidepressants, atypical antipsychotic drugs, the mood stabilizer lithium and the lipid-lowering drug pravastatin. The skin rash effect was most probably due, in first line, to olanzapine, but the cutaneous skin condition was triggered and aggravated by pravastatin, a 3-hydoxy-3-methylglutaryl-coenzyme A-(HMG-CoA)-reductase inhibitor, and lithium medication. The allergic reaction started to develop after co-administration of pravastatin. Therefore, the combination of atypical antipsychotics with statins should be carefully monitored and the benefits and disadvantages should be balanced.
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Baldassano, Claudia F. "Antidepressant Effect of Mood Stabilizers." CNS Spectrums 8, S12 (December 2003): 4–5. http://dx.doi.org/10.1017/s1092852900028777.
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Bipolar depression certainly poses the greatest challenge to clinicians treating bipolar patients. Having a widespread disability associated with it, bipolar depression is often chronic, is less responsive to medication treatment, and has a particularly high rate of suicide. There are currently no drugs approved by the Food and Drug Administration for the treatment of bipolar depression, although full trials have been conducted with lithium, the antipsychotic olan-zapine, and the antiepileptic (AED) lamotrigine. Data for the other AEDs are quite limited and not controlled. The American Psychiatric Association guidelines recommends maximizing the dose in patients who are already on a mood stabilizer and initiating lithium or lamotrigine in patients who are not on a mood stabilizer.Zornberg and Pope reviewed nine studies comparing lithium to placebo in bipolar depression. Among the 145 patients in these studies, there was detectable response in 79% and an unequivocal response in 36%. Although the studies varied in their methodological design and rigor, they argue quite strongly that lithium is an effective anti-depressant. In addition, six of the seven pre1990 studies evaluating lithium for bipolar depression indicated that the drug had significant antidepressant effects.The most recent study of lithium for bipolar depression randomly assigned 117 outpatients with acute bipolar depression to treatment with either placebo, Imipramine, or paroxetine. At the 10-week study endpoint, lithium monotherapy was as effective as the addition of an antidepressant, suggesting lithium's antidepressant properties.
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Corson, Timothy W., Karen K. Woo, Peter P. Li, and Jerry J. Warsh. "Cell-type specific regulation of calreticulin and Bcl-2 expression by mood stabilizer drugs." European Neuropsychopharmacology 14, no. 2 (March 2004): 143–50. http://dx.doi.org/10.1016/s0924-977x(03)00102-0.
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Rifaya, Annida, Risna Agustina, and Rolan Rusli. "Pola Penggunaan Obat Mood Stabilizer Pada Pasien Bipolar di Rumah Sakit Jiwa Daerah Atma Husada Mahakam." Proceeding of Mulawarman Pharmaceuticals Conferences 10 (October 31, 2019): 86–93. http://dx.doi.org/10.25026/mpc.v10i1.368.
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Bipolar disorder is a chronic mood disorder characterized by episodes of mania or hypomania that occur alternately or mixed with depressive episodes. This study aims to determine the characteristics of bipolar patients and patterns of drug use inpatient and outpatient bipolar patients at Atma Husada Mahakam Hospital. The type of this research is non experimental (descriptive) and done retrospectively. Data are collected from medical record. Research subjects were 84 inpatients and 137 outpatients with bipolar disorder diagnosis. Data are analyzed by describing research's objects. The results were obtained from inpatient and outpatient data showing 63% and 60% female sex, showing 26-35 years (early adulthood), not working, not married, and high school level education. The most usage pattern of drugs is a combination of 2 and 3 drugs, namely 74.99% for inpatient care and 73.71% for outpatient treatment. The drugs most commonly used are mood stabilizers (valproate acid) and atypical antipsychotics (risperidone).
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Teo, Regina, Jason King, Emma Dalton, Jonathan Ryves, Robin S. B. Williams, and Adrian J. Harwood. "PtdIns(3,4,5)P3 and inositol depletion as a cellular target of mood stabilizers." Biochemical Society Transactions 37, no. 5 (September 21, 2009): 1110–14. http://dx.doi.org/10.1042/bst0371110.
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Lithium (Li+) is the mood stabilizer most frequently used in the treatment of bipolar mood disorder; however, its therapeutic mechanism is unknown. In the 1980s, Berridge and colleagues proposed that Li+ treatment acts via inhibition of IMPase (inositol monophosphatase) to deplete the cellular concentration of myo-inositol. Inositol depletion is also seen with the alternative mood stabilizers VPA (valproic acid) and CBZ (carbamazepine), suggesting a common therapeutic action. All three drugs cause changes in neuronal cell morphology and cell chemotaxis; however, it is unclear how reduced cellular inositol modulates these changes in cell behaviour. It is often assumed that reduced inositol suppresses Ins(1,4,5)P3, a major intracellular signal molecule, but there are other important phosphoinostide-based signal molecules in the cell. In the present paper, we discuss evidence that Li+ has a substantial effect on PtdIns(3,4,5)P3, an important signal molecule within the nervous system. As seen for Ins(1,4,5)P3 signalling, suppression of PtdIns(3,4,5)P3 signalling also occurs via an inositol-depletion mechanism. This has implications for the cellular mechanisms controlling phosphoinositide signalling, and offers insight into the genetics underlying risk of bipolar mood disorder.
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Parker, Gordon, Gordon Parker, and Kay Parker. "Which Antidepressants Flick the Switch?" Australian & New Zealand Journal of Psychiatry 37, no. 4 (August 2003): 464–68. http://dx.doi.org/10.1046/j.1440-1614.2003.01207.x.
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Objective: The Black Dog Institute seeks to address issues of relevance to the clinical management of those with a mood disorder. This overview considers the capacity of antidepressant drugs, and particularly the new classes, to induce manic switching in depressed patients. Method: Relevant literature is reviewed. Results: It is unclear whether antidepressant drugs from any of the classes induce switching in unipolar depressed patients. In bipolar depressed patients, the broad-spectrum tricyclic and monoamine oxidase inhibitor drugs present a clear risk of switching, the selective serotonin re-uptake inhibitors do not appear (at standard doses) to increase the risk, while the capacity of the dual action (serotonergic and noradrenergic) drugs to induce switching remains unestablished but may be slight. Conclusions: As switching induced by narrow action antidepressants does not appear to present a substantive causal risk, clinicians can have confidence in prescribing certain antidepressants for managing bipolar depression, and without any necessity to first prescribe a mood stabilizer to pre-empt switching.
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Hebel, T., M. A. Abdelnaim, M. Deppe, P. M. Kreuzer, A. Mohonko, T. B. Poeppl, R. Rupprecht, B. Langguth, and M. Schecklmann. "Antidepressant effect of repetitive transcranial magnetic stimulation is not impaired by intake of lithium or antiepileptic drugs." European Archives of Psychiatry and Clinical Neuroscience 271, no. 7 (July 3, 2021): 1245–53. http://dx.doi.org/10.1007/s00406-021-01287-3.
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Abstract Introduction The effect of concomitant medication on repetitive transcranial magnetic stimulation (rTMS) outcomes in depression remains understudied. Recent analyses show attenuation of rTMS effects by antipsychotic medication and benzodiazepines, but data on the effects of antiepileptic drugs and lithium used as mood stabilizers or augmenting agents are sparse despite clinical relevance. Preclinical electrophysiological studies suggest relevant impact of the medication on treatment, but this might not translate into clinical practice. We aimed to investigate the role of lithium (Li), lamotrigine (LTG) and valproic acid (VPA) by analyzing rTMS treatment outcomes in depressed patients. Methods 299 patients with uni- and bipolar depression treated with rTMS were selected for analysis in respect to intake of lithium, lamotrigine and valproic acid. The majority (n = 251) were treated with high-frequency (10–20 Hz) rTMS of the lDLPFC for an average of 17 treatment sessions with a figure-of-8 coil with a MagVenture system aiming for 110% resting motor threshold, and smaller groups of patients were being treated with other protocols including intermittent theta-burst stimulation and bilateral prefrontal and medial prefrontal protocols. For group comparisons, we used analysis of variance with the between-subjects factor group or Chi-Square Test of Independence depending on the scales of measurement. For post-hoc tests, we used least significant difference (LSD). For differences in treatment effects between groups, we used an ANOVA with the between-subjects factor group (groups: no mood stabilizer, Li, LTG, VPA, Li + LTG) the within-subjects factor treatment (pre vs. post treatment with rTMS) and also Chi-Square Tests of independence for response and remission. Results Overall, patients showed an amelioration of symptoms with no significant differences for the main effect of group and for the interaction effect treatment by group. Based on direct comparisons between the single groups taking mood stabilizers against the group taking no mood stabilizers, we see a superior effect of lamotrigine, valproic acid and combination of lithium and lamotrigine for the response and remission rates. Motor threshold was significantly and markedly higher for patients taking valproic acid. Conclusion Being treated with lithium, lamotrigine and valproic acid had no relevant influence on rTMS treatment outcome. The results suggest there is no reason for clinicians to withhold or withdraw these types of medication from patients who are about to undergo a course of rTMS. Prospective controlled work on the subject is encouraged.
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Ephraim, E., and R. Prettyman. "Attitudes of old age psychiatrists in England and Wales to the use of mood stabilizer drugs." International Psychogeriatrics 21, no. 03 (March 4, 2009): 576. http://dx.doi.org/10.1017/s1041610209008667.
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Tillery, Erika E., Rikki L. Tonet, and Christine A. Trahan. "Oh baby! A review of mood stabilizers for bipolar disorder in the child-bearing woman." Mental Health Clinician 3, no. 2 (August 1, 2013): 61–70. http://dx.doi.org/10.9740/mhc.n163522.
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Background: Bipolar disorder is a brain disorder that can cause abnormal changes in a person's mood, cognitive function, and quality of life. Patients who are diagnosed with bipolar disorder often have intense emotional states that are characterized by either manic or depressive episodes. There is a strong correlation between women of child bearing age and the initial age of onset of the disease. Mood stabilizing drugs have been the mainstay of treatment for many decades; however, there is strong data supporting the teratogenic effects of these drugs on the fetus in pregnant and lactating women. Methods: Review articles, clinical trials, and practice guidelines were located using online databases PubMed, CINAHL, IDIS, and Medline. Search terms included at least one of the following: “bipolar disorder”, “breast-feeding”, “carbamazepine”, “epilepsy”, “lactation”, “lamotrigine”, “lithium”, “mood stabilizers”, “pregnancy”, “valproate”, and “valproic acid”. Online clinical databases Clinical Pharmacology and Lexi-Comp were also used in the study. Results: All mood stabilizer drugs are found to cause malformations in fetal development if given during the first trimester of pregnancy, thus use should be avoided if possible. Lamotrigine was found to cause lowest risk of adverse effects in both the mother and fetus during pregnancy; however, it should be avoided in breastfeeding women as it readily passes into breast milk. Lithium use during pregnancy and lactation has been associated with severe malformations and should only be used if maternal benefit outweighs fetal risk. Valproate is considered harmful to both the mother and fetus during pregnancy, but may be a compatible option for breastfeeding. Carbamazepine is found to cause serious malformations with the developing fetus as well as metabolic effects with the mother; however, it is found to cause little effects in breastfed infants as it does not readily pass through breast milk. Conclusion: The use of medications in pregnant and breastfeeding women suffering from bipolar disorder must be carefully considered for impacts on fetal development as well as risks to the mother. Mood stabilizers are readily marketed as first line treatment options for bipolar disorder; however, their use in pregnant and lactating women may cause limitations as preferred therapy. Studies show that though lamotrigine has not been as well studied as the other agents, it may be the best recommendation during pregnancy, for both fetal and maternal health concerns. For breastfeeding women, carbamazepine has been shown to be the better option, as it carries the lowest risk of adverse events to the infant.
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Rybakowski, Janusz K. "Recent advances in the understanding and management of bipolar disorder in adults." F1000Research 6 (November 21, 2017): 2033. http://dx.doi.org/10.12688/f1000research.12329.1.
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This article focuses on some aspects of recent progress in the neurobiology and treatment of bipolar disorder (BD) in adults. A molecular-genetic approach to the etiopathogenesis of the illness resulted in the findings of a genetic overlap between BD and other major psychiatric disorders. Furthermore, a poly-gene-environmental interaction in the development of the illness has been demonstrated. For the management of BD, new drugs with putative mood-stabilizing properties have been introduced in the past two decades. However, none of these can surpass lithium, the prototype mood-stabilizer, still considered the most specific drug for BD. Recent research on lithium, besides providing new data on the neurobiology of BD, has confirmed anti-suicidal, immunomodulatory, and neuroprotective properties of this drug.
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Freitas, R. M., S. M. M. Vasconcelos, F. C. F. Sousa, G. S. B. Viana, and M. M. F. Fonteles. "Pharmacological studies of the opioids, mood stabilizer and dopaminergic drugs on pilocarpine-induced seizures and status epilepticus." Neuroscience Letters 408, no. 2 (November 2006): 84–88. http://dx.doi.org/10.1016/j.neulet.2006.08.009.
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Scarr, Elizabeth, and Brian Dean. "Altered Neuronal Markers Following Treatment with Mood Stabilizer and Antipsychotic Drugs Indicate an Increased Likelihood of Neurotransmitter Release." Clinical Psychopharmacology and Neuroscience 10, no. 1 (April 28, 2012): 25–33. http://dx.doi.org/10.9758/cpn.2012.10.1.25.
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Betari, Nibal, Knut Teigen, Kristoffer Sahlholm, and Jan Haavik. "Synthetic corticosteroids as tryptophan hydroxylase stabilizers." Future Medicinal Chemistry 13, no. 17 (September 2021): 1465–74. http://dx.doi.org/10.4155/fmc-2021-0068.
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Background: Clinically, corticosteroids are used mainly for their immune-modulatory properties but are also known to influence mood. Despite evidence of a role in regulating tryptophan hydroxylases (TPH), key enzymes in serotonin biosynthesis, a direct action of corticosteroids on these enzymes has not been systematically investigated. Methodology & results: Corticosteroid effects on TPHs were tested using an in vitro assay. The compound with the strongest modulatory effect, beclomethasone dipropionate, activated TPH1 and TPH2 with low micromolar potency. Thermostability assays suggested a stabilizing mechanism, and computational docking indicated that beclomethasone dipropionate interacts with the TPH active site. Conclusion: Beclomethasone dipropionate is a stabilizer of TPHs, acting as a pharmacological chaperone. Our findings may inspire further development of steroid scaffolds as putative antidepressant drugs.
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Niell, L., J. Rodríguez, R. A. Baena, I. Alberdi-Paramo, G. Montero, M. M. Tenorio, M. Pereira, et al. "Is the use of long-acting injectable antipsychotic extended in the outpatient treatment of bipolar disorder? A brief description." European Psychiatry 41, S1 (April 2017): S424—S425. http://dx.doi.org/10.1016/j.eurpsy.2017.01.392.
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AimsObtain and analyze information on treatment guidelines, with particular emphasis on the use of antipsychotics, in patients diagnosed with bipolar disorder I and bipolar disorder II who are treated at a mental health center in a district of Madrid (Spain) under the conditions of habitual clinical practice.Then, compare with recently published literature.MethodsWe performed a descriptive study of a sample of 100 patients diagnosed with bipolar disorder (type I and type II) at any stage of the disease who receive regular treatment in a mental health center in a district of Madrid. Information regarding the treatment used, especially the use of antipsychotics (either in a single therapy or in combination with other drugs such as mood stabilizers, antidepressants, hypnotics or anxiolytics), was collected retrospectively from the data obtained from the medical record.ResultsNinety-four percent of patients are taking mood stabilizer treatment (68% lithium, 24% valproate, 1% and 1% carbamazepine and lamotrigine). Four percent take lithium and valproate in combination. Forty-eight percent of patients are taking some antipsychotic (atypical about 90%). Of these, only 10% in injectable form, and 5% take both oral and injectable antipsychotics.ConclusionsThe diminished use of injectable antipsychotics, well below recent publications, draws the attention. You can probably explain this low proportion of injectable medication because we are generally dealing with stable patients with a long-term disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Damri, Odeya, Nofar Shemesh, and Galila Agam. "Is There Justification to Treat Neurodegenerative Disorders by Repurposing Drugs? The Case of Alzheimer’s Disease, Lithium, and Autophagy." International Journal of Molecular Sciences 22, no. 1 (December 27, 2020): 189. http://dx.doi.org/10.3390/ijms22010189.
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Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug’s neuroprotective characteristics and, thereby, has raised the option of repurposing it as a drug for neurodegenerative diseases. Lithium’s neuroprotective properties rely on its modulation of homeostatic mechanisms such as inflammation, mitochondrial function, oxidative stress, autophagy, and apoptosis. This myriad of intracellular responses are, possibly, consequences of the drug’s inhibition of the enzymes inositol-monophosphatase (IMPase) and glycogen-synthase-kinase (GSK)-3. Here we review lithium’s neurobiological properties as evidenced by its neurotrophic and neuroprotective properties, as well as translational studies in cells in culture, in animal models of Alzheimer’s disease (AD) and in patients, discussing the rationale for the drug’s use in the treatment of AD.
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Himmerich, Hubertus, Stefanie Bartsch, Hajo Hamer, Roland Mergl, Jeremias Schönherr, Charlotte Petersein, Alexander Munzer, Kenneth Clifford Kirkby, Katrin Bauer, and Ulrich Sack. "Modulation of Cytokine Production by Drugs with Antiepileptic or Mood Stabilizer Properties in Anti-CD3- and Anti-CD40-Stimulated BloodIn Vitro." Oxidative Medicine and Cellular Longevity 2014 (2014): 1–11. http://dx.doi.org/10.1155/2014/806162.
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Increased cytokine production possibly due to oxidative stress has repeatedly been shown to play a pivotal role in the pathophysiology of epilepsy and bipolar disorder. Recentin vitroand animal studies of valproic acid (VPA) report antioxidative and anti-inflammatory properties, and suppression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. We tested the effect of drugs with antiepileptic or mood stabilizer properties, namely, primidone (PRM), carbamazepine (CBZ), levetiracetam (LEV), lamotrigine (LTG), VPA, oxcarbazepine (OXC), topiramate (TPM), phenobarbital (PB), and lithium on the production of the following cytokinesin vitro: interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-17, IL-22, and TNF-α. We performed a whole blood assay with stimulated blood of 14 healthy female subjects. Anti-human CD3 monoclonal antibody OKT3, combined with 5C3 antibody against CD40, was used as stimulant. We found a significant reduction of IL-1 and IL-2 levels with all tested drugs other than lithium in the CD3/5C3-stimulated blood; VPA led to a decrease in IL-1β, IL-2, IL-4, IL-6, IL-17, and TNF-αproduction, which substantiates and adds knowledge to current hypotheses on VPA’s anti-inflammatory properties.
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Frye, Mark A. "Treatment Guidelines for Acute Manic and Mixed Episodes of Bipolar Disorder." CNS Spectrums 14, S15 (December 2009): 8–11. http://dx.doi.org/10.1017/s1092852900004028.
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Bipolar disorder is a lifelong condition, and pharmacotherapy is essential to its long-term management. Once a comprehensive diagnostic assessment for acute or mixed mania has been completed, it is important to look at an evidence-based data set to guide treatment selection for mood stabilization.For most patients, lifetime adherence to pharmacotherapy is necessary for maximal mood stability. Pharmacotherapy is the primary treatment for bipolar disorder, as it has been found to be efficacious in treating acute episodes and preventing future episodes of bipolar I disorder. Combination therapy, including at least one mood stabilizer, may be necessary to treat acute depression and mania and to further prevent both depressive and manic recurrences. The goal is to minimize frequency, duration, and severity of depressive and manic symptoms with a treatment regimen, ideally a combination of pharmacotherapy and psychotherapy, that is positioned to maximize treatment adherence and minimize side effects.This discussion reviews some treatment guidelines for acute manic and mixed episodes associated with bipolar I disorder. Through the context of a case study, this discussion will attempt to provide an understanding and appreciation of Food and Drug Administration-approved and non-FDA-approved treatments for acute mania. In addition, the impact of alcohol as an example of drugs of abuse and its impact on the presentation of acute mania will be discussed.
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Krzystanek, Marek, and Artur Pałasz. "Possibility of a New Indication for Amantadine in the Treatment of Bipolar Depression—Case Series Study." Pharmaceuticals 13, no. 10 (October 21, 2020): 326. http://dx.doi.org/10.3390/ph13100326.
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Bipolar disorder is a chronic and remitting mental illness. Antidepressants are not effective in treating acute bipolar depression, and antipsychotic drugs used in the treatment of bipolar depression cause frequent side effects. This situation justifies the search for new drugs as well as the repurposing of drugs used in other indications. In an open and naturalistic serious case study, 4 patients diagnosed with bipolar I disorder, chronically treated with a mood stabilizer, in whom at least two antidepressants were ineffective in the depressive phase, were treated with amantadine. The woman received 100 mg/day and 3 men received the target dose of 200 mg/day. All patients treated with amantadine improved their depressive symptoms after 1 week of treatment. None of them experienced side effects or manic switch. To reduce the risk of a manic switch, the treatment with amantadine was discontinued 2 weeks after the improvement of depressive symptoms, and no recurrence of depressive symptoms was observed. Amantadine may be a further therapeutic option for the treatment of acute bipolar depression. The drug in this indication may act quickly and be well tolerated. Confirmation of the antidepressant efficacy of amantadine in this indication requires replication of the results and conducting clinical trials.
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Suppes, Trisha. "Reproductive Health and Bipolar Disorder." CNS Spectrums 11, S5 (May 2006): 1–16. http://dx.doi.org/10.1017/s1092852900025608.
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AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.
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Suppes, Trisha. "Gender Differences in Bipolar Disorder." CNS Spectrums 11, S5 (May 2006): 2–4. http://dx.doi.org/10.1017/s1092852900025670.
Full textAbstract:
AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.
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Ketter, Terence A. "Effects of the Female Reproductive System on Bipolar Disorder." CNS Spectrums 11, S5 (May 2006): 5–6. http://dx.doi.org/10.1017/s1092852900025682.
Full textAbstract:
AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.
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Rasgon, Natalie. "Selection of Appropriate Therapy: Valproate and Reproductive Function." CNS Spectrums 11, S5 (May 2006): 7–9. http://dx.doi.org/10.1017/s1092852900025694.
Full textAbstract:
AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.
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Morrell, Martha J. "Effects of In Utero Exposure to AEDs on Morphology and Neurodevelopment." CNS Spectrums 11, S5 (May 2006): 9–10. http://dx.doi.org/10.1017/s1092852900025700.
Full textAbstract:
AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.
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Cohen, Lee S. "Treatment of Bipolar Disorder During Pregnancy." CNS Spectrums 11, S5 (May 2006): 11–12. http://dx.doi.org/10.1017/s1092852900025712.
Full textAbstract:
AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.
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Viguera, Adele C. "Treatment of Bipolar Disorder During the Postpartum Period." CNS Spectrums 11, S5 (May 2006): 13–14. http://dx.doi.org/10.1017/s1092852900025724.
Full textAbstract:
AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.
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Ketter, Terence A., Trisha Suppes, Martha J. Morrell, Natalie Rasgon, Lee S. Cohen, and Adele C. Viguera. "Question-and-Answer Forum." CNS Spectrums 11, S5 (May 2006): 15–16. http://dx.doi.org/10.1017/s1092852900025736.
Full textAbstract:
AbstractThe presentations and clinical courses of patients with bipolar disorder differ greatly by gender. In addition, medical therapy must be tailored differently for men and women because of emerging safety concerns unique to the female reproductive system. In November 2005, these topics were explored by a panel of experts in psychiatry, neurology, and reproductive health at a closed roundtable meeting in Dallas, Texas. This clinical information monograph summarizes the highlights of that meeting.Compared to men with bipolar disorder, women have more pervasive depressive symptoms and experience more major depressive episodes. They are also at higher risk for obesity and certain other medical and psychiatric comorbidities. Mood changes across the menstrual cycle are common, although the severity, timing, and type of changes are variable. Bipolar disorder is frequently associated with menstrual abnormalities and ovarian dysfunction, including polycystic ovarian syndrome. Although some cases of menstrual disturbance precede the treatment of bipolar disorder, it is possible that valproate and/or antipsychotic treatment may play a contributory role in young women.Pregnancy does not protect against mood episodes in untreated women. Maintenance of euthymia during pregnancy is critical because relapse during this period strongly predicts a difficult postpartum course. Suspending therapy in the first months of pregnancy may be an option for some women with mild-to-moderate illness, or those with a long history of euthymia during pre-pregnancy treatment. However, a mood stabilizer should be reintroduced either in the later stages of pregnancy or in the immediate postpartum period. Preliminary data suggest that fetal exposure to some mood stabilizers may raise the risk of major congenital malformations and neurodevelopmental delays. For women planning to become pregnant, clinicians may consider switching to other drugs before conception. The value and drawbacks of breastfeeding during treatment must be considered in partnership with the patient, with close monitoring of nursing infants thereafter. The risks and benefits of medical treatment for women with bipolar disorder should be carefully reconsidered at each stage of their reproductive lives, with a flexible approach that is responsive to the changing needs of patients and their families.
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Vieta, E. "JS01-04 - Rational optimization of bipolar disorders’ treatment." European Psychiatry 26, S2 (March 2011): 1998. http://dx.doi.org/10.1016/s0924-9338(11)73701-4.
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Bipolar disorder is difficult to treat. There are several options to treat acute mania, but combination of two or more drugs is the rule rather than the exception, indicating the limitations of currently available therapies. The evidence base for the treatment of bipolar depression is much weaker, and again combination is the rule. Although patients with bipolar disorder may experience resolution of symptoms with acute treatment, many will continue to experience impaired functioning due to the episodic, chronic, and progressive nature of the illness. Maintenance therapy is needed for a variety of reasons, including prevention of relapse, reduction of subthreshold symptoms, decreasing the risk of suicide, and reducing the frequency of rapid cycling and mood instability. Although long-term therapy is usually required to maintain or improve functioning and quality of life, it has been a significant challenge to identify clinically effective treatments for long-term management. There are few currently-available, well-tolerated treatment options that are effective in all phases of bipolar disorder and which prevent recurrence of manic and/or depressive episodes. Questions concerning when to discontinue one of the drugs when two or more are used, or how to switch from one mood stabilizer to another, have not been addressed in clinical trials. Electroconvulsive therapy may be effective in treatment resistant cases and can be used as maintenance when pharmacotherapy is not enough. Psychoeducation may help to enhance treatment adherence and healthy lifestyle. A rational combination of the above mentioned strategies may help to optimize the outcome of this challenging condition.
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Porat, Daniel, Carmil Azran, Hasan Kais, and Arik Dahan. "Managing the Unpredictable: Mechanistic Analysis and Clinical Recommendations for Lamotrigine Treatment after Bariatric Surgery." Journal of Clinical Medicine 10, no. 23 (November 29, 2021): 5627. http://dx.doi.org/10.3390/jcm10235627.
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Bariatric surgery may alter the absorption and overall bioavailability of oral drugs. Lamotrigine is a major antiepileptic and mood stabilizer, that its use after bariatric surgery has not yet been studied. In this article, we provide a thorough mechanistic analysis of the effects of bariatric surgery on multiple mechanisms important for the absorption, bioavailability and overall pharmacokinetics of lamotrigine. Attributable to its pharmacokinetic properties and drug characteristics, the use of lamotrigine after bariatric surgery may be challenging. The complex situation in which some mechanisms may lead to increased drug exposure (e.g., decreased metabolism, weight loss) while others to its decrease (e.g., hampered dissolution/solubility, decreased gastric volume), may result in lowered, unchanged, or enhanced lamotrigine plasma levels after the surgery. We conclude with a set of clinical recommendations for lamotrigine treatment after bariatric surgery, aiming to allow better patient care, and emphasizing the extra caution that needs to be taken with these patients.
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Ghorbanalizadeh-Khalifeh-Mahaleh, B., S. Taheri, M. Sahengharani, A. Rezayof, A. Haeri-Rohani, and M. R. Zarrindast. "Intra-Dorsal Hippocampal Microinjection of Lithium and Scopolamine Induce a Cross State-Dependent Learning in Mice." European Psychiatry 24, S1 (January 2009): 1. http://dx.doi.org/10.1016/s0924-9338(09)71091-0.
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Background:Lithium a mood stabilizer may exert adverse effects on memory. We have previously shown that lithium induces state-dependent learning. Cholinergic systems of the brain may play an important role in memory function and mood regulation. In the present study, effects of intra-dorsal hippocampal (intra-CA1) injections of lithium and scopolamine on memory and cross state-dependent learning between two drugs were investigated.Methods:For memory assessment, a one-trial step-down inhibitory avoidance task was used in adult male NMRI mice.Results:Intra-CA1 administration of lithium (0.5 and 1 μg/mouse) after training or injection of the drug (0.5μg/mouse) before testing impaired memory when retrieval was tested 24 h later. The memory impairment by post-training lithium was reversed by pre-test administration of the drug (0.5μg/mouse, intra-CA1) suggesting lithium state-dependent learning. On the other hand, intra-CA1 administration of scopolamine (0.5, 1 and 2 μg/mouse) after training or injection of the drug (2μg/mouse) before testing impaired memory when retrieval was tested 24 h later. The impairment of memory by post-training injection of scopolamine (2μg/mouse) was restored by the pre-test injection of the drug (1 and 2 μg/mouse). Furthermore, memory impairment induced by post-training injection of lithium (0.5 μg/mouse) and scopolamine (2 μg/mouse) were reversed by pre-test administration of scopolamine (0.5, 1 and 2 μg/mouse) and lithium (0.5 and 1 μg/mouse) respectively. The impairment by lithium was also reversed by physostigmine.Conclusion:The results suggest that microinjection of both lithium and scopolamine induce state-dependent memory and there may be a cross state-dependency between two drugs.
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Monteith, Scott, Tasha Glenn, Michael Gitlin, and Michael Bauer. "Potential Drug interactions with Drugs used for Bipolar Disorder: A Comparison of 6 Drug Interaction Database Programs." Pharmacopsychiatry 53, no. 05 (April 30, 2020): 220–27. http://dx.doi.org/10.1055/a-1156-4193.
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Abstract Background Patients with bipolar disorder frequently experience polypharmacy, putting them at risk for clinically significant drug-drug interactions (DDI). Online drug interaction database programs are used to alert physicians, but there are no internationally recognized standards to define DDI. This study compared the category of potential DDI returned by 6 commercial drug interaction database programs for drug interaction pairs involving drugs commonly prescribed for bipolar disorder. Methods The category of potential DDI provided by 6 drug interaction database programs (3 subscription, 3 open access) was obtained for 125 drug interaction pairs. The pairs involved 103 drugs (38 psychiatric, 65 nonpsychiatric); 88 pairs included a psychiatric and nonpsychiatric drug; 37 pairs included 2 psychiatric drugs. Every pair contained at least 1 mood stabilizer or antidepressant. The category provided by 6 drug interaction database programs was compared using percent agreement and Fleiss kappa statistic of interrater reliability. Results For the 125 drug pairs, the overall percent agreement among the 6 drug interaction database programs was 60%; the Fleiss kappa agreement was slight. For drug interaction pairs with any category rating of severe (contraindicated), the kappa agreement was moderate. For drug interaction pairs with any category rating of major, the kappa agreement was slight. Conclusion There is poor agreement among drug interaction database programs for the category of potential DDI involving psychiatric drugs. Drug interaction database programs provide valuable information, but the lack of consistency should be recognized as a limitation. When assistance is needed, physicians should check more than 1 drug interaction database program.
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Walid, B., I. Marrag, R. Ben Soussia, F. Ellouze, and M. Nasr. "Therapy initiation during a first acute episode psychosis in the psychiatric department of Mahdia." European Psychiatry 41, S1 (April 2017): S390. http://dx.doi.org/10.1016/j.eurpsy.2017.02.438.
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IntroductionThe quality of the therapeutic care during a first episode psychosis (FEP) determines the middle- and long-term prognosis.ObjectivesThe aim of our study is to describe the therapeutic attitudes in front of a FEP and discuss them according to current international recommendations.MethodsThis is a retrospective descriptive study. All patients with a FEP, hospitalized in the psychiatric department of the university hospital, Mahdia during the period from 15 May 2000 to 31 December 2013 have been included.ResultsWe recruited 111 patients. The average age was 27 years, a male predominance was noted. Initially, the majority of patients were treated in monotherapy (55.9%) and mostly with typical antipsychotic drugs (80.2%), by injection. Among those under association, 63.4% received corrective treatment and 26.8% a benzodiazepine. The prescription of a mood stabilizer and an antidepressant was noted in respectively 5.6 and 2.8% of cases. The majority of patients received typical antipsychotic drugs (53.1%) while 39.6% were under atypical antipsychotic. The follow-up period, after which a reduction of the antipsychotic dose was decided, ranged from 1 to 66 months with an average of 8.26.ConclusionThe progression to a chronic psychosis, still has a severe connotation. The Early and adequate therapeutic care in accordance with the international recommendations, determines the prognosis and constitute a decisive moment in the evolutionary trajectory of the disease.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Gómez Sánchez-Lafuente, C., R. Reina Gonzalez, A. Gonzalez Moreno, F. Moreno de Lara, E. Mateos Carrasco, and A. De Severac Cano. "Partial Nephrectomy After Oncocytoma Causing Repeated Lithium Poisoning with Normal Renal Function." European Psychiatry 33, S1 (March 2016): S470. http://dx.doi.org/10.1016/j.eurpsy.2016.01.1713.
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IntroductionLithium has been widely used as mood stabilizer in bipolar disease, despite its narrow therapeutic range and its side effects. Sodium levels and water consumption could affect lithium renal elimination.AimsDescribe a lithium intoxication without risk factors and normal kidney function.MethodsA 71-year-old female, diagnosed with bipolar disorder, current episode euthymic. On treatment with lithium 800 mg/day, 6 months ago she started with hematuria and urologist found a multifocal oncocytoma in left kidney. She was operated with double lumpectomy and partial nephrectomy without complications. Normal preoperative and postoperative renal function. Two months ago, she started with dysarthria, dystonia and coarse tremor, and T wave inversion on the electrocardiogram. In the blood test, lythemia was 1.67 mEQ/L. Creatinine was 0.65 mg/dL. She was admitted to Internal Medicine Unit. She was treated with rehydration by serum. All psychoactive drugs were removed. Twenty days later, lithemia was undetectable in the blood analysis.ResultsTwo weeks ago, the patient was transferred to the mental health unit due to worsening her mood. Lithium was reintroduced 3 days ago, at doses of 200 mg per day. Today, the patient starts again with symptoms of poisoning by lithium. Lithemia was 1.78.ConclusionsOn this occasion, partial nephrectomy due to oncocytoma is the most likely cause two consecutive lithium poisonings. Although creatinine and glomerular filtration are in normal range, patients after partial nephrectomy may have a reduced sodium reabsorption in proximal convoluted tubule, which may cause lithium compensatory resorption. This could cause rising in blood lithium levels.Disclosure of interestThe authors have not supplied their declaration of competing interest.
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Jain, Amit P. "Evaluation of learning memory activity of Unmad Gaja Kesari Rasa II in Animal Models." Journal of Ayurveda and Integrated Medical Sciences (JAIMS) 5, no. 01 (February 25, 2020): 68–72. http://dx.doi.org/10.21760/jaims.5.1.12.
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In recent era there is competition in each and every field, so there is lot of mental stress or mental disorder seen. In modern medicine there are various drugs such as antipsychotic, antiepileptic, mood stabilizer etc. which have certain adverse effect such as drowsiness, dizziness, memory loss etc. But Ayurveda certainly has an answer, there are total 112 formulations mentioned in classical text for physco neurological disorder i.e., Unmad and Apasmar, out of these there are total 25 herbo-mineral formulations and Unmad Gaja Kesari Rasa II (UGK II) is one of them. Present study was done to evaluate Learning memory effect of Unmad Gaja Kesari Rasa II a herbo-mineral compound. Cook’s and widely model was used to evaluate learning memory activity. Total 30 wistar rats were classified into 5 groups each containing 6 rats. Human dose was extrapolated with extrapolating factor 0.018 and drug dose was given to control I and II, standard, test x and 2x group, after that learning and Relearning trails were given and avoidance, escape and no response was observed. It has been established that UGK II (Rasa Kamdhenu i.e.; R.K Unmad Chikitsa/9-12) has effective role in learning and memory activity.
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Wen, Jinhua, Darrell Sawmiller, Brendan Wheeldon, and Jun Tan. "A Review for Lithium: Pharmacokinetics, Drug Design, and Toxicity." CNS & Neurological Disorders - Drug Targets 18, no. 10 (January 17, 2020): 769–78. http://dx.doi.org/10.2174/1871527318666191114095249.
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: Lithium as a mood stabilizer has been used as the standard pharmacological treatment for Bipolar Disorder (BD) for more than 60 years. Recent studies have also shown that it has the potential for the treatment of many other neurodegenerative disorders, including Alzheimer’s, Parkinson’s and Huntington’s disease, through its neurotrophic, neuroprotective, antioxidant and anti-inflammatory actions. Therefore, exploring its pharmacokinetic features and designing better lithium preparations are becoming important research topics. We reviewed many studies on the pharmacokinetics, drug design and toxicity of lithium based on recent relevant research from PubMed, Web of Science, Elsevier and Springer databases. Keywords used for searching references were lithium, pharmacology, pharmacokinetics, drug design and toxicity. Lithium is rapidly and completely absorbed from the gastrointestinal tract after oral administration. Its level is initially highest in serum and then is evidently redistributed to various tissue compartments. It is not metabolized and over 95% of lithium is excreted unchanged through the kidney, but different lithium preparations may have different pharmacokinetic features. Lithium has a narrow therapeutic window limited by various adverse effects, but some novel drugs of lithium may overcome these problems. Various formulations of lithium have the potential for treating neurodegenerative brain diseases but further study on their pharmacokinetics will be required in order to determine the optimal formulation, dosage and route of administration.
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Barbosa, P., O. Nombora, J. Monteiro, and L. Ribeiro. "Valproate induced encephalopathy: Paradigm of normal ammonia levels." European Psychiatry 64, S1 (April 2021): S618. http://dx.doi.org/10.1192/j.eurpsy.2021.1642.
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IntroductionValproic Acid (VPA) is one of the most commonly used mood stabilizer drugs. Although uncommon, serious adverse effects have been reported. One particularly relevant side effect is the induced encephalopathy, usually secondary to Hyperammonemia. However, some descriptions have shown an altered mental state with normal serum levels of ammonia.ObjectivesWe aim to present a case of VPA induced-encephalopathy without hyperammonemia and emphasize its suspicion when patients taking VPA present altered mental states.MethodsWe present a clinical case of VPA induced-encephalopathy without Hyperammonemia and a qualitative review of this topic using the Pubmed database.ResultsA 66-year-old woman, with an history of Major Depressive Disorder, previously medicated with Venlafaxine 75mg/day and Mirtazapine 30mg/day, was admitted in our acute psychiatric inpatient unit due to a first manic episode. During the stay, her antidepressants were interrupted, and she was started on VPA, then optimized to 750mg/day. After that, she presented an altered mental state with confusion and prostration. Analytical results were normal including normal ammonia levels and no imagiological abnormalities. Despite these results, we decided to stop VPA empirically. The patient clinical status resolved the day after.ConclusionsStudies have shown that only a few patients have developed encephalopathy with normal serum levels of ammonia. Although the pathogenesis behind this remains unknown, a few mechanisms have been proposed. Therefore, it is important to remind that even without abnormal analytical status, VPA is a possible cause of encephalopathy. We also emphasize the need for further studies on the mechanisms behind this phenomenon.DisclosureNo significant relationships.
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Danevski, G. "Antiepileptics as mood stabilizers." European Psychiatry 26, S2 (March 2011): 199. http://dx.doi.org/10.1016/s0924-9338(11)71909-5.
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The field of bipolar affective disorders research now immence methodological challenges, some of which have only recently become obvious.It has become more clear that bipolar affective disorder should be viewed longitudinally rather than in terms of individual episodes. As result of these methodological challenges, more have been far a few mood stabilizers approwed for use in bipolar disorder. Lithium was the gold standard of treatment for bipolar disorder, but a number of studies over the past several decades shown that many drugs with antiepileptic properties are effective in the treatment of some patients with bipolar affective disorder, especially for those whose disorder inadequately responds to lithium, and those who are intolerant of treatment with lithium. These antiepileptic agents include two generations of drugs: cabamazepin and valproate as first generation, and lamotrigine, gabapentine and topiramate as second generation of mood stabilising antiepileptic agents. In this article are rewiew the pharmacological properties and their efficacy in the treatment of bipolar disorder.A series of 32 patients with bipolar affective disorder was reported. All patients were supervized in the Emergency psychiatry service in Psychiatric Hospital Skopje, as the greatest and most important psychiatric institution in Macedonia. We also summarise use of these agents in combination with other psychotropics.
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Bartoli, Francesco, Massimo Clerici, Carmen Di Brita, Ilaria Riboldi, Cristina Crocamo, and Giuseppe Carrà. "Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis." Journal of Psychopharmacology 32, no. 4 (January 17, 2018): 416–22. http://dx.doi.org/10.1177/0269881117749851.
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Background: Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. Methods: We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy (‘active drugs’) for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Results: Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Conclusions: Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.
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Bhavsar, D. B., U. S. Desai, A. A. Phatak, and P. D. Chaudhari . "A REVIEW ON USE OF LITHIUM IN BIPOLAR DISORDER." INDIAN DRUGS 50, no. 09 (September 28, 2013): 5–17. http://dx.doi.org/10.53879/id.50.09.p0005.
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Bipolar disorder (previously called manic depressive illness) is a medical condition involving changes in the brain function leading to dramatic mood swings. It is characterized by the occurrence of at least one manic or mixed-manic episode, commonly treated with mood stabilizers. Sometimes, antipsychotics and antidepressants are used along with mood stabilizers. Lithium, a very effective mood stabilizer, was the first anti-manic depressant drug approved by the USFDA in the 1970’s. Though the specific biochemical mechanism of its action is unknown, preclinical studies have shown that lithium alters sodium transport in nerve cells and effects a shift toward intraneuronal metabolism of catecholamine. Although lithium is drug of choice in the treatment of bipolar disorder, the safe dose range is relatively narrow, and therapeutic drug monitoring is needed in order to prevent toxic reaction after its oral administration. So, there is scope for the alternative route of administration of lithium, which gives optimum drug levels and produces effects in low dose.
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Völlm, B., J. Stoffers-Winterling, J. Mattivi, E. Simonson, O. J. Storebø, S. Nielsen, M. L. Kielsholm, and K. Lieb. "Do Mood Stabilizers Help in Borderline Personality Disorder?" European Psychiatry 41, S1 (April 2017): S47. http://dx.doi.org/10.1016/j.eurpsy.2017.01.203.
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BackgroundDespite the relatively weak evidence base, individuals with borderline personality disorder are often treated with pharmacological interventions. Amongst the drugs, which have shown most promise, are mood stabilizers, which were one of the two drug classes with the most beneficial effects in a previous cochrane review though the robustness of findings was described as low (Stoffers et al., 2010). Here we present data on the latest evidence for mood stabilizers based on an updated cochrane review currently underway.MethodsA systematic review and meta-analysis of randomized controlled trials was conducted. All randomized comparisons of drug vs. placebo, drug vs. drug, or drug vs. a combination of drugs in adult BPD patients were eligible for inclusion. Outcomes comprised BPD core pathology as depicted by DSM criteria, associated pathology, i.e., depression and anxiety, general measures of overall psychopathology severity, tolerability, and adverse effects. Two researchers selected trials, assessed quality and extracted data independently.ResultsOnly a limited number of additional trials using mood stabilizers was identified since the publication of the last cochrane review, mainly utilizing Sodium Valproate. This added to the evidence base for mood stabilizers though the overall evidence remains very limited.ConclusionMood stabilizers show some initial evidence for their effectiveness in borderline personality disorder. However, these have to be replicated before wider conclusions can be drawn for clinical practice.Disclosure of interestThe authors declare that they have no competing interest.
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Muzina, D. J., O. Elhaj, P. Gajwani, K. Gao, and J. R. Calabrese. "Lamotrigine and antiepileptic drugs as mood stabilizers in bipolar disorder." Acta Psychiatrica Scandinavica 111, s426 (May 2005): 21–28. http://dx.doi.org/10.1111/j.1600-0447.2005.00523.x.
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Kara, Nirit Z., Orit Karpel, Lilach Toker, Galila Agam, Robert H. Belmaker, and Haim Einat. "Chronic oral carbamazepine treatment elicits mood-stabilising effects in mice." Acta Neuropsychiatrica 26, no. 1 (May 29, 2013): 29–34. http://dx.doi.org/10.1017/neu.2013.23.
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ObjectiveThe underlying biology of bipolar disorder and the mechanisms by which effective medications induce their therapeutic effects are not clear. Appropriate use of animal models are essential to further understand biological mechanisms of disease and treatment, and further understanding the therapeutic mechanism of mood stabilisers requires that clinically relevant administration will be effective in animal models. The clinical regimens for mood-stabilising drugs include chronic oral administration; however, much of the work with animal models includes acute administration via injection. An effective chronic and oral administration of the prototypic mood stabiliser lithium was already established and the present study was designed to do the same for the mood stabiliser carbamazepine.MethodsMice were treated for 3 weeks with carbamazepine in food. ICR mice were treated with 0.25%, 0.5% and 0.75%, and C57bl/6 mice with 0.5% and 0.75%, carbamazepine in food (w/w, namely, 2.5, 5.0 or 7.5 g/kg food). Mice were then tested for spontaneous activity, forced swim test (FST), tail suspension test (TST) and amphetamine-induced hyperactivity.ResultsOral carbamazepine administration resulted in dose-dependent blood levels reaching 3.65 μg/ml at the highest dose. In ICR mice, carbamazepine at the 0.5% dose had no effect on spontaneous activity, but significantly reduced immobility in the TST by 27% and amphetamine-induced hyperactivity by 28%. In C57bl/6 mice, carbamazepine at the 0.75% dose reduced immobility time in the FST by 26%.ConclusionsThese results demonstrate a behaviourally effective oral and chronic regimen for carbamazepine with mood stabilising-like activity in a standard model for mania-like behaviour and two standard models for depression-like behaviour.
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Tohen, Mauricio, K. N. Roy Chengappa, Trisha Suppes, Robert W. Baker, Carlos A. Zarate, Charles L. Bowden, Gary S. Sachs, et al. "Relapse prevention in bipolar I disorder: 18-month comparison of olanzapine plus mood stabiliser v. mood stabiliser alone." British Journal of Psychiatry 184, no. 4 (April 2004): 337–45. http://dx.doi.org/10.1192/bjp.184.4.337.
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BackgroundFew controlled studies have examined the use of atypical antipsychotic drugs for prevention of relapse in patients with bipolar I disorder.AimsTo evaluate whether olanzapine plus either lithium or valproate reduces the rate of relapse, compared with lithium or valproate alone.MethodPatients achieving syndromic remission after 6 weeks'treatment with olanzapine plus either lithium (0.6–1.2 mmol/l) or valproate (50–125 μg/ml) received lithium or valproate plus either olanzapine 5–20 mg/day (combination therapy) or placebo (monotherapy), and were followed in a double-masked trial for 18 months.ResultsThe treatment difference in time to relapse into either mania or depression was not significant for syndromic relapse (median time to relapse: combination therapy 94 days, monotherapy40.5 days; P=0.742), but was significant for symptomatic relapse (combination therapy 163 days, monotherapy42 days; P=0.023).ConclusionsPatients taking olanzapine added to lithium or valproate experienced sustained symptomatic remission, but not syndromic remission, for longer than those receiving lithium or valproate monotherapy.
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Yang, Shu-Yu, Ya-Tang Liao, Hsing-Cheng Liu, Wei J. Chen, Chiao-Chicy Chen, and Chian-Jue Kuo. "Antipsychotic Drugs, Mood Stabilizers, and Risk of Pneumonia in Bipolar Disorder." Journal of Clinical Psychiatry 74, no. 01 (January 15, 2013): e79-e86. http://dx.doi.org/10.4088/jcp.12m07938.
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Muzina, David J., and Joseph R. Calabrese. "Maintenance Therapies in Bipolar Disorder: Focus on Randomized Controlled Trials." Australian & New Zealand Journal of Psychiatry 39, no. 8 (August 2005): 652–61. http://dx.doi.org/10.1080/j.1440-1614.2005.01649.x.
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Objective: Lithium remains the cornerstone of maintenance therapy for bipolar disorder despite growing use of other agents, including divalproex, lamotrigine, carbamazepine and the atypical antipsychotics. Lithium has the largest body of data to support its continued use as a prophylactic agent; however, most of this data comes from early studies that did not use contemporary analytic methods. Alternatives to lithium are needed because of the relatively high rate of non-response to lithium monotherapy and the drug's frequent side-effects. This article reviews available data with an emphasis on double-blind, placebo controlled studies that examine the efficacy of lithium and other putative mood stabilizers: carbamazepine, divalproex, lamotrigine and olanzapine. Method: The authors reviewed key literature using Medline searches using key words: bipolar disorder, controlled trials, mood stabilizer, lithium, lomotrigine, divalproex, olanzapine, carbamazepine. Results: Lithium remains the gold standard for overall preventative efficacy in bipolar disorder, especially to decrease manic or hypomanic relapse. Of the mood stabilizers that have marked prophylactic antimanic properties, lithium appears to possess the greatest antidepressant effect. Divalproexmay also prevent recurrent bipolar mood episodes but the relative lack of controlled maintenance studies makes this less certain. There now exists an extensive and well-designed research database supporting the use of lamotrigine in the acute and prophylactic management of bipolar I disorder. Lamotrigine offers a spectrum of clinical effectiveness that complements lithium, in that it appears to stabilize mood ‘from below baseline’ by preventing episodes of depression and has been shown to be effective in rapid-cycling bipolar II disorder. Carbamazepine may be a useful alternative to lithium, divalproex and lamotrigine, particularly for patients with a history of mood-incongruent delusions and other comorbidities, but controlled data is more equivocal and it may lose some of its prophylactic effect over time. Emerging data continue to support the growing use of atypical antipsychotics, particularly olanzapine. Conclusions: Any monotherapy for use as a maintenance therapy of bipolar disorder appears to be inadequate for long-term use in the management of the majority of patients with bipolar disorder. Combination therapy has become the standard of care in the treatment of bipolar disorder and particularly in patients with treatment-refractory variants such as those with rapid-cycling. The emerging consensus is that patients on monotherapy, if followed for sufficiently long periods, will eventually require concomitant treatment to maintain a full remission. There exists a need for controlled trials that use random assignment to parallel arms including combination therapy followed by data analyses that include both relapse rate and survival techniques.