Prophylaxis Of Bipolar Disorder Research Articles

Mood Stabilizers of First and Second Generation.

The topic of this narrative review is mood stabilizers. First, the author's definition of mood-stabilizing drugs is provided. Second, mood-stabilizing drugs meeting this definition that have been employed until now are described. They can be classified into two generations based on the chronology of their introduction into the psychiatric armamentarium. First-generation mood stabilizers (FGMSs), such as lithium, valproates, and carbamazepine, were introduced in the 1960s and 1970s. Second-generation mood stabilizers (SGMSs) started in 1995, with a discovery of the mood-stabilizing properties of clozapine. The SGMSs include atypical antipsychotics, such as clozapine, olanzapine, quetiapine, aripiprazole, and risperidone, as well as a new anticonvulsant drug, lamotrigine. Recently, as a candidate for SGMSs, a novel antipsychotic, lurasidone, has been suggested. Several other atypical antipsychotics, anticonvulsants, and memantine showed some usefulness in the treatment and prophylaxis of bipolar disorder; however, they do not fully meet the author's criteria for mood stabilizers. The article presents clinical experiences with mood stabilizers of the first and second generations and with "insufficient" ones. Further, current suggestions for their use in preventing recurrences of bipolar mood disorder are provided.

A 52-week prophylactic randomised control trial of omega-3 polyunsaturated fatty acids in bipolar disorder.

Previous work suggests supplementation with omega-3 polyunsaturated fatty acids (PUFAs) may improve mood symptoms in bipolar disorder (BD) although findings remain unclear. In this study, we assess the efficacy of omega-3 PUFA administration for prophylaxis in BD using a clinical trial design over 52-weeks (ClinicalTrials.gov Identifier: NCT04210804). Individuals with BD (n=80) were randomised to receive placebo (n=40) or 1g eicosapentaenoic acid (EPA) plus 1g docosahexaenoic acid (DHA; n=40) adjunctively for 52-weeks. The primary outcome measure comprised the number of mood episode relapses including hospital admissions and medication changes experienced. Secondary outcome measures included time to first mood episode relapse and change in psychometric measures of depression and elation (Hamilton Depression Rating Scale and Young Mania Rating Scale). No significant differences in the number of mood episode relapses (U=490.00, p=0.14) or the number of individuals requiring admission to hospital (χ2 =0.67, p=0.41) or medication adjustment in the omega-3 PUFA compared to the placebo group were noted. Time to relapse was not significantly different between groups (Log Rank χ2 =0.41, p=0.52). Change in Young Manic Rating Scale (F(3.12, 152.86)=2.71, p=0.05) was significantly different between treatment groups over 12-months, with scores at 9-months and 12-months significantly lower than those at 3-months in the omega-3 group and not in the placebo group. Change in Hamilton Depression Rating Scale, Global Clinical Impression and Global Assessment of Functioning were not different between groups. Despite a minor reduction in hypomania scores in the omega-3 PUFA group compared to placebo, we find little evidence that the supplementation of omega-3-PUFAs exhibits prophylactic benefit in BD.

Effectiveness of Zinc Supplementation on Lithium-Induced Alterations in Thyroid Functions.

Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression, and prophylaxis of bipolar disorders. Thyroid abnormalities have been associated with treatment with lithium. Zinc is an essential trace element that plays a role in several biological activities. Therefore, the present study was aimed at investigating the potential role of zinc in the thyroid gland following lithium administration to explore the role of zinc under such conditions. To achieve this goal, male Wistar rats (150-195g) were divided into four groups: Group 1 animals were fed standard pellet feed and tap water ad lib; Group 2 rats were fed lithium in the form of lithium carbonate through diet at a concentration of 1.1g/kg body weight; Group 3 animals received zinc treatment in the form of zinc sulfate (ZnSO4·7H2O) at a dose level of 227mg/L mixed with drinking water of the animals; and Group 4 animals were given lithium and zinc in a similar manner as was given to the animals belonging to groups 2 and 4 respectively. The role of zinc on thyroid functions in lithium-treated rats was studied after 2, 4, and 8weeks of different treatments. Zinc has been observed to have the capability to nearly normalize the altered 2-h uptake of 131I, biological and effective half-lives of 131I, and circulating T4 levels that were altered after lithium treatment. The present study concludes that zinc may be an effective agent in normalizing the adverse effects caused by lithium on thyroid functions.

Effect of lithium carbonate on the function of the thyroid gland: mechanism of action and clinical implications.

Lithium carbonate, a drug known for more than 100 years, has been successfully used as a psychiatric medication. Currently, it is a commonly used drug to treat patients with unipolar and bipolar depression, and for the prophylaxis of bipolar disorders and acute mania. Lithium salts may cause the development of goiter, hypothyroidism, or rarely hyperthyroidism. The present review examined the current state of knowledge on the effect of lithium carbonate on the thyroid gland. The Pubmed database and Google Scholar were searched for articles related to the effects of lithium therapy on the thyroid gland function published up to February 2020. Studies that examined the mechanism of action of lithium at the molecular level, including pharmacokinetics, and focused on its effects on the thyroid gland were included. Lithium as a mood-stabilizing drug has a complex mechanism of action. Because of the active transport of Na+/I- ions, lithium, despite its concentration gradient, is accumulated in the thyroid gland at a concentration 3 - 4 times higher than that in the plasma. It can inhibit the formation of colloid in thyrocytes, change the structure of thyroglobulin, weaken the iodination of tyrosines, and disrupt their coupling. In addition, it reduces the clearance of free thyroxine in the serum, thereby indirectly reducing the activity of 5-deiodinase type 1 and 2 and reducing the deiodination of these hormones in the liver. Taken together, this review provides recommendations for monitoring the thyroid gland in patients who require long-term lithium therapy. Prior to the initiation of lithium therapy, thyroid ultrasound should be performed, and the levels of thyroid hormones (fT3 and fT4), TSH, and antithyroid peroxidase and antithyroglobulin antibodies should be measured. If the patient shows normal thyroid function, TSH level measurement and thyroid ultrasound should be performed at 6- to 12-month intervals for long term.

Self-reported medication adherence and its correlates in a lithium-maintained cohort with bipolar disorder at a tertiary care centre in India.

Lithium remains a cornerstone of prophylaxis in bipolar disorder (BD), but adherence continues to be a major clinical challenge and merits a closer attention. There is scant literature available in Indian as well as Asian context. This study was conducted at Department of Psychiatry, AIIMS, New Delhi with an aim to assess the self-reported medication adherence and its correlates among a naturalistic, lithium-maintained cohort (n = 76) with bipolar disorder. Subjects were included if they were on lithium therapy ≥1 year, met DSM-5 diagnosis of bipolar disorder and were in clinical remission (≥1 month). Besides sociodemographic and clinical performa, participants were assessed on medication adherence rating scale (MARS), lithium questionnaire for knowledge and lithium attitude questionnaire (LAQ). Mean age was 35.7 ± 10.6 years (males: 59.2%); median duration of illness and lithium therapy was 84 months and 24.5 months, respectively. Mean MARS score was 6.95 ± 2.81. Regression analysis (with MARS total as dependent variable) found LAQ score to be the single most significant predictor variable (β=-0.681, p < 0.0001), explaining over 75% of the total variance. In regression model with MARS factor-1 score as dependent variable, the 'LAQ score' (β=-0.601, p < 0.0001) and 'being accompanied by family during psychiatric visits (always/mostly) in the past year' (β = 0.193, p = 0.010) emerged as significant predictor variables. Adherence in lithium-maintained treatment-seeking cohort of patients with BD remains far from ideal as observed in this naturalistic setting. Lithium-related attitudes and being accompanied by family during psychiatric visits were found to be significant predictors for adherence.

T29 - GSK-3b 50 T/C Polymorphism And Lithium Maintenance Treatment In Bipolar Disorder

Background Bipolar Disorder is a chronic debilitating mental illness requiring long term medications. Bipolar disorder also has heritability of 80%, thus probably indicating an underlying genetic etiology. Glycogen Synthase Kinase (GSK) is a serine/threonine kinase. GSK3-b is an essential element of the Wnt/beta-catenin pathway. GSK-3B gene has been mapped to chromosome 3q13.3, a potential susceptibility locus for bipolar disorder. GSK-3B 50 T/C single nucleotide polymorphism (SNP) falls into the effective promoter region (nt − 171 to + 29) of the GSK-3B gene and the presence of T allele is noted to increase the transcriptional activity. GSK-3B is also directly inhibited by Lithium which is widely used in the prophylaxis of Bipolar Disorder. Earlier Studies have also found a positive correlation between Mutant C allele carriers of 50 T/C SNP and better response to Lithium. Methods 441 patients with Diagnosis of Bipolar Disorder according to DSM-IV were recruited from all patients attending Outpatient Services of National Institute of Mental Health and Neurological Sciences (NIMHANS). The diagnosis was confirmed using Clinical Interview and MINI 5.0.0. Genotype analysis for 189 patients selected was done for GSK-3B -50 T/C using PCR-RFLP method. Treatment response has been assessed using “Retrospective Criteria of Long Term Treatment Response in Research Subjects with Bipolar Disorder” for 95 patients for whom NIMH life charts were available Results Of all the 441 patients who were selected for the study, demographic analysis was done with the mean age at onset being 21.40 years (SD- 6.940). Lifetime psychotic symptoms were noted among 377 subjects. The genotype Frequencies for the GSK-3B 50 T/C polymorphism CC-25.9%, TC-47.6%, TT-26.5% for 189 patients, did not deviate significantly from Hardy-Weinberg equilibrium. Of the patients who were C allele carriers (N=78) there were 14 subjects who were poor responders (score less than or equal 3) and 64 subjects who were good responders (score >3).However this difference was not significant(p>0.05,Spearman’s correlation p>0.05). No statistically significant correlation was found between GSK-3B 50 T/C SNP and the clinical parameters that were studied including age at onset(n=186), and presence of psychotic symptoms(n=186) (all p>0.05) Discussion The study did not duplicate the favorable response to Lithium among patients who carry C allele in GSK-3B 50T/C SNP using a well validated scale to assess lithium response like “Retrospective Criteria of Long Term Treatment Response in Research Subjects with Bipolar Disorder” scale probably owing to difference in the allelic frequencies in the studied population. In a previous study by Benedetti et al,2008 among 60 Caucasian subjects had CC- 5%, TC-40%, TT-55% which significantly varies with the frequencies noted in the studied population. The limitation being that study was under-powered to assess the allelic association and a larger study is being completed currently. The study though did not find any positive association of GSK-3B 50 T/C with other clinical parameters that were studied. No other previous studies have looked into the association between the studied SNP and clinical parameters of Bipolar Disorder in this population. We are also in the process of doing gene expression analysis from cell lines (lymphoblastoid, induced pluripotent) derived from patients with this SNP to obtain further insights into the mechanism of Lithium in bipolar disorder.

Lithium in Bipolar Disorder: Optimizing Therapy Using Prolonged-Release Formulations.

Lithium has been a gold standard in the treatment of bipolar disorder (BD) for several decades. Despite a general reduction in the use of lithium over the past several years, it is effective in the management of both manic and depressive episodes in BD and continues to be recommended as a first-line mood stabilizer. This review provides an overview of the pharmacology of lithium and highlights its clinical profile in the management of BD, focusing on the potential advantages of prolonged-release (PR) versus immediate-release (IR) formulations of lithium. A literature search using PubMed was performed to identify articles describing IR and PR lithium in BD using specific search terms like ‘lithium’, ‘prolonged-release’, ‘sustained-release’, ‘extended-release’, ‘bipolar disorder’, ‘adherence’ and ‘compliance’. Relevant pharmacodynamic and pharmacokinetic data were also included. Several clinical trials suggested that lithium is effective in the treatment of acute mania and prophylaxis of BD and reduces the risk of suicide in patients with BD; it may also be used in combination with other drugs in the treatment of bipolar depression. Treatment with lithium must be monitored to avoid lithium-associated toxicity. The prolonged PR formulation of lithium has several advantages including consistent serum lithium concentrations, fewer adverse events and improved adherence to therapy. Although direct comparative studies between PR and IR formulations of lithium are primarily limited to pharmacokinetic studies, PR formulation of lithium provides potential advantages over IR formulation and can be effectively used in the management of BD with lesser adverse events.

Curcumin mitigates lithium-induced thyroid dysfunction by modulating antioxidant status, apoptosis and inflammatory cytokines

Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. It has also been shown to reduce suicidal risk and short term mortality. Few experimental studies have demonstrated the thyroid toxicity caused by lithium as well as the possible protective effect of curcumin. Twenty four male albino rats were divided into three groups; group I (control group), group II received lithium carbonate daily for 6weeks and group III received the same dose of lithium carbonate as group II concomitantly with curcumin for 6weeks. The specimens were prepared for histopathological, immunohistochemical and biochemical examination. Lithium-induced thyroid dysfunction evidenced by the histopathological and immunohistochemical changes represented by detached cells and vacuolated cytoplasm of some follicular cells and highly significant increase in positive immunostained of thyroglobulin and caspase-3 respectively. Moreover, a significant decrease in serum free triiodothyonine (FT3), free thyroxine (FT4) concomitant with significantly increased thyroid stimulating hormone (TSH) and pro-inflammatory cytokines, and thyroid lipid peroxidation (MDA) and nitric oxide (NO) levels. Curcumin counteracted lithium-induced oxidative stress and inflammation as assessed by restoration of the antioxidant defenses and diminishing of pro-inflammatory cytokines and improvements in the degenerative changes of the thyroid gland. In conclusion, the present study provides evidence that curcumin exerts thyroprotective effects against lithium carbonate mediated by its antioxidant, anti-inflammatory and anti-apoptotic effect as indicated by caspase-3. This report also confers that the use of this drug should be justified for long treatment under direct medical supervision.

Interaction between dorsal hippocampal NMDA receptors and lithium on spatial learning consolidation in rats.

Previous investigations have shown that NMDA receptors play an important role in learning and memory process. Lithium is a primary drug for management and prophylaxis of bipolar disorder. It can regulate signal transduction pathways in several regions of the brain and alter the function of several neurotransmitter systems involved in memory processes. The present study aimed to test the interaction of NMDA glutamatergic system of the CA1 region of dorsal hippocampus and lithium on spatial learning. Spatial memory was assessed in Morris water maze task by a single training session of eight trials followed by a probe trial and visible test 24h later. All drugs were injected into CA1 regions, 5min after training. Our data indicated that post- training administration of lithium (20μg/rat, intra-CA1) significantly impaired memory consolidation. Intra- CA1administration of NMDA, a glutamate receptor agonist (0.001 and 0.01μg/rat) showed spatial learning facilitation. Infusion of D-AP5, a glutamate receptor antagonist (0.05 and 0.1μg/rat) showed impairment of spatial memory. Our data also indicated that post- training administration of ineffective dose of NMDA (0.0001μg/rat) significantly decreased amnesia induced by lithium in spatial memory consolidation. In addition, post-training intra-CA1 injection of ineffective dose of D-AP5 (0.01μg/rat) could significantly increase lithium induced amnesia. It seems probable that signaling cascades of NMDA receptors that regulates synaptic plasticity are targets of anti-manic agents such as lithium. Our results suggest that NMDA receptors of the dorsal hippocampus may be involved in lithium-induced spatial learning impairment in the MWM task.

A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development.

l-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this class of drugs has been rekindled by the discovery that LTCC genes are part of the genetic aetiology of bipolar disorder and related phenotypes. We have therefore conducted a systematic review of LTCC antagonists in the treatment and prophylaxis of bipolar disorder. We identified 23 eligible studies, with six randomised, double-blind, controlled clinical trials, all of which investigated verapamil in acute mania, and finding no evidence that it is effective. Data for other LTCC antagonists (diltiazem, nimodipine, nifedipine, methyoxyverapamil and isradipine) and for other phases of the illness are limited to observational studies, and therefore no robust conclusions can be drawn. Given the increasingly strong evidence for calcium signalling dysfunction in bipolar disorder, the therapeutic candidacy of this class of drugs has become stronger, and hence we also discuss issues relevant to their future development and evaluation. In particular, we consider how genetic, molecular and pharmacological data can be used to improve the selectivity, efficacy and tolerability of LTCC antagonists. We suggest that a renewed focus on LTCCs as targets, and the development of ‘brain-selective' LTCC ligands, could be one fruitful approach to innovative pharmacotherapy for bipolar disorder and related phenotypes.

Age-at-onset and comorbidity may separate depressive disorder subtypes along a descending gradient of bipolar propensity

Depressive illnesses with subthreshold bipolar features are still misdiagnosed as unipolar. The goal of this study was to identify depressive disorder subtypes at risk for bipolarity. Four hundred ninety three major depressive patients were submitted to a cluster analysis on the basis of affective illness history and symptoms of the current episode. Seven clusters were identified which were regrouped into three age-at-onset subgroups; subgroups were further differentiated into subtypes according to predominant comorbidities. The latter were found to precede the occurrence of the related depressive disorder subtypes, decrease their age-at-onset, and increase their risk of belonging to the bipolar spectrum: the earlier the comorbidity, the higher the bipolar propensity was. This is likely to have implications for the diagnosis, natural history, as well as prophylaxis of bipolar disorders.

Memantine: New prospective in bipolar disorder treatment.

We review preclinical and clinical evidences strongly suggesting that memantine, an old drug currently approved for Alzheimer's dementia, is an effective treatment for acute mania and for the prevention of manic/hypomanic and depressive recurrences of manic-depressive illness. Lithium remains the first line for the treatment and prophylaxis of bipolar disorders, but currently available treatment alternatives for lithium resistant patients are of limited and/or questionable efficacy. Thus, research and development of more effective mood stabilizer drugs is a leading challenge for modern psychopharmacology. We have demonstrated that 21 d administration of imipramine causes a behavioural syndrome similar to a cycle of bipolar disorder, i.e., a mania followed by a depression, in rats. Indeed, such treatment causes a behavioural supersensitivity to dopamine D2 receptor agonists associated with an increase sexual activity and aggressivity (mania). The dopamine receptor sensitization is followed, after imipramine discontinuation, by an opposite phenomenon (dopamine receptor desensitization) and an increased immobility time (depression) in the forced swimming test of depression. Memantine blocks the development of the supersensitivity and the ensuing desensitization associated with the depressive like behavior. On the basis of these observations we have suggested the use of memantine in the treatment of mania and in the prophylaxis of bipolar disorders. To test this hypothesis we performed several naturalistic studies that showed an acute antimanic effect and a long-lasting and progressive mood-stabilizing action (at least 3 years), without clinically relevant side effects. To confirm the observations of our naturalistic trials we are now performing a randomized controlled clinical trial. Finally we described the studies reporting the efficacy of memantine in manic-like symptoms occurring in psychiatric disorders other than bipolar. A randomized controlled clinical trial is needed to confirm our naturalistic observations. We believe that this review presents enough pharmacological and clinical information to consider the administration of memantine in the treatment of bipolar disorders that no respond to standard mood stabilizers.

Lithium carbonate induced Histological changes in the Liver of Albino Rats

Lithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. The aim of present study was to observe histological changes in the liver of lithium carbonate treated Albino rats. Sixty albino rats were taken and divided into two groups, group A (control group) of 15 animals, were fed with normal diet and group B of 45 animals, were fed normal diet along with lithium carbonate at the dose of 30mgs/kgm body weight daily. The animals were sacrificed at four, eight and twelve week's interval, liver excised, 5µm thick sections prepared and stained with Haematoxylin and Eosin stain. On microscopic examination, as drug treatment continued the capsule remained intact, there was hepatic degeneration, followed by necrosis and cyst formation. There was Kupffer cell hyperplasia, central vein congestion and portal triads were infiltrated with lymphocytes and plasma cells. Liver parenchyma was infiltrated with lymphocyte, giving hepatitis like picture. It can be concluded that Lithium carbonate on long term treatment in rats causes hepatic degeneration, hepatitis and necrosis. So, it is advised that patients on lithium therapy should be periodically evaluated for hepatic dysfunction.

EPA-1124 - Use of lithium in the clinical practice: Results from a multicentric italian study

Introduction According to several international guidelines, lithium is still the first choice for treating mania and for prophylaxis of bipolar disorder. Nevertheless, in the last decades clinicians prefer to use anticonvulsivant drugs such as valproate and carbamazepine to lithium, which are easier to manage and with less side effects. Objectives 1)to describe prescribing patterns in Italian mental health centres in patients with bipolar I disorder;2)to assess clinical and social characteristics of patients receiving lithium. Aims to assess the current status of use of lithium in the Italian clinical practice. Methods The study, coordinated by the Department of Psychiatry of the University of Naples SUN, was carried out in 11 randomly recruited Italian mental health centres. In each site, 16 patients were recruited if they had a diagnosis of bipolar I disorder, were aged between 18-65 years, were on the caseload of the local mental health centre for at least six months, and had experienced at least one affective episode in the past three years. Data on pharmacological treatments were obtained from clinical records. Results The sample consisted of 140 patients, 118(84%) were receiving mood stabilizers, 84(60%) antipsychotics, 57(41%) antidepressants and 45(32%)benzodiazepines. Valproate was the mood stabilizer more frequently prescribed(58%); lithium was prescribed to 35% of patients. Those receiving lithium had a longer contact with the local mental health centre(105.9±77.6monthsvs. 79.0±68.5;p Conclusions Our data confirm the general principle that lithium is not frequently prescribed in clinical practice and it is given only to more severe patients.

Spectrum of lithium induced thyroid abnormalities: a current perspective

BackgroundLithium is an integral drug used in the management of acute mania, unipolar and bipolar depression and prophylaxis of bipolar disorders. Thyroid abnormalities associated with treatment with lithium have been widely reported in medical literature to date. These include goitre, hypothyroidism, hyperthyroidism and autoimmune thyroiditis. This current review explores the varied thyroid abnormalities frequently encountered among patients on lithium therapy and their management, since lithium is still a fundamental and widely drug used in psychiatry and Internal Medicine.MethodsPubMed database and Google scholar were used to search for relevant English language articles relating to lithium therapy and thyroid abnormalities up to December 2012. The search terms used were lithium treatment, thyroid abnormalities, thyroid dysfunction, goitre, hypothyroidism, hyperthyroidism, thyrotoxicosis, autoimmune thyroiditis, lithium toxicity, treatment of affective disorders and depression and side effects of antipsychotic drugs. Reference lists of the identified articles were further used to identify other studies.ResultsLithium affects normal thyroid functioning through multiple mechanisms. At the cellular level, it decreases thyroid hormone synthesis and release. It also decreases peripheral deiodination of tetraiodothyronine (T4) or thyroxine by decreasing the activity of type I 5’ de-iodinase enzyme. Hypothyroidism and goitre (clinically and/ultrasonographically detected) are the most prevalent thyroid abnormalities among patients on long term lithium therapy. Lithium induced hyperthyroidism is very infrequent. Lithium increases the propensity to thyroid autoimmunity in susceptible individuals due to its effect of augmenting the activity of B lymphocytes and reducing the ratio of circulating suppressor to cytotoxic T cells.ConclusionsThyroid function tests (serum thyroid stimulating hormone, free thyroid hormones-T4 and triiodothyronine [T3] concentrations and thyroid auto-antibodies) and assessment of thyroid size clinically and by thyroid ultrasonography ought to be performed among patients initiating lithium therapy at baseline and later annually. More frequent assessment of thyroid function status and size during the course of therapy is recommended among middle aged females (≥50 years), patients with a family history of thyroid disease and those positive for thyroid auto-antibodies (anti-thyroid peroxidase and TSH receptor antibodies).

Lithium et anticonvulsivants dans la dépression bipolaire

For decades, lithium and anticonvulsants have been widely used in the treatment of bipolar disorder. Their efficacy in the treatment of mania is recognized. These drugs have been initially evaluated in old and methodologically heterogeneous studies. Their efficacy in bipolar depression has not always been confirmed in more recent and methodologically more reliable studies. Thus, lithium's efficacy as monotherapy was challenged by the study of Young (2008) that showed a lack of efficacy compared with placebo in the treatment of bipolar depression. In two recent meta-analyses, valproate has shown a modest efficacy in the treatment of bipolar depression. As for lithium, valproate appeared to have a larger antimanic effect for acute phase and prophylaxis of bipolar disorder. In contrast, lamotrigine is more effective on the depressive pole of bipolar disorder with better evidence for the prevention of depressive recurrences. The guidelines include these recent studies and recommend lamotrigine as a first-line treatment of bipolar depression and for maintenance treatment. Because of more discordant data concerning lithium and valproate, these two drugs are placed either as first or as second line treatment of bipolar depression. The different safety/efficacy ratios of mood stabilizers underlie the complementarity and the importance of combination between them, or with some second-generation antipsychotics, in the treatment of patients with bipolar disorder.

Polarity index of pharmacological agents used for maintenance treatment of bipolar disorder

Over one half of bipolar patients have been reported to be more prone to either depressive or manic relapses. This study aimed to define profiles of drugs used for maintenance treatment of bipolar disorder (BD) by the means of Polarity Index.Polarity Index is a new metric indicating the relative antimanic versus antidepressive preventive efficacy of drugs. Polarity Index was retrieved by calculating Number Needed to Treat (NNT) for prevention of depression and NNT for prevention of mania ratio, as emerging from the results of randomized placebo-controlled trials. Included trials were randomized and double blind, with a minimal duration of 24weeks, assessing effectiveness of a mood stabilizer or antipsychotic drug alone or in combination with a mood stabilizing agent versus a placebo comparator in BD maintenance treatment.Polarity Index value above 1.0 indicates a relative greater antimanic prophylactic efficacy, number below 1.0 a relative greater antidepressive efficacy. The polarity index for the drugs used in maintenance therapy for bipolar disorder was 12.09 for risperidone, 4.38 for aripiprazole, 3.91 for ziprasidone, 2.98 for olanzapine, 1.39 for lithium, 1.14 for quetiapine, and 0.40 for lamotrigine. Polarity index of valproate and oxcarbazepine may not be reliable due to the failure of their maintenance trials.The polarity index provides a measure of how much antidepressant versus antimanic a drug is in bipolar disorder prophylaxis, and may guide the choice of maintenance therapy in bipolar patients.

Behandling av bipolar lidelse under svangerskap og etter fødsel

Pharmacological treatment and prophylaxis of bipolar disorders during pregnancy and in the postpartum period imply complicated clinical assessments. This article is based on a non-systematic search in PubMed and the authors' clinical experience. If a woman is already using a prophylactic drug at the time of pregnancy, she can in general continue to do so during pregnancy, with the exception of valproate. If the disorder starts during pregnancy; lithium, lamotrigine or second generation antipsychotic drugs are suitable alternatives. In general, drugs used during pregnancy can also be used in the postpartum period, although some require special precautions if the mother wishes to breast-feed. If treatment is initiated after delivery, the mother's wish to breast-feed should be taken into consideration when choosing a drug. Although existing studies have weaknesses, there is sufficient evidence to give qualified advice regarding choice of medication for bipolar disorder during pregnancy and in the postpartum period.

Lithium Neurotoxicity at Normal Serum Levels

To the Editor: Lithium is used with great success in the treatment and prophylaxis of bipolar disorders, unipolar recurrent depression, and endogenous depression that is resistant to conventional treatment. It is also known to be neurotoxic at higher serum levels. In rare cases patients develop symptoms of intoxication even with normal lithium levels. 1

Lithium in bipolar and other affective disorders: prescribing practice in the UK

The use of lithium for the treatment of mania, prophylaxis of bipolar disorder and augmentation of antidepressants in treatment-refractory unipolar depression is supported by British Association for Psychopharmacology and National Institute for Health and Clinical Excellence guidelines. We describe prescribing patterns with lithium in a large sample of patients with affective disorders. Data were collected during a baseline clinical audit of the quality of lithium monitoring, conducted by the Prescribing Observatory for Mental Health. Thirty-five National Health Service Trusts submitted data for 2776 patients with a diagnosis of affective illness (ICD10 F30-39), 1919 (69%) of whom had bipolar affective disorder. The last recorded lithium level was below the therapeutic range (<0.4 mmol/L) in one in 10 patients. Co-prescribing was common; 57% of bipolar patients were prescribed an antipsychotic and 77% of those with other affective disorders, an antidepressant. We conclude that serum lithium levels within the therapeutic range are maintained in the majority of patients. A high proportion of patients are co-prescribed other psychotropic drugs; such prescribing is consistent with evidence-based treatment guidelines and may reflect difficulty managing the symptoms of affective disorders with lithium monotherapy. A significant minority of patients prescribed lithium had a sub-therapeutic blood level and so may be at high risk of relapse.