Mood Stabilizers (mood + stabilizer)

Distribution by Scientific Domains


Selected Abstracts


Mania associated with antidepressant treatment: comprehensive meta-analytic review

ACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2010
L. Tondo
Tondo L, Vzquez G, Baldessarini RJ. Mania associated with antidepressant treatment: comprehensive meta-analytic review. Objective:, To review available data pertaining to risk of mania,hypomania among bipolar (BPD) and major depressive disorder (MDD) patients with vs. without exposure to antidepressant drugs (ADs) and consider effects of mood stabilizers. Method:, Computerized searching yielded 73 reports (109 trials, 114 521 adult patients); 35 were suitable for random effects meta-analysis, and multivariate-regression modeling included all available trials to test for effects of trial design, AD type, and mood-stabilizer use. Results:, The overall risk of mania with/without ADs averaged 12.5%/7.5%. The AD-associated mania was more frequent in BPD than MDD patients, but increased more in MDD cases. Tricyclic antidepressants were riskier than serotonin-reuptake inhibitors (SRIs); data for other types of ADs were inconclusive. Mood stabilizers had minor effects probably confounded by their preferential use in mania-prone patients. Conclusion:, Use of ADs in adults with BPD or MDD was highly prevalent and moderately increased the risk of mania overall, with little protection by mood stabilizers. [source]


Are antidepressants warranted in the treatment of patients who present suicidal behavior?,

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2008
Michele Raja
Abstract Objective The aim of the study was to ascertain the clinical course of patients admitted to a psychiatric intensive care unit (PICU) just after a suicide attempt (SA) and to evaluate the effectiveness of 2nd generation antipsychotics and mood stabilizers in these patients. Methods We examined all the 129 patients discharged in a three-year period, who had been admitted after a SA and considered in the analysis the 82 cases non-transferred (in the first 72 h) to other PICUs for administrative or logistic reasons. Among them, 47 received a complete neuropsychiatric assessment. We distinguished between patients who had been treated with Antidepressants (AD) or not in the three months preceding hospitalization. Results We treated all patients with mood stabilizers and 2nd generation antipsychotics. Only one patient was treated with AD in the course of current hospitalization. Both cases treated and not treated with AD before admission improved significantly, especially in symptoms of anxiety and depression, as well as in suicidality. The suicidal risk abated without AD treatment. Conclusions In patients with impending suicide risk, AD should not be considered standard treatment. Mood stabilizers and 2nd generation antipsychotics can be effective. Copyright 2008 John Wiley & Sons, Ltd. [source]


Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials

BIPOLAR DISORDERS, Issue 4 2007
Lesley A Smith
Background:, Bipolar disorder (BD) is a leading cause of disability. Systematic reviews of randomized trials for the treatment of the maintenance phase of BD are lacking. Objectives:, To determine the efficacy and tolerability of mood stabilizers and antipsychotics in the maintenance treatment of BD. Methods:, We systematically reviewed randomized controlled trials of licensed medications for the treatment of any phase of BD. We included randomized controlled trials comparing a medication to placebo or another medication. Comprehensive searches of electronic databases were conducted to March 2005. Outcomes investigated were relapse due to mania, depression or any mood episode, and withdrawal due to any reason or due to an adverse event. Data were combined through meta-analysis. Results:, Fourteen studies (n = 2,526) met the inclusion criteria. Lithium, lamotrigine, olanzapine and valproate semisodium each demonstrated evidence to support long-term use. Compared with placebo, all medications were more effective at preventing relapse because of any mood episode. Hazard ratios (HR) were 0.68 [95% confidence interval (CI) = 0.53,0.86] for lithium, 0.68 (95% CI = 0.55,0.85) for lamotrigine, and 0.82 (95% CI = 0.57,1.20) for valproate semisodium; for olanzapine, the risk ratio (RR) was 0.58 (95% CI = 0.49,0.69). Lithium and olanzapine significantly reduced manic relapses (HR = 0.53; 95% CI = 0.35,0.79 and RR = 0.37; 95% CI = 0.24,0.57, respectively). Lamotrigine and valproate semisodium significantly reduced depressive relapses (HR = 0.65; 95% CI = 0.46,0.91 and RR = 0.40; 95% CI = 0.20,0.82, respectively). Lithium significantly reduced manic relapses compared with lamotrigine (HR = 0.56; 95% CI = 0.34,0.92) and olanzapine significantly reduced manic relapses compared with lithium (RR = 1.69; 95% CI = 1.12,2.55). Withdrawal due to an adverse event was approximately twice as likely with lithium compared with valproate semisodium (RR = 1.81; 95% CI = 1.08,3.03) and lamotrigine (RR = 2.20; 95% CI = 1.31,3.70). There were few data for carbamazepine or medications given as adjunct therapy. Conclusions:, Mood stabilizers have differing profiles of efficacy and tolerability, suggesting complementary roles in long-term maintenance treatment. [source]


Are antidepressants safe in the treatment of bipolar depression?

ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2008
A critical evaluation of their potential risk to induce switch into mania or cycle acceleration
Objective:, To address whether switch of depression into hypomania or mania or cycle acceleration in patients with bipolar disorder is caused by antidepressants or whether this phenomenon is attributable to the natural history of bipolar disorder itself. Method:, A critical review of the literature, pointing at sources of bias that have been previously overlooked. For examining the causation in question, the Bradford,Hill criteria were applied, i.e. specificity of the potential causative agent, strength of effect, consistency in findings, dose,response relation, temporal relation with exposure to agent preceding effect and biological plausibility. Results:, There is a scarcity of randomized studies addressing the question, and the available studies all suffer from various forms of bias. However, there is some evidence suggesting that antidepressants given in addition to a mood stabilizer are not associated with an increased rate of switch when compared with the rate associated with the mood stabilizer alone. Conclusion:, When combined with a mood stabilizer, antidepressants given for acute bipolar depression seemingly do not induce a switch into hypomania or mania. Whether antidepressants may accelerate episode frequency and/or may cause other forms of destabilization in patients with bipolar disorder remain to be properly studied. [source]


Plasma Concentrations of Risperidone and Olanzapine during Coadministration with Oxcarbazepine

EPILEPSIA, Issue 5 2005
Maria Rosaria Muscatello
Summary:,Purpose: Oxcarbazepine (OZC) is a second-generation antiepileptic drug (AED) that also may be used as a mood stabilizer. Unlike carbamazepine (CBZ), which is an inducer of the cytochrome P-450 isoforms and may accelerate the elimination of several therapeutic agents, OXC seems to have only a modest inducing action. The aim of this investigation was to evaluate the effect of a treatment with OXC on plasma concentrations of the new antipsychotics risperidone and olanzapine. Methods: OXC, at a dosage of 900,1,200 mg/day, was administered for 5 consecutive weeks to 25 outpatients, 10 men and 15 women, aged 25 to 64 years, with bipolar or schizoaffective disorder. Twelve patients were stabilized on risperidone therapy (2,6 mg/day) and 13 on olanzapine (5,20 mg/day). Steady-state plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) and olanzapine were measured by high-pressure liquid chromatography (HPLC) before addition of OXC and after 5 weeks from the start of adjunctive treatment. Results: OXC caused only minimal and no significant changes in the mean plasma levels of risperidone (from 5.6 3.6 ng/ml at baseline to 4.8 2.6 ng/ml at week 5), 9-OH-risperidone (from 23.6 7.5 to 24.7 7.4 ng/ml), and olanzapine (from 26.5 5.7 ng/ml at baseline to 27.8 5.1 ng/ml). OXC coadministration with either risperidone or olanzapine was well tolerated. Conclusions: Our findings indicate that OXC does not affect the elimination of risperidone and olanzapine, thus confirming its weak inducing effect on hepatic drug-metabolizing enzymes. [source]


Celecoxib as an adjunct in the treatment of depressive or mixed episodes of bipolar disorder: a double-blind, randomized, placebo-controlled study,,

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2008
Fabiano G. Nery
Abstract Objective To investigate whether the cox-2 inhibitor celecoxib has antidepressant effects in bipolar disorder (BD) patients during depressive or mixed phases. Methods We studied 28 DSM-IV BD patients who were experiencing a depressive or mixed episode and were on a stable dose of a mood stabilizer or atypical antipsychotic medication. Subjects were randomized to receive 6 weeks of double-blind placebo or celecoxib (400,mg/day) treatment. Current mood stabilizer or antipsychotic medication remained at the same doses during the trial. Results Intention-to-treat analysis showed that the patients receiving celecoxib had lower Hamilton Depression Rating Scale (HamD) scores after 1 week of treatment compared to the patients receiving placebo, but this difference was not statistically significant (p,=,0.09). The improvement in the first week of treatment was statistically significant when the analysis included only the subjects who completed the full 6-week trial (p,=,0.03). The two groups did not differ significantly on depressive or manic symptoms from the second week until the end of the trial. Celecoxib was well tolerated with the exception of two subjects who dropped out of the study due to rash. Conclusions Our findings suggest that adjunctive treatment with celecoxib may produce a rapid-onset antidepressant effect in BD patients experiencing depressive or mixed episodes. Copyright 2008 John Wiley & Sons, Ltd. [source]


Effect of risperidone on plasma catecholamine metabolites and brain-derived neurotrophic factor in patients with bipolar disorders

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2006
Reiji Yoshimura
Abstract A combination treatment with a mood stabilizer and an antipsychotic drug is often used in as many as 90% of subjects with acute mania. Recently, augmentation therapy with atypical antipsychotics has been investigated in both the acute and long-term treatment of bipolar disorder with or without psychosis. In the present study, the authors investigated the efficacy of risperidone treatment for both acute manic and depressive episodes in bipolar disorder. Eighteen patients (M/F: 8/10, age: 34,,15,yr) who met the DSM-IV criteria for bipolar I disorder (12 cases of manic episodes, 6 cases of depressive episodes) with risperidone treatment were evaluated regarding their clinical improvement using the Young Mania rating Scale (YMRS) and the Hamilton rating Scale for Depression (Ham-D). Plasma concentrations of HVA and MHPG were analyzed by HPLC-ECD and plasma brain-derived neurotrophic factor (BDNF) levels were detected by sandwich ELISA. The mean scores of the YMRS were 22, 18, 12, 8, and 5 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The mean scores of the Ham-D were 24, 25, 21, 21, and 19 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The plasma levels of HVA and 3-methoxy-4-hydroxyphenylglycol (MHPG) were observed to have decreased 4 weeks after risperidone administration in manic patients. The levels did not change in depressive patients. The plasma levels of BDNF were decreased in depressive patients compared with manic patients or healthy controls. However, the administration of risperidone did not alter plasma BDNF levels. Copyright 2006 John Wiley & Sons, Ltd. [source]


Novel targets for valproic acid: up-regulation of melatonin receptors and neurotrophic factors in C6 glioma cells

JOURNAL OF NEUROCHEMISTRY, Issue 5 2005
Lyda M. Rincn Castro
Abstract Valproic acid (VPA) is a potent anti-epileptic and effective mood stabilizer. It is known that VPA enhances central GABAergic activity and activates the mitogen-activated protein kinase,extracellular signal-regulated kinase (MAPK,ERK) pathway. It can also inhibit various isoforms of the enzyme, histone deacetylase (HDAC), which is associated with modulation of gene transcription. Recent in vivo studies indicate a neuroprotective role for VPA, which has been found to up-regulate the expression of brain-derived neurotrophic factor (BDNF) in the rat brain. Given the interaction between the pineal hormone, melatonin, and GABAergic systems in the central nervous system, the effects of VPA on the expression of the mammalian melatonin receptor subtypes, MT1 and MT2, were examined in rat C6 glioma cells. The effects of VPA on the expression of glial cell line-derived neurotrophic factor (GDNF) and BDNF were also examined. RT-PCR studies revealed a significant induction of melatonin MT1 receptor mRNA in C6 cells following treatment with 3 or 5 mm VPA for 24 h or 5 mm VPA for 48 h. Western analysis and immunocytochemical detection confirmed that the VPA-induced increase in MT1 mRNA results in up-regulation of MT1 protein expression. Blockade of the MAPK,ERK pathway by PD98059 enhanced the effect of VPA on MT1 expression, suggesting a negative role for this pathway in MT1 receptor regulation. In addition, significant increases in BDNF, GDNF and HDAC mRNA expression were observed after treatment with VPA for 24 or 48 h. Taken together, the present findings suggest that the neuroprotective properties of VPA involve modulation of neurotrophic factors and receptors for melatonin, which is also thought to play a role in neuroprotection. Moreover, the foregoing suggests that combinations of VPA and melatonin could provide novel therapeutic strategies in neurological and psychiatric disorders. [source]


Effects of 4-week Treatment with Lithium and Olanzapine on Levels of Brain-derived Neurotrophic Factor, B-Cell CLL/Lymphoma 2 and Phosphorylated Cyclic Adenosine Monophosphate Response Element-binding Protein in the Sub-regions of the Hippocampus

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2009
Michael D. Hammonds
It has been suggested that up-regulation of neurotrophic and neuroprotective factors including brain-derived neurotrophic factor (BDNF) and B-cell CLL/lymphoma 2 (Bcl-2) may underlie these neuroplastic actions of the drug. Olanzapine, an atypical anti-psychotic drug, has been shown to be an effective mood stabilizer. Olanzapine also has neurotrophic and neuroprotective actions, and these actions may underlie the efficacy of the drug for bipolar disorder and schizophrenia. However, the molecular mechanism by which the drug produces the neuroplastic actions is poorly understood. To understand a common molecular mechanism underlying the neuroplastic actions of lithium and olanzapine, we assessed the effect of 4-week lithium and olanzapine treatment on the levels of BDNF, Bcl-2 and cyclic adenosine monophosphate response element-binding protein (CREB), a transcription factor involved in expression of BDNF and Bcl-2, in the dentate gyrus and hippocampal area CA1. Our results show that 4-week treatment with both olanzapine and lithium increases the levels of Bcl-2 and CREB in the dentate gyrus and hippocampal area CA1. Four-week lithium treatment up-regulates BDNF in the dentate gyrus, and 4-week olanzapine treatment marginally did so. Neither drug altered BDNF levels in area CA1. These results suggest that the up-regulation of Bcl-2 and CREB may underlie the neuroplastic actions of olanzapine and lithium. [source]


Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo-controlled trials

BIPOLAR DISORDERS, Issue 2 2010
Christoph U Correll
Correll CU, Sheridan EM, DelBello MP. Antipsychotic and mood stabilizer efficacy and tolerability in pediatric and adult patients with bipolar I mania: a comparative analysis of acute, randomized, placebo-controlled trials. Bipolar Disord 2010: 12: 116,141. 2010 The Authors. Journal compilation 2010 John Wiley & Sons A/S. Objective:, To compare antipsychotic and mood stabilizer (MS) efficacy and tolerability in youth and adults with bipolar mania. Methods:, Medline/PubMed search for studies including: (i) youth (< 18 years) or adults (, 18 years); (ii) bipolar I disorder; (iii) double-blind, randomized, placebo-controlled trial (DB-RPCT); (iv) , 12 weeks of treatment; and (v) calculable effect sizes (ES) and/or numbers needed to treat/harm (NNT/NNH) 95% confidence intervals (CI). Non-overlapping 95% CIs determined significant group differences. Results:, We identified nine DB-RPCTs in youth (n = 1,609), 5 evaluating second-generation antipsychotics (SGAs) (n = 1,140) and 4 evaluating MSs (n = 469). We also identified 23 DB-RPCTs in adults (n = 6,501), 14 including SGAs (n = 3,297), 5 using haloperidol as an active comparator (n = 580), and 11 including MSs (n = 2,581). Young Mania Rating Scale scores improved significantly more with SGAs than MSs in youth (ES = 0.65, CI: 0.53,0.78 versus 0.24, CI: 0.06,0.41) and adults (ES = 0.48, CI: 0.41,0.55 versus 0.24, CI: 0.17,0.31). After excluding topiramate studies, SGAs had larger ES than MSs only in youth (ES = 0.65, CI: 0.53,0.78 versus 0.20, CI: 0.02,0.39), but not adults (ES = 0.48, CI: 0.41,0.55 versus 0.46, CI: 0.37,0.55). However, in adults SGAs had significantly larger ES regarding Clinical Global Impressions scores than MSs, even without topiramate (ES = 0.75, CI: 0.68,0.82 versus 0.24, CI: 0.07,0.41). Rates of response, remission, and discontinuation due to any reason compared to placebo were similar between medication and age groups, except for more favorable NNTs for remission with SGAs than MSs in adults after excluding topiramate. SGAs caused more weight gain than MSs in youth (ES = 0.53, CI: 0.41,0.66 versus 0.10, CI: ,0.12,0.33), but not in adults (ES = 0.13, CI: 0.05,0.22 versus 0.00, CI: ,0.08,0.08). However, results were heterogeneous and not significant in either age group after excluding topiramate. Nevertheless, SGA-related weight gain was significantly greater in youth than adults. In youth, SGA-related somnolence was greater than with MSs (NNH = 4.7, CI: 3.9,6.0 versus 9.5, CI: 6.3,23.5), and more likely than in adults (NNH = 7.1, CI: 6.1,8.8). Conversely, youth experienced less akathisia with SGAs than adults (NNH = 20.4, CI: 14.1,36.5 versus 10.2, CI: 8.1,13.7), likely due to lower doses/slower titration. Conclusions:, In treating mania, potentially greater short-term efficacy compared to placebo with SGAs versus MS needs to be balanced against increased adverse events, especially in youth. [source]


A magnetic resonance imaging study of mood stabilizer- and neuroleptic-nave first-episode mania

BIPOLAR DISORDERS, Issue 7 2007
Lakshmi N Yatham
Objectives:, Patients with bipolar disorder have changes in brain structures but it is unclear if these are present at disease onset and thus predispose subjects to develop the disorder, or whether they develop during the course of the disorder, either due to the effects of multiple episodes or as a consequence of treatment with psychotropic agents. Studies in first-episode (FE) manic patients have the potential to provide answers to these questions. Methods:, Voxel-based morphometry (VBM) was used to assess magnetic resonance imaging scans of 15 FE manic patients and 15 matched healthy controls. Results:, Using a priori defined statistical criteria, no significant differences in brain structures were noted between the two groups. However, there was approximately a 6% reduction in left anterior cingulate, left precuneus and right posterior cingulate volume in FE patients and these reductions were significant (p , 0.002) at uncorrected levels. Conclusions:, First-episode manic patients have reductions in left anterior, right posterior cingulate as well as left precuneus volumes, but these reductions are smaller and likely worsen with further mood episodes in bipolar patients. [source]


Mania associated with antidepressant treatment: comprehensive meta-analytic review

ACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2010
L. Tondo
Tondo L, Vzquez G, Baldessarini RJ. Mania associated with antidepressant treatment: comprehensive meta-analytic review. Objective:, To review available data pertaining to risk of mania,hypomania among bipolar (BPD) and major depressive disorder (MDD) patients with vs. without exposure to antidepressant drugs (ADs) and consider effects of mood stabilizers. Method:, Computerized searching yielded 73 reports (109 trials, 114 521 adult patients); 35 were suitable for random effects meta-analysis, and multivariate-regression modeling included all available trials to test for effects of trial design, AD type, and mood-stabilizer use. Results:, The overall risk of mania with/without ADs averaged 12.5%/7.5%. The AD-associated mania was more frequent in BPD than MDD patients, but increased more in MDD cases. Tricyclic antidepressants were riskier than serotonin-reuptake inhibitors (SRIs); data for other types of ADs were inconclusive. Mood stabilizers had minor effects probably confounded by their preferential use in mania-prone patients. Conclusion:, Use of ADs in adults with BPD or MDD was highly prevalent and moderately increased the risk of mania overall, with little protection by mood stabilizers. [source]


Treatment of schizoaffective disorder , a challenge for evidence-based psychiatry

ACTA PSYCHIATRICA SCANDINAVICA, Issue 1 2010
M. Jger
Objective:, Schizoaffective disorder is a common diagnosis in mental health services. The aim of the present article was to review treatment studies for schizoaffective disorder and draw conclusions for clinical decision making. Method:, We searched MEDLINE and Cochrane Library for relevant clinical trials and review articles up to the year 2008. Results:, Thirty-three studies using standardized diagnostic criteria, 14 of which were randomized controlled trials, could be identified. The comparability of studies is limited by the use of different diagnostic criteria. The studies reviewed do not permit consistent recommendations as to whether schizoaffective disorder should be treated primarily with antipsychotics, mood stabilizers or combinations of these drugs. The relevance of diverse subtypes of schizoaffective disorder for treatment recommendations is unclear. Conclusion:, The pertinent empirical database is small and heterogeneous. The lack of conclusive recommendations is related to issues of nosological status, plurality of diagnostic criteria and validity of the concept of schizoaffective disorder. [source]


Preliminary results of a fine-grain analysis of mood swings and treatment modalities of bipolar I and II patients using the daily prospective life-chart-methodology

ACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2009
C. Born
Objective:, The study aimed to increase the knowledge about the detailed course differences between different forms of bipolar disorder. Method:, Using the prospective life-chart-clinician version, we compared the fine-grain analysis of mood swings and treatment modalities of 18 bipolar II with 31 bipolar I patients. Results:, During an observational period of a mean of 26 months we observed an increase of euthymic days, and a decrease of (sub)depressive and (hypo)manic days. Days in a (sub)depressed state were more frequent than days of (hypo)mania as well as days of subdepression or hypomania in comparison to days of full-blown depression or mania. Bipolar II patients showed an increase in hypomanic days receiving more frequently antidepressants. Bipolar I patients, with a decrease of manic days, were significantly taking more often mood stabilizers. Conclusion:, Treatment in a specialized bipolar clinic improves the overall outcome, but bipolar II disorder seems to be still treated sub-optimally with a possible iatrogenic increase of hypomanic days. [source]


Bipolar disorder in women: reproductive events and treatment considerations

ACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2005
M. P. Freeman
Objective:, Bipolar disorders are prevalent in women. Women with bipolar disorder often present with different clinical features than men. Reproductive events and hormonal treatments may impact the course of bipolar disorder. Our main objectives are to i) assess the impact of reproductive events on the course of the disorder, and ii) to discuss the relationships between reproductive events and psychiatric treatments. Method:, A literature search was conducted of MEDLINE journals from 1965 to present. Manual literature searches were also conducted. We review the presentation, clinical course, and treatment considerations of bipolar disorder in women, with emphasis on treatment considerations in the context of reproductive events. Treatment-related issues such as teratogenicity, breastfeeding, polycystic ovarian syndrome, weight gain and obesity, and medication interactions with oral contraceptives are reviewed. Results:, Women with bipolar disorder may be more vulnerable to mood episodes in the context of reproductive events, particularly postpartum. In women of reproductive age, mood stabilizers must be selected with teratogenic risks in mind, with the highest reported risks in pregnancy with valproate, and the greatest concern during breastfeeding with lithium use. In the areas of the perimenopause and polycycstic ovarian syndrome, more data are needed to advise treatment decisions. Conclusion:, We urgently need further study in these areas to deliver care that is appropriate to women with bipolar disorder. [source]


Novel antipsychotics in bipolar and schizoaffective mania

ACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2004
G. J. R. Mensink
Objective:, Novel antipsychotics are increasingly used in the treatment of bipolar and schizoaffective mania. This paper presents an overview of the controlled studies in this field. Method:, Using cross-references, a computerized search was performed on MEDLINE and EMBASE psychiatry covering the period 1990,2002. Results:, Olanzapine and risperidone, added to mood stabilizers, and olanzapine as monotherapy enjoy the most evidential support in terms of efficacy and side-effect profile for their use in acute bipolar mania. The use of modern antipsychotics in bipolar prophylaxis and in both the short- and long-term treatment of schizomania has not been widely studied yet. Conclusion:, More controlled trials are still needed comparing modern antipsychotics as monotherapy and adjunctive to mood stabilizers with conventional antipsychotics, lithium, anticonvulsants and with each other in short-term and, especially, maintenance treatment of (schizo)mania. Partly based on controlled studies, olanzapine, risperidone and other modern antipsychotics could become preferable for these indications. [source]


Suicide, suicidality and suicide prevention in affective disorders

ACTA PSYCHIATRICA SCANDINAVICA, Issue 2003
H. J. Mller
Objective:, It is well known that functional psychiatric disorders are one of the main causes of suicidal behaviour. This paper discusses the epidemiology and risk factors of suicidal behaviour in affective disorders and goes on to describe the treatment and prevention of such suicidal behaviour. Method:, A narrative overview of relevant epidemiological and drug studies. Results:, About 60,70% of patients with acute depression experience suicidal ideas. There is a high incidence of suicide (10,15%) in depressive patients. Psychopharmacological treatment with antidepressants and/or mood stabilizers is the most successful approach to avoid the risk of suicidal behaviour. In addition, psychotherapeutic and psychosocial interventions are of importance. Conclusion:, Suicidal behaviour and suicide must be considered when treating patients with affective disorders. The complex causation of suicidality has to be borne in mind when considering methods of suicide prevention. In order to obtain the best results, psychosocial, psychotherapeutic and psychopharmacological approaches should be combined, depending on the risk factors of each individual patient. [source]


Genetic association between TNF-, ,308 G>A polymorphism and longitudinal weight change during clozapine treatment

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2010
Ying-Chieh Wang
Abstract Objective The aim of the study was to investigate the association between genetic variation in the tumor necrosis factor-alpha (TNF-,) gene and longitudinal weight change during long-term clozapine treatment. Methods Fifty-five patients with refractory schizophrenia treated with clozapine for 8 years were recruited. Gender, age, treatment response to clozapine in the first 14 months, baseline BMI, clozapine dose, concomitant use of mood stabilizers and other antipsychotics, and ,308 G,>,A polymorphism in the human TNF-, gene were analyzed using generalized estimating equations. Results In addition to having a lower baseline BMI (p,=,0.0013) and a longer treatment time (p,=,0.050), the ,308 GG carriers gained significantly more weight than the ,308 A allele carriers (p,=,0.0084) during 8 years of clozapine treatment, after controlling for other non-genetic factors. Conclusions The ,308 G,>,A genetic variant of the TNF-, gene is associated with longitudinal weight change during clozapine treatment. Follow-up duration is an important factor to consider when performing pharmacogenetic study of clozapine-induced weight gain. Copyright 2010 John Wiley & Sons, Ltd. [source]


Are antidepressants warranted in the treatment of patients who present suicidal behavior?,

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2008
Michele Raja
Abstract Objective The aim of the study was to ascertain the clinical course of patients admitted to a psychiatric intensive care unit (PICU) just after a suicide attempt (SA) and to evaluate the effectiveness of 2nd generation antipsychotics and mood stabilizers in these patients. Methods We examined all the 129 patients discharged in a three-year period, who had been admitted after a SA and considered in the analysis the 82 cases non-transferred (in the first 72 h) to other PICUs for administrative or logistic reasons. Among them, 47 received a complete neuropsychiatric assessment. We distinguished between patients who had been treated with Antidepressants (AD) or not in the three months preceding hospitalization. Results We treated all patients with mood stabilizers and 2nd generation antipsychotics. Only one patient was treated with AD in the course of current hospitalization. Both cases treated and not treated with AD before admission improved significantly, especially in symptoms of anxiety and depression, as well as in suicidality. The suicidal risk abated without AD treatment. Conclusions In patients with impending suicide risk, AD should not be considered standard treatment. Mood stabilizers and 2nd generation antipsychotics can be effective. Copyright 2008 John Wiley & Sons, Ltd. [source]


Risk factors for falling in a psychogeriatric unit

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 8 2001
A. John de Carle
Abstract Objective To identify risk factors associated with falls in a psychogeriatric inpatient population. Design Retrospective cohort study. Setting A psychogeriatric inpatient unit in a Brown University affiliated psychiatric hospital. Participants A total of 1834 men and women who represented all admissions to the psychogeriatric inpatient unit between January 1992 and December 1995. Results Over the study period a total of 175 falls were recorded, giving a fall rate of 9.5%. Using a logistic regression model, six variables were found to be independently associated with an increased risk of falling: female gender, electroconvulsive therapy (ECT), mood stabilizers, cardiac arrhythmias, Parkinson's syndrome and dementias. Falls and ECT were associated with longer hospital stay, when adjusted for confounders including ECT. Conclusions These findings support previous results and identify ECT as a possible risk factor for falling in a hospital setting. Copyright 2001 John Wiley & Sons, Ltd. [source]


The effectiveness of mood stabilizers and antiepileptic medication for the management of behaviour problems in adults with intellectual disability: a systematic review

JOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 2 2008
S. Deb
Abstract Background Psychotropic medications are used to manage behaviour problems in adults with intellectual disability (ID). One group of psychotropic medication are mood stabilizers such as lithium and some antiepileptic drugs. Method A comprehensive systematic review was performed to determine the evidence base for the effectiveness of mood stabilizers in the management of behaviour problems among adults with ID. Electronic searches of PsycInfo, Medline, Embase and Cinahl databases were conducted, as well as a thorough hand search for relevant literature. We reviewed primary trials relating to adults only that satisfied strict inclusion criteria. Results One randomized controlled trial (RCT) relating to lithium use and two non-RCTs, one on lithium and the other on carbamazepine, were revealed. In addition, one prospective non-controlled trial on sodium valproate and three retrospective case series studies were discovered, of which one considered the efficacy of lithium, one valproate and one topiramate. Conclusions The current evidence lends some support for the use of lithium and some antiepileptic mood stabilizer medication for the management of behaviour problems in adults with ID. However, because most studies reviewed here are riddled with obvious methodological constrains, the findings have to be interpreted with caution. [source]


Practitioner Review: Psychopharmacology in children and adolescents with mental retardation

THE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 9 2006
Benjamin L. Handen
Background:, The use of psychotropic medication to treat children and adults with mental retardation (MR) has a long and extensive history. There are no identified medications to address specific cognitive deficits among persons with MR. Instead, psychotropic medications are used to treat specific behavioral symptoms and/or psychiatric syndromes. The purpose of this review is to provide an overview of the recent literature regarding the use of psychotropic medications in this population, focusing primarily on children and adolescents. Methods:, The paper is divided into five general drug categories: psychostimulants, antipsychotics, antidepressants, mood stabilizers, and other drugs. Each section offers an overview of the research supporting the use of that class of medications in children and adolescents with MR as well as cautions regarding potential side effects. Finally, specific clinical recommendations are offered. Results:, The majority of studies in MR tend to be open trials, case reports, or controlled studies with small samples. The available data suggests that persons with MR respond to various psychotropic medications in ways similar to the typically developing population. However, rates of response tend to be poorer and the occurrence of side effects tends to be more frequent. Conclusions:, The use of psychotropic medications in children and adolescents with MR requires even greater monitoring and the use of lower doses and slower dosage increases than in the general population. [source]


White matter abnormalities in bipolar disorder: a voxel-based diffusion tensor imaging study

BIPOLAR DISORDERS, Issue 4 2008
Stefania Bruno
Objectives:, In bipolar disorder (BD), dysregulation of mood may result from white matter abnormalities that disrupt fronto-subcortical circuits. In this study, we explore such abnormalities using diffusion tensor imaging (DTI), an imaging technique capable of detecting subtle changes not visible with conventional magnetic resonance imaging (MRI), and voxel-based analysis. Methods:, Thirty-six patients with BD, all but two receiving antidepressants or mood stabilizers, and 28 healthy controls matched for age and gender were studied. Diffusion-weighted echoplanar images (DW-EPI) were obtained using a 1.5T scanner. Voxel-based analysis was performed using SPM 2. Differences between the groups in mean diffusivity and fractional anisotropy (FA) were explored. Results:, In the patient group, mean diffusivity was increased in the right posterior frontal and bilateral prefrontal white matter, while FA was increased in the inferior, middle temporal and middle occipital regions. The areas of increased mean diffusivity overlapped with those previously found to be abnormal using volumetric MRI and magnetization transfer imaging (MTI) in the same group of patients. Conclusions:, White matter abnormalities, predominantly in the fronto-temporal regions, can be detected in patients with BD using DTI. The neuropathology of these abnormalities is uncertain, but neuronal and axonal loss, myelin abnormalities and alterations in axonal packing density are likely to be relevant. The neuroprotective effects of some antidepressants and mood stabilizers make it unlikely that medication effects could explain the abnormalities described here, although minor effects cannot be excluded. [source]


Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials

BIPOLAR DISORDERS, Issue 4 2007
Lesley A Smith
Background:, Bipolar disorder (BD) is a leading cause of disability. Systematic reviews of randomized trials for the treatment of the maintenance phase of BD are lacking. Objectives:, To determine the efficacy and tolerability of mood stabilizers and antipsychotics in the maintenance treatment of BD. Methods:, We systematically reviewed randomized controlled trials of licensed medications for the treatment of any phase of BD. We included randomized controlled trials comparing a medication to placebo or another medication. Comprehensive searches of electronic databases were conducted to March 2005. Outcomes investigated were relapse due to mania, depression or any mood episode, and withdrawal due to any reason or due to an adverse event. Data were combined through meta-analysis. Results:, Fourteen studies (n = 2,526) met the inclusion criteria. Lithium, lamotrigine, olanzapine and valproate semisodium each demonstrated evidence to support long-term use. Compared with placebo, all medications were more effective at preventing relapse because of any mood episode. Hazard ratios (HR) were 0.68 [95% confidence interval (CI) = 0.53,0.86] for lithium, 0.68 (95% CI = 0.55,0.85) for lamotrigine, and 0.82 (95% CI = 0.57,1.20) for valproate semisodium; for olanzapine, the risk ratio (RR) was 0.58 (95% CI = 0.49,0.69). Lithium and olanzapine significantly reduced manic relapses (HR = 0.53; 95% CI = 0.35,0.79 and RR = 0.37; 95% CI = 0.24,0.57, respectively). Lamotrigine and valproate semisodium significantly reduced depressive relapses (HR = 0.65; 95% CI = 0.46,0.91 and RR = 0.40; 95% CI = 0.20,0.82, respectively). Lithium significantly reduced manic relapses compared with lamotrigine (HR = 0.56; 95% CI = 0.34,0.92) and olanzapine significantly reduced manic relapses compared with lithium (RR = 1.69; 95% CI = 1.12,2.55). Withdrawal due to an adverse event was approximately twice as likely with lithium compared with valproate semisodium (RR = 1.81; 95% CI = 1.08,3.03) and lamotrigine (RR = 2.20; 95% CI = 1.31,3.70). There were few data for carbamazepine or medications given as adjunct therapy. Conclusions:, Mood stabilizers have differing profiles of efficacy and tolerability, suggesting complementary roles in long-term maintenance treatment. [source]


Effects of mood stabilizers on the inhibition of adenylate cyclase via dopamine D2 -like receptors

BIPOLAR DISORDERS, Issue 3 2007
Liliana P Montezinho
Objective:, The mood stabilizing drugs lithium, carbamazepine and valproate modulate brain adenosine monophosphate (cAMP) levels, which are assumed to be elevated in bipolar disorder patients. The aim of this work was to investigate how these three mood stabilizing agents affect the regulation of cAMP levels by dopamine D2 -like receptors in vitro in rat cortical neurons in culture and in vivo in the rat prefrontal cortex. Methods:, The production of cAMP was measured in the cultured cortical neurons or in microdialysis samples collected from the prefrontal cortex of freely moving rats using the [8- 3H] and [125I] radioimmunoassay kits. Results:,In vitro and in vivo data showed that the treatment with the mood stabilizing drugs had no effect on basal cAMP levels in vitro, but had differential effects in vivo. Direct stimulation of adenylate cyclase (AC) with forskolin increased cAMP levels both in vitro and in vivo, and this effect was significantly inhibited by all three mood stabilizers. Activation of dopamine D2 -like receptors with quinpirole partially inhibited forskolin-induced increase in cAMP in untreated cultures, but no effect was observed in cortical neuron cultures treated with the mood stabilizing drugs. Similar results were obtained by chronic treatment with lithium and valproate in the prefrontal cortex in vivo. However, surprisingly, in carbamazepine-treated rats the activation of dopamine D2 -like receptors enhanced the responsiveness of AC to subsequent activation by forskolin, possibly as a consequence of chronic inhibition of the activity of the enzyme. Conclusions:, It was shown that each of these drugs affects basal- and forskolin-evoked cAMP levels in a distinct way, resulting in differential responses to dopamine D2 -like receptors activation. [source]


Special considerations in treating bipolar disorder in women

BIPOLAR DISORDERS, Issue 1 2004
Vivien K Burt
There are obvious gaps in research surrounding issues specific to women who suffer from bipolar disorder, including gender differences and their implications for management, the impact of the reproductive cycle, and evidence based treatment guidelines for pregnancy and the postpartum period. Gender differences have not been reported for the prevalence of bipolar disorder; however, women are more likely to experience rapid cycling, mixed mania, and antidepressant-induced manias. This may affect response to treatment, which has been found, in some cases, to differ in men and women. In addition, side effects in response to treatments may well differ in men and women, especially with regard to lithium and valproate prescription. The course of bipolar disorder in women may be influenced by the menstrual cycle, pregnancy, the postpartum period, and menopause, although many issues require further clarification. Treatment of bipolar disorder during pregnancy and the postmenopausal period requires careful consideration, as does treatment during the childbearing years, as some mood stabilizers influence the metabolism of oral contraceptives. This review article has attempted to evaluate existing literature regarding women with bipolar disorder in a comprehensive and critical way, and to consolidate into a single source the gender-specific aspects of the disorder that may have treatment implications for women. [source]


An overview of recent findings of the Stanley Foundation Bipolar Network (Part I)

BIPOLAR DISORDERS, Issue 5 2003
Robert M Post
Aim and Methods: Selected recent findings of the Stanley Foundation Bipolar Network are briefly reviewed and their clinical implications discussed. Results: Daily prospective ratings on the NIMH-LCM indicate a high degree of residual depressive morbidity (three times that of hypomania or mania) despite active psychopharmacological treatment with a variety of modalities including mood stabilizers, antidepressants, and benzodiazepines, as well as antipsychotics as necessary. The rates of switching into brief to full hypomania or mania during the use of antidepressants is described, and new data suggesting the potential utility of continuing antidepressants in the small group of patients showing an initial acute and persistent response is noted. Bipolar patients with a history of major environmental adversities in childhood have a more severe course of illness and an increased incidence of suicide attempts compared with those without. Preliminary open data suggest useful antidepressant effects of the atypical antipsychotic quetiapine, while a double-blind randomized controlled study failed to show efficacy of omega-3 fatty acids (6 g of eicosapentaenoic acid compared with placebo for 4 months) in the treatment of either acute depression or rapid cycling. The high prevalence of overweight and increased incidence of antithyroid antibodies in patients with bipolar illness is highlighted. Conclusions: Together, these findings suggest a very high degree of comorbidity and treatment resistance in outpatients with bipolar illness treated in academic settings and the need to develop not only new treatment approaches, but also much earlier illness recognition, diagnosis, and intervention in an attempt to reverse or prevent this illness burden. [source]


Emerging trends in the treatment of rapid cycling bipolar disorder: a selected review

BIPOLAR DISORDERS, Issue 4 2000
Robert M Post
Recent evidence suggests that lithium therapy (even as supplemented by antidepressants and neuroleptics) is inadequate for the majority of patients with bipolar illness, and particularly those with rapid cycling. Valproate and carbamazepine have emerged as adjuncts and alternatives, but they, too, often require additional approaches with lithium, thyroid hormones, and other putative mood stabilizers, including nimodipine (and related dihydropyridine calcium channel blockers), lamotrigine, gabapentin, topiramate, and the atypical neuroleptics. Evaluating how these agents and the unimodal antidepressants are optimally applied and sequenced in the treatment of bipolar illness with its multiple subtypes, patterns and comorbidities will require much future investigation and the development of new methodological clinical trial approaches. [source]


The high affinity inositol transport system , implications for the pathophysiology and treatment of bipolar disorder

BIPOLAR DISORDERS, Issue 2 2000
Dietrich van Calker
The ,inositol-depletion hypothesis' postulates that the therapeutic effects of lithium are due to inhibition of inositol monophosphatase, which leads to depletion of brain cells of myo-inositol and consequently to dampening of phosphoinositide (PI) signaling. This article examines the potential relevance of an alternative mechanism for inositol depletion: inhibition of myo-inositol uptake that proceeds via the sodium/myo-inositol cotransport (SMIT). We discuss recent in vitro experiments that show a pronounced downregulation of SMIT after chronic treatment with lithium, carbamazepine, and valproate at therapeutically relevant concentrations. It is concluded that downregulation of SMIT could represent a common mechanism of action of mood stabilizers. [source]


Lithium Restores Neurogenesis in the Subventricular Zone of the Ts65Dn Mouse, a Model for Down Syndrome

BRAIN PATHOLOGY, Issue 1 2010
Patrizia Bianchi
Abstract Down syndrome (DS), a high-incidence genetic pathology, involves brain hypoplasia and mental retardation. Emerging evidence suggests that reduced neurogenesis may be a major determinant of brain underdevelopment in DS. To establish whether it is possible to improve neurogenesis in DS, Ts65Dn mice,the most widely used model for DS,and euploid mice were treated with control or lithium chow for 1 month. During the last 3 days animals received one daily injection of 5-bromo-2-deoxyuridine (BrdU),a marker of proliferating cells,and were sacrificed 24 h after the last injection. Neurogenesis was examined in the subventricular zone (SVZ), a region that retains a neurogenic potential across life. We found that Ts65Dn mice had less (,40%) BrdU+ cells than euploid mice, indicating severe proliferation impairment. Treatment with lithium increased the number of Brdu+ cells in both euploid and Ts65Dn mice. In the latter the number of Brdu+ cells became similar to that of untreated euploid mice. Our study shows that lithium is able to restore cell proliferation in the SVZ of the Ts65Dn mouse and point at treatments with mood stabilizers as a potential tool to improve neurogenesis in patients with DS. [source]