Inflammation-Related Changes in Mood Disorders and the Immunomodulatory Role of Lithium

Epidemiologic studies suggest that the lifetime prevalence of bipolar spectrum disorders ranges from 2.8 to 6.5 percent of the population. To decrease morbidity and mortality associated with disease progression, pharmacologic intervention is indicated for the majority of these patients. While a number of effective treatment regimens exist, many conventional medications have significant side effect profiles that adversely impact patients’ short and long-term well-being. It is thus important to continue advancing and improving therapeutic options available to patients. This paper reviews the limitations of current treatments and examines the chemical compound Linalool, an alcohol found in many plant species, that may serve as an effective mood stabilizer. While relatively little is known about Linalool and bipolar disorder, the compound has been shown to have antiepileptic, anti-inflammatory, anxiolytic, anti-depressive, and neurotrophic effects, with mechanisms that are comparable to current bipolar disorder treatment options.

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Treatment of Bipolar Disorder During the Postpartum Period

CNS Spectrums ◽

10.1017/s1092852900025724 ◽

2006 ◽

Vol 11 (S5) ◽

pp. 13-14

Author(s):

Adele C. Viguera

Keyword(s):

Bipolar Disorder ◽

Postpartum Period ◽

Clinical Information ◽

Mood Stabilizer ◽

Mood Stabilizers ◽

Antipsychotic Treatment ◽

Close Monitoring ◽

Major Congenital Malformations ◽

Major Depressive Episodes ◽

Depressive Episodes

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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Effects of In Utero Exposure to AEDs on Morphology and Neurodevelopment

CNS Spectrums ◽

10.1017/s1092852900025700 ◽

2006 ◽

Vol 11 (S5) ◽

pp. 9-10

Author(s):

Martha J. Morrell

Keyword(s):

Bipolar Disorder ◽

Clinical Information ◽

Mood Stabilizer ◽

Mood Stabilizers ◽

Antipsychotic Treatment ◽

Close Monitoring ◽

History Of ◽

Major Congenital Malformations ◽

Major Depressive Episodes ◽

Depressive Episodes

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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Recurrence rates in stable bipolar disorder patients after drug discontinuation v. drug maintenance: a systematic review and meta-analysis

Psychological Medicine ◽

10.1017/s0033291720003505 ◽

2020 ◽

pp. 1-9

Author(s):

Taro Kishi ◽

Yuki Matsuda ◽

Kenji Sakuma ◽

Makoto Okuya ◽

Kazuo Mishima ◽

...

Keyword(s):

Bipolar Disorder ◽

Recurrence Rate ◽

Meta Analysis ◽

Mood Stabilizer ◽

Recurrence Risk ◽

Drug Discontinuation ◽

Recurrence Rates ◽

Double Blind ◽

Mood Episode ◽

Depressive Episodes

Abstract Background This random-effects model meta-analysis of double-blind, randomized placebo-controlled trials compared recurrence rates in bipolar disorder (BD) patients between antipsychotic/mood stabilizer discontinuation and maintenance groups. Methods We conducted systematic literature search of Embase, PubMed, and CENTRAL databases without language restriction from inception until 22 May 2020. Independent investigators assessed studies and extracted data. We calculated risk ratios (RRs) and numbers needed to benefit or harm (NNTB/NNTH). Primary outcome was the recurrence rate of any mood episode at 6 months. Secondary outcomes were recurrence rates of depressive episodes and manic/hypomanic/mixed episodes and all-cause discontinuation at 6 months. We also investigated these outcomes at 1, 3, 9, 12, 18, and 24 months. Results We identified 22 studies (n = 5462) receiving aripiprazole, asenapine, divalproex, long-acting injectable (LAI)-aripiprazole, LAI-risperidone, lamotrigine, lithium, olanzapine, paliperidone, or quetiapine. Mean study duration was 64.50 ± 69.35 weeks. The maintenance group demonstrated lower recurrence rates of any mood episode, depressive episodes, and manic/hypomanic/mixed episodes as well as reduced all-cause discontinuation at every observational point. The RRs (95% confidence interval, NNTB/NNTH) of recurrence rate at 6 months were 0.61 (0.54–0.70, 5) for any mood episode, 0.72 (0.60–0.87, 13) for depressive episodes, and 0.45 (0.36–0.57, 6) for manic/hypomanic/mixed episodes. The RR for all-cause discontinuation at 6 months was 0.71 (0.61–0.82, 6). Conclusions Maintaining drug treatment during clinically stable BD prevented recurrence for up to 24 months. Discontinuation of medications for ⩾1 month significantly increased recurrence risk. However, 47.3% of patients who discontinued drugs for 6 months did not experience recurrence.

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A broken heart

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.386 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S422-S423

Author(s):

M.J. Gordillo Montaño ◽

S. Ramos Perdigues ◽

S. Latorre ◽

M. de Amuedo Rincon ◽

P. Torres Llorens ◽

...

Keyword(s):

Heart Function ◽

Mood Stabilizer ◽

Psychotic Symptoms ◽

Emotional States ◽

Cardiac Syndrome ◽

History Of ◽

Competing Interest ◽

High Doses ◽

Depressive Episodes ◽

The Impact

IntroductionWithin the various cultures and throughout the centuries has observed the relationship between emotional states and heart function, colloquially calling him “heartbroken”. Also in the medical literature are references to cardiac alterations induced by stress.ObjectiveTakotsubo is a rare cardiac syndrome that occurs most frequently in postmenopausal women after an acute episode of severe physical or emotional stress. In the text that concerns us, we describe a case related to an exacerbation of psychiatric illness, an episode maniform.MethodWoman 71 years old with a history of bipolar I disorder diagnosed at age 20. Throughout her life, she suffered several depressive episodes as both manic episodes with psychotic symptoms. Carbamazepine treatment performed and venlafaxine. He previously performed treatment with lithium, which had to be suspended due to the impact on thyroid hormones and renal function, and is currently in pre-dialysis situation.She requires significant adjustment treatment, not only removal of antidepressants, but introduction of high doses of antipsychotic and mood stabilizer change of partial responders. In the transcurso income, abrupt change in the physical condition of the patient suffers loss of consciousness, respiratory distress, drop in blood pressure, confusion, making involving several specialists. EEG was performed with abnormal activity, cranial CT, where no changes were observed, and after finally being Echocardiography and coronary angiography performed when diagnosed Takotsubo.Results/conclusionsIn this case and with the available literature, we can conclude that the state of acute mania should be added to the list of psychosocial/stressors that can trigger this condition.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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The Duration of Undiagnosed Bipolar Disorder: Impact of Substance use Disorders co-morbidity

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1950 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S132-S132

Author(s):

S. Ben Mustapha ◽

W. Homri ◽

L. Jouini ◽

R. Labbane

Keyword(s):

Bipolar Disorder ◽

Substance Use ◽

Standard Deviation ◽

Substance Use Disorders ◽

Mood Stabilizer ◽

Type I ◽

Addictive Behaviour ◽

Bipolar Disease ◽

Co Morbidity ◽

The Impact

AimsStudy the impact of substance use disorders (SUD) co-morbidity on the duration of undiagnosed bipolar disorder (DUBP).MethodsCase-control study during a period of six months from July 2015 to December 2015. One hundred euthymic patients with BD (type I, II or unspecified) were recruited in the department of psychiatry C Razi Hospital, during their follow-up. Two groups were individualized by the presence or not of a SUD co-morbidity. In our study DUBP was defined as the period between the first symptoms and the beginning of treatment by a mood stabilizer.ResultsThe beginning of addictive behaviour preceded the installation of bipolar disease in 32% of cases. Installation of bipolar disorder preceded the installation of addictive behaviour in 12% of cases. The beginning of addictive behaviour was concomitant with the installation of bipolar disease in 6% of cases. The average DUBP in the full sample was 4.80 years with a standard deviation of 8.04 and extremes ranging from 0.08 to 37.5.The average DUBP in patients with SUD co-morbidity was 5.91 years with a standard deviation of 8.16 and extremes ranging from 0.08 to 35, and 3.68 years with a standard deviation of 7.84 and extremes ranging from 0.08 to 37.5 in patients without SUD co-morbidity.ConclusionsAccording to studies over two thirds of patients with bipolar disorder received misdiagnoses before diagnosis of BD, and among the factors involved can report the presence of SUD co-morbidity. Hence, we should detect BD among patients with SUD.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Novel therapeutic targets for bipolar disorder

10.1093/med/9780198748625.003.0030 ◽

2017 ◽

Author(s):

Ioline D. Henter ◽

Rodrigo Machado-Vieira

Keyword(s):

Bipolar Disorder ◽

Mood Disorders ◽

Bipolar Depression ◽

Nmda Antagonist ◽

Excitatory Neurotransmitter ◽

Residual Symptoms ◽

Antidepressant Effects ◽

The Central Nervous System ◽

Depressive Episodes

The long-term course of bipolar disorder (BD) comprises recurrent depressive episodes and persistent residual symptoms for which standard therapeutic options are scarce and often ineffective. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamate and its cognate receptors have consistently been implicated in the pathophysiology of mood disorders and in the development of novel therapeutics for these disorders. Since the rapid and robust antidepressant effects of the N-methyl-D-aspartate (NMDA) antagonist ketamine were first observed in 2000, other NMDA receptor antagonists have been studied in major depressive disorder (MDD) and BD. This chapter reviews the clinical evidence supporting the use of novel glutamate receptor modulators for treating BD—particularly bipolar depression. We also discuss other promising, non-glutamatergic targets for potential rapid antidepressant effects in mood disorders, including the cholinergic system, the melatonergic system, the glucocorticoid system, the arachidonic acid (AA) cascade, and oxidative stress and bioenergetics.

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Dysregulation of ion fluxes in bipolar affective disorder

Acta Neuropsychiatrica ◽

10.1017/s0924270800035468 ◽

2000 ◽

Vol 12 (3) ◽

pp. 81-85 ◽

Cited By ~ 1

Author(s):

H.C.R. Grunze ◽

J. Langosch ◽

C. Normann ◽

D. Rujescu ◽

B. Amann ◽

...

Keyword(s):

Bipolar Disorder ◽

Bipolar Affective Disorder ◽

Potassium Conductance ◽

Mood Stabilizer ◽

Mechanisms Of Action ◽

Ion Fluxes ◽

Mood Stabilizers ◽

Calcium Antagonism ◽

Sodium Calcium

ABSTRACTBipolar disorder has attracted numerous research from different neurobiological angles. This review will summarize selected findings focusing on the role of disturbed transmem-braneous ion fluxes. Several mood stabilizers exhibit a distinct profile including effects on sodium, calcium and potassium conductance. In summary, some decisive mechanisms of action as calcium antagonism and modulation of potassium currents may play a crucial role in the success of any given mood stabilizer in bipolar disorder.

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Effects of the Female Reproductive System on Bipolar Disorder

CNS Spectrums ◽

10.1017/s1092852900025682 ◽

2006 ◽

Vol 11 (S5) ◽

pp. 5-6

Author(s):

Terence A. Ketter

Keyword(s):

Bipolar Disorder ◽

Reproductive System ◽

Clinical Information ◽

Mood Stabilizer ◽

Mood Stabilizers ◽

Antipsychotic Treatment ◽

Close Monitoring ◽

Female Reproductive System ◽

Major Depressive Episodes ◽

Depressive Episodes

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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Bupropion Maintenance Treatment in Refractory Bipolar Depression: A Case Report

Clinical Practice and Epidemiology in Mental Health ◽

10.2174/1745017901713010043 ◽

2017 ◽

Vol 13 (1) ◽

pp. 43-48

Author(s):

Julia Dehning ◽

Heinz Grunze ◽

Armand Hausmann

Keyword(s):

Bipolar Disorder ◽

Case Report ◽

Maintenance Treatment ◽

Bipolar Depression ◽

Antidepressant Treatment ◽

Mood Stabilizer ◽

Obvious Benefit ◽

Insufficient Response ◽

Bipolar Patients

Background:The optimal duration of antidepressant treatment in bipolar depression appears to be controversial due to a lack of quality evidence, and guideline recommendations are either vague or contradictive. This is especially true for second line treatments such as bupropion that had not been subject to rigourous long term studies in Bipolar Disorder.Case presentation:We report the case of a 75 year old woman who presented with treatment refractory bipolar depression. Because of insufficient response to previous mood stabilizer treatment and refractory depressive symptoms, bupropion was added to venlafaxine and lamotrigine. From there onwards, the patient improved continuously without experiencing deterioration of depression or a switch into hypomania. Our patient being on antidepressants for allmost four years experienced an obvious benefit from longterm antidepressant administration.Conclusion:Noradrenergic/dopaminergic mechanisms of action may play a more prominent role in bipolar depression, and may still be underused as a therapeutic strategy in the acute phase as well as in long-term maintenance in at least a subgroup of bipolar patients. There is still a lack of evidence from RCTs, but this case report further supports antidepressant long-term continuation and the usefulness of a noradrenergic/dopaminergic antidepressant in the acute and maintenance treatment of bipolar disorder.

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