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(This is the first part of a discussion on lithium. The second part will appear in a subsequent issue--Ed.) Lithium remains underused for the treatment of patients with a history [...]

If I asked you to meet me at a restaurant but never mentioned a time for us to meet, it would be a useless invitation. A place without a time [...]

'What is the risk of driving thyroid stimulating hormone (TSH) below the lower limit of the normal lab range when using levothyroxine as an adjunct treatment for depression?' Here are [...]

Let's start with the treatment of acute mania. Lithium is a good treatment for classic, nonmixed mania, but if there are depression symptoms mixed in (per DSM-5-TR, if 3 or [...]

Once you have diagnosed acute bipolar II depression accurately according to the DSM-5 criteria (as we reviewed in detail in a recent Psychiatric Times[TM] column (1)), you are confronted with [...]

Mood problems can occur before puberty, with the prevalence more than doubling during and after puberty. Some of the mood problems will follow a bipolar course. The challenge is recognizing [...]

Bipolar disorder is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression; without treatment, 15% of patients commit suicide (1). Hence, it has been ranked [...]

The treatment of bipolar disorder changed in ways big and small in 2019. At the regulatory level, cariprazine (Vraylar) joined a select group of atypical antipsychotics with FDA-approval in bipolar [...]

The study attempts to evaluate the association between suicide-related events and antiepileptic drugs being given to patients with epilepsy, depression of bipolar disease. The results indicate that such drugs were not associated with an increased risk of suicide events in the case of epileptic patients; however, was associated with an increased risk in the case of patients with depression and those that did not have any of the above diseases.

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1545-5300.2009.01292.x Byline: AYSEGUL OZERDEM (*), MERAL OGUZ ([dagger]), DAVID MIKLOWITZ ([double dagger]), CAN CIMILLI ([dagger]) Keywords: Bipolar Disorder; Expressed Emotion; Family-Focused Therapy; Psychoeducation; Psychosocial Intervention; Cultural Adaptation Abstract: Family-focused therapy (FFT) is a 9-month, 21-session structured psychoeducational treatment for bipolar disorder. Several US-based studies have documented its efficacy as adjunctive to medication for depression stabilization and relapse prevention. However, FFT has never been applied outside of the United States. The objective of this case series is to explore the applicability of FFT in a non-Western culture. Ten patients with bipolar disorder and their family members attended the 9-month FFT as adjunctive to pharmacotherapy in an outpatient specialty clinic in Izmir, Turkey. Patients improved in Global Assessment of Functioning Scores and Clinical Global Impression Scores from pre- to posttreatment. Case studies are given, which illustrate the differences between Western and non-Western families coping with bipolar disorder. FFT was easily applied to a Turkish sample with few changes in format or focus. Adaptations included substitution of oral for written therapeutic tasks or homework assignments. Randomized controlled trials are needed to test the clinical effectiveness of FFT and other psychosocial interventions in non-Western cultures. Abstract (French) RESUMEN Objetivos: La terapia centrada en la familia (FFT, por sus siglas en ingles) es un tratamiento psicoeducativo estructurado para el trastorno bipolar con una duracion de 9 meses y 21 sesiones. Varios estudios realizados en los EE.UU. han documentado su eficacia como adyuvante de la medicacion para la estabilizacion de la depresion y la prevencion de recaidas. Sin embargo, la FFT nunca se aplico fuera de los Estados Unidos. El objetivo de este estudio de serie de casos es analizar la aplicabilidad de la FFT en una cultura no occidental. Metodo: Diez pacientes con trastorno bipolar y sus familiares asistieron a la FFT de 9 meses como adyuvante de la farmacoterapia en una clinica de especialidades medicas ambulatorias de Izmir, Turquia. Resultados: Los pacientes obtuvieron mejores puntajes en la evaluacion global del funcionamiento (Global Assessment of Functioning Scores) y en la impresion clinica global (Clinical Global Impression Scores) despues del tratamiento. Se presentan estudios de casos practicos que ponen de manifiesto las diferencias entre las familias occidentales y no occidentales que viven con trastorno bipolar. Conclusion: La FFT se aplico facilmente a una muestra de Turquia con pocas modificaciones de formato o tema central. Entre las adaptaciones realizadas se encontraron la sustitucion de tareas terapeuticas orales por tareas escritas o tareas para hacer en casa. Para evaluar la eficacia clinica de la FFT y otras intervenciones psicosociales en las culturas no occidentales se necesitan ensayos clinicos aleatorios controlados. Palabras clave: trastorno bipolar, emocion expresada, terapia centrada en la familia, psicoeducacion, intervencion psicosocial, adaptacion cultural Author Affiliation: (*)Department of Psychiatry, Dokuz Eylul University, Narlidere, Izmir, Turkey ([dagger])Department of Psychiatry, Dokuz Eylul University Medical School, Izmir, Turkey ([double dagger])Department of Psychology, University of Colorado, Boulder Article note: Correspondence concerning this article should be addressed to Aysegul Ozerdem, Department of Psychiatry, Dokuz Eylul University, Narlidere, Izmir 35340, Turkey. E-mail: aysegul.ozerdem@deu.edu.tr

A double-blind study that involves 150 patients aged 10-17 on the effect of divalproex extended-release in the treatment of bipolar disorder shows that the drug was similar to placebo based on adverse events and that no treatment effect was observed in the drug. The drug is not suitable for treatment of youths with bipolar I disorder, mixed or manic state.

Abstract: The mechanism of action of lithium, an effective treatment for bipolar disease, is still unknown. In this study, the mesenteric vascular beds of control rats and rats that were [...]

This study evaluated the cost effectiveness of olanzapine compared with lithium as maintenance therapy for patients with bipolar I disorder (BP1) in the UK. A Markov model was developed to assess costs and outcomes from the perspective of the UK National Health Service over a 1-year period. Patients enter the model after stabilization of a manic episode and are then treated with olanzapine or lithium. Using the ?ndings of a recent randomized clinical trial, the model considers the monthly risk of manic or depressive episodes and of dropping out from allocated therapy. Health care resources associated with acute episodes were derived primarily from a recent UK chart review. Costs of maintenance therapy and monitoring were also considered. Key factors in?uencing cost effectiveness were identi?ed and included in a stochastic sensitivity analysis. The model estimated that, compared to lithium, olanzapine signi?cantly reduced the annual number of acute mood episodes per patient from 0.81 to 0.58 (difference -0.23; 95% CI: -0.34, -0.12). Per patient average annual care costs fell by £799 (95% CI: £1,824, £59) driven by reduced inpatient days-but the cost difference was not statistically signi?cant. Sensitivity analysis found the results to be robust to plausible variation in the model's parameters. The model estimated that using olanzapine instead of lithium as maintenance therapy for BP1 would signi?cantly reduce the rate of acute mood events resulting in reduced hospital costs. Based on available evidence, there is a high likelihood that olanzapine would reduce costs of care compared to lithium. Keywords bipolar disorder, cost-effectiveness, olanzapine, Introduction Bipolar affective disorder (BPD) is a recurring illness and one of the leading causes of psychiatric dizability, especially in the 15-44 year age group (Murray and Lopez, 1997; World [...]

Structure-based design methods are used for designing and synthesizing a new series of 3-benzofuranyl-4-indolylmaleimides as potent and relatively selective glycogen synthase kinase-3[beta] (GSK-3[beta]) inhibitors. The analysis has demonstrated the efficacy of a GSK-3[beta] inhibitor in a novel mouse model of mania.

Abstract Ethyl-eicosapentanoic acid (ethyl-EPA) may be beneficial in the treatment of bipolar disorder (BD) and may have a neurotrophic/neuroprotective role in patients with neuropsychiatric disorders. To investigate this we examined [...]

Treatment of depression in patients with bipolar disorder with mood stabilizers and antidepressant medication was found to be just as beneficial as treatment with only mood stabilizing medicines. Further the use of adjunctive, standard antidepressant medication, as compared to the use of mood stabilizers, was not associated with increased efficacy or with increased treatment-emergent affective switch.

Objective: Valproate (VPA) is effectively used in the treatment of bipolar disorder, although the mechanism of action is unclear. In patients with bipolar disorder, 5-hydroxytryptamine (5-HT)-induced intraplatelet calcium (Ca) mobilization [...]

Bipolar disorder is characterized by a chronic and fluctuating course of illness. Although nonadherence to pharmacotherapy is a frequent problem in the disorder, few studies have systematically explored psychosocial factors related to treatment discontinuation. Previous research with depressed patients receiving psychotherapy has suggested that expectancies for improvement are related to treatment outcomes and that the therapeutic alliance may partially mediate this relationship. The current study found evidence for a similar relationship between patients' initial expectancies for improvement, patient-and doctor-rated alliance, and long-term outcomes in bipolar patients treated with pharmacotherapy for up to 28 months following an acute episode. The results highlight the need for the assessment of expectancies and alliance in bipolar treatment and suggest possible targets for psychosocial interventions. Keywords: bipolar disorder, expectancies, adherence, pharmacotherapy, alliance

Objective: Lithium remains the most widely used treatment for bipolar disorder; however, the molecular mechanisms underlying its therapeutic actions have not been fully elucidated. We studied the in-vivo effect of [...]

Regulation and dysregulation of intracellular calcium (Ca2+) signaling via the inositol 1,4,5-trisphosphate receptor (Ins[P.sub.3]R) has been linked to many cellular processes and pathological conditions. In the present study, addition of [...]

Valproate/divalproex appears to be considerably overused in the US; the use of lithium, second-generation antipsychotics, and carbamazepine should be more prominent in treatment decisions for patients with bipolar mania. Valproate/divalproex [...]

Bipolar disorder is described in numerous cultures over the course of history and is one of the most distinct syndromes in psychiatry. Increasing evidence for the efficacy of new atypical antipsychotic drugs in the treatment of and prophylaxis against bipolar illness has provided a major treatment alternative that may, in the future, blur the diagnostic and therapeutic boundaries between bipolar illness and schizophrenia.

This column offers a question-and-answer forum to help nurses maintain their knowledge of advances in prescribing and psychopharmacology, and implications for safe psychiatric care. Send your questions related to prescribing [...]

People with bipolar disorder who take Depakote have three times the risk of attempting suicide as those who take lithium, according to a study of 20,638 patients. Depakote is the most commonly prescribed mood stabilizer in the US. Bipolar disorder is the medical term for manic-depression.

Practicing psychologists are likely to be confronted with the diagnostic and treatment challenges associated with bipolar disorder, particularly the various classes of medication currently used in pharmacotherapy for the disorder. Although lithium remains a valuable resource, limitations associated with its use have prompted clinicians and researchers to explore the application of several different classes of agents, including anticonvulsants, calcium channel blockers, atypical antipsychotics, benzodiazepines and antidepressants, to the acute and long-term management of bipolar disorder. A review of these agents, as well as a summary of various psychotherapeutic modalities that can serve as adjunctive interventions to pharmacotherapy, is provided for psychologists.

This review examines the use of the 'mood stabilizers' as targeted therapeutics for treatment of bipolar disorder. Study reveals that many therapeutics, such as valproate and olanzapine are used for treating acute mania in USA and carbamazepine in other countries. Other anticonvulsants and antipsychotics are also being tested clinically.

Lithium is widely used to treat certain psychiatric conditions although its exact mechanism is unknown. It is also effective against viral infections, skin diseases, cancer, and AIDS. Whatever the mechanism is, it must affect a fundamental process because lithium is such a simple element.

Background There is limited, poorly characterized information about adverse events occurring during maintenance treatment of bipolar disorder. We aimed to determine adverse event rates during treatment with lithium, valproate, olanzapine, and quetiapine. Methods and Findings We conducted a propensity score adjusted cohort study using nationally representative United Kingdom electronic health records from January 1, 1995, until December 31, 2013. We included patients who had a diagnosis of bipolar disorder and were prescribed lithium (n = 2148), valproate (n = 1670), olanzapine (n = 1477), or quetiapine (n = 1376) as maintenance mood stabilizer treatment. Adverse outcomes were chronic kidney disease, thyroid disease, hypercalcemia, weight gain, hypertension, type 2 diabetes mellitus, cardiovascular disease, and hepatotoxicity. The propensity score included important demographic, physical health, and mental health predictors of drug treatment allocation. The median duration of drug treatment was 1.48 y (interquartile range 0.64-3.43). Compared to patients prescribed lithium, those taking valproate, olanzapine, and quetiapine had reduced rates of chronic kidney disease stage 3 or more severe, following adjustment for propensity score, age, and calendar year, and accounting for clustering by primary care practice (valproate hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.45-0.69; p < 0.001, olanzapine HR 0.57; 95% CI 0.45-0.71; p < 0.001, quetiapine HR 0.62; 95% CI 0.47-0.80; p < 0.001). Hypothyroidism was reduced in those taking valproate (HR 0.60; 95% CI 0.40-0.89; p = 0.012) and olanzapine (HR 0.48; 95% CI 0.29-0.77; p = 0.003), compared to those taking lithium. Rates of new onset hyperthyroidism (valproate HR 0.24; 95% CI 0.09-0.61; p = 0.003, olanzapine HR 0.31; 95% CI 0.13-0.73; p = 0.007) and hypercalcemia (valproate HR 0.25; 95% CI 0.10-0.60; p = 0.002, olanzapine HR 0.32; 95% CI 0.14-0.76; p = 0.008, quetiapine HR 0.23; 95% CI 0.07-0.73; p = 0.013) were also reduced relative to lithium. However, rates of greater than 15% weight gain on valproate, olanzapine, and quetiapine were higher (valproate HR 1.62; 95% CI 1.31-2.01; p < 0.001, olanzapine HR 1.84; 95% CI 1.47-2.30; p < 0.001, quetiapine HR 1.67; 95% CI 1.24-2.20; p < 0.001) than in individuals prescribed lithium, as were rates of hypertension in the olanzapine treated group (HR 1.41, 95% CI 1.06-1.87; p = 0.017). We found no significant difference in rates of chronic kidney disease stage 4 or more severe, type 2 diabetes mellitus, cardiovascular disease, or hepatotoxicity. Despite estimates being robust following sensitivity analyses, limitations include the potential for residual confounding and ascertainment bias and an inability to examine dosage effects. Conclusions Lithium use is associated with more renal and endocrine adverse events but less weight gain than commonly used alternative mood stabilizers. Risks need to be offset with the effectiveness and anti-suicidal benefits of lithium and the potential metabolic side effects of alternative treatment options., Author(s): Joseph F. Hayes 1,*, Louise Marston 2, Kate Walters 2, John R. Geddes 3, Michael King 1, David P. J. Osborn 1 Introduction Bipolar disorder (BPD) is a complex, [...]

Lithium is the most commonly used drug for the treatment of manic depressive illness. The precise mechanisms underlying its clinical efficacy remain unknown. We found that long-term exposure to lithium chloride dramatically protects cultured rat cerebellar, cerebral cortical, and hippocampal neurons against glutamate-induced excitotoxicity, which involves apoptosis mediated by N-methyl-Daspartate (NMDA) receptors. This neuroprotection is long-lasting, occurs at therapeutically relevant concentrations of lithium with an E[C.sub.50] of approximately 1.3 mM, and requires treatment for 6-7 days for complete protection to occur. In contrast, a 24-h treatment with lithium is ineffective. The protection in cerebellar neurons is specific for glutamate-induced excitotoxicity and can be attributed to inhibition of NMDA receptor-mediated calcium influx measured by 45[Ca.sup.2+] uptake studies and fura-2 fluorescence microphotometry. The long-term effects of lithium are not caused by down-regulation of NMDA receptor subunit proteins and are unlikely related to its known ability to block inositol monophosphatase activity. Our results suggest that modulation of glutamate receptor hyperactivity represents at least part of the molecular mechanisms by which lithium alters brain function and exerts its clinical efficacy in the treatment for manic depressive illness. These actions of lithium also suggest that abnormality of glutamatergic neurotransmission as a pathogenic mechanism underlying bipolar illness warrants future investigation.

Valproic acid and lithium are effective anti-bipolar drugs. We recently showed that lithium stimulated the release of glutamate in monkey and mouse cerebral cortex slices, which, through activation of the N-methyl-D-aspartate receptor, increased accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)[P.sub.3]]. We show here that valproate behaves similarly to lithium in that at therapeutic concentrations it stimulates glutamate release and Ins(1,4,5)[P.sub.3] accumulation in mouse cerebral cortex slices. The fact that these two effects are a common denominator for two structurally unrelated anti-bipolar drugs suggests that these effects are important in their antibipolar action. The effects of maximal concentrations of lithium and valproate on glutamate release are additive, suggesting different mechanisms for release, which are discussed. The additivity of the two drugs on glutamate release is consistent with the clinical benefit of combining the two drugs in the treatment of subsets of bipolar patients, e.g., in rapid cycling manic-depression. Unlike lithium, valproate does not increase accumulation of inositol monophosphates, inositol bisphosphates, or inositoi 1,3,4-trisphosphate. This is additional evidence against the 'inositol depletion' hypothesis, which states that, by trapping inositol in the form of inositol monophosphates and certain inositol polyphosphates, lithium exerts its antimanic action by inhibiting resynthesis of phosphoinositides with resultant blunting of Ins(1,4,5)[P.sub.3] signaling.

Attenuation of the phosphatidylinositol (PI) signal transduction pathway as a consequence of inhibition of inositol monophosphatase (IMPase) has been proposed as the mechanism for the efficacy of [Li.sup.+] in the treatment of bipolar disorder. Nevertheless, [Li.sup.+] also affects other aspects of PI signal transduction, and it is therefore not clear whether modulation of PI responses by [Li.sup.+] can be attributed solely to inhibition of IMPase. However, inhibitors of IMPase mimic the effects of [Li.sup.+] on some aspects of PI cell signalling, thus highlighting the potential of IMPase as a target for the treatment of bipolar disorder. The recent description of the three-dimensional structure of IMPase in conjunction with site-directed mutagenesis and kinetic studies has led to the elucidation of the enzyme mechanism. These structural and mechanistic data should prove useful in the development of novel inhibitors of IMPase that might ultimately prove useful clinically.