Treatment Of Bipolar Disorder Research Articles

Treatment of Bipolar Disorders in Older Adults: A Review.

Old age bipolar disorder has been an orphan of psychiatric research for a long time despite the fact that bipolar disorder (BD)-I and II together may affect 0.5-1.0% of the elderly. It is also unclear whether aetiology, course of illness and treatment should differ in patients with a first manifestation in older age and patients suffering from a recurrence of a BD known for decades. This narrative review will summarize the current state of knowledge about the epidemiology, clinical features, and treatment of BD in the elderly. We conducted a Medline literature search from 1970 to 2021 using MeSH terms "Bipolar Disorder" × "Aged" or "Geriatric" or "Elderly". Search results were complemented by additional literature retrieved from examining cross references and by hand search in text books. Varying cut-off ages have been applied to differentiate old age from adult age BD. Within old age BD, there is a reasonable agreement of distinct entities, early and late-onset BD. They differ to some extent in clinical symptoms, course of illness, and some co-morbidities. Point prevalence of BD in older adults appears slightly lower than in working-age adults, with polarity of episodes shifting towards depression. Psychopharmacological treatment needs to take into account the special aspects of somatic gerontology and the age-related change of pharmacokinetic and pharmacodynamic characteristics. The evidence for commonly used treatments such as lithium, moodstabilizing antiepileptics, antipsychotics, and antidepressants remains sparse. Preliminary results support a role of ECT as well as psychotherapy and psychosocial interventions in old age BD. There is an obvious need of further research for all treatment modalities of BD in old age. The focus should be pharmacological and psychosocial approaches, as well as their combination, and the role of physical treatment modalities such as ECT.Appeared originally in Ann Gen Psychiatry 2021; 20:1.

Molecular Mechanisms of Valproic Acid Action on Signalling Systems and Brain Functions

Valproic acid (valproate, VA) has been widely used as an antiepileptic agent for several decades, as well as in the treatment of bipolar affective disorder. For many years, the ability of VA to stop epileptic seizures of a different nature has been associated with increased GABAergic neurotransmission, inhibition of glutamatergic neurotransmission and a general decrease in CNS hyperactivity by acting on ion channels, however precise mechanisms of VA anticonvulsant effects are still not clear. Over time, the effects of VA on other neurotransmitter systems, enzymes and intracellular signalling pathways have been revealed, however they do not explain the effectiveness of the drug as an anticonvulsant and mood stabilizer, but only expand its pharmacological profile. Over the past 10 years, the focus of interest in valproate research has changed due to its ability to alter gene expression both by inhibiting histone deacetylases and by changing levels of DNA methylation. These new studies reveal alternative mechanisms of valproate action rather than trying to test and confirm hypotheses previously put forward.

Enhancing bipolar disorder treatment among employed college students through the integration of civic education and lamotrigine: a context of educational psychology

BackgroundThe current psychological problem of bipolar disorder among college students due to employment pressure is characterized by a long course of illness, high suicide, and disability rates. Traditional drug therapy not only accelerates the circulation frequency of manic and depressive episodes but also leads to drug tolerance. Therefore, the study aims to combine ideological and political education with lamotrigine in the context of educational psychology to achieve the combined treatment of bipolar disorder among employed college students.Subjects and MethodsThis study focused on 50 college students with bipolar disorder who were employed. The participants were divided into two groups, Group A and Group B, based on illness duration. Group A received a single lamotrigine treatment, while Group B received a combination of ideological and political education and lamotrigine treatment, with a total treatment time of six months. After the experimental results were processed using SPSS17.0 statistical software, and the Hamilton Depression Scale scores of the two groups of patients before and after treatment were compared.ResultsAfter three months of treatment, the score was 18.77 ± 2.37 points. After six months of treatment, the score decreased to 7.67 ± 2.57 points, significantly lower than the control group’s 14.34 ± 2.17 points at this time.ConclusionsThe integration of ideological and political education with lamotrigine treatment yields a substantial therapeutic impact on bipolar disorder among employed college students. This comprehensive approach underscores the importance of considering educational psychology when devising treatment strategies for psychological disorders.AcknowledgementThe Yancheng Social Science Fund Project 2023 (No. 23skA163).

Causal effects of gut microbiota on the risk of bipolar disorder: a Mendelian randomization study

BackgroundRecent studies have suggested a possible association between gut microbiota and bipolar disorder (BD). However, observational studies are limited and there are variations between the gut microbiota taxa found in different studies. Therefore, we aimed to explore whether there is a causal relationship between gut microbiota and bipolar disorder at the genetic level and to reveal trends in the effect of influential gut microbiota on the development of bipolar disorder.MethodsWe conducted a Mendelian randomisation (MR) study of summary statistics from a genome-wide association study (GWAS) of gut microbiota and bipolar disorder. Inverse variance weighting (IVW) was used as the primary method of statistical analysis, while results from the MR-Egger method, weighted median, weighted mode, and MR multiplicity residuals and outliers (MR-PRESSO) tests were used for additional validation.Cochrane’s Q test, MR-Egger intercept test, and MR-PRESSO global test were used to test MR results for stability and reliability.ResultWe identified 13 gut microbial taxa causally associated with bipolar disorder. Betaproteobacteria, Acidaminococcaceae, Eubacterium xylanophilum group, Butyricimonas, Peptococcus, Prevotella 7, Roseburia, Terrisporobacter, Burkholderiales and Desulfovibrionales increased the risk of BD, whereas Candidatus Soleaferrea, Ruminiclostridium 5 and Victivallis decreased the risk of BD. The results of the MR analysis were shown to be reliable in the sensitivity analysis.ConclusionWith the MR study, we analysed the causal relationship between 196 gut microbial taxa and bipolar disorder and also identified gut microbiota associated with the risk of developing bipolar disorder. Our findings provide new biomarkers and potential therapeutic targets for the prevention and treatment of BD.

Causes of Bipolar Disorder in Adolescents

Mood fluctuation is common in daily life, however, severe mood fluctuation may be a symptom of affective illness. Bipolar disorders as a severe affective illness have a high prevalence, especially among adolescents. Although one of the most frequently discussed psychiatric illnesses is bipolar disorder, the causes are still not precisely known. Through reviewing previous research, this paper analyzes the causes of bipolar disorder, including personal and social factors, as well as the intervention and treatment of bipolar disorder. Both personal and social factor serve as important variables in affecting bipolar disorder. Offspring of parents with bipolar disease undoubtedly have considerable genetic impact; nonetheless, an adolescent's individuality leads their mood to swing correspondingly, ultimately progressing to bipolar disorder. Social factors such as family environment have a huge impact on adolescents mental state; interpersonal relationships strongly affect adolescents mood status, and furthermore, social environment also hugely affects how adolescents interact with their peers, as a result causes bipolar disorder. The intervention and treatment of bipolar disorder should be further developed in future research.

The effect of smartphone-based monitoring and treatment including clinical feedback versus smartphone-based monitoring without clinical feedback in bipolar disorder: the SmartBipolar trial—a study protocol for a randomized controlled parallel-group trial

IntroductionA substantial proportion of patients with bipolar disorder experience daily subsyndromal mood swings, and the term “mood instability” reflecting the variability in mood seems associated with poor prognostic factors, including impaired functioning, and increased risk of hospitalization and relapse.During the last decade, we have developed and tested a smartphone-based system for monitoring bipolar disorder. The present SmartBipolar randomized controlled trial (RCT) aims to investigate whether (1) daily smartphone-based outpatient monitoring and treatment including clinical feedback versus (2) daily smartphone-based monitoring without clinical feedback or (3) daily smartphone-based mood monitoring only improves mood instability and other clinically relevant patient-related outcomes in patients with bipolar disorder.Methods and analysisThe SmartBipolar trial is a pragmatic randomized controlled parallel-group trial. Patients with bipolar disorder are invited to participate as part of their specialized outpatient treatment for patients with bipolar disorder in Mental Health Services in the Capital Region of Denmark. The included patients will be randomized to (1) daily smartphone-based monitoring and treatment including a clinical feedback loop (intervention group) or (2) daily smartphone-based monitoring without a clinical feedback loop (control group) or (3) daily smartphone-based mood monitoring only (control group). All patients receive specialized outpatient treatment for bipolar disorder in the Mental Health Services in the Capital Region of Denmark. The trial started in March 2021 and has currently included 150 patients. The outcomes are (1) mood instability (primary), (2) quality of life, self-rated depressive symptoms, self-rated manic symptoms, perceived stress, satisfaction with care, cumulated number and duration of psychiatric hospitalizations, and medication (secondary), and (3) smartphone-based measures per month of stress, anxiety, irritability, activity, and sleep as well as the percentage of days with presence of mixed mood, days with adherence to medication and adherence to smartphone-based self-monitoring. A total of 201 patients with bipolar disorder will be included in the SmartBipolar trial.Ethics and disseminationThe SmartBipolar trial is funded by the Capital Region of Denmark and the Independent Research Fund Denmark. Ethical approval has been obtained from the Regional Ethical Committee in The Capital Region of Denmark (H-19067248) as well as data permission (journal number: P-2019–809). The results will be published in peer-reviewed academic journals, presented at scientific meetings, and disseminated to patients’ organizations and media outlets.Trial registrationTrial registration number: NCT04230421. Date March 1, 2021. Version 1.

Zingerone neuroprotective effects in a rat model of manic-like behavior induced by ketamine

Bipolar disorder (BD), before known as manic depression, is a chronic illness and a mood disorder characterized by manic and depressive periods. Drugs used to treat bipolar disorder can cause side effects if used chronically. Therefore, new therapeutic approaches are needed for treatment of BD. Given that inflammatory parameters and oxidative markers increase in BD and on the other hand there are a lot of evidences that zingerone (ZGR) has antioxidant and anti-inflammatory effects, the aim of this study was to investigate the neuroprotective effects of ZGR as one of the active phytochemicals existing in ginger in a model of manic-like behavior (MLB) induced by ketamine (KET) in rats. Thirty-six rats were randomly divided into six groups, including three groups of healthy rats: control, lithium chloride (LiCl) (45 mg/kg, p.o.) and ZGR (50 mg/kg, p.o.), and three groups of MLB rats (received 25 mg/kg KET, i.p. from day 8 to day 15): control, lithium (45 mg/kg, p.o.) and ZGR (50 mg/kg, p.o.). Pre-treatment with ZGR (50 mg/kg) once daily or LiCl (45 mg/kg) twice a day for 14 days prevented all KET-induced changes except total sulfhydryl content (total SH), which was not significant. The data of this study showed that 25 mg/kg KET increased the number of crossings in the open-field test and induced oxidative and inflammatory damage in the rat hippocampus (HPC) and prefrontal cortex (PFC). KET increased thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), and tumor necrosis factor-alpha (TNF-α) levels; and decreased the activity of catalase (CAT) and superoxide dismutase (SOD) enzymes as well as the amount total SH in the HPC and PFC. These findings suggest that oxidative stress (OS) and inflammation may play an important role in BD, and ZGR as an anti-inflammatory and antioxidant agent might be able to reduce the oxidative and inflammatory damage related to the manic phase of this disorder.

Valproate regulates inositol synthesis by reducing expression of myo-inositol-3-phosphate synthase

Inositol depletion is a hypothesized mechanism of action of mood stabilization drugs used in the treatment of bipolar disorder. It was previously reported that the mood stabilizer valproate (VPA) increased phosphorylation of myo-inositol-3-phosphate synthases (MIPS), the rate limiting enzyme of inositol synthesis. Phosphosites were identified and examination of site-directed mutants suggested that phosphorylation leads to decreased enzymatic activity. In this study, we examined the extent of MIPS phosphorylation in response to VPA and used two interaction screens to identify protein kinases that interact with MIPS. Using an epitope tagged MIPS construct, we determined the fraction of phosphorylated MIPS to be very low (less than 2% of total), and we could not detect phosphorylation of untagged MIPS in response to VPA. In vitro analyses of phosphorylation revealed that putative protein kinases, PKC and CKII, have low specificity toward MIPS. These findings suggest that VPA likely depletes inositol via a mechanism other than MIPS phosphorylation. Consistent with this, mRNA levels of the MIPS-encoding gene INO1 and MIPS protein levels were significantly reduced during the mid-log growth phase in response to VPA treatment. These findings suggest that the mechanism whereby VPA causes inositol depletion is by reducing expression of the rate-limiting enzyme MIPS.

Modafinil's effects on cognition and sleep quality in affectively-stable patients with bipolar disorder: a pilot study.

Despite advances in the treatment of bipolar disorder (BD), most patients do not achieve complete inter-episode recovery and functional disability is common. During periods of relative remission, many patients continue to experience neurocognitive dysfunction, reduced daytime activity levels, and sleep disturbances. This 8-week, randomized, placebo-controlled pilot study evaluated the feasibility, safety and preliminary efficacy of the wake-promoting drug, modafinil (Provigil®), on neurocognitive functioning, daytime sleepiness, and sleep quality in affectively-stable BD patients. Twelve individuals with affectively-stable BD were recruited and randomized to a flexible dose of modafinil (100 to 200 mg/day) or placebo, adjunctive to a therapeutic dose of a mood stabilizer. Weekly in-person visits tracked sleep quality and daytime sleepiness as well as side effects and mood symptoms. Neurocognitive functioning was assessed at baseline, week 4, and week 8. No serious adverse events were reported. Newly emergent side effects in the modafinil group included heart palpitations, itching, fatigue, and decreased energy. Two patients discontinued modafinil owing to side effects and one of these patients withdrew from the study. One patient discontinued placebo and was withdrawn from the study. Preliminary evaluations of clinical efficacy showed a marginally significant interaction between treatment group and time in two cognitive domains (speed of processing and verbal learning), indicating greater improvement in the modafinil group versus placebo. Additionally, there was a marginally significant effect of treatment group on daytime sleepiness, suggesting lower daytime sleepiness in the modafinil group versus placebo. Counterintuitively, we found a significant treatment group by time interaction effect on sleep quality, suggesting greater improvement in sleep quality in the placebo group versus the modafinil group. Results suggest that modafinil is a relatively safe medication for affectively-stable BD patients when given with adjunctive mood stabilizers. Results are suggestive of cognitive benefit and improved daytime sleepiness, but worse sleep quality in those patients prescribed modafinil. A fully powered clinical trial is warranted with specific attention to the characteristics of patients who are most likely to benefit from treatment with modafinil and other methodological lessons learned from this pilot. ClinicalTrials.gov, identifier NCT01965925.

Racial differences in pathways to care preceding first episode mania or psychosis: a historical cohort prodromal study.

There is evidence suggesting racial disparities in diagnosis and treatment in bipolar disorder (BD) and schizophrenia (SZ). The purpose of this study is to compare psychiatric diagnoses and psychotropic use preceding a first episode of mania (FEM) or psychosis (FEP) in racially diverse patients. Using a comprehensive medical records linkage system (Rochester Epidemiology Project, REP), we retrospectively identified individuals diagnosed with BD or SZ and a documented first episode of mania or psychosis. Illness trajectory before FEP/FEM were characterized as the time from first visit for a mental health complaint to incident case. Pathways to care and clinical events preceding FEP/FEM were compared based on subsequent incident case diagnosis (BD or SZ) and self-reported race (White vs. non-White). A total of 205 (FEM = 74; FEP = 131) incident cases were identified in the REP. Duration of psychiatric antecedents was significantly shorter in non-White patients, compared to White patients (2.2 ± 4.3 vs. 7.4 ± 6.6 years; p < 0.001) with an older age at time of first visit for a mental health complaint (15.7 ± 6.3 vs. 11.1 ± 6.0 years; p = 0.005). There were no significant differences by race in FEM pathway to care or age of first seeking mental health. Overall non-White patients had lower rates of psychotropic use. These data are unable to ascertain reasons for shorter duration of psychiatric antecedents and later age of seeking care, and more broadly first age of initial symptom presentation. If symptoms are confirmed to be earlier than first time seeking care in both groups, it would be important to identify barriers that racial minorities face to access timely psychiatric care and optimize early intervention strategies.

Effects of Exercise on Functional Recovery in Patients with Bipolar Depression: A Study Protocol for a Randomized Controlled Trial.

Treatment of bipolar disorder is prone to prolongation despite various treatments, including medication. The efficacy of exercise treatment (i.e., interventions involving physical exercise and sports intervention) for major depressive disorders has been reported for depressive symptoms, cognitive function, and sleep disturbances. However, its efficacy for bipolar disorder has yet to be established. We designed a randomized, controlled, double-blind clinical trial that includes 100 patients with bipolar disorder aged 20-65 years. This will be a cluster-randomized, two-group trial that will be conducted in ten psychiatric hospitals. The hospitals will be randomly assigned to an exercise intervention + treatment as usual (exercise) group or a placebo exercise intervention (stretching) + treatment as usual (control) group. Patients will be assessed using an extensive battery of clinical tests, physical parameters, sleep status, biological parameters (cytokines, neurotrophic factors), and genetic parameters (DNA and RNA) at baseline after a 6-week intervention period, at 10-week follow-up, and at 6-month follow-up. This innovative study may provide important evidence for the effectiveness of exercise in the treatment of bipolar depression based on clinical, biological, genetic, and physiological markers.

Bipolar disorder: Diagnosis, treatment and future directions.

Bipolar disorder is a relatively common mental illness, characterised by recurrent episodes of mania (or hypomania) and major depression, and associated with a significant burden of morbidity and premature mortality. Physicians across all specialities are likely to encounter individuals with the condition within their clinical practice. This short review provides an up-to-date overview of the clinical features, epidemiology, pathophysiology, evidence-based management, prognosis and future directions for treatment and research in bipolar disorder. Aspects of cross-specialty relevance are highlighted, including the physical health burden associated with the condition, and the side effects and safety considerations of medication regimes used in bipolar disorder.

An Overview of the Neurotrophic and Neuroprotective Properties of the Psychoactive Drug Lithium as an Autophagy Modulator in Neurodegenerative Conditions.

For both short-term and long-term treatment of bipolar disorder, lithium is a prototypical mood stabilizer. Lithium's neuroprotective properties were revealed by cumulative translational research, which opened the door to reforming the chemical as a treatment for neurodegenerative illnesses. The control of homeostatic systems such as oxidative stress, autophagy, apoptosis, mitochondrial function, and inflammation underlies lithium's neuroprotective characteristics. The fact that lithium inhibits the enzymes inositol monophosphatase (IMPase) and glycogen synthase kinase (GSK)-3 may be the cause of the various intracellular reactions. In this article, we review lithium's neurobiological properties, as demonstrated by its neurotrophic and neuroprotective capabilities, as well as translational studies in cells in culture and in animal models of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Prion disease, amyotrophic lateral sclerosis (ALS), ischemic stroke, and neuronal ceroid lipofuscinosis (NCL), discussing the justification for the drug's use in the treatment of these neurodegenerative disorders.

Role of adjunctive nonpharmacological strategies for treatment of rapid-cycling bipolar disorder.

Rapid-cycling bipolar disorder (RCBD) is a phase of bipolar disorder defined by the presence of ≥ 4 mood episodes in a year. It is a common phenomenon characterized by greater severity, a predominance of depression, higher levels of disability, and poorer overall outcomes. It is resistant to treatment by conventional pharmacotherapy. The existing literature underlines the scarcity of evi-dence and the gaps in knowledge about the optimal treatment strategies for RCBD. However, most reviews have considered only pharmacological treatment options for RCBD. Given the treatment-refractory nature of RCBD, nonpharmacological interventions could augment medications but have not been adequately examined. This review carried out an updated and comprehensive search for evidence regarding the role of nonpharmacological therapies as adjuncts to medications in RCBD. We identified 83 reviews and meta-analyses concerning the treatment of RCBD. Additionally, we found 42 reports on adjunctive nonpharmacological treatments in RCBD. Most of the evidence favoured concomitant electroconvulsive therapy as an acute and maintenance treatment. There was pre-liminary evidence to suggest that chronotherapeutic treatments can provide better outcomes when combined with medications. The research on adjunctive psychotherapy was particularly scarce but suggested that psychoeducation, cognitive behavioural therapy, family interventions, and supportive psychotherapy may be helpful. The overall quality of evidence was poor and suffered from several methodological shortcomings. There is a need for more methodologically sound research in this area, although clinicians can use the existing evidence to select and individualize nonpharmacological treatment options for better management of RCBD. Patient summaries are included to highlight some of the issues concerning the implementation of adjunctive nonpharmacological treatments.

The immunomodulatory effect of lithium as a mechanism of action in bipolar disorder.

Bipolar disorder (BD) is a chronic mental disorder characterized by recurrent episodes of mania and depression alternating with periods of euthymia. Although environmental and genetic factors have been described, their pathogenesis is not fully understood. Much evidence suggests a role for inflammatory mediators and immune dysregulation in the development of BD. The first-line treatment in BD are mood-stabilizing agents, one of which is lithium (Li) salts. The Li mechanism of action is not fully understood, but it has been proposed that its robust immunomodulatory properties might be one of the mechanisms responsible for its effectiveness. In this article, the authors present the current knowledge about immune system changes accompanying BD, as well as the immunomodulatory effect of lithium. The results of studies describing connections between immune system changes and lithium effectiveness are often incoherent. Further research is needed to understand the connection between immune system modulation and the therapeutic action of lithium in BD.

Modafinil. Armodafinil. The use of eugeroics in assisting the treatment of depression, bipolar disorder, and schizophrenia. Benefits, drawbacks, and adverse effects

Modafinil is used to treat narcolepsy with cataplexy and is also being extensively studied to find new therapeutic uses. In recent years, there have been reports suggesting the potential benefits of modafinil in the treatment of psychiatric illnesses such as depression and bipolar depression. In the case of depression, modafinil can be used as an adjuvant or as monotherapy in patients who do not respond sufficiently to antidepressants. Studies have shown that modafinil improves symptoms of depression, reduces fatigue and improves cognitive function. There are also reports of a beneficial effect of modafinil in the treatment of seasonal depression. For bipolar depression, modafinil can be used as an adjunct therapy during the depressive phase, particularly in patients experiencing slowness, lethargy and loss of pleasure. Studies suggest that modafinil may improve depressive symptoms without inducing manic episodes. There are also data indicating modafinil's potential efficacy in treating negative symptoms and improving cognitive function in patients with schizophrenia. In conclusion, modafinil appears to be a promising drug in aiding the treatment of various psychiatric illnesses.

Real-world use of pharmacological treatments for incident bipolar disorder: A Finnish nationwide cohort study

BackgroundPharmacotherapy remains crucial for treating bipolar disorder (BD), but knowledge on the treatments actually used by newly diagnosed patients in real-world settings is sparse. MethodsIndividuals newly diagnosed with BD during 1996–2018, aged 15–65 years, were identified from national Finnish registers. The patients' use of different drug classes (mood stabilizers, antipsychotics and antidepressants) or combinations of these drug classes were followed from initial pharmacotherapy (first line) after BD diagnosis until the fifth line of treatment or until the two-year follow-up time ended. Clinical and sociodemographic factors associated with antidepressants-only as the first treatment line were assessed with logistic regression. Results82.6 % of all patients used BD medication during the follow-up. 33.9 % had antidepressants-only as the first, 22.9 % as the second and 19.7 % as the third treatment line. Use of combinations of mood stabilizers, antipsychotics and antidepressants increased by successive treatment lines. Factors associated with antidepressants-only as the first treatment line included older age (>45 years aOR 2.20, 95% CI: 2.01–2.40, 25–45 years: 1.55, 1.42–1.68, compared with those aged <25), diabetes (1.35, 1.17–1.55) and female sex (1.29, 1.21–1.37). BD diagnosis registered in 2016–2018 (0.48, 0.42–0.55) and substance abuse (0.77, 0.71–0.83) were associated with decreased odds. LimitationsDue to the register-based nature of this study, not all potentially important clinical factors influencing medication use could be controlled for. ConclusionsA large proportion of patients with bipolar disorder are not treated according to treatment guidelines, as use of antidepressants alone is common. Reasons for not following evidence-based recommendations need to be further researched.

Lithium treatment versus hospitalization in bipolar disorder and major depression patients

BackgroundPreventing hospitalization of major affective disorder patients is a fundamental clinical challenge for which lithium is expected to be helpful. MethodsWe compared hospitalization rates and morbidity of 260 patients with DSM-5 bipolar or major depressive disorder in the 12 months before starting lithium versus 12 months of its use. We evaluated duration of untreated illness, previous treatments, substance abuse, suicidal status, lithium dose, and use of other medicines for association with new episodes of illness or of symptomatic worsening as well as hospitalization, using bivariate and multivariate analyses. ResultsWithin 12 months before lithium, 40.4 % of patients were hospitalized versus 11.2 % during lithium treatment; other measures of morbidity also improved. Benefits were similar with bipolar and major depressive disorders. Independently associated with hospitalization during lithium treatment were: receiving an antipsychotic with lithium, suicide attempt during lithium treatment, lifetime substance abuse, and psychiatric hospitalization in the year before starting lithium, but not diagnosis. LimitationsParticipants and observation times were limited. The study was retrospective regarding clinical history, lacked strict control of treatments and was not blinded. ConclusionsThis naturalistic study adds support to the effectiveness of lithium treatment in preventing hospitalization in patients with episodic major mood disorders.

Optimization of Therapy in Patients with Epilepsy and Psychiatric Comorbidities: Key Points.

Psychiatric disorder comorbidity in patients with epilepsy (PWE) is very frequent with a mean percentage prevalence of up to 50% and even higher. Such a high frequency suggests that epilepsy and psychiatric disorders might share common pathological pathways. Various aspects contribute in making the matter very complex from a therapeutic point of view. Some antiseizure medications (ASMs), namely valproic acid, carbamazepine, and lamotrigine, have mood-stabilising effects and are routinely used for the treatment of bipolar disorder in patients who do not have epilepsy. Pregabalin and, to a lesser extent, gabapentin, exerts anxiolytic effects. However, several ASMs, in particular levetiracetam, topiramate, and perampanel, may contribute to psychiatric disorders, including depression, aggressive behaviour, and even psychosis. If these ASMs are prescribed, the patient should be monitored closely. A careful selection should be made also with psychotropic drugs. Although most of these can be safely used at therapeutic doses, bupropion, some tricyclic antidepressants, maprotiline, and clozapine may alter seizure threshold and facilitate epileptic seizures. Interactions between ASMs and psychotropic medication may make it difficult to predict individual response. Pharmacokinetic interactions can be assessed with drug monitoring and are consequently much better documented than pharmacodynamic interactions. Another aspect that needs a careful evaluation is patient adherence to treatment. Prevalence of non-adherence in PWE and psychiatric comorbidities is reported to reach values even higher than 70%. A careful evaluation of all these aspects contributes in optimizing therapy with a positive impact on seizure control, psychiatric wellbeing, and quality of life.

Polypharmacy in Outpatients with Bipolar Disorder: Associated Factors and Treatment Characteristics in Türkiye

Objective: Polypharmacy is frequently used in the treatment of the bipolar disorder. We aimed to investigate polypharmacy rates, associated factors, and the types of drugs preferred in treatment among outpatients with bipolar disorder. &#x0D; Method: A total of 209 bipolar disorder patients attending an outpatient psychiatry clinic were included in this study. Drug types, active substances, and combination forms were examined. &#x0D; Results: The rate of polypharmacy among bipolar outpatients was 79.40%. Antipsychotics were the most frequently preferred drug for the treatment. The most commonly used antipsychotic was quetiapine, whereas the mood stabilizer was sodium valproate and the antidepressant was paroxetine. The most common form of treatment for bipolar disorder was the combined use of a mood stabilizer and an antipsychotic. &#x0D; Conclusion: In contrast to treatment guidelines, polypharmacy has virtually become a standard in the treatment of bipolar disorder. It appears that the adoption of polypharmacy in treatment will persist for various reasons. As such, there is a need to develop new guidelines to guide psychiatrists in determining the patient groups and combinations in which combination therapy will be preferred. Moreover, interventions are needed to minimize the possible side effects, and risk of drug-drug interactions related to the use of multiple drugs, determine the benefit/harm ratio and reduce unnecessary psychotropic drug use.