Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials

Kishi, Taro; Ikuta, Toshikazu; Matsuda, Yuki; Sakuma, Kenji; Okuya, Makoto; Nomura, Ikuo; Hatano, Masakazu; Iwata, Nakao

doi:10.1038/s41380-021-01334-4

Cited by 88 publications

(84 citation statements)

References 38 publications

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“…In the review, 1 however, BD proportion with psychotic features was not always correlated with treatment response in meta‐regression analysis; however, this analysis had a “power” problem as it was derived based on combining the targeted drugs (antipsychotics + mood stabilizers + other drugs), treating them as “one covariate group.” 1 Therefore, to clarify this correlation and/or confirm our speculation regarding antipsychotics being a “versatile” drug, we conducted a subgroup‐analysis between such a proportion and improvement rate in acute mania, stratified by drug type, specifically for antipsychotics.…”

Section: Figmentioning

confidence: 99%

“…A recent systematic review and network meta‐analysis provided evidence that several antipsychotics and traditional mood stabilizers (e.g. lithium and valproate) were effective and tolerant for acute mania in bipolar disorder (BD) 1 . Specifically, the results regarding the antipsychotics are convincing for clinicians because such agents can improve (i) elevated/irritable mood and other manic symptoms by their immediate sedative effect and (ii) psychotic symptoms in BD, 1 although not consistently with a significant correlation 2 .…”

Section: Figmentioning

confidence: 99%

“…lithium and valproate) were effective and tolerant for acute mania in bipolar disorder (BD). 1 Specifically, the results regarding the antipsychotics are convincing for clinicians because such agents can improve (i) elevated/irritable mood and other manic symptoms by their immediate sedative effect and (ii) psychotic symptoms in BD, 1 although not consistently with a significant correlation. 2 This raises important speculation on whether antipsychotics should be regarded as “versatile” BD drugs, since they are the “best” treatment option, particularly in cases of difficult diagnosis (e.g.…”

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confidence: 99%

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Proportion of subjects with psychotic features in bipolar disorder correlated with treatment response by antipsychotics for acute mania

Ikeda

Takeo

Kanazawa

et al. 2022

Psychiatry Clin Neurosci

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Before the pandemic (2018)(2019), an average of 8.92 patients were treated for FND monthly, which increased during the pandemic to 19.25 patients per month (x 2 = 20.26, P < 0.001); overall, first trimester consultations increased significantly (x 2 = 41.26, P < 0.001). The pandemic to pre-pandemic FND case ratio was 3:1. (Fig 1).During the pandemic period studied (2020 to first quarter 2021), a total of 9252 emergency care consultations were registered, 231 of which were due to FND. Each pandemic phase was associated with increased FND cases, and phase 1 showed higher odds (OR = 5.2, 95% CI: 3.1-8.9, P < 0.001). During the pandemic, FND occurrence was predominant in females (201 vs. 167, P = 0.003). Patients were more prone to identify triggering stressors during than before the pandemic (115 vs. 80, P = 0.003); the main stressor identified was academic stressors (7 vs. 0, P = 0.006), followed by pandemic-related stressors (7 vs. 0, P = 0.006). Neurological comorbidities gained importance during the pandemic (111 vs. 41, P = 0.0031), as they became more prevalent in patients seeking medical attention due to FND when compared to the pre-pandemic period.The COVID-19 pandemic and the resulting social isolation measures have proven to be significant stressors for the general population and have a negative impact on the mental health of the global population. [5][6][7] Our study demonstrates that the ratio of patients receiving emergency care has increased significantly since the beginning of the COVID-19 pandemic at our center, whether evaluated by month, trimester, or year. In addition, this study analyzed the risk of presenting to the ED with FND symptoms during each phase of the pandemic. The increase in number corresponds to the peak in confirmed cases and may be associated with social distancing, mobility restrictions, and the lockdown, which is consistent with the increase in the incidence of anxiety disorders and moderate to severe depressive disorder in the same period reported in a previous study. 8 While Hull et al. (2021), reported a 60.1% increase in diagnoses of FND motor subtype. 3 Other studies have reported a stable course of the FND symptoms during the pandemic in patients with a diagnosis established previous to the pandemic which could be attributed to the role of the social context in this disease. 9,10 In conclusion, the demand for EC from patients suffering from FND during the pandemic has increased in a 3:1 ratio in Mexico. The peaks and valleys in the seeking of medical attention at our center by patients with FND coincided with the different phases of the pandemic as experienced in Mexico, with the implementation of social distancing measures, particularly with the lockdown and highest transmission of the virus. It remains important to track the collateral and post-pandemic impacts on patients who experience FND.

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Section: Figmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

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Proportion of subjects with psychotic features in bipolar disorder correlated with treatment response by antipsychotics for acute mania

Ikeda

Takeo

Kanazawa

et al. 2022

Psychiatry Clin Neurosci

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“…Valproic acid (VPA) is a widely used drug for the treatment of bipolar disorder, particularly for acute mania, and multiple seizure types such as generalized tonic-clonic seizures ( Hakami, 2021 ; Kishi et al, 2022 ). As a narrow therapeutic index drug, it is characterized by high pharmacokinetic variability ( Johannessen and Johannessen, 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Machine learning advances the integration of covariates in population pharmacokinetic models: Valproic acid as an example

et al. 2022

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Background and Aim: Many studies associated with the combination of machine learning (ML) and pharmacometrics have appeared in recent years. ML can be used as an initial step for fast screening of covariates in population pharmacokinetic (popPK) models. The present study aimed to integrate covariates derived from different popPK models using ML.Methods: Two published popPK models of valproic acid (VPA) in Chinese epileptic patients were used, where the population parameters were influenced by some covariates. Based on the covariates and a one-compartment model that describes the pharmacokinetics of VPA, a dataset was constructed using Monte Carlo simulation, to develop an XGBoost model to estimate the steady-state concentrations (Css) of VPA. We utilized SHapley Additive exPlanation (SHAP) values to interpret the prediction model, and calculated estimates of VPA exposure in four assumed scenarios involving different combinations of CYP2C19 genotypes and co-administered antiepileptic drugs. To develop an easy-to-use model in the clinic, we built a simplified model by using CYP2C19 genotypes and some noninvasive clinical parameters, and omitting several features that were infrequently measured or whose clinically available values were inaccurate, and verified it on our independent external dataset.Results: After data preprocessing, the finally generated combined dataset was divided into a derivation cohort and a validation cohort (8:2). The XGBoost model was developed in the derivation cohort and yielded excellent performance in the validation cohort with a mean absolute error of 2.4 mg/L, root-mean-squared error of 3.3 mg/L, mean relative error of 0%, and percentages within ±20% of actual values of 98.85%. The SHAP analysis revealed that daily dose, time, CYP2C19*2 and/or *3 variants, albumin, body weight, single dose, and CYP2C19*1*1 genotype were the top seven confounding factors influencing the Css of VPA. Under the simulated dosage regimen of 500 mg/bid, the VPA exposure in patients who had CYP2C19*2 and/or *3 variants and no carbamazepine, phenytoin, or phenobarbital treatment, was approximately 1.74-fold compared to those with CYP2C19*1/*1 genotype and co-administered carbamazepine + phenytoin + phenobarbital. The feasibility of the simplified model was fully illustrated by its performance in our external dataset. Conclusion: This study highlighted the bridging role of ML in big data and pharmacometrics, by integrating covariates derived from different popPK models.

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“…Currently, Clinical Practice Guidelines (CPGs) such as CANMAT, ISBD and NICE support the use of second-generation antipsychotics (SGAs) such as aripiprazole, quetiapine, olanzapine and risperidone for the treatment of acute bipolar mania as well as lithium and valproate for the long-term treatment of BD. 2,[4][5][6][7] While the treatment recommendations for bipolar depression are more controversial and less studied, 3,8 most CPGs agree on recommending against the use of antidepressants as a monotherapy and some even as an adjunctive. [8][9][10] Importantly, despite this discouragement towards antidepressant use, studies show that antidepressants are prescribed commonly for patients with bipolar depression.…”

Section: Introductionmentioning

confidence: 99%

Twenty‐year medication use trends in first‐episode bipolar disorder

Poranen

Koistinaho

Tanskanen

et al. 2022

Acta Psychiatr Scand

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Objectives To study the medication use patterns in patients newly diagnosed with bipolar disorder (BD) in Finland during the past 20 years. Methods All persons diagnosed with BD between 1996 and 2018, aged 16–65 years, with no previous BD diagnosis were identified from nationwide Finnish registers (N = 26,395). The point prevalences of medication use were observed up until 5 years after the first diagnosis. Five sub‐cohorts according to calendar year of first diagnosis were also formed and the prevalence of medication use was compared between sub‐cohorts 3 months after diagnosis. Medication data were modeled with the PRE2DUP‐method using dispensing data. Results The prevalence of overall medication use declined during the 5‐year follow‐up period in the total cohort. The highest prevalence of use was seen 3 months after diagnosis for the three main medication classes–antidepressants (40.8%), antipsychotics (30.8%) and mood stabilizers (29.2%). The prevalence of lithium use varied between 5.9% and 6.5% during the 5 years in the total cohort, and the lowest prevalence of use at 3 months was seen in sub‐cohort diagnosed in 2016–2018 (4.1%) versus 12.1% in 1996–2000 sub‐cohort. The prevalence of benzodiazepine use was between 12.4% and 13.5% and the prevalence of Z‐drugs was between 7.3% and 7.9% during the 5 years. The prevalence of long‐acting injectable antipsychotic (LAI) use was the highest in patients diagnosed in 2016–2018, although still only 0.8%. Conclusions (i) The use of antidepressants is too prevalent, (ii) the use of lithium is declining and needs to be increased, and (iii) LAIs are markedly underutilized as compared to their oral counterparts.

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Pharmacological treatment for bipolar mania: a systematic review and network meta-analysis of double-blind randomized controlled trials

Cited by 88 publications

References 38 publications

Proportion of subjects with psychotic features in bipolar disorder correlated with treatment response by antipsychotics for acute mania

Proportion of subjects with psychotic features in bipolar disorder correlated with treatment response by antipsychotics for acute mania

Machine learning advances the integration of covariates in population pharmacokinetic models: Valproic acid as an example

Twenty‐year medication use trends in first‐episode bipolar disorder

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