Predictors of somatic symptoms during the COVID-19 pandemic: a national longitudinal survey in Japan.

OBJECTIVES: The COVID-19 pandemic has highlighted the long-term consequences of SARS-CoV-2 infection, termed long COVID. However, in the absence of comparative groups, the differentiation of disease progression remains difficult, as COVID-19 symptoms become indistinguishable from symptoms originating from alternative etiologies. This study aimed to longitudinally investigate the association between COVID-19 exposure and the somatic symptoms in the Japanese general population. DESIGN: This was a longitudinal cohort study with 1-year follow-up. SETTING AND PARTICIPANTS: Longitudinal data from 19 545 individuals who participated in the Japan Society and New Tobacco Internet Survey (JASTIS) 2022 and 2023 were included. In this study, we used data from the 2022 JASTIS as baseline data and the 2023 JASTIS as follow-up data. Based on questionnaire responses, respondents were classified into three categories of exposure to COVID-19. OUTCOME MEASURES: The somatic symptoms were assessed by the Somatic Symptom Scale-8 (SSS-8). Using generalised linear models adjusted for baseline covariates, we calculated the ORs of having very high somatic symptoms assessed by SSS-8, attributable to COVID-19 exposure (no COVID-19 cases as the reference group). RESULTS: Follow-up completers were divided into three groups according to COVID-19 exposure (no COVID-19, n=16 012; COVID-19 without O2 therapy, n=3201; COVID-19 with O2 therapy, n=332). After adjusting for all covariates, COVID-19 cases with O2 therapy had a significant positive association (OR 7.60, 95% CI 5.47 to 10.58) with a very high somatic symptoms burden while other COVID-19 exposure groups did not. Pre-existing physical and psychological conditions were also associated with increased risk of somatic symptoms. CONCLUSION: The findings of our study suggest that the severity of COVID-19 symptoms requiring O2 therapy in the acute phase led to high somatic symptoms. Pre-existing conditions were also associated with a subsequent risk of somatic symptoms.

Continuous alcohol withdrawal delirium and physical illness-associated delirium in a man brought to the emergency department after a disaster: A case report.

BACKGROUND: Risk factors for alcohol withdrawal delirium include heavy drinking, prior alcohol withdrawal delirium or convulsions, nondrug sedative use, and a history of tachycardia, withdrawal, and infections. CASE PRESENTATION: A 76-year-old man with a history of heavy drinking and type 2 diabetes was hospitalized for hypothermia, rhabdomyolysis, and acute renal failure after a typhoon. He developed alcohol withdrawal symptoms 24 h after his last drink, leading to severe withdrawal delirium characterized by restlessness, delusions, and altered consciousness. Treatment included lorazepam, in addition to comprehensive care for his physical condition. His condition fluctuated, especially at night, with his psychiatric symptoms exacerbated by his physical illnesses, suggesting delirium due to the coexistence of severe and multiple physical illnesses. After 44 days, following substantial improvements in both mental and physical health with perospirone, the patient was discharged. CONCLUSION: This case emphasizes the need for multidisciplinary collaboration in the treatment of such patients, especially during disasters, and the importance of long-term monitoring for elderly patients with alcohol dependence syndrome after a disaster.

Vortioxetine-induced syndrome of inappropriate secretion of antidiuretic hormone: A case report.

BACKGROUND: Vortioxetine, known for its efficacy in treating depression through its effects on various neurotransmitters, has not been previously reported to induce syndrome of inappropriate secretion of antidiuretic hormone (SIADH). CASE PRESENTATION: This case report describes a 74-year-old man with major depressive disorder who developed SIADH 1 week after starting treatment with vortioxetine. SIADH is characterized by symptoms such as headache, nausea, disorientation, and seizures, stemming from hyponatremia (123 mEq/L), without dehydration or edema. Vortioxetine was discontinued, and an alternative drug, mianserin, was initiated. The patient was restricted from drinking water due to hyponatremia. The serum Na concentration improved over time to within the normal range by the second week after admission. CONCLUSION: This is the first case report of vortioxetine-induced SIADH.

Changes in suicidal ideation during treatment among patients with major depressive disorder: A 6-month naturalistic follow-up study.

AIM: There is limited evidence regarding predictors of changes in suicidal ideation (SI) in patients with major depressive disorder (MDD). The objective of this study was to describe changes in SI over a 6-month period and identify their predictors from naturalistic observations of MDD patients. METHODS: In the cross-sectional analysis, we examined 257 patients with MDD at the first-visit assessment. Among the patients, 119 who completed the 6-month assessment (completers) were included in the longitudinal analysis. For the evaluation of depressive symptoms, including SI, the Quick Inventory of Depressive Symptomatology-Japanese version was administered at both the first-visit and follow-up assessments. At baseline, we also administered the Japanese version of the Ten Item Personality Inventory to assess personality traits and the PRIME Screen-Revised to assess psychotic symptoms. RESULTS: In the cross-sectional analysis of first-visit patients, 36.2% (93/257) exhibited SI. Among completers, 14.3% (17/119) had prolonged SI. Among the completers with SI at the first-visit assessment, 38.6% (17/44) had SI at the follow-up assessment (prolonged SI). In linear regression models including all completers, prolonged SI was positively associated with endorsement of suspiciousness/persecutory ideas and negatively associated with higher age. CONCLUSION: More than one-third of completers who had SI at the first-visit assessment experienced prolonged SI (SI at follow-up). Our findings can help clinicians predict the course of MDD by identifying associated demographic and clinical characteristics.

Factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period: Retrospective cohort study.

BACKGROUND: Constipation is a common adverse effect of antipsychotics, but little investigation has been conducted. We aimed to address the factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period. METHODS: We enrolled patients with schizophrenia attending each hospital (n = 14) from April 1, 2021, and retrospectively examined all prescriptions as of April 1, 2016, 2011, 2006, and 2001, every 5 years starting in 2021, for this population. 716 participants with complete data were included in the analysis. The Cochran Q test followed by Bonferroni correction and the Cochran-Armitage trend test were used to determine the differences and trends of the frequency of each laxative. Multivariate logistic regression analysis was performed to assess the factors on the initiation of laxative use over a 20-year period. RESULTS: Of the patients, 25.1% were treated with laxatives in 2001, and 34.1% were treated in 2021. The numbers of patients treated with any laxatives significantly differed over the 20-year period, with a significant increasing trend. In all laxatives, the numbers of patients treated with magnesium oxide, lubiprostone and elobixibat differed with a significant increasing trend. Female sex, age, the total DZP equivalent dose, and the doses of levomepromazine maleate, olanzapine, quetiapine, zotepine, lithium, and carbamazepine in 2021 were significant factors associated with the initiation of laxative use over the 20-year period. CONCLUSIONS: Careful monitoring is needed for patients treated with levomepromazine maleate, olanzapine, quetiapine and zotepine. Optimizing prescriptions according to treatment guidelines could reduce antipsychotic-induced constipation.

Real-world predictors of divorce among outpatients with bipolar disorder: sex differences and clinical implications.

BACKGROUND: Bipolar disorder is a mental illness characterized by recurring episodes of mania and depression and is known to cause social impairment. Additionally, it has been revealed that bipolar disorder increases the risk of divorce and loss of family member support, which can worsen the prognosis. However, there is limited evidence regarding the predictive factors of divorce among patients with bipolar disorder in real-world settings. METHODS: This study utilized an observational approach and involved psychiatrists from 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. They were requested to conduct a retrospective review of medical records and complete a questionnaire focused on patients diagnosed with bipolar disorder. The data collection period for baseline patient characteristics spanned from September to October 2017. Next, we investigated the incidence of divorce over a 2-year period, ranging from baseline to September to October 2019. RESULTS: A total of 1071 outpatients with bipolar disorder were included in the analysis, and 2.8% (30/1071) experienced divorce during the first 2 years of observation. The incidence of divorce in this population was considerably higher than that in the general Japanese population. Binomial logistic regression analysis confirmed that a younger baseline age and lower BMI values were statistically significant predictors of divorce occurrence for all study participants. The predictors of divorce were then examined separately by sex. The results revealed that for men, a younger age at baseline and having bipolar I disorder compared to bipolar II disorder were statistically significant predictors of divorce. In contrast, for women, having a lower BMI and using anxiolytics emerged as statistically significant predictors of divorce. CONCLUSIONS: In this study, a younger baseline age and lower BMI values were statistically significant predictors of divorce in patients with bipolar disorder. Notably, the predictors of divorce varied significantly between men and women. These findings provide important insights from a family perspective regarding social support for individuals with bipolar disorder in real-world clinical settings.

Risk evaluation of diabetic ketoacidosis associated with antipsychotics among patients with schizophrenia in the Japanese adverse event report database.

OBJECTIVE: Diabetic ketoacidosis (DKA) is a serious life-threatening condition and can be associated with antipsychotic medication. Asian patients with diabetes exhibit less insulin resistance than Caucasians; however, all previous studies concerning antipsychotic-related DKA have been conducted in Western populations. We analyzed the rank order of the association of antipsychotic agents for schizophrenia with DKA using the Japanese Adverse Drug Event Report database, a spontaneous reporting system database. METHODS: We performed a retrospective pharmacovigilance disproportionality analysis using adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency between April 2004 and March 2021. The study population comprised 7435 patients with schizophrenia, and the total number of antipsychotic-related DKA reports was 55. RESULTS: Among the 55 cases of DKA in patients with schizophrenia, 6% (3/55) patients died after DKA. The signals of DKA were reported after treatment with olanzapine, with a significant adjusted reporting odds ratio (95% CI) of 3.26 (1.87-5.66). In 1399 olanzapine treatment cases, multivariable logistic regression analysis using a forward selection method showed that being male (adjusted RORs 2.72 (1.07-6.90)) was associated with the onset of DKA. CONCLUSION: Our study revealed that treatment with olanzapine was associated with the development of DKA among patients with schizophrenia. The results also clarified that male patients were at higher risk for DKA among patients treated with olanzapine. The application of these data will aid in risk monitoring and management that may reduce the occurrence of antipsychotic-related DKA in treatment for schizophrenia.

Relationship Between Diabetic Chorea and Timing of MRI Findings: A Systematic Review with Case Reports.

Background: Diabetic chorea is a rare complication of diabetes mellitus for which head MRI is the most common diagnostic imaging modality. Cases have been reported where CT and/or MRI findings are inconsistent or clinical symptoms and imaging findings do not appear simultaneously. We aimed to compile the cases in which imaging findings appeared on MRI retests and to examine in a systematic review whether temporal differences in the appearance of imaging findings correlate with clinical characteristics. Case Presentation: An 80-year-old man with type 2 diabetes mellitus came to a hospital with abnormal movements of the left upper and lower extremities. Two days after the first visit, his symptoms flared up, and his head MRI showed an old cerebral infarction and no new lesion. On day 14, he retested T1-weighted imaging and showed a high signal in the right putamen, which was considered diabetic chorea. Blood glucose was controlled with insulin, and the involuntary movements disappeared. Methods: PubMed and ICHUSHI were searched to identify patients with diabetic chorea who had undergone MRI retests. Patients grouped by the temporal change in the presence/absence of imaging findings were compared on age, sex, duration of diabetes mellitus, blood glucose level, HbA1c level, side of involuntary movement, time to first MRI, and follow-up MRI. Results: Of the 64 cases analyzed, 43 (67.2%) were female. The mean age was 69.0 years. 16 (25.0%) had worsening findings upon MRI retesting, 37 (57.8%) had improvement, and 10 (15.6%) had unchanged findings. There were no significant differences in age, sex, mean blood glucose level or HbA1c at onset among the groups. Conclusion: There was no association between the pattern of appearance of imaging findings over time and clinical characteristics, including glucose levels. If initial MRI findings are negative, MRI retesting after a certain time may help diagnose diabetic chorea.

Differences in self-reported psychotic symptoms between patients with autism spectrum disorder and those with schizophrenia.

AIM: Patients with autism spectrum disorder (ASD) are prone to develop overt psychosis and share symptom presentations with those with schizophrenia (SZ). This study aimed to explore differences in the distributions of psychotic symptoms among first-visit patients with ASD, SZ, or a nonpsychiatric diagnosis (N-PD). METHODS: Data from first-visit patients were retrospectively collected from medical records from the Department of Psychiatry, Dokkyo Medical University Hospital between June 2019 and May 2021. A total of 254 patients with data on the PRIME Screen-Revised (PS-R) assessments were included in our analysis. In the hospital, all psychiatric diagnoses were based on the DSM-5 diagnostic criteria. RESULTS: In the ASD, SZ, and N-PD groups, endorsements of perplexity and delusional mood were 15.6% (7/45), 41.5% (44/106), and 1.1% (1/88), and those of perceptual abnormalities were 11.1% (5/45), 40.6% (43/106), and 2.3% (2/88), respectively. Trend analysis clarified that the endorsement of these psychotic symptoms increased from N-PD to ASD and SZ. In the multivariate-adjusted multinomial logistic regression analysis, the ASD and N-PD groups were compared with the SZ group. Higher age and the presence of perceptual abnormalities were associated with lack of an ASD diagnosis, whereas male sex, lack of perplexity and delusional mood, and lack of perceptual abnormalities were associated with N-PD. CONCLUSION: Our results are preliminary; however, a detailed assessment of positive symptoms might facilitate differentiation between ASD and SZ.

Survey of Health Literacy Among Japanese Outpatients with Mental Illness.

Purpose: Low health literacy has been associated with adverse outcomes in health maintenance and the course of chronic physical illness. In particular, anxiety disorders can also affect one's physical health, causing issues including cardiovascular, respiratory, gastrointestinal and immune system disorders. However, there are no reports on physical health literacy among Japanese patients with mental illness. Patients and Methods: A patient background questionnaire, the Japanese version of the Ten-Item Personality Inventory, and the Japanese version of the Health Literacy Scale (HLS-EU-Q47; European Health Literacy Survey Questionnaire) were distributed face to face to 1000 psychiatric outpatients. A total of 785 valid responses including 211 patients with schizophrenia, 261 patients with mood disorders, and 234 patients with anxiety disorders were obtained by mail. Results: Health literacy was "limited" in 52% of patients with schizophrenia, 51% of those with mood disorders, and 38% of those with anxiety disorders. Among patients with mood disorders, there were no differences between those with major depressive disorder and those with bipolar disorder. Anxiety disorders were associated with higher health literacy than schizophrenia and mood disorders (odds ratio (OR) 1.85, 95% confidence interval (95% CI) 1.07, 3.34), and in terms of personality, neuroticism (OR 0.85, 95% CI 0.75, 0.97) and openness (OR 0.85, 95% CI 0.74, 0.98) were associated with limited health literacy, while agreeableness (OR 1.36, 95% CI 1.18, 1.57) and extraversion OR 1.34, 95% CI 1.17, 1.52) were associated with higher health literacy. Conclusion: The results of this study indicate limited health literacy in patients with mental illness, in particular, limited health literacy in outpatients with schizophrenia and mood disorders. In addition, gender and some personality traits were associated with physical health literacy. Based on these results, physical health education should be individualized.

Item response theory analysis of the University Personality Inventory in medical students.

AIM: Young adulthood has been recognized as an important period for the transition from adolescence to adulthood. The University Personality Inventory (UPI), a mental health questionnaire for young adulthood, is widely used to screen university students in East Asia. However, dichotomous systems do not allow respondent choose responses other than two options on each symptom. This study employed item response theory (IRT) to examine the properties and performance of UPI items for mental health problems. METHODS: Japanese medical students (n = 1185) participated in this study, and the UPI was completed at the time of university admission. The two-parameter IRT model was used to assess the measurement characteristics of the UPI items. RESULTS: Among all participants, 35.4% (420/1185) had total UPI score of 21 or more, and 10.6% (126/1185) indicated that they had the idea of wanting to die (item 25). For further IRT analysis, unidimensionality was confirmed by exploratory factor analysis, in which the primary factor accounted for 39.6% of the variance. The scale has sufficient discrimination power. In the test characteristic curves, the rising slopes of the lines were between θ 0 and 2. CONCLUSION: The UPI is useful to assess mild or moderate mental health problems, while precision may decline among individuals experiencing both little and extremely high levels of stress. Our findings provide a basis for identifying people who have mental health concerns.

A case of panic attack developing after THC-O acetate inhalation using an e-cigarette device.

AIM: Tetrahydrocannabinol acetate (THC-O) is a cannabinoid-based product, and few medical studies have evaluated the effects of THC-O on humans. Recently, e-cigarettes have become popular among teenagers and young adults worldwide. However, there have been reports of people misusing this device as a delivery system for drugs of abuse. CASE PRESENTATION: We herein report a case of panic attack after THC-O inhalation using an e-cigarette device in an 18-year-old male with no history of psychiatric disorders. Although he started smoking both regular cigarettes and e-cigarettes in junior high school, he had never vaped delta-9 THC or THC-O until the present episode. A total of 20 min after his first inhalation of THC-O, he experienced a sudden attack that lasted 2 h. After this episode, he did not inhale THC-O. Throughout the subsequent 6 months of follow-up, he maintained improvement with no panic attacks. CONCLUSION: In this case, we intend to emphasize that THC-O is not safe, even if the substance is regarded as loophole drug. The use of e-cigarette devices might accelerate substance abuse.

Prescribing Trends for the Same Patients with Schizophrenia Over 20 Years.

Background: Recent pharmacoepidemiology data show an increase in the proportion of patients receiving second-generation antipsychotic (SGA) monotherapy, but no studies have analyzed the same patients over a long period of time. Therefore, in this study, we retrospectively evaluated schizophrenia patients with available data for 20 years to determine whether the drug treatments in the same patients have changed in the past 20 years. Methods: The study began in April 2021 and was conducted in 15 psychiatric hospitals in Japan. Schizophrenia patients treated in the same hospital for 20 years were retrospectively examined for all prescriptions in 2016, 2011, 2006, and 2001 (ie, every 5 years). Results: The mean age of the 716 patients surveyed in 2021 was 61.7 years, with 49.0% being female. The rate of antipsychotic monotherapy use showed a slight increasing trend over the past 20 years; the rate of SGA use showed a marked increasing trend from 28.9% to 70.3% over the past 20 years, while the rate of SGA monotherapy use showed a gradual increasing trend over the past 20 years. The rates of concomitant use of anticholinergics, antidepressants, anxiolytics/sleep medications, and mood stabilizers showed decreasing, flat, flat, and flat trends over the past 20 years, respectively. Conclusion: The results of this study showed a slow but steady substitution of SGAs for first-generation antipsychotics (FGAs) over time, even in the same patients.

The relationship of stress coping styles on substance use, depressive symptoms, and personality traits of nurses in higher education institution.

AIM: This study examined the collective characteristics of nurses and their stress coping style. METHODS: We conducted a cluster analysis of the stress coping strategies of 841 nurses belonging to Dokkyo Medical University Hospital, as measured by the Brief COPE (Coping Orientation to Problems Experienced). We also conducted multivariate analyses of each cluster's sociodemographic characteristics, personality traits, depressive symptoms, work attitudes, sense of fairness, and turnover intention. RESULTS: The results of cluster analysis using the standardized z scores of the Brief COPE demonstrated that the study participants were classified into three clusters. The "emotional-response type" tended to favor the use of emotional support, venting, and self-blame. The "reality-escape type" tended to prefer alcohol and substance use, behavioral resignation, use of instrumental support, and lack of acceptance. The "problem-solving type" tended to prefer planning, positive reframing, and acceptance and to dislike "alcohol and substance use" and behavioral disengagement. A multinomial logistic regression analysis revealed that compared to the problem-solving type, the emotional-response type had a lower job title, a higher "neuroticism" score on the TIPI-J, and a higher K6 score. However, compared to the problem-solving type, the reality-escape type was younger, consumed more alcohol and substances, and had a higher K6 score. CONCLUSIONS: Stress coping styles were found to be associated with substance use, depressive symptoms, and personality traits among nurses in higher education institutions. Thus, the results suggest that nurses who choose maladaptive stress coping styles require mental support and early identification of depressive symptoms and alcohol problems.

Development and validation of the Japanese version of EPDS-P for indirect screening of paternal perinatal depression based on maternal reporting: Protocol for a prospective longitudinal observational study.

AIMS: The main purpose of this study is to develop an indirect screening system for paternal perinatal depression based on the female partner's assessment in the Japanese population. The Japanese version of the Edinburgh Postnatal Depression Scale-Partner (EPDS-P) will be used as the indirect screening tool, and its accuracy will be studied in this longitudinal prospective observational study. METHODS: Public health nurses and midwives at the participating community health center are currently inviting couples to participate, and are distributing self-rating scales to the participants. The primary evaluation scales being used in this study are the Japanese versions of the Center for Epidemiologic Studies Depression Scale (CES-D) and the Japanese version of the EPDS-P which evaluates paternal perinatal depression by women. We will evaluate EPDS-P performance against CES-D, including accuracy, sensitivity, specificity, and correlations. RESULTS AND CONCLUSIONS: Perinatal depression is a mental illness that occurs between pregnancy and postpartum within the 12 months, and it is known to increase the risk of adversely impacting on child development. Men may also experience a psychosocial crisis during their partners' perinatal period. Although it was recently reported that the EPDS-P can indirectly detect paternal perinatal depression, there is, as yet, insufficient evidence of this because the previous studies had relatively small sample sizes and were limited to cross-sectional studies in the postpartum period. The development of a screening system for paternal perinatal depression using the EPDS-P will lead to increased awareness of the disease and provide an opportunity to establish a family-based support system in Japan.

Effect of antipsychotic use by patients with schizophrenia on deceleration capacity and its relation to the corrected QT interval.

OBJECTIVE: Schizophrenia patients treated with antipsychotics are at higher risk of sudden cardiac death. Decreased deceleration capacity (DC) of the heart rate is an accurate predictor of cardiac mortality. We evaluated the risk of sudden cardiac death due to antipsychotic use by assessing DC and examining the association between DC and the corrected QT interval (QTc) in schizophrenia patients. METHODS: We measured the DC and QTc of 138 schizophrenia patients. We then compared the DC of 86 age- and sex-matched healthy controls with that of 86 schizophrenia patients. We investigated the correlation of DC of approximately 138 schizophrenia patients with prescribed doses of antipsychotics using linear regression analysis. We compared the DC of schizophrenia patients with and without prolonged QT intervals. RESULTS: We found DC significantly differed between schizophrenia patients on antipsychotic medication and healthy controls. Additionally, DC was negatively correlated with antipsychotic use, especially chlorpromazine, zotepine, olanzapine and clozapine, in a dose-dependent manner. There was no significant association between DC and the QTc. CONCLUSION: Assessing DC could facilitate monitoring and identification of increased risk of cardiac mortality in patients with schizophrenia that take antipsychotics. Assessing both DC and the QTc may enhance the accuracy of predicting sudden cardiac death.

Predictors of psychological distress and sleep deprivation in caregivers of stroke survivors.

BACKGROUND: Caregivers for stroke survivors (CSS) suffer from long hours of care, limited support, and financial difficulties, which often affect their mental health. OBJECTIVES: This study sought to determine the factors affecting psychological distress and sleep duration among CSS. METHODS: We analyzed cross-sectional data from the 2013 Comprehensive Survey of the Living Conditions for Stroke Survivors and CSS. Linked data from 841 pairs of stroke survivors and CSS were extracted. Kessler's Psychological Distress scale (K6) was used to evaluate psychological distress. CSS who slept less than 5 hours per day were classified as having short sleep duration. Factors predictive of psychological distress and short sleep duration were evaluated using multivariable logistic regression analysis with the forward selection method. RESULTS: The mean (SD) age of the CSS was 65.4 (12.5) years. A total of 5.6% of these caregivers presented with serious psychological distress, and 12.0% were sleep deprived. Serious psychological distress was associated with not having someone to consult with, having subjective symptoms within a few days, and having short sleep duration, while having their own houses reduced the risk of serious psychological distress. Furthermore, short sleep duration was associated with stroke survivors in long-term care levels 4 or 5, not having someone to consult with, participation in sponge baths as part of nursing care activities, and having serious psychological distress. CONCLUSIONS: This nationwide survey identified several risk factors for psychological stress and sleep deprivation among CSS and suggests the need for multidimensional approaches to reduce their distress.

Blood Levels of Ammonia and Carnitine in Patients Treated with Valproic Acid: A Meta-analysis.

Objective: Long-term valproic acid (VPA) administration is associated with adverse metabolic effects, including hyperammonemia and hypocarnitinemia. However, the pathogeneses of these adverse events remain unclear, and not enough reviews have been performed. The aim of this study was to conduct a meta-analysis of studies examining blood levels of ammonia and carnitine in patients treated with VPA. Methods: We conducted database searches (PubMed, Web of Science) to identify studies examining blood levels of ammonia and carnitine in patients treated with VPA. A meta-analysis was performed to conduct pre- and post-VPA treatment comparisons, cross-sectional comparisons between groups with and without VPA use, and estimations of the standardized correlations between blood levels of ammonia, carnitine, and VPA. Results: According to the cross-sectional comparisons, the blood ammonia level in the VPA group was significantly higher than that in the non-VPA group. Compared to that in the non-VPA group, the blood carnitine level in the VPA group was significantly lower. In the meta-analysis of correlation coefficients, the blood VPA level was moderately correlated with blood ammonia and blood free carnitine levels in the random effects model. Furthermore, the blood ammonia level was moderately correlated with the blood free carnitine level. Conclusion: Although the correlation between ammonia and free carnitine levels in blood was significant, the moderate strength of the correlation does not allow clinicians to infer free carnitine levels from the results of ammonia levels. Clinicians should measure both blood ammonia and free carnitine levels, especially in patients receiving high dosages of VPA.