A retrospective study on the diagnosis and treatment of dementia in patients referred to the Sagamihara Municipal Medical Center for Dementia for consultation.

AIM: In Japan, the Orange Plan was formulated in 2013 to promote community-based integrated care systems, and in 2015, it was revised as the New Orange Plan. Since the introduction of these programmes, adequate research has not been carried out on how these measures affect regional dementia care. The aim of this study was to investigate the state of community-based dementia treatment through a survey of medical consultation pathways, including dementia diagnosis, at the Sagamihara Municipal Medical Center for Dementia. METHODS: The participants included 1480 patients (585 men, 895 women) who presented for consultation at the Sagamihara Municipal Medical Center for Dementia for a differential diagnosis or treatment of dementia. The relationship between the path leading to medical consultation before pharmacotherapy and post-consultation diagnosis was investigated. RESULTS: Significantly more participants who presented for consultation without a referral were not diagnosed with dementia than diagnosed. Furthermore, among participants referred from a non-psychiatric clinic, significantly more patients were diagnosed with dementia than not. A significant difference was observed in a comparison of facility types and the use or non-use of anti-dementia drugs. Notably, the rate of anti-dementia drug prescriptions was significantly higher in psychiatric hospitals and non-psychiatric clinics. Furthermore, it is possible that approximately 30% of anti-dementia drugs prescribed at each facility were not covered by insurance. CONCLUSION: Community-based integrated care systems aim to promote collaboration within each region aimed. However, appropriate pharmacotherapy methods for dementia patients have not been adequately communicated to non-specialist physicians and local residents. For this reason, human resource solutions are needed to help medical staff deepen their understanding of dementia so that they can better provide dementia support to patients.

Changes in job stress and coping skills among caregivers after dementia care practitioner training.

BACKGROUND: Dementia care practitioner training is essential for professional caregivers to acquire medical knowledge and care skills for dementia patients. We investigated the significance of training in stress management by evaluating caregivers' job stress and coping style before and after they have completed training. METHODS: The subjects included 134 professional caregivers (41 men, 93 women) recruited from participants in training programmes held in Kanagawa Prefecture from August 2008 to March 2010. A survey using a brief job stress questionnaire and a coping scale was carried out before and after they completed their training. A t-test and multiple regression analysis were performed to evaluate the effects of the training. RESULT: After the training, the scores of modifiers on the job stress scale and of the coping scale increased, whereas the scores of stress reactions on the job stress scale decreased. However, there were no changes in participants' subjective cognition concerning their workplace environment. Furthermore, the change in stress reaction score tended to correlate with the change in consultation score in all participants and with the change in problem-solving and consultation in male participants. Among female participants, the change in stress reaction score tended to correlate with change in support from superiors and colleagues as modifiers. The factors that correlated to the change in stress reaction score differed between genders. CONCLUSION: The findings suggest that training caregivers improves their stress reaction and coping skills.

[Evaluation of Efficacy and Adverse Effects of Symptomatic Drugs for Alzheimer Disease].

The symptomatic drugs used for the treatment of Alzheimer disease (AD) are considered to exert their effect by suppressing the progression of dementia symptoms. Although clinical trials conducted on the drugs in Japan have revealed statistically significant differences in assessments of change in cognitive function, three of the four drugs have not shown any statis- tically significant differences in the clinician's global impression. There are many overseas reports indicating the efficacy of these drugs, whereas many other reports also indicate that the assessment procedures themselves are difficult and have many limitations. In order to determine the efficacy of the drugs in clinical practice, physicians need to determine whether the progression of dementia symptoms is inhibited. However, AD symptoms vary and are affected by the patient's living environment, personal relationships, and other factors. Although there are certain trends in the time of symptom onset according to disease stages, the symptoms progress by the year and greatly vary among patients. Comparison of progression rates to the average rate is a primary requirement for measurement of the drugs' inhibitory effects on progression. However, because progression rates greatly vary among patients, it is difficult to determine the average rate. In principle, drug therapy should be discontinued if it is not effective. However, because it is difficult to determine whether the drugs are effective, they are likely to be unnecessarily prescribed even when there is a lack of efficacy. The typical adverse effects of cholinesterase inhibitors (ChEIs) include gastrointestinal, neuropsychiatric, extrapyramidal, and cardiovascular symptoms. Transdermal patch formulations of ChEIs may cause pruritus. N-methyl-D-aspartic acid receptor antagonists may also cause various adverse effects. Patients with AD often have impaired ability to recognize psychosomatic changes and to inform people around them of the changes. Thus, detection of adverse effects is likely to be delayed. If the somatic symptoms caused by adverse effects appear as a lack of animation or irritation, the changes due to adverse effects will be likely misunderstood as symptoms caused by progression of AD, behavioral and psychological symptoms. Since the four symptomatic drugs became available, there have been more opportunities to discuss how the use of the drugs can be differentiated. However, the need for using these drugs should be reevaluated before differentiation of their use.

[Practice of Community Psychiatry for the Treatment of Depression].

The practice in the psychiatric division of Kitasato University East Hospital and Kitasato University Hospital has been emphasizing community psychiatry. The problems and proposed solutions are discussed. 1. Both hospitals are core hospitals located in Sagamihara City (Kanagawa Prefecture), which has no municipal hospital. 2. Kitasato University East Hospital has 94 beds in two closed wards and is one of the hospitals designated for psychiatric emergencies in Kanagawa Prefecture. 3. Over the last 10 years aroud Sagamihara City, cooperation between psychiatric hospitals and outpatient clinics, the treatment of patients with mental and physical diseases, improvement of the quality of psychiatric practice, emergency psychiatry, and imbalances in the incomes and workloads of psychiatrists have been problematic. 4. Problems that need to be solved in practice to treat depression involve inappropriate pharmacotherapy, disease mongering (the practice of widening the diagnostic boundaries of illnesses in order to expand the markets for drug treatment), clinical skills of psychiatrists, profitability, and medical institutions which cannot cope with regular patients in an emergency. 5. Up to now, we have established a consulting service ("Second opinion" clinic) at Sagamihara Mental Health and Welfare Center (Municipal institution), recommended patients' consultation with family pharmacists, and increased the frequency of conferences for doctors without the support of pharmaceutical companies. 6. In order to develop community psychiatric services for patients with depression, the author is preparing a community-based critical path for depression as well as community-based treatment network in the Sagamihara area. 7. The author believes that the urgent issue necessitates transparency and the increased visibility of psychiatric services.

[Conflict of Interest Guidelines of the Japanese Society of Psychiatry and Neurology: Current Status and Considerations in the Area of Psychiatry].

In 2011, the Japanese Society of Psychiatry and Neurology released the Guidelines on Conflict of Interest(COI) in Clinical Research and detailed regulations. According to the Guidelines, the COI Committee has been engaged in COI management for a one-year trial period. The members of the Society have to disclose their COIs at the time of presentations, manuscript submissions, and publications; the board and committees members have to disclose their COIs to the President of the Society; and the President reports these COI disclosures to the COI Committee. In this article, we provide a summary of this year's COI disclosures: among the 455 board and committees members, 297 were without COIs (68.5%); 98 (excluding the following two problematic cases) disclosed COIs (23.1%, excluding the following two cases); two cases were discussed regarding whether or not they were problematic (0.44%); 11 (2.4%) cases have not yet been reviewed because of a delay in disclosure; and 25 cases have yet to be disclosed (5.5%). Responding to serious COI-related affairs in other disease areas, public interest in the COI ssue has been increasing. Additionally, the Japanese Pharaceutical Manufacturers Association (JPMA) implemented Transparency Guidelines, and companies are disclosing their payments for lectures or manuscript fees to individual researchers. We should foster a deeper understanding of the concept of COI and discuss COI management in society more extensively.

The relationship between emotional suppression and psychological distress in breast cancer patients after surgery.

OBJECTIVE: The purpose of this study was to examine the relationship between emotional suppression and psychological distress in breast cancer patients after surgery. We examined this relationship using questionnaires at the first visit to the breast cancer outpatient clinic at our hospital and after surgery, as well as interviews after surgery. METHODS: A total of 31 breast cancer patients were asked to complete the Courtauld Emotional Control Scale and the Profile of Mood States at their first visit to the outpatient clinic. Patients were also asked to complete the Profile of Mood States between 1 and 6 months after surgery. Trained clinical psychologists conducted the interviews, asking patients to speak freely about their current anxieties, worries and thoughts. Based on the median Courtauld Emotional Control Scale score of 42 points, participants were divided into emotional suppression and emotional expression groups. RESULTS: The Total Mood Disturbance score, as well as each of the subscale (except vigor) scores of the Profile of Mood States, were significantly higher in the emotional suppression group than the emotional expression group. The emotional suppression group expressed significantly more negative emotions and fewer positive emotions than the emotional expression group. CONCLUSIONS: Patients with emotional suppression felt and expressed more psychological distress after surgery. This finding highlights the need for medical staff to comprehend the psychological traits of breast cancer patients, including emotional suppression, in the early stages of breast cancer in order to provide adequate psychological support.

[Implementation of Guidelines on Conflict of Interest in Clinical Research of the Japanese Society of Psychiatry and Neurology: actual status and future perspectives].

In May 2011, the Japanese Society of Psychiatry and Neurology released their Guidelines on Conflict of Interest (COI) in Clinical Research and detailed regulations. These guidelines cover clinical research, although each committee of the society may have a policy to cover basic research as well as clinical research. The COI Committee implemented the guidelines, including a one-year trial period. According to the guidelines, members of the society have to disclose their COIs at the time of presentations, manuscript submissions, and publications; the board and committees members have to submit their COIs to the president of the society. During the trial period, the latter was limited to the four committees involved in the development of the guidelines: Conflict of Interest; Pharmaceutical Affairs; Research Ethics; and Editorial Committees. The COI Committee reviewed the COIs submitted by the board and committee members. The COI Committee found that, among the 382 board and committee members, 298 were without COI; 31 COIs were regarded by one committee member as not necessary to be circulated to all the attending members (total of these 2 categories: 329, 87%); 31 COIs (8%) were regarded as necessary to be circulated; and 18 cases (4.7%) were problematic: not submitted or explicit rejection of submission. Considering the seriousness of scientific misconduct by a researcher in another disease area who resigned his professorship and is now under investigation, we should further discuss the implementation of our COI guidelines.

[Frequent psychiatric symptoms in the elderly patients].

In Japan, the elderly patients generally account for high percentages of both inpatients and outpatients. As aging of the population accelerates, it will become increasingly important to properly detect, assess and intervene for psychiatric symptoms of the elderly patients to establish differential diagnoses. Thus, we must assess all existing psychiatric symptoms by keeping in mind the brain/physical conditions and social circumstances of the elderly patients and considering not just their complaints but also objective information from other organizations/services. In doing so, particular emphasis should be placed on assessing consciousness. Decreased alertness should not be dismissed as "old age". Medical professionals and caregivers must carefully assess psychiatric symptoms in the elderly patients while respecting their self-esteem.

[How to improve the system of classification and diagnosis of depressive syndrome].

The confusion regarding the system of classification and diagnosis of depressive syndrome must be promptly addressed. One issue is to discriminate between antidepressant-effective and -resistant depression. Another is to diagnose depressive disorders even if depression is mild. It is important as an immediate response to appropriately use DSM and ICD and the treatment guideline of the Japanese Society of Mood disorders. The system of dimensional classifications and diagnoses of depressive syndrome, including the axes of symptoms, social backgroud, and social function, should be more fully utilized in psychiatry. It may be possible to modify it according to associated areas such as occupational mental health, liaison psychiatry, and suicide prevention.

Influence of Psychotropic Pro Re Nata Drug Use on Outcomes in Hospitalized Patients with Schizophrenia.

Objective: In the treatment of patients with schizophrenia, pro re nata (PRN) drugs are commonly prescribed for medical indications such as agitation, acute psychiatric symptoms, insomnia, and anxiety. However, high-quality evidence supporting the use of PRN medications is lacking, and these drugs are administered on the basis of clinical experience and habits. Therefore, the actual use of psychotropic PRN drugs and its influence on the patients' outcomes need to be investigated. Methods: This study included 205 patients who underwent inpatient treatment for schizophrenia. We investigated the prescription of psychotropic drugs before admission and at discharge, as well as the dosing frequency of PRN drugs during hospitalization. We also examined the influence of psychotropic PRN drug use on hospitalization days, antipsychotic polypharmacy, and readmission rates. Results: Patients who used psychotropic PRN drugs during hospitalization had significantly longer hospitalization days (p = 7.5 × 10-4) and significantly higher rates of antipsychotic polypharmacy (p = 2.4 × 10-4) at discharge than those who did not use psychotropic PRN drugs. Moreover, a higher number of psychotropic PRN drugs used per day was associated with higher readmission rates within 3 months of discharge (p = 4.4 × 10-3). Conclusion: Psychotropic PRN drug use is associated with prolonged hospitalization, antipsychotic polypharmacy, and increased readmission rates in inpatients with schizophrenia. Therefore, psychiatric symptoms should be stabilized with regularly prescribed medications without the extensive use of psychotropic PRN drugs. Moreover, a system for monitoring and reexamining PRN drug use needs to be established.

Analysis of depression in asthmatic patients using the Japanese version of Patient Health Questionnaire-9.

BACKGROUND: Previous studies show that depression plays an important role in asthma. However, the association between asthma control and severity, and depression is inconclusive. METHODS: To investigate the association between asthma control and severity, and depression, we assessed differences in asthma control and asthma severity between groups with various grades of depressive state as defined by the PHQ-9 score using data from the Japanese version of Patient Health Questionnaire-9 (J-PHQ-9) and a questionnaire survey including the Asthma Control Test (ACT). RESULTS: The ACT scores in the symptom-screen positive (SP) and major/other depressive disorder (MDD/ODD) group were significantly lower than those in the symptom-screen negative (SN) and non-MDD/ODD groups, respectively. The rate of step1 and of step 3 and 4 in the SP group were significantly lower and higher than those in the SN group, respectively. When the SP group was divided into three, that is minimal, mild, and more than mild (MTM) depressive state subgroups, the ACT scores in the mild and MTM depressive state subgroups were significantly lower than those in the minimal depressive state subgroup. When the MTM subgroup was divided into moderate, moderate-severe and severe depressive state groups, however, there was no significant variation in ACT score and asthma severity among these three depressive state groups. CONCLUSIONS: This study is the first, large-scale investigation of the use of the J-PHQ-9 in asthma patients. Using the J-PHQ-9 and the questionnaire, there was a clear association between asthma control and severity, and depression. As the depression became more severe, the existence of other depression-associated factors unrelated to asthma control and severity might be assumed, although further investigation will be required.

[How to prescribe psychotropic drugs in primary care].

What primary care physicians should consider when prescribing psychotropic drugs was described. (1) Diagnosis of mental disorders and target symptoms of pharmacotherapy should be clarified before prescribing psychotropic drugs. (2) Psychological treatments are as important as pharmacotherapy. (3) Psychotropic drugs should begin from a small amount and increased gradually. (4) Placebo effects are large in the pharmacotherapy of mental disorders. (5) Motor ataxia, dizziness, delirium and paradoxical reaction should be noted in prescribing benzodiazepines. (6) Headache, diarrhea, nausea, and activation and withdrawal syndromes are often seen in the treatment using SSRIs, though their side effects are believed to be few.

[Emotional suppression and psychological responses to a diagnosis of breast cancer].

This study examined the relationship between emotional suppression and psychological distress in response to a diagnosis related to breast cancer. After their first visit, 31 patients with breast cancer and 90 with benign breast conditions completed the courtauld emotional control scale (CECS) and the profile of mood states (POMS) and were interviewed about their concerns after being diagnosed. Breast cancer and benign breast condition patients were divided into separate emotional suppression groups or emotional expression groups based on their median CECS score. The POMS scores of breast cancer patients were higher than those of benign breast condition patients; scores in the emotional suppression groups were higher than in the emotional expression groups. Breast cancer patients in the emotional suppression group expressed more negative emotions and fewer positive emotions than benign breast condition patients. Our results suggest that patients who suppressed their emotions experienced and reported more psychological distress when diagnosed with breast cancer.

[Integrated care in community psychiatric medicine].

A common factor underlying the current issues in psychiatric medicine is the lack of visualization of the process of medical practice. An approach to visualization of this process facilitates solving the problems faced in this field. Psychiatric care often comes into effect based on the cooperation of a number of institutions and professions, rather than being completed within a single institution. To visualize the process of psychiatric care, it is important to establish face-to-face relationships between patients and psychiatrists, introduce the care system in which two doctors share the responsibility of managing a single patient, and formulate an integrated care pathway in the community. Although many consider the clinical pathway concept to be unsuitable for psychiatric practice, it is possible to introduce a community cooperation care pathway into psychiatric practice if consideration is first given to several significant issues. Community cooperation activities in the field of psychiatric care including the integrated care pathway help to harmonize the efforts of supporters, patients, and families, and increase the overall sense of security. It is also expected that such activities will allow us to obtain useful indices for assessing the quality of care.

Psychological stress of emergency medical staff after the largest mass murder incident in post-World War II era.

BACKGROUND: A mass-casualty incident occurred on July 26, 2016, at Tsukui Yamayuri-en, which is a welfare facility for people with intellectual disabilities. Nineteen residents with intellectual disabilities were killed, and 26 other residents and staff members were injured. Kitasato University Hospital Emergency and Disaster Medical Center treated many patients in serious condition at the site and in the hospital. AIMS: The authors investigated the symptom severity and distributions of posttraumatic stress disorder (PTSD) among the emergency medical staff in charge. The subjects of this study were the staff members, mostly working at the Emergency and Disaster Medical Center, who treated the people injured in the incident. METHODS: We conducted a questionnaire survey using Impact of Event Scale-Revised (IES-R) on 104 staff members, and 79 responded. RESULTS: The IES-R scores of nurses were significantly higher than those of doctors. There was no significant difference in the scores between male and female staff members, and there was no correlation between the score of each IES-R subscale and age. CONCLUSION: Results suggest that mental care should be provided to emergency medical staff, especially nurses who treat trauma patients involved in disasters and heinous crimes.

Predictors of psychological distress after diagnosis in breast cancer patients and patients with benign breast problems.

OBJECTIVE: The objective of this study was to determine how age and psychological characteristics assessed prior to diagnosis could predict psychological distress in outpatients immediately after disclosure of their diagnosis. METHODS: This is a longitudinal and prospective study, and participants were breast cancer patients and patients with benign breast problems (BBP). Patients were asked to complete questionnaires to determine levels of the following: trait anxiety (State-Trait Anxiety Inventory), negative emotional suppression (Courtauld Emotional Control Scale), life stress events (Life Experiences Survey), and psychological distress (Profile of Mood Status) prior to diagnosis. They were asked to complete a questionnaire measuring psychological distress after being told their diagnosis. We analyzed a total of 38 women diagnosed with breast cancer and 95 women diagnosed with a BBP. RESULTS: A two-way analysis of variance (prior to, after diagnosis × cancer, benign) showed that psychological distress after diagnosis among breast cancer patients was significantly higher than in patients with a BBP. The multiple regression model accounted for a significant amount of variance in the breast cancer group (model adjusted R(2) = 0.545, p < 0.001), and only trait anxiety was statistically significant (ß = 0.778, p < 0.001). In the BBP group, the multiple regression analysis yielded a significant result (model adjusted R(2) = 0.462, p < 0.001), with trait anxiety and negative life changes as statistically significant factors (ß = 0.449 and 0.324 respectively; p < 0.01). CONCLUSIONS: In both groups, trait anxiety assessed prior to diagnosis was the significant predictor of psychological distress after diagnosis, and might have prospects as a screening method for psychologically vulnerable women.

Validity and reliability of the Japanese version of the Temperament and Character Inventory: a study of university and college students.

OBJECTIVE: The Temperament and Character Inventory (TCI) is a widely used self-report measure of adult personality. METHOD: We studied 586 Japanese university and college students with the 125-item version of the Japanese TCI. RESULTS: The factor structure of the TCI scales was similar to that reported in other languages. Depression was positively correlated with Novelty Seeking and Harm Avoidance but inversely correlated with Persistence, Self-Directedness, and Cooperativeness. Good Self-Image in the framework of adult attachment was correlated positively with Self-Directedness but inversely with Harm Avoidance and Reward Dependence. Good Other-Image in the framework of adult attachment was positively correlated with Reward Dependence and Cooperativeness. The scores of the TCI scales were stable over a time span of 1.5 to 2 months. CONCLUSION: The Japanese version of the TCI may be a valid and reliable measure of temperament and character, at least among the adolescent and young adult population.

Changes in communication skills of clinical residents through psychiatric training.

AIM: The objective of this study was to clarify whether the communication skills (CS) of clinical residents change before and after psychiatric training and, if so, what factors are related to the change. METHODS: The 44 clinical residents who agreed to participate in this study were provided with an originally developed self-accomplished questionnaire survey on CS (communication skills questionnaire [CSQ]) and a generally used questionnaire on self-esteem, anxiety, and depressive mood considered to be related to CS at the start and end of a 2-month psychiatric training session. Statistical analysis was conducted for the 34 residents who completed both questionnaires. RESULTS: The CSQ score (t[32]: -2.17, P < 0.05) and assertive CS score, a subfactor of the CSQ (t[32]: -2.74, P < 0.01), were improved after the training. The cooperative CS score also tended to increase after the training. The amounts of change in total CS score and cooperative CS score, which increased after the training, correlated positively with self-esteem and negatively with anxiety and depressive tendency. The amount of change in assertive CS score showed a weakly positive correlation with self-esteem. CONCLUSIONS: The results suggested that CS, including assertive CS and cooperative CS, were improved by the psychiatric training. Increasing self-esteem and reducing the tendency toward depression and anxiety are considered to be useful for further improving CS.

Subjective experiences of family caregivers of patients with dementia as predictive factors of quality of life.

BACKGROUND: The aim of the present study was to investigate predictive factors of quality of life (QOL) in home caregivers of patients with dementia. METHODS: A total of 118 home caregivers (48 male, 70 female) were asked to complete the World Health Organization (WHO) Quality of Life 26 (WHO/QOL-26) questionnaire, the Pines Burnout Measure (BM), and the Beck Depression Inventory, second edition (BDI-II). Patient demographics and clinical data regarding cognitive impairment, neuropsychiatric symptoms, and dementia severity were obtained from medical records. RESULTS: Spearman rank correlation coefficients revealed that caregiver QOL was significantly correlated with patients' neuropsychiatric symptoms (r=-0.19; P < 0.05), as well as depressive symptoms (r=-0.59, P < 0.01) and burnout (r=-0.59, P < 0.01) in caregivers. Stepwise multiple regression analysis revealed that depressive symptoms in caregivers was the strongest predictor for caregiver QOL (R(2) = 0.37, P < 0.001) and that caregiver QOL was best predicted by the combination of depressive symptoms, burnout, and the cognitive impairment of patients (R(2) = 0.46, P < 0.05). CONCLUSION: The results of the present study demonstrate that subjective experiences of caregivers are more strongly correlated with caregiver QOL than patient-related variables and are thus powerful determinants of caregiver QOL. These findings suggest that caregiver intervention, which aims to increase QOL, may benefit from the incorporation of strategies to reduce depressive symptoms and burnout.

Factors associated with blood carnitine levels in adult epilepsy patients with chronic valproic acid therapy.

AIMS: Valproic acid (VPA) is a widely used antiepileptic drug for the treatment of epilepsy, seizures, and bipolar and psychiatric disorders. A deficiency of carnitine, a compound involved in energy production, is associated with chronic VPA use. However, the clinical factors affecting blood carnitine levels and their pathophysiology remain unclear. Hence, we aimed to identify the factors that correlated with serum carnitine levels in epilepsy patients receiving chronic VPA therapy. METHODS: This observational study included 138 epilepsy patients receiving chronic VPA therapy. Serum total and free carnitine levels, routine blood tests and drug concentrations were assessed. The correlation between carnitine levels and other factors were calculated using Spearman's rank correlation coefficients, and a principal component analysis (PCA) and a multiple linear regression analysis were performed. RESULTS: Overall, serum free carnitine levels showed significant negative correlations with epilepsy duration, VPA treatment duration, daily VPA dose, and blood VPA concentration. A significant positive correlation was observed with erythrocyte count, hemoglobin levels, and creatinine levels. Of the 138 patients, 21 (15.2 %) with serum free carnitine levels of <20 µmol/L had significantly longer disease duration, a higher daily VPA dose, and lower blood clobazam concentrations. In the 48 VPA monotherapy patients, serum free carnitine levels showed a significant negative correlation with disease duration and duration of VPA therapy. Furthermore, in the 2.1 % patients receiving VPA monotherapy, serum free carnitine levels were <20 µmol/L. PCA resulted in seven factor solution (eigenvalue >1; 71.67 % explained variance). Component 1 clearly revealed the maximal loading for serum free carnitine level (.792) and the most negative loading for disease duration of epilepsy (-.595). A linear regression analysis revealed that the duration of epilepsy, serum creatinine level, and daily dose of VPA were significant (p < .01) factors that affected serum free carnitine levels. CONCLUSIONS: The effects of combination therapy with VPA and other anti-epileptic drug(s) on carnitine levels are higher than that of VPA monotherapy. Additionally, epilepsy duration may affect serum free carnitine level.