Subacute myelo-optico-neuropathy (SMON) is a neurological disorder caused by an anti-diarrhea drug, chinoform. It was not easy to find the cause of SMON, because chinoform was believed to be one of safe drugs. Prescription of chinoform was stopped temporary to investigate the cause of SMON, then there were no new cases of SMON and SMON was confirmed to be caused by chinoform. It was not easy to find all of the side effects of new drug on clinical trials, especially adverse drug reactions (ADRs) emerged following a long administration. Because the duration of trials was not long enough and the number of patients was small. Drugs, especially new ones, should be kept under watch following marketing to find ADRs as soon as possible. Insert packages of most drugs for neurological or mental disorders give warn not to let patients to drive because of sleepiness induced by the drugs. However there are no information showing how much risky to drive on taking the drug. It is not appropriate to inhibit driving legally on taking the drug, but the drug should have any information in the insert package how it is risky on driving under the drug.
 Drug-drug interactions are one of important issues on the treatment. The information in the insert package says physicians should be careful in prescribing drugs on drug-drug interactions. However, in many drugs applied in the treatment, there are no information how much the interaction affects pharmacokinetics of the drug in the insert package. It is essential to know the pharmacokinetics of drug interactions. In putting the warning of drug-drug interactions, the information how much it effects the pharmacokinetics of the drug should be given in the insert package.
 Pharmacovigilance is an essential system to apply new drugs to the therapy. Research and development of new drugs is promoted by pharmaceutical companies and physicians are required to cooperated to develop new drugs, however, on pharmacovigilance, it is essential for physicians to collect the information from their patients properly and to report it promptly. All of physicians should have training on the idea and action of pharmacovigilance on drug treatments.

Objective: DNA methyltransferase 1 (DNMT1) is crucial to maintaining methylation during DNA replication and DNA repair. DNMT1 mutations have been identified in two neurological syndromes, including hereditary sensory and autonomic neuropathy type IE (HSAN IE) with dementia and hearing loss and autosomal dominant cerebellar ataxia, deafness and narcolepsy. It is likely that DNMT1 mutations lead to various symptoms of the central and peripheral nervous system. The aim of this study was to examine the clinical characteristics, especially the initial symptoms, in the cases of DNMT1 mutations. Methods: We investigated the clinical manifestation and examination findings of four cases of HSAN IE from one family with the DNMT1 mutation c.1531Y>C (p.Try511His). Results: All four cases exhibited sensory neuropathy, cerebellar ataxia, and hearing loss, all of which were demonstrated by the audiograms. The initial symptoms of the four cases included hearing loss (n=1), gait disturbance (n=1), and depressive mood (n=2). Depressive symptoms are reported in some cases with HSAN IE, however, there are currently no published reports that describe them as primary symptoms. The CSF orexin level was measured in three cases, revealing normal values in two cases and intermediate values in one case, in which the patient exhibited rapid eye movement (REM) sleep behavior disorder. Conclusion: Our findings suggest that in cases with HSAN IE or the DNMT1 mutation, psychiatric symptoms should be taken into account as one of the initial manifestations of the disease.