E. H. Reynolds

Enhancement of recovery from psychiatric illness by methylfolate

Abstract 41 (33%) of 123 patients with acute psychiatric disorders (DSM III diagnosis of major depression or schizophrenia) had borderline or definite folate deficiency (red-cell folate below 200 μg/l) and took part in a double-blind, placebo-controlled trial of methylfolate, 15 mg daily, for 6 months in addition to standard psychotropic treatment. Among both depressed and schizophrenic patients methylfolate significantly improved clinical and social recovery. The differences in outcome scores between methylfolate and placebo groups became greater with time. These findings add to the evidence implicating disturbances of methylation in the nervous system in the biology of some forms of mental illness.

Chronic Antiepileptic Toxicity: A Review

Introduction .............................................................. Definition ................................................................. Predisposing Factors .......................................................... Classification .............................................................. TheNervousSystem ........................................................ Thecerebellum ......................................................... PeripheralNeuropathy .................................................... Subacute or Chronic Encephalopathy ........................................ Other Mental Symptoms .................................................... ....... ........................................... Folic Acid Deficiency ..................................................... MegaloblasticAnemia ..................................................... Folic Acid and Vitamin B1 Metabolism in Nonanemic Epileptic Patients ................................................ ClinicalImplicatio ns ...................................................... Neonatal Coagulation Defects .............................................. TheSkeletalSystem ........................................................ Metabolic Bone Disease and Vitamin D Deficiency ConnectiveTissue ........................................................... GumHypertrophy ....................................................... Facial Skin Changes .............. : .......................................

Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine.

Cerebrospinal fluid (CSF) S-adenosylmethionine (SAM) levels were significantly lower in severely depressed patients than in a neurological control group. The administration of SAM either intravenously or orally is associated with a significant rise of CSF SAM, indicating that it crosses the blood-brain barrier in humans. These observations provide a rational basis for the antidepressant effect of SAM, which has been confirmed in several countries. CSF SAM levels were low in a group of patients with Alzheimers dementia suggesting a possible disturbance of methylation in such patients and the need for trials of SAM treatment.

Monotherapy or Poly therapy for Epilepsy

Summary: Although anticonvulsant polytherapy has been widely and traditionally used in the treatment of epilepsy, there is little evidence of its advantages over monotherapy. It does, however, lead to problems of chronic toxicity, drug interactions, failure to evaluate individual drugs, and sometimes exacerbation of seizures. There are many causes of polytherapy which could be avoided by more careful monitoring and supervision of therapy. Studies in new, previously untreated referrals suggest there is considerable potential for monotherapy. In the event of failure of optimum monotherapy, the value of polytherapy is not yet clear. In chronic patients on polytherapy there may be scope for careful rationalization to two or sometimes one drug, with reduction in chronic toxicity and sometimes improved seizure control. Reduction of therapy, however, may be impossible or hazardous due to withdrawal seizures. Even after successful reduction, seizure control is much less satisfactory than in new referrals. It is easier to avoid polytherapy than to reduce it. There is a need to define more carefully the limits of effective anticonvulsant therapy.

Phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed adult epilepsy: a randomised comparative monotherapy trial

Recent studies have shown that most newly diagnosed epileptic patients can be satisfactorily treated with a single antiepileptic drug. We therefore undertook a prospective randomised pragmatic trial of the comparative efficacy and toxicity of four major antiepileptic drugs, utilised as monotherapy in newly diagnosed epileptic patients. Between 1981 and 1987 243 adult patients aged 16 years or over, newly referred to two district general hospitals with a minimum of two previously untreated tonic-clonic or partial with or without secondary generalised seizures were randomly allocated to treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform with standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to enter one year remission. The overall outcome with all of the four drugs was good with 27% remaining seizure free and 75% entering one year of remission by three years of follow up. No significant differences between the four drugs were found for either measure of efficacy at one, two, or three years of follow up. The overall incidence of unacceptable side effects, necessitating withdrawal of the randomised drug, was 10%. For the individual drugs phenobarbitone (22%) was more likely to be withdrawn than phenytoin (3%), carbamazepine (11%), and sodium valproate (5%). In patients with newly diagnosed tonic-clonic or partial with or without secondary generalised seizures, the choice of drug will be more influenced by considerations of toxicity and costs.

Randomised comparative monotherapy trial of phenobarbitone, phenytoin, carbamazepine, or sodium valproate for newly diagnosed childhood epilepsy

BACKGROUND The medical treatment of childhood epilepsy is largely influenced by clinical trials in adult patients. We know of only one randomised comparative trial (of two drugs) in newly diagnosed childhood epilepsy. We have undertaken a long-term, prospective, randomised, unmasked, pragmatic trial of the comparative efficacy and toxicity of four standard antiepileptic drugs used as monotherapy in children with newly diagnosed epilepsy. METHODS Between 1981 and 1987, 167 children aged 3-16 years, who had had at least two previously untreated tonic-clonic or partial seizures, with or without secondary generalisation, were randomly allocated treatment with phenobarbitone, phenytoin, carbamazepine, or sodium valproate. The protocol was designed to conform to standard clinical practice. Efficacy was assessed by time to first seizure after the start of treatment and time to achieving 1-year remission. FINDINGS The overall outcome with all four drugs was good. 20% of children remained free of seizures and 73% had achieved 1-year remission by 3 years of follow-up. We found no significant differences between the drugs for either measure of efficacy at 1, 2, or 3 years of follow-up. The overall frequency of unacceptable side-effects necessitating withdrawal of the randomised drug was 9%. This total included six of the first ten children assigned phenobarbitone; no further children were allocated this drug. Of the other three drugs, phenytoin (9%) was more likely to be withdrawn than carbamazepine (4%) or sodium valproate (4%). INTERPRETATION Our data will inform choice of drug and outcome with four of the standard drugs available for newly diagnosed tonic-clonic or partial seizures with or without secondary generalisation in children.

The neuropsychiatry of megaloblastic anaemia.

The neuropsychiatric states of 50 patients with vitamin B12 deficiency and 34 patients with folate deficiency presenting with megaloblastosis in a general hospital were examined and compared. Abnormalities of the nervous system were found in two-thirds of both groups. Peripheral neuropathy was the most common condition associated with vitamin B12 deficiency and affective disorder with folate deficiency. The proportions of patients with organic mental change were similar in the two groups. Subacute combined degeneration of the cord was an uncommon complication and occurred only in the patients with vitamin B12 deficiency. There was no relation between haematological and neuropsychiatric abnormalities. The neuropsychiatry of megaloblastic anaemia seen in this study of patients presenting to haematologists or general physicians contrasts with that reported previously, before haematological techniques for separating the two deficiencies were introduced.

Reduction in polypharmacy for epilepsy.

A two-year prospective study of 40 adult outpatients with chronic epilepsy was carried out in which blood drug concentrations were monitored, and anticonvulsant polypharmacy was reduced to treatment with a single drug in 29 patients (72%). In the year after the reduction of treatment the control of seizures was improved in 16 patients (55%), unchanged in eight(28%), and worse in five (17%). Mental function was improved in 16 (55%). The main reason for failure to reduce to or maintain treatment with a single drug was exacerbation of seizures during the difficult withdrawal period, especially in patients with frequent seizures, taking several drugs, or with additional neuropsychological handicaps. It is more difficult to reduce polypharmacy than to avoid it in the first place. Polypharmacy may sometimes aggravate control of seizures.

METHYLATION AND MOOD

S-adenosylmethionine (SAM) has antidepressant properties. The commonest neuropsychiatric complication of severe folate deficiency is depression. These independent observations suggest that methylation in the nervous system may underlie the expression of mood and related processes and may be implicated in some affective disorders; suggest new biological approaches to the understanding and treatment of some affective disorders; and may explain why methionine sometimes aggravates schizophrenia.

Anticonvulsant-induced dyskinesias: a comparison with dyskinesias induced by neuroleptics.

Anticonvulsants cause dyskinesias more commonly than has been appreciated. Diphenylhydantoin (DPH), carbamazepine, primidone, and phenobarbitone may cause asterixis. DPH, but not other anticonvulsants, may cause orofacial dyskinesias, limb chorea, and dystonia in intoxicated patients. These dyskinesias are similar to those caused by neuroleptic drugs and may be related to dopamine antagonistic properties possessed by DPH.