[A case report of mania precipitated by use of DHEA]. / A propos d'un cas de manie sous DHEA.

Dehydroepiandrosterone (DHEA) and its sulfate ester metabolite (DHEA-S) are precursors to testosterone and, to a lesser extent, to estrogen, and, for both sexes, they are produced in the adrenal cortex. They are among the most abundant steroids in the human body, yet their physiological roles remain unknown. DHEA and DHEA-S appear to have diverse biochemical activities, including actions within the central nervous system. So DHEA is produced in the central nervous system as well as the human adrenals and is present in the brain, concentrated in limbic regions, in levels much higher than other steroids. DHEA has been postulated to function as an excitory neuroregulator, antagonizing g-aminobutyric acid transmission. The main characteristic of DHEA is that its level of concentration in plasma varies throughout life, such level being low during the early childhood and after the age of 60 years. Adrenal production and serum concentrations of DHEA are then known to peak between ages 25 and 30 years and thereafter decrease with age, severe illness and chronic stress. The decrease of DHEA over time would appear to be responsible for morbidity related to aging process. Previous reports have found low levels of DHEA in association with physical and with frailty in the elderly (immunosenescence, increased incidence of osteoporosis, atherosclerosis and cancer, decreased cognitive functions and/or well-being). As it has been touted as a fountain of youth and a sexual tonic and promoted for a variety of illnesses associated with aging, DHEA is widely available over all the United States (since 1994) as a dietary supplement. In France, as a result of a massive advertising campaign, DHEA is already the subject of a widespread use and a growing demand although it has not yet been approved by the relevant authorities for sale as drug to the public. In practice, DHEA is prescribed and delivered under the sole responsibility of both doctor and chemist who ascertain the benefit-risk ratio and the quality of the product. DHEA may then be purchased on the internet or in the form of magistral preparations delivered on the basis of such prescription. Accordingly, there is little information or data on efficacy, drug interactions, results of long-term use, abrupt discontinuation or potential adverse effects related to the use of DHEA. We report a case of mania possibly precipitated by the use of high doses of DHEA (150-200 mg/day at the time of presentation) during several weeks in a 68 years old man who had already been hospitalized for an acute mania many years ago. Although, in this case, the patient suffered a bipolar diathesis in the past, oral DHEA may have played a role in the induction of his acute manic episode. Further research is required to assess the mood effects of DHEA, including its potential risk for patients with bipolar disorder.

[Chloral hydrate: a hypnotic best forgotten?]. / L'hydrate de chloral, un hypnotique à oublier?

Synthesised by Justin Liebig in 1832 chloral hydrate is one of the oldest synthetic agents. Since 1869 it has been in use for hypnotic or sedative purposes. Chloral hydrate was used a lot from the end of the 19th century to the middle of the 20th century. Since then chloral hydrate has been less frequently in use as a hypnotic. In the 1990's, the principal use of chloral hydrate in pediatrics was the sedation of children for minor surgery during dental or diagnostic procedures. In general practice, it is an analgesia found in topical preparations. It was known as safe and easy to use. Now it is shown to be potentially dangerous (risk of death in case of intoxication) and there is doubt about genotoxicity and carcinogenecity. The pharmacological property was known in 1948 when Butler discovered the principal active metabolite, trichloroethanol. The gastro-intestinal tract rapidly absorbs chloral hydrate after oral or rectal use. The sedative and hypnotic effects appear in 20 to 60 minutes. The main metabolites [trichloroethanol (TCE) and trichloroacetic acid (TCA)] are formed by hepatocytes and erythrocytes. The half-life of chloral hydrate is short (a few minutes), the half lives of the metabolics are longer, 8 to 12 hours for TCE and 67 hours for TCA. The affinity for lipids is high. It is eliminated principally by the kidneys. Its mechanism of action is unknown. It is a depressor of the SNC, and the sedation is attributed to chloral hydrate and the hypnotic effect to TCE. The interactions appear with: alcohol, anticoagulants, amitriptyline and furosemide. The use of flumazenil (a gaba antagonist), in case of intoxication, indicates a possible action of GABA. The posology is usually between 0.5 to 2 g per day. Chloral hydrate is taken during meals to prevent gastric irritation. The main side effects are digestive, cardiologic (risk of rhythm disorder), dermatologic, neuropsychiatric (withdrawn, delusions, hallucination, dependence) and ophthalmologic. Death occurs after absorption of doses of around 10 g of hydrate chloral, some cases were reported with 5 g. The use of hydrate chloral is contra-indicated in cases of gastric ulcers, hepatic insufficiency, porphyry, respiratory insufficiency, association with anticoagulants and hyper sensibility. Nowadays should we be using chloral hydrate in cases of insomnia in adult and older people? A recent preclinical working group of the French Agency for evaluation of medicinal products reassessed the benefit/risk ratio of chloral hydrate. Many references are found about genotoxicity and carcinogenicity in recent literature. In France, since the end of 2000, chloral hydrate has been withdrawn from many medications for external use in dermatology and in stomatology. Chloral hydrate can be used as a pediatric sedative only once in a lifetime. The psychiatric indication for insomnia is no longer justified and especially in older people.

[Use of methylphenidate in adults with attention deficit disorder with hyperactivity]. / Utilisation du méthylphénidate chez l'adulte dans le trouble: déficit de l'attention avec hyperactivité.

Attention deficit, hyperactivity disorder was recently described in adults. The clinical individualization of this syndrome progressed but the categorical approach remains to be entirely completed. The residual form of the childhood disorder does not generate diagnostic problem when childhood previous history is known. ADHD without childhood history refer us to retrospective difficulties of diagnosis and various evolutions of the infantile form linked or not, with other psychiatric pathologies. Etiology remains unknown, hypothesis of an hereditary disfunction of neurotransmitters is the more studied. These patients can benefit from a psychostimulant treatment. Four controlled studies with methylphenidate demonstrated to be significantly superior to placebo. Even if there are methodological difficulties not resolved (comorbidity, homogeneous population) results are encouraging.