The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression and Mood Disorders.

Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the available data on ten AEDs - valproate, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide, gabapentin and tiagabine - in an attempt to assess evidence for the efficacy of AEDs in the treatment of aggression in pediatric populations. Our review revealed modest evidence that some of the AEDs produced improvement in pediatric aggression, but controlled trials in pediatric bipolar disorder have not been promising. Valproate is the best supported AED for aggression and should be considered as a first line of treatment. When monotherapy is insufficient, combining an AED with either lithium or an atypical anti-psychotic can result in better efficacy. Additionally, our review indicates that medications with predominately GABA-ergic mechanisms of action are not effective in treating aggression, and medications which decrease glutaminergic transmission tended to have more cognitive adverse effects. Agents with multiple mechanisms of action may be more effective.

Neuropsychiatric sequelae of neuroleptic malignant syndrome.

The authors review the literature on persistent sequelae of neuroleptic malignant syndrome (NMS). They highlight the clinical presentations, assessment, and management of persistent sequelae and stress the need to take preventive steps to minimize their occurrence. The authors conducted a Medline and PubMed search for papers on residual sequelae of NMS. They cross-referenced the available papers and "operationalized" the diagnostic criteria for persistent neuropsychiatric sequelae. A total of 31 cases of neuropsychiatric sequelae of NMS were identified. With reduction in mortality from NMS, persistent sequelae of NMS have assumed clinical importance. Long-term sequelae persist for weeks to months after amelioration of an acute episode. Individuals with a preexisting CNS insult are more predisposed to develop persistent sequelae. A high index of awareness for persistent sequelae is warranted because antipsychotics are widely used for psychiatric disorders besides schizophrenia. Awareness of such outcomes and the use of evidence-based strategies to minimize risk factors will help clinicians in reducing the persistent sequelae of NMS.

The syndrome of irreversible lithium-effectuated neurotoxicity.

OBJECTIVES: Persistent sequelae of lithium intoxication gained clinical attention in the 1980s and were named Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT). The authors review the published cases of SILENT reported in the literature and discuss various clinical manifestations. METHODS: The authors' inclusion criteria included persistence of sequelae for at least 2 months after the cessation of lithium administration. They conducted a MEDLINE and Pub Med search for journal articles from the year 1965 to 2004. They also cross-referenced available papers. RESULTS: The authors identified 90 cases of SILENT in peer-reviewed publications. Persistent cerebellar dysfunction was the most commonly reported sequela. Other atypical presentations have also been reported. CONCLUSION: Although the biologic mechanism remains unclear, the authors hypothesize that the putative cause of SILENT is demyelination caused by lithium at multiple sites in the nervous system, including the cerebellum. Recent advances in the understanding of the molecular basis of lithium-induced neurotoxicity may be able to provide a means of defining a pathway associated with the long-term prophylactic properties of lithium, distinct from its toxicity profile. This identification of differential gene expression patterns that distinguish between therapeutic and toxic actions of lithium may help in the discovery of new drugs for mood stabilization. Clinically and heuristically, it is important to raise the awareness of this syndrome so that clinicians are able to avoid it. A precise definition, operational diagnostic criteria, and a descriptive name will aid in the early identification and prevention of SILENT.