Discovery and development of lamotrigine for bipolar disorder: a story of serendipity, clinical observations, risk taking, and persistence.

This paper briefly reviews and comments on the development of lamotrigine as a treatment for bipolar disorder. The events described include astute clinical observations by epileptologists, serendipitous coupling of the drug's clinical profile to unmet need of two refractory bipolar patients by a practicing psychiatrist, risk taking on the part of an industry sponsor, and persistence on the part of a few key internal and external advocates to see development through to its conclusion, taking place against a backdrop of a disease area which, at the time of the earliest events described here, had not seen the development of any new pharmacologic treatments for decades. Fortunately for patients, since that time there has been a veritable explosion of research into treatments for bipolar disorder, both old and new, so that now patients and physicians have multiple evidence-based options for the treatment of this devastating illness.

Child and adolescent psychopharmacology in the new millennium: a workshop for academia, industry, and government.

Objective: To give academic researchers, government officials, and industry scientists an opportunity to assess the state of pediatric psychopharmacology and identify challenges facing professionals in the field.

Method: Increased federal spending and the introduction of pediatric exclusivity led to large increases in pediatric psychopharmacology research in the 1990s. Despite the increase in research, concerns exist about methods and incentives for making new medications available for use in pediatric psychiatric disorders.

The Child and Adolescent Psychiatry Trials Network (CAPTN).

Objective: The current generation of clinical trials in pediatric psychiatry often fails to maximize clinical utility for practicing clinicians, thereby diluting its impact.

Method: To attain maximum clinical relevance and acceptability, the Child and Adolescent Psychiatry Trials Network (CAPTN) will transport to pediatric psychiatry the practical clinical trials model widely used in other areas of medicine.

Results: CAPTN, a collaborative effort of the Duke Clinical Research Institute and the American Academy of Child and Adolescent Psychiatry, will conduct large, simple "practical" trials that provide generalizable answers to important clinical questions without bias.

A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently depressed patients with bipolar I disorder.

Background: The anticonvulsant lamotrigine was previously shown to be effective for bipolar depression. This study assessed the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of mood episodes in bipolar disorder.

Method: During an 8- to 16-week open-label phase, lamotrigine (titrated to 200 mg/day) was added to current therapy for currently or recently depressed DSM-IV-defined bipolar I outpatients (N = 966) and concomitant drugs were gradually withdrawn.

A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder.

Background: Lamotrigine has been shown to be an effective treatment for bipolar depression and rapid cycling in placebo-controlled clinical trials. This double-blind, placebo-controlled study was conducted to assess the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of relapse or recurrence of mood episodes in recently manic or hypomanic patients with bipolar I disorder.

Methods: After an 8- to 16-week open-label phase during which treatment with lamotrigine was initiated and other psychotropic drug regimens were discontinued, patients were randomized to lamotrigine (100-400 mg daily), lithium (0.

Developing strategies for psychopharmacological studies in preschool children.

Objective: To identify the obstacles and special challenges-ethical, practical, scientific, and regulatory-faced by investigators who attempt to conduct psychopharmacological studies in preschoolers.

Method: In a workshop held at the 47th Annual Meeting of the American Academy of Child and Adolescent Psychiatry, featuring interactive sessions designed to elicit discussion of the theory and feasibility of research in this young population, several key domains were identified: diagnosis and assessment, ethics, research design, special considerations for preschoolers, regulatory/industry issues, and education/training.

Results: A Pediatric Psychopharmacology Initiative is needed to consolidate recommendations from this and other workshops and current federal, research, and regulatory committees.

GW320659 for the treatment of attention-deficit/hyperactivity disorder in children.

Objective: To assess the safety, tolerability, and efficacy of GW320659, a chemically novel inhibitor of norepinephrine and dopamine reuptake, in pediatric attention-deficit/hyperactivity disorder (ADHD).

Method: This was a multicenter, open-label, dose-titration study of seven daily dose levels of GW320659: 1.25, 2.