USF Study: Nicotine Antagonist Relieves Depression In Children With Tourette's

The multicenter, placebo-controlled study of the drug mecamylamine is published in the latest issue of the journal Depression and Anxiety.

"These preliminary findings are consistent with anecdotal observations that mecamylamine stabilizes mood," said lead author Douglas Shytle, PhD, assistant professor in the USF Departments of Neurosurgery and Psychiatry. "In addition, this is the first clinical evidence supporting the hypothesis that many antidepressants function, in part, by inhibiting nicotinic receptors."

Dr. Shytle emphasized that larger clinical studies are needed to determine if nicotine antagonists like mecamylamine would provide a new avenue for treating depression and other mood disorders.

In a 1998 study, the USF researchers reported that small doses of mecamylamine (trade name Inversine™), a drug originally used to treat hypertension, seemed to reduce the rage reactions and irritability that many children with Tourette's experience.

In this national randomized study, the researchers examined the effect of mecamylamine on symptom improvement in a group of 50 children and adolescents co-diagnosed with Tourette's syndrome and at least one of several mood disorders. The mood disorders were major depression, attention deficit hyperactivity disorder (ADHD), oppositional defiance disorder, obssessive compulsive disorder, and hypomania.

Of the 50 participants, 38 completed the full 8-week trial -- 17 on mecamylamine and 21 receiving a placebo pill.

The four Tourette's patients co-diagnosed with major depression showed the greatest mecamylamine-related improvements in behavioral and emotional symptoms, including significant decreases in sudden mood changes, irritability, demanding attention, inattention, restlessness, anxiety and impulsiveness. The medication's most beneficial effect appeared to be stabilizing mood.

The depressed patients treated with the placebo showed no benefit.

In a report published this summer in the journal Molecular Psychiatry, the USF researchers suggest that many newer, more selective antidepressants such as Prozac work, in part, by inactivating nicotine receptors in the brain. These receptors appear to be overstimulated by the biochemical messenger acetylcholine in patients who are depressed.

The most common current explanation for how antidepressants work is by boosting levels of serotonin, a brain biochemical that is low in people with depression.

"Our preliminary findings with mecamylamine suggest that another way antidepressants may improve depressed moods is by blocking acetylcholine's excess activation of nicotine receptors," said investigator Paul R. Sanberg, PhD, DSc, professor and director of the USF Neuroscience Program.

"It allows us to explore a new class of drugs for neuropsychiatric disorders," said investigator Archie Silver, MD, director of the USF Center for Infant and Child Development.

The USF research team recently started a controlled study of mecamylamine in children and adolescents with bipolar disorder, also known as manic depression. This latest study is funded in part by the Stanley Medical Research Institute.

Other authors of study in Depression and Anxiety were Kathy Sheehan, PhD; and David Sheehan, MD.

The study was supported in part by a grant from the USF High-Tech Corridor Project. The researchers got mecamylamine through Layton BioScience, Inc., a California biotechnology firm that owned rights to the medication at the time of the study.

Mecamylamine (Inversine™) is now owned and marketed by Targacept, a Salem, NC pharmaceutical company that licenses USF's patent covering the use of nicotine antagonists for the treatment of neuropsychiatric disorders."