New test drug for schizophrenia sans serious side effects

6 September, 2007:

A new, experimental drug for treating schizophrenia has shown promise in human trials. The drug targets glutamate receptors in the brain rather than dopamine.

Unlike current anti-psychotic drugs, which block the uptake of a naturally occurring chemical called dopamine, the new drug acts on a different neurotransmitter, glutamate, involved in learning and memory.

Imbalances in the brain of these chemicals are largely responsible for schizophrenia’s disabling symptoms, which range from hallucinations and delusions to a severely impaired ability to express emotion.

Schizophrenia is a severe and debilitating psychosis. It is frequently characterized by acute episodes of false beliefs that cannot be corrected by reason (delusions), hallucinations which generally appear in the form of voices which are not there, diminished emotion over the long term, lack of interest, and signs and symptoms of depression. Schizophrenia patients may hear voices, and believe their thoughts are being broadcast or that people are trying to harm them.

About 24 million people suffer from schizophrenia worldwide.

The volunteers in the new study experienced significant improvements in their symptoms while suffering few side effects. The drug is currently called LY2140023.

The study, sponsored by Eli Lilly and Company of the United States, has been published in the September 2, 2007, issue of Nature Medicine.

In the randomized, double-blind, placebo-controlled clinical trial, patients received four weeks treatment either with LY2140023, olanzapine, or a placebo. It was found that:

LY2140023 and olanzapine improved patients’ symptoms significantly within one week compared to the placebo. The researchers used the Positive and Negative Syndrome Scale to measure symptoms.

The patients taking LY2140023 did not appear to experience any of the side effects commonly associated with modern schizophrenia drugs. There was no weight gain, prolactin levels did not rise and there were no extrapyramidal symptoms (involuntary movements or muscle stiffness.).

The trial concluded that LY2140023, taken twice daily, appears to be safe and well-tolerated. Adverse events were mild-to-moderate and did not limit treatment.

Dr Steven Paul, Eli Lilly and Company’s executive vice-president of science and technology, said these data provide compelling new evidence that mGlu2/3 receptor agonists have anti-psychotic properties and may provide a completely new therapeutic approach for treating schizophrenia and, perhaps, other neuropsychiatric disorders. Additional and longer-term studies are needed to confirm and extend the initial findings. However, these data suggest that LY2140023 may provide a new alternative to the treatment of schizophrenia.

It was a proof of concept study, the aim being to decide whether LY2140023 was superior to a placebo. Olanzapine was used as an active control. 196 people who suffered from schizophrenia were randomly selected to either receive LY2140023 at 40 mg twice daily, olanzapine at 15 mg daily or a placebo.

All the volunteers remained in hospital before the trial and during it. They were all tapered of their existing medications before the trial began.