Schizophrenia Could Be Treated with Fewer Side Effects

A new drug that addresses schizophrenia symptoms has shown considerably less side effects than the “traditional” medication, promising more efficient treatments in the future.

Schizophrenia is a severe mental disorder that affects around 1% of the general population, with 2 million men and women being diagnosed every year in the United States as having this disease. It is one of the most mysterious mental illnesses, since the brain of the affected patients is organically “intact”, unlike Alzheimer’s disease or Parkinson’s disease, where the brain shows distinctive signs of degradation (like the deposition of beta-amyloid protein that kills neurons and leads to dementia).

Treatments for schizophrenia’s symptoms are numerous and effective at reducing chances of relapse, however they also have numerous and sometimes very visible side effects. Included in the panoply of treatments are prescription of antipsychotics, antidepressants and psychotherapy, although supplements of glycine (an amino acid), Omega-3 fats (found in fish oils) and antioxidants also help alleviate the manifestations of the chronic disease.

Most side effects quoted by medical reports are related to drowsiness and dizziness in patients receiving treatment, but these are the “easy” ones. Violent tremor (similar to Parkinson tremor) and considerable weight gain are among the worse, along with low blood pressure, rigidity in muscles, severe headaches and different symptoms associated with euphoria.

What Dr Sandeep Patil and colleagues, from drug firm Eli Lilly, have tried to do with their new "LY2140023" treatment is to address both the problem of the side effects and the efficiency of the overall medication, by taking a different path. As a side note, Eli Lilly is renowned for its other drug called Zyprexa, introduced in 1996, whose side effects were ironically downplayed by the company from fear that it would hurt sales.

This time, Patil, who continued the breakthrough work of Dr. Darryle D. Schoepp, a toxicologist and pharmacologist who joined Lilly in 1988, worked on the relationship between glutamate receptors in the brain and the symptoms of schizophrenia.

Current anti-psychotic drugs block the uptake of a naturally occurring chemical called dopamine, which is both a hormone and a very important neurotransmitter. Excessive levels of dopamine are thought to trigger psychotic episodes in patients suffering from schizophrenia, which is why anti-psychotics’ main purpose is to inhibit the influence of dopamine.

However, Patil’s team avoided the “dopamine-filled brain” path and concentrated instead on another neurotransmitter, called glutamate, whose involvement in psychotic episodes has been a long debate among scientists. The debate started when psychiatrists noticed that the use of a drug called PCP, also known as angel dust, induced symptoms similar to schizophrenic episodes in consumers, by blocking glutamate’s receptors.

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS), including humans of course. Its receptors and associated proteins are likely to be located on every neuron in the brain. Thus, glutamatergic transmission may affect every central neuron and is critical to all mental, sensory, motor, and affective function. For this reason alone, the glutamatergic transmitter system has received attention in examinations of schizophrenia.

In the brains of individuals with schizophrenia, glutamatergic signaling may well contribute to the functional changes in neural networks that account for the progression of the disease through its various stages, as well as for temporal variations in the severity of symptoms at each stage.

Since glutamatergic signaling inside the brain plays such an important role in the development of neural circuitry and in schizophrenia, altered glutamate function, either primarily or as a downstream consequence of some other event, may be part of the pathogenic mechanism leading to psychosis.

Psychotic episodes are characterized by a general loss of contact with reality, involving hallucinations, delusional beliefs, disorganized thinking and an alteration of personality. Because of the fact that these symptoms involve superior cognitive functions, Schoepp and Patil have narrowed their research domain to the study of pre-frontal cortex (PFC), the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.

This part of the brain is mainly involved in the so-called executive function, which gives us the ability to decide between conflicting thoughts, determine good or bad or anticipated different consequences of our current actions. Many authors have indicated an integral link between a person's personality and the functions of the prefrontal cortex.

“This is a system that is so fundamental to the function of your brain that it is quite powerful,” said Dr. Schoepp.

During the evaluation period, which lasted for four weeks, LY2140023 was administered to 97 patients alongside smaller groups given placebos or olanzipine, a commonly prescribed anti-psychotic medication. The results show that Russian olanzipine-treated patients (the experiment took place in Russia between August 2005 to June 2006) and those who received LY2140023 showed roughly the same encouraging effects. LY2140023 matched the effectiveness of olanzipine for both "positive" symptoms such as hallucinations as well as "negative" ones, including withdrawal.

Of course, results need further confirmation, and a new trial, involving 870 patients, is expected to be complete in January 2009. Eli Lilly will re-evaluate the findings from this second phase of the clinical tests, and if things turn out as expected a larger phase III will commence, with more than 2,000 patients.

“We have to confirm safety and efficacy with multiple studies,” Dr. Steven Paul, the president of Lilly Research Laboratories said. “We are very actively working on this target and related targets because we believe that this mechanism is now validated,” he added.
Source :http://www.efluxmedia.com