Many psychiatrists are now prescribing second-generation or 'atypical' antipsychotics.

Antipsychotic medications have long been the primary treatment for patients with schizophrenia. Unfortunately, many traditional drugs come with a host of disagreeable side effects related to the inhibition of the neurotransmitter dopamine. As a result many psychiatrists are now prescribing second-generation or “atypical” antipsychotics that are less likely to block dopamine transmission in brain areas not directly affected by the disorder. But is this new class of therapeutic agents more effective and tolerated better by patients than the first-generation therapies? Most are not, according to work in 2005 and 2006 by Jeffrey Lieberman and colleagues. Research published in 2005 revealed no difference in effectiveness between the first- and second- generation antipsychotics.1 In terms of tolerability, olanzapine, a second-generation drug, showed a slightly lesser rate of discontinuation by patients of their medication compared to other drugs, but it was associated with unpleasant weight gain and metabolic side effects. Lieberman’s group continued their work in 2006, publishing two papers in the American Journal of Psychiatry that examined antipsychotic treatment in more detail. The group found that chronic schizophrenic patients were more likely to continue treatment if they were taking olanzapine and risperidone rather than other atypical antipsychotics. Correspondingly, in patients who did not respond to previous atypical antipsychotic medication at all, the investigators looked at the effectiveness of clozapine, a “last-resort” medication with strong side effects for treatment-resistant patients. They found that these patients responded better to clozapine than to a second atypical antipsychotic.3 In an independent study across the Atlantic, Peter Jones at Cambridge and his team of researchers also studied the effectiveness of second-generation antipsychotic medications in treating chronic schizophrenia. Participants were randomly prescribed either a first- or a second-generation antipsychotic drug and were evaluated for one year by a clinician who did not know which medication they had been assigned. Symptoms, adverse effects, and quality of life were measured and compared. Jones’s team expected to find that the atypical drugs were more effective than their predecessors but, in fact, they found the opposite to be true. Patients responded better and scored higher on quality-of-life scales when taking the first-generation drugs.4 As might be expected, this finding, coupled with Lieberman’s research, has caused some consternation among psychiatrists. Together, these results suggest that atypical antipsychotic drugs generally should be tried primarily if patients are resistant to first-generation antipsychotic medications. Research on the elusive causes of schizophrenia continues to focus on the role of dopaminergic neurons. Early research implicated excessive dopamine transmission in the disorder’s behavioral symptoms. But Michael O’Donovan, Michael Owen, and their collaborators studied the abnormal function of brain cells called glia as another possible precursor to the disorder, based on prior postmortem and neuroimaging evidence of both structural and volume differences in brain white matter (the neural connections) between patients with schizophrenia and healthy controls. Glial cells interact with neurons to produce myelin, a fatty insulator that helps facilitate transmission of electrical signals from one brain cell to another. The group’s findings, published in Proceedings of the National Academy of Sciences, indicate that variation in a gene called OLIG2, which regulates the creation of myelin, makes carriers vulnerable to schizophrenia. This finding suggests that further research into the genes governing glial function on the production of myelin may provide important insights into the complex processes involved in schizophrenia.

schizophrenia, medication, drug, antipsychotic, psychosis, dopamine, lieberman, olanzapine