Magazine article Clinical Psychiatry News
Getting the NAC of a Novel Schizophrenia TX
VIENNA -- N-acetylcysteine, an inexpensive supplement widely available over the counter in health food stores, proved safe and effective as adjunctive therapy for chronic schizophrenia in a 6-month, double-blind, placebo-controlled trial, Dr. Michael Berk said at the annual congress of the European College of Neuropsychopharmacology.
"We saw a clinical effect on mood that was really quite exciting," said Dr. Berk, vice president of the International Society for Bipolar Disorders and professor of psychiatry at the University of Melbourne.
The improvement involved the negative symptoms of the disease. The gains arrived slowly and accumulated over time, with a benefit first becoming apparent after about a month, and then disappeared completely during a month-long poststudy washout phase. N-acetylcysteine (NAC) had no effect at all on positive symptoms, as measured by scores on the positive subscale of the widely used Positive and Negative Symptoms Scale (PANSS).
The mechanism of benefit for this novel therapy is believed to be enhanced scavenging of excess neurotoxic free radicals in the brain. NAC readily crosses the blood-brain barrier. It is the biochemical precursor to glutathione, an antioxidant that functions as the primary free-radical scavenger in the brain. Years ago, it was shown that glutathione levels in the cerebral cortex and cerebrospinal fluid are markedly decreased in schizophrenia. Moreover, two genes in the glutathione pathway--glutathione S-transferase T1 and glutamate cysteine ligase modifier--have been identified as candidate schizophrenia-susceptibility genes, the psychiatrist said.
After establishing in animal studies that oral NAC reverses brain glutathione deficiency, Dr. Berk conducted a formal double-blind clinical trial, sponsored by the Stanley Medical Research Institute, with decidedly positive results.
"NAC, a glutathione precursor, reduces the symptoms of schizophrenia. This, for us, openly implicates glutathione deficiency in the pathology of schizophrenia, and it implicates oxidative stress as a mediator of the disease process," according to Dr. Berk.
The study participants were 140 patients with schizophrenia of an average of 12 years' duration. They were randomized in a double-blind fashion to 1 g of NAC b.i.d. or placebo in addition to background therapy. They were a largely treatment-resistant group, with 40% on clozapine (Clozaril). …