March 12, 2014
Sodium-Based Lithium May Be Less Toxic Way To Treat Bipolar Disorder
redOrbit Staff & Wire Reports - Your Universe Online
Researchers from the University of South Florida (USF) have reportedly discovered that an alternative salt form of lithium might be a safer, less toxic way to treat bipolar disorder and other neuropsychiatric conditions.Publishing a paper in a recent edition of RSC Advances, the journal of the Royal Society of Chemistry, the study authors discuss how oral lithium salicylate was able to produce steady lithium levels for up to 48 hours in rats – without the toxic side effects typically linked with the rapid absorption of current FDA-approved lithium carbonate.
While lithium carbonate has been tremendously effective in treating the mania associated with bipolar disorder, as well as reducing the likelihood of suicide during the depressive phases of the condition, it can also cause such side effects as diarrhea, vomiting, weight gain, hand tremors and even decreased thyroid function.
As a result of those adverse effects, patients often stop taking the medication, and alternative treatments that are less toxic than lithium carbonate but equally as effective are not forthcoming, the researchers said. However, they report that the discovery that lithium salicylate could potentially be more effective than lithium carbonate in treating these conditions, only without the toxicity, could be an important step forward in the field of lithium-based treatments.
“Despite its narrow therapeutic window and the emergence of proprietary alternatives, U.S. FDA-approved lithium therapeutics are still regarded as the ‘gold standard’ for the treatment of the manic phase of bipolar disorder,” Dr. Adam J. Smith, a neuroscientist at the USF Health Center of Excellence for Aging and Brain Repair, said in a statement.
“Our previous research suggested that re-engineering lithium therapeutics by crystal engineering might produce better performance with reduced toxicities,” he continued, explaining that crystal engineering is the design and synthesis of molecular solid crystal structures with desired properties using intermolecular interactions.
As part of the study, Dr. Smith and his colleagues examined the impact of two previously untested lithium salts (salicylate and lactate) on laboratory rats. They found that these two substances, each of which is structurally different from lithium carbonate, demonstrated “profoundly different pharmacokinetics” – or absorption and distribution of the drug – when compared to the more widely used version of the substance.
According to Dr. Smith, this is likely the first pharmacokinetic study of lithium salicylate and lithium lactate in lab animals, and the results support previous findings suggesting that an ideal method of lithium preparation would both even-out the high blood level peaks while also slowing declining blood concentrations.
“This is exactly the pharmacokinetic profile produced by lithium salicylate in our study,” said senior author Dr. Doug Shytle, also of the USF Health Center of Excellence for Aging and Brain Repair. “Remarkably, lithium salicylate produced elevated levels of lithium in the blood and brain 48 hours after the dose, but without the sharp peaks that contribute to the toxicity problems of lithium in the currently used form.”
The 48-hour time frame represents a crucial difference between between lithium salicylate and current FDA-approved lithium therapeutics, according to the study authors. If they can manage to duplicate these preclinical outcomes in humans, it would allow for patients to take less frequent doses and experience fewer problematic side effects than current conventional lithium treatments.
“Psychiatry has long struggled with the fact that, while lithium is highly effective for treating bipolar disorder, the narrow therapeutic window and side effect profile often makes lithium both difficult and sometimes dangerous to work with clinically,” explained Dr. Todd Gould, an expert in the neurobiology of bipolar disorder and the lithium at the University of Maryland.
“The pharmacokinetic data by Dr. Smith and colleagues suggests that lithium salts other than the commonly used lithium carbonate may have a broader therapeutic window and potentially fewer side effects,” he added. “Studies in humans will be needed to confirm safety and demonstrate that the pharmacokinetic profile observed in rats is similarly observed in humans.”