The US Food and Drug Administration has approved the first-ever injectable antipsychotic that lasts for three months, according to a press release from the pharmaceutical company Janssen. The approval occurred on the basis of one clinical trial in which the injectable drug prevented relapses more effectively than did placebo. The patients randomly switched to placebo, however, were put into sudden withdrawal from the antipsychotics they’d been taking.
The study, published in March in JAMA Psychiatry by a team of researchers from the pharmaceutical companies Janssen and Johnson & Johnson, was a randomized, multicenter trial that ran from April of 2012 to April of 2014 in 8 countries. Of 506 patients diagnosed with schizophrenia originally enrolled in the study, 305 were given the oral version of the antipsychotic drug paliperidone palmitate for about seven months, and after several months on a one-month injection they were then randomized to taking either the 3-month injectable version of paliperidone palmitate (Invega Trinza) or a placebo.
It was not detailed how long the patients were taking antipsychotics before the study began. But the patients who were suddenly switched (and apparently to a degree unknowingly switched at the time, due to the double-blinded nature of the study) from the antipsychotic to placebo were significantly more likely to experience “symptoms,” “relapses” or land in hospitals, stated the authors.
Though not mentioned in the abstract or press release, in the study itself the authors stated that putting some of the patients through this abrupt withdrawal without any tapering or special supports was purposeful. “The use of a randomized withdrawal design mimics sudden discontinuation of treatment, which commonly occurs under typical clinical conditions in patients with schizophrenia,” the authors wrote.
Some studies have suggested that abrupt withdrawal from antipsychotics can itself exacerbate symptoms and induce relapses.
“With this new treatment option, healthcare providers can give patients greater independence by enabling them to focus less on taking their medication and more on other aspects of their treatment plan,” stated the press release from Janssen.
Though they were not as likely to have been hospitalized, the study authors noted that the people who received the injection were two to six times as likely to have experienced symptoms like headaches, weight gain, inflammation of the nasal passages and upper pharynx, and akathisia.
Berwaerts J, Liu Y, Gopal S, and et al. “Efficacy and Safety of the 3-Month Formulation of Paliperidone Palmitate vs Placebo for Relapse Prevention of Schizophrenia: A Randomized Clinical Trial.” JAMA Psychiatry, March 29, 2015. doi:10.1001/jamapsychiatry.2015.0241. (Abstract)
U.S. FDA Approves INVEGA TRINZA, First and Only Four-Times-A-Year Treatment for Schizophrenia (Janssen Pharmaceuticals press release, May 19, 2015)
Moncrieff, J. “Does Antipsychotic Withdrawal Provoke Psychosis? Review of the Literature on Rapid Onset Psychosis (supersensitivity Psychosis) and Withdrawal-Related Relapse.” Acta Psychiatrica Scandinavica 114, no. 1 (July 1, 2006): 3–13. doi:10.1111/j.1600-0447.2006.00787.x. (Abstract)