Lithium vs. quetiapine
Finnish investigators used prospective national databases to examine the rates of psychiatric and all-cause hospitalization during a mean 7.2 years of follow-up in all 18,018 Finns hospitalized for bipolar disorder. The purpose was to assess the impact of various mood stabilizers on overall health outcomes in a real-world setting.
The big winner was lithium. In an analysis adjusted for concomitant psychotropic medications, duration of bipolar illness, and intervals of drug exposure and nonexposure, lithium was associated with the lowest risks of psychiatric rehospitalization and all-cause hospitalization, with relative risk reductions of 33% and 29%, respectively. In contrast, quetiapine, the most widely used antipsychotic agent, paled by comparison, achieving only an 8% reduction in the risk of psychiatric rehospitalization and a 7% decrease in all-cause hospitalization (JAMA Psychiatry. 2018 Apr 1;75[4]:347-55).
In addition, long-acting injectable antipsychotics were significantly more effective for prevention of hospitalization than oral antipsychotics.
“That is kind of shocking, because in some countries, long-acting injectables are not authorized and cannot be used. But I think after this article some regulatory changes are going to take place as a result,” Dr. Grande predicted.
“Another issue I thought was interesting, although it was not the main aim of the study, involved benzodiazepines. They increased the risk of hospitalizations, both for psychiatric illness and all other causes. So apart from giving lithium and long-acting injectable antipsychotics to our bipolar patients, we should also be really careful about the use of benzodiazepines,” she commented.
Intranasal esketamine for suicidality?
Esketamine nasal spray, a fast-acting N-methyl-D-aspartate antagonist whose application for marketing approval in combination with a standard oral antidepressant in treatment-resistant depression is now under Food and Drug Administration review, also is being developed for another indication: reduction of suicidality in patients at imminent suicide risk. In a proof-of-concept study, intranasal esketamine resulted in a significant reduction in suicidal thoughts 4 hours after administration, compared with usual care – but not at 24 hours (Am J Psychiatry. 2018 Jul 1;175[7]:620-30).
New and effective medications for this indication are sorely needed. The only drug approved for the indication of suicide prevention is clozapine.
‘Latest thinking’ on bipolar disorders
Dr. Grande coauthored a comprehensive review article on bipolar disorders that she recommended as worthwhile reading (Nat Rev Dis Primers. 2018 Mar 8;4:18008. doi: 10.1038/nrdp.2018.8).
“It covers all the latest thinking. It focuses on the early stages of the disorder, how epigenetic factors are essential, and many other topics, including the bipolarity index being developed at the University of Barcelona to classify drugs in terms of their capacity to prevent episodes of mania or depression in terms of number needed to treat and number needed to harm. It emphasizes the importance of intervening early and focusing on cognitive dysfunction,” Dr Grande said.
Psychedelics making a comeback
German and Swiss investigators used a facial expression discrimination task to demonstrate that psilocybin, a 5-hydroxytryptamine2A–receptor agonist, decreases connectivity between the amygdala and regions of the brain important in emotion processing, including the striatum and frontal pole. The investigators theorized that this might be the mechanism for the psychedelic’s apparent antidepressant effects (Eur Neuropsychopharmacol. 2018 Jun;28[6]:691-700).