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NEW ORLEANS -- The American Psychiatric Association (APA) annual meeting included news on adjunctive cariprazine (Vraylar) for depression, a potential paradigm shift for mental healthcare delivery, and harnessing telepsychiatry for schizophrenia patients on long-acting injectables. Below are a few more APA research highlights.

Best Combo for Depression?

Adults with major depressive disorder saw the biggest drop in Montgomery-Åsberg Depression Rating Scale (MADRS) score when treated with a combination of esketamine nasal spray (Spravato) plus an oral antidepressant. This treatment combo had a 9.16-point greater improvement in total score compared with those treated with an atypical antipsychotic and an oral antidepressant, according to a meta-analysis of 12 studies.

Additionally, the bigger drops in depression severity rating with esketamine in comparison to aripiprazole (Abilify) and brexpiprazole (Rexulti) were apparent as early as the first week of treatment. At week 1, esketamine-treated patients had a 1.71 and 2.05-point greater drop in total MADRS score than treatment with both antipsychotics, respectively. However, all treatment combinations did show an improvement in depressive symptoms.

The meta-analysis included 2,565 patients treated with atypical antipsychotics or esketamine plus an antidepressant, and 1,711 patients on an antidepressant alone. Esketamine trials lasted 4 weeks, while the atypical antipsychotic trials included lasted 6 to 12 weeks.

"The mechanistically different adjunctive or conjunctive antidepressant agents (esketamine or atypical antipsychotics) appear to differ in their antidepressant outcomes," Guang Chen, MD, PhD, of Janssen Research & Development in San Diego, and colleagues wrote in an APA poster.

Youth Suicidality and Drug Use

Injection drug use was closely tied with suicidal thoughts and behaviors, such as suicide attempts, according to a compilation of data on 217,340 U.S. high school students (1991-2019) in the Youth Risk Behavior Surveillance System. More specifically, heroin had the strongest link with suicidality in teens, with users being 14 times more likely to die from suicide, reported Michael Hennig, BS, of of Cornell University in Wantagh, New York, and Wenna Xi, PhD, of Weill Cornell Medicine in New York City.

"The idea is that injection drug use results in faster and more intense highs that promote binging behavior, which is associated with drug addiction and thereby correlated with higher risk for suicide thoughts and behaviors," Hennig told 番茄社区.

"The increased risk of suicide attempts might be a result of the effects of intoxication or self-medication," he added. "Self-medicating might work in the short term. However, long-term self-medicating tends to prolong [and] exacerbate the mental health disorder, forming a bidirectional relationship between substance use and suicidal behaviors."

Another explanation behind the strong link between heroin, as well as methamphetamine use, with suicidality could also point to fentanyl lacing over time, Hennig said, "which raises the drugs potency, making it more difficult to manage drug addiction and increasing the risk of accidental overdose."

Novel Antipsychotic for Schizophrenia

The investigational schizophrenia treatment xanomeline/trospium (KarXT) yielded significantly greater improvements in all five Positive and Negative Syndrome Scale (PANSS) Marder factors versus placebo, according to the phase II study. These improvements were significant by week 2 of treatment, and included positive and negative symptoms, disorganized thought, uncontrolled hostility, and depression/anxiety.

In the 5-week randomized trial among 170 inpatients with schizophrenia, those treated with a maximum of 125 mg/30 mg twice daily also had significant improvements in Clinical Global Impressions Scale categorical responses as early as week 2 of treatment.

"If confirmed in ongoing phase 3 studies and approved by the [FDA], KarXT may represent a novel class of treatment for patients with schizophrenia based on muscarinic receptor agonism," Christoph Correll, MD, of the Zucker Hillside Hospital in Glen Oaks, New York, and colleagues said in an APA poster.