In an open-label extension study involving patients aged 10 to 17 years, up to 2 years of treatment with lurasidone was associated with continued improvement in depressive symptoms. There were progressively higher rates of remission, recovery, and sustained remission.
Coinvestigator Manpreet K. Singh, MD, director of the Stanford Pediatric Mood Disorders Program, Stanford University, California, noted that early onset of BD is common. Although in pediatric populations, prevalence has been fairly stable at around 1.8%, these patients have “a very limited number of treatment options available for the depressed phases of BD,” which is often predominant and can be difficult to identify.
“A lot of youths who are experiencing depressive symptoms in the context of having had a manic episode will often have a relapsing and remitting course, even after the acute phase of treatment, so because kids can be on medications for long periods of time, a better understanding of what works…is very important,” Singh told Medscape Medical News.
The findings were presented at the virtual American Society of Clinical Psychopharmacology (ASCP) 2020 Annual Meeting.
The US Food and Drug Administration approved lurasidone as monotherapy for BD in children and adolescents in 2018. The aim of the current study was to evaluate the drug’s long-term efficacy in achieving response or remission in this population.
A total of 305 children who completed an initial 6-week double-blind study of lurasidone vs placebo entered the 2-year, open-label extension study. In the extension, they either continued taking lurasidone or were switched from placebo to lurasidone 20 to 80 mg/day.
Of this group, 195 children completed 52 weeks of treatment, and 93 completed 104 weeks of treatment.
Efficacy was measured with the Children’s Depression Rating Scale, Revised (CDRS-R) and the Clinical Global Impression, Bipolar Depression Severity scale (CGI-BP-S).
Functioning was evaluated with the Clinician-rated Children’s Global Assessment Scale (CGAS). On that scale, a score of 70 or higher indicates no clinically meaningful functional impairment.
Responder criteria were met if a patient achieved at least a 50% reduction in the CDRS-R total score. Remission criteria were met if a patient achieved a CDRS-R total score of 28 or less, a Young Mania Rating Scale (YMRS) total score of 8 or less, and a CGI-BP-S depression score of 3 or less.
Recovery criteria were met if a patient achieved remission and had a CGAS score of at least 70.
Sustained remission, a more stringent outcome, required that the patient meet remission criteria for at least 24 consecutive weeks.
Table. Long-term Results With Lurasidone in Pediatric BD
|Outcome||Baseline (n = 305 Patients)||Week 52 (n = 195 Patients)||Week 104 (n = 93 Patients)|
|Sustained remission rate||n/a||37.2%||57.0%|
In addition, there was a strong inverse correlation (r = –0.71) between depression severity, as measured by CDRS-R total score, and functioning, as measured by the CGAS.
“That’s the cool thing: as the depression symptoms and severity came down, the overall functioning in these kids improved,” Singh noted.
“This improvement in functioning ends up being much more clinically relevant and useful to clinicians than just showing an improvement in a set of symptoms, because what brings a kid or even an adult, for that matter, to see a clinician to get treatment is because something about their symptoms is causing significant functional impairment,” she said.
“So this is the take-home message: you can see that lurasidone…demonstrates not just recovery from depressive symptoms but that this reduction in depressive symptoms corresponds to an improvement in functioning for these youths,” she added.
Commenting on the study for Medscape Medical News, Christoph U. Correll, MD, professor of child and adolescent psychiatry, Charite Universitatsmedizin, Berlin, Germany, noted that BD is difficult to treat, especially for patients who are going through “a developmentally vulnerable phase of their lives.”
“Lurasidone is the only monotherapy approved for bipolar depression in youth and is fairly well tolerated,” said Correll, who was not part of the research. He added that the long-term effectiveness data on response and remission “add relevant information” to the field.
However, he noted that it is not clear whether the high and increasing rates of response and remission were based on the reporting of observed cases or on last-observation-carried-forward analyses.
“Given the naturally high dropout rate in such a long-term study and the potential for a survival bias, this is a relevant methodological question that affects the interpretation of the data,” he said.
“Nevertheless, the very favorable results for cumulative response, remission, and sustained remission add to the evidence that lurasidone is an effective treatment for youth with bipolar depression. Since efficacy cannot be interpreted in isolation, data describing the tolerability, including long-term cardiometabolic effects, will be important complementary data to consider,” Correll said.
The study was funded by Sunovion Pharmaceuticals, Inc. Singh is on the advisory board for Sunovion, is a consultant for Google X and Limbix, and receives royalties from American Psychiatric Association Publishing. She has also received research support from Stanford’s Maternal Child Health Research Institute and Department of Psychiatry, the National Institute of Mental Health, the National Institute on Aging, Johnson and Johnson, Allergan, PCORI, and the Brain and Behavior Research Foundation. Correll has been a consultant or advisor to and has received honoraria from Sunovion, as well as Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Supernus, Takeda, and Teva.
American Society of Clinical Psychopharmacology (ASCP) 2020 Annual Meeting: Abstract 3002335, presented May 29, 2020.
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