[Cariprazine image courtesy of PubChem]
About four out of 10 patients see a noticeable benefit from an antidepressant after six to eight weeks, according to Dr. Arif Khan, a board-certified psychiatrist.
For the six out of ten who don’t see a benefit, “the first choice is to switch to a different class of an antidepressant,” said Khan, an adjunct professor of psychiatry at Duke University School of Medicine and the Pacific Northwest University of Health Sciences. “Usually two of the six will benefit,” Khan added.
Dr. Arif Khan
Some patients don’t see a tangible benefit after cycling through multiple antidepressants. One challenge is that “there are no widespread and accepted methods about choosing antidepressant medications,” Khan said.
The treatment landscape for major depressive disorder (MDD) is evolving. In late 2022, AbbVie (NYSE:ABBV) won FDA approval to use the novel atypical antipsychotic drug Vryalar (cariprazine) as an adjunctive therapy to antidepressants to treat MDD in adults.
The adjunctive therapy could offer hope to patients who don’t respond to traditional antidepressant therapy, Khan said. “Atypical antipsychotics, in lower doses, are the most commonly used medications,” he noted.
Vraylar offers the convenience of once-a-day dosing and the ability to increase the dose if the lower dose does not work, Khan said.
A depression epidemic
Julie Adams
AbbVie also believes that approval to use cariprazine as adjunctive therapy for MDD could help address the spiraling rates of MDD. “Data from the U.S. Census Bureau Household Pulse Survey shows that the prevalence of depressive symptoms has increased by almost three times since 2019,” said Julie Adams, executive medical director of neuroscience clinical development at AbbVie.
Adams notes that there has been a renewed focus on developing more effective treatment options for patients who have cycled through multiple rounds and antidepressants and are not experiencing adequate relief. “Vraylar is a new adjunctive treatment option for these patients, and its approval reflects progress in the treatment of psychiatric disorders,” Adams said.
Vraylar has a novel mode of action for depression
Traditional selective serotonin reuptake inhibitors (SSRIs) inhibit the reuptake of serotonin. Vraylar is the first and only dopamine and serotonin partial agonist approved for adjunctive therapy to antidepressants for treating MDD and bipolar I depression. “Vraylar is thought to work by helping to adjust the response to dopamine and serotonin levels in the brain, both of which affect mood,” Adams said.
Adams notes that adults with MDD who are taking an antidepressant but have unresolved symptoms may benefit from an adjunctive medication like Vraylar, which “may build on the progress made with the initial antidepressant therapy and prevent delays that result from switching medications and starting over.” She adds that by combining different treatment modalities, adjunctive treatments can help address mood symptoms in multiple ways.
MADRS scores improved for those on Vraylar and antidepressants
In clinical studies of adults with MDD with moderate to severe residual symptoms of depression after taking approved antidepressants, adding Vraylar to their antidepressant therapy (ADT) helped improve overall depressive symptoms [as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) total score] as compared to those taking an antidepressant alone. “The MADRS is a gold standard measure of depressive symptoms,” Adams said. “Scores range from 0 for no symptoms to 60 for highest symptom burden.”
In the six-week Phase 3 Study 3111-301-001, the mean change from baseline in MADRS total score at six weeks for recipients of Vraylar 1.5 mg/day + ADT (n=250) was -14.1 (baseline mean: 32.8, P=0.0050). Those who received Vraylar 3 mg/day + ADT (n=252) had a -13.1 change in MADRS score (baseline mean: 32.7, P=0.0727). Conversely, placebo recipients who received ADT (n=249) had a -11.5 change in MADRS score (baseline mean: 31.9).
In a separate 8-week study, the mean change from baseline in MADRS total score at eight weeks for recipients of Vraylar 1–2 mg/day + ADT (n=273) changed by -13.4 points. (baseline mean: 29.0, P=0.2404). Those who received 2-4.5 mg/day of Vraylar daily with ADT (n=271) had a -14.6 point change (baseline mean: 29.3, P=0.0114). Those who received a placebo with ADT (n=264) had a -12.5 point MADRS score change (baseline mean: 28.9).
Post-hoc analysis
“We also conducted a post hoc analysis looking at the effect on MADRS total score in MDD patients, stratified by the presence or absence of anxiety symptoms at baseline,” Adams said.
The analysis defined the presence or absence of anxiety symptoms with a score of > 7 at baseline on the Hamilton Depression Rating Scale (HAM-D) anxiety/somatization factor. The anxiety/somatization factor comprises six items from the HAM-D, including psychic anxiety, somatic anxiety, gastrointestinal somatic symptoms, general somatic symptoms, hypochondriasis and insight.
“Overall, 83% of patients had anxiety symptoms at baseline. On average, patients on Vraylar + ADT experienced an improvement in depressive symptoms as compared to those on placebo + ADT as measured by the MADRS total score, regardless of the patient’s baseline anxiety symptoms status,” Adams said.
The analyses were not prespecified endpoints and were not adjusted for multiplicity. “Therefore, treatment differences cannot be regarded as statistically significant,” Adams said. “This analysis did not assess the effect of treatment on symptoms of anxiety.”
Adams notes that the efficacy of Vraylar as an adjunctive therapy to antidepressants to treat MDD was evaluated in two trials in adult patients meeting DSM-IV-TR or DSM-5 criteria for MDD.
The two studies included patients with or without symptoms of anxiety who had an inadequate response to one to three courses of prior ADT. “However, further studies are warranted to assess cariprazine’s impact on patients with MDD and who have high co-morbid anxiety,” Adams said.
Filed Under: Psychiatric/psychotropic drugs
