New exploration highlights the opportunity position of an atypical antipsychotic to deal with anxiety, a common and undertreated symptom in bipolar I disorder (BPD). Notably, investigators claimed, the drug comes without the standard metabolic aspect results, like weight achieve, affiliated with this drug course.
A publish hoc assessment of pooled facts from two trials evaluating two distinct doses of cariprazine (Vraylar) to placebo confirmed it was constantly powerful not only in alleviating bipolar depression but also in enhancing indicators of anxiety.
“Due to the fact this was a write-up hoc analysis, 1 has to be watchful about not overstating the findings,” analyze investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, College of Toronto, Toronto, Ontario, Canada, and head of the Temper Conditions Psychopharmacology Device, advised Medscape Health care News.
“But what we can say is that anxiety has been an below-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are pretty promising,” reported McIntyre, chair and executive director of the Brain and Cognition Discovery Basis, Toronto, Canada.
The evaluation was posted in Intercontinental Scientific Psychopharmacology and was offered as a poster at the 2023 Neuroscience Instruction Institute, Colorado Springs, Colorado.
Ubiquitous, Common, Harmful
Anxiety in BPD is “ubiquitous, typical, and harmful,” McIntyre reported. “We communicate so significantly about depression and mania as cardinal displays, but a person could make a situation that in that trifecta, we’re lacking anxiety.”
In patients with BPD and anxiety, “the index episode is substantially more difficult to handle, you can find a more time time to remission, decrease prices of restoration, and a shorter time to recurrence,” famous McIntyre, chair of the board of the Depression and Bipolar Aid Alliance.
Anxiety also might “symbolize a portent of other things that can add a lot more to the problems, like liquor, illicit medication, or cannabis use — in particular now that cannabis is no lengthier unlawful,” McIntyre reported.
Regrettably, he stated, “there has not been an organized, systematic strategy to creating a remedy for anxiety in BPD.” Somewhat, individuals are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have constraints, he extra.
Some atypical antipsychotics this sort of as quetiapine have been revealed to be valuable with anxiety but “have a whole lot of baggage and aspect results — especially sedation, somnolence, body weight acquire, and metabolic problems,” McIntyre famous.
Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has revealed anxiolytic-like activity in rodent styles.
It was authorized by the US Food items and Drug Administration to address mania, depression, and blended episodes of BPD in 2015 and BPD in 2019.
McIntyre and his staff believed there was an prospect in the completed randomized managed trials of cariprazine in BPD to perform a write-up hoc assessment of its influence on anxiety.
‘Cornerstone Mood Stabilizer’
The researchers pooled facts from two section 3, randomized, double-blind, placebo-controlled reports in adults with BPD going through a present-day main depressive episode.
The pooled intention-to-deal with population consisted of 952 sufferers with BPD (imply age, ~43 several years 62% feminine) randomized to obtain either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Sufferers ended up divided into two subsets: Lower or bigger anxiety (outlined as a Hamilton Anxiety Rating Scale [HAM-A] full score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).
A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.
Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The fee of remission was appreciably larger for cariprazine 1.5 mg/d in the greater and reduced anxiety subsets (P = .0172 and P = .0004, respectively).
In addition, the adjust in HAM-A full score adjust was statistically major for cariprazine 1.5 mg/d in the bigger anxiety subgroup (P = .0105) and the 3 mg/d dose in the decrease anxiety subgroup (P = .0441).
McIntyre hopes these conclusions can be replicated in other trials.
“Clinically, I obtain that several people who get cariprazine you should not require as many benzodiazepines or other remedies for anxiety, and it is a single of the much better-tolerated prescription drugs with no metabolic issues or weight get, so it really is turn out to be a cornerstone mood stabilizer,” he claimed.
Polypharmacy Avoided
A different latest examine retrospectively analyzed healthcare data of close to 40 adult individuals with BPD I who have been obtaining cure with aripiprazole for bipolar depression and then switched to cariprazine.
“We needed to perform a study in frustrated individuals who experienced received pounds on aripiprazole and then right switched to cariprazine. It improved their mood and aided mitigate body weight gain, therefore staying away from polypharmacy of further antidepressants and weight decline agents,” analyze investigator Maxwell Zachary Selling price, a clinical college student at Hackensack Meridian School of Medicine, Nutley, New Jersey, instructed Medscape Health care Information.
“In our basic outpatient psychiatry exercise, we have dealt with a lot of adult individuals with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Selling price, MD, medical assistant professor of psychiatry at Weill Cornell Health care University, New York Metropolis, extra.
Aripiprazole is linked with fat gain. In addition, aripiprazole “hasn’t demonstrated efficacy in running BPD,” he said.
Most sufferers in Price’s apply are insured via Medicaid, which mandates procedure with aripiprazole before covering cariprazine. “We observed their excess weight had been creeping up over the many years, and they also have been going through depressive signs and symptoms,” he reported.
The necessity to initiate treatment method with aripiprazole right before switching to cariprazine presented Price tag an opportunity to review the two brokers in this real-environment setting by retrospectively reviewing the charts of 37 clients with BPD (23 ladies and 14 males who manufactured the swap). The sufferers had been having aripiprazole for a indicate duration of 94.9 weeks and experienced professional a indicate maximize in physique fat of 16.1% ± 12.3% on aripiprazole right before switching.
Clients who were being taking 2 mg-10 mg of aripiprazole were being switched to 1.5 mg of cariprazine, though those using ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.
“Clients tolerated the change very well and managed steadiness throughout the changeover,” and “no sufferers discontinued cariprazine all through the study,” Value stated.
Just after a necessarily mean length of 36.7 weeks (selection, 1-127 weeks), the clients confirmed a lessen in Clinical World wide Perception-Bipolar Severity of Ailment Scale score from a suggest of 5. ± .9 to a mean of 2.8 ± .7 (t = −12.75, P < .00001).
The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).
Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.
“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Price. He hopes that further research in randomized blinded trials will corroborate the findings.
Hypothesis-Generating Research
Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”
Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”
On the other hand, the submit hoc assessment was a secondary examination of an efficacy demo wherever people today with concurrent anxiety disorders were excluded. “So, a following move may possibly be to evaluate this and other therapies in persons with BPD and concurrent anxiety ailments,” he stated.
The review by Jain et al was funded by AbbVie. McIntyre had acquired investigate grant help from CIHR/GACD/Nationwide Normal Science Foundation of China and the Milken Institute speaker/consultation costs from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Overall health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Mobile Therapies, NewBridge Prescription drugs, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the unique paper. Richard Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Mobile Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Maxwell Price tag and Cerimele noted no pertinent money associations.
Batya Swift Yasgur MA, LSW is a freelance writer with a counseling exercise in Teaneck, NJ. She is a standard contributor to quite a few healthcare publications, such as Medscape and WebMD, and is the author of numerous customer-oriented well being guides as nicely as Driving the Burqa: Our Lives in Afghanistan and How We Escaped to Flexibility (the memoir of two brave Afghan sisters who explained to her their story).
