Thinking Back and Looking Forward, Good Neighbor Pharmacy Is Ready for the Next 40 Years

Patients on Dupixent (dupilumab) who have controlled atopic dermatitis (AD) can successfully have their dose reduced and maintain stable low disease activity. The findings were published in 

Allergy: European Journal of Allergy & Clinical Immunology

Researchers in the Netherlands evaluated a patient-centered dosing regimen for patients with controlled AD with 90 adults with AD who were treated with Dupixent. Type 2 inflammation is common in atopic diseases, and Dupixent targets key drivers of type 2 inflammation, including interleukin (IL)-4 and IL-13.

“Continuing the standard dosage in patients with persistently controlled AD might lead to overtreatment and an increase in adverse events (e.g. injection side reactions, conjunctivitis),” the researchers noted.

The patient-centered dosing regimen is based on tapering protocols of biologics in other diseases, such as rheumatoid arthritis. In this study, patients were eligible for their dose to be reduced after being treated with Dupixent for 52 weeks and when disease activity was controlled, which was defined as Eczema Area and Severity Index (EASI) score of 7 or less.

For patients with EASI ≤ 7, their dosage interval was prolonged to every 3 weeks, which reduced dosage to 66% of the standard dosage. Patients who continued to have controlled disease activity then prolonged interval to every 4 weeks (double the original interval), which reduced dosage to 50% of the standard dosage. Patients with persistently controlled disease reduced their dosage even more to every 6 weeks, and finally to every 8 weeks. The dosage interval was shortened for patients with increased pruritus scores or physician-reported disease severity scores.

After 52 weeks of treatment, patients were divided into 3 groups:

Group A was patients with uncontrolled disease or those who wanted to continue their dosing and did have not their dose reduced.

Group B prolonged their dose interval to every 4 weeks

Group C prolonged dose interval to every 6 weeks or every 8 weeks

The patients were followed up for at least 91 weeks. The mean age of patients was 42.4 years, and the majority were male (65.6%). During the first 52 weeks of treatment with Dupixent, the median EASI score dropped from 17.9 at baseline to 2.7.

Group A maintained stable disease severity with a median EASI score of 6.4 after 52 weeks and 5.4 after a mean duration of 115 weeks. At 52 weeks, 50% had controlled AD; at 85 weeks, 40% had controlled AD; and at 115 weeks, 50% had controlled AD.

Groups B and C also maintained stable disease with no significant difference in EASI score between 52 weeks, when the tapering started, and the end of the study (mean 141 weeks for Group B and 140 weeks for Group C). After at least 3 months on a dosage interval of every 4 weeks, 83.3% of patients in group B and 86.7% of patients in group C had controlled AD. At the end of the study, when patients in group C had moved to dosing every 6 or 8 weeks, 93.3% of patients had controlled AD.

Numeric Rating Scale (NRS) pruritus temporarily increased after prolonging the dosing interval, but these changes were small and scores remained low, the researchers noted. “The clinical relevance of these differences are questionable as the changes in NRS scores were small and inconsistent and median NRS scores remained ≤4, which is also considered as a treatment target,” they wrote.

One of the limitations noted was that more research is needed to understand unsuccessful dose reduction because patients who shortened their intervals were not included. In addition, a direct comparison between patients on standard dosing and dose reduction is not feasible since patients in group A who did not have their dose tapered had higher disease severity scores than patients in groups B and C.

“These findings are the first step toward personalized dupilumab treatment for controlled AD patients in clinical practice,” the authors concluded.

Articles

Patients with persistently controlled atopic dermatitis who had their doses reduced were able to maintain their low disease activity.

Atopic Dermatitis Remains Controlled Even After Reduction of Dupixent Dose

An important type 2 diabetes medication — also approved for weight loss indication — is in high demand which is causing limited supply in some areas.

Semaglutide (Novo Nordisk), approved by the FDA as Ozempic to treat type 2 diabetes in 2017

 was cleared as the chronic weight loss management medication Wegovy in June 2021.

When Novo Nordisk experienced a problem with a contract manufacturer in March, it began limiting doses of Wegovy, Michael Ganio, Pharm.D., senior director of pharmacy practice and quality for the American Society of Health-System Pharmacists, told 

 obtaining Wegovy at that time, but the American Society of Health-System Pharmacists (ASHP) has not received reports of shortages since the spring. “Supply to the United States is improving. Novo Nordisk temporarily paused production of the lower doses of Wegovy — those are the doses you need to get started…so newer patients couldn’t start with lower supplies,” Ganio said.

“From the outset of our supply constraints, the top priority for our organization has been to avoid disruption to patient care and meet the needs of patients who have started treatment with Wegovy to be able to stay on therapy,” Allison Schneider, director of media relations and issues management at Novo Nordisk, told 

"We have been taking measures in support of that, including pausing promotion and advertising of Wegovy and asking health care providers to not start new patients on therapies,” Schneider added.

Novo Nordisk expects that all dose strengths of Wegovy will be available in the United States towards the end of this year, according to Schneider. “We will ensure that we have all dose strengths within our inventory before we support new patients being initiated and before we start other promotional efforts, consistent with our commitment to continuity of care,” she said.

Although supply of Ozempic in the United States has been “fairly consistent”, according to Ganio, patients in other countries are having difficulty obtaining the medication.

For example, the Australia Department of Health and Aged Care Therapeutic Goods Administration (TGA), along with health organizations in the country, issued an alert on Ozempic availability on August 4.

Novo Nordisk notified the TGA of a Ozempic products “due to an unexpected increase in consumer demand,” the agency said. "The increased demand is due to extensive prescribing for obesity management, for which Ozempic is not indicated. The shortage is significantly affecting people using Ozempic for its approved use for type 2 diabetes.”

Novo Nordisk has advised the TGA that the intermittent availability of Ozempic will continue until the end of December 2022, according to TGA. “Health professionals are reminded to continue prioritizing the supply of Ozempic for people with type 2 diabetes,” the alert said.

“We are experiencing stronger than anticipated demand for Ozempic, which might result in intermittent availability in a limited number of markets,” Schneider told 

®. “For those affected markets, we are in a dialogue with the health authorities and other relevant stakeholders to ensure a continuous supply of products.”

Ozempic is available in the United States currently, Erin R. Fox, Pharm.D., senior pharmacy director at the University of Utah Health, which provides drug shortages data to ASHP, told 

®. However, Novo Nordisk is not “forthcoming about their supplies and exactly what is going on, so it’s impossible to speculate exactly how much is available or if more presentations will be affected, or if supplies will start to recover,” Fox said.

1. FDA approves new drug treatment for chronic weight management, first since 2014. News release. FDA. June 4, 2021. Accessed August 10, 2022. 

https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014

2. Joint statement: Prioritisation of semaglutide (Ozempic) supply for people with type 2 diabetes during shortage. Alert. Australia Department of Health and Aged Care Therapeutic Goods Administration. August 4, 2022. Accessed August 10, 2022. 

https://www.tga.gov.au/alert/joint-statement-prioritisation-semaglutide-ozempic-supply-people-type-2-diabetes-during-shortage

Issues with a contract manufacturer have led to limited availability for semaglutide.

Wegovy Still on Limited Dosing, Ozempic Has “Intermittent” Availability in Some Countries

The US Food and Drug Administration (FDA) sent a Complete Response Letter (CRL) regarding the supplemental new drug application (sNDA) for pimavanserin (Nuplazid) for the treatment of hallucinations and delusions associated with Alzheimer disease psychosis (ADP), according to Acadia Pharmaceuticals.

The CRL indicated that the FDA has completed review of the application and could not approve the sNDA in its present form. The FDA recommended that Acadia conduct an additional trial in ADP.

“We are disappointed with this outcome. The treatment of Alzheimer disease psychosis continues to be an area of high unmet need, for which there is no approved therapy,” said Steve Davis, chief executive officer. “We want to express our gratitude to all of the patients, their families and investigators who have participated in our clinical trials.”

In Study 019, the FDA agreed the results demonstrated a statistically significant treatment effect on its primary endpoint, but the agency concluded there are limitations in the interpretability of said results. The FDA also stated that the positive treatment effect of pimavanserin on dementia-related psychosis in Study 045 (HARMONY) appeared to be driven by the robustly positive results in the Parkinson disease dementia subgroup, a condition they stated is subsumed within the currently approved Nuplazid Parkinson disease psychosis (PDP) indication.

This recent sNDA was Acadia's second attempt to secure approval for expanded use of the drug. In early 2021, the FDA rejected Acadia’s clinical trial data, which they stated were not sufficient to support approval of pimavanserin in patients with dementia-related psychosis.

This article originally appeared on Psychiatric Times.

1. Acadia Pharmaceuticals receives complete response letter from U.S. FDA for supplemental new drug application for pimavanserin for the treatment of hallucinations and delusions associated with Alzheimer’s disease psychosis. Business Wire. August 4, 2022. Accessed August 8, 2022. 

https://www.businesswire.com/news/home/20220804006095/en/Acadia-Pharmaceuticals-Receives-Complete-Response-Letter-from-U.S.-FDA-for-Supplemental-New-Drug-Application-for-Pimavanserin-for-the-Treatment-of-Hallucinations-and-Delusions-Associated-with-Alzheimer’s-Disease-Psychosis

2. U.S. FDA declines to approve expanded use of Acadia's antipsychotic drug. Reuters. August 5, 2022. Accessed August 8, 2022. 

https://www.reuters.com/business/future-of-health/us-fda-declines-approve-expanded-use-acadias-antipsychotic-drug-2022-08-05/

Alzheimer disease psychosis treatment pimavanserin receives Complete Response Letter from the FDA.

FDA Asks for More Info on Expanded Use of Pimavanserin

Recently-updated guidelines from the American Gastroenterological Association (AGA) strongly recommend Linzess (linaclotide) to treat irritable bowel syndrome with constipation (IBS-C), and conditionally recommend against using some anti-depressants such as Prozac.

 outline, for the first time, when to use newly introduced IBS drugs, when to rely on older medications, and when to use over-the-counter drugs, AGA said in a statement.

“We have so many treatment options, we can now take a targeted treatment approach to patient symptoms,” says author Shahnaz Sultan, M.D., AGAF. “It’s very important for patients to be open about their IBS symptoms and just as important for gastroenterologists to set realistic expectations for this chronic disease to ensure the best quality of life for their IBS patients.”

Linzess was the only treatment that the technical review committee recommended “with high certainty”. It made conditional recommendations or “moderate certainty” for tenapanor (Isbrela), plecanatide (Trulance), tegaserod (Zelnorm), and lubiprostone (Amitiza).

The panel had “low certainty” on polyethylene glycol laxatives such as Miralax, tricyclic antidepressants (Elavil, Norpramin, others), and antispasmodics (Bentyl, Lobrax).

AGA also made a conditional recommendation against the use of selective serotonin reuptake inhibitors (SSRIs) like Prozac, Celexa, and others.

“SSRIs did not significantly improve global symptoms or abdominal pain in IBS, although the overall certainty in evidence is low,” AGA wrote.

In some patients, SSRIs may improve the perception of overall IBS symptoms and well-being by improving gastrointestinal symptoms, coexistent alterations in mood and extraintestinal symptoms.

In addition, the panel said it is possible that SSRIs may have a greater effect on abdominal pain in IBS due to their effects on both serotonin and norepinephrine reuptake. “Serotonin-norepinephrine reuptake inhibitors have been shown to be efficacious in other pain conditions, but clinical trials in IBS are lacking,” AGA wrote.

Meanwhile, the panel gave linaclotide a “strong” recommendation because, across 4 randomized controlled trials, linaclotide improved global assessment of IBS-C symptoms (FDA responder), abdominal pain, Complete Spontaneous Bowel Movement response, and adequate global response.

Chang L, Sultan S, Lembo A, Verne GN, Smalley W, Heidelbaugh JJ. AGA clinical practice guideline on the pharmacological management of irritable bowel syndrome with constipation. 

. 2022 Jul;163(1):118-136. doi: 10.1053/j.gastro.2022.04.016.

AGA issues clinical guidelines outlining drug treatment plans for patients with irritable bowel syndrome (IBS). News release. American Gastroenterological Association. June 21, 2022. Accessed August 8, 2022. 

https://www.eurekalert.org/news-releases/956376

The American Gastroenterological Association has released updated guidelines for treating irritable bowel syndrome with constipation (IBS-C).

Guidelines Strongly Recommend Linzess for IBS-C

With the continuing rise in monkeypox infections in the United States, the US Food and Drug Administration has granted Emergency Use Authorization (EUA) of the Jynneos (Bavarian Nordic) vaccine for pediatric patients <18 years who are at high risk of monkeypox infection.

Now, the vaccine is authorized for a series of 2, 0.5 mL doses via subcutaneous injection administered 28 days apart in patients <18 years and patients of any age who have a history of developing keloid scars under the new EUA. Additionally, an alternative regimen of 2, 0.1 mL doses via intradermal injections administered 28 days apart is authorized for use in patients ≥18 years.

“In recent weeks the monkeypox virus has continued to spread at a rate that has made it clear our current vaccine supply will not meet the current demand,” said FDA Commissioner Robert M. Califf, MD “The FDA quickly explored other scientifically appropriate options to facilitate access to the vaccine for all impacted individuals. By increasing the number of available doses, more individuals who want to be vaccinated against monkeypox will now have the opportunity to do so.”

Jynneos, a Modified Vaccinia Ankara (MVA) vaccine, was approved for the prevention of smallpox and monkeypox in adults 18 years and older in 2019.

This article originally appeared on Contemporary Pediatrics.

1. Monkeypox update: FDA authorizes emergency use of Jynneos vaccine to increase vaccine supply. FDA. Published August 9, 2022. Accessed August 10, 2022. 

https://www.fda.gov/news-events/press-announcements/monkeypox-update-fda-authorizes-emergency-use-jynneos-vaccine-increase-vaccine-supply

The FDA has granted Emergency Use Authorization EUA of the Jynneos vaccine for pediatric patients <18 years who are at high risk of monkeypox infection.

FDA Gives OK to Pediatric Use of Monkeypox Vaccine

/Gallup poll found that nearly four in 10 Americans in the last six months have delayed or skipped health care treatments, trim regular household expenses, or borrow money, because of rising health care costs. Extrapolated across the entire population, that means 98 million adults are having to figure out how to afford health care.

While half of adults in households earning less than $48,000 per year report cutting spending, the effects also extend to more influential households. For those earning at least $180,000, 19% said they have pared back spending to pay for health care.

According to the report, women under 50 are disproportionately being compelled to cut back on health care with 36% reporting they have done so, compared to 22% of men. having done so, compared with 22% of men.

Overall, 26% of adults report delaying or avoiding medical care or purchasing prescription drugs in the prior six months due to higher health care prices. This rises to 43% among adults in lower-income households (those making less than $24,000 annually).

For those cutting costs, health care is usually on the chopping block with other expensed. The report found:

Of those who cut back on utilities, 59% also cut back on medical care and medicine.

Of those who skipped a meal, 71% also cut back on medical care and medicine.

Of those who borrowed money, 60% also cut back on medical care and medicine.

Of those who drove less, 55% also cut back on medical care and medicine.

The effect of inflation exacerbates an already significant issue for millions of Americans struggling to pay for health care and medicine. Prior findings from the 2021 West Health-Gallup Healthcare Study showed that an estimated 18% of adults, or about 46 million people, 

could not afford needed care if they required it today

unable to pay for prescribed drugs in the prior three months

Health care inflation, which stood at 4.5% in June, is lagging overall inflation, which spiked to 9.1% in June, a new 40-year high primarily because of rising prices for gas, food and rent. According to the report, inflation has not yet fully hit health care prices due to prenegotiated contracts with insurers and providers for 2022, but inflation is likely to impact prices later in the year -- something that consumers may not fully appreciate given the mere 3% that cite health care as the service expected to rise in price the most in the next six months.

This article originally appeared on Medical Economics.

Patients are either skipping care completely, cutting costs elsewhere, or borrowing money to pay for health care

Nearly 40% of Americans Say Inflation Has Impacted Health Care

To date, there are only 2 medications that have US Food and Drug Administration (FDA) approval for the acute treatment of major depressive disorder in children and adolescents: fluoxetine (ages 8 to 17 years) and escitalopram (ages 12 to 17 years). Placebo response rates in the 50% range have contributed to negative findings in double-blind placebo-controlled antidepressant trials for the treatment of major depression in youth. Further evidence-based antidepressant treatments are needed for children and adolescents with depression. Recent studies provide new information about treatment for depression in youth.

There have been 2 prior randomized double-blind placebo-controlled trials that evaluated the efficacy of duloxetine in the treatment of major depression in children and adolescents.

 Fluoxetine was the active control in these studies. Duloxetine was not statistically different from placebo on change from baseline to endpoint on the Children’s Depression Ratings Scale-Revised (CDRS-R) total score. Similarly, fluoxetine did not statistically differ from placebo. These studies were considered to be inconclusive since neither duloxetine nor fluoxetine separated from placebo on the primary outcome measure.

To further evaluate the efficacy and safety of duloxetine, Saito et al conducted a 6-week randomized double-blind placebo-controlled trial for treatment of children and adolescents with major depressive disorder in Japan.

 In this trial, 149 youth aged 9 to 17 years were randomized to duloxetine or placebo. All participants received 4 video sessions of psychoeducation.

Duloxetine final doses were either 40 or 60 mg/day. There was no significant difference on CDRS-R total score from baseline to endpoint between the duloxetine group and placebo group. Response rates (> 50% improvement on CDRS-R) were similar between duloxetine (32.4%) and placebo (32.4%) groups. The most common treatment-emergent adverse events for duloxetine were nausea, somnolence, decrease appetite, and nasopharyngitis.

The efficacy and safety of vortioxetine was assessed in adolescents (aged 12 to 17 years) with major depressive disorder.

 To minimize placebo response, this study used a 4-week single-blind lead-in period during which adolescents received a standard 3 session Brief Psychosocial Intervention (BPI) plus placebo. To reduce expectation bias, participants and their families were blinded to the time of the randomization. After the 4-week lead-in period, those patients who did not respond to treatment were randomized to 8 weeks of continued BPI plus double-blind treatment with vortioxetine 10 mg, vortioxetine 20 mg, fluoxetine 20 mg (active control), or placebo.

In the lead-in, 784 patients were enrolled and 616 were randomized to 1 of the 4 treatments. The primary outcome measure was change in CDRS-R total score from randomization to week 8. The average effect of the 2 doses of vortioxetine was compared to placebo, and there was no significant difference between vortioxetine and placebo on the primary outcome measure. There was a statistically significant difference between fluoxetine and placebo on the primary endpoint. Response rates (≥ 50% change from randomization in CDRS-R total score) were 42% for vortioxetine 10 mg, 43% for vortioxetine 20 mg, 50% for fluoxetine, and 36% for the placebo groups. Importantly, the placebo response rate in this study was lower than the typical 50% range for other antidepressant trials in adolescents. This may be attributable to the single-blind lead-in and blinding for participants and families as to the timing of randomization employed in this study design. Of note, 13% (103 of 777 patients) of participants responded to treatment during the single-blind treatment phase. Treatment-emergent adverse events with an incidence of 5% or more for vortioxetine treatment were nausea, headache, vomiting, nasopharyngitis, diarrhea, and dizziness.

Antipsychotics are used to treat depression in children and adolescents who have not responded to prior treatment with an antidepressant. To date, there are no controlled trials of combination 

 and antidepressants to treat major depression in youth. Jeon et al examined whether there were neurological adverse events with the adjuvant use of antipsychotics with antidepressants in children and adolescents with depression.

 Their aim was to determine the risks of adjuvant use with antipsychotics compared to antidepressant only use in children with depression.

This retrospective cohort study used the Health Insurance Review and Assessment claims database criteria in Korea. Children and adolescents aged 2 to 18 years with depression who began treatment with antidepressants between 2010 and 2018 were included in the study population. The incidence of movement disorders (Parkinsonism, dystonia, extrapyramidal symptoms, chorea, and tics) and seizures were assessed in 4 time-varying exposures with antidepressant-only use, antipsychotic-only use, concomitant use, and no use.

The final cohort included 9890 children and adolescents. The risk of movement disorders increased during the period of concomitant use (adjusted hazard ratio [aHR], 3.68) and antipsychotic-only use (aHR, 3.84) compared with antidepressant-only use. Similarly, the risk for seizures increased during the period of concomitant use (aHR, 2.06) and antipsychotic-only use (aHR, 2.05) compared to antidepressant-only use. For both cohorts, the antipsychotic dose in the concomitant use was lower than the dose in the antipsychotic-only use group. Higher dose of antipsychotics was associated with an increased risk of movement disorders (low dose: aHR, 3.28; high dose: aHR, 5.38). Similarly, increasing the daily dose of antipsychotics was associated with an increased risk of seizure development (low dose: aHR, 1.91; high dose: aHR, 2.30).

During the period of concomitant use of antipsychotic and antidepressants, the risk of movement disorder was highest with haloperidol, followed by polypharmacy, aripiprazole, risperidone, and quetiapine. Risk of seizure was highest with polypharmacy, followed by 

, aripiprazole, and risperidone. These results suggests that the potential development of movement disorders and seizure should be carefully considered with the use of adjunctive antipsychotics for the treatment of depression in children and adolescents.

Although not commercially available in the United States, agomelatine efficacy and safety were evaluated for the treatment of children and adolescents with major depressive disorder receiving psychosocial counseling in 9 countries.

 After a 3-week run-in period, 400 children and adolescents (aged 7 to 17 years) who were unresponsive to psychosocial therapy were randomized to agomelatine (10 mg/day or 25 mg/day), active control (fluoxetine 10 to 20 mg), or placebo for a 12-week trial. Standardized manualized psychosocial counseling was continued throughout the double-blind randomized controlled trial. At week 12, agomelatine 25 mg/day was statistically significant from placebo on the primary outcome measure of change in the CDRS-R a total score from baseline. Similarly, fluoxetine was significantly superior to placebo. Although statistically significant, Cohen’s effect size for agomelatine 25mg/day was small (0.29) and similar to fluoxetine (0.26).

The most frequent adverse events with agomelatine were thirst, dry mouth, and weight increase. Agomelatine has been associated with the potential to increase liver enzyme concentrations in the blood. The incidence of reversible aminotransferase increases more than 3 times the upper limit of normal was 1% in both agomelatine groups, 2% in fluoxetine group, and 0% in the placebo group in this trial.

In a case series, the effectiveness of a single esketamine administration either subcutaneous (SC) or intravenous (IV) on reducing depressive symptoms and 

 for adolescents with major depressive disorder and suicidal ideation was examined (Faria-Guimaraes et al 2022).

 Eight patients received 0.5 mg/kg esketamine SC, and 2 patients received 0.5 mg/kg esketamine IV.

A significant decrease in depressive symptoms (mean total Montgomery-Asberg Depression Rating Scale score) and suicidal ideation was found from baseline to 24-hour postadministration. The most frequently reported adverse events were dissociation (50%), dizziness (40%), and drowsiness (30%). There was no treatment-emergent suicidality. Although the results are promising, large-scale controlled trials are necessary to further assess the efficacy of esketamine for treatment of depression and suicidality in adolescents with major depression.

In addition to antidepressant medication, 

 (ECT) is an option for treatment resistant depression. To date, there are no controlled trials of ECT for the treatment of children and adolescents with major depression. A recent systematic review examined the effectiveness and adverse-event profile of ECT for treatment-resistant mood disorders in children and adolescents.

 The review included 41 studies (20 case series, 2 case-controlled studies, and 19 case reports). Out of 601 patients, 322 were diagnosed with unipolar depressive disorder. Patients received an average of 12 ECT treatments.

Most studies used the Clinical Global Impression Scale as a measure of improvement and reported response rates for depression ranging from 53% to 77%. For those studies that used objective depression symptom ratings scales, treatment improvement averaged 64%. For those studies with n > 30, response rates for depression were 70 to 82%. The Mini-Mental State Exam was used in 7 studies, and there was no evidence of significant posttreatment cognitive impairment. However, subjective reports of cognitive symptoms were common, particularly short-term memory complaints. Other common adverse effects reported were headache, nausea, vomiting, confusion, agitation, and muscle soreness. Treatment-emergent mania and prolonged seizures were reported in some cases. Discontinuation due to adverse effects occurred in 1.5% of cases.

Based on this review, the investigators suggest that ECT is safe and effective for the treatment of mood disorders in child and adolescent populations and should be considered in severe and treatment-refractory cases. The investigators acknowledge the limitation of the data since most of the literature was case series. Further investigation of the efficacy of ECT for treatment-resistant mood disorders in children and adolescents is needed.

1. Atkinson SD, Prakash A, Zhang Q, et al. A double-blind efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder. 

2. Emslie GJ, Prakash A, Zhang Q, et al. A double-blind efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder. 

3. Saito T, Ishida M, Nishiyori A, et al. Efficacy and safety of duloxetine in children and adolescents with major depressive disorder in Japan: a randomized double-blind placebo-controlled clinical trial followed by an open-label long-term extension trial. 

4. Findling RL, DelBello MP, Zuddas A, et al. Vortioxetine for major depressive disorder in adolescents: 12- week randomized, placebo-controlled, fluoxetine-referenced, fixed-dose study. 

5. Jeon SM, Park H-Y, Park S, et al. Association of treatment with antipsychotics, antidepressants, or both with movement disorders and seizures among children and adolescents with depression in Korea. 

5. Faria-Guimarães D, Vieira F, Souza-Marques B, et al. Letter to the editor: antidepressant and antisuicidal effects of esketamine in adolescents with major depressive disorder and suicidal ideation: a case series. 

6. Arango C, Buitelaar JK, Fegert JM, et al. Safety and efficacy of agomelatine in children and adolescents with major depressive disorder receiving psychosocial counselling: a double-blind, randomized, controlled, phase 3 trial in nine countries. 

7. Faria-Guimarães D, Vieira F, Souza-Marques B, et al. Letter to the editor: antidepressant and antisuicidal effects of esketamine in adolescents with major depressive disorder and suicidal ideation: a case series. 

8. Castaneda-Ramirez S, Becker TD, Bruges-Boude A, et al. Systematic review: electroconvulsive therapy for treatment-resistant mood disorders in children and adolescents. 

Further evidence-based antidepressant treatments are needed for children and adolescents with depression.

Latest on Pediatric Depression Treatments

How does it feel to be back at ThoughtSpot in person?

 (President, Community and Specialty Pharmacy and Long-term Care, AmerisourceBergen): It feels amazing. So much energy, so much excitement. What I think about most, I think I feel humble. I feel honored. And I feel inspired because of the customers we have here. What they've done over the past 2 years has been amazing, inspirational and makes me proud to be part of the profession.

 (Pharmacist): Usually at work, we’re right there in thick of things and you feel all the pressures of the day- to-day job. What I love about being here is that you get to kind of breathe for a moment and hear some more positive perspectives from fellow pharmacists.

 (AmeriSource Bergen Business Coach): I think ThoughtSpot is a great place to connect with your peers. A lot of learning actually comes from your peers: what they're doing in a community, how they can learn, how they can take those processes back to their location in their community.

 (Pharmax Pharmacy, St. Louis, Missouri): Of course coming off not being able to go to meetings, this one has been incredible. Love to see my peer groups and everything else at these meetings. Getting to see the executives firsthand again and listening to their passionate story about what they believe in pharmacy and what we're doing, how we're adapting.

 (EVP & President of Customer Operations, Animal Health, and Community & Specialty Pharmacy, AmerisourceBergen): It is so exciting to be here. The energy in this building, I can't think of a better way to celebrate 

 40th anniversary than being here in Orlando with all of our customers who we've missed so much.

 (CEO & Pharmacist-in-charge, Springfield Pharmacy, Springfield, Pennsylvania): I was excited to come to this year's ThoughtSpot because there's so much happening in the pharmacy world and a lot of changes. I'm just so excited about it.

 What’s your favorite thing about ThoughtSpot?

Pharmacy): It's hard to choose. My favorite thing I would say is watching all of our pharmacy owners connect and collaborate. I get to meet with pharmacies on a regular basis. But to see someone from Kentucky meeting with someone from Iowa, they share the same set of concerns and issues and to see them be able to network and bounce ideas off one another is really, really rewarding.

 (McCarthy Drugs, Santa Monica, California): We've been coming to ThoughtSpot for many years, so it's good to see the community back together from different parts of the United States.

 I think the Pharmacy of the Year is always so exciting. You walk down the halls, you can see all the names of past winners. We see last year's winner when you walk into the trade show floor, in bright lights. It's really exciting to see all of the pharmacies and who will win this year. I think Pharmacy of the Year is just the most exciting thing.

 The best thing about ThoughtSpot is connecting with everyone and just sharing ideas, planning for the future.

 Probably my most favorite thing is just seeing people in the hallways reconnect, friends that have known each other for a long time. It's like seeing family, a family reunion, and at the end of the day you walk away from this meeting thinking ‘that was amazing’.

 Are you enjoying your first ThoughtSpot meeting?

 (Medicine Man Pharmacy, Wahoo, Nebraska): So this is my very first ThoughtSpot and I didn't really know what to expect. But since being here, it's been really fun to meet new people and also to see what we can bring back from here to our community.

 (Association Professor, West Virginia University, Pharmacist, Westfront Family Pharmacy, Morgantown, West Virginia): So it's great. I've enjoyed seeing so many pharmacists that I've worked with over the course of my career and getting to collaborate, getting to network. It's so wonderful to be back in person and see people again.

(Pharmacy Student, South Carolina): So it's definitely huge. It's definitely a big experience. I'm excited to be here. I’m thankful my boss has sent me. I just am thankful to be here and be able to learn more and apply this to my future as a health care provider.

 Why is it important to celebrate independent pharamacy?

 You know independent community pharmacy has always been just such a core anchor in their community. So that's always something to celebrate, but this year in particular, community pharmacy has stepped up in a way that has helped revive this country. That certainly needs to be celebrated. I think it's an important time because the American public now has a whole new appreciation for what community pharmacy is and can do and should do within their communities and that's certainly worth celebrating.

 What do you hope attendees will take away from this year’s meeting?

 I hope they walk away feeling energized about the future of independent pharmacy. Because over the last 3 years, they've proven how valuable they are to their patients and to their communities. So I hope they leave energized, refreshed, and really excited about the future.

I hope attendees can leave here and know that they're not alone. I know they're in their pharmacy often by themselves, don't feel like they have a network. But we are here for them, all the time. They get to interact with all of their colleagues, from all over the country and just leave here knowing that they have a support system that will always be here unwavering.

 If you could share one message with this year’s ThoughtSpot attendees, what would that message be?

I think that it's really important for everybody to see what other folks are doing and take that back to their own areas, so that they're not reinventing the wheel and that they can learn from others and get to do very cool things in their own areas too.

 The one message I would leave for everyone is: AmerisourceBergen will always be here in support of pharmacy, and specifically independent pharmacy. We have an unwavering commitment to that. It's the core of what AmerisourceBergen does and we think about you every day.

 That the ThoughtSpot community really aims to help the pharmacies and independent pharmacy. And they've got a lot of opportunities for learning and for connecting, so take advantage of it. Make sure you visit every booth. Make sure you visit with every one of your representatives. It's a great opportunity to get together.

 I think that's really simple. Thank you. Thank you for all that you do for your patients and in your communities. And thank you for letting us support you and those efforts and being amazing partners. Our pharmacies are very easy to support and to champion and to advocate for. So I think just a hearty thank you.

 It's time to activate. It's time to advocate and it's time to unify. We have an opportunity right now to transform this profession for years to come. And we need everybody to join together in that message to communicate the value that we provide each and every day.

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Acne is an extremely common skin disease and while particularly prevalent in adolescents, it can persist into adulthood as well. Most dermatology providers are very familiar with treating acne, as approximately 15% of the US population has suffered from acne and, by some estimates, nearly 9 out of 10 adolescents have also suffered from this condition. Julie Harper, MD, a board-certified dermatologist in private practice in Birmingham, Alabama, a founding director and past president of the American Acne and Rosacea Society, gave a presentation on acne treatment updates at the Maui Derm NP+PA Summer 2022 conference.

Before discussing treatments, Harper took time to highlight the goals of acne treatment and she shared her CLEAR acronym for effective treatment. The 3 most important goals of acne treatment are achieving meaningful improvements in lesion count, preventing sequalae, and improving quality of life. The CLEAR acronym can help accomplish this by reminding providers how to best counsel patients on effective treatment—C: communicate expectations, L: listen to customize treatment, E: treat early, A: treat aggressively, R; don’t resist isotretinoin. This was followed by a brief discussion on the role of topical therapy in acne treatment. Topical therapy is considered first-line treatment in most mild to moderate patients and it can be used as monotherapy or as combination therapy. However, topical antibiotics should rarely be used as monotherapy. There is also some utility for topical therapy in the treatment of acne sequelae.

Harper began her focused update on treatments with topical retinoids, which work by binding to the retinoic acid receptor, which modulates genes associated with acne etiology. Specifically, topical retinoids normalize follicular epithelial hyperkeratinization and are anti-inflammatory in nature. There have been 4 generations of FDA-approved topical retinoids, with the most recent approval for trifarotene 0.005% cream in 2019. This novel topical therapy is the first new retinoid molecule the FDA has approved in over 20 years and was studied on facial and truncal acne. In phase 3 clinical trials, trifarotene achieved a 42% IGA/PGA success rate at week 12 and a 65% absolute reduction in inflammatory lesions for both face and trunk.

 “Topical retinoids remain a cornerstone of acne treatment. I am grateful that we have seen innovation in this space. We have a whole new retinoid molecule, trifarotene, created to specifically and precisely target the retinoic acid receptors (RAR) receptor,” Harper said.

Harper followed her discussion of trifarotene with another retinoid, tazarotene lotion 0.045%. This medication was FDA approved in 2019 for daily use in patients 9 years and older with moderate-to-severe acne. In a phase 2 study, tazarotene lotion performed better than tazarotene 0.1% cream in percent change in mean inflammatory and non-inflammatory lesions at week 12.

 The novel vehicle, polymeric emulsion technology, allows for a lower percentage of active ingredients, which improves the tolerability of tazarotene, traditionally an irritating agent. Before moving on to oral agents, Harper mentioned 2 other important topical therapies. First was E-tretinoin 0.1%/E-BPO 3% cream, which can be stabilized together through microencapsulation technology. This technology also allows for improved tolerability of the medication. Next, clascoterone was highlighted and the unique mechanism of action was displayed. Clascoterone is a topical anti-androgen that binds to the androgen receptor and has limited systemic activity.

 In 1 clinical trial, IGA treatment success for clascoterone was 16.1% vs 7% for the vehicle. This medication is the first topical antiandrogen for acne and is appropriate for use in both male and female patients. “We all have a tendency to think of our oral antibiotics in the management of acne as being the heavy lifter once they are added to a treatment regimen, but in fact the topicals are the unsung heroes,” Harper said. “While there are no head-to-head studies, clinical trials consistently show more acne patients achieve clear or almost clear with topical agents than with oral antibiotics.”

Harper also discussed oral therapy, which she said is equally as important as topical therapy. Oral therapy is recommended for moderate-to-severe acne that does not respond to other treatments or for inflammatory acne that is nonresponsive to topical antibiotics. Sarecycline, the newest oral antibiotic therapy, offers a narrow spectrum of therapy because it has a minimal effect against gram-negative bacilli. The advantage of this narrow spectrum may be a reduced tendency to disrupt normal gut flora.

 Sarecycline is taken once a day with or without food, and adverse events, while uncommon, include nausea and vaginal yeast infections. Its activity against C acnes is equivalent to that of doxycycline and minocycline.

Harper highlighted spironolactone oral therapy, which is not FDA approved for acne treatment but remains a popular option. She reviewed some high-yield pearls when using spironolactone. There is no need to check potassium in healthy women (between aged 18 and 45 years).

 There is no evidence of an increased risk of breast cancer, despite its FDA black box warning stating that “spironolactone has been shown to be a tumorigen in chronic toxicity study in rats.”

 Spironolactone takes 2 to 3 months to achieve optimal efficacy. An ideal way to use this medication is in combination with other acne treatments (topical therapies or oral antibiotics) and it even can be used in combination with oral contraceptives.

 Practically, dosage should be between 25 and 200 mg, but Harper prefers a maximum dose of 100 mg. A higher dose of spironolactone will lead to a high rate of side effects.

Harper ended her talk with isotretinoin, one of the most commonly used medications for the treatment of acne. She noted that the goal of isotretinoin therapy is complete clearance with 1 course of treatment while minimizing adverse effects and risks. An appropriate end point often varies by provider but a study by Tan et al found that the traditional end point dose of 120 to 150 mg/kg appears to vary with severity.

 Optimal end point dosing of isotretinoin has the goal of preventing relapse. Relapse can be defined in different ways, such as deterioration in acne requiring systemic therapy and those who require retreatment with oral isotretinoin.

 Relapses still occur in 20% to 30% of cases and less than 120 mg/kg is considered a cumulative dose that is too low. Patient characteristics that make relapse more common include younger age, male gender, severe presentation, females with polycystic ovary syndrome, and patients who present with a large number of comedones.

Harper reviewed laboratory monitoring with isotretinoin therapy. A study by Zane et al found that the greatest perturbation in laboratory abnormalities on isotretinoin were in triglycerides and total cholesterol.

 As such, the FDA package insert states that “blood lipid determination should be performed before isotretinoin is given and then at intervals until lipid response is established, which is usually about 4 weeks.” A meta-analysis on laboratory evaluation of isotretinoin found that while lab values demonstrated a change from baseline, none of them were considered high risk changes.

 The authors recommended performing lipid and hepatic panels at baseline and 2 months after therapy, with repeat labs dictated by medical history.

Harper wrapped up her presentation with a discussion on the risk of depression and suicide in patients on isotretinoin therapy, a traditionally contentious topic. A systematic review on the topic conducted by Huang et al in 

The Journal of The American Academy of Dermatology

 analyzed 31 studies and found that only 1 had evidence to show that isotretinoin significantly increased the risk of depression.

 The authors concluded that although individual susceptibility to depression cannot be ruled out, isotretinoin can be safely used without increasing the risk of depression. Another medical expenditure panel survey study, which utilized questionnaires like the Kessler 6-Item Psychological Distress Scale, found that patients on isotretinoin had fewer depressive symptoms than those on oral antibiotics and had less psychological distress.

It is exciting to see new innovation in the treatment of acne and review the critical data on traditional therapies. Given the frequency with which this condition is seen in the dermatologist’s office, the management of acne is always an important topic to stay updated on.

This article originally appeared on Dermatology Times.

Julie Harper, MD, a board-certified dermatologist in private practice in Birmingham, Alabama, a founding director and past president of the American Acne and Rosacea Society, offers the latest in acne treatment.

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