Ariann Chelli, LCSW, LCADC, MBA, is the clinical director at Desert Hope Treatment Center, an American Addiction Centers facility.

Methamphetamine use disorder presents one of the most challenging clinical scenarios in 

medicine today. While national attention has focused on the opioid epidemic, methamphetamine-related overdose deaths increased nearly 5-fold between 2012 and 2018, with polysubstance use involving stimulants now driving a significant portion of overdose mortality.

Treatment admissions for methamphetamine use continue to rise, yet our clinical toolkit remains frustratingly limited compared to what we can offer patients with opioid or alcohol use disorders.

 This needs to change, sooner rather than later.

Methamphetamine Use Disorder Has No Standard Medical Detox Protocol

The fundamental challenge is straightforward: we have no FDA-approved medications for methamphetamine use disorder and no established medical detox protocols.

 Clinicians must manage acute withdrawal and support early recovery using only symptomatic treatment and behavioral interventions. This represents a significant disparity in our healthcare system that directly affects patient outcomes.

Methamphetamine’s mechanism of action—massive dopamine release and reuptake inhibition—creates profound neurochemical disruption. Chronic use depletes dopamine stores and downregulates receptors, resulting in severe anhedonia and cognitive impairment.

Unlike opioid withdrawal, which is time-limited and medically manageable with established protocols, methamphetamine withdrawal can persist for weeks with symptoms including intensive cravings; hypersomnia (sometimes > 20 hours daily initially); depression severe enough to warrant suicide precautions; vivid dreams or nightmares; a slowing of thoughts, actions, and speech; as well as increased appetite.

The absence of standardized detox protocols means clinical approaches vary significantly between facilities. Some programs provide comprehensive psychiatric monitoring with targeted symptom management, such as antipsychotics for persistent psychosis, sleep aids for the initial hypersomnia phase, and antidepressants when indicated. Others offer minimal medical intervention. This inconsistency contributes to high rates of treatment dropout during the acute withdrawal phase when symptoms are most severe and patients have the fewest internal resources to manage them.

Post-acute withdrawal syndrome (PAWS) presents additional challenges. Patients may experience episodic cravings, mood instability, cognitive difficulties, and anhedonia for months into recovery.

Executive function deficits can impair patients’ ability to engage with traditional talk therapy or follow complex treatment plans. Neuroimaging studies show that while significant recovery occurs, some changes may persist for a year or more, requiring clinicians to adjust expectations and treatment intensity accordingly.

Evidence-Based Treatment Options for Methamphetamine Use Disorder: What Clinicians Can Use Now

Current evidence-based approaches rely heavily on behavioral interventions. Contingency management, which provides tangible rewards for verified abstinence, shows the strongest evidence for efficacy.

 Cognitive-behavioral therapy, community reinforcement approaches, and peer support all demonstrate benefits.

The Matrix Model, an intensive outpatient approach combining these elements, has shown promise specifically for stimulant use disorders.

 However, these interventions require significant patient engagement during a period when neurochemical changes make engagement extraordinarily difficult.

Research into pharmacological options continues, with studies examining various approaches: bupropion and naltrexone combination therapy, modafinil, topiramate, and others targeting different neurotransmitter systems.

While some show modest promise in reducing use or supporting abstinence, none have achieved FDA approval. The field urgently needs continued investment in medication development research.

Clinicians can optimize outcomes within current limitations by providing a comprehensive assessment for co-occurring disorders, particularly 

, PTSD, and ADHD, which are prevalent in this population.

Extended residential treatment or intensive outpatient programming during the initial months allows for appropriate structure and support during neurological recovery. Harm reduction approaches, including safer use education and connection to services regardless of abstinence status, keep patients engaged and reduce mortality risk.

Addressing methamphetamine use disorder requires clinical creativity, patience, and realistic expectations about recovery timelines. Until we develop effective medications and standardized protocols, clinicians must rely on comprehensive behavioral programming, treatment of co-occurring conditions, and sustained support through the extended recovery period this disorder demands.

 Drug Overdose Deaths in the United States, 1999–2018

. National Center for Health Statistics; 2020. NCHS Data Brief No. 356.

SAMHSA. Key Substance Use and Mental Health Indicators in the United States: Results from the 2021 National Survey on Drug Use and Health. www.samhsa.gov. Published 2021. 

https://www.samhsa.gov/data/sites/default/files/reports/rpt39443/2021NSDUHNNR122322/2021NSDUHNNR122322.htm

An Update on Epidemiology, Pharmacology, Clinical Phenomenology, and Treatment Literature

Loss of Dopamine Transporters in Methamphetamine Abusers Recovers with Protracted Abstinence

Fleury MJ, Cao Z, Grenier G, Huỳnh C. Predictors of dropout from treatment among patients using specialized addiction treatment centers. 

Volkow ND, Michaelides M, Baler R. The Neuroscience of Drug Reward and Addiction. 

Brown HD, DeFulio A. Contingency management for the treatment of methamphetamine use disorder: A systematic review. 

Lee NK, Rawson RA. A systematic review of cognitive and behavioural therapies for methamphetamine dependence. 

Obert JL, McCann MJ, Marinelli-Casey P, et al. The matrix model of outpatient stimulant abuse treatment: history and description. 

Trivedi MH, Walker R, Ling W, et al. Bupropion and Naltrexone in Methamphetamine Use Disorder. 

Anderson AL, Li SH, Biswas K, et al. Modafinil for the treatment of methamphetamine dependence. 

Moszczynska A. Current and Emerging Treatments for Methamphetamine Use Disorder. 

Articles

Methamphetamine use disorder is escalating, with a sharp rise in overdose deaths and treatment admissions, yet lacks FDA-approved pharmacotherapies and standardized detoxification protocols. Withdrawal is often protracted, featuring severe hypersomnia, depression, cravings, and cognitive slowing, with PAWS extending symptoms for months. Facility-to-facility variability in medical and psychiatric support likely contributes to early dropout. Current best-supported treatments are behavioral, particularly contingency management, alongside CBT-based and community reinforcement approaches, including the Matrix Model. Optimizing care requires structured programming, comorbidity management, harm reduction, and sustained longitudinal support.

Without FDA-approved medications or standardized detox protocols, clinicians face unique challenges treating methamphetamine addiction.

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Treating Methamphetamine Use Disorder Without FDA-Approved Medications

Joseph Murray, MD, is a gastroenterologist at Mayo Clinic.

Celiac Disease in 2026: Diagnosis, Management, and the Drug Pipeline

Celiac disease is one of the most common autoimmune conditions in the world, yet it carries a distinction that sets it apart from nearly every other chronic GI disease gastroenterologists manage: there is no approved drug to treat it. While the inflammatory bowel diseases have benefited from decades of investment and a crowded therapeutic pipeline, celiac disease has largely been left behind.

At Digestive Disease Week (DDW) 2026 in Chicago, IL, Joseph Murray, MD, a gastroenterologist and professor of medicine at Mayo Clinic, outlined where the field stands on diagnosis, long-term management, and the road ahead for drug development.

For decades, celiac disease diagnosis required endoscopic biopsy of the small intestine, but that paradigm is shifting. When the tissue transglutaminase IgA (tTG-IgA) antibody test returns at > 10 times the upper limit of normal, the probability of celiac disease is high enough that a biopsy-avoidance strategy is now established practice in pediatrics and is increasingly being considered for adults.

The 2023 ACG guidelines recommend EGD with multiple duodenal biopsies for confirmation of diagnosis in both children and adults, but also suggest that in adults who are unwilling or unable to undergo endoscopy, a combination of high-level tTG-IgA exceeding 10 times the upper limit of normal with a positive endomysial antibody on a second blood sample may serve as a diagnosis of likely celiac disease. A follow-up biopsy should be considered at 2 years, given that the median time to achieve mucosal healing is 3 years.

Murray emphasized, however, that at least half of patients do not reach that serologic threshold and still require endoscopy, and timing is critical. If a patient goes gluten-free before the biopsy is performed, intestinal healing may produce a false-negative result, obscuring the diagnosis entirely.

"It's very important that as a specialty we recognize the time dependency of accurate diagnosis," Murray told 

. "We want patients to get a diagnosis so they can get on treatment quickly — but they need to still be eating gluten when that biopsy is done."

Murray additionally stressed that a celiac disease diagnosis should not end with dietary counseling. Newly diagnosed patients require evaluation for nutritional deficiencies, anemia, and bone density loss, which can be substantial. Referral to a dietitian with celiac-specific expertise is essential, as well as long-term gastroenterologist follow-up, including repeat serology at 6 months to confirm antibody decline and follow-up biopsy at 1 to 2 years to verify mucosal healing.

Ongoing symptoms despite a gluten-free diet should prompt evaluation for commonly associated conditions, including microscopic colitis, small intestinal bacterial overgrowth, and pancreatic exocrine insufficiency, and, in some cases, a reassessment of the original diagnosis.

"We would not discharge a patient with Crohn's disease from our care," Murray said. "It shouldn't be any different for celiac disease."

The most consequential gap in celiac disease management is pharmacologic, with no drug currently approved for the condition. Murray acknowledged the field's checkered history with drug development: roughly a dozen agents have entered clinical development, with many stumbling or failing.

The pipeline now includes more than 30 investigational agents across multiple stages of development, with active programs targeting IL-15-mediated inflammation, enzyme therapies, and immune tolerance induction. Among the more closely watched candidates is TEV-53408, an anti-IL-15 monoclonal antibody from Teva that recently received FDA Fast Track designation and is currently in phase 2 evaluation.

Murray noted that the gluten-free diet, the current standard of care in celiac disease, fails more patients than is widely appreciated. An estimated 30 to 40% do not achieve mucosal healing despite their best efforts, and a similar proportion experience significant symptoms from accidental gluten exposures.

“The gluten free diet is very easy for me to say ‘go gluten free.’ That's sounds easy, but the living of that is not easy, and it's not particularly effective,” he said. "I'm optimistic that we will have better treatments, but we have to prove that they work."

Editor's note: Murray reports no relevant disclosures.

Murray JA. DRUG DEVELOPMENT IN CELIAC DISEASE: HOW CAN WE GET FROM THE LAB TO CLINIC? Session presented at: Digestive Disease Week (DDW) 2026; Chicago, IL; May 2–5, 2026.

Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology Guidelines Update: Diagnosis and Management of Celiac Disease. 

. 2023;118(1):59-76. doi:10.14309/ajg.0000000000002075

Teva. Teva Celiac Disease Candidate Granted Fast Track Designation by US FDA. May 27, 2025. Accessed May 3, 2026. 

https://ir.tevapharm.com/news-and-events/press-releases/press-release-details/2025/Teva-Celiac-Disease-Candidate-Granted-Fast-Track-Designation-by-US-FDA/default.aspx

Videos

Murray breaks down what gastroenterologists need to know about celiac disease diagnosis and management.

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Gastroenterology condition center page is a comprehensive resource for clinical news and insights on digestive and GI conditions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for 

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Strategic Alliance Partnership

Confronting Unmet Needs in Celiac Disease, With Joseph Murray, MD

Marla Dubinsky, MD, is chief of the division of pediatric gastroenterology and nutrition and co-director of the Susan and Leonard Feinstein IBD Clinical Center, Mount Sinai Kravis Children's Hospital, Icahn School of Medicine.

The Drug Holiday Dilemma in IBD — and How SC Infliximab Changes It

Treatment interruptions with anti-TNFs are common in clinical practice, driven by loss of response, safety concerns, pregnancy, or patient preference. Historically, reintroducing the drug intravenously has carried meaningful risk.

However, new post hoc data from the phase 3 LIBERTY trials suggest that subcutaneous (SC) infliximab may offer a safer, more durable path back to disease control for patients with 

Crohn's disease (CD) or ulcerative colitis (UC)

 following a drug holiday. The analysis was presented by Marla Dubinsky, MD, a gastroenterologist and professor of medicine at the Icahn School of Medicine at Mount Sinai, at Digestive Disease Week (DDW) 2026 in Chicago, IL.

"Historically, about 50% of patients are off anti-TNF therapy over the first 2 to 3 years," Dubinsky told 

. "Before we understood drug levels and antibodies, we just waited for people to lose response and then moved on."Before we understood drug levels, safety, antibodies, there were quite a number of patients who were stopping it, predominantly for loss of response, with a large number of them associated with anti drug antibodies because they were not proactively optimized. We just waited for people to lose response, got a drug level and said ‘You've now got antibodies, I have to move on.’”

The LIBERTY-CD and LIBERTY-UC trials randomly assigned patients who responded to IV infliximab induction to either SC infliximab 120 mg or placebo every other week through week 54. Patients in the placebo arm who experienced disease recurrence after a minimum 16-week drug holiday were eligible to receive SC infliximab 240 mg, double the approved maintenance dose, as a form of reintroduction.

The present post hoc analysis evaluated 51 CD and 77 UC patients from the placebo arms, assessing clinical, biochemical, endoscopic, and pharmacokinetic outcomes through week 102.

Early clinical responses emerged within 8 weeks of SC infliximab initiation and were sustained throughout the study period, with partial clinical response rates of 92.3% in CD and 96.6% in UC at treatment end. Fecal calprotectin remission was achieved in 61.1% of CD patients and 65.2% of UC patients, with endoscopic response rates of 64.0% and 68.8%, respectively. Additionally, treatment persistence through week 102 was 72.3% in CD and 61.9% in UC.

Dubinsky highlighted the parallel between clinical recapture and pharmacokinetic recovery as a key finding. Serum infliximab levels rose markedly after SC reintroduction and remained stable, a pattern that tracked directly with clinical response.

“You see this parallel where you get this recapturing in 8 weeks, and when you look at the trough level, you then see you've recaptured the trough level that you stay at throughout that period of you now being in the 240 arm,” she said. “I think the fact that you see that association of the PK coming back after no drug level, or a honeymoon during that period, and you see that clinical response parallel the recapture of the trough level, or that consistent, sustained drug level that we're used to, really tells you that you recapture because you're able to bring back the drug concentration that's associated with response.”

Dubinsky additionally highlighted immunogenicity findings as among the most clinically significant data from her research. Reintroduction of IV infliximab after a drug holiday carries well-documented risk of infusion reactions, driven by a surge in anti-drug antibodies (ADAs) upon re-exposure. SC reintroduction appeared to sidestep this problem. Despite high ADA rates at the time of SC reintroduction, antibody status had minimal impact on outcomes, with approximately three quarters of patients maintaining treatment persistence regardless of ADA status.

Dubinsky noted that SC infliximab 240 mg is not currently FDA-approved for this indication in the US, but expressed hope that publication of these data would support conversations with payers and health authorities about its clinical utility.

Editor's note: Dubinsky reports relevant disclosures with AbbVie, Abivax, Astra Zeneca, BMS, Celltrion, Eli Lilly, Janssen, Johnson and Johnson, Merck, Pfizer, Prometheus Labs, Roche, Sanofi, Spyre, Takeda, and others.

Dubinsky MC, Sands BE, Abraham BP, et al. Recapturing Disease Control With Subcutaneous Infliximab After a Drug Holiday Following Intravenous Infliximab Induction: A Post Hoc Analysis of LIBERTY-CD and -UC Studies. Presented at Digestive Disease Week (DDW) 2026; Chicago, IL; May 2–5, 2026.

Rubin DT. Restarting Biologic Agents After a Drug Holiday. 

Marla Dubinsky, MD, explains LIBERTY post hoc data showing SC infliximab 240 mg recaptured clinical response within 8 weeks in CD and UC patients following a drug holiday.

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Subcutaneous Infliximab Recaptures Disease Control After Treatment Interruption in IBD

Laurie Keefer, PhD, is a clinical health psychologist and professor of medicine at Icahn School of Medicine at Mount Sinai.

The Brain-Gut Connection in GI Clinical Practice

The gut microbiome has become a fixture of consumer wellness culture, but for practicing gastroenterologists, the clinical reality of gut health is considerably more nuanced.

At Digestive Disease Week (DDW) 2026 in Chicago, IL, Laurie Keefer, PhD, a health psychologist and professor of medicine at the Icahn School of Medicine at Mount Sinai, led a session calling on clinicians to expand their framework for gut health, one that accounts for the psychosocial forces shaping their patients' lives and explicitly integrates mental health into GI care.

"Gut health is a hot topic right now," Keefer told 

. "If you go on TikTok, it means one thing. If you come to DDW, it means another."

The Social Determinants Shaping Gut Health

For clinicians, gut health encompasses far more than diet or supplement use. Keefer emphasized that the full range of social determinants and lifestyle factors, including chronic stress, physical inactivity, loneliness, and ongoing exposure to conflict and geopolitical instability, all influence the gut microbiome and contribute to dysbiosis. Research has increasingly linked social isolation and loneliness to reduced gut microbial diversity, itself associated with a range of inflammatory and cardiometabolic conditions.

"All of our patients should be concerned about their gut health, because they live in this world today," Keefer said.

The Bidirectional Mental Health Connection

A central theme of Keefer's session was the inseparability of gut health and mental health. The United States is in the midst of a recognized mental health crisis, and the gut-brain axis sits squarely at the intersection of these public health challenges. The microbiota-gut-brain axis is a complex, bidirectional communication network linking the central nervous system and the gastrointestinal tract, with growing evidence that gut health can impact mental well-being and vice versa. For clinicians, this means that anxiety and depression are not merely comorbidities to be managed separately, but rather act as active drivers of gut dysfunction, and gut dysfunction can perpetuate them.

"You can have depression and anxiety that affects your gut health, and your gut health can lead to depression and anxiety," Keefer explained. "We really can't disentangle those two things."

The third pillar of Keefer's session addressed the clinical role of brain-gut behavior therapies (BGBTs), a class of interventions that includes cognitive behavioral therapy, gut-directed hypnotherapy, and other psychologically informed approaches. These therapies target not only lifestyle and mental health, but also the way patients perceive and respond to GI symptoms.

BGBTs are short-term, clinician-administered interventions, and a 2025 systematic review and network meta-analysis published in 

 found that several, particularly those classified as brain-gut behavior therapies, are efficacious for global IBS symptoms.

Keefer framed this perceptual component as underappreciated in routine care. How a patient interprets mild bloating, and what behavioral response that triggers, can meaningfully shape the downstream course of their gut symptoms.

"We're targeting things like lifestyle and behaviors and mental health, but also the way symptoms are perceived," she said. "Really full circle, but not separating gut health from mental health."

Editors’ note: Keefer reports relevant disclosures with AbbVie, Ardelyx, Eli Lilly, Janssen, Pfizer, and others.

Keefer L. PSYCHOLOGICAL APPROACHES TO IMPROVE GUT HEALTH. Session presented at: Digestive Disease Week (DDW) 2026; Chicago, IL; May 2–5, 2026.

Culli L. Nearly 1 in 10 Adults in the U.S. Experienced a Mental Health Crisis Last Year. Johns Hopkins. August 19, 2025. Accessed May 3, 2026. 

https://publichealth.jhu.edu/2025/mental-health-crisis-hits-nearly-1-in-10-us-adults

Thakur ER, Khasawneh M, Moayyedi PM, et al. Efficacy of behavioural therapies for irritable bowel syndrome: a systematic review and network meta-analysis. The Lancet Gastroenterology & Hepatology. doi:

Laurie Keefer, PhD, makes the case for integrating mental health, social determinants, and brain-gut behavior therapies into routine GI care.

Rethinking Gut Health: Social Determinants, Mental Health, and Brain-Gut Therapies

Anjali Byale, MD, is a fellow at West Virginia University School of Medicine.

EUS-Guided Procedures vs Traditional Interventions for High Risk GI Patients

As endoscopic ultrasound (EUS)-guided procedures continue to gain traction in 

, a pair of new network meta-analyses presented at Digestive Disease Week (DDW) 2026 in Chicago, IL, offer the most comprehensive comparative data to date on their performance across key clinical outcomes.

Anjali Byale, MD, a gastroenterologist at West Virginia University, presented findings evaluating EUS-guided gallbladder drainage (EUS-GBD) for high-risk acute cholecystitis and direct EUS-guided gastroenterostomy (EUS-GE) for malignant gastric outlet obstruction (GOO), 2 conditions that have historically required surgical management.

"In the last 10 to 12 years, the trend has been more toward EUS-guided procedures," Byale told HCPLive. "These are procedures we can do on an outpatient basis — patients come in the morning and, if everything goes well, go home the same day."

EUS-GBD for High-Risk Acute Cholecystitis

The first study pooled data from 14 comparative studies published between 2012 and 2021, encompassing 1410 patients with a weighted mean age of 67.8 years. EUS-GBD was compared against laparoscopic cholecystectomy (LC), percutaneous gallbladder drainage (PC-GBD), endoscopic transpapillary gallbladder stenting (ETGS), and endoscopic naso-gallbladder drainage (EN-GBD).

Results showed EUS-GBD demonstrated superior clinical success compared with ETGS and was non-inferior to LC and PC-GBD. Technical success and adverse event rates were comparable across modalities. The most striking finding, however, was in reintervention: patients who underwent PC-GBD were nearly 9 times more likely to require reintervention than those who received EUS-GBD (odds ratio [OR], 8.76; 95% CI, 4.38-174.39).

"For someone who is a poor surgical candidate, we don't want to put them through anesthesia multiple times," Byale said. "Reintervention rates really matter, and EUS-GBD has a clear advantage there."

Direct EUS-GE for Malignant Gastric Outlet Obstruction

The second meta-analysis drew from 23 retrospective studies published between 2017 and 2025, totaling 2604 patients, comparing direct EUS-GE against enteral stenting (ES) and surgical gastrojejunostomy (SGJ) for malignant GOO.

Clinical success was comparable across all three modalities. However, SGJ carried significantly higher adverse event rates than EUS-GE (OR, 6.55; 95% CI, 3.38–12.69), and ES was associated with substantially higher reintervention rates (OR, 4.18; 95% CI, 1.60–10.90), largely driven by stent migration. While ES demonstrated the highest technical success, Byale cautioned against prioritizing that metric at the expense of durability and safety.

"We cannot compromise clinical success, that is the most important thing," she said. "But once procedures are comparable on that front, adverse events and reintervention become critical factors, especially for patients who are expected to live longer."

Institutional Capabilities and Patient Selection

Byale noted that EUS-guided procedures require advanced endoscopy expertise not available at all centers, and that LC, PC-GBD, and ES remain viable options where EUS capability is limited. The overarching message, she emphasized, is that clinical decision-making must weigh institutional resources, patient prognosis, and the full constellation of outcomes, not technical success alone.

Editors’ note: Byale reports no relevant disclosures.

Byale A, Adoor DM, Moond V, et al. EUS-GBD STRIKES THE OPTIMAL BALANCE OF SUCCESS, SAFETY, AND REINTERVENTION IN HIGH-RISK ACUTE CHOLECYSTITIS: A NETWORK META-ANALYSIS. Presented at Digestive Disease Week (DDW) 2026 in Chicago, IL, May 2-5, 2026.

Byale A, Adoor DM, Moond V, et al. DIRECT EUS-GE OUTPERFORMS ES AND SGJ IN SAFETY AND REINTERVENTION WHILE MATCHING CLINICAL SUCCESS: A 23-STUDY NETWORK META-ANALYSIS. Presented at Digestive Disease Week (DDW) 2026 in Chicago, IL, May 2-5, 2026.

Anjali Byale, MD, reviews data supporting EUS-guided procedures as first-line options for high-risk patients with cholecystitis or malignant gastric outlet obstruction.

EUS-Guided Procedures Outperform Traditional Interventions for High-Risk GI Patients

Chelsie Derman is an associate editor for 

who covers allergy and  psychiatry. She joined MJH Life Sciences in September 2023 after graduating from The College of New Jersey with a bachelor’s degree in journalism and professional writing. In her free time, she enjoys creative writing and reading.

FDA expands lumateperone for relapse prevention in schizophrenia, White House boosts psychedelics research, and AI reshapes psychiatry care debates in April 2026.

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Victoria Johnson joined MJH Life Sciences in 2020 and has written for NeurologyLive, CGTLive, and is now an assistant managing editor for HCPLive and RheumatologyLive. She doesn’t have enough time for her numerous hobbies. You can reach her at vjohnson@mjhlifesciences.com.

April 2026 saw new data from pivotal clinical trials and a new approval in asthma.

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Latest News

Treating Methamphetamine Use Disorder Without FDA-Approved Medications

Confronting Unmet Needs in Celiac Disease, With Joseph Murray, MD

Subcutaneous Infliximab Recaptures Disease Control After Treatment Interruption in IBD

Rethinking Gut Health: Social Determinants, Mental Health, and Brain-Gut Therapies

EUS-Guided Procedures Outperform Traditional Interventions for High-Risk GI Patients