Discontinuation of Aducanumab, Nociceptive Pain Syndromes, and Lamotrigine Indications and Side Effects

This newsletter provides details about the discontinuation of aducanumab and its associated ENVISION clinical study. The decision was made following a strategic review that identified financial shortcomings as a critical issue.

We also share key points from an interview on nociceptive pain syndromes, which have a connection to fibromyalgia; a presentation on lamotrigine, elaborating on its approved uses and potential cardiac adverse effects; and our practical research summaries of child, adolescent, and adult psychiatry.

Discontinuation of Aducanumab (Aduhelm) for Alzheimer’s Treatment

On January 31, 2023, the pharmaceutical company behind aducanumab (Aduhelm) decided to halt its development and sales, despite the drug having received accelerated approval from the FDA for the treatment of Alzheimer’s disease. The company also terminated the ENVISION clinical study.

What is aducanumab?
- It is a monoclonal antibody that selectively targets and reduces the amount of aggregated beta-amyloid forms, potentially slowing neurodegeneration and Alzheimer’s disease progression.
- It received accelerated approval for use in Alzheimer’s disease treatment, although its effectiveness remains under investigation.
What are the reasons for discontinuing aducanumab?
- The decision to discontinue came after a strategic review in 2023, which identified financial shortcomings as a key issue. The drug failed to generate sufficient revenue, prompting the company to cease its support.
- The decision was primarily driven by commercial considerations rather than scientific ones.
What were the challenges faced by aducanumab?
- An independent advisory committee of the FDA voted against its approval prior to the official decision.
- The drug was priced prohibitively high, and combined with insufficient insurance coverage, this made it difficult for patients to access it.
- Also, there was uncertainty about the efficacy of the drug, and it was not widely prescribed.
What was the objective of the ENVISION clinical study?
- The study was necessary to validate the benefits of aducanumab, as mandated by the FDA under its 2021 accelerated approval.
- It was initiated on June 2, 2022, and was projected to conclude by October 31, 2026.
What will happen to the patients participating in the ENVISION clinical study?
- Patients who are presently undergoing treatment with aducanumab will have the ability to continue until May 2024.
- The study encompasses approximately 2,500 individuals globally.
What other potential avenues will be available for patients diagnosed with Alzheimer’s disease?
- The company of aducanumab plans to pivot its focus towards exploring alternative therapeutic strategies, such as lecanemab. It received full FDA approval in July 2023 and has demonstrated significant potential. Learn more here.
- Donanemab is also currently seeking FDA approval as another potential treatment for Alzheimer’s disease. Learn more here.
- Nonetheless, there is still a significant question about the worth of monoclonal antibodies and the overall balance of their risks and benefits.

In conclusion, although aducanumab had received FDA’s accelerated approval for Alzheimer’s treatment, it failed to generate sufficient revenue due to its high cost, limited insurance coverage, and controversy over its efficacy. Read more here.

Nociceptive Pain Syndromes: Focus on Fibromyalgia With Daniel Clauw, M.D.

In this interview, Dr. Daniel Clauw discusses the concept of nociplastic pain syndromes, including fibromyalgia. He explores why these conditions affect women more than men and shares tips for management. The discussion further covers the use of pharmacologic strategies and neuromodulatory therapies in managing chronic pain, as well as the importance of considering nondrug integrative therapies, such as sleep improvement and increased physical activity.

Interview highlights include the following:

Excessive endogenous opioids may play a role in the pathogenesis of nociplastic pain syndromes. Hence, giving such patients opioids may worsen the condition in the long run.
Neuromodulation strategies, such as TENS, TMS, and transcutaneous vagal nerve stimulators, may be helpful in the management of nociplastic pain syndromes.

Learn more and earn 0.75 CME credits here.

Lamotrigine: From Current Indications to Cardiac Side Effects

In this presentation, Dr. Scott Beach unravels the world of lamotrigine, from its current applications to potential cardiac considerations. He reviews lamotrigine’s mechanism of action and titration techniques, providing valuable insights for effective administration. Dr. Beach also explores potential cardiac side effects and presents evidence-based monitoring strategies for patients with cardiac risk factors. Finally, he illustrates clinical learning by conveying all the information through a real-world clinical case example.

Strategies for Safe Usage and Proper Monitoring of Lamotrigine

For patients without a history of conduction disorder, ventricular arrhythmia, or Brugada syndrome, no EKG monitoring is indicated.
For patients with a history of conduction disorder or ventricular arrhythmia, check a baseline and follow-up EKG.
For patients with a known bundle branch block or a family history of Brugada syndrome, consider agents that do not widen the QRS interval.
Do not use lamotrigine in patients with Brugada syndrome.

Learn more and earn 0.5 CME credits here.

Quick Takes: Research, Digested

Comparative Safety of Oral Antipsychotics for Adverse Events in Adults After Surgery

The study found that oral haloperidol is just as safe as atypical antipsychotics in older patients after surgery, challenging common misconceptions about its risks, particularly cardiac arrhythmias.
Intravenous haloperidol, preferred for its quick action and low EPS incidence, is shown to be safe and effective for delirium management, without significant QTc prolongation or necessity for adjunctive sedatives or anticholinergics. Learn more.

Listen to or read the full volume and earn 0.5 CME credits here.

CAP Smart Takes: Research, Digested

The Role of Escitalopram in Treating Generalized Anxiety Disorder in Youth

Escitalopram was found to be significantly effective in reducing anxiety symptoms in children and adolescents with GAD.
It was well-tolerated, with no significant differences regarding discontinuation due to adverse events. Learn more.