Where We Are with Mood Disorders, Part 2

Scott T. Aaronson

Scott T. Aaronson, MD
Director, Clinical Research Programs
Sheppard Pratt Health System

Our Mental Health Awareness Month series continues with Dr. Scott Aaronson talking about depression treatment developments and what’s on the horizon.

Care for Your Mind (CFYM): Continuing on the subject of treatment, can we expect anything new or different – and hopefully improved – with regard to addressing mood disorders?

Scott T. Aaronson, MD: Yes, I believe we can! I’m encouraged by the research, which shows potential to yield effective new drug and device development. We haven’t had much change in the way that we treat depression for the last three decades, so it’s exciting that there are so many potential treatments emerging.

There are medications under review at the Food and Drug Administration (FDA) and in research that are entirely new, in that they operate through other mechanisms than the existing depression treatment. Although SSRIs, SNRIs , and NDRIs inhibit the reuptake – or reabsorption – of various neurotransmitters in the brain (respectively serotonin, serotonin plus norepinephrine, and norepinephrine and dopamine), the way in which they function is the same. And SSRIs, SNRIs, and NDRIs are effective for treating depression in most people.

But those are not the people who come to me. My practice is for adults with treatment-resistant depression, people for whom two or more of these medications (administered in appropriate doses for appropriate lengths of time) have not alleviated their depressive symptoms. A drug that works through the opioid system – the first non-monoamine medication – is in FDA fast-track review.

Another treatment in the fast-track FDA process involves NMDA antagonists (N-methyl-D-aspartate receptor antagonist), of which the drug ketamine is a frontrunner. One highlight of ketamine is that it appears to have a near-immediate effect of reducing suicidality. We are also hoping to find a better response to ketamine treatment for those with treatment-resistant depression. The challenge is that ketamine is most effective when administered intravenously (i.e., through an IV), so it is not something that would be self-administered. There is current research about whether intranasal administration of esketamine (one of the isomers of ketamine) would be effective.

As Care for Your Mind has covered (e.g., here and here), postpartum depression (PPD) is a significant issue for women and their families. We are anticipating the introduction of a drug targeted at PPD, to be taken orally. A medication that better addresses PPD without causing adverse effects on nursing babies would be a great addition to the antidepressants currently available.

CFYM: And how about on the device front?

Dr. Aaronson: Neurostimulation has been shown to be effective and the treatments are finally becoming more available. For example, with some insurance, transcranial magnetic stimulation (TMS) is a covered treatment. Non-pharmacological treatment has significant benefits as compared to medication, such as faster response to treatment and no systemic side effects, so we would like to be able to use it for the people who will benefit. We know that the brain is a combination of electrical and chemical, so there’s no reason for us to think that relying only on the chemical will provide all of the answers. Neuromodulation has shown that we can affect the brain through the use of magnets and electricity.

CFYM: In what ways can the FDA’s regulatory process be changed to bring more needed treatments to market while still preserving patient safety?

Dr. Aaronson: I think the FDA would benefit from updating and clarifying its approval process. Treatment developers – researchers and companies – don’t currently have a clear sense of what constitutes adequate information that would more or less guarantee approval. There is also the question of what time frame is appropriate and there, in my experience, it would help to have flexibility to show longer-term effects, as not all treatments are likely to show results in the same short time period. There are circumstances where a randomized controlled trial is not practical (e.g., variable dosages or a long time to see meaningful improvement) or even ethical (e.g., studying suicidality or requiring the use of sham or placebo treatment for many months) and the FDA should be able to better account for this. I hope we will soon have more of these promising treatments available to the patients and families who need them.

Read last week’s post, too.

 What do you think?

Which potential treatment do you find most exciting or interesting, and why? Do you have other ideas? Tell us on Facebook!

Editor’s Note: This post addresses pharmacological and electromagnetic approaches to depression. These are not the only treatments for depression, though they can play a crucial role depending on the circumstances. The Families for Depression Awareness Clinical Advisory Board holds that a combination of medication and talk therapy is the most effective treatment for moderate to severe depression, and that other factors such as sleep, exercise, family and social support, and stress reduction can help people improve their depressive symptoms. Caregivers can learn about their role in depression treatment on the Families for Depression Awareness website. For information on lifestyle changes to support better mental health, see, for example, this post from the University of Minnesota.

Additional Reading

Note: Care for Your Mind does not endorse any particular of these websites or organizations. Use discretion in sharing your personal information and make sure you understand the risks associated with any clinical trial you are considering.


Scott T. Aaronson, MD, is Director of Clinical Research Programs at Sheppard Pratt Health System in Baltimore, Maryland. He has been particularly involved with the development of new strategies to alleviate the symptoms in treatment resistant mood disorders. Dr. Aaronson earned his medical degree with honors from Harvard Medical School and completed a residency in psychiatry at McLean Hospital in Belmont, MA.  He is a Clinical Associate Professor of Psychiatry at the University of Maryland, School of Medicine.

Dr. Aaronson provides expert consultation across the system of care for patients with difficult to treat mood and psychotic disorders. He has published numerous articles on his research including pivotal studies in the use of devices – Transcranial Magnetic Stimulation (TMS) and Vagus Nerve Stimulation (VNS) – in the treatment of severe refractory mood disorders.

Dr. Aaronson is board-certified in Psychiatry and he is a member of several professional organizations, including Distinguished Fellowship in the American Psychiatric Association and the Maryland Psychiatric Society, for which he served as President. He is also a fellow of the American College of Psychiatrists.

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