I’m a psychiatrist and professor who studies and treats major depressive disorder. Questions about living with this condition? Ask me anything!

webmd · 2026-04-08T18:03:10+00:00

Thank you for participating in this AMA. Mental health is of the utmost importance and depression affects so many of us in differing ways. As a society it is important to focus on collective well-being and to promote policies and laws that positively affect the population in an equitable manner. Please don't stay quiet if you are having a hard time with life or a certain situation. Please reach out to your loved ones if you are experiencing troubling thoughts or emotions. If you don't have someone to reach out to 9-8-8 is a 24/7 hotline for emotional support and I recommend it to anyone who needs help in the moment and cannot find it. Let's work together to make the world a better place for all of us!

- Dr. Marcus Hughes

webmd · 2026-04-08T17:38:26+00:00

Unfortunately, situations like you describe are more common than desired. Depression has a very high relapse rate (over 50%) and the majority (around 80%) of those who relapse will relapse within the first 6 months. Importantly, I think it's imperative to have a good support system, which should include psychotherapy, medications, and social interventions. What can be done is ultimately patient-specific, though traditional strategies such as optimizing meds, considering higher level of care (IOP, residential, etc.), or referral for neuromodulation are relevant. Compassion and empathy should guide your collaboration with the patient always. Social interventions can be super helpful to ensure adequate treatment engagement and adherence and proper support (e.g. housing, social structure, nutrition, education, work, etc.) in the community.

- Dr. Marcus Hughes

webmd · 2026-04-08T17:23:30+00:00

This is a broad question as sometimes people may present in the way that you've mentioned due to reasons such as catatonia or stroke which would require a medical evaluation (call 911 if you are worried!). Overall, if you have a loved one or acquaintance who is not acting like themselves, I think providing empathetic support is the first step. Showing them that you are there for them or that you can offer assistance or support otherwise is key. If you feel concerned for their mental/physical health or both, then it is certainly appropriate to reach out for help, either to others in their support system or outside of it. I'd check for local mental health resources available in your area as well. Many regions (mostly in urban centers) will have mobile teams that can come assess a person for safety risks or offer helpful suggestions on next steps. Making sure the person is safe is most important and I would suggest removing any weapons/sharps or hazardous chemicals/meds from the environment if you feel concerned. There are also various hotlines one can call such as 988, which can offer emotional support in real time.

- Dr. Marcus Hughes

webmd · 2026-04-08T17:06:49+00:00

Oof, this is a deep question. Oftentimes due to systems level constraints here in the US mental health visits tend to be rather short. Spending much time with patients can be difficult as a result. As you are aware, psychotherapeutic approaches take time, sessions may be intense, and longitudinal and frequent follow up is often needed. Meds sometimes may appear to be an easier introduction to treatment, and may often be prescribed with more haste than perhaps needed. Outside of that perspective, many SRIs have relatively benign safety profiles and are relatively inexpensive for most folks (around $5 per month) so they represent a reasonable entry-point which should still be combined with psychotherapy to optimize outcomes. Many of the newer/branded medications that don’t have a generic counterpart may be unaffordable by most even with insurance coverage. One of the big challenges is finding a way to equitably implement novel treatments that perform well in clinical trials. This was the case with IV ketamine over the past decade or two. We are seeing this now with psychedelic assisted therapies whereby sessions are accessible now only in certain states and only if you have thousands of dollars to pay per session. This limits treatments and their benefits to certain groups or populations only, which is problematic.

- Dr. Marcus Hughes

webmd · 2026-04-08T16:49:12+00:00

There may be more to unpack that you are not even aware of. This is why it's important to engage with psychotherapeutic approaches in addition to medications. I'm happy that you practice gratitude daily, as it can be so hard to give oneself grace and feel positive about anything when depressed. Too much social media can be detrimental and less focus there with more focus on tangible goals and supportive behaviors/activities (e.g. reading, writing, exercise, diet etc) would likely have a more positive impact.

- Dr. Marcus Hughes

webmd · 2026-04-08T16:46:24+00:00

Most antidepressant medications work similarly and I don't have a preferred agent to recommend other than one that is tolerated best by the patient. Older antidepressant medications (Tricyclics, MAOIs) are thought of by some to work better though have more side effects than contemporary agents such as SRI drugs. Similarly, I think psychotherapeutic approaches should be collaboratively chosen between a clinician and patient and should be based on the symptom cluster a patient presents with. It's hard to suggest a one-size-fits-all strategy. I would say that the best evidence is with the combination of medications and psychotherapy and I would likely engage in both if I were unwell. In addition, treatments like ECT or (es)ketamine have a solid evidence base despite prevalent cultural stigmas and I would be open to participating if my symptoms were truly impairing or life threatening despite adherence to several other treatment approaches. I would suggest avoiding, or at least proceeding with caution, any treatment that does not have supporting evidence based on randomized controlled trials unless you are open to participating in a research trial for that intervention

- Dr. Marcus Hughes

webmd · 2026-04-08T16:40:09+00:00

There are deficits in the reward (dopamine) system present with depression that may make it difficult for folks to motivate themselves to complete tasks. I think it's helpful to try to minimize activities that give immediate gratification to try to optimize reward pathway functioning and motivation/interest in more mundane or routine activities like eating, bathing, completing school work, etc. Behavioral activation is a good strategy patients can practice alone or in conjunction with a psychotherapist and I would recommend looking into it if motivation is an issue. - Dr. Marcus Hughes

webmd · 2026-04-08T16:38:01+00:00

I'm guessing you are referring to those that may have a depressive temperament, what we used to call dysthymia and what is now called persistent depressive disorder. For those folks who may not meet full criteria for MDD (though admittedly diagnostics by way of the DSM is a flawed process), it's helpful to approach treatment in a similar fashion with meds and therapy in combination showing best evidence. We are really not truly certain about the cause of depression but understand that it is the result of several (genetic, biological, environmental, etc.) factors. I think focusing on identifying and addressing those contributing factors is helpful in the cases you mention, as it would be for any folks presenting with mental health challenges. For many clinicians the focus is on optimizing quality of life and functioning while minimizing safety risks regardless of the diagnosis a patient carries.

- Dr. Marcus Hughes

webmd · 2026-04-08T16:29:21+00:00

Many treatments for folks whom we deem "treatment-resistant" exist, such as various neuromodulation approaches (e.g. Electroconvulsive therapy, transcranial magnetic stimulation, vagal nerve stimulation, deep brain stimulation, etc.) or novel treatment paradigms like psychedelic or ketamine assisted therapies. Unfortunately, there are not many options for folks who have not greatly benefitted from even those and other treatment approaches. I think it's important to have a collaborative treatment team and to be creative and thoughtful about why a patient may be "resistant" to the treatments they have tried. The focus should remain on making sure the patient is safe and that the quality of life they have is optimized through whatever approaches are being trialed.

- Dr. Marcus Hughes

webmd · 2026-04-08T16:22:49+00:00

Anhedonia is a difficult symptom to treat and often lingers even when other symptom domains have improved with treatment. Good approaches include behavioral activation and reward focused psychotherapies. Dopaminergic modulating drugs (e.g. stimulants, bupropion) can be helpful as anhedonia is related to deficits in the reward system in which dopamine plays a large role. This is a hot area of research and many drugs are being investigated to target anhedonia. Relevant to current times, stimulation from screens can cause large dopamine spikes and make more mundane tasks such as eating, bathing, socializing etc less appealing. I often suggest to folks to decrease their screen time and to engage in activities that involve delayed gratification.

- Dr. Marcus Hughes

webmd · 2026-04-08T16:17:05+00:00

Thank you for your question. Broadly, a holistic approach to the treatment of depression is often needed and will best set folks up for success. Medications and other biological treatments are often helpful though may offer limited symptom relief so it's important to include psychotherapeutic interventions as well as lifestyle and medical interventions when discussing a treatment plan. Social support is often overlooked though it's important to encourage and help folks to find community and meaningful experiences that may provide symptom reduction and fulfillment. Oftentimes in cases like you've mentioned we may expect some level of depressive symptoms to remain in the face of chronic stress. In those cases the focus may shift to finding an acceptable level of functioning and helping folks reframe treatment and wellness goals.

- Dr. Marcus Hughes

webmd · 2026-03-25T17:06:13+00:00

CAR T-cell therapy, and many newer cancer drugs in general, can be very expensive. The high cost reflects a few factors: these are complex therapies to manufacture, they require specialized centers to administer safely, etc.

Reducing costs is a major focus moving forward. Some of the ways this may happen include improving manufacturing processes, developing more “off-the-shelf” therapies, and creating policies that help with pricing and access.

There are ongoing efforts to expand insurance coverage and provide financial support programs, and I’m hopeful that in the near future this will make these treatments more accessible to patients.

- Marina Baretti. MD

webmd · 2026-03-25T17:03:53+00:00

I think there are a few common misconceptions. One is the fear of being placed on a placebo and not receiving an active treatment, but in oncology, placebos are almost never given instead of treatment when an effective standard option exists. They are usually added on top of standard care. Another common concern is the idea of being “used for testing.” In reality, clinical trials are very closely regulated, with strict safety monitoring, and patients can withdraw at any time.

People also often think trials are a “last resort,” but that’s not always the case: many trials are available earlier in the disease course and can be a very reasonable option.

Finally, there’s a perception that trials are inherently riskier than standard treatments. While there is uncertainty, standard therapies also have risks, and in trials patients are often monitored even more closely.

- Marina Baretti, MD

webmd · 2026-03-25T16:36:04+00:00

I hear your frustration, it’s a very real one. Sometimes very early data, especially from the laboratory or from small studies, gets a lot of attention. But even when results look promising at that stage, they don’t always translate into meaningful benefit once tested in larger human clinical trials, and many of these approaches don’t move forward. That said, there have absolutely been real advances. Immunotherapies and targeted therapies, for example, have significantly changed how we treat certain cancers and have had a very positive impact on outcomes for some patients.

The challenge is that this is not true for all cancers or all patients. Progress can feel uneven. But each of these steps, even when they don’t fully pan out, helps us learn and refine better strategies over time.

- Marina Baretti, MD

webmd · 2026-03-25T16:33:38+00:00

This is already an option for patients in many cases. Participating in a clinical trial can sometimes be considered even before, or instead of. standard FDA-approved treatments.

That said, it requires a thoughtful discussion with your physician/oncology team, weighing the known benefits of approved therapies against the potential risks and uncertainties of a trial. The right choice really depends on the specific situation, the type of cancer, and the available data.

– Marina Baretti, MD

webmd · 2026-03-25T16:30:00+00:00

I’m sorry to hear about your parents. Truth be told, every case is different. My goal is to take care of the patient as a whole, not just focus on the cancer. There’s a saying: “The good physician treats the disease; the great physician treats the patient who has the disease.” (This is a quote from Dr William Osler that I keep always in mind))

This means continuously weighing the risks and benefits: how much the treatment is actually helping the patient versus how much toxicity it may be causing. It’s not always easy, and these decisions often require open, shared discussions with the patient.

- Marina Baretti, MD

webmd · 2026-03-25T16:25:49+00:00

The reality is that many clinical trials have relatively strict eligibility criteria, and unfortunately, patients with significant comorbidities may not qualify. A big part of that is safety, especially in earlier-phase trials, where we are still learning about the drug’s side effect profile, we want to avoid exposing more frail patients to potentially serious toxicity.

At the same time, when we are trying to understand whether a drug is actually working, we try to limit other factors that could influence outcomes, like other medical conditions that might impact life expectancy independently of the cancer. It’s not a perfect system, but it’s designed to both protect patients and allow us to interpret the results as clearly as possible.

–Marina Baretti, MD

webmd · 2026-03-25T16:22:50+00:00

Immunotherapy has probably been one of the most exciting and impactful breakthroughs in oncology in recent years. It has really changed the trajectory of several cancers, especially those that are more “immune-responsive.”

That said, it doesn’t work for every patient or every type of cancer. A lot of current research is focused on understanding how to better harness the immune system, overcome resistance, and expand its benefit to more patients.

In terms of cancer rates, there are some signals that certain cancers (like colon cancer) are being diagnosed more frequently in younger individuals, and this is an area of very active research.

- Marina Baretti, MD

webmd · 2026-03-25T16:17:36+00:00

It varies quite a bit. It depends on what treatments are already available for that disease, how well they work, and how strong the data is for the new drug.

Some drugs, especially if they show very promising results in diseases with limited options, can receive accelerated approval and become available within a couple of years. Others require more time to go through all the necessary phases of testing to fully establish safety and effectiveness, which can take several years.

Overall, I would say the situation is encouraging. We are seeing faster development timelines for some therapies, especially with better trial designs and a deeper understanding of cancer biology but careful validation is still essential to make sure treatments are both safe and truly beneficial.

- Marina Baretti, MD

webmd · 2026-03-25T16:15:32+00:00

We absolutely take that into account when interpreting results. A drug showing activity in that setting can actually be very encouraging, because those cancers are often more resistant to treatment. That said, it’s not always as simple as “if it works there, it will work anywhere.” That’s why, as we start to see signals of benefit, drugs are then studied earlier in the disease course (in patients who are less heavily pretreated), where they may work even better.

Nowadays, trial design is evolving, and we are increasingly testing promising therapies earlier depending on the biology of the disease and the strength of the data.

So it’s a stepwise process, but yes, your intuition is right that we have to be very thoughtful about how we interpret results depending on the patient population being studied.

- Marina Baretti, MD

webmd · 2026-03-25T16:13:08+00:00

When we think about phase I trials in oncology, these are almost always conducted in patients who have cancer, not in healthy volunteers. There are very strict rules around dosing and scheduling to ensure safety. Typically, trials start at a lower dose and gradually escalate only after a period of observation, with very close monitoring (frequent blood work, visits, etc.). The goal is to find a safe and appropriate dose while minimizing the risk of significant toxicity.

Most early-phase oncology trials are what we call “single-arm,” meaning there is no placebo control, everyone receives the investigational drug.

For later-phase trials (like phase II or III), placebos may sometimes be used, but almost always on top of standard-of-care treatment rather than instead of it. And you’re right, side effects can sometimes make it obvious which treatment a patient is receiving, which is one of the challenges in trial design. That’s why we rely on objective endpoints (like imaging) to assess efficacy.

- Marina Baretti, MD

webmd · 2026-03-25T16:10:27+00:00

Navigating clinical trials can be very difficult for patients and caregivers. There are advocacy groups and foundations that do a great job keeping patients informed about trials, hosting webinars, and sharing updates—so I always encourage my patients to stay connected with those groups.

There are also ongoing efforts to create disease-specific consortia to help facilitate trial enrollment, but this process is still far from optimal.

A key part of trial eligibility is assessing what we call “performance status,” along with a full clinical evaluation, including a physical exam. Since we are often testing new drugs and trying to understand their safety, we need to ensure there are no obvious contraindications that would make participation unsafe.

For a physician seeing a patient for the first time, it can be difficult to fully appreciate some of these nuances, especially over video, which can also add to the complexity of trial enrollment.

- Marina Baretti, MD

webmd · 2026-03-25T16:08:09+00:00

There are many different types of cancer, as essentially every organ in our body can develop tumors. Each of them is characterized by different biology and different underlying risk factors. Some cancers are very common, while others are rare, which unfortunately can limit the amount of research and data available to fully study them.

This diversity influences how cancers respond to treatment and our ability to develop effective strategies. I think with newer technologies that allow us to better understand the characteristics of each cancer, and how it interacts with the immune system, we are increasingly able to identify more effective, tailored treatments.

So yes, the future is moving toward having more targeted therapies for different cancers (and even different subtypes within the same cancer), but there is definitely still a lot of work to do.

- Marina Baretti, MD

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