When Standard Treatment Isn’t Enough: Understanding Treatment-Resistant Depression, PTSD, and Suicide Risk during National Suicide Prevention Month
With clinical insights from Christina Sullivan, Psychiatric Mental Health Nurse Practitioner (PMHNP) at Advanced Psychiatry
Every September, National Suicide Prevention Month asks us to talk openly about a subject that’s too often kept quiet or considered taboo. This year, we’re not only speaking openly about suicide prevention, but also focusing on a group of people who face a particularly difficult version of that struggle: those living with Treatment-Resistant Depression (TRD), often alongside PTSD.
If you’ve tried medication after medication and still don’t feel like yourself, or if you love someone in that position, you already know the particular kind of exhaustion that comes with it. It’s not just depression – it’s depression that hasn’t responded to treatment, paired with a growing fear that maybe nothing will work. That frustration and hopelessness are real, and they deserve to be named rather than glossed over.
We sat down with Christina Sullivan, PMHNP at Advanced Psychiatry, to talk through what treatment-resistant depression actually means, how it intersects with PTSD and suicide risk, what warning signs matter most, and what options and hope actually exist.
What “Treatment-Resistant” Actually Means
First, let’s clarify what it means to be “treatment resistant.” This term can make a diagnosis sound like a dead end, but it’s not. According to Sullivan, “One of the biggest misconceptions that people have about Treatment-Resistant Depression (TRD) is there is less hope for the person suffering it to get better, and that it is rare.” In reality, she specifies, “TRD is generally defined as a person living with depression that has tried at least 2 different antidepressant options without symptom improvement.”
The numbers back up just how common this is. Sullivan notes that only 1 in 3 people with depression are symptom free with the first medication they’re prescribed, and even fewer find relief from additional medication trials after the initial trial fails (National Institute of Mental Health). The key takeaway, Sullivan says, is that “for these individuals, looking at only medication options for treatment may not be enough. There are many additional options including, but not limited to: lifestyle changes, neuromodulation options (TMS, Spravato, Ketamine), psychotherapy, and other holistic approaches.”
It’s also worth noting that PTSD and depression frequently occur together, and when they do, treatment becomes more complicated, and suicide risk climbs. This overlap is worth understanding on its own.
The Link Between Depression, PTSD, and Elevated Suicide Risk
Depression alone raises suicide risk. Add PTSD to the mix, and that risk increases substantially. Suicide risk, Sullivan explains, “is increased 3 to 7 times when that person is also diagnosed with PTSD, even after adjusting for any other psychiatric comorbidities” (Fox et al., 2021). And the overlap between the two conditions is significant, as PTSD is prevalent in those with depression, occurring 50% to 70% of the time (Thomas Reinhardt).
Because of this link, Sullivan screens every patient for trauma, looking for specific risk factors in those with PTSD. For example:
What is the current severity of the PTSD symptoms?
Is there increased intrusive thinking, feelings of guilt/shame/anger, flashbacks, or increased impulsivity?
How long ago and what type of trauma did the person survive?
Has there been any additional social stress or loss of important support(s)?
It’s important to note that these are risk factors, not predictions. No one can say with certainty what any individual will experience, but understanding them helps both clinicians and loved ones know what to watch for, and when to act.
Warning Signs Loved Ones and Patients Should Know
Not every warning sign looks like obvious distress. Sullivan points to one in particular that’s often missed: “One of the earliest and most overlooked warning signs is withdrawal from others. It can be hard to recognize, especially if withdrawal isn’t accompanied by more obvious signs of sadness."
That’s the tricky part, she explains, because people who are severely depressed are often good at “masking,” or putting on that “happy, everything is good” façade despite feeling something very different on the inside. This is exactly why checking in on people, even the ones who seem “fine,” matters. Someone who appears to be holding it together may still be struggling significantly underneath.
Beyond withdrawal and masking, there are other signs worth watching for, whether in yourself or someone you love. According to the American Foundation for Suicide Prevention, warning signs generally fall into a few categories:
Talk: Verbally expressing wanting to die, feeling hopeless, feeling trapped or in unbearable pain, feeling like a burden to others, or having no reason to live
Behavior: Withdrawing from friends, family, or activities; increased use of substance abuse (alcohol, drugs); giving away prized possessions; saying goodbye to people in non-applicable environments or situations; a sudden sense of calm after a depressive episode
Mood: Depression, anxiety, irritability, humiliation, or dramatic mood swings that seem out of character
Physical Changes: Noticeable changes in sleep (too much or too little), appetite, or energy level
No single sign confirms risk on its own, and not everyone who is struggling will show all (or even most) of these. That’s part of what makes this hard, and part of why paying attention matters.
How to Actually Help Someone with Depression/PTSD
If someone you love is in a dark place, having tried multiple treatments without relief, how you respond matters. Sullivan is clear that it’s crucial to both validate their experiences and reassure them that there are still other options available. “Most of the time, these individuals have tried multiple medications over the course of months (if not years) without adequate symptom relief. It doesn’t mean that their efforts have been in vain – they are doing all the right things.”
Often, the most helpful thing you can offer isn’t advice, but information. “They may not have known that there are other options out there or have not had access to them before, which is an exciting conversation to have,” Sullivan says.
In practice, that means leading with validation rather than solutions, resisting the urge to pressure someone toward a specific treatment, and gently making sure they know that running out of options with one approach doesn’t mean running out of options entirely. If you’re ever concerned that someone is in immediate danger, don’t wait. Involve professional or emergency help right away.
Treatment Options for TRD and PTSD
If you’ve noticed warning signs or had difficult yet imperative conversations, but first-line medications haven’t worked, the path forward doesn’t end. Beyond standard antidepressants, a range of interventional and holistic options exist. One area that often comes with fear or misinformation attached is neuromodulation treatments like IV ketamine therapy, Transcranial Magnetic Stimulation (TMS), and Spravato nasal spray. Sullivan wants people to understand that all of these interventional psychiatric methods have a vast amount of evidence to support their effectiveness in significantly improving symptoms of treatment-resistant depression.
She also hears the same fears come up again and again: “Often, I encounter people that have heard what happened to Matthew Perry or fear becoming addicted or overdosing. However, those situations are extremely rare and different from the reality of someone seeking medical care.”
In fact, the safety protocols around these treatments are extensive. All clinicians at Advanced Psychiatry follow strict guidelines created through rigorous medical research and testing to maximize their benefits while maintaining safety. This includes ensuring patients stay physically in the clinic for the entire length of their treatment so they may be directly monitored in the event that, no matter how rare, immediate medical intervention is required.
For anyone who feels like they’ve exhausted their options, Sullivan’s advice is simple: “Keep looking. There is always another treatment, another medication, or another therapy out there that may be the right fit. It could be the next one you try or the 2nd, 3rd, 4th, or 5th thing. We can never predict 100% accuracy when we will find that right treatment BUT we can predict the same results when repeating the same cycles.”
A Note of Hope
If there’s one thing to take from this piece, whether for a loved one or a reader in the middle of this fight, it’s this: “Don’t give up. When we feel lost and in the very darkest of days, know that they won’t last forever. You are more valuable, more cared for, and more wanted in this world than you may ever know. You are worth fighting for each and every day. And if you ever lose hope, reach out. Sometimes a little hope is just the spark needed to light a way out of the darkness.”
If you or someone you love is struggling with treatment-resistant depression, PTSD, or thoughts of suicide, help is available:
988 – Call, text, or chat online the Suicide & Crisis Lifeline (24/7)
Crisis Text Line – Text HOME to 741741for the Crisis Text Line
For Veterans – Call 988 then press “1”, text 838255, or chat online
For Survivors of Violence or Abuse – Call 1-800-799-SAFE (72336), text “START” to 88788, or chat online with National Domestic Violence Hotline
For Survivors of Sexual Assault – Call 800-656-4673, text “HOPE” to 6473, or chat online
For Members of the LGBTQ+ Community – Call 1-866-488-7386, text “START” to 678-678, or chat online with the Trevor Project
911 – For immediate emergencies
To learn more about treatment options for treatment-resistant depression, PTSD, and other mental health conditions, as well as neuromodulation therapies like ketamine, TMS, and Spravato, reach out to the team at Advanced Psychiatry.
This blog post is for informational and awareness purposes and is not a substitute for professional mental health care. If you are in crisis, please contact 988 or your local emergency services immediately.
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Resources for National Suicide Prevention Month:
Risk Factors, Protective Factors, and Warning SignsAmerican Foundation for Suicide Prevention (AFSP)
Thomas Reinhardt. (2026, 02/12). PTSD Suicidal Death Statistics. Worldmetrics.
Fox V., Dalman C., Dal H., Hollander A. C., Kirkbride J. B., Pitman A. (2021). Suicide risk in people with post-traumatic stress disorder: A cohort study of 3.1 million people in Sweden. Journal of Affective Disorders, 279, 609–616. https://doi.org/10.1016/j.jad.2020.10.009
