TCPR: What qualities in a provider contribute to enhanced patient outcomes?

Dr. Mintz: Warmth, empathy, our investment in the patient, and our optimism about treatment. This latter one is tricky when you work with treatment-resistant patients, where medications are unlikely to do the work alone. But you can have optimism about the patient’s role in the treatment, about what happens when you foster an alliance that mobilizes the patient’s agency.

TCPR: What would you say to a patient with depression as you prescribe an antidepressant?

Dr. Mintz: If it’s their first antidepressant, it makes sense to talk up the medication. There is, after all, some realistic hope that they will recover with it. But where I work at Austen Riggs, most of the patients have already failed multiple medications. What I want is for them to feel like they have agency in the recovery process. Otherwise, they are just waiting to be fixed. 

TCPR: That’s unlikely to happen with meds. I recall one study where the chance of remission after five failed medication trials was zero (Petersen T et al, J Clin Psychopharmacol 2005;25(4):336–341).

Dr. Mintz: Yes, these patients are often demoralized about treatment and they don’t respond well when we come across with too much optimism (Priebe S et al, BMC Psychiatry 2017;17(1):26). I’ll say that medications are helpful, but they are not everything. If they really want to get better, they’ve got to do the rest. That leads us into discussions of antidepressant lifestyle and psychotherapy and other psychosocial factors that promote optimal outcomes.

TCPR: What psychological factors predict a good response on the patient’s side?

Dr. Mintz: Readiness to change is a big one. In a large trial of a benzodiazepine in panic, patients who were ready to change and got the placebo had better outcomes than those who got the benzo but entered the study with little readiness to change. “Readiness” was assessed with answers to prompts like “I have problems and I really think I should work on them.” Those with low scores had little motivation to work on the problems and saw them as something outside of their control and responsibility (Beitman BD et al, Anxiety 1994;1(2):64–69). 

TCPR: How do you talk to patients about their readiness for change?

Dr. Mintz: I explore their ambivalence. Most patients have some ambivalence about treatment and about medications. So, I ask “What does it feel like to take medications?” They may, for example, say “I can’t stand it because I hate to be dependent.” Then I’ll ask “How far back does this go? Do you have any ideas about why it started?” Often that leads to problems with their early caregivers. Patients who are ambivalent about caregiving often had parents with some early adversity in those important relationships. If they share those experiences with me, I tend to bring it back to the present, asking “How does that affect the way you relate to caregivers now?”

TCPR: I’m guessing most patients who come for an evaluation for treatment-resistant depression are not expecting to talk about these things.

Dr. Mintz: That’s true, but it’s important to start the conversation about psychological factors early on. If you wait to explore this until there is frustration with how the treatment is going, it is much more likely to make the patient defensive. You want to come at the topic from a position of curiosity and set the stage that you are interested in learning about psychological factors that affect their recovery. Often patients deeply appreciate that you are trying to grasp them as a human and not just as a DSM diagnosis. 

TCPR: What about external factors that reinforce the illness?

Dr. Mintz: There are all kinds of secondary gains that reinforce illness, from getting out of responsibilities to disability benefits. Often, however, the patient is not directly conscious of the gain, and you have to handle this tenderly. I’ll ask “Is there anything you would stand to lose if you got better?” Two thirds don’t have an answer, but for others it opens up a conversation. We may not address it right away, but I’ll flag it and later will raise it with empathy: “I could see why it would be hard to give that up.”

TCPR: Most of us probably think our therapeutic alliance is better than it is. How can we look for signs that something is wrong?

Dr. Mintz: At the first session, I talk to the patient about the importance of the alliance for promoting positive outcomes. I’ll say “One of the implications of a strong alliance is that if I am doing something that you don’t like, I need you to tell me. How good are you at that?” If they are not good at speaking up for themselves, I’ll say “From time to time I’ll ask you about how we’re doing together because that is going to influence how well the medications are working.”

TCPR: What kinds of things do patients complain of?

Dr. Mintz: A common complaint is that they felt like I leapt to a conclusion too quickly or I didn’t hear something. Often just talking about it makes things better.

TCPR: It sounds like we need to be receptive to criticism, including from patients who have distorted perceptions. 

Dr. Mintz: Yes. We need to acknowledge our contribution to why things are going awry just as we expect the patient to. The first thing to do is to ask ourselves “How is the patient right?” Not “Is the patient right?” There are times when we make genuine errors and need to apologize, but more often this isn’t a flaw. It’s a subtle mismatch. It’s about our limitations. When we presume a kind of expertise that we don’t have, we undermine the patient’s authority and create conditions for distrust. 

"I don’t generally start an interview by asking about symptoms. I’ll start with 'Where are you trying to get in your life and how do your symptoms get in the way of that?'”
-David Mintz, MD

TCPR: I don’t want to trivialize these therapeutic techniques as a placebo, but it sounds like they would enhance the placebo effect in treatment.

Dr. Mintz: Yes, placebo contributes substantially to our outcomes, so we need to understand how to maximize it. In research there is an attempt to minimize the placebo effect, but even there it often outsizes the effects of the treatment.

TCPR: How powerful is the placebo effect?

Dr. Mintz: In depression, the placebo effect accounts for nearly half of an antidepressant’s effect. But that may be an underestimate because there is a publication bias where negative studies with large placebo effects tend not to get published. If we look at a less biased sample, like the FDA database of registered trials, the placebo effect accounts for as much as 76%–81% of antidepressant effect. Another way to look at it is through effect size. Antidepressants have a small effect size (0.30–0.35), just barely noticeable to the casual observer, while the placebo effect size is large (1.05), suggesting it contributes three times as much than the actual drug in depression. In other disorders like mania and psychosis it is smaller but still high, with the placebo contributing around twice as much as the active treatment. 

TCPR: Isn’t the placebo effect baked into every medication we prescribe?

Dr. Mintz: Not automatically. You can give a sugar pill and get no effect at all, or things may get worse. Part of the “placebo” effect is the natural course of illness, and some of it depends on patient factors that are beyond our control. But a lot of the placebo effect varies by provider.

TCPR: How so?

Dr. Mintz: Back in the 1980s, a large trial funded by the National Institute of Mental Health compared antidepressant medication with two kinds of psychotherapy and placebo. The main outcome was that all the active treatments were equivalent and probably the combination of medication and psychotherapy was a little more effective than either alone. But when they looked at the data through the lens of the provider, a new pattern emerged. If a provider got positive results with one patient, they tended to get positive results with all of their patients—regardless of whether medication or placebo was used. And if someone got a poor result, they tended to get poor results across the board. When they stratified the providers by outcome, the doctors who were in the highly effective group got better results with placebo than the doctors in the bottom group got with an active drug. 

TCPR: What do we need to do to move into the highly effective group?

Dr. Mintz: We don’t know exactly what they were doing, but one branch of this study compared outcomes based on the treating doctor’s perspective. Outcomes were better when the doctor had a more psychological understanding of depression as opposed to a more reductionistically biomedical view. This study lumped all the clinicians together—whether they were in the psychotherapy or the medication arm—so we don’t know how well that would hold up for psychopharmacology work, but other studies suggest it does.

TCPR: Tell us about that. 

Dr. Mintz: One study enrolled college students with depression, who were told that the aim of the study was to determine if their depression was psychological or biological (Kemp JJ et al, Behav Res Ther 2014;56:47–52). Somebody in a white coat came in and did a sham cheek swab and came back 15 minutes later. Then the students were randomly informed that their depression was either psychological or biological and genetic in its origins. Contrary to expectations, and to some other studies, telling students that their depression was biological did not reduce their self-blame. But more importantly, the students who received the biological explanation experienced an increase in prognostic pessimism. In other words, they felt more hopeless and helpless, as if they were not going to get better because depression was part of who they were. This is in line with another study, which found that patients with a more biological frame of mind were less likely to recover from depression (Sullivan MD et al, J Am Board Fam Pr 2003;16:22–23).

TCPR: What are some psychosocial factors about the medication—or the way the patient takes it—that may enhance the outcome?

Dr. Mintz: One thing I do is to give choices. In one study, patients who were hospitalized for depression were randomized into two groups. One group took escitalopram once a day—the way it is usually delivered. Patients in the other group were given a choice of taking the medication once a day or three times a day. Medically, that is a meaningless choice, but just being given that choice more than doubled the likelihood that the patient would still be taking the antidepressant at three months ­post-discharge (Woolley SB et al, J Clin Psychopharm 2010;30:716–719). This doesn’t mean giving the patient all the benzos they think they need. But where we have reasonable options, we should hand the choice over to the patient. 

TCPR: On the other hand, can medications be countertherapeutic on a psychological level?

Dr. Mintz: I think this is one of the most underappreciated challenges facing psychiatrists. Imagine a patient who wants more medications. Every time you add one, they say it’s helpful, but you find yourself wanting to put on the brakes. Something just feels icky. What happens is that the patient is becoming progressively deskilled because emotionally, they are now increasingly relying on medications rather than more mature coping strategies. And so, to the extent that you keep prescribing without doing anything else, you are participating in that patient becoming a chronic patient.

TCPR: This doesn’t have to do with whether or not their regimen is evidence based. It’s about their relationship to it.

Dr. Mintz: Yes. One sign of this is that the symptoms are getting better, but the patient is not getting better. They are not more functional.

TCPR: How do you assess “functioning” with your client?

Dr. Mintz: I don’t generally start an interview by asking about symptoms. I’ll start with “Where are you trying to get in your life and how do your symptoms get in the way of that?” Then it is easier to see when treatment is addressing symptoms but is not getting them closer to the patient’s broader aims in life.

TCPR: Thank you for your time, Dr. Mintz.