Jose Rey on Psychotropic Medications: A Primer for Psychotherapists

Jose Rey: That's an excellent question. I still would like to think that areas like mild to moderate anxiety and depression are very responsive to psychotherapy, and so that question would ideally come in the middle or late stages of treatment where frustration may have set in and therapeutic response is not occurring. We should really give psychotherapy it's best chance to work first.

Medication might give us a little bit of a faster response, but it doesn’t seal the effect the way psychotherapy can. What I mean by seal the effect is that a drug doesn’t teach you anything. If you're taking a Xanax for anxiety and if you're so anxious and so distraught that you can't engage in therapy, well then by all means use something that helps you get into the room. But if you are only taking Xanax every day for your anxiety, for instance, then what have you learned about the cause of your anxiety? What have you learned about any coping mechanisms or other areas or ways to deal with the anxiety other than the behavior of popping a pill. I don’t like drugs alone, I prefer psychotherapy with medications.

Medications also are not curing anybody, they are tools. If you go with evidence-based medicine, you really don’t have a lot of great long-term information regarding the use of these medications. Yes, we know they can work in limited four to 12 week trials, but we really don’t always follow patients for 12 months or 24 months after treatment ends. And therefore, I think that using these agents up front to help a patient with more severe forms of anxiety or depression to engage in therapy is the best place for it, but you have to gauge the severity of the illness. Someone who is having the occasional anxiety attack should not be taking a Xanax or a Prozac every day. If you're having debilitating anxiety so that you can't engage in social or occupational activities, then you're already at a moderate to severe level in my book, and therefore the idea of pharmacotherapy seems attractive.

I just don’t want to think of all of us as just bags of chemicals and that a new chemical like a Prozac, Xanax, Paxil or Buspar will somehow correct an underlying problem. Our medications manage symptoms. They do it very well, but they don’t generally treat underlying issues. Even if the underlying issue is biological like genetics, these drugs aren’t going to correct your genetics. You're always going to have that genetic aspect of the illness. They can only change the chemical availability of a neurotransmitter like serotonin, but even that wears off over time. And now we're back to where we started from.

Sometimes, these medications only work for a few months or a short period of time, and then your body finds a way to become tolerant to them. One of the smartest things I heard from a psychotherapist years and years ago about a person who was breaking through their antidepressants was, “if the brain wants to be depressed, it will find a way to be depressed.” And therefore, we can use multiple antidepressants with this individual, but they find a way to overcome them. And that does speak well to genetics and the other aspects of depression such as our view on the world and our expectations of the world. I don’t like to think that drugs can insert thoughts. Therefore, they can help our sleep or our level of anxiety but they won't teach us anything. 

JR: No, not at the point when you’re in phase one through three or in premarketing stages of drug development. It is extremely odd to see a drug go head to head with therapy. Historically speaking, for mild to moderate depression, psychotherapy and pharmacotherapy did very well. You only might see a separation for pharmacotherapy doing a little bit better than psychotherapy in the most severe cases. But in one of our best antidepressant trials, the STAR*D trial which was published more than 15 years ago, everybody had been given Citalopram, the drug Celexa. If they had done poorly on Celexa then they were then randomized to receive other treatments to see if they failed on one drug would they have a preferential response to the next drug. And in that case, they went from Celexa to Zoloft, Celexa to Wellbutrin, Celexa to Effexor, and there was a fourth arm, Celexa to cognitive therapy. And in all four of those arms, they had the same outcome, about 25 percent of the patients.

JR: Cognitive therapy did as well as any of those three antidepressants in achieving remission. And it was just fantastic to see that because we could argue that they had already failed Celexa, and even though they now met criteria for adding an antipsychotic, cognitive therapy did as well as any of our medications.

Guiding the Prescriber

JR: I like that. That's a more concise way of saying what I was alluding to especially, when it comes to those periods where there might be more stress. Again, we're back to something like benzodiazepines like valium or Xanax. They're great on an as-needed basis, i.e. I need the effect to happen in 20 minutes or I need it to happen in 30 minutes, but I don’t want the individual to take the medication every day in an almost avoidance behavior and not engage with that anxiety. I prefer that benzodiazepines, for instance, be used only sparingly on a PRN bases and not on a regular daily basis.

JR: That's a very good way to look at it or to ask that particular question, because I would like to think that the physicians would have that conversation with their patients.

JR: But I don’t think they do. Most physicians these days are not engaging in any form of psychotherapy beyond 10, 15 minutes a session. Hopefully they are preparing the patient for medications, maybe what to expect including side effects and positive and/or negative types of outcomes. But they are probably not addressing these questions of how long will we be using this medication, when will we be using this medication, what does this medication represent? It should represent a tool and something to assist in the treatment outcome. But if you say a drug is all you need, then you're saying your problem is almost all biological. And let’s face it, it's not that.

JR: Some psychologists or some therapists may overstep the boundary and say, “I recommend we use this particular drug.” And the prescriber will almost immediately say, “you didn't go to medical school,” or “you didn't do this, and that sort of thing.” I wouldn’t approach it like that. I would approach it as “there are some aspects of our therapy sessions that make me think that along with the trauma that they may have gone through or the family issues that may be going on, they have some symptoms that might be very responsive to pharmacotherapy.”

The therapist can be recommending pharmacotherapy without a specific drug. But I think if the therapist could give [the prescriber] a list of the target symptoms, then that should guide their prescribing. Sometimes we lose sight of the fact that we're managing symptoms most of the time anyway. We could say for example that the patient is having this specific type of insomnia which is dominated by anxiety. The prescriber is then given a better assessment of the patient’s symptoms because it's hard for them to pick up on all the symptoms with a five or ten minute interaction with the patient.

There are primary and secondary selection criteria for a drug such as a psychotropic, and one of our primary selection criteria should be matching the patient’s clinical presentations to the other aspects of the drug, maybe its side effect profile. If the person is having insomnia, I might pick a sedating antidepressant. I have 30 antidepressants to choose from so why not pick a sedating antidepressant with a side effect that can have a therapeutic benefit to the patient. And therefore, instead of waiting four, six, or eight weeks for an antidepressant to kick in – when I match the side effects like sedation to an insomnia symptom of the patient, then that patient can sleep better today and tomorrow and they don’t have to wait a month to start sleeping better. When that therapist can give me the target symptoms that the patient is experiencing, that should guide the choice of the antidepressant. 

Speaking Their Language

JR: It depends on the age of the patient. As I review the medical literature, I remember geriatrics. I know a good prescriber is someone who will stop a medication before they start a new one. Many of our patients have had multiple prescribers and have accumulated medications or accumulated disease states.

JR: That's hard to find. I won't say it's a unicorn, but it's a pretty rare situation. Of course, your patients are going to have to look at their insurance list.

Many of our physicians are specialized and they're very good at what they do, but I get worried about general practitioners, family practitioners and internists prescribing psychotropic medications because they weren’t specifically trained in that area. And unfortunately, but maybe fortunately depending on which insurance company you're talking to, they are the gatekeepers. A majority of our psychotropic medications are prescribed by non-psychiatrists and non-neurologists. They're prescribed by general practitioners and that is the system that we've developed.

JR: It is a very difficult situation when a patient is experiencing a problem due to accumulation and approaching levels of drug toxicity. It may be a non-psych drug, maybe a medical medication that they're not clearing either, but their presenting symptoms might look like depression or anxiety.

JR: If they're not going to become experts at pharmacotherapy, then at least maybe some psychotherapists could learn more medical terminology. If you're going to have a meaningful conversation with a prescriber, then use the same terminology that they're going to use. You can go online and take a course on medical terminology. At least when you're having conversations with those prescribers, you're better informed on the language.

JR: Even courses in basic anatomy and physiology. Let the therapist take it upon themselves to learn something about the medical world, as the medical world needs to take it upon themselves to learn more about the psychotherapeutic world.

A Place for Medications

JR: Exactly.

JR: Stimulate the appetite or reduce the appetite.

JR: Exactly.

JR: Sure, especially with schizophrenia and bipolar disorder and other severe forms of mental illness, where it's an issue of whether the medications are managing symptoms. But we're back to an individual suffering from schizophrenia or having to deal with those issues, and they may not even be able to engage in therapy or even educational or occupational interventions until their level of paranoia or hostility or insomnia has been addressed. And so these medications manage symptoms so that the person can then achieve a level of functioning that will allow them to engage in other activities.

JR: That's a great example. Let me give you a hypothetical, but a very common case. Let’s say that we are dealing with therapy and the therapist is doing everything right. Their therapeutic relationship has been established and the patient is coming to see them. They're doing the work, they seem to be engaged in therapy, but they are not fully responding.

JR:  Exactly. Now let’s say that despite the therapy, the patient is still very anergic, they're sleeping a lot, have no energy and a lot of fatigue. This therapist might actually be obligated to refer the patient for a medical workup because all the therapy in the world won't reverse hypothyroidism. It's a relatively common medical condition where the first presenting symptom is depression, but not including negative cognitive thought, just the physical manifestations.

When therapists are feeling that they’ve hit a wall, that therapy is no longer benefiting the patient or you're doing everything right and nothing is improving, well then yes let’s refer. Let’s work out anemia. Let’s work out hormonal dysfunction, whether it's hypothyroidism or low testosterone or estrogen occurrences. Maybe we're getting the person in the very beginnings of a perimenopausal state and hormones are changing but the person is feeling anxious. They don’t recognize anxiety as anxiety. They recognize sweating, palpitations and hot flashes. This is a great area where the therapist should say the target symptoms could be medical conditions. I think it does behoove a therapist to have more than a passing acquaintance with medical conditions that could present with symptoms of depression and anxiety. 

JR: Absolutely.

JR: Absolutely. In an ideal world, every patient who is getting therapy should probably be medically cleared.  If they're not being seen on a regular basis by a physician then yes, I would love for things like hypothyroidism to be ruled out early so we don’t waste a lot of time engaging in certain activities when all they needed was some Synthroid or hormonal replacement.

JR: I had a case presented to me just a couple of weeks ago where this person was dealing with a lot of depression and anxiety. They also suffered from migraine headaches but sleep apnea was an issue. And really one of the roles of the therapist is to help the patient recognize their conditions that need to be addressed, and even use something as simple as motivational interviewing to get them to use a CPAP machines or to more be adherent to their medications. If we can address these medical conditions, their secondary depressive and anxious symptoms will be addressed as well. If you have sleep apnea and you're not sleeping well, you're fatigued during the day. You're not concentrating during the daytime. You're checking off a list of DSM criteria for depression but you may have sleep apnea.

JR: Absolutely. Every time we take a pill, no matter what the condition is, we are at least briefly reminded of why we have to take that pill. And sometimes the patient doesn’t want to be reminded that they have a medical condition.

JR: Exactly. Schizophrenia, bipolar disorder, depression, every day you take that pill, that Lithium or that Prozac or that Risperdal or that Haldol, and you're reminded of the problem. That is actually a barrier to adherence. If you don’t want to be reminded of your conditions every day, a good way to avoid it is to simply not take your medications.

Everything Old is New Again

JR: Well, I think every therapist should engage in whatever continuing education that they can to try to stay on top of it. Our current and future therapies are still not offering cures, they are managing symptoms. If the patient stops taking these medications we see high relapse rates. We have not discovered a cure coming down the pike. Everybody wants the magic pill. And this is where I think a lot of our patients might engage in illicit drug use or using prescription drugs from somebody else off-label and without a proper indication. Everybody is looking for that but it's not going to happen for us anytime soon.

We are expanding the pharmacology so that the newer drugs that are coming in the pipeline are going to be working a little bit differently from our current medications. That makes for interesting and hopeful expectations regarding their efficacy, but they're not going to be changing the landscape in any significant way. You had mentioned SSRI’s, which were never shown to be superior to our older tricyclics or monoamine oxidase inhibitors. They were safer but not superior in efficacy. The newer SNRI’s [selective norepinephrine reuptake inhibitors] or our other antidepressants that have come out in the last few years are still working on serotonin and norepinephrine. We might be coming out with different medications, but we're still locked into a very simplified view of the problem.

That's what I love about psychiatry and depression, schizophrenia, bipolar disorder, no two patients are alike. We are different genetically and experientially; everything that makes us who we are makes us different. And therefore, we can't just apply one drug to treat all problems. We reach this wall where two out of three people get better meaning that a lot of our patients are still partial responders or resistant. And that is the research ground for our newer medications; trying to treat SSRI partial responders, the patients taking Prozac or Paxil who have gotten better but haves not achieved remission. Or our threshold can change for adding an antipsychotic to the patient’s medication list like Rexulti that you see advertised on TV. As an adjunct to an SSRI or SNRI partial responder, we can ideally achieve a greater level of symptom reduction.

It's interesting that if we were having this conversation in the ‘70s, and ‘80s, and ’90s, we wouldn’t have added antipsychotics. One of my favorite antidepressants is a drug called Amoxapine. It is kind of in the tricyclic group although it's a tetracyclic and it's a serotonin and norepinephrine reuptake inhibitor. It has some serotonin receptor antagonism as well. But one thing that everybody remembers about Amoxapine was that it was the antidepressant with EPS (extrapyramidal symptoms). It had a little bit of dopamine blockade because it was derived from an antipsychotic. And we said, “oh no,” I don’t want to use Amoxapine because it might cause EPS.” And now our threshold for that has changed because all of our drugs that are FDA approved for resistant or refractory depression have the ability to cause extrapyramidal symptoms because they all belong to the atypical antipsychotic class. 

JR: I think it's just very interesting that even some of our older drugs had the qualities then, and we found a way not to like them. And now 20, 30 years later, we're back to combining then in treatment for depression.

Enhancing Normal

JR: Okay, now that's a bit of a soapbox for me. Cosmetic psychopharmacology as I define it and how it has been defined by others in other cases like cosmetic neurology or neuropharmacology, is using medications to enhance normal. Let’s not talk about pathology and medications that were created to either treat it or prevent it, but now let’s take whatever definition you want for normal and enhance that. We've been using cosmetic pharmacology for a great number of years. We used amphetamines in World War I and World War II allowing a soldier or pilot to stay awake longer than normal. The soldier or the pilot did not have pathology, but we gave them amphetamines. And we still do this today, by the way.

JR: Students are a great example of using the Adderalls and the Ritalins. We all drink coffee when we, study which is cosmetic pharmacology. I have a problem with the excessive use of cosmetic pharmacology in certain areas. I worry about teenagers in high school and about the college students using Adderall and Ritalin; thinking and believing, an urban myth by the way, that it will enhance their grades or their test performance. That has not been proven because every medication becomes the means of getting a better grade and then they believe that “this gives me a better grade so I will take it for this test. But I need to make a good grade in this class, so every test matters. I need to make a very good grade in all of my classes, so every class matters.”

Every test including the MCATs, PCATs or some GRE becomes a high stakes exam. And now what we thought might have been occasional one time, as-needed medication use becomes weekly, if not daily, use of these medications over the course of high school, undergraduate, and graduate school. Some of our children and young adults might be taking these medications for a period of at least eight to twelve years. And I don't know what's going to happen to their brain because your brain isn't done cooking until you're about 25-years-old, so there is still neuro-development going on. And I think it's interesting how some individuals have rationalized the use of stimulants for brain enhancement for lack of a better word. Now, every time a professional athlete trying to make money, trying to win an award, using maybe some steroids or using some oxygen enhancement drug is getting an asterisk put on their names.

If you have the most home runs and you did an anabolic steroid designed to enhance muscle performance whether it's strength or conditioning, why is it that we have somehow criminalized the use of steroids for muscle performance, but we are not criminalizing the use of the stimulants for brain performance? 

Medicating Children

JR: I worry that sometimes we're requesting medication for symptoms that could be easily managed behaviorally or through psychotherapy. I worry about the snowball effect in child psychopharmacology. I will refer to the typical ADHD child as Timmy. Little Timmy has developed or has demonstrated some symptoms of ADD or ADHD and someone prescribes Adderall or Ritalin or some other stimulant. Now Timmy is highly activated because those symptoms may not have been true symptoms of ADD or ADHD. Add to that that our teachers have a fairly low threshold and they want a perfect classroom. You can't deviate from the norm very often in a large classroom setting. Timmy is now looking highly agitated, revved up, a little manic and now we're having to give him something at night to help him sleep or to bring him down. I use the term that we're “speedballing” little Timmy or he won't eat and won't sleep.

And now the drug that we give him to help bring him down brings him too far down and now someone entertains the idea of depression. Little Timmy is now getting an antidepressant along with a stimulant and some kind of medication that would reduce the neurotransmitters, these newer agents like Guanfacine, Clonidine or an atypical antipsychotic also approved for children with bipolar disorders. Our prescribers can rationalize that they're approved for use in these children. Follow me here! You’ve started with a stimulant, you end it possibly with an antipsychotic or neurotransmitter decreasing agent which looks like a downer. The downer results in someone saying depression and now we're back to an antidepressant. Timmy is now on three drugs, but drug number two and three could have only been in response to the side effects generated by drug number one which may not have been necessary. Our threshold for using, what I think are powerful medications in 5, and 6 and 7-year-olds is both impressive and sad at the same time. We really aren’t wanting to invest as much time in the therapy and the behavioral modification options. It takes work.

JR: Absolutely. And the side effects that those drugs cause might look like other therapeutic issues to be addressed.

Psychotropic Drug Dependence

JR: Oh, that's a very good question. Well, it depends on the psychotropic medication. For argument’s sake, let’s say a person has been prescribed Xanax and told to take it only as needed in more extreme situations of stress and anxiety. If they are refilling their prescription every 30 days as if they are using it and consuming it on a regular basis, then this sends a message to the therapist, as it should to the prescriber, that this person is having anxiety every day to the point to where either they are taking their medications even when they don’t need it to avoid anxiety, or their level of response is not where we want it to be, or physical dependence has set in. Physical dependence on a drug like Xanax probably sets in as early or earlier than even addiction. The reason why that is – and this is why I think benzodiazepines can be a trap for a lot of our patients, is that if I give you a benzodiazepine like a Xanax or an Ativan or a Valium for longer than two to four weeks, then when you don’t take the medication, the first symptoms that occur are anxiety and insomnia which are the very reasons why they were prescribed in the first place. Their continued use is reinforced and if this person is now having to take their medications on a regular basis and that was never the treatment plan, then you're looking at the signs of at least physical dependence.

Here’s an example. Grandma might have lost Grandpa 15 years ago. It was unfortunate and it was sad and she was having grief and couldn’t sleep. They gave her some medication for sleep or they gave her some medication for anxiety during the day. And 15 years later, she’s still taking that medication, way beyond the grief reaction time frame. Someone says to Grandma: “you know what I think, it's time that you stop taking the Halcion or the Valium or the Xanax.” First, she has a regular anxious reaction but then says, “you know what, you're a healthcare professional”, or “my daughter said something, so I will stop taking that medication as you recommend.”

That first night is the worst night of her life. It is insomnia and anxiety and it sends the message to Grandma that “I still need the medication. I've got the same problem I had 15 years ago.” Physical dependence sets in nicely with some of these controlled substances that we have.

If a person is demonstrating an avoidance behavior to stopping their medication, then they're avoiding withdrawal symptoms. Now if they are drug seeking and more overt and they’re taking more than prescribed, I think those symptoms are a little bit easier to see for individuals trained in substance abuse and addiction. It's the avoidance of withdrawal symptoms that look like the psychopathology for which we started the medications in the first place. That's why Grandma gets in trouble. That's why she’s still taking Ambien 10 or 20 years later or Xanax that much later.

LR: It goes back to this idea that as psychotherapists who work in the province of the mind in this age of medication and era of the brain, we have to be so much more aware of the relationship between the behavioral, cognitive and emotional changes in our patients and the possibility of their drug using behavior, whether licit or illicit. 

Health Literacy

JR: At first blush, I don’t like it. Okay, let me qualify that. The appropriate answer is that direct to consumer advertising when it was approved did one good thing to a lot of our patients which was that it told them that they were not alone. A lot of individuals are in their psychopathology-depression and anxiety, and they might think they're the only ones who feel that way and that no one understands them. They might even be fearful of seeking out treatment. Direct to consumer advertising usually casts a wide net of symptoms such as anxiety, depression or mania so the individual says: “wow, it looks like there are other people out there with this problem.”

JR: Right. It might reduce their reluctance to seek out treatment, which is good. However, telling you a very specific drug is the drug for you is not a good way to go. These newer drugs that are in direct to consumer advertising are sitting in the sample closet of every prescriber and the prescribers may be thinking, “I don’t want the patient to spend a lot of money.” They give their patient a sample box with a seven, ten, twelve or thirty-day supply for free.

If that drug works then great. However, that drug might cost $100 or $200 per month. And who’s going to pay for it? If that patient doesn’t have the financial resources or the insurance, then why did we just pick an expensive drug that they can't use beyond seven or fourteen days? Now we have to go to our generically available medications that aren’t advertised. For this reason, I don’t like direct to consumer advertising about a specific drug. I prefer for patients to tell me about a disease state and not mention the name of the drug. That's the better advertising. 

JR: Health literacy goes beyond learning about your own disease state and your disease state’s management. I think it goes into this area of being informed consumers, asking the right questions to the prescriber. And therapists can help their patients become health literate by referring them to the right resource, or at least helping them ask those questions. Now, granted, what have we asked for our therapists to do in the last hour? We've asked them to be well- informed through continuing education regarding pharmacotherapy, prescribing, laboratories and basic medical terminologies. We want that for their patients as well. I really wish more of my patients would take responsibility for their disease state and its management. The patient really is the center and one thing that we don’t do as often as we probably should is let the patient be part of the decision-making process. Not just a recipient but an active member of the treatment team. Because all our efforts will be for nothing if they don’t do their part of the treatment plan.

Wrapping Up

JR: Well, given that we should ideally all belong to some interprofessional collaborative practice, I think that a psychotherapist really needs to do their very best at keeping up to speed, going to educational programming, continuing psychopharmacology education, and learning medical terminology so that they can have meaningful conversations with other practitioners. When they are referring a patient who is seemingly resistant to psychotherapy and the depressive symptoms are continuing, they could say this might be hypothyroidism. At least then we can do the thyroid function test, at least we can do iron levels, at least we can do a complete blood cell count, to make sure that the patient doesn’t have a certain anemia.

JR: Yes.

JR: Given our world of psychotherapy, I think that would be prudent-absolutely.