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Discussing Side Effects With Patients
Rajnish Mago, MD
Director, Mood Disorders Program, Associate Professor of Psychiatry, Thomas Jefferson University
Dr. Mago discloses that he has received research grants from Alkermes, Allergan (formerly Forest Laboratories), Genomind, and Takeda, and that he has been a paid consultant to Genomind, Guidepoint Global, Otsuka, and Lundbeck. Dr. Carlat has reviewed this article and found no evidence of bias in this educational activity.
TCPR: Dr. Mago, you’ve taken quite an interest in teaching about side effects of medications.
Dr. Mago: Yes, I got interested in doing research on and teaching about side effects because I could not get answers to the questions that came up in my patients. I think that as clinicians, we need to fully understand the importance of side effects for our patients. Do you know what is the most important problem in psychopharmacology? It is that patients stop taking their medication sooner or later. And what is the most frequent single reason for their stopping the medication? Side effects.
TCPR: Don’t we already understand this?
Dr. Mago: Not necessarily. If we do a systematic assessment, we find more side effects than the treating clinician would be aware of. Many side effects are under-recognized: sexual dysfunction such as excessive sweating, or extrapyramidal symptoms with atypical antipsychotics.
TCPR: How do such adverse effects impact patient care?
Dr. Mago: They lead to patients stopping medications prematurely. According to one study, half of the people who are started on an antidepressant do not finish the initial course of treatment. During the first two weeks of starting an antidepressant is when many of the side effects occur, such as nausea, activation, or insomnia and so on. If you ask patients who stop antidepressants, “Why did you stop?” at two weeks, 61% of them say, “I stopped because of side effects.” That number decreases after a few weeks, so that for those who stopped taking medications at 12 weeks, 47% say the reason is side effects (Crawford AA et al, Psychopharmacology (Berl) 2014;231(15):2921–2931). So especially early on, it’s very important for us to be proactive in order to reduce this non-adherence.
TCPR: So it sounds like we need to do a better job preparing our patients about the possibility of side effects even before they start taking a medication.
Dr. Mago: Absolutely. When I prescribe medications, I tell my patients, “Listen, most of the side effects of this medication tend to be mild and time-limited. That means that they tend to diminish within approximately two weeks. So if we can manage them and help you to stay on the medication, the great majority will disappear.”
TCPR: Not all side effects disappear, however.
Dr. Mago: Right, there are some that usually don’t go away, like sexual dysfunction, excessive sweating, or weight gain. But most of the common ones that lead to stopping the medications—like activation, nausea, headache, or insomnia—they tend to diminish within the first 30 days. The other thing I say to patients is, “These are nuisance side effects.” This is a very important point. We must help patients to distinguish between nuisance side effects, which are irritating but not harmful, and medically serious side effects. So I say, “If you have any of these nuisance side effects, don’t stop the medication right away, but instead call me and we can do something to diminish them.” These are simple interventions, but I have been amazed at what a difference they make in my patients.
TCPR: So in your day-to-day treatment, it sounds like you make three main points about side effects when starting medications: that most are mild and time-limited, that they are nuisance side effects but not medically serious, and that patients can call you to do something about them. Do you have a list that you give patients of the common side effects of certain medications along with the things that you are likely to do about them?
Dr. Mago: Yes, whether it is a new medication I am prescribing or one that they are already taking, I hand them a list of what I consider to be the common side effects of that particular medicine. But the surprisingly difficult question is what should be put on that list.
TCPR: In what way?
Dr. Mago: I suspect that if you took three psychiatrists and mentioned any commonly used medicine like escitalopram, lithium, or zolpidem, each clinician would mention different adverse effects as being the most common side effects. One of the challenges that I faced when I addressed this problem was that in clinical trials, we use the term “adverse events.” While reading the literature or the PDR, clinicians should understand the distinction between an adverse event and an adverse effect. An adverse event just means any undesirable thing that happened during the study. A patient slipped and fell down—that’s coded as an adverse event. Or a patient gets a cold—this is coded as an upper respiratory infection. In other words, when an adverse event is listed, you can’t be sure that it has actually been caused by the drug.
TCPR: So how do you determine what side effects to share with patients?
Dr. Mago: My solution is to tell patients about common adverse effects based on the following criteria: A side effect is “common” if it occurs in 5% or more of persons on the drug; and consider an adverse event to be an adverse effect if it occurs at least twice as often as on placebo. This is actually the approach taken by the FDA, and if we take this approach, we don’t end up with hundreds of adverse effects. For most medications, there are around five to 10 such adverse effects that I tell my patients about. Based on these two criteria, I have created side effect lists for the common medications that we prescribe. One part of the sheet lists all the adverse effects that occur in 5% or more of patients, and another lists those that occur less commonly in 1%–5% of patients on the drug. I tell my patients, “Here are the side effects documents; please take a look at them. This shows you the possible common side effects that occur. There might be others that occur rarely, but these are the common ones.” They also need to know the chances of developing a side effect, so on my sheets I also list what percentage of patients get each side effect. [Ed note: You can access many of Dr. Mago’s side effect handouts on his website.]
TCPR: I like your approach of handing them the list of side effects and going over them. Most of us tend to rattle off a list verbally.
Dr. Mago: Yes, patients don’t need to hear and try to memorize a list of the 10–20 possible side effects; they need to have easy access to that information. In addition to common and adverse side effects, if a medicine has a particularly serious adverse effect, even if it is uncommon, we have to carefully discuss that possibility and document the discussion. Examples include Stevens-Johnson syndrome with lamotrigine or renal impairment in long-term lithium treatment—both are very uncommon but nevertheless need to be discussed.
TCPR: Some clinicians are reluctant to tell patients about very serious side effects that are very rare, for fear of scaring a patient away from a medication that might be very helpful for them.
Dr. Mago: True, but that is an interesting mindset. The question we should ask ourselves is: If you were the patient, would you want the doctor to hide information from you that is important for fear that you might not take the treatment? Why should clinicians take on this extraordinary responsibility? The patients must know the pros and cons and then make an educated decision. It’s their choice in the end, right? But that said, I do understand the clinicians’ concern. One problem is that often if you tell the person about the adverse event, they automatically assume that they are going to get that adverse event.
TCPR: Right. Do you have any suggestions from your own practice of how to effectively address this?
Dr. Mago: Sure. Say you have diagnosed a patient with bipolar disorder, and after explaining your course of treatment with lamotrigine, the patient says, “Oh, no, having a serious rash sounds very scary.” There are a few things I would say to this. The first deals with the facts: “Listen, the first thing is that about one in 1000 persons with bipolar disorder develop a serious rash when treated with lamotrigine, but 999 out of 1000 do not! Secondly, to reduce the chances of your developing a serious rash, we are starting on a low dose and going up slowly. We are also avoiding giving you any medication that may increase the lamotrigine level. And thirdly, the risk is mainly in the first few months and after that, the risk becomes much less.” The next thing is to reassure them that you are going to be monitoring for this. I’ll say, “Therefore, you should check yourself front and back every day after you shower. If any rash appears, you must immediately call me and we will make a decision as to what should be done.” The reassurance that the adverse effect will be carefully monitored seems to calm people down in addition to emphasizing the very high proportion of people who don’t have that adverse effect.
TCPR: Okay, and what about after that initial visit is over? The patient comes back, and how do we ascertain whether they’ve had any side effects? Do we go back over the entire checklist each visit?
Dr. Mago: It would probably work well, but that would be time-consuming, so it’s not very practical for clinical use.
TCPR: Often we’ll at least ask a general question about side effects such as, “Have you had any side effects of the medication since you started taking it?”
Dr. Mago: Right, we should do that, but we can do even better. I’ve done studies in which we asked patients this type of general question and then later on had the doctor interview the patient in detail about side effects, and we compared the two answers. We found that when you ask patients an open-ended question like, “Have you had any side effects?” the patient reports only about one-third of the side effects that the doctor later identified (Mago R et al, J Clin Psychopharmacol 2012;32(6):828–831).
TCPR: So it sounds like we’re back to a time-consuming checklist if we want to do a good job?
Dr. Mago: Not necessarily. We have tested a sort of in-between technique. You say, “Have you had any side effects from the medication since you started it?” And the person mentions one or two symptoms. You should then say, “Anything else?” The patient may mention another symptom. You should say again, “Anything else?” until the person says, “No, that’s it.” Almost always this happens after asking “Anything else?” one or two times. The next step is to ask one more question that has a different wording: “Have you had any new symptoms since you started taking the medication?” Combining these two approaches is a big improvement on the current clinical practice, and it takes maybe two to three minutes. Try it. You’ll find that it is helpful and not time-consuming.
TCPR: Now, what about the issues of side effects like drowsiness, insomnia, or anxiety, which could be side effects of medications, but are also very commonly symptoms of the underlying condition that we are treating? Do you have any advice on how to disentangle those?
Dr. Mago: That’s a great question. In general, patients do have a reasonably good ability to distinguish between symptoms of their illness and a side effect of the medication. First, you can ask them about the timing of the symptom. If it’s clearly worse since the medication was started, that can help you to know that it may be an adverse effect of the medication. If we use rating scales in our clinical practices, it makes it easier to know that the severity of a symptom has worsened. Secondly, sometimes the quality of the symptom changes. I have had many patients say to me something like, “I used to have headaches intermittently, but this is a different kind of headache.” They then describe in what way the headache is different from what they used to have.
TCPR: How do you deal with discussing drug discontinuation symptoms as a potential side effect?
Dr. Mago: I think that all you need to say—and I say this for all medications, not only for antidepressants—is, “For any reason, if we need to stop your medication, it is very important that we don’t do that abruptly. So please discuss it with me and I’ll advise you how to reduce it gradually.” This is true for lithium, benzodiazepines, or antidepressants, and so on. We can just make a general statement—I don’t list all possible discontinuation symptoms.
TCPR: How do you discuss addiction as a side effect of certain meds, such as benzodiazepines or stimulants?
Dr. Mago: Of course we should not deny the possibility of abuse of certain medications. But the much more common and important issue is that people often do not understand the difference between being physically used to the medication and being addicted. So when they ask about the issue of addiction, I say, “To me, addiction means that the person starts taking the medicine not for its medical benefit, but because it gives them a high and they can’t control their use. In that sense it is not likely that these medications are going to make you addicted. But it is true that, like with many psychiatric and non-psychiatric medications, your body will become used to taking this medication. So you can’t suddenly stop it, because you may have some withdrawal symptoms. That is being physically used to the medication. So if the time comes when we have to stop the medication, we will reduce it slowly and taper it off, in which case the great majority of patients don’t have many problems.” This reassures them. You don’t want them misusing the term “addiction” and assuming that because they can’t just abruptly stop the medication means that they are addicted to it.
TCPR: Thank you, Dr. Mago, for sharing these tips with our readers.
Suggested reading:
Mago R. Side Effects of Psychiatric Medications: Prevention, Assessment, and Management. Amazon Digital Services, Inc, 2014.
Mago R. Adverse effects of psychotropic medications: a call to action. Psychiatr Clin North Am 2016;39(3):361–373. PubMed PMID: 27514294.
General PsychiatryDr. Mago: Yes, I got interested in doing research on and teaching about side effects because I could not get answers to the questions that came up in my patients. I think that as clinicians, we need to fully understand the importance of side effects for our patients. Do you know what is the most important problem in psychopharmacology? It is that patients stop taking their medication sooner or later. And what is the most frequent single reason for their stopping the medication? Side effects.
TCPR: Don’t we already understand this?
Dr. Mago: Not necessarily. If we do a systematic assessment, we find more side effects than the treating clinician would be aware of. Many side effects are under-recognized: sexual dysfunction such as excessive sweating, or extrapyramidal symptoms with atypical antipsychotics.
TCPR: How do such adverse effects impact patient care?
Dr. Mago: They lead to patients stopping medications prematurely. According to one study, half of the people who are started on an antidepressant do not finish the initial course of treatment. During the first two weeks of starting an antidepressant is when many of the side effects occur, such as nausea, activation, or insomnia and so on. If you ask patients who stop antidepressants, “Why did you stop?” at two weeks, 61% of them say, “I stopped because of side effects.” That number decreases after a few weeks, so that for those who stopped taking medications at 12 weeks, 47% say the reason is side effects (Crawford AA et al, Psychopharmacology (Berl) 2014;231(15):2921–2931). So especially early on, it’s very important for us to be proactive in order to reduce this non-adherence.
TCPR: So it sounds like we need to do a better job preparing our patients about the possibility of side effects even before they start taking a medication.
Dr. Mago: Absolutely. When I prescribe medications, I tell my patients, “Listen, most of the side effects of this medication tend to be mild and time-limited. That means that they tend to diminish within approximately two weeks. So if we can manage them and help you to stay on the medication, the great majority will disappear.”
TCPR: Not all side effects disappear, however.
Dr. Mago: Right, there are some that usually don’t go away, like sexual dysfunction, excessive sweating, or weight gain. But most of the common ones that lead to stopping the medications—like activation, nausea, headache, or insomnia—they tend to diminish within the first 30 days. The other thing I say to patients is, “These are nuisance side effects.” This is a very important point. We must help patients to distinguish between nuisance side effects, which are irritating but not harmful, and medically serious side effects. So I say, “If you have any of these nuisance side effects, don’t stop the medication right away, but instead call me and we can do something to diminish them.” These are simple interventions, but I have been amazed at what a difference they make in my patients.
TCPR: So in your day-to-day treatment, it sounds like you make three main points about side effects when starting medications: that most are mild and time-limited, that they are nuisance side effects but not medically serious, and that patients can call you to do something about them. Do you have a list that you give patients of the common side effects of certain medications along with the things that you are likely to do about them?
Dr. Mago: Yes, whether it is a new medication I am prescribing or one that they are already taking, I hand them a list of what I consider to be the common side effects of that particular medicine. But the surprisingly difficult question is what should be put on that list.
TCPR: In what way?
Dr. Mago: I suspect that if you took three psychiatrists and mentioned any commonly used medicine like escitalopram, lithium, or zolpidem, each clinician would mention different adverse effects as being the most common side effects. One of the challenges that I faced when I addressed this problem was that in clinical trials, we use the term “adverse events.” While reading the literature or the PDR, clinicians should understand the distinction between an adverse event and an adverse effect. An adverse event just means any undesirable thing that happened during the study. A patient slipped and fell down—that’s coded as an adverse event. Or a patient gets a cold—this is coded as an upper respiratory infection. In other words, when an adverse event is listed, you can’t be sure that it has actually been caused by the drug.
TCPR: So how do you determine what side effects to share with patients?
Dr. Mago: My solution is to tell patients about common adverse effects based on the following criteria: A side effect is “common” if it occurs in 5% or more of persons on the drug; and consider an adverse event to be an adverse effect if it occurs at least twice as often as on placebo. This is actually the approach taken by the FDA, and if we take this approach, we don’t end up with hundreds of adverse effects. For most medications, there are around five to 10 such adverse effects that I tell my patients about. Based on these two criteria, I have created side effect lists for the common medications that we prescribe. One part of the sheet lists all the adverse effects that occur in 5% or more of patients, and another lists those that occur less commonly in 1%–5% of patients on the drug. I tell my patients, “Here are the side effects documents; please take a look at them. This shows you the possible common side effects that occur. There might be others that occur rarely, but these are the common ones.” They also need to know the chances of developing a side effect, so on my sheets I also list what percentage of patients get each side effect. [Ed note: You can access many of Dr. Mago’s side effect handouts on his website.]
TCPR: I like your approach of handing them the list of side effects and going over them. Most of us tend to rattle off a list verbally.
Dr. Mago: Yes, patients don’t need to hear and try to memorize a list of the 10–20 possible side effects; they need to have easy access to that information. In addition to common and adverse side effects, if a medicine has a particularly serious adverse effect, even if it is uncommon, we have to carefully discuss that possibility and document the discussion. Examples include Stevens-Johnson syndrome with lamotrigine or renal impairment in long-term lithium treatment—both are very uncommon but nevertheless need to be discussed.
TCPR: Some clinicians are reluctant to tell patients about very serious side effects that are very rare, for fear of scaring a patient away from a medication that might be very helpful for them.
Dr. Mago: True, but that is an interesting mindset. The question we should ask ourselves is: If you were the patient, would you want the doctor to hide information from you that is important for fear that you might not take the treatment? Why should clinicians take on this extraordinary responsibility? The patients must know the pros and cons and then make an educated decision. It’s their choice in the end, right? But that said, I do understand the clinicians’ concern. One problem is that often if you tell the person about the adverse event, they automatically assume that they are going to get that adverse event.
TCPR: Right. Do you have any suggestions from your own practice of how to effectively address this?
Dr. Mago: Sure. Say you have diagnosed a patient with bipolar disorder, and after explaining your course of treatment with lamotrigine, the patient says, “Oh, no, having a serious rash sounds very scary.” There are a few things I would say to this. The first deals with the facts: “Listen, the first thing is that about one in 1000 persons with bipolar disorder develop a serious rash when treated with lamotrigine, but 999 out of 1000 do not! Secondly, to reduce the chances of your developing a serious rash, we are starting on a low dose and going up slowly. We are also avoiding giving you any medication that may increase the lamotrigine level. And thirdly, the risk is mainly in the first few months and after that, the risk becomes much less.” The next thing is to reassure them that you are going to be monitoring for this. I’ll say, “Therefore, you should check yourself front and back every day after you shower. If any rash appears, you must immediately call me and we will make a decision as to what should be done.” The reassurance that the adverse effect will be carefully monitored seems to calm people down in addition to emphasizing the very high proportion of people who don’t have that adverse effect.
TCPR: Okay, and what about after that initial visit is over? The patient comes back, and how do we ascertain whether they’ve had any side effects? Do we go back over the entire checklist each visit?
Dr. Mago: It would probably work well, but that would be time-consuming, so it’s not very practical for clinical use.
TCPR: Often we’ll at least ask a general question about side effects such as, “Have you had any side effects of the medication since you started taking it?”
Dr. Mago: Right, we should do that, but we can do even better. I’ve done studies in which we asked patients this type of general question and then later on had the doctor interview the patient in detail about side effects, and we compared the two answers. We found that when you ask patients an open-ended question like, “Have you had any side effects?” the patient reports only about one-third of the side effects that the doctor later identified (Mago R et al, J Clin Psychopharmacol 2012;32(6):828–831).
TCPR: So it sounds like we’re back to a time-consuming checklist if we want to do a good job?
Dr. Mago: Not necessarily. We have tested a sort of in-between technique. You say, “Have you had any side effects from the medication since you started it?” And the person mentions one or two symptoms. You should then say, “Anything else?” The patient may mention another symptom. You should say again, “Anything else?” until the person says, “No, that’s it.” Almost always this happens after asking “Anything else?” one or two times. The next step is to ask one more question that has a different wording: “Have you had any new symptoms since you started taking the medication?” Combining these two approaches is a big improvement on the current clinical practice, and it takes maybe two to three minutes. Try it. You’ll find that it is helpful and not time-consuming.
TCPR: Now, what about the issues of side effects like drowsiness, insomnia, or anxiety, which could be side effects of medications, but are also very commonly symptoms of the underlying condition that we are treating? Do you have any advice on how to disentangle those?
Dr. Mago: That’s a great question. In general, patients do have a reasonably good ability to distinguish between symptoms of their illness and a side effect of the medication. First, you can ask them about the timing of the symptom. If it’s clearly worse since the medication was started, that can help you to know that it may be an adverse effect of the medication. If we use rating scales in our clinical practices, it makes it easier to know that the severity of a symptom has worsened. Secondly, sometimes the quality of the symptom changes. I have had many patients say to me something like, “I used to have headaches intermittently, but this is a different kind of headache.” They then describe in what way the headache is different from what they used to have.
TCPR: How do you deal with discussing drug discontinuation symptoms as a potential side effect?
Dr. Mago: I think that all you need to say—and I say this for all medications, not only for antidepressants—is, “For any reason, if we need to stop your medication, it is very important that we don’t do that abruptly. So please discuss it with me and I’ll advise you how to reduce it gradually.” This is true for lithium, benzodiazepines, or antidepressants, and so on. We can just make a general statement—I don’t list all possible discontinuation symptoms.
TCPR: How do you discuss addiction as a side effect of certain meds, such as benzodiazepines or stimulants?
Dr. Mago: Of course we should not deny the possibility of abuse of certain medications. But the much more common and important issue is that people often do not understand the difference between being physically used to the medication and being addicted. So when they ask about the issue of addiction, I say, “To me, addiction means that the person starts taking the medicine not for its medical benefit, but because it gives them a high and they can’t control their use. In that sense it is not likely that these medications are going to make you addicted. But it is true that, like with many psychiatric and non-psychiatric medications, your body will become used to taking this medication. So you can’t suddenly stop it, because you may have some withdrawal symptoms. That is being physically used to the medication. So if the time comes when we have to stop the medication, we will reduce it slowly and taper it off, in which case the great majority of patients don’t have many problems.” This reassures them. You don’t want them misusing the term “addiction” and assuming that because they can’t just abruptly stop the medication means that they are addicted to it.
TCPR: Thank you, Dr. Mago, for sharing these tips with our readers.
Suggested reading:
Mago R. Side Effects of Psychiatric Medications: Prevention, Assessment, and Management. Amazon Digital Services, Inc, 2014.
Mago R. Adverse effects of psychotropic medications: a call to action. Psychiatr Clin North Am 2016;39(3):361–373. PubMed PMID: 27514294.
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