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Psych News Special Report: Antidepressant Withdrawal with Dr. Bryan Shapiro · The Medical Mind

• 0:11
  Welcome to the Psychiatric News Special Report podcast, a monthly podcast produced by Psychiatric News for the APA's Medical Minds channel.
• 0:19
  I'm Dr.
• 0:20
  Adrian Preda, Editor-in-Chief of Psychiatric News and Professor of Clinical Psychiatry and Human Behavior at UC Irvine School of Medicine.
• 0:28
  Today, I'm joined by Dr.
• 0:29
  Brian Shapiro to discuss a critical and often under-recognized clinical issue that affects millions of patients, antidepressant withdrawal.
• 0:38
  Dr.
• 0:38
  Shapiro,
• 0:39
  He's an assistant clinical professor of psychiatry and human behavior at UC Irvine, where he's developed extensive expertise in antidepressant pharmacology and withdrawal symptoms.
• 0:49
  He's the lead author of this month's special report titled Antidepressant Withdrawal, co-authored with Dr.
• 0:56
  Daniel Kors, a fourth-year psychiatry resident at USC.
• 1:00
  Their comprehensive review tackles a condition that affects an estimated third to almost more than a half of patients discontinuing antidepressants.
• 1:08
  yet remains inadequately addressed in clinical practice.
• 1:12
  With one in eight Americans, adults currently prescribed an antidepressant and the median treatment duration of five years, understanding how to safely taper these medications has
• 1:22
  never been more crucial.
• 1:25
  Brian, let me start by asking about your journey into psychiatry.
• 1:29
  What initially drew you to the field and how did you become interested in this very particular uh topic, antidepressant discontinuation, and his role?
• 1:39
  Yeah, so I had a very early exposure to the world of psychiatry.
• 1:44
  When I was seven or eight years old, I was briefly prescribed Paxil for separation anxiety.
• 1:51
  And I remember, you know, taking these medications, but particularly when I was coming off of medications, I just had a very early memory of going into my mother's bedroom because
• 2:01
  she would cut little slivers of the Paxil pills to give me every night.
• 2:08
  And she would notice that I was just not myself when she was just giving me a lower dose based on the psychiatrist recommendations.
• 2:16
  uh And so uh that kind of stuck with me, that early exposure to medications and mental health and anxiety.
• 2:25
  uh And that uh kind of oriented me towards towards mental health and thinking about a career in psychiatry and maybe helping people.
• 2:35
  And the same way actually that the medication I feel like did help me initially, but also considering uh the idea of coming off of medication.
• 2:42
  So tapering, deep prescribing uh as an element that was just as important as the prescribing of the medication itself.
• 2:53
  that is a powerful story.
• 2:56
  So you had personally experienced the withdrawal symptoms from an antidepressant.
• 3:02
  And so it's interesting, right, because for a long time that was considered sort of like, you know, something that would happen here and there.
• 3:10
  as a field, we did not become aware of the antidepressant withdrawal being really a distressing condition that needs to be considered on a regular basis.
• 3:21
  So
• 3:22
  Let's go to the special report because you start by making the point that this is not just something that happens here and there.
• 3:29
  It's just not some low numbers type of a problem.
• 3:32
  In fact, the people who are at risk for antidepressant withdrawal, the numbers are high and the condition has been in fact recognized in the SM-4 text revision as a diagnosis.
• 3:45
  Now we're looking at an antidepressant discontinuation syndrome, right?
• 3:49
  Yes.
• 3:50
  And there's a lot to discuss here because even the phrase, the term antidepressant discontinuation syndrome is a little bit of a euphemism that at least gives a perception
• 4:00
  that this is a more mild kind of condition compared to an actual withdrawal syndrome.
• 4:06
  so I think historically, I think once Prozac was introduced to the market, it was the benzodiazepines that were maligned and those are the ones that are...
• 4:16
  going to become addicted to and there's a lot of withdrawal associated with them.
• 4:20
  with these antidepressants, withdrawal is very, quote unquote, mild and short lived, which has turned out not to be the case.
• 4:28
  So from mild to short-lived, we now know that in fact, oftentimes that could be a significant clinical concern, which is associated with potential substantial morbidity and
• 4:40
  even functional impairment, isn't it?
• 4:43
  Yes.
• 4:43
  And to be fair, there is a lack of data on the higher end where, know, where prevalence is, you know, 50, 60, 70%.
• 4:51
  These are typically survey based studies.
• 4:53
  Um, on the lower end, such as the recent Lancet article in 2024, uh, where they reported 15 % of incidents of withdrawal with 3 % of instance, uh, of, uh, severe cases.
• 5:05
  There were a lot of limitations to that sort of data because a lot of our control trials are less than 12 weeks.
• 5:12
  Whereas just as you had mentioned, median duration of antidepressant use is now five years.
• 5:18
  So let's uh unpack that a bit because I think that's such important information.
• 5:24
  first, the rates, the overall incidence of withdrawal is high, right?
• 5:31
  So you're quoting a systematic review which gives a range which goes from about 33 % to 56%.
• 5:38
  So that's one third to a little bit more than a half of the patients who
• 5:44
  are facing a scenario of those decrease or discontinuation are at risk for experiencing those symptoms.
• 5:52
  That's a high number.
• 5:53
  It is, and one in eight American adults are prescribed antidepressant drugs, one in five women.
• 6:00
  um This is millions of Americans we're talking about.
• 6:04
  So lots and lots of people.
• 6:05
  And from these people, the other point that your report is making is that a good number of these people are actually at risk, not only for just discontinuation symptoms and
• 6:16
  withdrawal symptoms, but potentially severe forms of withdrawal.
• 6:21
  And then, you know, one of the things that I'm curious about, so you make the point that the numbers there, it's about 25%, but there is some variability depending on the study.
• 6:30
  So can you talk about that?
• 6:32
  Yes.
• 6:33
  So we know that, you know, with, with survey-based studies, a lot of these come out of the UK, there was a reporting bias, there's a response bias and, you know, people who have had
• 6:42
  terrible experiences with, with coming off of their antidepressants are more likely to respond and report symptoms.
• 6:51
  On the lower end, you know, honing in specifically on, you know, some of the reviews of controlled trials.
• 7:00
  These studies, uh they had a lot of methodological limitations.
• 7:06
  First of all, nearly half of trials were shorter than 12 weeks, which is kind of an analogy is assessing the safety of a car by doing crash testing at five miles an hour and
• 7:18
  saying that it's safe on the highway because people are taking these drugs a very long time.
• 7:25
  Additionally, a lot of these controlled studies did not uh actually
• 7:30
  did not actually do structured assessments of withdrawal.
• 7:32
  Oftentimes these withdrawal symptoms were self-reported.
• 7:35
  Very few had actually structured assessments using validated tools to assess for withdrawal symptoms.
• 7:42
  So understandably, we're seeing a lot of variation in the reported prevalence, but even on the lower end or the higher end, mean, these are millions and millions of Americans uh
• 7:53
  that are potentially at risk for these withdrawal.
• 7:56
  got it.
• 7:57
  So it seems like there is maybe some unclarity about the numbers because the initial studies which give high numbers of people who are at risk for severe withdrawal, 25 %
• 8:08
  studies.
• 8:09
  Those are studies that are somewhat limited by the fact that they are based on self-reports and maybe self-selection bias.
• 8:15
  Now at the lower end, and the statistic that you put in your report is about 3 % 3 % or so, those studies unfortunately well
• 8:24
  they present good quality data.
• 8:25
  The data is contaminated if we, you know, maybe it's a way to think about it, about the fact that the limitation there is that these are shorter trials with shorter exposures and
• 8:36
  maybe even lower doses, which in turn could decrease the risk for withdrawal to occur in the first place.
• 8:42
  So this range of three to 25%, you know, if you're going to kind of look the frequency of withdrawal, it's somewhat orientative and it's probably safe to say that
• 8:53
  that we need better research to understand what's happening.
• 8:55
  But this is a good number of people who are at risk for withdrawal.
• 8:59
  Yes, exactly.
• 9:00
  um And we're talking about, we're talking about missed work days, we're talking about suicidal behavior, um significant functional impairments.
• 9:09
  It's a huge problem.
• 9:10
  So let's get into that.
• 9:12
  What are the typical symptoms that patients might experience and how long do they typically last?
• 9:18
  Yes.
• 9:19
  And this is a really important point because antidepressant withdrawal and when we say antidepressant withdrawal, because most of the studies examined serotonin reuptake
• 9:28
  inhibitors, we're usually referring to serotonin withdrawal.
• 9:32
  The issue is that these are a very non-specific constellation of symptoms, psychological, cognitive, physical symptoms.
• 9:39
  And there is, I know we talked about this personally, there is one relatively specific symptom, just one that's pretty common.
• 9:46
  called brain zaps or electric shock like sensations that are felt in the, it feels like it's in the brain, exacerbated by head movement.
• 9:55
  Other than that, these are very nonspecific symptoms.
• 9:59
  We did some research on this, survey-based research and of these withdrawal symptoms, the ones that are most common, and if they don't have these symptoms, usually it's not
• 10:10
  antidepressant withdrawal.
• 10:12
  It's dizziness, irritability,
• 10:14
  electric shock like sensations or brain zaps, just agitation.
• 10:20
  Usually it's the physical symptoms that are the clue.
• 10:24
  So it's a combination of physical symptoms, sensations, then mood and thinking symptoms.
• 10:31
  this very, very strange sensation of brain zaps.
• 10:36
  And what's interesting about that one is that, know, patients, they're very clear that that's what they experience.
• 10:42
  uh It's kind of a pain type of a problem, but it's not really plain pain.
• 10:47
  It's an electroshock.
• 10:48
  And what's interesting about that is there are no pain receptors in the brain.
• 10:52
  And that tends to be very characteristic of this antidepressant withdrawal type of presentation, isn't it?
• 10:58
  That's right.
• 10:59
  Very mysterious.
• 11:00
  We don't see these brain zaps with other withdrawal from other psychotropic drugs.
• 11:06
  So very fascinating, interesting phenomenon.
• 11:09
  And then also the other part, which then it's really significant, is that it's not just sensations and symptoms.
• 11:16
  These presentations could result in missed work days, reduced productivity, increased healthcare costs.
• 11:23
  So this is not a trivial issue.
• 11:26
  not a trivial issue.
• 11:27
  uh Exactly.
• 11:31
  It can be very, very distressing.
• 11:33
  Just the malaise and just the sense of feeling unwell and not yourself.
• 11:36
  em It's really subjectively very distressing to experience.
• 11:43
  Let's talk about risk factors.
• 11:44
  Do we know what is it that could increase the risk for withdrawal?
• 11:48
  We do, we do.
• 11:50
  What we know is that the risk of withdrawal, there are a few factors that are pretty clearly correlated.
• 11:56
  Although even without these, withdrawal symptoms can be significant.
• 12:00
  But we're thinking about antidepressants, specifically serotonin reuptake inhibitors that have short elimination half-lives.
• 12:09
  So we think about Paxil 21 hours, Venlafaxine, five hours, active metabolite, Pristique with 11 hours, those drugs.
• 12:17
  duloxetine or Cymbalta, I think around 12 hours.
• 12:22
  So these drugs have much higher risks.
• 12:25
  Although even acetalipram, cetalipram, when you're thinking 30 or more hours, also can have significant risk, but just not quite as high.
• 12:33
  We're talking about drugs ah that uh really have a limited formulary.
• 12:40
  This is a real uh key because even with perfect information, it can be very hard to taper these drugs.
• 12:47
  For instance, uh drugs like Cymbalta, Diloxetine, and I just wrote about this, even the lowest available dose of 20 milligram capsule has about 70, at least 71 % activity at the
• 12:59
  serotonin transporter.
• 13:01
  Long-term treatment, although we don't have a lot of gray data on this, long-term treatment, so more than six months, you're gonna see an incremental increase in risk that
• 13:11
  tends to around two to three years.
• 13:14
  ah
• 13:17
  So it seems like there are a couple of significant red flags.
• 13:22
  So one is the type of medications and the more serotonin-ergic the antidepressant is, the higher the risk, which then includes, of course, the typical serotonin reuptake
• 13:31
  inhibitors, but also some of the serotonin or pyrinephrine reuptake inhibitors.
• 13:38
  Now there are antidepressants who are not serotonin-ergic, right?
• 13:44
  And then for those probably,
• 13:46
  that the risk is decreased and it seems like that's what the literature has consistently shown.
• 13:52
  So the type of drugs.
• 13:53
  And then you are making the point that the half-life is very important.
• 13:59
  it's the summary of this is that the longer the half-life, the lower the risk, meaning that the shorter the high life, the higher the risk, right?
• 14:07
  And then the next one that you mentioned is duration of exposure and the fourth one, the dose.
• 14:14
  Am I missing anything?
• 14:15
  Yeah, so doses is interesting.
• 14:19
  While yes, exposure to higher doses may have a slightly higher risk.
• 14:24
  um This is a different topic, but very relevant is that even these minimum therapeutic doses, Prozac 20, Lexapro 10, these have 80 % activity at the receptor.
• 14:37
  So there's this significant exposure that incurs very high withdrawal risk, even though the dose is ostensibly quite low.
• 14:45
  uh Exactly.
• 14:47
  And the science, you will get into that.
• 14:49
  found it fascinating, the whole radio ligand study.
• 14:52
  So we'll get into that in a little bit.
• 14:55
  So we'll discuss the dose, but is it correct then to say though that the higher the dose, so even low doses are at risk.
• 15:03
  think that's something that people tend to not appreciate, but do the data also indicates that the higher the dose, the higher the risk or that's not really confirmed.
• 15:14
  It does, but with diminishing returns in terms of additional risk.
• 15:18
  Got it.
• 15:19
  So it does.
• 15:21
  And then the other point is that the duration of exposure matters.
• 15:24
  Can you talk about that?
• 15:26
  Yes.
• 15:26
  So we know that it takes usually about four weeks for the brain to undergo adaptive processes that incurs risk of withdrawal.
• 15:36
  That's why we suggest that patients on benzodiazepines, maybe short-term, keep it between two to four weeks.
• 15:42
  But in terms of the duration of treatment, as you go from three months to six months to a year to two years, there's a pretty linear increase in risk, although we do need more
• 15:54
  research.
• 15:54
  in this area to better characterize, stratify the risk and tends to plateau after about a few years of treatment.
• 16:03
  Is there a specific duration?
• 16:06
  And I realized this kind of trying to draw a line in the sense.
• 16:09
  do we have a sense of what is kind of a critical duration after which the risk significantly increases, duration of exposure?
• 16:19
  Now, there's been kind of sub-analyses of these controlled studies because the best data is coming from controlled trials.
• 16:28
  And there have been analyses of just the longer trials, the ones that were six months or longer, which showed that the incidence of withdrawal was upwards of 50 % or higher
• 16:40
  compared to studies that were much shorter.
• 16:43
  So what I tell patients is, you
• 16:48
  you know, six months is really my best estimate of that threshold.
• 16:53
  Got it.
• 16:53
  Yeah, that's helpful.
• 16:55
  All right.
• 16:56
  So let's get into the science of it, which I found fascinating.
• 16:59
  You are discussing actually PET studies and the data that can be used as a way to understand how to go about treating withdrawal symptoms.
• 17:11
  So can you talk about that?
• 17:13
  Yeah.
• 17:13
  So basically, you know, we've, we've always inferred the effect of a drug, you know, based on its, on its, its, you know, patient's self reports, um, the objective signs, but based
• 17:26
  on the dose, we, we can image the brain, uh, to study the occupancy by serotonin reuptake inhibitors on the serotonin transporter, in various regions of the brain.
• 17:40
  Usually we use the striatum, but
• 17:43
  Very fascinating that even after these drugs were marketed and established, you know, the minimum therapeutic dose, this amazing pattern emerged, which is that across the board for
• 17:55
  these SSRIs, for instance, the minimum therapeutic dose, Lexapro 10, Prozac 20, Zoloft 50, very consistently show about 80 % occupancy or activity on the uh serotonin transporter,
• 18:12
  which
• 18:13
  has a number of corollaries to it.
• 18:15
  The first of which is that there are diminishing, this concept of diminishing returns that going through the therapeutic dosage range, very small incremental increases in occupancy,
• 18:26
  maybe up to 90%.
• 18:28
  But the corollary is also that there is steep declines in activity as you start to decrease below the minimum therapeutic dose, but that even subtherapeutic doses have
• 18:41
  considerable activity on these transporters.
• 18:44
  Wow, so that's somewhat counterintuitive, isn't it, looking at what we do in our clinical practices?
• 18:52
  So there are so many points in there, so I don't know if we can cover them all, but a couple of things that I think is really important to clarify.
• 18:59
  One is that it seems like maybe we should give it some thought because when we are at the minimally effective dose, we are already at 80 % occupancy.
• 19:09
  which is good enough.
• 19:10
  And maybe we shouldn't be too ambitious because being very pushable to the dose will not result in greater occupancy.
• 19:17
  I mean, you go from 80 % to what, 90%, but you're already at 80%.
• 19:21
  So there is not a lot of therapeutical gain, but probably we have a lot of gain in terms of tolerability and then the risk for withdrawal, right?
• 19:30
  You know, have this theoretical scenario so that our listeners can better understand this story here.
• 19:37
  We have a drug that at 100 milligrams drug X, let's call it, uh results in an 80 % occupancy.
• 19:47
  Then what happens if we go to 150 and what happens if we go to 250?
• 19:53
  Walk us through those scenarios.
• 19:55
  So let's say we have this drug X, as you mentioned, that has 80 % occupancy at 100 milligrams.
• 20:01
  So if you would increase to 150, and this drug kind of resembles Zoloft a little bit, you would probably see 82 or 83 % occupancy.
• 20:10
  Whereas if you drop, maybe let's drop to 75 milligrams or 50 milligrams, we're gonna see maybe 70 % occupancy, and then it's gonna become more precipitous.
• 20:20
  If you do it linearly, you're gonna see exponential increases.
• 20:24
  or decreases in occupancy so that you go from 50 to 25, you might go to 50 % occupancy.
• 20:30
  So we can even be more concrete.
• 20:32
  We can use Zoloft, for example, where, and this is the main issue is that let's say you're a psychiatrist working with a patient on 200 milligrams of Zoloft looking to taper.
• 20:43
  You feel like you've gradually tapered going from 200 every month, know, 200 to 150 to 100 to 50.
• 20:51
  And then you're like, okay.
• 20:52
  We've gone all the way over four months from the highest dose to the minimum dose.
• 20:57
  Let's stop here.
• 20:58
  When actually the imaging data suggests that you basically reduced occupancy from 85 % to 80 % and then you're stopping.
• 21:08
  So you can see this kind of difference in.
• 21:12
  In kind of intuitively, we feel like we've made a big change in dose, but we haven't made much progress at all in terms of mitigating withdrawal risk.
• 21:20
  And I think this idea, is really nicely captured by the concept of hyperbolic dose occupancy, which really highlights the fact that even very small subtherapeutic doses
• 21:32
  demonstrate considerable serotocupancy.
• 21:36
  And that means that to significantly reduce the withdrawal risk, what we need to do is to really look at incorporating very small subtherapeutic doses into the taper.
• 21:49
  Exactly, exactly.
• 21:50
  The issue here is that the formulary for these drugs, they're built for efficacy.
• 21:58
  are not, uh the formularies are not conducive to a gradual taper, meaning very often they have, they were inadequate in terms of helping patients get off ah in this manner.
• 22:12
  that is concerning, right?
• 22:13
  Because some antidepressants, because of the doses that are available, simply don't allow for gradual tapering.
• 22:19
  then what can we do?
• 22:22
  That's right.
• 22:22
  Now, some of these antidepressants, the SSRIs, for instance, many of them come in commercially available liquid formulations.
• 22:30
  And the liquid formulations are very helpful because they're titratable and can help achieve those intermediate or subtherapeutic dosages to support a gradual taper.
• 22:39
  But the newer antidepressants, or even SNRIs, for instance, these drugs often come in their capsules or they don't come in liquids, uh and options are very limited.
• 22:50
  ah which leads us ah to ah consider compounding for these patients.
• 22:56
  But compounding is something that's very often cost prohibitive.
• 22:59
  There's access issues.
• 23:01
  And so uh it really requires, in my opinion, higher level intervention in terms of regulation in order to address this issue.
• 23:09
  And that's an important point, right?
• 23:11
  It seems like with what we have right now, there is uh little formal guidance either from the uh FDA or uh the APA or other regulatory or professional bodies on how to safely taper
• 23:24
  antidepressants to mitigate withdrawal.
• 23:26
  So what's, you know, if you look at the guidelines, I know that the most recent guidelines, the APA guidelines of the 2010 guidelines, what is it that we can get from the
• 23:36
  guidelines as it is now?
• 23:37
  So Adrian, the APA guidelines from 2010, they do mention antidepressant withdrawal.
• 23:43
  The guidance is very vague.
• 23:46
  It says to mitigate withdrawal, it's best to taper over a few weeks, at least a few weeks.
• 23:52
  And so that does not speak to the rate of reductions.
• 23:57
  It does not speak to the doses to reduce to in order to taper off successfully.
• 24:04
  It does not speak concretely to the length that's needed.
• 24:08
  And we see this also in the FDA package inserts.
• 24:10
  They do acknowledge antidepressant withdrawal symptoms mostly, but the guidance is extremely vague and doesn't really help our patients or help us um strategize a plan.
• 24:25
  So this is a significant issue and then it's fair to say that this is an ongoing area of significant unmet need.
• 24:34
  How do patients are currently coping with this lack of formal guidance?
• 24:39
  patients feel can feel very frustrated.
• 24:41
  uh Because this means that oftentimes their provider, their clinician is not aware, they're experiencing experiencing distressing symptoms.
• 24:50
  And maybe the psychiatrist uh is saying that this is a relapse, or ah that there may be some underlying neurologic condition and make some referral to a another specialist.
• 25:04
  So what's happened is that patients are very often
• 25:08
  resorting to online peer support communities, which are growing at an extremely fast rate.
• 25:14
  um Kind of grassroots kind of effort to help each other uh where the medical establishment has not been helpful.
• 25:23
  So there are a number of different websites, Surviving Antidepressants is one that comes to mind.
• 25:30
  uh There are various social media groups with tens or hundreds, even hundreds of thousands of members.
• 25:37
  ah that are designed to address this issue.
• 25:41
  And I think that's inspiring.
• 25:43
  It's really inspiring to see how patients are empowering each other.
• 25:47
  But this also highlights that we could do better, right?
• 25:51
  We could step up our research and then really come up with first, you know, a better understanding of what's happening.
• 25:57
  And secondly, it seems like we can benefit from research that's going to result in clear recommendations about how withdrawals can be prevented and then treated.
• 26:09
  So
• 26:09
  The question to you, Brian, is with what's going on right now, when you look at what's happening in psychopharm research and regulatory requirements, what do you think that
• 26:20
  could help future directions?
• 26:22
  future reactions, of course, there needs to be a research element to this.
• 26:26
  evaluating these hyperbolic tapers is what we call them, um is definitely actionable.
• 26:34
  But I think practically speaking, I don't think it's unreasonable for a regulatory arm to mandate the manufacturing or the availability of a couple of subtherapeutic dosages of
• 26:48
  these antidepressants, very low dosages.
• 26:51
  that can be used kind of in like uh a coin change method of taking uh multiple of a couple different low doses to achieve these intermediate doses.
• 27:01
  Let's say some Balta 1 and some Balta 5 milligrams.
• 27:04
  That would do wonders to mitigate this issue.
• 27:09
  Yes.
• 27:10
  Let's switch gears here.
• 27:11
  So from theory into practice in your report, Brian, you very nicely present all these significant issues by discussing a composite case.
• 27:21
  Mrs.
• 27:22
  L, a 36-year-old woman treated with sertraline, 200, high dose for a long time, 12 years.
• 27:29
  She has a diagnosis of depression.
• 27:32
  And her psychiatrist initially tries a gradual four-month taper.
• 27:36
  gets a dose down from 200 to 50 and then stops it.
• 27:40
  So then, then what?
• 27:43
  So this is why detection is so important because these symptoms, psychiatrists, know, here's the symptoms, brain zaps, peristhesia, tingling in your hands and feet.
• 27:55
  We've tapered you down to a minimum dose.
• 27:57
  mean, this can't really be the antidepressant.
• 28:00
  Let's refer you to a neurologist.
• 28:03
  So the first step is awareness that these are temporally related to the antidepressant reductions, a brain imaging kind of informed
• 28:12
  you know, psychiatrists will recognize that even at these low doses, the Soloft 50 milligrams, these are very typical and common symptoms.
• 28:22
  ah And the thing about antidepressant withdrawal is that these symptoms reliably and rapidly abate with the reinstatement of the dose.
• 28:32
  So if Mrs.
• 28:33
  L would go to her higher dose that was not associated with withdrawal, she would feel better very quickly, which can confirm the diagnosis.
• 28:41
  So what do you do with Mrs.
• 28:43
  L after you reinstate is you're going to need to go more gradually.
• 28:48
  And for very sensitive patients, it's not unusual to reduce by 10 % or 25 % of their dose carried forward.
• 28:57
  So reducing at each interval by 10 to 25%.
• 29:00
  And what we're going to use for her Zoloft is we're going to use the liquid formulation, is commercially available.
• 29:07
  And we're going to show her how to measure the liquid.
• 29:11
  to achieve these intermediate dosages.
• 29:13
  And she's been on her Zoloft for 12 years.
• 29:17
  It would not be unusual for her to um well over a year to come off completely.
• 29:25
  Right.
• 29:25
  And to make this even more complicated, right, when it goes to from 50, then the decision is like, okay, no, it's those low enough.
• 29:33
  And to go to the point that you made before, 50 to zero, which is going to be like, it's not a big deal.
• 29:39
  went all the way down from 200 to 50, 50 to zero might be opening the gates of withdrawal, so to speak, right?
• 29:47
  And the complication there is that there are going to be withdrawal symptoms, but also changes in mood.
• 29:53
  So how do you distinguish between a relapse of depression versus true withdrawal?
• 29:59
  So the clue is twofold.
• 30:00
  The clue, first of all, are physical symptoms.
• 30:03
  mood symptoms can be accompanied by physical symptoms, of course.
• 30:07
  But things like dizziness, brain zaps, if you see that coinciding with a reduction, with that temporal element, the time-related element as well, confirmed by the resolution of
• 30:20
  those mood symptoms and physical symptoms with the reinstatement of the dose, that makes it quite clear that this is not a relapse.
• 30:26
  uh but antidepressant withdrawal.
• 30:30
  But certainly sometimes it can be hard to tell because sometimes withdrawal can be characterized by isolated changes in mood.
• 30:37
  So in that case, the clue would be the abatement of those symptoms when reinstating the higher dose.
• 30:44
  That's a very important sort of differentiation point right there.
• 30:49
  So Brian, as we wrap up, what's the single most important thing that you would want our listeners to remember from this discussion?
• 31:00
  think the number one thing to keep in mind is that antidepressant withdrawal is very common.
• 31:05
  And to remember that very low subtherapeutic doses are usually needed to safely and successfully taper antidepressant drugs and to prevent uh major issues ah with uh coming
• 31:21
  off and even switching medications.
• 31:27
  Ryan, thank you so much for this enlightening discussion and for your important work in addressing the significant gap in psychiatric care.
• 31:34
  Your research and clinical insights provide much needed guidance for safely managing antidepressant discontinuation.
• 31:41
  And I know our listeners will find this information invaluable.
• 31:46
  Thank you so much for being here today.
• 31:48
  Thank you so much for writing the special report and thank you so much for your work.
• 31:52
  Thank you, Adrian.
• 31:53
  To our listeners, if you found this episode valuable, please subscribe to the Psych News Special Report podcast, rate and review us on your preferred platform and share this
• 32:02
  episode with colleagues who may benefit from this information.
• 32:05
  The knowledge shared today could make a real difference in patients' care and safety.
• 32:10
  You could find the complete Special Report anti-depressant withdrawal in the current issue of Psych News, along with detailed tables.
• 32:17
  showing self-occupancy data and antidepressant characteristics that can serve as practical clinical references.
• 32:24
  This has been the Psychiatric News Special Report podcast.
• 32:27
  I'm Dr.
• 32:28
  Adrian Preda.
• 32:29
  Until next month, thank you for listening.
• 32:31
  And remember, safe deep prescribing is an essential component of high quality psychiatric care.