TCPR: Before we talk about your experience with tapering medications, tell us about the population you work with.
Dr. Gupta: In the past, I worked at the Connecticut Mental Health Center for Yale University. There I saw patients with pretty serious mental illness: mainly psychotic disorders, severe trauma, addictions, and serious psychosocial stressors like homelessness. In 2020 I moved to Mount Sinai St. Luke’s, and now I see a more varied outpatient mix: milder cases of panic disorder or depression along with bipolar disorder and schizophrenia.

TCPR: Let’s start with antidepressants. How long should we continue them in unipolar depression?
Dr. Gupta: At a minimum, we should continue them for 6 months after ­remission. We know from dozens of studies that tapering before then raises the risk of relapse 11-fold (Baldessarini RJ et al, J Clin Psychopharmacol 2015;35(1):75–76). But that’s about relapse, which is going back into the current episode, not recurrence, which means that a new episode has come on. We know a lot less about whether antidepressants prevent recurrences of future episodes.

TCPR: What do we know?
Dr. Gupta: Rif El-Mallakh looked at this in 2012 and found only 18 randomized, blinded trials comparing antidepressants with placebo over the long term (≥ 1.5 years). On the one hand, nearly all the trials found that continued antidepressant use prevented depressive symptoms. On the other hand, their prophylactic benefits were limited to the first 6 months, suggesting that they kept people out of the original episode but didn’t necessarily prevent future episodes (El-Mallakh RS and Briscoe B, CNS Drugs 2012;26(2):97–109).

TCPR: When would you consider coming off an antidepressant?
Dr. Gupta: If someone has recovered from a first episode of mild to moderate depression for 6–9 months, I’d consider coming off the antidepressant.

TCPR: What would steer you away from discontinuation?
Dr. Gupta: If the episode was severe, I’d be more hesitant to taper off the antidepressant. There’s also some evidence that patients with multiple past episodes are at greater risk for relapse after discontinuation. The recommendation for indefinite continuation of antidepressants in patients who have had more than 3 episodes of depression is based on this finding. However, the syndrome of antidepressant withdrawal was not taken into consideration in these discontinuation studies. Antidepressant withdrawal can encompass emotional lability, insomnia, anxiety, and a host of other symptoms that could easily be mistaken for a recurrence of depression (Récalt AM and Cohen D, Psychother Psychosom 2019;88(2):105–113). Another consideration is how clear the patient’s response to the antidepressant was. Patients who have a true treatment response are more likely to relapse if the antidepressant is withdrawn (Berwian IM et al, Psychol Med 2017;47(3):426–437).

TCPR: What about antipsychotics in psychotic depression?
Dr. Gupta: You could consider tapering off the antipsychotic after the psychotic features have subsided completely, but there is a risk of relapse if you taper the antipsychotic. In one study of psychotic depression, relapses were 2–3 times greater in those who were randomized to taper off olanzapine while staying on the antidepressant. On the other hand, the ones who came off olanzapine had better metabolic profiles and fewer falls (Flint AJ et al, JAMA 2019;322(7):622–631).

TCPR: How do you taper an SSRI or SNRI?
Dr. Gupta: I would suggest the hyperbolic taper that Horowitz and Taylor developed last year (see TCPR, Jun/Jul 2019). It’s an exponential taper that goes faster at first and then slows down toward the end, much like we use for benzodiazepines. A rough way to estimate it is to drop the dose first by 50%, then wait about 3 months and reevaluate; then lower by 50% of what is left over, wait and evaluate again; then by 50% of the remaining, etc, until they are successfully off. Generally I wait 3 months between each step, but I may go faster or slower depending on how the patient responds to the first reduction. A successful taper could take several years. The theory behind all this is that the binding at the serotonin receptor falls off exponentially (or “hyperbolically”) as the dose is lowered (Horowitz MA and Taylor D, Lancet Psychiatry 2019;6(6):538–546). To taper like this, you usually can’t depend on the tablet sizes that are on the market and may need to get creative with liquid forms or compounding pharmacies. Some patients create microdoses of antidepressants or benzos on their own with compounding solutions like Ora-Plus. (Editor’s note: While professional compounding is preferred, we’ve printed directions for Ora-Plus in the table below so you can guide patients if they go that route.)

TCPR: Lithium is one where a slow taper is usually recommended. How slow would you go?
Dr. Gupta: I would probably taper it off over 3–6 months. With lithium we actually have the data that coming off too fast can lead to rebound episodes, particularly if it was tapered off over less than a month. For the anticonvulsants, there isn’t much data.

TCPR: Are there times when you think it’s appropriate to keep a person on a benzo long term?
Dr. Gupta: That’s a hard question in some ways, and it’s an easy question in some ways. I think that there are no situations where I would keep people on a high dose of a benzo for a long time, but if I’m able to drop the dose down to 0.25–0.5 mg/day of clonazepam and can’t get down to zero, I’d be comfortable leaving them on that dose for a long time. About 10%–15% of patients have protracted withdrawal symptoms after stopping a benzo that can last from months to years. Sometimes it’s just not worth the suffering that complete discontinuation would cause.

TCPR: How would you handle this case: A patient presents for their first visit with a history of depression but no clear history of ADHD or panic disorder. They are taking an antidepressant, but they’ve also been on Adderall 80 mg/day and clonazepam 3 mg/day for a decade.
Dr. Gupta: First I would find out how they got on this combination of medications and whether it’s helping them. I would spend one or two sessions trying to understand what they think about these drugs and what they feel about them because there are a lot of powerful feelings attached to the medications that we prescribe. Once I have a good idea of what’s going on for the patient, then I might say, “Well, look, these two medications have opposite effects. One enhances cognitive functioning and can increase energy and worsen sleep (Adderall). The other is a sedative that dulls cognition (clonazepam). I’m concerned that one drug is treating the effects of the other, which may be why you are on high doses of both. What do you think?” And over five or six sessions, hopefully, we’ll be able to reach some sort of consensus.

TCPR: And if the patient says, “No way, I’m not going to stop them”?
Dr. Gupta: I would probably drop the conversation for a few weeks and then bring it up again: “You know, as a responsible physician, I cannot continue to prescribe two drugs with significant abuse potential to you without adjusting the dose, and the Adderall 80 mg is pretty high.” Establishment of that trust is important, and we must clearly ­convey that we are not just being withholding. You don’t want countertransference to influence prescribing or deprescribing, such as withholding a drug because you don’t like a patient. The patient needs to be assured that you have their best interest at heart.

TCPR: OK, so let’s say the patient is convinced. How would you taper them?
Dr. Gupta: First we’d decide together on which drug to taper first. Unless there’s a serious medical issue at stake, I’d be flexible on where we start. Let’s say we start with the clonazepam 3 mg/day. I would prescribe 2.5 mg/day and give them 5 separate 0.5 mg tablets and say, “Hold on to them. If the taper feels like it’s intolerable, take one. You may not need to, but you’ve got 5 per month to use as needed because I don’t want you to suffer.” That way they have some control in the taper. It also helps them gain perspective on their anxiety. Since they only have a limited amount, they have to ask themselves, “Is it really so bad that I need to take this?” Anything that helps patients see the big picture is good for anxiety, because anxiety narrows perspective.

TCPR: How long does it take to taper a benzo?
Dr. Gupta: It can vary from a few weeks to a few years. At the slow end, I may lower the dose by as little as 5%–10% a month. It all depends on the patient. Things that point to the need for a longer taper are long-term use, high doses, and preexisting anxiety disorders.

Table: Tips for Benzodiazepine Tapers

(Click to view full-size PDF.)

TCPR: What makes stimulant withdrawal difficult?
Dr. Gupta: As with other medications, it’s usually the end of the taper, when you’re down to the smallest dose and trying to stop it, that becomes difficult. Outside of that, stimulant withdrawal is not a big problem. Sometimes patients have insomnia, fatigue, and slowing for the first 2 or 3 days, but that gradually goes away. You may also see depression, irritability, agitation, high appetite, vivid dreams, and aches and pains. It can take a long time, though. A successful taper off Adderall 60–80 mg/day usually takes me 2–3 years if you count all the sessions where we discuss the issue but don’t lower the dose.

TCPR: Do you ever use antidotes for withdrawal, like gabapentin for benzos or modafinil for stimulants?
Dr. Gupta: Generally no. It’s getting out of one hole and digging another one, especially with gabapentin. During benzo withdrawal, some doctors use trazodone or melatonin for sleep, or hydroxyzine or propranolol PRN for anxiety. Many antidotes have been tested for benzodiazepine withdrawal, but none have worked. However, one study noted some benefit from a specialized form of CBT that employs a lot of relaxation skills (deep breathing, progressive muscle relaxation) and cognitive work on decatastrophizing—similar to what is used in CBT for panic disorder (Otto MW et al, Am J Psychiatry 1993;150(10):1485–1490; the treatment manual is Stopping Anxiety Medication by Otto & Pollack).

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

To learn more, listen to our 3/22/21 podcast, “How to Stop Antidepressants, Benzos, and Stimulants: An Interview With Swapnil Gupta.” Search for “Carlat” on your podcast store.