From the Editor

He feels better and he wants to go off medications, what should you recommend?

Patients raise this question often in depression management. For some, antidepressants are rich in side effects; others simply dislike the idea of long-term medications. For years, the response was simple: outline the risks of going off medications. Depression guidelines, after all, mention the need for continued antidepressants, especially for those who have had multiple past episodes. But, more recently, several papers have suggested that certain psychotherapies reduce the risk of relapse and can rival antidepressants.

But, until now, there hasn’t been a good meta-analysis. This week, in our first selection, we consider a new JAMA Psychiatry paper. Josefien J. F. Breedvelt (of the University of Amsterdam) and co-authors do an individual data meta-analysis comparing antidepressants and psychotherapies for relapse prevention – Zen versus Zoloft, if you will. They write: “The sequential delivery of a psychological intervention during and/or after tapering may be an effective relapse prevention strategy instead of long-term use of antidepressants.” We consider the big paper and its clinical implications.

Pills spill out of a prescription pill bottle on a graduated gray background. The negative space created by the gray background provides ample room for text and copy.

And in the second selection, Dr. Rebecca Grossman-Kahn (of the University of Minnesota) writes about a patient encounter in Minneapolis after the murder of George Floyd. Noting his manic episode, she wonders about larger questions, including diagnosis and coercion. This resident of psychiatry writes: “Training has taught me to recognize the signs of mania and psychosis. But nothing prepared me to ask courageous protesters to put their crucial work for change on hold due to mental illness.”



Selection 1: Continuation of Antidepressants vs Sequential Psychological Interventions to Prevent Relapse in Depression: An Individual Participant Data Meta-analysis”

Josefien J. F. Breedvelt, Fiona C. Warren, Zindel Segal, et al.

JAMA Psychiatry, 19 May 2021


“Antidepressant medication is the foremost strategy to prevent relapse or recurrence of depression. Clinical guidelines recommend antidepressants as a maintenance strategy after remission (ie, at least 2 years) for patients at high risk of relapse. However, antidepressants have been associated with adverse effects, safety concerns, and an increased risk of relapse when tapering. For patients who wish to taper, a dilemma regarding tapering or continuing the use of antidepressants, given the associated risks (including withdrawal syndrome), remains. Psychological interventions (eg, preventive cognitive therapy [PCT], mindfulness-based cognitive therapy [MBCT], and well-being therapy) can be delivered sequentially after antidepressant medication for preventing relapse of depression. Compared with antidepressants alone, these interventions can be especially protective when offered in combination with antidepressant medication, equally efficacious compared with antidepressant tapering, and more effective at preventing relapse when added to tapering. Moreover, the sequential integration of psychological interventions delivered after response to short-term antidepressant therapy was recently confirmed to be effective at reducing the risk of relapse in depression.”

So begins a paper by Breedvelt et al.

Here’s what they did:

  • The authors performed an individual data meta-analysis of several trials.
  • To start, they did a search of various databases, including Pubmed.
  • They selected RCTs that compared the use of a psychological intervention while tapering antidepressant medication with antidepressant monotherapy for relapse prevention (as determined by a structured interview).
  • Patients had to be in full or partial remission from depression.
  • The analysis “included 10 predefined sociodemographic and clinical characteristics: age, age at onset of depression, relationship status, number of therapy sessions attended, sex, presence of a comorbid psychiatric disorder, number of previous depressive episodes, educational attainment, months in remission, and baseline residual depressive symptoms measured with the Hamilton Depression Rating Scale (HDRS).”

Here’s what they found:

  • 236 full-text articles were reviewed with 4 RCTs included.
  • There were 714 participants.
  • Demographics: most patients were female (73.1%); the median age was 49.2.
  • The studies were conducted in the UK, Canada, and the Netherlands.
  • The intervention: “PCT and MBCT consisted of brief 8-weekly interventions.”
  • “Two-stage random-effects meta-analysis found no significant difference in time to depressive relapse between use of a psychological intervention during tapering of antidepressant medication vs antidepressant therapy alone (hazard ratio [HR], 0.86…).” See figure below.
  • Higher overall risk of relapse was found for: participants with a younger age at onset (HR, 0.98), a shorter duration of remission (HR, 0.99), and higher levels of residual depressive symptoms at baseline (HR, 1.07).


A few thoughts:

  1. This is a good study.
  1. The above summary doesn’t completely capture the detailed analysis found in this paper. Note that it isn’t a systematic review and meta-analysis, but rather an individual participant data meta-analysis, which drew on the individual data from each study.
  1. A five-word summary: Antidepressants weren’t superior to psychotherapies.
  1. And that held true even taking into account individual sociodemographic and clinical characteristics.
  1. Note that the paper only considered two psychotherapies: preventive cognitive therapy and mindfulness-based cognitive therapy.
  1. This study has great clinical relevance. In a podcast for JAMA, Dr. John Torous (of Harvard University) jokes that the title of the paper is really: “Can I stop my antidepressant?” That interview, by the way, is excellent and can be found here:

  1. There are limitations. The authors note some challenges with bringing together different RCTs; for example, “the coding of variables was different among studies (eg, employment).”
  1. The time window is 15 months. Would the result be different if participants had been followed longer?
  1. What are the clinical implications? Well, let’s remember that the best approach for patients with depression is that they remain on antidepressants coupled with some form of psychotherapy. But if patients are interested in stopping antidepressants, this meta-analysis suggests that two psychotherapies may bestow the same benefits against relapse. The authors are very bullish, commenting in an interview that psychopharmacology is not the only evidence-based choice for relapse prevention. This is an important paper published in a big journal, though clinicians may wish to temper their enthusiasm pending further work in the area.

The full JAMA Psychiatry paper can be found here:


Selection 2: “Beyond the Rubble of Lake Street – Minds in Crisis in a City in Crisis”

Rebecca Grossman-Kahn

The New England Journal of Medicine, 8 April 2021


It is May 2020 in Minneapolis. Covid-19 reached us a few months ago, bringing daily routines to a halt. The few cars on the roads speed by, but the city is hushed. We are still wearing sweaters indoors, biding our time until summer heat arrives and until life returns to normal.

Then George Floyd is murdered on the street, and the city ruptures. Bursting out of their Covid cocoons, people unfurl their rage and flow into the streets. Summer heat arrives overnight. The threat of Covid fades in comparison to the weight of injustice.

The protests center on Lake Street, a commercial thoroughfare of South Minneapolis. Nearby, beyond the rubble of the burned storefronts, is the hospital where I’m training to be a psychiatrist…

One morning, I meet a man whose wife brought him in the previous night. His hair is thick with grease and grime from Lake Street, where he’s been protesting for a week since George Floyd’s murder. He sits erect, his eyes scanning the room. ‘I need to leave,’ he pleads. ‘I have important work waiting for me out there.’

So begins a paper by Dr. Grossman-Kahn.

She describes the patient: “‘I am needed out there in the fight for racial justice. I’ve been chosen as the leader.’ The man stands up and paces the exam room with electric energy. ‘I’ve never been a political person,’ he continues, his words pulsing in time with his steps. ‘I don’t know much about activism, but when this started I drove downtown and watched the throng of people. I went home that night and the words on all those marching cardboard signs… they kept flashing in my mind. I tucked my son into bed and thought, What will be different for him?’”

She notes the cause is close to her heart:

“Why is he at the hospital for raising his voice against injustice? My impulse is to thank him for his leadership and send him back to the protest. He denies being sick with the same fervency with which he calls on Minneapolis to face racism. ‘I feel amazing,’ he says. ‘I’m finally fighting for my children’s future.’”

She also considers the moment:

“The diagnosis is clear, she notes how unclear our times are: “Explosive energy despite lack of sleep, euphoric mood, periods of depression, rapid speech, risk taking – all are textbook criteria. But another standard diagnostic consideration gives me pause: behavior should be a significant change from one’s baseline. True, these people had never acted like this before, but the country had also changed overnight. We saw yet another Black man murdered by police, and a movement crystallized. The script for diagnosing mania asks me to compare these people’s current behavior with their behavior before Floyd’s murder. But change is imperative. As we reckon with racist, violent policing, how can we judge what an expected response might be? The moment deserves expansive emotions; it demands urgent action, including raising our voices and taking risks.”

A few thoughts:

  1. This is a good and moving paper.
  1. She also touches on the crudeness of our diagnoses.
  1. And she touches on the uncomfortable truth about psychiatry and dissent. “Psychiatry has a history of exerting control over people, policing behavior. Psychiatric diagnoses have been wielded as tools to silence political dissidents and social activists around the world. The ghosts of my profession’s past haunt me.”
  1. A quick word of congratulations to our colleague for publishing in such a prestigious journal during her training.

The full NEJM paper can be found here: 


Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.