From the Editor

“Once I start taking them, I’m stuck.” When discussing the possible initiation of an antidepressant trial, a patient recently expressed his fear: that he wouldn’t be able to stop the medication because of discontinuation symptoms. These symptoms are debated. Some claim they are very common – though that’s not widely reported in the literature. 

How frequently do these symptoms occur? What percentage of patients experience severe symptoms? Are some antidepressants more associated with this problem than others? Dr. Jonathan Henssler (of the University of Cologne) and his co-authors attempt to answer these questions with an impressive, new systematic review and meta-analysis, published in Lancet Psychiatry. They drew on 79 studies involving more than 21 000 people. “The incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication.” We consider the paper and its clinical implications.

Will the stigma around ECT fade? Will ECT eventually be replaced by ketamine and MST? What’s the future of neuromodulation? We answer these questions and more in the second selection, the latest Quick Takes podcast interview. Dr. Daniel Blumberger, scientific director of CAMH’s Temerty Centre for Therapeutic Brain Intervention and professor at the University of Toronto, notes that ECT still has a unique place. “As far as medical treatments go, ECT is the safest medical procedure in all of medicine.”

And in the third selection, Dr. John Torous (of the Harvard University) and his co-authors focus on digital mental health in a new Viewpoint published in JAMA Psychiatry. They argue that we tend to both overstate and underappreciate the risks and benefits of digital mental health interventions. “Patients and clinicians should not assume wellness digital health technologies are always dangerous, nor should they assume health technologies are always safe.”


Selection 1: “Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis”

Jonathan Henssler, Yannick Schmidt, Urszula Schmidt, et al.

The Lancet Psychiatry, 5 June 2024

The occurrence of adverse symptoms following the discontinuation of antidepressants is increasingly becoming a topic of research in psychiatry, and is also gaining attention in clinical practice, with patients, and in the general media. The emergence of adverse symptoms was described as early as 1959, but remained largely neglected until the late 1990s. Until very recently, guidelines have been criticised for referring to the duration of typical antidepressant discontinuation symptoms as 1-2 weeks, ignoring evidence of longer courses… 

Today, the existence of symptoms emerging after antidepressant discontinuation or dose-reduction is no longer questioned: recent national and transnational clinical practice guidelines recommend informing patients on the risks of abrupt antidepressant discontinuation and suggest tapering of antidepressive agents. Antidepressant discontinuation symptoms can be highly variable and non-specific, with the most frequently reported symptoms being dizziness, headache, nausea, insomnia, and irritability. It has been reported that symptoms typically occur within a few days and are usually transient, but can last up to several weeks or months.

What remains controversial is the incidence and severity of symptoms. Some reviewers estimated antidepressant discontinuation symptoms occurred in the majority of patients (56% [range 14–86%]), with almost half of cases classed as severe. These previous attempts at assessment, however, have been questioned on methodological grounds, especially for including online surveys or other studies prone to selection and dissatisfaction bias. Medical professionals continue to hold polarised positions on the incidence and severity of antidepressant discontinuation symptoms, and the debate continues in public media.

So begins a paper by et al.

Here’s what they did:

  • They searched databases (including PubMed) for randomized controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms.
  • “To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder.”
  • They excluded studies using antidepressants for physical conditions. 
  • After the studies were selected, they did a summary data extraction. Data was then pooled to random-effects meta-analyses.
  • Main outcome: “the incidence of symptoms after antidepressant discontinuation or placebo discontinuation (ie, the number of patients having any discontinuation symptom in relation to the total number of patients discontinuing).”

Here’s what they found:

  • 6 095 articles screened with 79 studies selected (44 RCTs and 35 observational studies), covering 21 002 patients.
  • Demographics and diagnoses. The majority were female (72%) with a mean age of 45 years. Ethnicity were not consistently reported. Many patients had major depressive disorder (57%) or anxiety disorders (28%).
  • Incidence. “Incidence of at least one antidepressant discontinuation symptom was 0.31… in 62 study groups after discontinuation of antidepressants, and 0.17… in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0.08…” 
  • Incidence of severe discontinuation. “The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0.028 compared with 0.006 after discontinuation of placebo.”
  • Antidepressants. “Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms.”

A few thoughts:

1. This is a good paper, drawing on an impressive number of studies, published in a prestigious journal, with practical implications.

2. The core findings in a sentence: antidepressant discontinuation symptoms were common but severe symptoms were relatively rare.

3. There are obvious clinical implications.

4. Start here: tapering is important for some patients.

5. What to say to patients who are thinking about stopping their antidepressants about discontinuation symptoms? The UK Royal College of Psychiatrists put together a readable summary which you can find here:,taper%20your%20antidepressants%20more%20slowly.

6. Of course, the strength of this paper is its weakness. That is, the paper included many studies, even from the non-English literature (two were in Italian). But the studies included those with short tapering periods and no tapering, and with different antidepressants used. The studies were uneven in quality (about a third had higher risk of bias, for example). Should the numbers be taken with a pinch of salt, then? The authors did several analyses to address this, including excluding lower quality studies, and found consistency in the incidence of symptoms.

The full Lancet Psych paper can be found here:

Selection 2: “The past, present, and future of neuromodulation”

Daniel Blumberger

Quick Takes, 16 June 2024

In this episode of Quick Takes, I speak with Dr. Daniel Blumberger. 

In our interview, we review the evolution of neuromodulation. We also discuss various topics: MST and ketamine (compared to the effectiveness of ECT), advice when talking to patients about ECT, and whether ECT will ultimately be replaced.

Here, I highlight several comments:

On his interest in the field

“I had a patient who had a severe psychotic depression and catatonia. The primary treatment for psychotic depression and for catatonia is ECT. Treating this patient – who was in her mid- to late-70s – was a tremendously rewarding experience. It was incredible to see the awakening and resolution of someone who was immobilized in bed. It was like being Oliver Sacks and discovering L-dopa.”

On ECT and stigma

“ECT has evolved. It’s not the same treatment that it was in the 1950s and 60s. 

“There’re some pretty negative depictions of ECT in the media, most notably One Flew Over the Cuckoo’s Nest, where ECT is depicted as a punitive treatment. And, if you look across media and the depictions, it’s the evil psychiatrist delivering ECT. 

“But it’s a lifesaving treatment that has been the most effective treatment over time.”


“I’m very enthusiastic. I believe that MST is potentially a first-line convulsive therapy. Some patients don’t want to consider ECT but are likely to consider MST because of the likely better side-effect profile. And even if it’s not quite as good as ECT but similar, patients would still benefit from trying that treatment as it may be a way to get them better.”

On the future of ECT

“I don’t think ECT will ever be replaced. ECT is too effective. Even if MST becomes a treatment option, there will still be patients who need to consider ECT. There are some patients that may need to go straight to ECT because their depression is so severe and ECT likely works faster than MST and requires fewer treatments…”

The above answers have been edited for length.

The podcast can be found here, and is just over 26 minutes long:

Selection 3: “Digital Mental Health’s Unstable Dichotomy – Wellness and Health”

John Torous, Joseph Firth, and Simon B. Goldberg

JAMA Psychiatry, 17 April 2024

For at least the last decade, digital mental health technologies (DMHTs) such as smartphone apps, virtual reality, and wearables have been expanding in scope and potential. Today, generative artificial intelligence (AI) has joined the list of guided (coached) and unguided (self-help) digital tools that aim to deliver mental health interventions. A groundswell of interest and investment in these technologies underscores their potential to increase access to care and deliver scalable interventions. And yet the clinical benefits of these DMHTs remain largely unrealized. How can research, investment, and innovation better align to improve mental health outcomes for patients?

So begins a paper by Torous et al

“The first step is to move past the appealing narrative of a dichotomy between wellness and health devices. Today, wellness DMHTs such as mindfulness apps are often viewed as having no risks and being exempt from requiring substantial data to prove efficacy. Medical DMHTs, such as prescription therapeutics, present the opposite scenario, often claiming substantial potential risk and presenting (often weak) efficacy data.”

They argue that “[e]vidence for harm from even these wellness-focused treatment tools is mounting.” They review the literature:

  • “In a 2022 study of nearly 19 000 people with frequent suicidal ideation, those randomized to an online low-intensity format of dialectical behavior therapy had higher rates of nonfatal or fatal self-harm over the 18-month trial compared with control groups.” 
  • “A lack of full awareness of potential harm may have led to the 2023 rollout of the Tessa chatbot for eating disorders by the National Eating Disorders Association without a clear safety plan – resulting in users taking to social media to beg that the chatbot be turned off before the association realized the full extent of harm.”
  • “Privacy concerns have also become rampant, with the Federal Communications Commission calling for a probe into how the Crisis Text Line service shared users’ text messages with a sister for-profit AI company in 2022.” 

The authors write: “Instead of assuming no risk, we must discuss implementing safety plans offered by DMHTs that go beyond asking users to call helplines. We need to start reporting harm so that we can create plans to minimize risk.”

With regard to “those digital mental health interventions that have taken a more medical approach,” they note: “the focus is often on proving their product is evidence based. However, the current quality of that evidence is often limited…” They highlight:

  • “An analysis of clinical studies conducted on digital health products authorized by the FDA as of November 2022 found the majority lacked rigor, with most studies conducted on a postmarket basis, without blinding or a digital control group, and self-funded by manufacturers.” 
  • “In 2022, the Centers for Medicare and Medicaid Services announced they would not provide automatic Medicare coverage, noting FDA-cleared devices often lacked sufficient protection for patients and evidence of clinical benefit.”
  • “Concerns about research quality apply broadly, with text-messaging interventions also criticized for having lower-quality research and inconclusive results regarding benefits in depression or anxiety. Nonetheless, in November 2023, New York City signed a $26 million contract with a text-messaging–based company to increase access to mental health services for children…”

They also write about a common challenge: engagement (or the lack thereof). “In one study, an app that included human support was reported to be effective for both depression and anxiety, but when offered during the height of the COVID-19 pandemic to approximately 50 000 college students without human support and study incentives, only 117 downloaded that same app.”

They close with several suggestions, including that: “Regulators should better enforce the delineation of health and wellness products and discourage the current trend of products skating the line between both.”

A few thoughts: 

1. This is a well-argued paper.

2. They raise several important points.

3. They highlight good studies. The online DBT skills study (showing higher rates of self-harm in the intervention group) is particularly memorable. Digital mental health isn’t a panacea.

4. Digital mental health has been discussed in past Readings. In November, a podcast interview with Dr. Torous was featured. “I think the best way to think of ChatGPT is a new modality to put together and share information – just like Wikipedia was a new modality to put together and share information. No one lost their job to Wikipedia. If anything, people were excited; Wikipedia made it easier for people to look up information. There’s always risks of misinformation on Wikipedia. People know that. But overall, it helped elevate everyone.”

That Reading can be found here:

The full JAMA Psych Viewpoint can be found here:

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