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Potential Pitfalls of Using Antidepressants for Anxiety Disorders

May 19, 2019

SAN FRANCISCO—Clinicians should consider their long-term strategy before initiating antidepressants in patients with anxiety disorders, researchers urged at the American Psychiatric Association’s annual meeting, warning of high relapse rates and hazards of later discontinuation.

Although the idea seems simple, it often isn’t, said psychiatrist Neeltje Batelaan, MD, PhD, 1 of 4 clinicians from the Netherlands who spoke to hundreds of attendees on the issue. Treatment guidance is based on the best available evidence, she said, but the best studies focus only on acute episodes.

Existing research leaves many questions on treating anxiety disorders with antidepressants unanswered, the presenters said.

Dr. Batelaan outlined a systematic review and meta-analysis the group did, which was published in the BMJ in 2017. It summarized results from 28 studies, with follow-up periods of 8 to 52 weeks, and a total of more than 5000 patients.

It found that more than one-third of patients (36.4%) relapsed within the follow-up period. Other research has shown most such relapses take place within the first few months after discontinuation.

In addition, the meta-analysis found 16.4% of patients relapsed while still taking an antidepressant, and there was no evidence that staying on antidepressant for more than 1 year was beneficial.

Willemijn Scholten, MD
Willemijn Scholten, MD

Psychotherapist Willemijn Scholten, MD, said the team has seen patients with anxiety disorders who relapsed after discontinuation, and patients who wanted to discontinue treatment but feared relapse. The clinicians have often felt they had no answers to give the patients, she said.

Dr. Scholten, an expert in cognitive behavioral therapy (CBT), presented another study conducted by the group: a multisite randomized controlled trial on whether CBT could help prevent relapse of anxiety when discontinuing antidepressants.

The study concluded it did not. There were high relapse rates in both the CBT and non-CBT groups, and only 28% of patients overall succeeded in discontinuing their medication and not relapsing.

“I think we should our inform our patients at the beginning of the treatment about all of these issues. We should tell them that there are high relapse rates,” Dr. Scholten said. “We should inform patients that it’s not always easy for people to discontinue their antidepressants… We should also inform people that treatment is not always guaranteed for a long-lasting effect, even for CBT.”

Anton A. Van Balkom, MD, PhD
Anton A. Van Balkom, MD, PhD

Presenter Anton A. Van Balkom, MD, PhD, an expert on anxiety disorders, presented another manuscript the group has had published: a systematic review on tachyphylaxis, which is when an antidepressant becomes ineffective  after a patient goes off it then restarts it. The study found it to have a 17% prevalence rate.

The biology behind tachyphylaxis is unknown, Dr. Van Balkom said. One theory is that the serotonin system becomes inflexible when antidepressants are stopped and started.

There is some evidence that tachyphylaxis is seen more with selective serotonin reuptake inhibitors (SSRIs), and that more instances of stopping and restarting antidepressants raises the risk of it, he said. It may also be a reflection of the severity of the underlying disorder.

To help prevent tachyphylaxis, Dr. Van Balkom suggested clinicians try using therapy first and do not use antidepressants as a first-line treatment. He also advised that patients should be told when starting antidepressants that they may need to use them long-term.

These issues apply to many clinical situations, the speakers said. Although treatment guidelines recommend using antidepressants for 6 to 24 months, two-thirds of patients in the United States and over 50% in the Netherlands who take them do so for more than 2 years, said PhD student Renske Bosman, MSc.

“Long-term use is increasing worldwide. The question is ‘why?’ ” Dr. Batelaan said. “Why are so many patients using antidepressants long-term?”

—Terri Airov


“Beyond the initial successful treatment of anxiety disorders with antidepressants: evidence and pitfalls for clinical practice.” Presented at: the American Psychiatric Association Annual Meeting; San Francisco, CA; May 18, 2019.

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