Intended for healthcare professionals

CCBYNC Open access

Rapid response to:


Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system

BMJ 2017; 356 doi: (Published 21 February 2017) Cite this as: BMJ 2017;356:j603

Rapid Response:

Re: Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system

Dear Sir/Madam,

Wong et al. (BMJ 2017; 365:j603) found that more than one-third of antidepressants are prescribed off-label. However, we argue that a more detailed analysis tells a different story.

Firstly, when patients present to their primary care doctors with insomnia, clinicians may feel that the patient is also depressed and prescribe trazodone, mirtazapine or amitriptyline to address both the primary presenting complaint and also the secondary diagnosis. However, the diagnosis on the patient’s electronic health record often remains insomnia because, a) one click is easier than two, b) it is implicit that insomnia is a criterion for depression, and c) co-occurrence of insomnia and depression is common. Similarly, chronic pain, (e.g., back pain) and depression, are frequently comorbid but if the presenting complaint is back pain, even in the presence of comorbid depression, the back pain diagnosis is more likely to be registered as the diagnosis of record. Therefore, in the absence of self-reported screening for depression, databases such as the one studied, will underestimate the comorbidity of pain and/or insomnia with depression and overestimate “off-label use.”

Secondly, while “inefficacious antidepressant prescribing is a concern,” the lack of efficacy comes less from off-label prescribing than from a failure to treat to remission. Patients frequently remain on antidepressant doses that are too low to be clinically efficacious or they remain on medications unnecessarily for several more years than required. Databases such as the one utilized in this study do not have the ability to discern inefficacious prescribing in the absence of depression severity measures, hence the danger of conflating inefficacious prescribing with off-label prescribing. In fact, it could be argued that, because of the increasing incidence of depression, primary care providers should be prescribing antidepressants more readily and more broadly. Off-label might be good when viewed from this perspective.

Thirdly, a majority of clinicians would consider intra-class prescribing – the example given by Wong et al. was using escitalopram and citalopram interchangeably – as acceptable clinical practice. Wong et al. cite cervivastatin, which was withdrawn from the market due to a higher rate of rhabdomyolysis, as a reason to avoid same-class prescribing, but their reasoning does not follow routine clinical practice. This is a peculiar side effect of this medication but it was approved because it has the same lipid-lowering potential as other statins. We teach our medical students, residents and fellows that all antidepressants have similar efficacy for treating depression, and are interchangeable, side effect profile aside. This is a broadly accepted principle in psychiatry.

We believe that another way of designing this study might have been to categorize the FDA/Health Canada approved drugs together with the intra-class prescribing and the drugs for which there were DRUGDEX data to support reasonable prescribing.

Tomer T. Levin MBBS
Joseph DeFerio, MPH
Judith Cukor, PhD
Samprit Banerjee, PhD
Rozan Abdulrahman, MPH
Jyotishman Pathak, PhD

Competing interests: No competing interests

06 April 2017
Tomer Levin
Collaborative Care Psychiatrist
Joseph DeFerio, Judith Cukor, Samprit Banerjee, Rozan Abdulrahman, Jyotishman Pathak
Weill Cornell Medicine
240 East 69th St, New York, NY 10065, USA