Off-label prescribing of antidepressants
BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j849 (Published 21 February 2017) Cite this as: BMJ 2017;356:j849
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Given the figures from the associated study in Canada, (1) about 1/3 of Citalopram prescriptions were for the unlicensed indications of Anxiety and Panic. Citalopram (N=19480) was the most common antidepressant drug cited for off-label anxiety treatment and made up 18% of the total prescriptions studied (N = 106,873). It has been reported (2) that, in the UK, £5.5million per week is spent on antidepressant drugs by the NHS. On the Inaccurate but broadly realistic simplification that all the antidepressant prescriptions were of similar value, then 6% of the antidepressant drug spend would have been for unlicensed prescriptions of Citalopram for Anxiety and Panic. Thus about £17million per annum is being spent in the NHS on unlicensed Citalopram for Anxiety related conditions with associated side effects and interactions.
Ashworth & Dutton described a simple physiological method (3) of treating anxiety that has now been found to be deliverable in a single 10 minute consultation with follow up and repeat instructions available on YouTube (4).
Non-pharmacological management of Anxiety (which has a global prevalence of 7.3% (5) ) are safer with evidence that they may be at least as efficacious as unlicensed drugs despite the huge research budgets of pharmaceutical companies: they have the added potential to release significant funds for other treatments across Health Services
1. doi:10.1136/bmj.j603
2. The Times July 6 2016
3. http://oatext.com/Baby-Gaze-A-neurobiological-method-of-anxiety-relief-i...
4. https://youtu.be/8uqjNBKyPz8
5. Baxter AJ1, Scott KM, Vos T, Whiteford HA.Global prevalence of anxiety disorders: a systematic review and meta-regression.Psychol Med. 2013 May;43(5):897-910. doi: 10.1017/S003329171200147X. Epub 2012 Jul 10.
Competing interests: We discovered the Baby-Gaze method of anxiety management and have made it available on YouTube at no cost to patients
Morales and Guthrie highlight an area of concern for many GPs. There is also a growing demand for requests for off label prescribing from secondary care specialists: we have seen requests for this from several specialties, not just with regard to antidepressant use. Aside from professional guidance on prescribing for practitioners, there should be robust systems in place that ensure prescribing off license medication should be undertaken by the initiating specialist ( who should have counselled the patient or parent in the case of paediatric prescribing) rather than passed on to a third party with the accompanying patient expectation that a prescription be issued. Local prescribing support teams should help to ensure safe practice within expected parameters. Systems also need to be supportive rather than adversarial. Increasing workloads and pressures on primary care and reduced secondary care budgets are potential risks which should be taken into account when considering systems. Electronic prescribing in shared systems might facilitate such a process. Avoiding harm and providing efficacious treatment is everyone's aim.
Competing interests: No competing interests
Administered antidepressants increase suicide risks by 2-5 times. [1][2][3][4][5]
A recent meta-analysis, level I evidence, clearly demonstrated that SSRIs double the risk of suicide and violence in adults. [3]
References
[1] http://journals.sagepub.com/doi/pdf/10.1177/0141076816666805
[2] http://www.bmj.com/content/348/bmj.g3510
[3] http://www.bmj.com/content/352/bmj.i65
[4] http://nordic.cochrane.org/sites/nordic.cochrane.org/files/public/upload...
[5] http://www.bmj.com/content/355/bmj.i6103
Competing interests: No competing interests
Prescription of antidepressants - and the inexorable rise of this - is a major issue of concern.
It has become apparent that many patients experience very significant associated issues with side-effects, adverse effects, dependence and withdrawal problems , whether antidepressants prescribed on- or off-label, and these harms have not been adequately acknowledged or recognised.
The BMA Board of Science has highlighted this issue:
https://www.bma.org.uk/collective-voice/policy-and-research/public-and-p...
I would like to draw particular attention to the work of Fava and Carvalho et al:
http://www.karger.com/Article/FullText/370338
http://www.karger.com/Article/FullText/447034
(I have detailed my own observations in my writing and further references – all accessible at and via http://www.bmj.com/content/356/bmj.j268/rr-1 )
Competing interests: No competing interests
The difficult discussion on the role of antidepressants in patient care
I agree with Morales & Guthrie that the strength of evidence for a particular drug is what matters the most (1). Sometimes even more than whether the drug has already been licensed.
It is also reasonable to discuss whether the evidence base for the licensed indications of antidepressants can justify the extent to which they are currently being recommended and prescribed. Considering the management of depression with selective serotonin reuptake inhibitors (SSRIs), for example, the latest comprehensive meta-analysis found that the effect sizes over placebo were uniformly below of what the investigators could regard as clinically significant (2). On average, the magnitude of effect was 1.9 points on a depression rating scale that measures from 0 to 52.
Different guidelines recommend antidepressants at varying levels of depression severity. The National Institute for Health and Care Excellence (NICE) states that “you should not usually be offered an antidepressant if you have mild depression (3).” I can agree with this conclusion on mild depression. The Finnish equivalent for the NICE guideline is the Current Care Guideline (CCG), which states on depressive disorders that “treatment with an antidepressant is usually of benefit even in mild depression (4).” However, even the 2009 Cochrane review found that 86% of depressed patients in a primary care setting (calculated from the number needed to treat of 7) do not benefit from SSRIs over placebo, yet patients in the trials had more severe than mild forms of depression (5). I find it very difficult to agree with the CCG conclusion that antidepressants could be recommended for patients with mild depression.
It appears that psychiatrists have not been very active in re-evaluating our current position on who should be treated with drugs and why. This is probably why much of the recent criticism has come from outside the field of psychiatry. The role of antidepressants in patient care is currently being debated in Finland. Professor Peter Gøtzsche, the director of the Nordic Cochrane Centre, recently submitted an article to the Finnish Medical Journal (FMJ) to communicate his research findings and opinion about antidepressants (6). The FMJ responded initially that the article could be published in a shorter version if there is a permission to republish the content from the original publisher. The article was later rejected with the reason that the contents of the article had been originally published elsewhere. Gøtzsche noted that the FMJ didn’t have such a problem with the article initially or with his 2012 article on breast cancer screening. This contradiction led him call this incident “editorial misconduct (6).” Even in 2014, Gøtzsche approached the chair of the CCG on depression with an open letter to address concerns on methodological shortcomings of trials, and whether the effect sizes can be considered clinically significant (7). We have not heard of a response to these relevant concerns. Even a late response would be a welcomed contribution to the common goal of both sides of any debate in medical science – deeper evidence-based understanding of the issue for the best of patient care.
The British Medical Journal, among others, has previously participated in this difficult but clinically relevant debate on the benefits and harms of antidepressants (8, 9). Finnish journals should also do that. There certainly is a need to openly discuss the strength of evidence in the case of both licensed and unlicensed uses of antidepressants.
References:
1. Morales DR, Guthrie B. Off-label prescribing of antidepressants. BMJ 2017;356:j849.
2. Jakobsen JC, Katakam KK, Schou A, Hellmuth SG, Stallknecht SE, Leth-Møller K, et al. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry. 2017 Feb 8;17(1):58.
3. National Institute for Health and Care Excellence. Depression in adults: recognition and management. Clinical guideline, 2009.
4. Depression (online): Current Care Guideline, 2016. Suomalaisen Lääkäriseuran Duodecimin ja Suomen Psykiatriyhdistys ry:n asettama työryhmä. Available from http://www.kaypahoito.fi
5. Arroll B, Elley CR, Fishman T, Goodyear-Smith FA, Kenealy T, Blashki G, et al. Antidepressants versus placebo for depression in primary care. Cochrane Database Syst Rev. 2009 Jul 8;(3):CD007954.
6. Mad in America. Editorial Misconduct: Finnish Medical Journal Rejects Paper on Suicide Risk. 22 Feb 2017. https://www.madinamerica.com/2017/02/editorial-misconduct-finnish-medica...
7. Deadly Medicines and Organised Crime. Do antidepressants work for severe depression? Meeting in Helsinki 1 Sept 2014. http://www.deadlymedicines.dk/do-antidepressants-work-for-severe-depress...
8. Gøtzsche PC, Young AH, Crace J. Does long term use of psychiatric drugs cause more harm than good? BMJ 2015;350:h2435.
9. Hedlund F. Peter Gøtzsche på krigsstigen mot psykiatrin. Lakartidningen 2016;113:D9FU.
Competing interests: No competing interests