Post Selective Serotonin Reuptake Inhibitor Sexual
Dysfunction (PSSD) is a proposed disorder of sexual dysfunction that continues
after antidepressant medication has been discontinued. The symptoms include (2) prior treatment
with an SSRI, a change in genital sensation after the SSRI has been stopped,
decreased libido, anorgasmia, erectile dysfunction, and a duration of symptoms
for 3 months following the cessation of the SSRI. It is also a diagnosis of exclusion since
pre-SSRI sexual dysfunction and other medications or medical conditions that
could account for the symptoms need to be ruled out. It is a controversial
diagnosis at this point because the true prevalence of the condition is unknown
and the studies of the condition are generally low quality.
The diagnostic criteria for PSSD and PGAD are listed in the
graphic above. It is not clear at this point what the diagnostic standard is
for these disorders and heterogeneity is clearly an issue. For example, do a
certain number or pattern of symptoms need to be present or could a single
symptom be present with SSRI exposure and qualify for the diagnosis.
The controversy about PSSD reached its zenith with a recent
article suggesting that antidepressants caused “chemical castration.” When I first heard about this issue a few
years ago it reminded me of the decades old problem of priapism (persistent
painful erections) associated with trazodone use. At the time (now about 27 years ago) I did a
literature search on the incidence of spontaneous priapism in adult males and
found that it matched the frequency suggested with trazodone use - but there were problems with determination of the true prevalence in both cases.
Prevalence estimates in the literature are approximate
because they depend either on voluntary reporting (since there is no formal
pharmacovigilance system in the United States) or available survey samples that
typically have some obvious bias. In the 27 years since, I have warned every
male patient I prescribed trazodone to and what to do about the problem. None
of those patients developed priapism.
Two noticed they had AM erections that seemed unusual but did not
develop priapism. They ignored the
erections, did not call me, and noticed that everything went back to normal. In my experience, that is how most people
manage side effects – even when you tell them they are potentially severe and
may require medical or surgical intervention.
My experience with sexual side effects of antidepressants
is similar. Since these side effects are common with antidepressants – it is
one of many that I verbally advised patients about. My protocol was to provide
people with the MedlinePlus handouts, advise them how to access the package insert
for all of the detailed information, but then discuss the side effects they are
most likely to encounter including antidepressant withdrawal, rare side effects
that can be very serious like serotonin syndrome and drug induced liver
disease, and a general advisory to call me with any questions about what might
be a drug side effect: "If you feel ill assume it may be the medication and call me." On the latter, I
emphasize the call to me should been as soon as the problem develops and that I
never expect that a person will “get used to” medication side effects.
The literature suggests that direct discussion of sexual
side effects is more likely to result in patient reports if those side effects
occur. In my experience it generally requires an explanation of what to look
for in terms of libido and actual sexual functioning. Assessment is complicated
by the high prevalence of these symptoms in depression and the fact that some
people prefer the antidepressant effect over any lack of effect or deleterious
effects on sexual functioning.
A logical place to start considering PSSD is to look at
prevalence estimates from available studies.
A 19-year retrospective observational analysis of 12,302 men in an HMO
setting (1) estimated the prevalence of PSSD to be 1 in 216
patients (0.46%) treated with SSRIs. The prevalence of PSSD was 4.3 per 100,000. Cases were identified by exposure to SSRI and
treatment of (erectile dysfunction) ED with PDE-5 inhibitors. Other conditions were ruled out on an
administrative basis based on BMI and medications that that potentially cause
ED. The authors point out that the
design had limitations in that the trade-off of medical treatment as a proxy
for ED diagnoses may underestimate the prevalence of ED/PSSD.
In a second systematic review (2) – look at
PSSD and Persistent Genital Arousal Disorder (PGAD). PGAD can occur in the context of no treatment
with an SSRI but it has also been reported after SSRI treatment. The main differentiating point is that is has
sensations of persistent genital arousal or genital dysesthesias. It may also
be associated with uncontrolled orgasms.
Time criteria suggested is greater than 3 months.
These authors reference the European Medicines Agency (EMA)
recognizing the PSSD diagnosis in 2019 (3). Unfortunately, the EMA web site is only slightly more user
friendly that the FDA website. I have
linked to the referenced document and included the relevant text at the top of
this post. I could find no more detailed
information about the rationale for inclusion.
The suggested links just brought me back to the original document.
References or even regulatory documents would be useful in this case to
determine the EMA rationale for this position. It appears to have been based on
a pharmacovigilance signal and that could be generated from registries in
Europe, but at this point I cannot confirm the information.
The available literature on PSSD consists primarily of case
reports, speculation about the biological plausibility of the disorder, and in
the discussions calls for more studies of the true prevalence of the
disorder. 19 studies were included in
the review. Incidence or prevalence of PGAD could not be determined.
Physical causes of some of these symptoms are obviously important. Herpes zoster or shingles infections cause about 100,000 cases of genital dysesthesias per year. There have been reports of Herpes simplex genital viral infections (HSV-1, HSV-2) causing similar symptoms. HSV-1 and HSV-2 cause significant neuropathic symptoms during acute recurrences, but that has been thought to resolve with each recurrence. Local and systemic neurological conditions affecting pelvic nerves and the autonomic nervous system are also potential causes. There are many complicating factors when considering sexual
dysfunction in the population as a whole, in untreated depression and in
treated depression.
1: Baseline rate/causes
of sexual dysfunction:
In the largest post Kinsey study (7,8) , a national probability
sample in the US looked at 7 indicators of sexual dysfunction including
decreased desire for sex, arousal difficulties, inability to achieve climax,
anxiety about sexual performance, climaxing or ejaculating too soon, physical
pain during intercourse, and not finding sexual intercourse pleasurable. Only
sexually active respondents were analyzed. 43% of women and 31% of men reported
a problem. Psychosocial and medical
factors were also investigated and found to be relevant. The authors conclude that sexual dysfunction
is a significant public health problem.
The codebook for the original study was downloaded and medication history
was not included.
2: Baseline rate of
sexual dysfunction due to depression:
Rates of sexual dysfunction in both sexes due to depression are similarly high. A comprehensive review of that literature by Gonçalves, et al (9) showed high rates of dysfunction in women than men. Their data is summarized in the far right column in the table below. These researchers also pointed out an important methodological problem with studies that depend on standard rating scales - some do not ask if the respondent considers the symptom to significantly affect their level of functioning. It is possible to do a rating scale experiment that show impairment when the respondent does not believe they are impaired.
3: Antidepressant
sexual side effects:
Sexual side effects are a well-known side effect of modern
antidepressants. Various strategies have
been suggested over the years to reduce or eliminate these side effects. The only strategy I found effective was to
change to a different antidepressant.
Prevalence rates of these side effects were initially available from
package inserts and comparisons with placebo in drug trials. The last summary information I have looking
at those numbers is from the 2012 Drug Facts and Comparisons. In a comparison of all of the available SSRIs
at the time the following rates were suggested: decreased libido 1-12%,
paresthesia (non-specific) 1-4%, abnormal ejaculation 6-27%, female genital
disorders 2-10%, male genital disorders 4-10%, sexual
dysfunction/impotence/anorgasmia 1-13%.
Comparisons across antidepressant classes is difficult because of
changing categories. For example, SNRIs (venlafaxine, desvenlafaxine,
duloxetine, milnacipran) generally have lower sexual dysfunction figures. By the time duloxetine was marketed the
package insert contained ratings from the Arizona Sexual Experiences Scale
(ASEX) and comparisons with placebo.
Conclusions:
There are several problems with the current conceptualization
of PSSD including:
1: The evidence
basis is largely anecdotal case reports, case series and abundant speculation
based on those case reports. There are
no controlled studies so the prevalence of PSSD in populations untreated with
antidepressants is unknown. Experts in the PSSD field also suggest this is due
to changing diagnostic criteria (Goldstein).
2: Both untreated
depression and treated depression have significant symptom overlap with the
suggested diagnosis of PSSD
3: The incidence of
sexual dysfunction in the general population without depression who have never
been treated with antidepressant medication is high and varies as expected with
comorbidities, age and other medical treatments. (Laumann).
4: There are no
validated instruments or protocols to identify cases of PSSD. Multiple authors
suggest determining the prevalence of the problem more accurately but that
study would have to be carefully designed.
5: Opinions in the
popular press can bias prevalence studies at this point. In the past, survey studies have proven that
they can elicit any predetermined opinions and should be avoided. How to eliminate this factor introduced by
the press and anti-antidepressant advocates is not clear.
6: The determination
of the pharmacovigilance signal by the EMA should be clarified. It is possible that I did not find it. In that case, I would appreciate being
directed to that source. I emailed the European Medicines Agency asking for
clarification on July 10 and am still waiting for a response. The process also has
lessons for the United States. I have
long been an advocate for a more formal pharmacovigilance system in the
US. The next step would be a system like
the Netherlands where any person could call in a suspected adverse event and
there would be a connection to formal regulation as wording in package inserts.
7: For psychiatrists
in the US, I would see the current situation as comparable to the FDA warnings
on suicidal behavior and suicidality on SSRIs and treat it the same way. Even though pharmacovigilance in the US is
basically post marketing surveillance, it makes sense to add PSSD/PGD to the
informed consent discussion with patients as a potential risk of antidepressant
treatment. It can be mentioned in the same discussion as sexual side effects
from these medications. I would also describe these diagnoses as a work in
progress at this point due to the limiting factors.
8: The impact of the
current level of discussion in the press and the effect it may have on patients
taking antidepressants has not been determined at this point. In my practice in
the past, most people make their own determinization of whether these warnings
apply to them and may discuss it in the office, but it is reasonable to ask if
they have any concerns while discussing side effects.
9: Ideological bias – there is clearly a faction of
criticism that conflates pharmaceutical interests with psychiatry and makes it
seem like there is a psychiatric agenda to overprescribe medications and
cover-up side effects. This same faction
has a very limited to non-existent scientific basis and an equally robust
clinical approach to psychiatric problems. More importantly they appear to not
treat serious problems and at times have criticized people who find both
psychiatric diagnosis and treatment helpful. An awareness of this bias is
necessary when evaluating literature focused on the characterization and
prevalence of PSSD.
10: Ratings from
existing trials: The current controversy is reminiscent of the emotional
blunting controversy (10) and the suggestion that antidepressants work by blunting
emotions. Ron Pies and I reviewed studies that used the Montgomery–Åsberg
Depression Rating Scale (MADRS) to show that decreased feeling was correlated
with depression and that emotional blunting improved with treatment. Existing rating scales for antidepressant
trials have only 1 item that rates sexual functioning and that it the Hamilton
Depression Rating Scale (HAMD). There is limited opportunity to do
retrospective studies on existing clinical trials on that basis.
11: The nocebo
effect: The nocebo effect is essentially a negative expectation or expectancy
that affects both the potential efficacy and side effect profile of a
medication. The effect is significant
for all medication including antidepressants.
In antidepressant trials an analysis
of the placebo exposed group showed that 63.9% reported treatment
emergent adverse events, 11.2% experienced worsening depression, and 4.7%
discontinued the trial due to an adverse event – all while taking placebo. In a
recent review Colloca and Barsky discuss the importance of the media, press,
and direct exposure to people with adverse events “all foster nocebo
responses.” They give an example of how negative press coverage led to a 2,000
fold increase in adverse event reporting when a new medication covered by the
national health plan came out.
If you have followed
my various lines of reasoning so far it is probably apparent that I take any
pharmacovigilance signal seriously. You must when you are a clinician who warns
people about side effects that occur in the 1 in 10,000 to 1 in 50,000 range. I consider the best prevalence estimate in
this case to be less than 1 in 1,000, but all the experts clearly acknowledge
problems with the diagnostic criteria and changing criteria. In order to take the PSSD problem seriously
it must be considered a multidisciplinary problem. Psychiatrists, neurologists,
OBGYN specialists, urologists, psychologists, and physical therapists have all
written about the problem and in many cases documented successful treatments.
In some of those papers, multiple individual or combined treatments were highly
successful. From a psychiatric standpoint, SSRIs have been resumed and
treatment like adding bupropion or vortioxetine have seen successful – but the
evidence basis is very limited. If this condition came to my attention in a
patient, I was treating my preferred approach would be to discontinue the SSRI
or SNRI if possible and develop a referral source where I could refer the
patient for the necessary evaluation looking for neuropathic causes and
documenting the level of sexual dysfunction. In my region that would probably
involve referrals of men and women to a well-known Urology clinic that has sub-specialists
in this area. The ultimate plan would also depend on patient preference,
individual history of treated depression, and where the research in this
disorder was at the time. Every individual needs a unique plan and looking at
the heterogeneity of findings in this research – unique plans will be the rule
and not the exception.
Currently, prevalence studies as well as studies that look
at the issue of how these symptoms vary as people transition during episodes of
treatment for depression and/or anxiety are required. That will be a significant undertaking. Observational studies based on active treatment
may be a suitable substitute but safeguards need to be taken to assure adequate
documentation of baseline sexual dysfunction, a clearly defined diagnosis and diagnostic
thresholds, correlation with antidepressant treatment, and hopefully resolution
both with or without treatment.
Lastly, if you are a person with any of the sexual problems
described in this post – antidepressant related or not the best potential solution
is a direct discussion with your personal physician or psychiatrist. If necessary,
send them a link to this post and suggest they read the last two paragraphs. As
always my posts are intended to be educational informed by clinical practice
and not suggest that I know more than anyone else.
George Dawson, MD, DFAPA
References:
1: Ben-Sheetrit J,
Hermon Y, Birkenfeld S, Gutman Y, Csoka AB, Toren P. Estimating the risk of
irreversible post-SSRI sexual dysfunction (PSSD) due to serotonergic
antidepressants. Ann Gen Psychiatry. 2023 Apr 21;22(1):15. doi:
10.1186/s12991-023-00447-0. PMID: 37085865; PMCID: PMC10122283.
2: Tarchi L, Merola
GP, Baccaredda-Boy O, Arganini F, Cassioli E, Rossi E, Maggi M, Baldwin DS,
Ricca V, Castellini G. Selective serotonin reuptake inhibitors, post-treatment
sexual dysfunction and persistent genital arousal disorder: A systematic
review. Pharmacoepidemiol Drug Saf. 2023 Jun 9. doi: 10.1002/pds.5653. Epub
ahead of print. PMID: 37294623.
3: European
Medicines Agency. Pharmacovigilance Risk Assessment Committee recommendations
on safety signals. 11 June 20191 EMA/PRAC/265221/2019 Pharmacovigilance Risk
Assessment Committee (PRAC). https://www.ema.europa.eu/en/documents/other/new-product-information-wording-extracts-prac-recommendations-signals-adopted-13-16-may-2019-prac_en.pdf
4: Healy D, Bahrick
A, Bak M, Barbato A, Calabrò RS, et al. Diagnostic criteria for enduring sexual
dysfunction after treatment with antidepressants, finasteride and isotretinoin.
Int J Risk Saf Med. 2022;33(1):65-76. doi: 10.3233/JRS-210023. PMID: 34719438;
PMCID: PMC8925105.
5: Lewer, D.,
O'Reilly, C., Mojtabai, R., & Evans-Lacko, S. (2015). Antidepressant use in
27 European countries: Associations with sociodemographic, cultural and
economic factors. The British Journal of Psychiatry, 207(3), 221-226.
doi:10.1192/bjp.bp.114.156786
6: Goldstein I,
Komisaruk BR, Pukall CF, et al. International Society for the Study of Women's
Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a
Consensus Nomenclature and Process of Care for the Management of Persistent
Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD). J Sex Med. 2021
Apr;18(4):665-697. doi: 10.1016/j.jsxm.2021.01.172. Epub 2021 Feb 19. PMID:
33612417.
7: Laumann EO, Paik
A, Rosen RC. Sexual dysfunction in the United States: prevalence and
predictors. JAMA. 1999 Feb 10;281(6):537-44. doi: 10.1001/jama.281.6.537.
Erratum in: JAMA 1999 Apr 7;281(13):1174. PMID: 10022110.
8: Laumann, Edward
O., Gagnon, John H., Michael, Robert T., and Michaels, Stuart. National Health
and Social Life Survey, 1992: [United States]. Inter-university Consortium for
Political and Social Research [distributor], 2008-04-17. https://doi.org/10.3886/ICPSR06647.v2
9: Gonçalves WS,
Gherman BR, Abdo CHN, Coutinho ESF, Nardi AE, Appolinario JC. Prevalence of
sexual dysfunction in depressive and persistent depressive disorders: a
systematic review and meta-analysis. Int J Impot Res. 2023 Jun;35(4):340-349.
doi: 10.1038/s41443-022-00539-7. Epub 2022 Feb 21. PMID: 35194149
10: Dawson G, Pies
RW. Antidepressants do not work by
numbing emotions. Psychiatric Times. Sept 26, 2022: https://www.psychiatrictimes.com/view/antidepressants-do-not-work-by-numbing-emotions
11: LiverTox:
Clinical and Research Information on Drug-Induced Liver Injury [Internet].
Bethesda (MD): National Institute of Diabetes and Digestive and Kidney
Diseases; 2012-. Adverse Drug Reaction Probability Scale (Naranjo) in Drug
Induced Liver Injury. [Updated 2019 May 4]. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK548069/
12: Colloca L,
Barsky AJ. Placebo and Nocebo Effects. N Engl J Med. 2020 Feb 6;382(6):554-561.
doi: 10.1056/NEJMra1907805. PMID: 32023375.
13: Haanpää M, Paavonen J. Transient urinary retention and chronic neuropathic pain associated with genital herpes simplex virus infection. Acta Obstet Gynecol Scand. 2004 Oct;83(10):946-9. doi: 10.1111/j.0001-6349.2004.00500.x. PMID: 15453891.
14: Ooi C, Zawar V. Hyperaesthesia following genital herpes: a case report. Dermatol Res Pract. 2011;2011:903595. doi: 10.1155/2011/903595. Epub 2011 Apr 18. PMID: 21747842; PMCID: PMC3130996.
15: Whalen AM, Mateo CM, Growdon AS, Miller AF. Sacral Myeloradiculitis: An Uncommon Complication of Genital Herpes Infection. Pediatrics. 2019 Jul;144(1):e20182631. doi: 10.1542/peds.2018-2631. PMID: 31217310.
16: Reisman Y. Sexual Consequences of Post-SSRI Syndrome. Sex Med Rev. 2017 Oct;5(4):429-433. doi: 10.1016/j.sxmr.2017.05.002. Epub 2017 Jun 20. PMID: 28642048.
Case Reports (not exhaustive – truncated at 10 – I think
these references capture the largest numbers):
1: Ekhart GC, van
Puijenbroek EP. Blijvende seksuele functiestoornissen na staken van een SSRI?
[Does sexual dysfunction persist upon discontinuation of selective serotonin
reuptake inhibitors?]. Tijdschr Psychiatr. 2014;56(5):336-40. Dutch. PMID:
24838589.
From 2002 to 2012, 19 cases reported to
Netherlands Pharmacovigilance Centre, Lareb occurring after patients has
stopped the medications for 2 months to 3 years. Approximately 1 million people
per year are prescribed antidepressants in the Netherlands. See: https://www.statista.com/statistics/718241/usage-of-dispensed-antidepressants-in-the-netherlands/
2: Patacchini A,
Cosci F. A Paradigmatic Case of Postselective Serotonin Reuptake Inhibitors
Sexual Dysfunction or Withdrawal After Discontinuation of Selective Serotonin
Reuptake Inhibitors? J Clin Psychopharmacol. 2020 Jan/Feb;40(1):93-95. doi:
10.1097/JCP.0000000000001154. PMID: 31834096.
3: Bolton JM, Sareen
J, Reiss JP. Genital anaesthesia persisting six years after sertraline
discontinuation. J Sex Marital Ther. 2006 Jul-Sep;32(4):327-30. doi:
10.1080/00926230600666410. PMID: 16709553.
Single case of a 26-year-old man.
4: Waldinger MD, van
Coevorden RS, Schweitzer DH, Georgiadis J. Penile anesthesia in Post SSRI
Sexual Dysfunction (PSSD) responds to low-power laser irradiation: a case study
and hypothesis about the role of transient receptor potential (TRP) ion
channels. Eur J Pharmacol. 2015 Apr 15;753:263-8. doi:
10.1016/j.ejphar.2014.11.031. Epub 2014 Dec 4. PMID: 25483212.
43 yr old man with loss of smell, taste, and
skin sensation shortly after he started to take paroxetine for depression. He has associated problems with sexual
functioning and sensation for 2 years after the paroxetine was
discontinued. Full
Text
5: De Luca R,
Bonanno M, Manuli A, Calabrò RS. Cutting the First Turf to Heal Post-SSRI
Sexual Dysfunction: A Male Retrospective Cohort Study. Medicines (Basel). 2022
Sep 1;9(9):45. doi: 10.3390/medicines9090045. PMID: 36135826; PMCID:
PMC9503765.
13 male patients referred for treatment. PSSD sx onset 2-4 weeks after discontinuation
of SSRI. Retrospective, uncontrolled
treatment study. Most patients were significantly improved at 12 month follow
up after treatment with vortioxetine, bupropion, or mechanical stimulation on a
standard scale.
6: Reisman Y,
Jannini TB, Jannini EA. Post-selective serotonin reuptake inhibitor sexual
dysfunctions (PSSD): clinical experience with a multimodal approach. Journal of
Men's Health. 2022 Aug 1;18(8):165.
12 male patients with a “high probability” of
PSSD 9-26 months post treatment with an SSRI (one patient was treated with
amitriptyline). Retrospective, uncontrolled treatment study with all patients
improving at 12 months.
7: Chinchilla Alfaro
K, van Hunsel F, Ekhart C. Persistent sexual dysfunction after SSRI withdrawal:
a scoping review and presentation of 86 cases from the Netherlands. Expert Opin
Drug Saf. 2022 Apr;21(4):553-561. doi: 10.1080/14740338.2022.2007883. Epub 2021
Nov 27. PMID: 34791958.
86 cases reported to the Netherlands
Pharmacovigilance Center of Lareb from 1992 to 2021. Longest duration was 23 years. Common symptoms were loss of libido, erectile
dysfunction, and anorgasmia.
8: Dannon PN, Iancu
I, Cohen A, Lowengrub K, Grunhaus L, Kotler M. Three year naturalistic outcome
study of panic disorder patients treated with paroxetine. BMC Psychiatry. 2004
Jun 11;4:16. doi: 10.1186/1471-244X-4-16. PMID: 15191617; PMCID: PMC441384.
143 patients with panic disorders treated with
paroxetine were followed for one an acute treatment phase followed by either 12
month or 24-month paroxetine maintenance.
Relapse rates in both groups were similar. Sexual side effects were
determined clinically rather than a structured interview asking about sexual
desire and sexual function. Prevalence of sexual side effects was 30% in both
groups and the presence of agoraphobia potentiated these side effects –
consistent with some psychological theories.
Not clear about the status of sexual side effects during the
discontinuation phase.
9: Healy D, Le Noury
J, Mangin D. Enduring sexual dysfunction after treatment with antidepressants,
5α-reductase inhibitors and isotretinoin: 300 cases. Int J Risk Saf Med.
2018;29(3-4):125-134. doi: 10.3233/JRS-180744. PMID: 29733030; PMCID:
PMC6004900.
300 cases (221 on antidepressants) solicited
through a web site established by the authors. They acknowledge the design of
the likely encouraged reporting. The authors calculate a causality score
based on the Naranjo algorithm that is described as the “probability of an
adverse drug reaction.” This paper has a
unique take on the effects of antidepressants that are not seen in any other
references. It is available online and I encourage anyone who is interested to
access it and read it. One example that
is incredible and seems uncomplicated by clinical experience: “The ability of
serotonin reuptake inhibitors to reduce genital sensation is well known. Almost
everyone who takes one will experience some degree of genital numbing, often
within 30 minutes of taking the first dose.”
10. Csoka AB,
Bahrick A, Mehtonen OP. Persistent sexual dysfunction after discontinuation of
selective serotonin reuptake inhibitors. J Sex Med. 2008 Jan;5(1):227-33. doi:
10.1111/j.1743-6109.2007.00630.x. Erratum in: J Sex Med. 2008 Dec;5(12):2977..
Csoka, A [corrected to Csoka, AB]. PMID: 18173768.
3 cases of persistent sexual dysfunction 3 of 1300 subjects
from an Internet group that were assessed as credible were interviewed. No medical causes for the sexual dysfunction
were determined.
I received a reply today from the European Medicines Agency on my request for information on their regulatory decision to include language on sexual dysfunction from SSRIs. The entire response is given below.
Thank you for your request for access to documents.
We are writing to inform you that the Agency is not in a position to process your request.
Transparency is an important feature of the European Medicines Agency's operations. As for any public authority, the Agency strives to be as open as possible about how it works and how it comes to its decisions.
However, due to the increasingly high volume of access to documents requests resulting in an excessive workload, and in order to avoid the core business tasks of the Agency and its performance being jeopardised by the administrative workload related to activities within Regulation (EC) 1049/2001 regarding public access to European Parliament, Council and Commission documents (the Regulation), the Agency has taken the decision to process only access to documents requests submitted by citizens of the European Union and natural or legal persons residing or having their registered office in a EU Member State. This approach reflects Article 2(1) of Regulation (EC) No 1049/2001 and was agreed by the EMA Executive Board on 15 June 2018.
Thank you for your understanding.
