RESEARCH

Patients’ perceptions of isotretinoin, depression and suicide A qualitative study

Parker Magin, MFM (Clin), FACPsychMed, FRACGP, is a NHMRC medical postgraduate scholar, Discipline of General Practice, University of Newcastle, New South Wales. [email protected] Jon Adams, BA, DipStats, MA, PhD, is Senior Lecturer in Health Social Science, Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, New South Wales. Gaynor Heading, BA, GradDipHSS, PhD, is Senior Lecturer, PHCRED Program, Discipline of General Practice, University of Newcastle, New South Wales. Dimity Pond, MBBS, BA, DipEd, DipSocSci, PhD, FRACGP, is Professor of General Practice, Discipline of General Practice, University of Newcastle, New South Wales. Wayne Smith, BMath, BMed, MPH, PhD, FFPHM, is Professor of Epidemiology, Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, New South Wales.

BACKGROUND Isotretinoin (Roaccutane) is an effective than the background incidence.14 Isotretinoin is an effective acne and widely used therapy for severe acne.1– However the media overseas have made medication. The evidence for it causing 3 But there are a wide range of adverse much of the possible link;15,16 as have, more depression and suicide, although widely effects. The most notable is teratogenicity;3 recently, Australian media.17,18 We wondered to publicised, remains uncertain. although mucocutaneous, ophthalmic, and what extent this possibility influences patients’ METHODS musculoskeletal side effects, and changes decisions to use isotretinoin. Twenty-six semi-structured interviews to plasma lipids and liver function tests are with patients with acne were coded and also important.1,2,4 Methods subjected to thematic analysis. Whether or not it causes depression and We undertook semi-structured interviews RESULTS suicide is controversial. The Federal Drug with patients currently suffering acne as Isotretinoin was perceived to be effective but dangerous. The most well Administration received 394 reports of cases part of a study into the psychiatric sequelae known adverse effects were depression of depression, and 37 suicides occurring of skin disease. We mailed invitations and suicide. in patients exposed to isotretinoin during to participate to subjects from an earlier DISCUSSION 1982–2000.5,6 However, other observational quantitative phase of the project (patients The overemphasis of serious data analyses have failed to confirm this with skin diseases recruited from the psychological adverse events in patients association.7,8 Furthermore, there have been practices of dermatologists and general might discourage the use of isotretinoin observations of improvement in depression practitioners). This was supplemented with by those who might benefit from it. scores in patients with acne with invitations posted in the waiting rooms of isotretinoin treatment.9–11 This is reinforced some GPs who had participated previously. by case series 12 and cross sectional Participants provided written consent studies13 suggesting an association of acne according to the protocol approved by itself and suicide or suicidality. A review of the Human Research Ethics Committee, the evidence in this area suggests that the University of Newcastle, New South Wales. incidence of depression and suicide during We developed the interview themes from isotretinoin therapy is probably no greater both the literature and our own ideas, and

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used a modified grounded theory approach. perspective were fed back into the analysis previously used isotretinoin, although none The discussions were informant led as much to cross check codes and themes, and were currently. After 22 interviews there as possible and as data collection progressed, develop an overall interpretation of the data. were no new thematic ideas. additional themes for exploration were added We also searched for negative cases in code Attitudes to ‘medical’ treatments as new areas of interest emerged. and theme development. We audiotaped and transcribed the We found attitudes to medical interventions interviews for coding, filing and retrieval Results generally, and to isotretinoin in particular, of thematically related data ‘chunks’, We interviewed 26 participants with were complex. Many were wary of therapies analysing as we went. Each transcript was acne with: an equal sex distribution, age deemed ‘medical’ (topical retinoids, topical separately coded by two members of the range 13–52 years, and with different and oral antibiotics, isotretinoin) because of research team, and differences in researcher acne severity. Six of the participants had potential side effects, preferring over-the- counter treatments (creams, lotions and Table 1. Perceptions regarding adverse effects of medical treatments including washes, and in particular, complementary, isotretinoin alternative or herbal preparations), even if less effective (Table 1). ‘I probably go for the more natural stuff. I probably prefer the teatree oil face wash cause it’s just a bit more natural. I guess you are not putting too many foreign chemicals in your body... Perceptions regarding isotretinoin and When something’s very chemical you never know what might happen’ (male, age 19 years) adverse effects ‘Some of my mates got real dry faces and dry lips [on isotretinoin]’ (male, age 15 years) Isotretinoin was known as particularly ‘When I was on Roaccutane the first time, I was younger, I had really, really severe dry effective, but also toxic and dangerous. lips. They would crack and bleed and that, and a really dry nose’ (male, age 22 years) The mucocutaneous side effects were well ‘It seemed to help their faces but... I’ve heard bad reports about other side effects, sort of, I recognised (Table 1). Some were based don’t know how accurate they were, but they sort of made me, cautious’ (male, age 15 years) on misinformation such as one girl’s ‘No I didn’t use it but I was told about [isotretinoin] and to see if I wanted to use this, but wrong advice from her mother regarding I had heard something about it having testosterone in it as well and that was one of the androgenicity (Table 1) and another things in it and I thought: ‘Not really, no thank you’ (female, age 19 years) woman’s concerns regarding the duration ‘I hadn’t completely given up on the idea that I would have a child one day and there is a of isotretinoin’s potential for teratogenicity huge issue with Roaccutane. I’ve read that it’s about 12 months waiting period after you after treatment (Table 1). have been on it’ (female, age 32 years) Perceptions of psychological effects

Participants knew about possible links of isotretinoin with depression and suicide, Table 2. Perceptions regarding isotretinoin, depression and suicide worrying those who had taken isotretinoin, and acting as a disincentive to those who ‘So... some of the suicide things and... Well there was a few different side effects but I don’t know how accurate they were, but I’d have had to look into it carefully if I’d have had to’ had not (several had rejected the idea (male, age 15 years) because of putative psychiatric effects, even One of my friend’s boyfriends had severe acne and they put him on this medication which after it had been recommended by their made him really, really depressed. And I don’t know how much truth there is to it, but I think doctors) (Table 2). For some whose acne at the same time they found out that some of these medications were making boys so upset was only mild or moderate, this was not and depressed that it might be a cause for suicide or something like that. So I don’t know, I serious enough to warrant a therapy with think that sounds a lot worse than the actual acne itself’ (female, age 20 years) any risk (Table 2). Even those who regarded ‘Well I’ve heard news reports in the last couple of years about Roaccutane to do with side its efficacy as superior saw it as powerful effects, depression and other stuff. I’m glad I’m not taking it anymore’ (male, age 41 years) and dangerous (Table 2). ‘Oh, I think it’s reasonable if it’s not doing something worse for the person. I mean, it would be nice to cure severe acne, but not at the expense of emotional health. I definitely don’t Experiences of psychological sequelae think it’s worth it if it’s driving boys to such a point in depression that they’d consider suicide Some previous users of isotretinoin a viable option’ (female, age 20 years) remembered a possible adverse psychiatric ‘Cleared it up straight away. It was the ‘H’ bomb of acne treatments, yeah [...] It was a effect, usually a perception of the family rather serious drug, and still is, you know’ (male, age 46 years) than the subject (Table 3). Others remembered more positive psychological effects (Table 3).

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Michas T. Psychological and sympatho-adrenal Table 3. Experiences of psychological sequelae of isotretinoin status in patients with cystic acne. J Eur Acad Dermatol Venereol 1999;13:24–7. ‘Apparently I was more moody while I was on the Roaccutane, but I didn’t really 12. Cotterill JA, Cunliffe WJ. Suicide in dermatological notice but my family did... generally more sullen’ (male, age 19 years) patients. Br J Dermatol 1997;137:246–50. 13. Gupta MA, Gupta AK. Depression and suicidal ‘I felt much better about myself. And, ah, it was almost like I wanted to show off. And ideation in dermatology patients with acne, alo- when it got dramatically better with Roaccutane, that was fantastic. I was really, really pecia areata, atopic dermatitis and psoriasis. Br J happy about that’ (male, age 19 years) Dermatol 1998;139:846–50. 14. Magin PJ, Pond CD, Smith W. Isotretinoin, depres- ‘It goes back to the Roaccutane and what I said that meeting new people was a lot sion and suicide: a review of the evidence, the easier with clear skin because of the Roaccutane. It gave you more confidence’ (male, controversy, and its relevance to general practice. Br age 46 years) J Gen Pract 2005;55:134–8. 15. Rogers L. Suicides linked with acne drug. Sunday Times 1998; Mar 15,12. Discussion 16. Luek S. Congressman blames Accutane, an acne drug, Implications of this study for son’s suicide. Wall Street Journal 2000; Oct 6,7. for general practice This was a qualitative study of a limited 17. Ravens T. Acne drug linked to teens hanging. number of acne patients. Nevertheless Courier Mail 2004; Oct 29. • Patients for whom acne may be used are 18. Carson V. Acne drug in ‘bubbly’ girl’s death spiral. important themes were established. Many concerned about depression and suicide The Australian 2004; Oct 29. participants were aware of the proposed link with isotretinoin use. 19. Koo J. The psychosocial impact of acne: patients’ of isotretinoin to depression and suicide. • Many probably overestimate the risks. perceptions. J Am Acad Dermatol 1995;32:S26–30. Others had a less defined impression AFP of a powerful drug that called for considerable caution. Presumably this Conflict of interest: none declared. Correspondence comes from mainstream media attention. Email: [email protected] The validity of these fears is contentious. References Participants, however, were not aware 1. Brecher AR, Orlow SJ. Oral retinoid therapy for of the weak level of evidence for the dermatologic conditions in children and adoles- cents. J Am Acad Dermatol 2003;49:171–82. association, and tended not to frame the 2. Ellis CN, Krach KJ. Uses and complications of prospect of treatment with isotretinoin in a isotretinoin therapy. J Am Acad Dermatol 2001;45: risk/benefit manner. S150–7. 3. Lowenstein EJ. Isotretinoin made SMART and It would of course be prudent to assess simple. Cutis 2002;70:115–20. psychiatric parameters before using 4. Hanson N, Leachman S. Safety issues in isotretinoin isotretinoin, and to monitor patients using therapy. Semin Cutan Med Surg 2001;20:166–83. 5. Wysowski D, Pitts M, Beitz J. Depression and it for depression and suicidal ideation.14 suicide in patients treated with isotretinoin. New But a greater challenge may be in providing Engl J Med 2001;344:460–61. patients with an informed perspective 6. Wysowski D, Pitts M, Beitz J. An analysis of reports of risk-benefit decisions in choosing of depression and suicide in patients treated with isotretinoin. J Am Acad Dermatol 2001;45:515–9. acne therapy. 7. Jick S, Kremers H, Vasilakis-Scaramozza C. Much of the public perception and Isotretinoin use and risk of depression, psychotic public debate in this area is seemingly symptoms, suicide and attempted suicide. Arch Dermatol 2000;136:1231. informed by a trivialisation of the impact 8. Hersom K, Neary MP, Levaux HP, Klaskala W, of acne on the sufferer. Acne may be a Strauss JS. Isotretinoin and antidepressant phar- transient accompaniment of adolescence, macotherapy: a prescription sequence symmetry analysis. J Am Acad Dermatol 2003;49:424–32. but for many (especially those with severe 9. Strauss JS, Leyden JJ, Lucky AW, et al. Safety of nodulo-cystic acne for whom isotretinoin is a new micronised formulation of isotretinoin in most often used) it can be have important patients with severe recalcitrant nodular acne: a psychological consequences.19 The clinician randomised trial comparing micronised isotretinoin with standard isotretinoin. J Am Acad Dermatol then must set out the possible risks and 2001;45:196–207. benefits in a way that is meaningful and 10. Rubinow DR, Peck GL, Squillace KM, Gantt GG. practical. To this end, perhaps understanding Reduced anxiety and depression in cystic acne patients after successful treatment with oral isotreti- of the nature of lay perceptions of risks noin. J Am Acad Dermatol 1987;17:25–32. regarding isotretinoin is helpful. 11. Schulpis K, Georgala S, Papakonstantinou ED,

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