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Isotretinoin and Depression

A review of the association between the acne medication Isotretinoin and depression is outlined below. It is free of any influence from the pharmaceutical industry and is presented in a concise and unbiased form with appropriate medical reference.

Isotretinoin - the medication

Isotretinoin (known by the brand names Accutane, Roaccutane and others) is derived from the vitamin A molecule. The vitamin A group of molecules, known as retinoids, play an important role in the function of many organs of the body (1).

Isotretinoin works in treating acne by inhibiting oil gland function, decreasing keratinisation (keeping pores open), and suppressing inflammation. It is considered to be the most effective medication in the treatment of severe acne and has been a registered medication in many countries for decades. Because of its effectiveness it is often used in mild to moderate forms of acne at patient request (2).

Acne and depression - the need to treat

Acne is considered by many as a minor inconvenience and a 'right of passage' through adolescence. However, there is significant medical evidence which shows that the impact of acne can be extremely detrimental causing feelings of embarrassment, frustration and anger (3).Acne sufferers are more likely to be troubled at school, home and in their social lives, and be more prone to depression, anxiety and social phobia (4,5). Suicidal ideation and suicide attempts are also approximately twice as common in individuals affected by acne (6).

Successful treatment of acne can result in a significant improvement of the patients' quality of life (7), less embarrassment about their appearance, (8), and reduced levels of anxiety and depression.(9).
Therefore, leaving acne untreated at times can be very detrimental to the individual.

Isotretinoin and depression - concerns about treatment

A recent systematic medical review presented evidence to suggest a causal association between Isotretinoin and mental illness, specifically depression and suicide (10). This conclusion was substantiated from a number of different means.

Firstly, there is a theoretical plausibility as it is known that pure vitamin A in high doses can cause psychiatric symptoms (11).

There have been a number of cases of a striking temporal relationship with Isotretinoin and depression and many that have had the association 'recur with re-challenge' - that is, depression has occurred shortly after the onset of the medication, a return to normal mood shortly after cessation and then occurrence again with re-introduction of the medication.

It is a significant concern that there have been many patient reports of suicidal ideation, suicide attempts and suicide while taking the medication (12). Given that the medication has been used by millions of teenagers, reports of suicide do not necessarily indicate causation by the medication. However, the number of reports have been enough for the Food and Drug Administration (FDA) in America to issue a 'black box warning' on the medication regarding depression and suicidal behaviour.

When larger groups of individuals have been looked at to determine if there is a significant relationship between Isotretinoin and depression, results vary considerably(10). Many studies have shown no association whereas other studies have shown depression rates occurring between 1-11%. When larger population database studies have been assessed, once again some have shown no association, whereas others have shown a slight but real increased risk of depression (13).

The reason for the varied results of these studies is likely due to the differing methods of the studies in defining their terms and collecting their results. For example, if an individual who became depressed on Isotretinoin stopped taking the medication and did not attend for review appointment, in some studies they would not be included in the study results.

Summary

There would appear to be a definite justification for some with acne to use medications such as Isotretinoin because of the very negative potential impact of acne on their mental health. However, for all medications, it is important that the effect is not outweighed by the side effects.

It is difficult to absolutely prove cause of depression by a medication that is used for many months primarily in teenagers who are already susceptible because of their age group as well as their skin disease. However, the number of reports and studies would indicate that depression and potentially other psychiatric symptoms are a very real side effect, but occur in only a minority who take the medication. Of course, for those who are in this minority and suffer depression because of the medication, this is extremely important.

Recommendation for monitoring of mood

The consensus of many recent medical reviews on this topic has recommended that some form of mood assessment and monitoring during the course of Isotretinoin is necessary (10, 14, 15, 16, 17). Monitoring of mood should take many forms including awareness and self-assessment of mood, discussion of feelings with family and close friends and regular medical reviews.

Mood Monitor app has been designed to help objectively measure mood on a regular basis, and to help provide an early warning when subjective assessment may not be accurate enough or may be forgotten in a busy life. The assessment is based upon the World Health Organization short depression questionnaire which has been proven to be one of the most simple and accurate measures of depression in this patient population (18).

Bibliography

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(2) Goulden V, Layton AM, Cunliffe WJ. Current indications for isotretinoin as a treatment for acne vulgaris. Pharm Treatment. 1995;190:284 - 287

(3) Baldwin HE. The interaction between acne vulgaris and the psyche. Cutis 2002; 70: 133 - 139t

(4) Bez Y, Yesilova Y, Kaya MC et al. High social phobia frequency and related disability in patients with acne vulgaris. Eur. J. Dermatol. 2011; 21: 756 - 760

(5) Purvis D, Robinson E, Merry S et al. Acne, anxiety, depression and suicide in teenagers: a cross-sectional survey of New Zealand secondary school students. J. Paediatr. Child Health 2006; 42: 793 - 796

(6) Halvorsen JA, Stern RS, Dalgard F et al. Suicidal ideation, mental health problems, and social impairment are increased in adolescents with acne: a population-based study. J. Invest. Dermatol. 2011; 131: 363 - 370

(7) McGrath EJ, Lovell CR, Gillison F et al. A prospective trial of the effects of isotretinoin on quality of life and depressive symptoms. Br. J. Dermatol. 2010; 163: 1323 - 1329

(8) Myhill JE, Leichtman SR, Burnett JW. Self-esteem and social assertiveness in patients receiving isotretinoin treatment for cystic acne. Cutis 1988; 1: 171 - 173

(9) Klassen AF, Newton JN, Mallon E. Measuring quality of life in people referred for specialist care of acne: comparing generic and disease-specific measures. J. Am. Acad. Dermatol. 2000; 43 (2 Pt 1): 229 - 233

(10) Bremner JD, Shearer KD, McCaffery PJ. Retinoic acid and affective disorders: the evidence for an association. J. Clin. Psychiatry 2012; 73: 37 - 50

(11) Silverman AK, Ellis CN, Voorhees JJ. Hypervitaminosis A syndrome: A paradigm of retinoid side effects. J Am Acad Dermatol. 1987;16:1027 - 1039

(12) Wysowski DK, Pitts M, Beitz J. An analysis of reports of depression and suicide in patients treated with isotretinoin. J Am Acad Dermatol. 2001;45:515 - 519

(13) Azoulay L, Blais L, Koren G, LeLorier J, Berard A. Isotretinoin and the risk of depression in patients with acne vulgaris: A case-crossover study. J Clin Psychiatry. 2008;69:526 - 532

(14) Rowe C1, Spelman L, Oziemski M, Ryan A, Manoharan S, Wilson P, Daubney M, Scott J. Isotretinoin and mental health in adolescents: Australian consensus. Australas J Dermatol. 2014 May;55(2):162-7

(15) D'Erme AM, Pinelli S, Cossidente A et al. Association between isotretinoin and mood changes: myth or reality? An updated overview. Int. J. Dermatol. 2013; 52: 499 - 500

(16) Thiboutot D, Zaenglein A. Isotretinoin and affective disorders: thirty years later. J. Am. Acad. Dermatol. 2013; 68: 675 - 676

(17) Brasic JR. Monitoring people treated with isotretinoin for depression. Psychol Rep. 2007;100:1312 - 1314

(18) Henkel V, Moehrenschlager M, Hegerl U, Moeller HJ, Ring J, Worret WI. Screening for depression in adult acne vulgaris patients: tools for the dermatologist. J Cosmet Dermatol. 2002 Dec;1(4):202-7