Clarifying the Diagnostic Criteria for Anabolic-Androgenic Steroid ...

Editorial As the American Psychiatric Association committees begin formal work on DSM-V, we welcome brief editorials on issues that should be considered in its formulation.

Issues for DSM-V: Clarifying the Diagnostic Criteria for Anabolic-Androgenic Steroid Dependence

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llicit anabolic-androgenic steroid (AAS) use represents a growing worldwide public health problem (1, 2). Some AAS users consume only a few courses of these drugs in a lifetime, but others progress to a maladaptive pattern of almost continuous use, despite adverse medical, psychological, and social effects (3, 4). In the last 20 years, accumulating animal and human studies have documented and characterized this syndrome of AAS dependence. For example, rats and mice will select AAS in conditioned place preference models (5), and hamsters will self-administer testosterone even to the point of death (6). Unlike rodents, humans may initially develop a pattern of AAS dependence as a result “An important difference of “muscle dysmorphia”—a form of body dysbetween classical drugs of morphic disorder characterized by preoccupation with the idea that one does not look adeabuse and anabolicquately muscular (7). In later stages, however, androgenic steroids is that AAS dependence comes to resemble classical the latter are not ingested drug dependence, with a well-defined withdrawal syndrome mediated both by neuroendoto achieve an immediate crine factors and by a variety of cortical neurotransmitter systems, especially the opioidergic ‘high.’” system (5, 8). Dependence on AAS may be associated with substantial medical morbidity, including hypertension, dyslipidemia, cardiomyopathy, and persistent hypogonadism, together with psychoactive effects, such as manic or hypomanic episodes during AAS use (sometimes associated with aggression and violence), major depressive episodes during AAS withdrawal (with occasional reported suicides), and progression to other forms of substance abuse and dependence, especially opioid dependence (2). The full magnitude of these risks is still unknown, because widespread AAS abuse did not spread from the athletic world to the general population until the 1980s (2), and only now are many AAS users becoming old enough to have developed a dependence pattern with an increased risk for these adverse outcomes. Although AAS users historically have been reluctant to seek treatment (1, 9), these adverse outcomes may now bring increasing numbers to clinical attention. An important difference between classical drugs of abuse and AAS is that the latter are not ingested to achieve an immediate “high” of acute intoxication but, instead, are consumed over a preplanned course of many weeks to achieve a delayed reward of increased muscularity. Therefore, the existing DSM-IV criteria for substance dependence, which were designed primarily for acutely intoxicating drugs, do not apply precisely to AAS. For example, criteria such as “the substance is often taken in larger amounts...than was intended” and “important social, occupational, or recreational activities are given up or reduced because of substance use” apply more easily to alcohol or cocaine than to AAS. But these considerations should not obscure the fact that AAS have definite psychoactive effects, including a potential for addiction, which is likely underestimated because attention has focused on the drugs’ muscle-building properties (1). On the basis of the available literature (2–4, 10) and clinical experience with AAS-dependent individuals, we suggest that the existing DSM criteria be adapted for diagnosing AAS dependence with only small interpretive changes (Figure 1). Presently, AAS are the only major class of drugs scheduled by the Drug Enforcement Administration for 642

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Am J Psychiatry 166:6, June 2009

EDITORIAL FIGURE 1. DSM-IV Substance Dependence Criteria, Interpreted for Diagnosing Anabolic-Androgenic Steroid Dependence Bold type indicates DSM-IV criteria Regular type indicates additions for anabolic-androgenic steroid (AAS) dependence A maladaptive pattern of AAS use, leading to clinically significant impairment or distress, as manifested by three (or more) of the following, occurring at any time in the same 12-month period: (1) tolerance, as defined by either of the following: (a) a need for markedly increased amounts of the substance to achieve intoxication or desired effect; for AAS, this progression to markedly larger doses may be related to dissatisfaction with the previous level of desired effect (e.g., level of muscle mass) (b) markedly diminished effect with continued use of the same amount of the substance (e.g., failure to maintain the same level of lean muscle mass on a given dose of AAS) (2) withdrawal, as manifested by either of the following: (a) the characteristic withdrawal syndrome, characterized for AAS by two or more of the following features: depressed mood, prominent fatigue, insomnia or hypersomnia, decreased appetite, and loss of libido (b) AAS are used to relieve or avoid withdrawal symptoms (3) the substance is often taken in larger amounts or over a longer period than was intended; for AAS, this may be manifested by repeatedly resuming courses of AAS use after a shorter “off” period than the individual had originally planned, or by eliminating "off" periods entirely

(4) there is a persistent desire or unsuccessful efforts to cut down or control substance use; for AAS, this may be manifested by unsuccessful attempts to reduce or stop AAS use because of prominent anxiety about losing perceived muscular size (5) a great deal of time is spent in activities necessary to obtain the substance, use the substance, or recover from its effects; for AAS, this may be manifested by extensive time spent participating in muscle-related activities surrounding AAS use (e.g., time spent in weight training, attending to diet and supplement use, and associating with other AAS users) in addition to actual time spent obtaining and administering AAS (6) important social, occupational, or recreational activities are given up or reduced because of substance use; for AAS, this may be manifested by giving up important outside activities because of an extreme preoccupation with maintaining a supraphysiologic AAS-induced level of muscularity (e.g., the individual relinquishes outside activities for fear that these activities will cause him to miss workouts, violate dietary restrictions, or compromise his ability to use AAS) (7) the substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance; for AAS, this includes medical problems such as gynecomastia, sexual dysfunction, hypertension, dyslipidemia, and cardiomyopathy; or psychological problems such as dysphoric mood swings, severe irritability, or increased aggressiveness

which DSM-IV does not explicitly recognize a dependence syndrome (11); this omission could be rectified in DSM-V by offering these proposed interpretations for AAS dependence in the substance dependence section. Alternatively, DSM-V could initially propose these criteria only for research purposes, pending further evidence of their reliability and validity. In either case, clarified criteria for AAS dependence will likely improve recognition of this diagnosis among clinicians and researchers encountering the syndrome, and they should stimulate increased attention to this emerging public health problem. References 1. Pope HG, Brower KJ: Anabolic-androgenic steroid-related disorders, in Comprehensive Textbook of Psychiatry, 9th ed. Edited by Sadock B, Sadock V. Philadelphia, Lippincott Williams & Wilkins, 2009, pp 1419–1431 2. Kanayama G, Hudson JI, Pope HG Jr: Long-term psychiatric and medical consequences of anabolic-androgenic steroid abuse: a looming public health concern? Drug Alcohol Depend 2008; 98:1–12 3. Brower KJ: Anabolic steroid abuse and dependence. Curr Psychiatry Rep 2002; 4:377–387 4. Perry PJ, Lund BC, Deninger MJ, Kutscher EC, Schneider J: Anabolic steroid use in weightlifters and bodybuilders: an Internet survey of drug utilization. Clin J Sport Med 2005; 15:326–330



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EDITORIAL 5. Wood RI: Anabolic-androgenic steroid dependence? insights from animals and humans. Front Neuroendocrinol 2008; 29:490–506 6. Peters KD, Wood RI: Androgen dependence in hamsters: overdose, tolerance, and potential opioidergic mechanisms. Neuroscience 2005; 130:971–981 7. Kanayama G, Barry S, Hudson JI, Pope HG Jr: Body image and attitudes toward male roles in anabolic-androgenic steroid users. Am J Psychiatry 2006; 163:697–703 8. Kashkin KB, Kleber HD: Hooked on hormones? an anabolic steroid addiction hypothesis. JAMA 1989; 262: 3166–3170 9. Pope HG, Kanayama G, Ionescu-Pioggia M, Hudson JI: Anabolic steroid users’ attitudes towards physicians. Addiction 2004; 99:1189–1194 10. Copeland J, Peters R, Dillon P: A study of 100 anabolic-androgenic steroid users. Med J Aust 1998; 168:311– 312 11. United States Code Title 21; Controlled Substances Act; Section 812: Schedules of Controlled Substances. http://www.usdoj.gov/dea/pubs/csa/812.htm

GEN KANAYAMA, M.D., PH.D. KIRK J. BROWER, M.D. RUTH I. WOOD, PH.D. JAMES I. HUDSON, M.D., SC.D. HARRISON G. POPE, JR., M.D. Address correspondence and reprint requests to Dr. Pope, Biological Psychiatry Laboratory, McLean Hospital, 115 Mill St., Belmont, MA 02178; [email protected] (e-mail). Editorial accepted for publication January 2009 (doi: 10.1176/appi.ajp.2009.08111699). The authors all report having no competing interests. Supported in part by National Institute on Drug Abuse (NIDA) grant DA-016744 (to Drs. Pope, Kanayama, and Hudson) and NIDA grant DA-12843 (to Dr. Wood). Editorials discussing other DSM-V issues can be submitted to the Journal at http://mc.manusriptcentral.com/ appi-ajp. Submissions should not exceed 500 words.

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LETTERS TO THE EDITOR

Our study examined the efficacy and safety of combination treatment with quetiapine and either lithium or divalproex in the prevention of mood event recurrence in patients stabilized while receiving the combination treatment. The results showed that quetiapine combination treatment is an effective option, for those patients who can tolerate this treatment, in the prevention of recurrent mood episodes in stabilized patients, irrespective of the nature of the index episode. The study is particularly strong in that it 1) featured a long stabilization phase prior to randomization, 2) included patients with mania, depression, and mixed index episodes, and 3) followed patients over a prolonged period of time (up to 104 weeks). Reference 1. Storosum JG, van Zwieten BJ, Vermeulen HD, Wohlfarth T, van den Brink W: Relapse and recurrence prevention in major depression: a critical review of placebo-controlled efficacy studies with special emphasis on methodological issues. Eur Psychiatry 2001; 16:327–335

TRISHA SUPPES, M.D., PH.D. Palo Alto, Calif. EDUARD VIETA, M.D., PH.D. Barcelona, Spain

The authors’ disclosures accompany the original article. Dr. Vieta is affiliated with Centro de Investigacion Biomedica En Red de Salud Mental (CIBERSAM). This letter (doi: 10.1176/appi.ajp.2009.09050700r) was accepted for publication in July 2009.

Complexities in Clarifying the Diagnostic Criteria for Anabolic-Androgenic Steroid Dependence TO THE EDITOR: In their recent editorial on anabolic-androgenic steroid dependency, published in the June 2009 issue of the Journal, Gen Kanayama, M.D., Ph.D., et al. (1) highlighted a number of areas for consideration and closer examination. The two most widely accepted standards for def in in g, c l a ss if yi ng , a nd d ia g no s in g d r ug a b u se a nd dependence are DSM-IV and ICD-10. In DSM-IV, anabolicandrogenic steroid dependency is found in the “other substance-related disorder” section and can be coded, depending on which diagnostic criteria are met. ICD-10 codes steroids and hormones in a section on “abuse of nondependence producing substances.” ICD-10 goes on to state that “although it is usually clear that the patient has a strong motivation to take the substance, there is no development of dependence or withdrawal symptoms as in the case of the psychoactive substances.” This difference in approach for coding anabolic-androgenic steroids prompts debate as to whether or not anabolicandrogenic steroids are dependence producing substances. In 1994, the DSM-IV Sourcebook (2) evidence review stated that “despite increasing clinical descriptive data on anabolic steroid withdrawal, dependence, and abuse, there are insufficient substantial basic or clinical research data to support the inclusion of these syndromes in DSM-IV” (p. 140). Am J Psychiatry 166:10, October 2009

Anabolic-androgenic steroids are a class of medicines that have been poorly studied. Since DSM-IV, research has demonstrated anabolic-androgenic steroid properties that have been previously denied. Anabolic steroids positively affect muscle mass and strength, and there is a clear dose-response effect of androgen administration and increasing muscle mass and strength (3). Further, cessation of anabolic steroid administration leads to a loss of muscle mass and strength (4). Anabolic steroid-induced hypogonadism is an important consideration in the complete understanding of anabolic-androgenic steroids (5). The signs and symptoms of hypogonadism are identical to many of those described for the adapted anabolic-androgenic steroid dependency criteria. As such, anabolic steroid-induced hypogonadism is a possible confounding variable in the diagnosis of anabolic-androgenic steroid dependency. These properties must be taken into consideration regarding an anabolic-androgenic steroid dependency syndrome. There is little question that steroids are misused by an increasing number of individuals for a variety of anticipated effects, including, most prominently, an enhancement of physique and athletic performance. Future consideration of anabolic-androgenic steroid dependency criteria must take into account anabolic-androgenic steroid properties. The development of treatments to restore hypothalamic pituitary testicular axis function will clearly prove to be both insightful and productive in the understanding of anabolic steroid-induced hypogonadism and anabolic-androgenic steroid dependency. Individuals who do not suffer from anabolic steroid-induced hypogonadism might represent a class of anabolic steroid users that fulfills the criteria for dependency. References 1. Kanayama G, Brower KJ, Wood RI, Hudson JI, Pope HG Jr: Issues for DSM-V: clarifying the diagnostic criteria for anabolicandrogenic steroid dependence. Am J Psychiatry 2009; 166: 642–645 2. Tsuang JW: Anabolic steroids withdrawal, dependence, and abuse, in DSM-IV Sourcebook, vol 1. Edited by Widiger TA. Washington, DC, American Psychiatric Publishing, 1994 3. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, Chen X, Yarasheski KE, Magliano L, Dzekov C, Dzekov J, Bross R, Phillips J, Sinha-Hikim I, Shen R, Storer TW: Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab 2001; 281:E1172–E1181 4. Schroeder ET, Zheng L, Yarasheski KE, Qian D, Stewart Y, Flores C, Martinez C, Terk M, Sattler FR: Treatment with oxandrolone and the durability of effects in older men. J Appl Physiol 2004; 96:1055–1062 5. Tan RS, Scally MC: Anabolic steroid-induced hypogonadism: towards a unified hypothesis of anabolic steroid action. Med Hypotheses 2009; 72:723–728

MICHAEL C. SCALLY, M.D. ROBERT S. TAN, M.D. Houston, Tex.

Dr. Scally is affiliated with HPT/Axis Inc. Dr. Tan is affiliated with HPT/Axis, Inc. and OPAL medical clinic. This letter (doi: 10.1176/appi.ajp.2009.09060846) was accepted for publication in July 2009. ajp.psychiatryonline.org

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LETTERS TO THE EDITOR

Dr. Pope Replies TO THE EDITOR: We agree with virtually all of the points raised by Drs. Scally and Tan, except for a minor semantic issue regarding their suggestion that anabolic steroid-induced hypogonadism represents a possible “confounding variable” in the diagnosis of anabolic-androgenic steroid dependence. To explain, we need to carefully define our terms. Anabolic steroid-induced hypogonadism is certainly a common physiologic response to chronic anabolic-androgenic steroid exposure, and it may contribute to anabolic-androgenic steroid withdrawal symptoms. Withdrawal symptoms, in turn, are a cluster of physical and psychological symptoms that may occur after discontinuing a drug that induces physiological dependence. Withdrawal symptoms are only one of the seven DSM-IV criteria for substance dependence and are neither necessary nor sufficient for a DSM-IV diagnosis of substance dependence. With these definitions in mind, then, we would say that anabolic steroid-induced hypogonadism represents simply one underlying mechanism for the etiology of anabolic-androgenic steroid withdrawal symptoms and should not be considered a confounder for making a DSM-IV diagnosis of anabolic-androgenic steroid dependence. As an example, opioid withdrawal is caused in part by abnormal signaling at central opioid receptors (1). However, this abnormal receptor activity is not a “confounding variable” in diagnosing opioid dependence. Rather, it is one of the underlying mechanisms of opioid withdrawal, and opioid withdrawal, in turn, is a frequent (but not necessary) criterion for diagnosing opioid dependence. Similarly, if an anabolic-androgenic steroid user suppresses his own testosterone production as a result of prolonged exogenous anabolic-androgenic steroid administration and then develops consequent hypogonadal symptoms upon withdrawing (2), these withdrawal symptoms would legitimately count as one criterion (although not a necessary criterion) for the diagnosis of anabolic-androgenic steroid dependence. On the basis of these considerations, we would agree with Drs. Scally and Tan that anabolic steroid-induced hypogonadism needs to be differentiated from anabolic-androgenic steroid dependence, since not all patients who suffer from anabolic steroid-induced hypogonadism will qualify for a diagnosis of anabolic-androgenic steroid dependence. However, we would suggest that anabolic steroid-induced hypogonadism does not disqualify an individual from a diagnosis of anabolic-androgenic steroid dependence either. Instead, anabolic steroid-induced hypogonadism represents one of the primary mechanisms of anabolic-androgenic steroid withdrawal and physiological dependence. References 1. Waldhoer M, Bartlett SE, Whistler JL: Opioid receptors. Annu Rev Biochem 2004; 73:953–990 2. Kanayama G, Brower KJ, Wood RI, Hudson JI, Pope HG: Anabolic-androgenic steroid dependence: an emerging disorder. Addiction 2009 (in press)

HARRISON G. POPE, Jr., M.D. Belmont, Mass.

The author’s disclosures accompany the original editorial.

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This letter (doi: 10.1176/appi.ajp.2009.09060846r) was accepted for publication in July 2009.

A Different Perspective in Listening: Understanding Transference Interpretation and the Nature of Therapeutic Action in Dynamic Psychotherapy TO THE EDITOR: In their Treatment in Psychiatry article, published in the May 2009 issue of the Journal, Glen O. Gabbard, M.D. and Mardi J. Horowitz, M.D. (1) offered a finely delineated psychotherapeutic approach in the treatment of borderline personality disorder. I wish to suggest an alternative perspective on listening to the patient and thereby on understanding of transference and the nature of therapeutic action. I refer to a position not limited to patients of a specific diagnostic category, but rather to a central shift in outlook on how we listen and its impact on clinical work. It is my view (e.g., reference 2) that therapeutic action occurs more profoundly when the therapist—rather than attempting, however subtly, to dissuade the patient from his or her own felt experience (as to correct “misinterpretations”)— seeks instead to locate the patient’s vantage point and its inherent legitimacy. A statement such as “the therapist is not verbally abusing her” (1, p. 520) when the patient feels that he is would then require the qualifier “from his vantage point” (i.e., the therapist’s vantage point), with her vantage point (i.e., the patient’s vantage point) yet to be found. The transference, then, is understood as a perceptual experience to illuminate, not a distortion or projection to alter. This perspective does not preclude the therapist’s addressing concerns regarding what seems to be dangerous or worrisome behavior, but that is a determination different from one attempting to negate or “correct” what is felt or perceived. It is striking how outer behaviors and symptoms may abate—ideations about the therapist’s mal intent or lack of care genuinely ease—when the inner world is recognized. In the hypothetically drawn example, “Ms. A” spoke of her embarrassment. She had shouted at the clerk, who would not accept her credit card, then noticed people staring at her. Had the clerk not been “rude and curt,” she would not have shouted. These were the feelings she described coming into the hour. The therapist did not speak of them, asking instead about the store’s credit card policy. The patient then became furious, feeling that he was suggesting she had overreacted. “What difference does it make? [H]e still should have been courteous!” (p. 517) she exclaimed. Were the therapist to reconsider her perspective, heeding her rage and increasing sense of injury, rather than suggest that she is “making herself miserable,” he might regard how uncaring his response felt to her in failing to acknowledge her difficult experience. In saying “the same thing that happened in the store is happening with me” (p. 517) to highlight a parallel in her seemingly maladaptive response, he might note the parallel between his response and that of the clerk’s, both as critics. This is not to echo the patient’s words as a feel-good measure, but a moment of recognition. Feeling her perspective to be given credence, its inherent legitimacy located, the patient’s own capacity for reflection may be enhanced. Memories may be awakened, recent or long-term, of analogous experience, shedding light on deAm J Psychiatry 166:10, October 2009