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Psychiatric Effects of Anabolic Steroids After Burn Injuries

Received March 24, 1999; revised May 28, 1999; accepted August 20, 1999. From the Department of Psychiatry, University of Oklahoma Health Sciences Center, Tulsa Campus. Address correspondence and reprint requests to Dr. Morton, Department of Psychiatry, University of Oklahoma Health Sciences Center, Tulsa Campus, 2808 South Sheridan Road, Tulsa, OK 74137.

Key Words: Steroids • Burns • Psychopathology

Burns are the fourth leading cause of injury death in the United States each year, and over 60,000 people are hospitalized annually for burn treatment.¹ There has been a suggestion in the literature that the incidence of Axis I and Axis II disorders was higher in burn-unit patients than in the normal population. Fauerbach et al.,² in a prospective study, confirmed a high pre-burn prevalence (64%) of DSM-III-R Axis I psychopathology. This population also displayed higher levels of neuroticism, as measured by the NEO Personality Inventory, that was negatively correlated with their adjustment at discharge, as measured by the Burn Specific Health Scale (BSHS).

To minimize catabolic complications and shorten disability time, anabolic agents with nutrient support have been recently recommended to be used in populations of critically ill and severely injured patients.³ A recent randomized and prospective study showed an increase in weight gain and presumed muscle mass during the recovery phase when oxandrolone, an anabolic steroid, and a high-protein diet were administered to burn patients suffering deep burns of 30%–50% of total body surface.⁴ Despite the fact that no behavioral changes were noted in that study population, recent reviews of anabolic–androgenic steroid use in various populations suggest that steroid use can cause significant psychiatric symptoms.^5–7 The excellent review by Rubinow and Schmidt⁸ suggests that these varied responses to anabolic steroids may be context-dependent, with the context influenced by genetic, environmental, and historical circumstances. We are reporting one such circumstance that illustrates the potential complications of indiscriminant steroid use in burn patients who have underlying premorbid psychopathology.

Case Report

A 31-year-old male patient was admitted to the burn unit critically ill with deep second- and third-degree burns to 75% of his body surface area. The patient had been painting, and when he approached an open-flame water heater while cleaning himself with a volatile substance, he suffered a severe burn injury. Ventilator support was required in the early days of his hospitalization, which was complicated by a left lower-lobe pneumonia that responded to antibiotic therapy. Large doses of narcotics were needed for pain control, as was intravenous lorazepam for agitation, which started on Hospital Day 6. Oxandrolone (10 mg bid) was initiated 5 days after admission. Multiple autografts, homografts, and dermal templates were used in his burn management, with minimal surgical complications. On Hospital Day 12, he became extremely agitated and extubated himself, describing visual and auditory hallucinations. Substance-induced and burn injury-complicated delirium was diagnosed. Haloperidol was started, and dosages of 40 mg–60 mg/day were required to control the patient's combative behavior. On Hospital Day 20, a psychiatric consultation was obtained. At that time, a possible history of premorbid mania was obtained, and divalproex was added at 750 mg/day and increased in 3 days to 1,500 mg/day. Despite this intervention, the patient continued to show marked mood lability, agitation, and irritability. During this period, all his metabolic parameters were stable, and there was no evidence of active infection. Persecutory hallucinations would intermittently appear, and he would lash out physically and verbally at his therapists, stating that he wanted to be "left alone" so he could "kill himself." During this period, high dosages of narcotics were required for pain control and were gradually tapered during his hospital stay, such that by Hospital Day 40 they were used only for prophylactic pain control before his physical therapy sessions. The narcotics were discontinued on Day 55.

By the Hospital Day 35, the patient no longer had hallucinatory activity; however, his disruptive behavior in the unit, associated with his resistance to following the protocol, constantly put him at risk of shearing his grafts, and restraints had to be periodically used. By Hospital Day 43, the patient had developed extrapyramidal symptoms, and despite our tapering the haloperidol and using anticholinergics, his tremor became disabling. These symptoms eventually subsided with propanolol (60 mg/day) and risperidone (3 mg/day). The risperidone was necessary for continual control of his persistently aggressive behavior. Oxandrolone was decreased to 10 mg/day on Hospital Day 58 at the request of the psychiatric consult service, on the basis of concerns about the possibility of oxandrolone-induced agitation and mood lability. The patient continued during this rehabilitation period to be very concrete in his thinking, showing very little insight about how his behavior was negatively affecting his recovery. He continued to be belligerent and uncooperative, frequently cursing and physically threatening the nursing staff. Oxandrolone was discontinued on Hospital Day 70, when he was discharged.

Historical information was obtained from the state mental health facility in his community, where he was seen 6 years prior to admission after a referral for assessment of multiple incidences of family violence. After a psychiatric evaluation, a diagnosis of personality disorder with impulsivity was made, for which the patient briefly received antipsychotics. Two years later, a diagnosis of mania was considered after an exacerbation of his aggressive behavior, and valproic acid was given for a short time period. He did not return for further follow-up counseling sessions; however, his family insisted that the negative character traits he had manifested years earlier had significantly subsided since 1995. His family members also maintained that the aggressive and hostile behavior he demonstrated in the hospital was much more extreme than any he had manifested since 1995 and was very uncharacteristic of how he had been doing since that time.

Follow-up evaluation of this patient at 1, 2, and 4 months post-hospitalization revealed that his emotional lability, agitation, and impulsivity had subsided significantly, occurring within a few days of discontinuing the oxandrolone. His family and friends stated that his personality resembled that of his more recent, functional prehospitalization state. His outpatient rehabilitation therapists also noted that he was much more cooperative and nonbelligerent in his outpatient program, compared with their inpatient experience with him. He was not taking psychotropic medication and denied experiencing any symptoms of mood, anxiety, or posttraumatic stress disorders.

A posthospitalization psychiatric evaluation revealed a listing of childhood abuse and conduct disorder disturbances. His history of affectual instability, mood dysphoria, and impulsivity were more compatible with a primary Axis II disturbance, such as antisocial and borderline personality disorder, than with Axis I psychopathology. These observations were confirmed with the administration of a Personality Diagnostic Questionnaire–R⁹ and a complete psychiatric assessment using the Structured Clinical Interview for DSM-III-R Personality Disorders.¹⁰ The posthospitalization quiescence of the aggressive and hostile personality trait expressions was also confirmed by the interviewer.

DISCUSSION

It is difficult to determine in a situation such as this a direct cause-and-effect relationship between androgen use and exacerbation of psychopathology. This difficulty is, in the main part, a result of the unique nature of androgen's context dependent activity, as mentioned earlier.⁸ The constantly changing dynamic interactions among such factors as the patient's premorbid mental health status, the severity and intensity of and reactivity to the traumatic experience, the length of hospitalization and rehabilitation, and the level of support from family and professional staff result in a circumstance that will vary considerably from patient to patient. Therefore, individual sensitivity and vulnerability to excess androgens in these situations may be difficult to predict but must be considered a possibility in anyone confronted with a multitude of complex interacting stressors such as noted earlier. This concern, however, is particularly more relevant when one extrapolates from the literature reports and studies that indicate how profoundly androgens affect neurobehavioral systems in various populations.

Su et al.,¹¹ in a placebo-controlled prospective trial, found that anabolic steroids affect mood and behavior at both low and high doses, with irritability, mood swings, violent feelings, anger, and hostility occurring in normal volunteers with no predisposing Axis I or II pathology. Hannan et al.¹² showed high scores of "overt hostility" and "resentmental aggression" on the Minnesota Multiphasic Personality Inventory subscales of normal volunteers who received androgens for 6 weeks. A recent randomized, controlled, double-blind study by Yates et al., in which the researchers administered testosterone cypionate to healthy men between the ages of 21 and 40, revealed similar findings to both studies just mentioned.¹³

These conclusions confirmed the earlier reports by Pope and Katz,^14,15 Perry et al.,¹⁶ and Yates et al.,¹⁷ who observed increased hostility, anxiety, aggression, and depression, as well as full affective syndromes, in athletes and bodybuilders who used steroids at varying doses. Case reports of psychosis manifested as delusions of reference and visual and auditory hallucinations have been described,¹⁸ as well as acute schizophrenic episodes,¹⁹ delirium,²⁰ mania,¹² and hypomania.^13,21

Androgens extensively affect neurotransmitter systems, including the serotonin, dopamine, acetylcholine, norepinephrine, gamma-aminobutyric acid, and neuropeptide transmitter systems and are mediated through both nongenomic and genomic receptor mechanisms.⁸ Because of their extensive neurotransmitter effects and because psychopathology will develop in 5% of normal volunteers given androgens, awareness should be raised for the potential adverse effects created by use of androgens in burn-patient populations. Given that this group is also at high risk for developing affective, psychotic, and anxiety disorders as a result of the stress of their burn injury, diagnostic dilemmas will inevitably occur as one differentiates and treats the developing psychopathology. Therefore, we would urge caution in the routine administration of androgens in this population of patients, particularly if there is a history of impulsivity and explosivity. As our case history demonstrates, steroid use may create a situation that jeopardizes both the health and safety of the staff and the patient. Thus, the benefits of continuing to use androgens in burn patients with developing psychotic or manic symptoms or with persistent disruptive behavior should be weighed against the risks of graft disruption and rehabilitation delay that steroid use may cause. Although a mood stabilizer, beta-blocker, and neuroleptics did give partial control of the manifestations of the patient's presumed androgen-induced toxicity, the striking improvement in his attitude and behavior during outpatient rehabilitation became apparent only after discontinuation of oxandrolone.

Further investigations of the influence of exogeneously administered androgens on patients with histories of Axis I and II disorders appear to be needed. Until more data can be accumulated in this regard, increased awareness of the possible adverse effects of androgens is warranted before their routine use in populations of critically ill burn patients can be recommended. A careful psychiatric history, which is not always readily accessible in burn patients, should be obtained as soon as possible so one can closely monitor these patients for any psychopathology that may be induced or exacerbated by anabolic androgen administration.

REFERENCES

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