Abstract Mukai A, Costa JL. The effect of modafinil on self-esteem in spinal cord injury patients: a report of 2 cases and review of the literature. We report on 2 cases of the effect of modafinil on the self-esteem of patients with spinal cord injury (SCI). The first patient was a 33-year-old man with history of polysubstance abuse and a C6 American Spinal Injury Association (ASIA) grade A injury, who presented for follow-up to the outpatient rehabilitation clinic for depression, decreased motivation, and lowered self-esteem. The patient had tried a selective serotonin reuptake inhibitor (SSRI) without success, and reported increasing social and legal stressors. Within 1 month of starting on modafinil, he reported increased self-esteem and motivation, as well as decreased self-consciousness. The second patient was a 36-year-old woman with history of depression and a T11 ASIA grade A injury. She tried various SSRIs for depression and adjustment issues before she was started on modafinil. She lost weight and became more assertive and less self-conscious within 1 month after starting on modafinil. These 2 cases suggest that modafinil should be studied as a therapeutic option for treating lowered self-esteem in patients with SCI.

1 Pierce C.A.

Richards J.S.

Gordon W.

Tate D. Life satisfaction following spinal cord injury and the WHO model of functioning and disability. 2 Stiens S.A.

Bergman S.B.

Formal C.S. Spinal cord injury rehabilitation. 4. Individual experience, personal adaptation, and social perspectives. 3 Krause J.S.

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Coker J. Depression after spinal cord injury relation to gender, ethnicity, aging, and socioeconomic indicators. 1 Pierce C.A.

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Gordon W.

Tate D. Life satisfaction following spinal cord injury and the WHO model of functioning and disability. 3 Krause J.S.

Kemp B.

Coker J. Depression after spinal cord injury relation to gender, ethnicity, aging, and socioeconomic indicators. , 4 Shackelford M.

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Farley T. Identifying psychosocial characteristics in adults with spinal cord injury. 5 Reidy K.

Caplan B. Causal factors in spinal cord injury patients’ evolving perceptions and association with depression. SPINAL CORD INJURY (SCI) is a devastating event that produces dramatic physical and psychologic changes in patients. Perhaps one of the most important changes is the change in their quality of life (QOL). QOL is a subjective measure of well-being and satisfaction with one’s life. In 1999, the World Health Organization categorized the effect of a health condition on function and disability into 3 domains: body function and structure, activities, and participation.It has also been shown that the perception of health, and not necessarily the objective measures of health, contributes to one’s QOL.In patients with SCI, the actual severity of the injury does not correlate with the subjective perception of QOL.Because the demographic characteristics of patients with SCI are such that a relatively higher proportion of patients are young and male, even the slightest change in physical functioning, sexuality, and independence can be detrimental to patients in the prime of their lives.Many patients led very active lifestyles before the injury, and the physical limitation alone is enough to trigger feelings of frustration, worthlessness, and helplessness. The level of education as well as other socioeconomic factors have also been correlated with symptoms of depression.There has also been research into the effect of “self-blame” and mechanism of injury on rehabilitation.

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Chang E. The influence of spinal cord injury on coping styles and self-perceptions two years after the event. 10 Dijkers M. Quality of life after spinal cord injury. 7 Frank R.G.

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Frank R.G. Depression following spinal cord injury. 16 Hulse K.L. Psychological health issues for individuals with spinal cord injury. Research has shown that patients with SCI tend to have lower self-esteem, which leads to lower self-worth and less motivation.Some physicians have theorized that this change in self-worth is a stage that patients with SCI must go through in order to accept and adapt to the injury and its related changes.However, recent research has shown that this stage theory may not be as viable as previously thought. Two longitudinal studiesthat followed the same patients with SCI for 2 years postinjury showed that patients’ distress was not alleviated with time. Persistent low self-esteem is unhealthy and may lead to long-term depression, stagnation of rehabilitation efforts, and even suicide. In fact, suicide is the leading cause of death in SCI patients younger than 55 years of age.Some patients with SCI also have other life stressors and preexisting psychiatric conditions that may negatively affect their recovery. Life events after SCI can severely stress patients’ coping skills and lead to a cycle of depression, lowered self-worth, suspicion of others, and decompensation.The role of a physician in caring for patients with low self-esteem and motivation is to give them hope and maximize their function in everyday life.The successful rehabilitation of patients with SCI involves giving them the tools to cope with the sequelae of their injuries and successfully improve their motivation and self-perception. Depression and its symptoms are disabling and therefore must be treated as an obstacle to successful rehabilitation.When cognitive, somatic, and affective symptoms of depression are compared, the cognitive aspects have been found to be less amenable to conventional pharmacologic interventions.The cognitive skills of a patient with SCI are crucial in attaining the maximum possible level of function in daily living. Many interventions have been proposed to improve the self-esteem of patients with SCI, including psychologic support and role performance.However, few pharmacologic interventions have been explored as treatment for lowered self-esteem.

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Rogers A.E.

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et al. Health-related quality of life effects of modafinil for treatment of narcolepsy. 18 Lou J.S.

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Sexton G. Fatigue and depression are associated with poor quality of life in ALS. 19 Menza M.A.

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Castellanos A. Modafinil augmentation of antidepressant treatment in depression. 20 BLTC Research. Good drug guide. Available at: www.modafinil.com. Accessed February 1, 2005. 3 receptor, and in particular to increase the release of histamine at the pyramidal-cell level (cortex), increasing alertness and sensory processing. 21 Dackis C.A.

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et al. Modafinil and cocaine a double-blind, placebo-controlled drug interaction study. 21 Dackis C.A.

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et al. Modafinil and cocaine a double-blind, placebo-controlled drug interaction study. 22 MacDonald J.R.

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Tarnopolsky M.A. Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy. , 23 Teitelman E. Off-label uses of modafinil. 24 Willoughby E. Modafinil for fatigue in multiple sclerosis. 25 Turner D.

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Sahakian B.J. Cognitive enhancing effects of modafinil in healthy volunteers. Modafinil, a medication used to treat narcolepsy, has increased self-esteem in patients with narcolepsy, as measured by the Medical Outcomes Study 36-Item Short-Form Health Survey.It is not known if this improvement in QOL and mood is solely due to the alleviation of fatigue and low energy, because fatigue and depression have been associated with poor QOL.Because of this reported beneficial secondary effect, modafinil has been used to augment the treatment of depression with antidepressants.The exact mechanism with which modafinil stimulates the central nervous system is not fully understood. It appears to promote the release of dopamine in the nucleus accumbens, is a direct alpha-1 agonist, and increases glutamatergic transmission, which reduces γ-aminobutyric acid A receptor signaling on the mesolimbic dopamine terminals.It apparently works on the hypocretin-orexin system of the hypothalamus in narcoleptic patients. It has also been reported to increase histamine release via action at the Hreceptor, and in particular to increase the release of histamine at the pyramidal-cell level (cortex), increasing alertness and sensory processing.Modafinil also may have less potential for abuse compared with other stimulants, possibly because of differing mechanism of action. Further research is needed to elucidate clearly the mechanism of action.Off-label uses of modafinil have been reported to increase QOL and function in patients with excessive daytime sleepiness without narcolepsy.Patients with closed-head brain injury, patients on sedating psychiatric drugs, and patients with myotonic dystrophy have also been reported to have benefited from modafinil. A study of the use of modafinil in patients with multiple sclerosis found that it was effective in combating fatigue in this population as well.A study of modafinil in healthy volunteers found that it had cognitive enhancing effects, including the reduction of impulsive responses.This enhancement of cognitive function in addition to the increase in energy may also benefit rehabilitation efforts in patients with SCI. A search of MEDLINE in July 2004 found no reference to use of modafinil in patients with SCI.

Case descriptions Case 1 This patient was a 33-year-old white man with medical history significant for polysubstance abuse, who had sustained a C6 American Spinal Cord Injury Association (ASIA) grade A injury secondary to a motor vehicle collision (MVC) in 2002. The patient was drunk at the time of his MVC, and he continued to abuse cocaine and marijuana for several months postinjury. He had been followed by the rehabilitation clinic physician since he completed his acute hospital stay. His medication on discharge from the rehabilitation unit included oxybutynin, baclofen (Lioresal), cyclobenzaprine, oxycodone, and omeprazole. Medications for his depressed mood and anxiety included 20mg of citalopram every morning and 5mg of diazepam every night. The patient had an episode of simple partial status epilepticus 3 months postinjury, and at the time had a positive urine screen for cocaine and cannabis. He refused substance-abuse treatment and at discharge was prescribed 1000mg of valproic acid twice daily. The patient followed up at the outpatient rehabilitation clinic 6 months postinjury with complaints of feeling “lousy” and increased stress about his ongoing court case related to his MVC. He also complained of increased spasms, and was started on metaxalone. He presented 2 months later with increased depression and reported difficulty sleeping. He was started on 50mg of trazodone every night instead of diazepam (Valium) to facilitate sleep; his citalopram was increased to 40mg every morning. He declined a referral to psychiatry. One month later (9mo postinjury), he continued to report problems at work, including being demoted. He said that it was “weighing heavy on my mind.” He also reported sleeping a lot more. His mother noticed that he was not following his self-catheterization regimen as closely as before. He appeared depressed and became tearful several times during the clinic visit. At this time, he was started on 50mg of modafinil every morning to be slowly titrated as tolerated over the next month up to 100mg every morning for his depression, decreased motivation, and low self-esteem. The patient was instructed to increase his dose as long as he did not have significant insomnia or any other unwanted effects. He again declined a referral to psychiatry. One month after starting on modafinil, he described his depression as a “little better.” We increased his modafinil to 200mg every morning and he reported that his work was going “pretty good.” He still refused to see a psychiatrist, but he reported improvement in his symptoms. Two months later (1y postinjury), he reported he had been sexually active recently. He reported that he could cope with his spasms much better, and said that he was “feeling pretty good.” He reported decreased self-consciousness and improved attitude. He was also able to ask his work supervisor for a raise. He requested and was given a trial of sildenafil (Viagra). Two months later, he continued to report feeling better. His history of substance abuse did not become an issue during the time he was treated with modafinil. Case 2 The patient was a 36-year-old white woman with a medical history significant for depression, who had sustained a T11 ASIA grade A injury secondary to an all-terrain vehicle collision in 2001. She had been followed by the outpatient rehabilitation physician since she completed rehabilitation. Her medication on discharge from the rehabilitation unit included warfarin, rabeprazole, lamotrigine, oxycodone, and gabapentin. Medications for her mood included 40mg of citalopram every night and 2.5mg of olanzapine every night. She called the clinic 2 weeks after discharge to complain that “I have no energy and I cry all the time.” Her olanzapine was increased to 2.5mg twice daily at this time. She also asked for a referral to a psychologist for family counseling. She was hospitalized at another facility for acute rehabilitation 6 months postinjury. At her follow-up visit to the clinic (9mo postinjury), she complained of weight gain on the olanzapine and was switched to 300mg of bupropion every morning and citalopram was decreased to 20mg every morning. During her psychologic evaluation (10mo postinjury), she complained of some denial, depression, and frustration with not being able to work. She also felt guilty about being dependent on her husband and 3 children. She complained of feeling that she was a burden, and was grieving her loss of control and independence. On her follow-up visit (1y postinjury), she said she was “disgusted with myself,” and complained of weight gain and difficulty in adjusting to her injury. At this time, she was started on 200mg of modafinil every morning, up to 400mg every morning as tolerated. She was continued on bupripion and citalopram, as prescribed. The patient reported feeling better 1 month after starting modafinil. Her clothes fit better, although she had not actually weighed herself, and she felt good about herself. She was now willing to do things that she previously had not wanted to do. She reported increased social interactions, decreased self-consciousness, and increased assertiveness. She was fitted for bilateral knee-ankle-foot orthoses and restarted physical therapy sessions. Unfortunately, her insurance plan changed and she was unable to continue as our patient. However, she has kept in touch and recently informed us of her efforts to return to work.

Discussion These 2 cases focus on the effect of modafinil on self-esteem in 2 patients with SCI. The first patient had many social and legal stressors in his life, which contributed to his increasing depression and anxiety. His depression worsened for several months despite treatment with a selective serotonin reuptake inhibitor (SSRI). His mood negatively affected his rehabilitation efforts and he began neglecting his self-catheterization regimen. His motivation and self-esteem continued to decrease until we prescribed modafinil. Its effect was seen within 1 month of initiating that treatment. His self-esteem increased and his mood was elevated. He was motivated enough to date, and to ask his employer for a raise. His history of polysubstance abuse and possible active substance use made us hesitant to use other stimulant medications with higher abuse potential. During his treatment with modafinil, he increased the dose only once, and did not show any signs of dependence or tolerance. His 1 episode of seizure activity was also considered, but because modafinil has not been shown to lower seizure threshold, we felt that it could safely be used in this patient. The second patient had difficulty adjusting to her injury and had an ongoing history of depression. She tried various SSRIs, with only modest success. She was frustrated by the pace of her rehabilitation, and tried inpatient rehabilitation twice to accelerate the pace. At her psychologic evaluation, she complained of being a burden to her family, and lamented her loss of control and independence. She also complained of weight gain, which decreased her self-esteem and social interactions. Although modafinil is not currently indicated for weight loss, in this patient, it appeared to help her lose weight. This may have resulted from increased motivation and energy. In addition, modafinil helped her social skills and self-consciousness. One of the physical consequences of SCI is the change in physical appearance secondary to the use of assistive devices. Adjustment to this change is crucial in the ultimate success of rehabilitation efforts of the patient, and modafinil appears to have helped our patient in this process. Better understanding of the physiology behind self-esteem and motivation is also needed to elucidate the ultimate solution for the problem of low esteem. Good social support and physician-patient relationships are also crucial in helping to increase self-worth and improve rehabilitation efforts of patients with SCI.

Conclusions The long-term effect of modafinil is not known, and it is not clear whether an increase in self-esteem and motivation is sustainable over a longer time period. We have also had patients who did not respond to modafinil or could not tolerate it. However, as these cases indicate, modafinil may be beneficial for some patients. These cases also demonstrate the importance of asking patients about their feelings of self-worth and motivation during clinic visits, in order to properly and efficiently diagnose and treat declining self-esteem and mood. We suggest a formal trial of modafinil to examine its efficacy in treating decreased self-esteem in patients with SCI.

Acknowledgment We thank Karen Thompson, RN, for her help in this research.