BRIEF report Methylphenidate in the Treatment of Coma Michael Worzniak, MD; Michael D. Fetters, MD, MPH; and Maureen Comfort, MPH Dearborn and Ann Arbor, Michigan While there is significant morbidity and mortality involving patients in semicomatose and comatose states, the care of such patients has traditionally been limited to supportive measures. We report two cases of patients treated with methylphenidate hydrochloride: the first, a patient in a semicomatose state resulting from traumatic brain injury, and the second, a patient in a comatose state secondary to a subdural hematoma that occurred after a fall. Treatment with methylphenidate may provide neurostimulations by augmenting the activity of injured neuronal tissue within the reticular activating system, and by amplifying the net effect of the reduced number of viable neurons. Methylphenidate is a low-cost, potentially efficacious intervention for reducing the duration of comas, for preventing life-threatening and costly complications of prolonged unconsciousness, and for promoting early ambulation and recovery. Further research using more rigorous research designs to ascertain the effectiveness of methylphenidate in the treatment of patients in semicomatose and comatose states is needed. KEY WORDS. Methylphenidate; coma; brain injuries; Glascow Coma Scale. (J Farm Pract 1997; 44:495-498) wo case series1,2 and case reports34 sug­ decreased levels o f consciousness using ocular, gest a role for methylphenidate in the verbal, and motor responses to stimulation. The reversal of coma resulting from various GCS provides an effective, simple, and repro­ causes. Recent research suggests that ducible method of assessing the degree of coma methylphenidate can improve attention (Table). A patient with a score of 15 is considered andT functional outcomes during rehabilitation of normal, a score between 9 and 14 denotes a acutely brain-injured adults,5 and a recent review6 decreased level of consciousness or semicoma, suggests that psychostimulants are potential treat­ and a score of 8 or less corresponds to coma.7 ment options for neuropsychiatric sequelae of stroke and traumatic brain injury including depres­ ■ Case Reports sive disorders, impulsiveness, apathy, irritability, attention, concentration, and memory problems. Case 1 Despite these initial intriguing results, little follow ­ A 19-year-old man sustained cerebral lacerations up investigation o f the drug’s utility, safety, and and contusions resulting in severe cerebral edema efficacy in the treatment of comatose and semico­ and a small subdural hematoma after a motor vehi­ matose states has been conducted. cle accident. Initial interventions included ventila­ In the following case reports, two patients were tory support and care at a major trauma center. treated successfully with methylphenidate. In the Despite aggressive supportive treatment, he first case, a patient was in a semicomatose state remained in a semicomatose state, and was trans­ due to traumatic brain injury, and in the second, a ferred to a community hospital for nursing home patient was in a comatose state secondary to the placement. When transferred to a community hos­ subdural hematoma after a fall. pital, he had decreased mental awareness, and The patients’ degree of coma was evaluated responded minimally to pain. With deep stimula­ using the Glasgow Coma Scale (GCS). The scale tion his eyes fluttered and he yawned before slip­ has been used widely to classify the severity of ping back into a semicomatose state. His pupils Submitted, revised, February 10, 1997. reacted sluggishly to light, and he responded to From the Family Practice Residency, Oakwood Hospital and loud verbal commands by moving his left hand, Medical Center (M. W.), Dearborn, and the Department of which had a very weak grip. The baseline GCS Family Practice, University of Michigan Medical Center (M.F. and M.C.), Ann Arbor, Michigan. Requests fo r score was 8. reprints should be addressed to Michael Worzniak, MD, Four days after admission, with the family’s con­ Family Practice Residency Program, Oakwood Hospital and sent, treatment with methylphenidate 10 mg twice Medical Center, 18101 Oakwood Blvd, PO B ox 2500, Dearborn, M I 48123-2500. a day through a gastrostomy tube was initiated. ® 1997 Appleton & Lange/ISSN 0094-3509 The Journal o f Family Practice, Vol. 44, No. 5 (May), 1997 4 95 TREATMENT OF PATIENTS IN COMA sorrow that it had happened. The dosing interval The Glasgow Coma Scale was increased to three times a day on the 14th day Test Response Score* of treatment. After 18 days of treatment, he was verbal, ambulatory, and following commands. The GCS score was 15. He was discharged to a head Eye opening Spontaneous 4 injury facility for more intensive speech and physi­ To sp e e c h 3 cal therapy. To pa in 2 N one 1 Case 2 An 89-year-old woman was admitted to a commu­ nity hospital unresponsive and comatose. Her Best verbal Oriented 5 past medical history included hypertension, ath­ response Confused 4 erosclerosis, and cerebral thrombosis 1 year ear­ Inappropriate 3 lier that resulted in minimal residual deficit. A Incomprehensible 2 verbal woman at baseline, she had previously N one 1 lived in a supervised adult care home, where she read and interacted with other patients and fami­ ly. One week before admission she fell, and Best motor Obedience to commands 6 appeared to have sustained only minor injury. In response (arm) Localization of pain 5 the 24 hours before hospital admission, however, Withdrawal response to pain 4 she appeared confused, and upon taking a nap, Flexion response to pain 3 she became unresponsive. Extension response to pain 2 At initial examination at the hospital, she N one 1 appeared deeply comatose. She did not respond 'Scores are summed across the 3 categories. A score of 15 is normal, to pain, temperature testing, or touch. Her pupils 9 to 14 indicates semicoma, and a score of 8 or less indicates coma. were minimally reactive to light, and the right Data for table adapted from Teasdale G, Murray G, Porker L, et al. pupil was larger than the left. Her baseline GCS Adding up the Glasgow Coma Score. Acta Neuochirurgica Supplementum (Wien) 1979; 28:13. score was 3. A computed tomography scan of the head revealed a large subdural hematoma with herniation o f the right cerebral hemisphere Twenty-four hours later, there was a dramatic across the midline into the left cranium. As neu­ improvement in his level of consciousness. He rosurgical consultation estimated surgical mor­ appeared more alert, his pupils were more active, tality at near 100%, supportive care with intra­ he touched his face with his hand, and he exhib­ venous fluids and nasal gastric feeding was elect­ ited other spontaneous movements. The GCS ed. The patient was stabilized and transferred to score was 10. On day 3 of treatment, the dosage a long-term care home 1 week after admission. was increased to 20 mg tw ice a day, and on day 5, She remained totally unresponsive, requiring he responded to voice commands by holding his nursing care, tube feeding, and frequent turning, head up and making eye contact. When his par­ suctioning, and bowel and bladder care. ents brought in his class yearbook, he turned the After 1 month of unchanged status at the long­ pages with his left hand, although it was unclear term care home, the family consented to treat­ whether he could identify anyone. Seven days ment with methylphenidate. Six days after initia­ after initiation of treatment, he began showing tion of methylphenidate at 5 mg twice a day, she emotions such as anger and crying. His GCS exhibited spontaneous eye movement and spoke score was 14. one or two words. A GCS score of 10 was record­ On day 9, he began to feed himself, and asked to ed. On day 15 o f treatment, she could hold her be discharged. He briefly stood on his own and head up and speak in short phrases. A GCS score transferred into a chair. On day 10, he conversed of 14 was recorded. On day 27 of treatment, the with a girlfriend, and while talking with his mother, dosage was increased to 10 mg twice a day and he recalled the accident and cried as he expressed she began to remain awake most of the time. She 496 The Journal o f Family Practice, Vol. 44, No. 5 (May), 1997 TREATMENT OF PATIENTS IN COMA became more alert and in contact with her sur­ Kraus6 postulates that depletion of monoaminer- roundings, and continued to use short phrases to gic transmission may underlie the neurobehavior communicate with the staff. disorders in traumatic brain injury and poststroke Further improvement occurred after the disorders. By analogy, there may be even more dosage of methylphenidate was increased to 10 profound deficiencies of monoamine-like sub­ mg three times a day. The nasal gastric tube was stances in patient with loss of consciousness. removed, and she was fed orally. Four days later Hence, methylphenidate may provide neurostimu­ she was alert and talkative and had a good lation by augmenting the activity of injured tissue appetite. She could sit in a chair and converse within the ascending reticular activating system, with the staff with appropriate speech and com­ and by amplifying the net effect of the reduced prehension. Her GCS score was 15. She continued number of viable neurons. to do well until almost a year later, when she died There are no clear guidelines established for of an acute cardiac event. daily dosage of methylphenidate in brain-injured patients; therefore, gradual titration o f dosage with I Discussion close monitoring for side effects is advised. In patients with brain injury due to stroke or trauma, This report describes the dramatic improvement methylphenidate can be started at 5 mg twice a of a patient in a semicomatose state from trau­ day.