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Extrapyramidal side effects of antiemetics presenting as psychiatric illness
Extrapyramidal Side Effects of Antiemetics Presenting as Psychiatric Illness Carla Rodgers, M.D.
Abstract: Although extrapyramidal side effects of two commonly used antiemetics, metoclopramide and prochlorperazine, are well known, it may be difficult for even the experienced practitioner to distinguish some of these extrapyramidal reactions from such psychiatric symptoms as anxiety, depression, or catatonia. Certain patient groups have increased susceptibility to these extrapyramidal reactions, including patients under 30, those with AIDS, those with renal disease, oncology patients, and possibly women. Physicians should maintain a high index of suspicion for depression, anxiety, or catatonia if their patients are taking antiemetics. These symptoms may be extrapyramidal side effects of the antiemetic rather than indications of a prima y mental disorder.
Introduction Metoclopramide and prochlorperazine are commonly used antiemetics in both inpatient and outpatient settings. Prochlorperazine is a phenothiazine, whereas metoclopramide is a benzamide derivative of methyldopa, but the latter has a side chain that resembles the phenothiazines. Among the side effects described in the literature are akathisia, parkinsonism, and acute dystonias and dyskinesias. [l-4] The overall incidence of such extrapyramidal reactions due to these antiemetics in patients without oncologic disorders is up to 2%. [3,5,6] Certain patient groups exhibit increased susceptibility, including patients under 30, those with AIDS, renal disease, cancer, and possibly women. The usual dose of prochlorperazine is 5-10 mg P.O.
or I.M. every three-four hours with a recommended maximum total dose of 40 mg. The total maximum intravenous dose is also 40 mg [7]. The usual dose of metoclopramide for postoperative nausea and vomiting is lo-20 mg I.M. every 4-6 hours; no upper limit is listed by the manufacturer. For chemotherapy patients, however, an intravenous infusion of l-2 mg/kg is recommended [8]. Extrapyramidal side effects from these antiemetics occurred in 100% of patients in one oncology study [9]. Because the doses used to control emesis in cancer patients are generally higher than the recommended therapeutic dose, it is unclear whether the debilitated physical state of the patient is the primary contributing factor to the development of these side effects or whether these side effects are dose related. Unfortunately, the presentation of antiemeticinduced extrapyramidal side effects may vary widely and can mimic a number of primary psychiatric conditions. In a recent 2-month period, the psychiatric service at our institution was consulted on three medical patients: the first for anxiety, the second for depression, and the third for evaluation of catatonia. In each of these cases, the presumed psychiatric condition was actually an extrapyramidal reaction to prochlorperazine, metoclopramide, or a combination of the two.
Case Reports Case 1
From the Division of Psychiatry and Human Behavior, Jefferson Medical College, Philadelphia, Pennsylvania. Address reprint requests to: Carla Rodgers, M. D., 1652 Thompson Building, 1020 Sansom Street, Philadelphia, PA.
192 ISSN 0X3-8343/92/$5.00
A 34-year-old Hispanic male with AIDS had been admitted for fever, night sweats, blurred vision, weight loss, and anorexia. The patient also comGeneralHospitalPsychiatry14, 192-195, 1~2 0 1992 EIsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010
Extrapyramidal
plained of nausea and vomiting with hematemesis. Blood, sputum, and urine cultures were all negative. The patient had magnetic resonance imaging and computed tomography of the head which were also negative. He was started on naproxen 375 mg twice a day for the fever, which was attributed to the HIV infection. Additional standing medications included multivitamins P. o. daily; acyclovir 200 mg P.O. four times a day; megestrol acetate 80 mg P.O. four times a day; and clotrimazole troche five times per day. The patient was scheduled to receive 2,3 dideoxyinosine, an investigational drug, which was withheld because emesis persisted: to treat this problem, prochlorperazine 10 mg every six hours P.O. or I.M. was prescribed. Four days later, the unit social worker noted a significant change in the patient’s mental status. She stated he had a vacuous look, a flattened affect, and tremulous lips and hands. The following day the patient received an additional 10 mg of metoclopramide intravenously for continued vomiting. Psychiatry was then consulted to evaluate the patient’s increasing withdrawal and catatonia. Psychiatric examination revealed a coarse resting tremor, masked face, cogwheeling in both upper extremities (right greater than left), and a festinating gait. The patient denied suicidal or homicidal ideation and stated he wanted to go home. He would not answer any other questions, but it was not clear whether he was unwilling or unable to so. It was determined that the cause of his psychiatric symptoms was actually severe parkinsonism, and both prochlorperazine and metoclopramide were immediately discontinued. The patient then received two doses of diphenhydramine hydrochloride 50 mg I.M., and during the next day he recovered significantly from antiemetic-induced catatonia. At that time a repeat mental status examination was conducted, and revealed the patient to be oriented to time, place, and person, with no suicidal ideation, auditory or visual hallucinations, and no evidence of delusional thinking or a formal thought disorder. The tremor, cogwheeling, and festinating gait were significantly diminished, and he was discharged 5 days later.
Case 2 A 70-year-old white female with recurrent melanoma was admitted for chemotherapy with cisplatin 40 mg I.V. daily, and dacarbazine 350 mg I.V.
Side Effects of Antiemetics
daily. To diminish the side effects of nausea, her physicians prescribed metoclopramide 75 mg I.V. just prior to and every 6 hours during the chemotherapy. Two days later, the patient became increasingly anxious, for which psychiatry was consulted. When seen, the patient had akathisia, masked face, cogwheeling bilaterally, and involuntary leg movements. She felt increasingly restless and anxious but denied suicidal ideation. Psychiatry diagnosed an organic anxiety disorder, akathisia, and parkinsonism, all secondary to metoclopramide, which was then discontinued. The patient then received lorazepam 0.5 mg every 6 hours to manage her nausea, vomiting, anxiety, and akathisia, and was discharged after her course of chemotherapy without further side effects.
Case 3 A 1Pyear old Asian female was admitted for resection of a benign hepatic mass, and underwent left hepatic lobectomy without complications. Her postoperative medication included cefazolin sodium 1 g I.V. every six hours, ranitidine hydrochloride 150 mg P.O. twice/day, and aluminum and magnesium hydroxide suspension 30 cc P. o. every 4 hours. The patient received morphine sulfate 58 mg I.M. every two-three hours as needed for pain until the fourth postoperative day, when it was discontinued. She had an episode of emesis on the fifth postoperative day, for which she was given one dose of metoclopramide, 10 mg P.O. She continued to have nausea on the sixth postoperative day and received prochlorperazine, 10 mg I.M. During the evening, the nursing staff reported that the patient was anxious, shifting restlessly back and forth and unable to stay in bed. Although the patient denied further nausea, she was given another lo-mg injection of prochlorperazine the next evening. The following day psychiatry was consulted to evaluate the patient’s depression and anxiety. She paced back and forth in the hallway and was unable to sit or to stop pacing during the evaluation. She stated that she was so agitated she felt like jumping out the window. Although she denied suicidal ideation and stated her mood was not depressed, she was unable to assure us that she would not jump. The patient had received two doses of lorazepam 0.5 mg P.o., but reported no relief of anxiety. We diagnosed severe akathisia and recommended one-to-one nursing care. We rec-
193
C. Rodgers
ommended that both metoclopramide and prochlorperazine be immediately discontinued, and placed the patient on alprazolam 0.25 mg four times a day. Follow-up 24 hours later revealed significant improvement, with the patient reporting decreased restlessness and no further impulse to jump out the window. She was discharged in good condition 1 week after the initial psychiatric consult.
Comment Three cases of extrapyramidal side effects due to the antiemetics metoclopramide and prochlorperzine have been presented. These cases were initially thought to be primary psychiatric disorders of anxiety, depression, and catatonia. Misdiagnosis and underdiagnosis of extrapyramidal side effects have been widely reported [lo]. In a study of 48 patients on antipsychotic medication that has similar central dopamine-blocking action as these two antiemetics, treating physicians identified extrapyramidal reactions in 45% of patients, and the study found that 100% of these patients were afflicted to some degree with extrapyramidal side effects [ll]. Neuroleptic-induced catatonia, which can be treated with amantadine, has also been reported. It is hypothesized that this syndrome may represent part of a continuum of dopamine blockade, which also includes the life-threatening neuroleptic malignant syndrome [12]. These side effects have also been reported to be diagnosed as hysteria, epilepsy, and meningitis [4]. A large prospective study by Bateman et al. [13] on first-time users of both antiemetics (metoclopramide and prochloperazine) concluded that marked extrapyramidal reactions are more common than expected and seem to be age-related: an incidence of l/81 patients less than 30 years of age, and l/572 patients over age 30. According to the authors, this study may have underestimated the actual incidence. Bateman, et al. have not found gender to correlate with increased risk. Miller and Jankovic [3], however, conclude that women are more susceptible to metoclopramide-induced movement disorders. They hypothesize that the mechanism of action may be related to continuous blockade of D2 receptors by estrogen, resulting in increased sensitivity of these receptors in women. It is also possible that a genetic predisposition may exist [3]. In addition to age and gender, previous case 194
reports cite increased susceptibility in physically compromised patients, including those with AIDS [14,15]. Specific mechanisms are not yet known, but increased sensitivity of AIDS patients to developing these extrapyramidal side effects may relate to basal ganglia damage by the retrovirus [15]. Renal disease is another impairment that may increase a patient’s susceptibility. One report describes hemodialysis patients at increased risk of developing extrapyramidal signs on metoclopramide [16]. As this drug is excreted by the kidney, impaired renal function may result in elevated metoclopramide levels, producing more frequent extrapyramidal reactions in these patients [16,17]. Oncology patients also seem to be more likely to develop extrapyramidal side effects to these antiemetics, but it is unclear if this susceptibility is the result of high doses-often four to seven times the usual therapeutic dose-which are used to control nausea and vomiting during chemotherapy. Extrapyramidal reactions to prochlorperazine have been reported to occur more often at higher dosages [9], whereas other investigators have found no relationship between the incidence of extrapyramidal reactions and either dose or plasma concentration of metoclopramide [ 181. Although certain groups of patients seem to be at increased risk, the development of extrapyramidal reactions to these antiemetics may be idiosyncratic. This assertion is supported by two suicide attempts involving the ingestion of 360 and 800 mg of metoclopramide, respectively, in which neither patient developed extrapyramidal signs [6]. It should also be noted that long-term use of metoclopramide can cause tardive dyskinesia, even at recommended therapeutic doses [19]. In summary, physicians using metoclopramide and/or prochlorperazine should be aware that extrapyramidal reactions can occur in sensitive patients, even at usual therapeutic doses. These reactions can present and masquerade as anxiety, depression, and catatonia, as well as hysterical or neurologic disorders. A high index of suspicion, a careful history, a review of records for use of these antiemetics, and a specific physical examination may be necessary to distinguish these drug side effects from other types of psychiatric syndromes. I wish to thank Troy L. Thompson, II, M.D., Professor and Chairman of Psychiatry at Jefferson Medical College, and Howard L. Field, M.D., Professor and Director of Consulfafion-Liaison Psychiaty at ]ef@son Medical College, for their useful commenta y on an earlier version of this manuscript.
Extrapyramidal
References 1. Hyser CL, Drake ME Jr: Myoclonus induced by metoclopramide therapy. Arch Intern Med 143:22012202,- 1983 2. Brunton L: Agents affecting gastrointestinal water flux and motilitv, digestants, and bile acids. In Gilman AG, Rall TW, ties A, Taylor I’ (eds). The Pharmacologic Basis of Therapeutics, 8th ed. New York, Pergaman Press, 1990, pp 914-932 dis3. Miller LG, Jankovic J: Metoclopramide-induced orders. Clinical findings with a review of the literature. Arch Intern Med 149:2486-2492, 1989 4. Pall HS, Williams AC: Extrapyramidal disturbances caused by inappropriate prescribing. Br Med J-Clin Res 295:30-l, 1987 5. Boston Collaborative Drug Surveillance Program. Drug-induced extrapyramidal symptoms. A cooperative study. JAMA. 2243889-891, 1973 6. Ponte CD, Nappi JM: Review of a new gastrointestinal drug-metoclopramide. Am J Hosp Pharm 38:829-833, 1981 7. Physians’ Desk Reference@ 46th ed: Medical Economics Co, Oradell, NJ. 1992, pp 2201-2203 8. Physicians’ Desk Reference@ 46th ed: Medical Economics Co Oradell, NJ. 1992, pp 1869-1871 9. Olver IN, Webster LK, Bishop JF, Clark J, Hillcoat BL: A dose-finding study of prochlorperazine as an antiemetic for cancer chemotherapy. Eur Cancer Clin Oncol25:1457-1461, 1989 10. DeSilva KL, Muller PJ, Pearce J: Acute drug-induced extrapyramidal syndromes. Practitioner 211:316320, 1973 11. Weiden PJ, Mann JJ, Hass G, Mattsson M, Frances A: Clinical nonrecognition of neuroleptic-induced
12.
13.
14.
15.
16.
17.
18.
19.
Side Effects of Antiemetics
movement disorders: a cautionary study. Am J of Psychiatry 144:1148-1153, 1987 Brown CS, Wittkowsky AK, Bryant SG: Neurolysticinduced catatonia after abrupt withdrawal of amantadine during neuroleptic therapy. Pharmacotherapy 6:193-195, 1986 Bateman DN, Darling WM, Boys R, Rawlins MD: Extrapyramidal reactions to metoclopramide and prochlorperazine. Quart J Med 71:307-311, 1989 Swenson RJ, Erman M, Labelle J, Dimsdale JE: Extrapyramidal reactions: neuropsychiatry mimics in patients with AIDS. Gen Hosp Psych 11:248-253, 1989 Hollander H, Golden J, Mendelson F, Cortland D: Extrapyramidal symptoms in AIDS patients given low-dose metoclopramide or chlorpromazine. Lancet 2:1186, 1985 Sirota R, Kimmel I’, Trichtinger M, Diamond F, Stein H, Yudis M: Metoclopramide-induced parkinsonism in hemodialysis patients. Arch Intern Med 146:20702071, 1986 Albibi R, McCallum RW: Metoclopramide: pharmacology and clinical application. Am Intern Med 98:86-95, 1983 Roila F, Tonato M, Basurto C, et al: Protection from nausea and vomiting in cisplatin-treated patients: high-dose metoclopramide combined with methyl prednisone versus metoclopramide combined with dexamethasone and diphenhydramine. A study of the Italian Oncology Group for clinical research. J Clin Oncol7:1693-1700, 1989 Lazarra R, Stoudemire A, Manning D, et al: Metoclopramide-induced tardive dyskinesia: a case report. Gen. Hosp. Psychiatry 8:107-109, 1986
195
Abstract: Although extrapyramidal side effects of two commonly used antiemetics, metoclopramide and prochlorperazine, are well known, it may be difficult for even the experienced practitioner to distinguish some of these extrapyramidal reactions from such psychiatric symptoms as anxiety, depression, or catatonia. Certain patient groups have increased susceptibility to these extrapyramidal reactions, including patients under 30, those with AIDS, those with renal disease, oncology patients, and possibly women. Physicians should maintain a high index of suspicion for depression, anxiety, or catatonia if their patients are taking antiemetics. These symptoms may be extrapyramidal side effects of the antiemetic rather than indications of a prima y mental disorder.
Introduction Metoclopramide and prochlorperazine are commonly used antiemetics in both inpatient and outpatient settings. Prochlorperazine is a phenothiazine, whereas metoclopramide is a benzamide derivative of methyldopa, but the latter has a side chain that resembles the phenothiazines. Among the side effects described in the literature are akathisia, parkinsonism, and acute dystonias and dyskinesias. [l-4] The overall incidence of such extrapyramidal reactions due to these antiemetics in patients without oncologic disorders is up to 2%. [3,5,6] Certain patient groups exhibit increased susceptibility, including patients under 30, those with AIDS, renal disease, cancer, and possibly women. The usual dose of prochlorperazine is 5-10 mg P.O.
or I.M. every three-four hours with a recommended maximum total dose of 40 mg. The total maximum intravenous dose is also 40 mg [7]. The usual dose of metoclopramide for postoperative nausea and vomiting is lo-20 mg I.M. every 4-6 hours; no upper limit is listed by the manufacturer. For chemotherapy patients, however, an intravenous infusion of l-2 mg/kg is recommended [8]. Extrapyramidal side effects from these antiemetics occurred in 100% of patients in one oncology study [9]. Because the doses used to control emesis in cancer patients are generally higher than the recommended therapeutic dose, it is unclear whether the debilitated physical state of the patient is the primary contributing factor to the development of these side effects or whether these side effects are dose related. Unfortunately, the presentation of antiemeticinduced extrapyramidal side effects may vary widely and can mimic a number of primary psychiatric conditions. In a recent 2-month period, the psychiatric service at our institution was consulted on three medical patients: the first for anxiety, the second for depression, and the third for evaluation of catatonia. In each of these cases, the presumed psychiatric condition was actually an extrapyramidal reaction to prochlorperazine, metoclopramide, or a combination of the two.
Case Reports Case 1
From the Division of Psychiatry and Human Behavior, Jefferson Medical College, Philadelphia, Pennsylvania. Address reprint requests to: Carla Rodgers, M. D., 1652 Thompson Building, 1020 Sansom Street, Philadelphia, PA.
192 ISSN 0X3-8343/92/$5.00
A 34-year-old Hispanic male with AIDS had been admitted for fever, night sweats, blurred vision, weight loss, and anorexia. The patient also comGeneralHospitalPsychiatry14, 192-195, 1~2 0 1992 EIsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010
Extrapyramidal
plained of nausea and vomiting with hematemesis. Blood, sputum, and urine cultures were all negative. The patient had magnetic resonance imaging and computed tomography of the head which were also negative. He was started on naproxen 375 mg twice a day for the fever, which was attributed to the HIV infection. Additional standing medications included multivitamins P. o. daily; acyclovir 200 mg P.O. four times a day; megestrol acetate 80 mg P.O. four times a day; and clotrimazole troche five times per day. The patient was scheduled to receive 2,3 dideoxyinosine, an investigational drug, which was withheld because emesis persisted: to treat this problem, prochlorperazine 10 mg every six hours P.O. or I.M. was prescribed. Four days later, the unit social worker noted a significant change in the patient’s mental status. She stated he had a vacuous look, a flattened affect, and tremulous lips and hands. The following day the patient received an additional 10 mg of metoclopramide intravenously for continued vomiting. Psychiatry was then consulted to evaluate the patient’s increasing withdrawal and catatonia. Psychiatric examination revealed a coarse resting tremor, masked face, cogwheeling in both upper extremities (right greater than left), and a festinating gait. The patient denied suicidal or homicidal ideation and stated he wanted to go home. He would not answer any other questions, but it was not clear whether he was unwilling or unable to so. It was determined that the cause of his psychiatric symptoms was actually severe parkinsonism, and both prochlorperazine and metoclopramide were immediately discontinued. The patient then received two doses of diphenhydramine hydrochloride 50 mg I.M., and during the next day he recovered significantly from antiemetic-induced catatonia. At that time a repeat mental status examination was conducted, and revealed the patient to be oriented to time, place, and person, with no suicidal ideation, auditory or visual hallucinations, and no evidence of delusional thinking or a formal thought disorder. The tremor, cogwheeling, and festinating gait were significantly diminished, and he was discharged 5 days later.
Case 2 A 70-year-old white female with recurrent melanoma was admitted for chemotherapy with cisplatin 40 mg I.V. daily, and dacarbazine 350 mg I.V.
Side Effects of Antiemetics
daily. To diminish the side effects of nausea, her physicians prescribed metoclopramide 75 mg I.V. just prior to and every 6 hours during the chemotherapy. Two days later, the patient became increasingly anxious, for which psychiatry was consulted. When seen, the patient had akathisia, masked face, cogwheeling bilaterally, and involuntary leg movements. She felt increasingly restless and anxious but denied suicidal ideation. Psychiatry diagnosed an organic anxiety disorder, akathisia, and parkinsonism, all secondary to metoclopramide, which was then discontinued. The patient then received lorazepam 0.5 mg every 6 hours to manage her nausea, vomiting, anxiety, and akathisia, and was discharged after her course of chemotherapy without further side effects.
Case 3 A 1Pyear old Asian female was admitted for resection of a benign hepatic mass, and underwent left hepatic lobectomy without complications. Her postoperative medication included cefazolin sodium 1 g I.V. every six hours, ranitidine hydrochloride 150 mg P.O. twice/day, and aluminum and magnesium hydroxide suspension 30 cc P. o. every 4 hours. The patient received morphine sulfate 58 mg I.M. every two-three hours as needed for pain until the fourth postoperative day, when it was discontinued. She had an episode of emesis on the fifth postoperative day, for which she was given one dose of metoclopramide, 10 mg P.O. She continued to have nausea on the sixth postoperative day and received prochlorperazine, 10 mg I.M. During the evening, the nursing staff reported that the patient was anxious, shifting restlessly back and forth and unable to stay in bed. Although the patient denied further nausea, she was given another lo-mg injection of prochlorperazine the next evening. The following day psychiatry was consulted to evaluate the patient’s depression and anxiety. She paced back and forth in the hallway and was unable to sit or to stop pacing during the evaluation. She stated that she was so agitated she felt like jumping out the window. Although she denied suicidal ideation and stated her mood was not depressed, she was unable to assure us that she would not jump. The patient had received two doses of lorazepam 0.5 mg P.o., but reported no relief of anxiety. We diagnosed severe akathisia and recommended one-to-one nursing care. We rec-
193
C. Rodgers
ommended that both metoclopramide and prochlorperazine be immediately discontinued, and placed the patient on alprazolam 0.25 mg four times a day. Follow-up 24 hours later revealed significant improvement, with the patient reporting decreased restlessness and no further impulse to jump out the window. She was discharged in good condition 1 week after the initial psychiatric consult.
Comment Three cases of extrapyramidal side effects due to the antiemetics metoclopramide and prochlorperzine have been presented. These cases were initially thought to be primary psychiatric disorders of anxiety, depression, and catatonia. Misdiagnosis and underdiagnosis of extrapyramidal side effects have been widely reported [lo]. In a study of 48 patients on antipsychotic medication that has similar central dopamine-blocking action as these two antiemetics, treating physicians identified extrapyramidal reactions in 45% of patients, and the study found that 100% of these patients were afflicted to some degree with extrapyramidal side effects [ll]. Neuroleptic-induced catatonia, which can be treated with amantadine, has also been reported. It is hypothesized that this syndrome may represent part of a continuum of dopamine blockade, which also includes the life-threatening neuroleptic malignant syndrome [12]. These side effects have also been reported to be diagnosed as hysteria, epilepsy, and meningitis [4]. A large prospective study by Bateman et al. [13] on first-time users of both antiemetics (metoclopramide and prochloperazine) concluded that marked extrapyramidal reactions are more common than expected and seem to be age-related: an incidence of l/81 patients less than 30 years of age, and l/572 patients over age 30. According to the authors, this study may have underestimated the actual incidence. Bateman, et al. have not found gender to correlate with increased risk. Miller and Jankovic [3], however, conclude that women are more susceptible to metoclopramide-induced movement disorders. They hypothesize that the mechanism of action may be related to continuous blockade of D2 receptors by estrogen, resulting in increased sensitivity of these receptors in women. It is also possible that a genetic predisposition may exist [3]. In addition to age and gender, previous case 194
reports cite increased susceptibility in physically compromised patients, including those with AIDS [14,15]. Specific mechanisms are not yet known, but increased sensitivity of AIDS patients to developing these extrapyramidal side effects may relate to basal ganglia damage by the retrovirus [15]. Renal disease is another impairment that may increase a patient’s susceptibility. One report describes hemodialysis patients at increased risk of developing extrapyramidal signs on metoclopramide [16]. As this drug is excreted by the kidney, impaired renal function may result in elevated metoclopramide levels, producing more frequent extrapyramidal reactions in these patients [16,17]. Oncology patients also seem to be more likely to develop extrapyramidal side effects to these antiemetics, but it is unclear if this susceptibility is the result of high doses-often four to seven times the usual therapeutic dose-which are used to control nausea and vomiting during chemotherapy. Extrapyramidal reactions to prochlorperazine have been reported to occur more often at higher dosages [9], whereas other investigators have found no relationship between the incidence of extrapyramidal reactions and either dose or plasma concentration of metoclopramide [ 181. Although certain groups of patients seem to be at increased risk, the development of extrapyramidal reactions to these antiemetics may be idiosyncratic. This assertion is supported by two suicide attempts involving the ingestion of 360 and 800 mg of metoclopramide, respectively, in which neither patient developed extrapyramidal signs [6]. It should also be noted that long-term use of metoclopramide can cause tardive dyskinesia, even at recommended therapeutic doses [19]. In summary, physicians using metoclopramide and/or prochlorperazine should be aware that extrapyramidal reactions can occur in sensitive patients, even at usual therapeutic doses. These reactions can present and masquerade as anxiety, depression, and catatonia, as well as hysterical or neurologic disorders. A high index of suspicion, a careful history, a review of records for use of these antiemetics, and a specific physical examination may be necessary to distinguish these drug side effects from other types of psychiatric syndromes. I wish to thank Troy L. Thompson, II, M.D., Professor and Chairman of Psychiatry at Jefferson Medical College, and Howard L. Field, M.D., Professor and Director of Consulfafion-Liaison Psychiaty at ]ef@son Medical College, for their useful commenta y on an earlier version of this manuscript.
Extrapyramidal
References 1. Hyser CL, Drake ME Jr: Myoclonus induced by metoclopramide therapy. Arch Intern Med 143:22012202,- 1983 2. Brunton L: Agents affecting gastrointestinal water flux and motilitv, digestants, and bile acids. In Gilman AG, Rall TW, ties A, Taylor I’ (eds). The Pharmacologic Basis of Therapeutics, 8th ed. New York, Pergaman Press, 1990, pp 914-932 dis3. Miller LG, Jankovic J: Metoclopramide-induced orders. Clinical findings with a review of the literature. Arch Intern Med 149:2486-2492, 1989 4. Pall HS, Williams AC: Extrapyramidal disturbances caused by inappropriate prescribing. Br Med J-Clin Res 295:30-l, 1987 5. Boston Collaborative Drug Surveillance Program. Drug-induced extrapyramidal symptoms. A cooperative study. JAMA. 2243889-891, 1973 6. Ponte CD, Nappi JM: Review of a new gastrointestinal drug-metoclopramide. Am J Hosp Pharm 38:829-833, 1981 7. Physians’ Desk Reference@ 46th ed: Medical Economics Co, Oradell, NJ. 1992, pp 2201-2203 8. Physicians’ Desk Reference@ 46th ed: Medical Economics Co Oradell, NJ. 1992, pp 1869-1871 9. Olver IN, Webster LK, Bishop JF, Clark J, Hillcoat BL: A dose-finding study of prochlorperazine as an antiemetic for cancer chemotherapy. Eur Cancer Clin Oncol25:1457-1461, 1989 10. DeSilva KL, Muller PJ, Pearce J: Acute drug-induced extrapyramidal syndromes. Practitioner 211:316320, 1973 11. Weiden PJ, Mann JJ, Hass G, Mattsson M, Frances A: Clinical nonrecognition of neuroleptic-induced
12.
13.
14.
15.
16.
17.
18.
19.
Side Effects of Antiemetics
movement disorders: a cautionary study. Am J of Psychiatry 144:1148-1153, 1987 Brown CS, Wittkowsky AK, Bryant SG: Neurolysticinduced catatonia after abrupt withdrawal of amantadine during neuroleptic therapy. Pharmacotherapy 6:193-195, 1986 Bateman DN, Darling WM, Boys R, Rawlins MD: Extrapyramidal reactions to metoclopramide and prochlorperazine. Quart J Med 71:307-311, 1989 Swenson RJ, Erman M, Labelle J, Dimsdale JE: Extrapyramidal reactions: neuropsychiatry mimics in patients with AIDS. Gen Hosp Psych 11:248-253, 1989 Hollander H, Golden J, Mendelson F, Cortland D: Extrapyramidal symptoms in AIDS patients given low-dose metoclopramide or chlorpromazine. Lancet 2:1186, 1985 Sirota R, Kimmel I’, Trichtinger M, Diamond F, Stein H, Yudis M: Metoclopramide-induced parkinsonism in hemodialysis patients. Arch Intern Med 146:20702071, 1986 Albibi R, McCallum RW: Metoclopramide: pharmacology and clinical application. Am Intern Med 98:86-95, 1983 Roila F, Tonato M, Basurto C, et al: Protection from nausea and vomiting in cisplatin-treated patients: high-dose metoclopramide combined with methyl prednisone versus metoclopramide combined with dexamethasone and diphenhydramine. A study of the Italian Oncology Group for clinical research. J Clin Oncol7:1693-1700, 1989 Lazarra R, Stoudemire A, Manning D, et al: Metoclopramide-induced tardive dyskinesia: a case report. Gen. Hosp. Psychiatry 8:107-109, 1986
195