- Email: [email protected]
Acute dystonic reaction due to diazepam
The Journal
of Emergency
Medune.
Vol 6, pp 491-493,
1988
ACUTE DYSTONIC
Printed in the USA
REACTION
Edmond A. Hooker, Reprint
address.
Edmond
A. Hooker,
MD,
University of Louisville, Louisville, Kentucky MD, Department of Emergency Medicine, University
k:
1988
Pergamon
Press plc
MD
of Louisville,
Loulsville,
KY 40292
approximately nine hours prior to arrival. Medical and psychiatric past history were noncontributory. The patient’s vital signs were oral temperature 35.8”C (965°F); pulse 102; B/P 130/90 mmHg; and respiratory rate 20. Neurological examination was normal. Physical examination was normal except for muscle stiffness in the neck. The patient began developing torticollic posturing with her neck drawn to the right and inability to relax her neck muscles. Symptoms resolved within five minutes of intravenous administration of diphenhydramine 50 mg. The patient was discharged to home on a three-day course of oral diphenhydramine.
0 Keywords - dystonic reaction; dyskinesia; extrapyramidal syndrome; diazepam
INTRODUCTION Drug-induced dyskinesias occur commonly with use of neuroleptic agents. These extrapyramidal movement disorders, consisting of involuntary motor movements, occur in approximately 10% of all patients treated with neuro1eptics.r Other agents causing apparent dystonic reactions include levodopa, bromocriptine, lithium, metoclopramide, diphenylhydantoin, carbamazepine, primidone, baclofen, phenobarbital, tricyclic antidepressants, amphetamines, and diphenhydramine. There have been thirteen previous cases of extrapyramidal syndromes associated with diazepam therapy reported in the literature.3-6 We report two patients who experienced apparent acute dystonic reactions after diazepam ingestion. One was confirmed by toxicologic analysis.
Case 2 A 39-year-old female came to the hospital complaining of generalized “muscle spasms.” She denied recent drug ingestion. Psychiatric history included an admission two years previously for major depression. The patient reported that similar symptoms had developed three years earlier after ingesting diazepam. The patient’s vital signs were oral temperature 35.2”C (95.3”F); pulse 82; B/P 153/90 mmHg; and respiratory rate 11. Physical examination was remarkable for involuntary repetitive tongue protusions. The buccolingual dystonic reaction resolved within five minutes of intravenous administration of diphenhydramine 50 mg. The toxicology report showed diazepam, nicotine, and caffeine in the serum, and ethanol and nicotine in the urine. No neuroleptics were identified. The patient was discharged to home on a threeday course of oral diphenhydramine. Past medical records revealed a previous presentation to the emergency department three years earlier
Case I A 25year-old female arrived at the emergency department complaining of inability to move her neck. She admitted to ingestion of three 10 mg diazepam (Valium@) and four caffeine pills (unknown amount)
-
CopyrIght
DUE TO DIAZEPAM
and Daniel F. Danzl,
0 Abstract-Two cases of acute dystonic reactions associated with diazepam ingestion are reported. This report is a brief review of drug-induced extra-pyramidal syndromes, and a mechanism for diazepam-induced dystonic reactions is proposed. Intravenous dipbenhydramine was successful in treating both patients.
l
Toxicology-one of the most critical and challenging areas confronting the emergency department staff -is coordinated by Kenneth Ku&, MD, of the Rocky Mountain Poison Center.
RECEIVED: 8 June 1987; SECOND SUBMISSION RECENED: ACCEPTED: 5 November 1987
22 September 1987 491
0736-4679/88 $3.00 + .OO
Edmond
492
with complaints of a “thick tongue” and “neck pulls to left.” The patient had claimed that she had ingested only “Valium,“@ and symptoms resolved after intravenous administration of diphenhydramine. It was assumed she had probably ingested haloperidol instead of diazepam since it is commonly sold as Valium@ on the street.
DISCUSSION There are three distinct extrapyramidal syndromes: parkinsonism, akathisia, and dystonia.’ Parkinsonism is similar to idiopathic Parkinson’s syndrome. Tremor, rigidity, mask-like facial expression, and bradykinesia may be present alone or in combination. The tremor is rhythmical, alternately affecting flexors and extensors, and worse at rest. Rigidity is readily evident on passive movement at a joint, and is manifested by a series of incomplete jerks (cog-wheel rigidity). Bradykinesias are manifested by slow initiation of movement and sudden unexpected arrests of volitional movements. Akathisia, the second extrapyramidal syndrome, is a subjective feeling of restlessness. The patient does not want to sit down and will tend to march in place. When sitting, the patient will constantly shift his legs and appear very anxious. The exact classification of dystonic reactions is confusing since some authors consider dyskinesia synonymous with dystonia.8 Others subdivide dystonic reactions into dystonias, which are prolonged abnormal tonic contractions of muscles, and dyskinesias, which are clonic muscular contractions.9 Most authors, however, do further subdivide dystonic reactions. Buccolingual dystonia, the most common form, consists of a combination of dysphagia, dysarthria, mutism, trismus, protruding or retracting of the tongue, facial grimacing, and facial distortions. The second most common form, torticollic dystonia, consists of contraction of the neck muscles. Other less common forms include oculogyric, opisthotonic and tortipelvic dystonia.lO The differential diagnoses of these reactions include tetanus, stroke, encephalitis, meningitis, drug intoxication, arachnidism, calcium deficiency, and hysterical conversion reaction. The symptoms of dystonic reactions complicating drug therapy begin within the first four and one half days of treatment in over 90% of patients.* The physical examination is normal except for intermittent and bizarre neuromuscular manifestations. A literature review of extrapyramidal movement disorders attributed to diazepam revealed thirteen potential cases. Kaplan reported one case of a buccolin-
A. Hooker and Daniel F. Danzl
gual dystonic reaction.2 Dystonia was reported as a side effect of diazepam therapy in anxiety and brain fag syndrome.3.4 Another report reviewed six cases of movement disorders that the author classified as tardive dyskinesia.5 Of the six cases, two had dyskinesia, which began after five months and four years of therapy. The other four cases, although not reported in detail, appeared to have been acute dystonic reactions and not “tardive” dyskinesia. There was a report of four cases of drug-induced parkinsonism after treatment with high-dose diazepam.6 All of these patients had parkinsonian symptoms that started later than one week after initiation of therapy and would not be well classified as an acute dystonic reaction. We report two apparent benzodiazepine-induced acute dystonic reactions. The first presented as an acute torticollic dystonia. Some authors have observed that patients presenting with ingestion of small blue tablets have often ingested Haldol@ and not [email protected]’J~‘lBoth tablets are small and blue with a central hole. The first patient stated that she received the “Valium@” from a friend who had a prescription. The second patient had diazepam confirmed by a toxicologic screen. Of interest, this patient was evaluated three years previously with a similar torticollic dystonic reaction attributed to haloperidol since the patient was unsure what she had taken. The exact mechanism for acute dystonic reactions is not clear. According to the cholinergic dopaminergic neurotransmitter model, there is a balance between acetylecholine and dopamine. In the extrapyramidal system, acetylcholine is an excitatory neurotransmitter and dopamine is an inhibitory neurotransmitter. Neuroleptics block the dopamine receptors. This allows acetylcholine to become dominant, resulting in an acute dystonic reaction.‘O Diazepam facilitates presynaptic inhibition in a manner similar to gamma-aminobutyric acid (GABA). This is an effect that could account for the pharmacological actions of benzodiazepines. However, by altering the balance of neurotransmitters in the brain, extrapyramidal syndromes may be induced.
CONCLUSION Acute dystonic reactions, although most frequently associated with neuroleptics, can be seen with many other agents. We report two cases of acute dystonic reactions to diazepam. One of the patients had isolated diazepam ingestion confirmed by toxicologic testing. Diazepam should be considered as a possible cause of acute dystonic reactions. Standard anticholinergic therapy is indicated in these cases.
Acute Dystonic Reaction
493
REFERENCES 1. Sovner R, DiMascio A: Extrapyramidal syndromes and other neurological side effects of psychotropic drugs, in Lipton MA, DiMascio A, Killam KF (ed): Psychopharmacology: a generution of progress, New York, Raven Press, 1978. 2. Kaplan SR, Murkotsky C: Oral-buccal dyskinesia symptoms associated with low-dose benzodiazepine treatment. Am JPsychiatry 1978; 135:1558-1559. 3. Anumonye A: Treatment of ‘brain fag’ syndrome. Current Medical Research and Opinion 1975; 3:367-370. 4. Anhalt HS, Young RY, Roginshy M: Double-blind comparison at ketazolam, diazepam and placebo in one-a-day vs. T.I.D. Dosing. J Clin Psychiatr 1980; 41:386-392. 5. Rosenbaum AH, DeLaFuente JR: Benzodiazepines and tardive dyskinesia. Luncet 1979; 2:900. 6. Suranyi-Cadotte BE, Nestoros JN, Nair NPV, et al: Parkinsonism induced by high doses of diazepam. Biol Psychiatry 1985; 20:451-460.
7. Keepers GA, Casey DE: Clinical management of acute neuroleptic-induced extrapyramidal syndromes. Curr Psychiutr Ther 1986; 26:13,9-157. 8. Ayd FS: A survey of drug induced extrapyramidal reactions. JAMA 1961; 175:1054-1060. 9. Greenblatt DJ, Shader RI, DiMascio A: Extrapymmidal effects, in Shader RI, DiMascio A (ad): Psychotropic drug side effects: clinical and theoretical perspectives. Baltimore, Williams and Wilkins, 1970. 10. Lee AS: Drug induced dystonic reactions. MCEP 1977; 6:351354. 11. Bryant SO: Street drug misrepresentation. JAMA 1970; 144: 2160-2164. 12. Snyder SH, Enna SJ, Young AB: Brain mechanisms associated with therapeutic actions of benzodiazepines: focus on neurotransmitters. Am JPsychiatry 1977; 174~662-664.
of Emergency
Medune.
Vol 6, pp 491-493,
1988
ACUTE DYSTONIC
Printed in the USA
REACTION
Edmond A. Hooker, Reprint
address.
Edmond
A. Hooker,
MD,
University of Louisville, Louisville, Kentucky MD, Department of Emergency Medicine, University
k:
1988
Pergamon
Press plc
MD
of Louisville,
Loulsville,
KY 40292
approximately nine hours prior to arrival. Medical and psychiatric past history were noncontributory. The patient’s vital signs were oral temperature 35.8”C (965°F); pulse 102; B/P 130/90 mmHg; and respiratory rate 20. Neurological examination was normal. Physical examination was normal except for muscle stiffness in the neck. The patient began developing torticollic posturing with her neck drawn to the right and inability to relax her neck muscles. Symptoms resolved within five minutes of intravenous administration of diphenhydramine 50 mg. The patient was discharged to home on a three-day course of oral diphenhydramine.
0 Keywords - dystonic reaction; dyskinesia; extrapyramidal syndrome; diazepam
INTRODUCTION Drug-induced dyskinesias occur commonly with use of neuroleptic agents. These extrapyramidal movement disorders, consisting of involuntary motor movements, occur in approximately 10% of all patients treated with neuro1eptics.r Other agents causing apparent dystonic reactions include levodopa, bromocriptine, lithium, metoclopramide, diphenylhydantoin, carbamazepine, primidone, baclofen, phenobarbital, tricyclic antidepressants, amphetamines, and diphenhydramine. There have been thirteen previous cases of extrapyramidal syndromes associated with diazepam therapy reported in the literature.3-6 We report two patients who experienced apparent acute dystonic reactions after diazepam ingestion. One was confirmed by toxicologic analysis.
Case 2 A 39-year-old female came to the hospital complaining of generalized “muscle spasms.” She denied recent drug ingestion. Psychiatric history included an admission two years previously for major depression. The patient reported that similar symptoms had developed three years earlier after ingesting diazepam. The patient’s vital signs were oral temperature 35.2”C (95.3”F); pulse 82; B/P 153/90 mmHg; and respiratory rate 11. Physical examination was remarkable for involuntary repetitive tongue protusions. The buccolingual dystonic reaction resolved within five minutes of intravenous administration of diphenhydramine 50 mg. The toxicology report showed diazepam, nicotine, and caffeine in the serum, and ethanol and nicotine in the urine. No neuroleptics were identified. The patient was discharged to home on a threeday course of oral diphenhydramine. Past medical records revealed a previous presentation to the emergency department three years earlier
Case I A 25year-old female arrived at the emergency department complaining of inability to move her neck. She admitted to ingestion of three 10 mg diazepam (Valium@) and four caffeine pills (unknown amount)
-
CopyrIght
DUE TO DIAZEPAM
and Daniel F. Danzl,
0 Abstract-Two cases of acute dystonic reactions associated with diazepam ingestion are reported. This report is a brief review of drug-induced extra-pyramidal syndromes, and a mechanism for diazepam-induced dystonic reactions is proposed. Intravenous dipbenhydramine was successful in treating both patients.
l
Toxicology-one of the most critical and challenging areas confronting the emergency department staff -is coordinated by Kenneth Ku&, MD, of the Rocky Mountain Poison Center.
RECEIVED: 8 June 1987; SECOND SUBMISSION RECENED: ACCEPTED: 5 November 1987
22 September 1987 491
0736-4679/88 $3.00 + .OO
Edmond
492
with complaints of a “thick tongue” and “neck pulls to left.” The patient had claimed that she had ingested only “Valium,“@ and symptoms resolved after intravenous administration of diphenhydramine. It was assumed she had probably ingested haloperidol instead of diazepam since it is commonly sold as Valium@ on the street.
DISCUSSION There are three distinct extrapyramidal syndromes: parkinsonism, akathisia, and dystonia.’ Parkinsonism is similar to idiopathic Parkinson’s syndrome. Tremor, rigidity, mask-like facial expression, and bradykinesia may be present alone or in combination. The tremor is rhythmical, alternately affecting flexors and extensors, and worse at rest. Rigidity is readily evident on passive movement at a joint, and is manifested by a series of incomplete jerks (cog-wheel rigidity). Bradykinesias are manifested by slow initiation of movement and sudden unexpected arrests of volitional movements. Akathisia, the second extrapyramidal syndrome, is a subjective feeling of restlessness. The patient does not want to sit down and will tend to march in place. When sitting, the patient will constantly shift his legs and appear very anxious. The exact classification of dystonic reactions is confusing since some authors consider dyskinesia synonymous with dystonia.8 Others subdivide dystonic reactions into dystonias, which are prolonged abnormal tonic contractions of muscles, and dyskinesias, which are clonic muscular contractions.9 Most authors, however, do further subdivide dystonic reactions. Buccolingual dystonia, the most common form, consists of a combination of dysphagia, dysarthria, mutism, trismus, protruding or retracting of the tongue, facial grimacing, and facial distortions. The second most common form, torticollic dystonia, consists of contraction of the neck muscles. Other less common forms include oculogyric, opisthotonic and tortipelvic dystonia.lO The differential diagnoses of these reactions include tetanus, stroke, encephalitis, meningitis, drug intoxication, arachnidism, calcium deficiency, and hysterical conversion reaction. The symptoms of dystonic reactions complicating drug therapy begin within the first four and one half days of treatment in over 90% of patients.* The physical examination is normal except for intermittent and bizarre neuromuscular manifestations. A literature review of extrapyramidal movement disorders attributed to diazepam revealed thirteen potential cases. Kaplan reported one case of a buccolin-
A. Hooker and Daniel F. Danzl
gual dystonic reaction.2 Dystonia was reported as a side effect of diazepam therapy in anxiety and brain fag syndrome.3.4 Another report reviewed six cases of movement disorders that the author classified as tardive dyskinesia.5 Of the six cases, two had dyskinesia, which began after five months and four years of therapy. The other four cases, although not reported in detail, appeared to have been acute dystonic reactions and not “tardive” dyskinesia. There was a report of four cases of drug-induced parkinsonism after treatment with high-dose diazepam.6 All of these patients had parkinsonian symptoms that started later than one week after initiation of therapy and would not be well classified as an acute dystonic reaction. We report two apparent benzodiazepine-induced acute dystonic reactions. The first presented as an acute torticollic dystonia. Some authors have observed that patients presenting with ingestion of small blue tablets have often ingested Haldol@ and not [email protected]’J~‘lBoth tablets are small and blue with a central hole. The first patient stated that she received the “Valium@” from a friend who had a prescription. The second patient had diazepam confirmed by a toxicologic screen. Of interest, this patient was evaluated three years previously with a similar torticollic dystonic reaction attributed to haloperidol since the patient was unsure what she had taken. The exact mechanism for acute dystonic reactions is not clear. According to the cholinergic dopaminergic neurotransmitter model, there is a balance between acetylecholine and dopamine. In the extrapyramidal system, acetylcholine is an excitatory neurotransmitter and dopamine is an inhibitory neurotransmitter. Neuroleptics block the dopamine receptors. This allows acetylcholine to become dominant, resulting in an acute dystonic reaction.‘O Diazepam facilitates presynaptic inhibition in a manner similar to gamma-aminobutyric acid (GABA). This is an effect that could account for the pharmacological actions of benzodiazepines. However, by altering the balance of neurotransmitters in the brain, extrapyramidal syndromes may be induced.
CONCLUSION Acute dystonic reactions, although most frequently associated with neuroleptics, can be seen with many other agents. We report two cases of acute dystonic reactions to diazepam. One of the patients had isolated diazepam ingestion confirmed by toxicologic testing. Diazepam should be considered as a possible cause of acute dystonic reactions. Standard anticholinergic therapy is indicated in these cases.
Acute Dystonic Reaction
493
REFERENCES 1. Sovner R, DiMascio A: Extrapyramidal syndromes and other neurological side effects of psychotropic drugs, in Lipton MA, DiMascio A, Killam KF (ed): Psychopharmacology: a generution of progress, New York, Raven Press, 1978. 2. Kaplan SR, Murkotsky C: Oral-buccal dyskinesia symptoms associated with low-dose benzodiazepine treatment. Am JPsychiatry 1978; 135:1558-1559. 3. Anumonye A: Treatment of ‘brain fag’ syndrome. Current Medical Research and Opinion 1975; 3:367-370. 4. Anhalt HS, Young RY, Roginshy M: Double-blind comparison at ketazolam, diazepam and placebo in one-a-day vs. T.I.D. Dosing. J Clin Psychiatr 1980; 41:386-392. 5. Rosenbaum AH, DeLaFuente JR: Benzodiazepines and tardive dyskinesia. Luncet 1979; 2:900. 6. Suranyi-Cadotte BE, Nestoros JN, Nair NPV, et al: Parkinsonism induced by high doses of diazepam. Biol Psychiatry 1985; 20:451-460.
7. Keepers GA, Casey DE: Clinical management of acute neuroleptic-induced extrapyramidal syndromes. Curr Psychiutr Ther 1986; 26:13,9-157. 8. Ayd FS: A survey of drug induced extrapyramidal reactions. JAMA 1961; 175:1054-1060. 9. Greenblatt DJ, Shader RI, DiMascio A: Extrapymmidal effects, in Shader RI, DiMascio A (ad): Psychotropic drug side effects: clinical and theoretical perspectives. Baltimore, Williams and Wilkins, 1970. 10. Lee AS: Drug induced dystonic reactions. MCEP 1977; 6:351354. 11. Bryant SO: Street drug misrepresentation. JAMA 1970; 144: 2160-2164. 12. Snyder SH, Enna SJ, Young AB: Brain mechanisms associated with therapeutic actions of benzodiazepines: focus on neurotransmitters. Am JPsychiatry 1977; 174~662-664.