ATYPICAL
TARDIVE
DYSKINESIA
drug) was selected for multivariate analysis. The risk of dystonia was indeed related to dosage-patients who received daily doses of 300 mg or higher more commonly had dystonia. However, even when allowance was made for the influence of dosage, the sex- and age-specific side effects remained; i.e., dystonia was significantly more common in men and in younger patients. A dose effect has not been previously reported, although other studies (5, 6) have shown that the extrapyramidal reactions, as a group, arc more commonly observed with large, cumulative doses of phenothiazines. It is possible that other studies have failed to identify a dose effect because age and sex were not considered. As has been reported for extrapyramidal reactions in general (1, 7), the frequency of dystonia was highest for those who received haloperidol, generally high among phenothiazine recipients who were administered derivalives of piperazine, lower in those who received aliphatics, and still lower in those who received piperidines.
Atypical
Tardive
BY
A.
RONALD
MOLINE,
1968
reports
CRANE (1) reviewed the literature and found 23 encompassing over 500 patients of the symptom
cago,
534
Am
State
Psychiatric
I. Ayd FJ Jr: A survey of drug-induced extrapyramidal reactions. JAMA 175:1054-1060, 1961 2. Miller R: Drug surveillance utilizing epidemiologic methods: a report from the Boston Collaborative Drug Surveillance Program. Am J Hosp Pharm 30584-592, 1973 3. Cox DR: Analysis of Binary Data. London, Methuen, 1970 4. Chase TN: Drug-induced extrapyramidal disorders. Res PubI Assoc Res Nerv Ment Dis 50’.448-471, 1972 5. Guttman H, Lehmann HE, Ban TA: A survey of extrapyramidal manifestations in patients attending an after care clinic of a psychiatric hospital. Laval Medicine 41:449-455, 1970 6. Lehmann HE, Ban TA, Saxena BM: A survey of extrapyramidal manifestations in the inpatient population of a psychiatric hospital. Laval Medicine 41:909-916, 1970 7. Cole J, Clyde D: Extrapyramidal side effects and clinical response to phenothiazines. Rev Can Biol 20:565-574, 1961
cidence among brain-damaged individuals, and 3) women with the syndrome outnumbered men 3 to 1. He also pointed out, however, that there were reports of the syndrome in individuals as young as 27 and occasionally in patients who had received relatively little neuroleptic medication. One such patient was reported as developing this symptom complex after 4 months of therapy with 4 mg of trifluoperazine daily. In the past several years, there has been a proliferation of reports on this syndrome from many different countries confirming the central findings Crane reported (37). Many articles have also appeared in the literature affirming the irreversible nature of this phenomenon (8, 9) and the lack of response to various attempts at treatment (10, 11). The following is an unusual case in that it runs counter to the prevailing literature in several aspects: age of onset, dosage of neuroleptics preceding onset, and reversibility.
Institute,
1601
/32:5,
May
/975
REPORT
Pritzker Inpatient
W. Taylor St.,Chi-
A.B., a 19-year-old single male, was admitted
ric unit
J Psychiatry
for the re-
REFERENCES
CASE
Dr. Moline is Clinical Associate, Department of Psychiatry, School of Medicine, University of Chicago, and Chief, Adult Illinois Ill.60612.
too few recipients of thioxanthenes to represent stable frequencies.
M.D.
complex that Uhrbrand and Faurbyc (2) had labeled tardive dyskinesia 8 years earlier. In his review, Crane noted that 1) the syndrome occurred predominantly in older patients who had been on neuroleptic medication for prolonged periods and in high doses, 2) there was a higher in-
Service,
were rates
Dyskinesia
The author reports an atypical case oftardive dyskinesia in a I 9-year-old male who had been given relatively low dosages ofneuroleptic medicationfor less than 6 months. The symptoms cleared within 3 months after the medication was discontinued. The author reviews the literature regarding similar atypical cases and suggests that increased reporting and careful description of such cases might be useful in furthering our understanding of this syndrome.
IN
There action
because
of increasing
belligerence
to the psychiattoward his parents,
RONALD
culminating in his entering their bedroom one night and striking his mother. He had a history of markedly diminished functioning after high school (where he had achieved scholastic cxcellence), marked obsessive-compulsive ritualistic behavior, and constricted, repetitive ideational content. On admission, findings of a physical examination were unremarkable, with the cxception
of
moderate
dary sexual findings were paroxysmal areas. Skull negative. In his first 10 months
gynecomastia.
Other
primary
and
secon-
characteristics were normal. Routine laboratory unremarkable. An EEG was reported as showing low-voltage slow activity in both frontoparietal films and repeated neurological examinations were psychiatric
hospitalization
later.
He
was
he
(at
another
institution
been placed on 6 mg of tnfluopenazine daily and 100 mg of chlorpromazine daily. Two days later, for reasons not clean from the record, this regimen was discontinued and the patient was given 150 mg of pipenacetazine daily and 2 mg of benztropine daily. Piperacetazine was lowered to 100 mg daily after 10 days and to 75 mg daily 5 days
before),
discharged
had
on
this
medication
52 days
after
admission. During that hospitalization, he also occasionally received 75 mg of chlorpromazine as needed. According to the patient and his family, he continued to take his medication after discharge only sporadically, stopping altogether within a few weeks. At the time of his admission to our hospital, our impression was that the patient was in the early stages of a schizophrenic decompensation. He was placed on 100 mg of chlorpromazine at bedtime for 1 week. This was increased to 600 mg for 1 day and then discontinued and the patient was started on 7 mg of haloperidol and 1 mg of benztropine daily. Slightly more than 3 months after it was begun, the halopenidol was discontinued because of marked parkinsonism and a question of facio-lingual dyskinesia.
The
parkinsonism
improved
within
3 days,
but
the
oral symptoms worsened markedly, with protrusion of the tongue, chewing movements, movement of the chin, and contraction of the upper lip exposing the upper teeth. In addition, the patient exhibited rocking movements when seated, spoke for the first time of wanting to become a monk, and became preoccupied
with
evangelical
religious
tract
literature.
After 4 months, the mouth movements and mental status were greatly improved.’ The benztropine was also discontinued at that time, without apparent effect. Two months later, the symptoms had cleaned completely.
DISCUSSION
Crane (12) documented a case ofa 41-year-old woman who developed tardive dyskinesia after less than a year of neuroleptic medication, and whose symptoms subsequcntly cleared completely. Simpson (1 3) also reported the syndrome developing within 6 months of beginning treatment, with symptoms clearing after treatment was discontinued; however, the cases were not documented in his report. He also reported a neurotic patient who was given up to 10 mg of trifluoperazine for under a year and developed tardive dyskinesia that did not remit. Other authors have reported patients who developed the syndrome after relatively low dosages of neuroleptic medica-
‘At this point, Dr. G.E. Crane patient, confirming our diagnosis
visited the facility of tardive dyskinesia.
and
examined
this
A. MOLINE
tion, but who were on medication for more than I year(l4, 15). In 1968, Kline ( 16) questioned whether the irreversibility of this syndrome had been adequately documented. Although the subsequent literature has abundantly delineated an irreversible syndrome occurring in older patients on prolonged regimens of neuroleptic medication, the cases I have referred to, together with the case report in this paper, must also be accounted for in any attempt to define and theorize about tardive dyskinesia. Previous reports of exceptional cases have tended to be brief and fragmentary, possibly contributing to the tendency in the literature to equate the typical syndrome with the syndrome in its entirety. It is apparent that such a viewpoint could easily lend itself to faulty hypothesis formation, such as the assumption that the appearance of symptoms is indicative of irreversible changes in brain tissue. Further elucidation of this most recent of iatrogenic syndromes in psychiatry could perhaps result from increased careful description of exceptional cases in addition to studies ofthe typical syndrome.
REFERENCES I. Crane GE: Tardive dyskinesia: a review ofthe literature. Am J Psychiatry 124 (suppl):40-48, 1968 2. Uhrbrand L, Faurbye A: Reversible and irreversible dyskinesia aften treatment with perphenazine, chlorpromazine, reserpine, and ECT. Psychopharmacologica 1:408-415, 1960 3. Turek I, Kurland AA, Hanlon TE, et al: Tardive dyskinesia: its relation to neuroleptic and anti-depressant drugs. Br J Psychiatry 121:605-612, 1972 4. Gralewski Z: Chronic facio-lingual dyskinesia in patients treated with neuroleptics. Neurol Neurochir Pol 7:393-398, 1973 5. Tikare SK, Tikare SS: Extrapyramidal motor disorders due to toxic effect ofphenothiazines. J Indian Med Assoc 58:39-42, 1972 6. Dom R, Van Lommel R, Baro F: A quantitative study of neuroleptic-induced extrapyramidal symptoms and their response to dexetimide, a potent and long-acting antiparkinsonian agent. Acta Psychiatr Scand 47:399-410, 1971 7. Schiele BC, Gallant D, Simpson G, et al: Tardive dyskinesia: a persistent neurological syndrome associated with antipsychotic drug use. Ann Intern Med 79:99-100, 1973 8. Faurbye A, Rosch PJ, Peterson PB, et al: Neurological signs in pharmacological treatment of psychosis. Acta Psychiatr Scand 4&lO-27, 1964 9. Hunter R, Earl CJ, Janz D: A syndrome of abnormal movements and dementia in leucotomized patients treated with phenothiazines. J Neurol Neurosurg Psychiatry 27:219-222, 1964 10. Klawans HL Jr. McKendall RR: Observations on the effect of levodopa on tardive lingual-facial-buccal dyskinesia. J Neurol Sci 14:189-192, 1971 I I. Bullock RJ: Efficacy of thiopropazate dihydrochloride (Dartalan) in treating persisting phenothiazine-induced choreo-athetosis and akathesia. Med J Aust 2:314-316, 1972 12. Crane GE: Rapid reversal of tardive dyskinesia (ltr to ed). Am J Psychiatry l3&.1159, 1973 13. Simpson GM: Tardive dyskinesia (Itr to ed). Br J Psychiatry 122:618, 1973 14. Thornton WE, Thornton BP: Tardive dyskinesia and low dosage (ltr toed). AmJ Psychiatry 13th1401, 1973 15. Paulson GW: Movement disorders secondary to drugs. Ohio State Med J 69:685-686, 1973 16. Kline NS: On the rarity of irreversible oral dyskinesia following phenothiazines. Am J Psychiatry 124 (suppl): 48-54, 1968
A mJ
Psychiatry
132:5,
May
1975
535
TARDIVE
DYSKINESIA
drug) was selected for multivariate analysis. The risk of dystonia was indeed related to dosage-patients who received daily doses of 300 mg or higher more commonly had dystonia. However, even when allowance was made for the influence of dosage, the sex- and age-specific side effects remained; i.e., dystonia was significantly more common in men and in younger patients. A dose effect has not been previously reported, although other studies (5, 6) have shown that the extrapyramidal reactions, as a group, arc more commonly observed with large, cumulative doses of phenothiazines. It is possible that other studies have failed to identify a dose effect because age and sex were not considered. As has been reported for extrapyramidal reactions in general (1, 7), the frequency of dystonia was highest for those who received haloperidol, generally high among phenothiazine recipients who were administered derivalives of piperazine, lower in those who received aliphatics, and still lower in those who received piperidines.
Atypical
Tardive
BY
A.
RONALD
MOLINE,
1968
reports
CRANE (1) reviewed the literature and found 23 encompassing over 500 patients of the symptom
cago,
534
Am
State
Psychiatric
I. Ayd FJ Jr: A survey of drug-induced extrapyramidal reactions. JAMA 175:1054-1060, 1961 2. Miller R: Drug surveillance utilizing epidemiologic methods: a report from the Boston Collaborative Drug Surveillance Program. Am J Hosp Pharm 30584-592, 1973 3. Cox DR: Analysis of Binary Data. London, Methuen, 1970 4. Chase TN: Drug-induced extrapyramidal disorders. Res PubI Assoc Res Nerv Ment Dis 50’.448-471, 1972 5. Guttman H, Lehmann HE, Ban TA: A survey of extrapyramidal manifestations in patients attending an after care clinic of a psychiatric hospital. Laval Medicine 41:449-455, 1970 6. Lehmann HE, Ban TA, Saxena BM: A survey of extrapyramidal manifestations in the inpatient population of a psychiatric hospital. Laval Medicine 41:909-916, 1970 7. Cole J, Clyde D: Extrapyramidal side effects and clinical response to phenothiazines. Rev Can Biol 20:565-574, 1961
cidence among brain-damaged individuals, and 3) women with the syndrome outnumbered men 3 to 1. He also pointed out, however, that there were reports of the syndrome in individuals as young as 27 and occasionally in patients who had received relatively little neuroleptic medication. One such patient was reported as developing this symptom complex after 4 months of therapy with 4 mg of trifluoperazine daily. In the past several years, there has been a proliferation of reports on this syndrome from many different countries confirming the central findings Crane reported (37). Many articles have also appeared in the literature affirming the irreversible nature of this phenomenon (8, 9) and the lack of response to various attempts at treatment (10, 11). The following is an unusual case in that it runs counter to the prevailing literature in several aspects: age of onset, dosage of neuroleptics preceding onset, and reversibility.
Institute,
1601
/32:5,
May
/975
REPORT
Pritzker Inpatient
W. Taylor St.,Chi-
A.B., a 19-year-old single male, was admitted
ric unit
J Psychiatry
for the re-
REFERENCES
CASE
Dr. Moline is Clinical Associate, Department of Psychiatry, School of Medicine, University of Chicago, and Chief, Adult Illinois Ill.60612.
too few recipients of thioxanthenes to represent stable frequencies.
M.D.
complex that Uhrbrand and Faurbyc (2) had labeled tardive dyskinesia 8 years earlier. In his review, Crane noted that 1) the syndrome occurred predominantly in older patients who had been on neuroleptic medication for prolonged periods and in high doses, 2) there was a higher in-
Service,
were rates
Dyskinesia
The author reports an atypical case oftardive dyskinesia in a I 9-year-old male who had been given relatively low dosages ofneuroleptic medicationfor less than 6 months. The symptoms cleared within 3 months after the medication was discontinued. The author reviews the literature regarding similar atypical cases and suggests that increased reporting and careful description of such cases might be useful in furthering our understanding of this syndrome.
IN
There action
because
of increasing
belligerence
to the psychiattoward his parents,
RONALD
culminating in his entering their bedroom one night and striking his mother. He had a history of markedly diminished functioning after high school (where he had achieved scholastic cxcellence), marked obsessive-compulsive ritualistic behavior, and constricted, repetitive ideational content. On admission, findings of a physical examination were unremarkable, with the cxception
of
moderate
dary sexual findings were paroxysmal areas. Skull negative. In his first 10 months
gynecomastia.
Other
primary
and
secon-
characteristics were normal. Routine laboratory unremarkable. An EEG was reported as showing low-voltage slow activity in both frontoparietal films and repeated neurological examinations were psychiatric
hospitalization
later.
He
was
he
(at
another
institution
been placed on 6 mg of tnfluopenazine daily and 100 mg of chlorpromazine daily. Two days later, for reasons not clean from the record, this regimen was discontinued and the patient was given 150 mg of pipenacetazine daily and 2 mg of benztropine daily. Piperacetazine was lowered to 100 mg daily after 10 days and to 75 mg daily 5 days
before),
discharged
had
on
this
medication
52 days
after
admission. During that hospitalization, he also occasionally received 75 mg of chlorpromazine as needed. According to the patient and his family, he continued to take his medication after discharge only sporadically, stopping altogether within a few weeks. At the time of his admission to our hospital, our impression was that the patient was in the early stages of a schizophrenic decompensation. He was placed on 100 mg of chlorpromazine at bedtime for 1 week. This was increased to 600 mg for 1 day and then discontinued and the patient was started on 7 mg of haloperidol and 1 mg of benztropine daily. Slightly more than 3 months after it was begun, the halopenidol was discontinued because of marked parkinsonism and a question of facio-lingual dyskinesia.
The
parkinsonism
improved
within
3 days,
but
the
oral symptoms worsened markedly, with protrusion of the tongue, chewing movements, movement of the chin, and contraction of the upper lip exposing the upper teeth. In addition, the patient exhibited rocking movements when seated, spoke for the first time of wanting to become a monk, and became preoccupied
with
evangelical
religious
tract
literature.
After 4 months, the mouth movements and mental status were greatly improved.’ The benztropine was also discontinued at that time, without apparent effect. Two months later, the symptoms had cleaned completely.
DISCUSSION
Crane (12) documented a case ofa 41-year-old woman who developed tardive dyskinesia after less than a year of neuroleptic medication, and whose symptoms subsequcntly cleared completely. Simpson (1 3) also reported the syndrome developing within 6 months of beginning treatment, with symptoms clearing after treatment was discontinued; however, the cases were not documented in his report. He also reported a neurotic patient who was given up to 10 mg of trifluoperazine for under a year and developed tardive dyskinesia that did not remit. Other authors have reported patients who developed the syndrome after relatively low dosages of neuroleptic medica-
‘At this point, Dr. G.E. Crane patient, confirming our diagnosis
visited the facility of tardive dyskinesia.
and
examined
this
A. MOLINE
tion, but who were on medication for more than I year(l4, 15). In 1968, Kline ( 16) questioned whether the irreversibility of this syndrome had been adequately documented. Although the subsequent literature has abundantly delineated an irreversible syndrome occurring in older patients on prolonged regimens of neuroleptic medication, the cases I have referred to, together with the case report in this paper, must also be accounted for in any attempt to define and theorize about tardive dyskinesia. Previous reports of exceptional cases have tended to be brief and fragmentary, possibly contributing to the tendency in the literature to equate the typical syndrome with the syndrome in its entirety. It is apparent that such a viewpoint could easily lend itself to faulty hypothesis formation, such as the assumption that the appearance of symptoms is indicative of irreversible changes in brain tissue. Further elucidation of this most recent of iatrogenic syndromes in psychiatry could perhaps result from increased careful description of exceptional cases in addition to studies ofthe typical syndrome.
REFERENCES I. Crane GE: Tardive dyskinesia: a review ofthe literature. Am J Psychiatry 124 (suppl):40-48, 1968 2. Uhrbrand L, Faurbye A: Reversible and irreversible dyskinesia aften treatment with perphenazine, chlorpromazine, reserpine, and ECT. Psychopharmacologica 1:408-415, 1960 3. Turek I, Kurland AA, Hanlon TE, et al: Tardive dyskinesia: its relation to neuroleptic and anti-depressant drugs. Br J Psychiatry 121:605-612, 1972 4. Gralewski Z: Chronic facio-lingual dyskinesia in patients treated with neuroleptics. Neurol Neurochir Pol 7:393-398, 1973 5. Tikare SK, Tikare SS: Extrapyramidal motor disorders due to toxic effect ofphenothiazines. J Indian Med Assoc 58:39-42, 1972 6. Dom R, Van Lommel R, Baro F: A quantitative study of neuroleptic-induced extrapyramidal symptoms and their response to dexetimide, a potent and long-acting antiparkinsonian agent. Acta Psychiatr Scand 47:399-410, 1971 7. Schiele BC, Gallant D, Simpson G, et al: Tardive dyskinesia: a persistent neurological syndrome associated with antipsychotic drug use. Ann Intern Med 79:99-100, 1973 8. Faurbye A, Rosch PJ, Peterson PB, et al: Neurological signs in pharmacological treatment of psychosis. Acta Psychiatr Scand 4&lO-27, 1964 9. Hunter R, Earl CJ, Janz D: A syndrome of abnormal movements and dementia in leucotomized patients treated with phenothiazines. J Neurol Neurosurg Psychiatry 27:219-222, 1964 10. Klawans HL Jr. McKendall RR: Observations on the effect of levodopa on tardive lingual-facial-buccal dyskinesia. J Neurol Sci 14:189-192, 1971 I I. Bullock RJ: Efficacy of thiopropazate dihydrochloride (Dartalan) in treating persisting phenothiazine-induced choreo-athetosis and akathesia. Med J Aust 2:314-316, 1972 12. Crane GE: Rapid reversal of tardive dyskinesia (ltr to ed). Am J Psychiatry l3&.1159, 1973 13. Simpson GM: Tardive dyskinesia (Itr to ed). Br J Psychiatry 122:618, 1973 14. Thornton WE, Thornton BP: Tardive dyskinesia and low dosage (ltr toed). AmJ Psychiatry 13th1401, 1973 15. Paulson GW: Movement disorders secondary to drugs. Ohio State Med J 69:685-686, 1973 16. Kline NS: On the rarity of irreversible oral dyskinesia following phenothiazines. Am J Psychiatry 124 (suppl): 48-54, 1968
A mJ
Psychiatry
132:5,
May
1975
535
