Pain, 45 (1991) 167-170 e 1991 Elsevier Science Publishers ADONIS 0304395991001216
167 B.V. 0304-3959/91/$03.50
PAIN 01749
Clinical Note
Tardive dyskinesia and chronic pain I.M.C. Clarke Dept.
ofAnaesthesia,University of Calgary, and Pain Relief Clinic, Foothills Hospital, (Received
Summary
complication discussed.
Psychotropic of such therapy,
Key words: Tardive
dyskinesia;
12 August
1989, revision received
15 August
University of Calgav, Calgay (Canada)
1990, accepted
13 December
1990)
dyskinesia is a serious drugs are frequently used to treat chronic pain. Tardive but is not mentioned in the pain literature. Two cases are reported and the implications
Psychotropic
drugs;
Medico-legal;
Introduction Psychotropic drugs are frequently employed in the treatment of chronic pain patients, especially where nerve damage is implicated; tardive dyskinesia is a serious complication of their use. Most chronic pain management services are organized by non-psychiatrists, frequently with little or no psychiatric input to the service, and physicians involved in the management of chronic pain do not routinely read psychiatric or neurological journals. There has been an exponential growth in the number of papers appearing each year describing tardive dyskinesia or its complications (over 1500 papers, in English alone, 50% in the last 5 years) but a ‘Medline’ search of the last 25 years found no accounts of tardive dyskinesia in the ‘pain’ literature or anaesthetic journals, and only one previous case recently reported in the psychiatric press in relation to the treatment of chronic pain [3]. Tardive dyskinesia is a disorder of movement caused principally by dopamine antagonist drugs, which include all neuroleptics and some antinauseants (perphenazine and metoclopramide), but also can be induced by a wide, variety of pharmaceutical agents and can occur spontaneously. The most common symptom is orofacial dyskinesia, but abnormal involuntary movements may occur in any part of the body. The condition can be very difficult to distinguish from other move-
Correspondence to: Dr. I.M.C. Clarke, Pain Relief Clinic, Foothills Hospital, 1403-29 Street N.W., Calgary, Alberta T2N 2T9, Canada.
Chronic
pain
ment disorders and a high level of suspicion is often required for early diagnosis. Choreo-athetoid movements of buccal, lingual, and facial muscles are seen, so that the patient ‘chews the cud,’ grimaces, protrudes the tongue, etc. Any or all muscle groups may be involved, and whilst myoclonic, dystonic, ballistic, or tic-like movements are frequent, tremor is never seen. Movements may range from mild and inconspicuous to cosmetically disfiguring, severe holokinetic, and occasionally life threatening. The symptoms may very rarely begin at the onset of treatment and, much more commonly, whilst on or being withdrawn from chronic (over 6 months) treatment. There are suggestions that there may be several distinct clinical syndromes [4]. Numerous methods of assessment and grading are available including the abnormal involuntary movements scale (AIMS), Rockland, and parkinsonism scales, of which the AIMS probably offers the best discrimination for neuroleptic mediated tardive dyskinesia [7,10,11,13]. A complicated and variable clinical presentation means that differential diagnosis may be difficult, but is clearly of great importance. This should include: (1) neuroleptic withdrawal dyskinesia or other transient acute dyskinesias; (2) stereotyped movements of schizophrenia; (3) dyskinesias associated with advanced age, including Alzheimer’s dementia; (4) oral dyskinesias related to dental conditions; (5) idiopathic torsion dystonia; (6) focal dystonias such as oromandibular dystonia, blepharospasm, spasmodic torticollis, habit spasms; (7) Huntington’s disease; (8) Gilles de la
Tourette; (9) heavy metal poisoning including Wilson’s disease; (10) calcification of basal ganglia, including Fahr’s syndrome; (11) postanoxic, postencephalitic, and encephalitic extrapyramidal syndromes; (12) rheumatic chorea; (13) drug intoxication, especially L-DOPA, amphetamines; (14) CNS complications of systemic metabolic disorders; (15) cerebral tumor (American Psychiatric Association Task Force Report [21]). A similar movement disorder occurs in psychotic patients treated without medication, and it can also occur in healthy untreated elderly patients [19]. High risk factors include: old age, brain damage, schizophrenia, and affective conditions [17]. There may also be a link with cognitive dysfunction in patients with bipolar affective disorder. In schizophrenia, tardive dyskinesia is more often associated with intellectual impairment and negative symptoms (with overrepresentation of structural brain damage) and less with type or duration of medication [18]. Abnormal movements were recognized many years ago and reported frequently by Kraepelin in his early descriptions of schizophrenia where grimacing and gesticulation were included as typical features [8]. Numerous other reports in recent years indicate an incidence of 557% of tardive dyskinesia in untreated schizophrenics and about 30% in treated schizophrenics, regardless of the medication used [8,10,12]. Abnormal movements are also seen unrelated to neuroleptic drug use in a variety of conditions, including essential tremor (7.7%), Alzheimer’s dementia (16.8%) and mixed dementia (17-38%) [19]. The common factor appears to be an implication of an organic brain syndrome, although this may be very subtle [18]. Nonetheless. the frequency of tardive dyskinesia is higher in all patient groups when neuroleptic drugs have been used, with duration and dosage as risk factors. Tardive dyskinesia-implicated drugs are often used in combination for chronic pain patients who also display some of the risk factors mentioned above, especially age. concurrent affective disorder, and social isolation. The drugs include all tricyclics, all anticholinergics, ail anticonvulsants, all benzodiazepines. some antihistamines, and also metoclopramide, propranolol and even non-steroidal anti-inflammatories including mefenamic acid and ibuprofen. When treatment relieves the pain, it may be prolonged for many years, with relatively little follow-up; and even treatment ‘trials’ may last long enough for tardive dyskinesia to become a real possibility. Although tardive dyskinesia can occur after single exposure, this is rare, and most cases are reported after treatment for at least 6 months and sometimes following drug withdrawal. Following diagnosis, initial treatment is usually drug withdrawal with a 25-50% chance of remission within 1 year. Paradoxically, increasing the dose of the drug involved may suppress symptoms at least temporarily.
For those cases where symptoms persist after withdrawal, treatment options include a bewildering variety of drugs, most with actions which seem to have little to do with the theoretical causation of the condition. This includes pyridoxine. cyproheptidine, clonidine, naloxone, L-DOPA, calcium channel blockers, carbamazepine, gamma-aminobutyric acid, phosphotidile choline, ceruletide, ritanserin, bromocriptine. sulpiride, baclofen, amantidine. methylphenidate. propranolol, metoclopramide, isosorbide, dantrolene. ergot. choline, lecithin, L-tryptophan, papaverine, pimozide, dianol, ECT, and even monosodium glutamate. Many of the drugs used in treatment may also precipitate the condition. Pathophysiology remains a matter for considerable discussion. First, it was felt that because of the common mode of action of neuroleptics and the demonstration of increases in number and affinity of dopamine receptors following prolonged administration of neuroleptic drugs, dopamine supersensitivity was a plausible explanation for the development of tardive dyskinesia [15]. This has not been supported by further studies. although it may still be that dopamine supersensitivity is the mechanism in withdrawal dyskinesia [14]. Recently, attention has focused more on gamma-aminobutyric acid when it has been shown that glutamic acid decarboxylase (the GABA synthetic enzyme) declines. at least in rats and monkeys, as dyskinetic activity increases. This activity is seen after neuroleptic administration and is persistent after neuroleptic withdrawal, occurring only in those individuals who show neuroleptic induced dyskinesia [6]. GABA is found to be decreased in the cerebrospinal fluid of schizophrenic patients with tardive dyskinesia compared with schizophrenic patients without tardive dyskinesia and pharmacological augmentation of brain GABA activity reduces dyskinetic symptoms in tardive dyskinesia patients [16]. It seems more likely, therefore, that GABA systems are more important in the pathophysiology of tardive dyskinesia than are dopaminergic systems. Unfortunately, none of this helps with diagnosis or even subsequent treatment.
Case reports Case no. I A 67-year-old Hungarian female developed burning in both feet. Numerous consultations followed without a clear diagnosis, and eventually she was seen by a psychiatrist who recommended, on purely empirical grounds, the use of flupenthixol. For the next 3 years the patient took this in a dose of 1 mg b.i.d., but without relief of her pain. She gradually developed involuntary facial grimacing, protrusion movements of her tongue, and chewing motions of her mouth. She was
169
ultimately referred to the Pain Clinic, where a diagnosis of major depression was made. Treatment with amitriptyline improved her affect and abolished the pain within 8 weeks, but withdrawal of the flupenthixol did not relieve her tardive dyskinesia which persists at follow-up 3 years later. Case no. 2 A 79-year-old woman was admitted to hospital following a suicidal attempt by drinking lavatory cleaner. The attempt was precipitated by being told that nothing could be done for her involuntary movements. Eight years earlier she had exhibited depressive symptoms of which chronic pain was most prominent and had been treated with amitriptyline 50 mg/h and perphenazine 2 mg t.i.d. (a common combination for chronic pain). This was continued for the next 7 years with little evidence of any change in pain or affect. One year before the suicidal attempt, the medication was stopped. Within a few weeks she had developed movements which led to her suicidal attempt. In her suicide note she describes these as follows ‘I have no control of my tongue and can’t wear my teeth, so can’t go out like this, not even to church. I can’t stand to take any more of this pain day and night, and knowing that it is something I will have to live with forever.’ On examination, she had uncontrollable rapid protrusion of the tongue and continuous rolling movements of the mouth. A diagnosis of tardive dyskinesia was made, and treatment with haloperidol was largely successful in suppressing her symptoms.
Discussion A condition such as tardive dyskinesia, which may be so devastating to the patient, requires not only heightened awareness of its occurrence but also an avoidance strategy. Failure to be cognisant of these measures may increase the incidence of the condition and encourage more litigation in this field which has already generated awards of considerable sums in compensation. Legal decisions include the following: ‘By 1973 tardive dyskinesia was, or should have been, looked for and reacted to by any regularly prescribing physician’ (i.e., not just psychiatrists) [1,5]. Tardive dyskinesia must be fairly common in chronic pain patients unless they are chemically different or somehow ‘protected’ compared with individuals receiving medication for psychiatric reasons. Both of these options seem unlikely, and there is clearly no evidence at present to suggest such a hypothesis. Rather, we suspect that tardive dyskinesia is unnoticed and mis-diagnosed. The American Psychiatric Association introduced recommendations in 1980 for the use of drugs likely to produce tardive dyskinesia [21]. Six years later Gualtieri et al. noted: ‘It is our opinion that these
have been honored more in the breach than the keeping. Nothing has succeeded in galvanizing the profession in the direction of altering its day to day practice with respect to neuroleptic drugs. It is no longer necessary to predict an impending flood of tardive dyskinesia litigation, because the flood gates are open, and the flood waters have already begun to rise’ [5]. The treatment of non-malignant chronic pain by neurolytic injection and other ablative treatments appears to be declining [2,9]. This may be due to a growing understanding of the complicated nature of chronic pain but is also because of an increased awareness of the poor long term efficacy coupled with risk. The literature suggests occasional cases of tardive dyskinesia occurring as a result of many different drugs as well as neuroleptics: this risk may seriously limit the long term use of medication in the treatment of chronic pain. It would be useful to assess the problem accurately by reporting to a central body such as the International Association for the Study of Pain. Until the risk is known, informed consent as described in the following guidelines should be the rule, especially when neuroleptics are to be used.
Suggested guidelines for the avoidance and management of tardive dyskinesia (adapted from APA Task Force Report 1211) 1. Consider carefully the indications for prolonged therapy. The indications should be serious and there should be objective evidence of benefit. 2. Seek alternative therapies. 3. Use lower doses with elderly patients and children. Strive for minimum effective doses. Avoid multiple drugs. 4. Advise patients and families of risks and benefits. Arrive at a mutual decision when one of these drugs is to be used, particularly for more than 1 year. Note discussion and agreement in clinical record. 5. Review patients regularly looking for early signs of choreo-athetosis and oro-lingual dyskinesia. Consider differential neurologic diagnoses. 6. Review patient and document indications in response at least every 3-6 months and attempt to reduce dose. 7. At earliest sign of dyskinesia, lower the dose, change to a less potent agent, or ideally stop treatment. Await remission as long as clinical condition permits. 8. Treat dyskinesia with benign agents, e.g., diazepam, possibly lithium. Stay alert to new experimental therapy, if only to bide time and offer hope. Re-institute treatment only as an extreme measure for disabling symptoms using lowest doses feasible.
170
Acknowledgements
My thanks are due to Dr. D. Barnes, Department of Psychiatry, University of Calgary, who suggested the report and made many useful comments throughout the preparation. Dr. M. Trew allowed me to report the second patient. MS E. Ellis and MS S. Hodgkinson tolerantly typed the numerous revisions.
References 1 Amabile, T.E. and Cavanaugh, J.L., Legal liability for tardive dyskinesia. In: Progress in Psychiatry. Tardive Dyskinesia, American Psychiatric Press, Washington. DC, 1988. pp. 261-279. 2 Bonica. J.J., Neurolytic blockade and hypophysectomy. In: J.J. Bonica (Ed.), The Management of Pain, 2nd Edn.. Vol. II, Lea and Febiger, Philadelphia, PA, 1990, pp. 1980-1981. 3 Earl. J. and Patterson, W.M., Chronic pain. neuroleptics. and tardive dyskinesia, Psychosomatics, 27 (1986) 291-293. 4 Glazer, W.M.. Morgenstern, H., Niedzwiecki. D. and Hughes. J.. Heterogeneity of tardive dyskinesia, a multivariate analysis, Br. J. Psychiat.. 152 (1988) 253-269. 5 Gualtieri. C.T.. Sprague, R.L. and Cole, J.O., Tardive dyskinesia litigation and the dilemmas of neuroleptic treatment. J. Psychiat. Law. 14 (1986) 187-216. 6 Gunne, L.M.. Levine. E.D. and Johansson. E.E.. The GABA theory of tardive dyskinesia. In: Progress in Psychiatry. Tardive Dyskinesia, American Psychiatric Press. Washington, DC. 1988, pp. 31-38. 7 Guy, W., Assessment Manual for Psychopharmacology, Department of Health, Education and Welfare, Washington, DC, 1976, pp. 5344537. X Kraepelin, E.. Lectures in Clinical Psychiatry (Transl. T. Johnston), 3rd Edn., Balliere, Tindall and Cox. London. 1913. 9 Loeser. J.D.. Ablative neurosurgical operations. In: J.J. Bonica (Ed.), The Management of Pain, 2nd Edn., Vol. II, Lea and Frhiger, Philadelphia, PA, 1990, p. 2041.
IO Owens, D.G.C., Johnston, EC. and Thrtff. C.D., Spontaneous involuntary disorders of movement. Arch. Gen. Psychiat.. 39 (19X2) 452-461. 1 I Rao. J.M., Cowi. V.A. and Matthew, B.. Tardive dvxkinesin in neuroleptic medicated mentally handicapped SubJects. Acta Psvchiat. &and.. 76 (1987) 5077513. 12 Robinson. A.D.T. and McCreadie. R.G.. The Nithsdale schizophrenia survey. V. Follow-up of tardive dyskinesia at three anti ;I half years. Br. J. Psychiat.. 149 (1986) 621623. I3 Simpson. G.M., Lee, J.H., Zoubok, V. et al.. A rating scale for tardive dyskinesia. Psychopharmacology (Berl.). 64 (1979) 17 I - I79 14 Smith. R.C.. 1s the dopaminergic supersensitivity theory of tardive dyskinesia valid? In: Progress m Psychiatry. Tardive Dyskinesia. American Psychiatrtc Press, Washington, DC. 1988, pp. 3321. 15 Thaker, G.E., Ferraro, T.N.. Hrare, T.A. and Tamminga. C.A.. Pathophysiology and therapy of tardive dyskineaia. In: Progress in Psychiatry. Tardive Dyskinesia, American Psychiatric Press. Washington. DC, 198X. pp. 199-215. 16 Thaker, G.K.. Tamminga. C.4.. Alphs. L.D. et al.. Bram gammaaminohutyric actd abnormality in tardive dyskinesia. Arch. Gen. Psychiat.. 44 (1987) 5222529. 17 Waddington, J.L. and Youssef. H.A., Tardive dyskineaia in bipolar affective disorder. aging, cogmtive dysfunction, course of illness and exposure to neuroleptics and lithium. Am. J. Psychiat., 145 (19X8) 613-616. IX Waddington. J.L. and Youssef. H.A.. Late onset involuntary movements in chronic schizophrenia. Br. J. Psychiat.. 149 (1986) 616-620. 19 Waddington. J.L. and Crow. T.J.. Abnormal involuntary movements and psychosis in the pre-neuroleptic era and in unmedicated patients. In: Progress in Psychiatry. Tardive Dyskinesia, American Psychiatric Press, Washington, DC, 1988, pp. 51-66. 20 Department of Health, Education and Welfare, Abnormal lnvoluntary Movement Scale (AIMS). Alcohol, Drug Abuse and Mental Health Administration, Washington, DC, 1974. 21 Tardive dyskinesia. Summary of a task force report of the American Psychiatric Association, Am. J. Psychiat., 137 (1980) 11631172.
167 B.V. 0304-3959/91/$03.50
PAIN 01749
Clinical Note
Tardive dyskinesia and chronic pain I.M.C. Clarke Dept.
ofAnaesthesia,University of Calgary, and Pain Relief Clinic, Foothills Hospital, (Received
Summary
complication discussed.
Psychotropic of such therapy,
Key words: Tardive
dyskinesia;
12 August
1989, revision received
15 August
University of Calgav, Calgay (Canada)
1990, accepted
13 December
1990)
dyskinesia is a serious drugs are frequently used to treat chronic pain. Tardive but is not mentioned in the pain literature. Two cases are reported and the implications
Psychotropic
drugs;
Medico-legal;
Introduction Psychotropic drugs are frequently employed in the treatment of chronic pain patients, especially where nerve damage is implicated; tardive dyskinesia is a serious complication of their use. Most chronic pain management services are organized by non-psychiatrists, frequently with little or no psychiatric input to the service, and physicians involved in the management of chronic pain do not routinely read psychiatric or neurological journals. There has been an exponential growth in the number of papers appearing each year describing tardive dyskinesia or its complications (over 1500 papers, in English alone, 50% in the last 5 years) but a ‘Medline’ search of the last 25 years found no accounts of tardive dyskinesia in the ‘pain’ literature or anaesthetic journals, and only one previous case recently reported in the psychiatric press in relation to the treatment of chronic pain [3]. Tardive dyskinesia is a disorder of movement caused principally by dopamine antagonist drugs, which include all neuroleptics and some antinauseants (perphenazine and metoclopramide), but also can be induced by a wide, variety of pharmaceutical agents and can occur spontaneously. The most common symptom is orofacial dyskinesia, but abnormal involuntary movements may occur in any part of the body. The condition can be very difficult to distinguish from other move-
Correspondence to: Dr. I.M.C. Clarke, Pain Relief Clinic, Foothills Hospital, 1403-29 Street N.W., Calgary, Alberta T2N 2T9, Canada.
Chronic
pain
ment disorders and a high level of suspicion is often required for early diagnosis. Choreo-athetoid movements of buccal, lingual, and facial muscles are seen, so that the patient ‘chews the cud,’ grimaces, protrudes the tongue, etc. Any or all muscle groups may be involved, and whilst myoclonic, dystonic, ballistic, or tic-like movements are frequent, tremor is never seen. Movements may range from mild and inconspicuous to cosmetically disfiguring, severe holokinetic, and occasionally life threatening. The symptoms may very rarely begin at the onset of treatment and, much more commonly, whilst on or being withdrawn from chronic (over 6 months) treatment. There are suggestions that there may be several distinct clinical syndromes [4]. Numerous methods of assessment and grading are available including the abnormal involuntary movements scale (AIMS), Rockland, and parkinsonism scales, of which the AIMS probably offers the best discrimination for neuroleptic mediated tardive dyskinesia [7,10,11,13]. A complicated and variable clinical presentation means that differential diagnosis may be difficult, but is clearly of great importance. This should include: (1) neuroleptic withdrawal dyskinesia or other transient acute dyskinesias; (2) stereotyped movements of schizophrenia; (3) dyskinesias associated with advanced age, including Alzheimer’s dementia; (4) oral dyskinesias related to dental conditions; (5) idiopathic torsion dystonia; (6) focal dystonias such as oromandibular dystonia, blepharospasm, spasmodic torticollis, habit spasms; (7) Huntington’s disease; (8) Gilles de la
Tourette; (9) heavy metal poisoning including Wilson’s disease; (10) calcification of basal ganglia, including Fahr’s syndrome; (11) postanoxic, postencephalitic, and encephalitic extrapyramidal syndromes; (12) rheumatic chorea; (13) drug intoxication, especially L-DOPA, amphetamines; (14) CNS complications of systemic metabolic disorders; (15) cerebral tumor (American Psychiatric Association Task Force Report [21]). A similar movement disorder occurs in psychotic patients treated without medication, and it can also occur in healthy untreated elderly patients [19]. High risk factors include: old age, brain damage, schizophrenia, and affective conditions [17]. There may also be a link with cognitive dysfunction in patients with bipolar affective disorder. In schizophrenia, tardive dyskinesia is more often associated with intellectual impairment and negative symptoms (with overrepresentation of structural brain damage) and less with type or duration of medication [18]. Abnormal movements were recognized many years ago and reported frequently by Kraepelin in his early descriptions of schizophrenia where grimacing and gesticulation were included as typical features [8]. Numerous other reports in recent years indicate an incidence of 557% of tardive dyskinesia in untreated schizophrenics and about 30% in treated schizophrenics, regardless of the medication used [8,10,12]. Abnormal movements are also seen unrelated to neuroleptic drug use in a variety of conditions, including essential tremor (7.7%), Alzheimer’s dementia (16.8%) and mixed dementia (17-38%) [19]. The common factor appears to be an implication of an organic brain syndrome, although this may be very subtle [18]. Nonetheless. the frequency of tardive dyskinesia is higher in all patient groups when neuroleptic drugs have been used, with duration and dosage as risk factors. Tardive dyskinesia-implicated drugs are often used in combination for chronic pain patients who also display some of the risk factors mentioned above, especially age. concurrent affective disorder, and social isolation. The drugs include all tricyclics, all anticholinergics, ail anticonvulsants, all benzodiazepines. some antihistamines, and also metoclopramide, propranolol and even non-steroidal anti-inflammatories including mefenamic acid and ibuprofen. When treatment relieves the pain, it may be prolonged for many years, with relatively little follow-up; and even treatment ‘trials’ may last long enough for tardive dyskinesia to become a real possibility. Although tardive dyskinesia can occur after single exposure, this is rare, and most cases are reported after treatment for at least 6 months and sometimes following drug withdrawal. Following diagnosis, initial treatment is usually drug withdrawal with a 25-50% chance of remission within 1 year. Paradoxically, increasing the dose of the drug involved may suppress symptoms at least temporarily.
For those cases where symptoms persist after withdrawal, treatment options include a bewildering variety of drugs, most with actions which seem to have little to do with the theoretical causation of the condition. This includes pyridoxine. cyproheptidine, clonidine, naloxone, L-DOPA, calcium channel blockers, carbamazepine, gamma-aminobutyric acid, phosphotidile choline, ceruletide, ritanserin, bromocriptine. sulpiride, baclofen, amantidine. methylphenidate. propranolol, metoclopramide, isosorbide, dantrolene. ergot. choline, lecithin, L-tryptophan, papaverine, pimozide, dianol, ECT, and even monosodium glutamate. Many of the drugs used in treatment may also precipitate the condition. Pathophysiology remains a matter for considerable discussion. First, it was felt that because of the common mode of action of neuroleptics and the demonstration of increases in number and affinity of dopamine receptors following prolonged administration of neuroleptic drugs, dopamine supersensitivity was a plausible explanation for the development of tardive dyskinesia [15]. This has not been supported by further studies. although it may still be that dopamine supersensitivity is the mechanism in withdrawal dyskinesia [14]. Recently, attention has focused more on gamma-aminobutyric acid when it has been shown that glutamic acid decarboxylase (the GABA synthetic enzyme) declines. at least in rats and monkeys, as dyskinetic activity increases. This activity is seen after neuroleptic administration and is persistent after neuroleptic withdrawal, occurring only in those individuals who show neuroleptic induced dyskinesia [6]. GABA is found to be decreased in the cerebrospinal fluid of schizophrenic patients with tardive dyskinesia compared with schizophrenic patients without tardive dyskinesia and pharmacological augmentation of brain GABA activity reduces dyskinetic symptoms in tardive dyskinesia patients [16]. It seems more likely, therefore, that GABA systems are more important in the pathophysiology of tardive dyskinesia than are dopaminergic systems. Unfortunately, none of this helps with diagnosis or even subsequent treatment.
Case reports Case no. I A 67-year-old Hungarian female developed burning in both feet. Numerous consultations followed without a clear diagnosis, and eventually she was seen by a psychiatrist who recommended, on purely empirical grounds, the use of flupenthixol. For the next 3 years the patient took this in a dose of 1 mg b.i.d., but without relief of her pain. She gradually developed involuntary facial grimacing, protrusion movements of her tongue, and chewing motions of her mouth. She was
169
ultimately referred to the Pain Clinic, where a diagnosis of major depression was made. Treatment with amitriptyline improved her affect and abolished the pain within 8 weeks, but withdrawal of the flupenthixol did not relieve her tardive dyskinesia which persists at follow-up 3 years later. Case no. 2 A 79-year-old woman was admitted to hospital following a suicidal attempt by drinking lavatory cleaner. The attempt was precipitated by being told that nothing could be done for her involuntary movements. Eight years earlier she had exhibited depressive symptoms of which chronic pain was most prominent and had been treated with amitriptyline 50 mg/h and perphenazine 2 mg t.i.d. (a common combination for chronic pain). This was continued for the next 7 years with little evidence of any change in pain or affect. One year before the suicidal attempt, the medication was stopped. Within a few weeks she had developed movements which led to her suicidal attempt. In her suicide note she describes these as follows ‘I have no control of my tongue and can’t wear my teeth, so can’t go out like this, not even to church. I can’t stand to take any more of this pain day and night, and knowing that it is something I will have to live with forever.’ On examination, she had uncontrollable rapid protrusion of the tongue and continuous rolling movements of the mouth. A diagnosis of tardive dyskinesia was made, and treatment with haloperidol was largely successful in suppressing her symptoms.
Discussion A condition such as tardive dyskinesia, which may be so devastating to the patient, requires not only heightened awareness of its occurrence but also an avoidance strategy. Failure to be cognisant of these measures may increase the incidence of the condition and encourage more litigation in this field which has already generated awards of considerable sums in compensation. Legal decisions include the following: ‘By 1973 tardive dyskinesia was, or should have been, looked for and reacted to by any regularly prescribing physician’ (i.e., not just psychiatrists) [1,5]. Tardive dyskinesia must be fairly common in chronic pain patients unless they are chemically different or somehow ‘protected’ compared with individuals receiving medication for psychiatric reasons. Both of these options seem unlikely, and there is clearly no evidence at present to suggest such a hypothesis. Rather, we suspect that tardive dyskinesia is unnoticed and mis-diagnosed. The American Psychiatric Association introduced recommendations in 1980 for the use of drugs likely to produce tardive dyskinesia [21]. Six years later Gualtieri et al. noted: ‘It is our opinion that these
have been honored more in the breach than the keeping. Nothing has succeeded in galvanizing the profession in the direction of altering its day to day practice with respect to neuroleptic drugs. It is no longer necessary to predict an impending flood of tardive dyskinesia litigation, because the flood gates are open, and the flood waters have already begun to rise’ [5]. The treatment of non-malignant chronic pain by neurolytic injection and other ablative treatments appears to be declining [2,9]. This may be due to a growing understanding of the complicated nature of chronic pain but is also because of an increased awareness of the poor long term efficacy coupled with risk. The literature suggests occasional cases of tardive dyskinesia occurring as a result of many different drugs as well as neuroleptics: this risk may seriously limit the long term use of medication in the treatment of chronic pain. It would be useful to assess the problem accurately by reporting to a central body such as the International Association for the Study of Pain. Until the risk is known, informed consent as described in the following guidelines should be the rule, especially when neuroleptics are to be used.
Suggested guidelines for the avoidance and management of tardive dyskinesia (adapted from APA Task Force Report 1211) 1. Consider carefully the indications for prolonged therapy. The indications should be serious and there should be objective evidence of benefit. 2. Seek alternative therapies. 3. Use lower doses with elderly patients and children. Strive for minimum effective doses. Avoid multiple drugs. 4. Advise patients and families of risks and benefits. Arrive at a mutual decision when one of these drugs is to be used, particularly for more than 1 year. Note discussion and agreement in clinical record. 5. Review patients regularly looking for early signs of choreo-athetosis and oro-lingual dyskinesia. Consider differential neurologic diagnoses. 6. Review patient and document indications in response at least every 3-6 months and attempt to reduce dose. 7. At earliest sign of dyskinesia, lower the dose, change to a less potent agent, or ideally stop treatment. Await remission as long as clinical condition permits. 8. Treat dyskinesia with benign agents, e.g., diazepam, possibly lithium. Stay alert to new experimental therapy, if only to bide time and offer hope. Re-institute treatment only as an extreme measure for disabling symptoms using lowest doses feasible.
170
Acknowledgements
My thanks are due to Dr. D. Barnes, Department of Psychiatry, University of Calgary, who suggested the report and made many useful comments throughout the preparation. Dr. M. Trew allowed me to report the second patient. MS E. Ellis and MS S. Hodgkinson tolerantly typed the numerous revisions.
References 1 Amabile, T.E. and Cavanaugh, J.L., Legal liability for tardive dyskinesia. In: Progress in Psychiatry. Tardive Dyskinesia, American Psychiatric Press, Washington. DC, 1988. pp. 261-279. 2 Bonica. J.J., Neurolytic blockade and hypophysectomy. In: J.J. Bonica (Ed.), The Management of Pain, 2nd Edn.. Vol. II, Lea and Febiger, Philadelphia, PA, 1990, pp. 1980-1981. 3 Earl. J. and Patterson, W.M., Chronic pain. neuroleptics. and tardive dyskinesia, Psychosomatics, 27 (1986) 291-293. 4 Glazer, W.M.. Morgenstern, H., Niedzwiecki. D. and Hughes. J.. Heterogeneity of tardive dyskinesia, a multivariate analysis, Br. J. Psychiat.. 152 (1988) 253-269. 5 Gualtieri. C.T.. Sprague, R.L. and Cole, J.O., Tardive dyskinesia litigation and the dilemmas of neuroleptic treatment. J. Psychiat. Law. 14 (1986) 187-216. 6 Gunne, L.M.. Levine. E.D. and Johansson. E.E.. The GABA theory of tardive dyskinesia. In: Progress in Psychiatry. Tardive Dyskinesia, American Psychiatric Press. Washington, DC. 1988, pp. 31-38. 7 Guy, W., Assessment Manual for Psychopharmacology, Department of Health, Education and Welfare, Washington, DC, 1976, pp. 5344537. X Kraepelin, E.. Lectures in Clinical Psychiatry (Transl. T. Johnston), 3rd Edn., Balliere, Tindall and Cox. London. 1913. 9 Loeser. J.D.. Ablative neurosurgical operations. In: J.J. Bonica (Ed.), The Management of Pain, 2nd Edn., Vol. II, Lea and Frhiger, Philadelphia, PA, 1990, p. 2041.
IO Owens, D.G.C., Johnston, EC. and Thrtff. C.D., Spontaneous involuntary disorders of movement. Arch. Gen. Psychiat.. 39 (19X2) 452-461. 1 I Rao. J.M., Cowi. V.A. and Matthew, B.. Tardive dvxkinesin in neuroleptic medicated mentally handicapped SubJects. Acta Psvchiat. &and.. 76 (1987) 5077513. 12 Robinson. A.D.T. and McCreadie. R.G.. The Nithsdale schizophrenia survey. V. Follow-up of tardive dyskinesia at three anti ;I half years. Br. J. Psychiat.. 149 (1986) 621623. I3 Simpson. G.M., Lee, J.H., Zoubok, V. et al.. A rating scale for tardive dyskinesia. Psychopharmacology (Berl.). 64 (1979) 17 I - I79 14 Smith. R.C.. 1s the dopaminergic supersensitivity theory of tardive dyskinesia valid? In: Progress m Psychiatry. Tardive Dyskinesia. American Psychiatrtc Press, Washington, DC. 1988, pp. 3321. 15 Thaker, G.E., Ferraro, T.N.. Hrare, T.A. and Tamminga. C.A.. Pathophysiology and therapy of tardive dyskineaia. In: Progress in Psychiatry. Tardive Dyskinesia, American Psychiatric Press. Washington. DC, 198X. pp. 199-215. 16 Thaker, G.K.. Tamminga. C.4.. Alphs. L.D. et al.. Bram gammaaminohutyric actd abnormality in tardive dyskinesia. Arch. Gen. Psychiat.. 44 (1987) 5222529. 17 Waddington, J.L. and Youssef. H.A., Tardive dyskineaia in bipolar affective disorder. aging, cogmtive dysfunction, course of illness and exposure to neuroleptics and lithium. Am. J. Psychiat., 145 (19X8) 613-616. IX Waddington. J.L. and Youssef. H.A.. Late onset involuntary movements in chronic schizophrenia. Br. J. Psychiat.. 149 (1986) 616-620. 19 Waddington. J.L. and Crow. T.J.. Abnormal involuntary movements and psychosis in the pre-neuroleptic era and in unmedicated patients. In: Progress in Psychiatry. Tardive Dyskinesia, American Psychiatric Press, Washington, DC, 1988, pp. 51-66. 20 Department of Health, Education and Welfare, Abnormal lnvoluntary Movement Scale (AIMS). Alcohol, Drug Abuse and Mental Health Administration, Washington, DC, 1974. 21 Tardive dyskinesia. Summary of a task force report of the American Psychiatric Association, Am. J. Psychiat., 137 (1980) 11631172.
