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J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.46.7.666 on 1 July 1983. Downloaded from

Journal of Neurology, Neurosurgery, and Psychiatry 1983;46:666-668

Short report State-dependent in manic-depressive illness

RW de POTTER, P LINKOWSKI, J MENDLEWICZ From the Department ofPsychiatry, Erasme Hospital, University ofBrussels, Brussels, Belgium

SUMMARY We report the occurrence of a drug-resistent tardive dyskinesia coexistent with -like symptoms in a manic-depressive patient. The tardive dyskinesia completely disappeared during the manic phases and recurred after remission over the course of different mood-cycles.

Tardive dyskinesia is an extrapyramidal hyperkine- Case report tic syndrome which mainly affects the face, produc- ing stereotyped and rhythmic movements of mouth, Mr S. was 40 years old when first seen by a psychiatrist. He Protected by copyright. had no prior history of psychiatric illness other than a brief lips, tongue and jaws. These abnormal movements episode of a tic-syndrome during childhood. occur mainly following chronic neuroleptic drug In 1976, following the death of his father, his wife treatment. The aetiology of this dyskinetic syn- noticed the emergence of periods of lassitude, alternating drome still is uncertain, the favoured hypothesis with periods of increased activity and nervousness. In Feb- being the emergence of striatal -receptor ruary 1977, he developed a psychotic melancholic depres- supersensitivity after chronic dopamine-receptor sive syndrome, of acute onset, characterised by paranoid blockade.1-3 State-dependency of tardive dyskinesia delusions, guilt feelings, self-accusations and visual hal- in manic-depression has previously been reported lucinations (devils and hell) threatening him with eternal by Ashcroft et a14 and Davies et a15 who indicated condemnation for his sins. Neuroleptic treatment was started (: 2*5 mg/day); a progressive improve- that abnormal movements deteriorated during ment of the psychotic symptomatology followed but with mania and improved during depression. Cutler et a16 no mood changes. A few days later the patient manifested reported the reverse, namely two cases of tardive a typical depressive syndrome with marked psychomotor dyskinesia in manic-depression with dyskinetic retardation, clinophilia, guilt and hopelessness. Neurolep- symptoms recurring during depression and disap- tic treatment was continued for three months (haloperidol:

pearing during mania. These observations are sug- 5 mg/day), with slow improvement. The neuroleptics were http://jnnp.bmj.com/ gestive of an interaction between the biological replaced by a antidepressant (: 100 changes associated with manic-depression and those mg/day). On October 1977, the patient relapsed and pre- mediating spontaneous or tardive dyskinesia. The sented a new psychotic episode characterised by mystical delusions, hyperactivity and insomnia. The neuroleptic present report is of a state-dependent tardive dys- treatment (haloperidol: 3 mg/day) was re-started and con- kinesia in a patient with manic-depressive illness: tinued for 3 months, then was replaced by a benzodiazepine the tardive dyskinesia disappeared during the manic (bromazepam, dose unknown). A few months later, a new phases but reappeared in the euthymic interphases. psychotic manic-like episode occurred and was successfuliy

treated with haloperidol (3 mg/day). Neuroleptic treat- on September 28, 2021 by guest. ment was continued up to 1979. In March 1979, a typical oro-bucco-lingual dyskinetic syndrome was first observed worsening after discontinuing neuroleptic treatment (fig). Various treatments were tried with unconvincing Address for reprint requests: Prof J Mendlewicz, Dept of results aman- Psychiatry, Hopital Erasme, 808 Route de Lennik, B-1070 Bruxel- (clonazepam pyridoxine, a-methyldopa, les, Belgium. tadine, valproic acid). After initiating deanol (an acetyl- choline precursor) the patient became agitated and the Received 4 June 1982 and in revised form 8 January 1983. dyskinesia disappeared. The patient then developed an Accepted 10 February 1983. acute mania (insomnia, agitation and mystical delusions). 666 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.46.7.666 on 1 July 1983. Downloaded from

State-dependent tardive dyskinesia in manic-depressive illness 667

-- Manic episode and during the manic phases (to a lesser extent dur- -- Oyskinesia ing hypo-mania), and its early reoccurrence in the euthymic interphases (fig). The sequence of the

k--1. L- tardive in our .f I O 01 ----T- state-dependent dyskinesia patient 199 Qrh Sep Oct Dec I80May 1981IFe ct,: did not seem to be influenced by drug treatment and withdrawal, and was similar to the observations by

C Cutler et al.6 Our patient however presented tardive and Parkinsonism-like Of .0C o. c dyskinesia symptoms. 3 b C. -6 N C these two coexistent extrapyrimidal pathologies, J. E 0 -4t210 only the tardive dyskinesia disappeared during the c 7 4> I RCU C:la manic phases whereas the Parkinsonian symptoms remained unchanged. Figure Time course ofdyskinetic and manic symptoms, in If tardive dyskinesia results from the emergence relation to therapy. of post-synaptic dopamine-receptor supersensitivity in the striatum, following prolonged neuroleptic Deanol was discontinued but the mania persisted neces- treatment,'-3 it is difficult to reconcile this state- sitating hospitalisation. Haloperidol (3 mg/day) was initi- dependent tardive dyskinesia with the current ated and the manic state remitted. The dyskinetic symp- neurochemical hypotheses of affective disorders. toms, however, reappeared with the clinical remission. Indeed, if we assume that mania is associated with a Haloperidol was replaced by levo-mepromazine and in predominance of systems,9 we would December 1979, lithium carbonate (750 mg/day) was hardly expect an amelioration of the dyskinesia dur- added and continued thereafter. Severe tremor of an extrapyramidal nature were observed in the upper ing manic phases. If mania results from a relative extremities. In May 1980, the patient developed a manic hypoactivity of central cholinergic systems,'0 an syndrome and the dyskinetic symptoms again completely aggravation of the dyskinesia and a relief of the disappeared. was administered (intramuscu- Parkinsonism-like symptoms would also be Protected by copyright. larly 25 mg) and the psychotic state improved markedly expected during mania. In this respect, it is interest- but the dyskinesia reappeared with the clinical remission. ing to notice that the first manic switch associated Following clonazepam (2-5 mg/day) and with a complete disappearance of dyskinesia was treatment (75 mg/day), the patient became hypomanic and preceded by deanol treatment. The cyclical course the dyskinesia diminished. Clonazepam was withdrawn of the dyskinesia observed in our patient is not con- and a new manic state developed accompanied by a com- plete disappearance of the dyskinesia but not of the tre- sistent with a single biogenic amine hyper- and mor. After increasing thioridazine, the mania improved hypoactivity balance hypothesis of bipolar depres- and the dyskinesia reappeared. sion. Rather these rare occurrences of cyclical In October 1981, the patient was admitted in our mood-dependent dyskinesia in bipolar rapid cycler department in a normothymic state and treated with prop- patients suggest the presence of a common ranolol (up to 70 mg/day). The dyskinetic symptoms dopamine receptor instability in the courses of improved but propranolol had to be discontinued because manic depression and tardive dyskinesia. Because of of cardiovascular side-effects. A presynaptic dopamine the reported high incidence of tardive dyskinesia depleting agent, tetrabenazine (up to 175 mg/day) pro- induced by neuroleptics in depressed our duced a temporary amelioration of the dyskinesia, a patients," worsening of the Parkinsonism-like symptoms and no data should also caution against the prolonged use http://jnnp.bmj.com/ mood changes. Finally, caeruleine (up to 0 03 J,g/kg of neuroleptics in patients suffering from affective intramuscularly), a neuropeptide with antistereotypic illness. effects in mice,7 had no effect on the dyskinetic nor on the Parkinsonism-like symptoms. References Discussion 'Baldessarini RJ. The pathophysiological basis of tardive

The diagnosis of bipolar depression (rapid cycler) is dyskinesia. Trends in Neuroscience 1979:133-5. on September 28, 2021 by guest. consistent with the symptoms and episodic course of 2 Marsden CD, Jenner P. The pathophysiology of the illness. Despite lithium therapy, several manic extrapyramidal side-effects of neuroleptic drugs. relapses occurred, as observed in rapid cycler Psychol Med 1980;10:55-72. Klawans HL, Goetz CG, Perlik S. Tardive dyskinesia- patients, less responsive to lithium prophylaxis.8 review and update. Am J Psychiatry After two years of neuroleptic treatment, the patient 1980;137(8):900-8. developed a dyskinetic syndrome. The most striking 4Ashcroft G, Eccleston D, Murray LG, Glen IM. Mod- observation was the complete remission of the dys- ified amine hypothesis for the etiology of affective ill- kinetic symptoms concomitant with a manic switch ness. Lancet 1972;u:573-7. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.46.7.666 on 1 July 1983. Downloaded from 668 de Potter, Linkowski, Mendlewicz

Davies KL, Berger PA, Hollister LE. Tardive dyskinesia nate prophylaxis failure. Arch Gen Psychiatry and depressive illness. Psychopharmacology Com 1 974;30:229-33. 1976;2: 125-30. 'Garver DL, Davis JM. Minireview: biogenic amine 6 Cutler NR, Post RM, Rey AC, Bunney WE. hypotheses of affective disorders. Life Sci Depression-dependent dyskinesias in two cases of 1 979;24:383-94. manic-depressive illness. N Engl J Med Janowsky DS, Davis JM, El-Youssef MK, Sekerke HJ. 1980;304: 1088-9. Cholinergic-adrenergic hypothesis of mania and Zetler G. Differential cataleptogenic and antistereotypic depression. Lancet 1972;Hi:632-5. effects of caerulein and haloperidol. Neurophar- Rush M, Diamond F, Alpert M. Depression as a risk macology 1981 ;20:681-6. factor in tardive dyskinesia. Biol Psychiatry 8 Dunner DL, Fieve RR. Clinical factors in lithium carbo- 1982;17(3):387-92. Protected by copyright. http://jnnp.bmj.com/ on September 28, 2021 by guest.