Tardive dyskinesia reversibility

Jeste DV, Potkin SG, Sinha S, Feder S, Wyatt RJ. Tardive dyskinesia—reversible and persistent. Arch Gen Psychiatry 1979 36(5) 585-90. 

The anainoacridines, tacrine (19) and its 1-hydroxy metaboUte, velnacrine (20), are reversible inhibitors of AChE. Tacrine was synthesi2ed in the 1940s and has been used clinically for the treatment of myasthenia gravis and tardive dyskinesia (115). Placebo-controUed studies have indicated modest efficacy of tacrine to treat AD dementia (122,123) and in 1993 the dmg was recommended for approval by the PDA under the trade name Cognex. Tacrine (19) has been shown to interact with sites other than AChE, such as potassium channels (124) and muscarinic receptors. However, these interactions are comparatively weak and are not thought to contribute to the biological activity of the dmg at therapeutic levels (115). 

Tardive dyskinesia presents itself as involuntary movements that involve the face but sometimes also the extremities or trunk. One has to bear in mind that in a large segment of these patients the symptoms are not reversible and there are estimates that 10-20% of hospitalized psychiatric patients and 40% of the elderly on long-term antipsychotic therapy display some signs of tardive dyskinesia. 

Greene JG, Greenamyre JT (1995) Characterization of the excitotoxic potential of the reversible succinate dehydrogenase inhibitor malonate. J Neurochem 64 430-436 Gunne LM, Andren PE (1993) An animal model for coexisting tardive dyskinesia and tardive parkinsonism—a glutamate hypothesis for tardive dyskinesia. Clin Neuropharmacol 16 90-95... 

Tardive dyskinesia is a late-occurring syndrome of abnormal movements of the face and tongue with widespread choreoathetosis. It is the most serious adverse effect of the antipsychotic drugs. It can be expected to occur in 20 to 40% of chronically treated patients there is no established treatment, and reversibility may be limited. These reactions are more frequent and severe in the elderly. 

Although there are difficulties in establishing a reference figure for the incidence or prevalence of dyskinesia, Australian psychiatrists seem to underestimate the prevalence of tardive dyskinesia. According to a survey of 139 psychiatrists, 80% estimated the prevalence of mild reversible tardive dyskinesia as being 5% of those treated with neuroleptic drugs (277). 

The rate of reversibility of tardive dyskinesia after drug withdrawal is 0-90% (269). Since patients with tardive dyskinesia rarely have subjective complaints (304), periodic assessment of dyskinetic movements is essential in making an early diagnosis and can increase the chance of reversing the disorder. Some reports are relatively encouraging regarding reversibility (305,306) the characteristics of reversible and irreversible forms have been reviewed, but no firm conclusion can be drawn (307). However, the prognosis of tardive dyskinesia was better in patients treated for a shorter duration and in those treated with lower doses (308). 

Chouinard G, Bradwejn J. Reversible and irreversible tardive dyskinesia a case report. Am J Psychiatry 1982 139(3) 360-2. 

The dibenzodiazepine clozapine (Table 12-14, X = NH), which is an antischizophrenic, has been approved on a limited basis (1989). Its atypical properties are that it does not bind to DA receptors and, as a result, does not appear to cause extrapyramidal symptoms. It may even reverse tardive dyskinesia. Unfortunately, reports of a high incidence of agranulocytosis severely restricts its use to patients who are refractory to standard antipsychotic medications. Fluperlapine (Table 12-14) is currently being investigated as an alternative... 

Adverse Effects The major side effects of metoclopramide include extrapyramidal effects. Dystonias, usually occurring acutely after intravenous administration, and parkinsonian-like symptoms that may occur several weeks after initiation of therapy generally respond to treatment with antichohn-eigic or antihistaminic drugs and are reversible upon metoclopramide discontinuation. Tardive dyskinesia also can occur with chronic treatment (months to years) and may be irreversible. Metoclopramide can elevate prolactin levels by blocking the inhibitory effect of dopamine on pituitary lactotropes. Methemoglobinemia has been reported in premature and fuU-term neonates receiving metoclopramide. 

The concurrent use of tricyclic antidepressants and phenothiazines is common, but the tricyclic levels are increased by many of the phenothiazines, and the levels of some phenothiazines are also increased by the tricycUcs. It has been su ested that concurrent use might contribute to an increased incidence of tardive dyskinesia. Nevertheless, fixed-dose combined preparations are available. Tricyclics have also been shown to reverse the therapeutic effects of chlorpromazine. 

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