• Present clinical and research methods of differential diagnosis of schizophrenia and affective psychoses rely very heavily on presenting symptoms and signs, especially in acute psychosis. We have reviewed studies bearing on this issue, including studies of the phenomenology of psychotic illness, outcome, family history, response to treatment with lithium carbonate, and cross-national and historical diagnostic comparisons. We conclude that most so-called schizophrenic symptoms, taken alone and in cross section, have remarkably little, if any, demonstrated validity in determining diagnosis, prognosis, or treatment response in psychosis. In the United States, particularly, overreliance on such symptoms alone results in overdiagnosis of schizophrenia and underdiagnosis of affective illnesses, particularly mania. This compromises both clinical treatment and research.

Diagnosis in schizophrenia and manic-depressive illness: a reassessment of the specificity of 'schizophrenic' symptoms in the light of current research.

A rating scale for tardive dyskinesia was developed, consisting of nearly all signs seen by two groups of investigators over a 5-year period. Thirty-four items were included in the scale with a possibility of writing in idiosyncratic signs. The scale was shown to have good reliability and validity in studies carried out by both the New York and Boston groups. It is recommended as a suitable instrument for describing the breadth of tardive dyskinesia syndrome and also for quantifying the disorder. A second scale, “the abbreviated dyskinesia scale”, contains 13 items which are more global than the items in the original scale. It also has been shown to be both reliable and valid. Its use is suited to situations requiring less extensively detailed assessments.

A rating scale for tardive dyskinesia.

Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders.

Tardive dyskinesia is an extrapyramidal syndrome associated with the chronic administration of major neuroleptic agents. The pathogenesis of the disorder appears to relate to chronic striatal dopaminergic receptor site blockade; the pathophysiology of tardive dyskinesia appears to relate to the resultant denervation hypersensitivity. Agents that deplete the brain of dopamine are the mainstay of therapy for tardive dyskinesia. Cholinergic agents that potentially modulate the balance between dopamine and acetycholine in the striatum offer possible additional therapeutic options. Clearly, resumption of neuroleptic therapy is treatment with the presumed pathogenic agent and is to be avoided whenever possible.

Tardive dyskinesia: review and update.

• We reviewed 285 treatment studies involving more than 3,000 patients with neuroleptic-induced tardive dyskinesia (TD). Neuroleptic withdrawal is found to reverse dyskinesia in about 37% of patients. There is no satisfactory treatment for persistent TD. Although neuroleptics are significantly superior to most other methods of treatment in suppressing signs of dyskinesia, the safety of their long-term use in dyskinetic patients remains to be demonstrated. Putative β-aminobutyric acid (GABA)—ergic drugs and noradrenergic blockers deserve careful study. A strategy for determining biochemical and pharmacologic subtypes of TD appears promising. The value of the available cholinergic agents in the treatment of TD is uncertain. Caution is warranted in interpreting "positive" results with a number of other drugs, which might act as placebos or as nonspecific sedatives. Anticholinergic drugs are generally not recommended for treating dyskinetic patients. Current theories of the pathophysiology of TD may need revision. Drug-free periods do not seem to prevent TD. Antipsychotic drugs without neuroleptic side effects should be developed.

Therapeutic strategies against tardive dyskinesia. Two decades of experience.

A single blind trial and a placebo controlled double blind trial of lithium were carried out in elderly patients with tardive dyskinesia. In the pilot study, neuroleptics were continued: in the controlled trial, neuroleptics were discontinued. The results of both studies were essentially negative. Thus, the suppression effect of neuroleptics is much more dramatic than anything seen in the two studies. Several reasons for this were discussed namely, the severity and chronicity of the symptoms.

G M Simpson

Papers

Lithium in tardive dyskinesia