Prediction of lithium response

Abstract

T HE FOUNDATIONS of psychiatric nosology have remained essentially unchanged since the early days of scientific psychiatry. Specific etiologic factors have not been identified for most mental disorders, and classification therefore still rests on symptomatology and clinical course. The shortcomings of this approach in terms of reliability and validity have become increasingly obvious, in particular with advances in relevant areas of biologic research. However, much has been done to remedy the situation, partly by standardizing the way psychiatric symptoms are elicited,’ and partly by studies of genetic and pharmacologic factors. The discovery of psychotropic drugs with potentially specific effects on target symptoms and psychiatric syndromes has led to extensive investigations of the response of psychiatric illnesses to the main forms of physical treatment, drugs, and electroconvulsive therapy (ECT). This work has focused on four areas. Firstly, attempts to classify psychotropic drugs according to their therapeutic effects,’ and secondly, thereby to improve psychiatric classification.“*4 Thirdly, the proposed modes of action of these drugs have provided etiologic hypotheses for some psychiatric disorders. The fourth objective derives from the other three, namely to find the right drug for the right patient by identifying predictive indicators of treatment response. May and Goldberg5 have recently reviewed studies evaluating response differences of schizophrenic patients to phenothiazines. Response has generally been shown to be associated with thought disorder and paranoid symptoms. Women respond better than men and better premorbid social adjustment also predicts a better response. Patients with very poor prognostic signs are thought to benefit least, if at all. Attempts to predict treatment response in the affective disorders have generally been more successful. Good response is positively correlated with endogenous symptoms, and the bipolar subgroup shows consistent drug responses, possibly in association with a number of pretreatment biologic measures. Bielski and Friede16 have reviewed the literature on descriptive variables as predictive indicators of tricyclic antidepressant response. Upper socioeconomic class, insidious onset, anorexia, weight loss. middle and late insomnia, and psychomotor disturbance are predictors of good response. On the other hand, neurotic, hypochondriacal, and hysterical traits, multiple prior episodes, and delusions are associated with poor response. A further review of this area, including biologic predictors, emphasizes the potential use of biologic measures such as 5-HIAA in CSF and MHPG in urine as predictive indicators of drug response.7 In the case of MAO inhibitors, attempts to distinguish