IS SUBCORTICAL DISEASE-ASSOCIATED WITH A POOR RESPONSE TO ANTIDEPRESSANTS - NEUROLOGICAL, NEUROPSYCHOLOGICAL AND NEURORADIOLOGICAL FINDINGSIN LATE-LIFE DEPRESSION

Background. Late-life depression is associated with increased subcorti cal white matter hyperintensities. There is some evidence that they ar e associated with a poorer response to acute treatment. Neurological s igns and neuropsychological dysfunction are further evidence of abnorm alities in the brain, but they have not been studied in relation to th erapy resistance. Methods. A prospective study of 24 normal controls a nd 75 consecutive elderly (aged 65 to 85) patients with DSM-III-R majo r depression entered a naturalistic study of treatment. Assessment of response to monotherapy and then lithium augmentation or ECT created t hree outcome groups. Investigations included magnetic resonance brain imaging, neuropsychological and neurological examination. Results. Res ponse to monotherapy within 12 weeks was shown by 42.7%, a further 37. 3% responded to lithium augmentation or ECT within 24 weeks and 20 % h ad responded poorly to all treatments at 24 weeks. Subcortical hyperin tensities were significantly increased in the more resistant patients. These included confluent deep white matter, multiple (> 5) basal gang lia lesions and pontine reticular formation lesions. Most of the neuro psychological impairment was restricted to the resistant groups and wa s of a subcortico-frontal type. Extrapyramidal, frontal and pyramidal neurological signs characterized the resistant groups. The combination of extrapyramidal signs, pyramidal tract signs and impairment of moto r hand sequencing strongly predicted resistance to 12 weeks of antidep ressant monotherapy with 89 % sensitivity and 95% specificity. Conclus ion. In late-life depression a poor response to antidepressant monothe rapy can be expected in those patients with a frontal lobe syndrome, e xtrapyramidal signs or if MRI T-2-weighted lesions are present in both the basal ganglia and the pontine reticular formation.