There are few clinical or biologic predictors of response to treatments for depression. This article reviews growing evidence that electrophysiologic and neurocognitive measures of brain function may be of value as predictors of therapeutic response to antidepressants. Initial studies using dichotic listening, quantitative electroencephalography, or event-related brain potential measures have found differences between treatment responsive and nonresponsive subgroups of depressed patients. The neurophysiologic basis for these differences and the potential clinical utility of electrophysiologic and dichotic predictors of treatment out come remain to be determined in future studies.

Background. This randomized controlled trial investigates the efficacy of two non-pharmacologic treatments, bright light and high-density negative air ions for non-seasonal chronic depression. Both methods have shown clinical success for seasonal affective disorder (SAD).

Method. Patients were 24 (75%) women and 8 (25%) men, ages 22–65 years (mean age±S.D., 43·7±12·4 years), with Major Depressive Disorder, Single Episode (DSM-IV code, 296.2), Chronic (episode duration [ges ]2 years). Patients were entered throughout the year and randomly assigned to exposure to bright light (10000 lux, n=10), or high-density (4·5×1014 ions/s flow rate, n=12) or low-density (1·7×1011 ions/s, n=10, placebo control) negative air ions. Home treatment sessions occurred for 1 h upon awakening for 5 weeks. Blinded raters assessed symptom severity weekly with the Structured Interview Guide for the Hamilton Depression Rating Scale – Seasonal Affective Disorder (SIGH-SAD) version. Evening saliva samples were obtained before and after treatment for ascertainment of circadian melatonin rhythm phase.

Results. SIGH-SAD score improvement was 53·7% for bright light and 51·1% for high-density ions v. 17·0% for low-density ions. Remission rates were 50%, 50% and 0% respectively. The presence or severity of atypical symptoms did not predict response to either treatment modality, nor were phase advances to light associated with positive response.

Conclusions. Both bright light and negative air ions are effective for treatment of chronic depression. Remission rates are similar to those for SAD, but without a seasonal dependency or apparent mediation by circadian rhythm phase shifts. Combination treatment with antidepressant drugs may further enhance clinical response.

We summarise a series of studies using a MAOI to help establish the validity of a subgroup of depressives referred to as atypical depressives. Patients with reactive mood meeting DSM-III criteria for depressive illness who had associated atypical features (which include hyperphagia, hypersomnolence, leaden paralysis, and rejection sensitivity) were randomised to imipramine, phenelzine and placebo. Non-responders were crossed over, and in all there were over 400 patient trials. Phenelzine consistently was found to be superior to imipramine. Only in trials which included patients lacking atypical, vegetative symptoms was imipramine found to equal phenelzine. We conclude that the researcher and the clinician should consider the relevance of the atypical depressive syndrome.