Clinical symptoms of major depression are associated with the intensity dependence of auditory event-related potential components.

The intensity (loudness) dependent amplitude change (IDAP) of the auditory event-related potential (ERP) has been shown to be associated with the outcome of treatment with selective serotonin reuptake inhibitors in major depression. The purpose of the present study is to evaluate associations between clinical symptoms of major depression and the IDAP as an indirect indicator of cortical serotonergic function. We assessed 40 in-patients suffering from a major depressive episode (DSM-IV) prior to antidepressant treatment. Psychometric characteristics of depression were assessed by means of psychiatric rating scales (CGI, HDRS, HAMA, STAI and BDI) and evaluated for associations with auditory evoked P1, N1, P2 as well as P1/N1 and N1/P2 peak to peak amplitude slopes. Our data revealed a positive correlation of the intensity dependent N1 amplitude slope with the degree of certain somatic symptoms of depression: loss of appetite and weight, insomnia, and sexual dysfunction. The results of our study might contribute to a more specific clinical basis in the differential indication of serotonergic versus noradrenergic antidepressants.

Treatment effects of serotonergic and noradrenergic antidepressants on the intensity dependence of auditory ERP components in major depression.

The intensity dependent amplitude change of auditory evoked potentials (IDAP), an assumed indicator of the level of central nervous serotonergic neurotransmission, was measured in major depressive disorder (MDD, DSM-IV: 296.2, 296.3; APA 1994) before and after treatment with either a selective serotonin reuptake inhibitor or a selective noradrenaline reuptake inhibitor antidepressant and compared with the results of a healthy control group. Auditory evoked P1, N1, P2, P1/N1 and N1/P2 peak-to-peak amplitudes were evaluated in 26 in-patients with MDD prior to and after antidepressant treatment with citalopram (24 days, n=14) or reboxetine (25 days, n=12), and in 43 healthy control subjects. Clinical symptoms of MDD were assessed by means of standardized psychiatric rating scales (CGI, HDRS, HAMA and BDI). The IDAP within the control group remained stable over 24 days (N1 amplitude slope retest ANOVA p=.79). Neither applied antidepressants nor decrease of HDRS total score during treatment had a significant effect on the IDAP in the patients' sample. The conclusion that the IDAP does not reflect the temporary depressive state in MDD is discussed.

The intensity dependence of auditory ERP components in unmedicated patients with major depression and healthy controls. An analysis of group differences.

BACKGROUND: The intensity dependent amplitude change (IDAP) of auditory evoked Event Related Potential (ERP) components has been found to correlate with the level of central serotonergic neurotransmission and to be associated with response to certain antidepressants. However, it is currently unknown whether there is a general abnormality of the IDAP in patients with major depression. Therefore, the purpose of the present study was to compare the IDAP in unmedicated depressed patients with that of healthy control subjects. METHODS: We report the results of a study evaluating the change of auditory evoked P1, N1, P2 as well as P1/N1 and N1/P2 peak to peak amplitudes in 34 in-patients with major depressive episode prior to antidepressant treatment, and 44 healthy control subjects. Clinical symptoms of depression were assessed by means of standardized psychiatric rating scales (CGI, HDRS, HAMA and BDI). RESULTS: In multivariate analyses of variance we found no group differences in the intensity dependent increase neither of the P1, N1, and P2 nor of the P1/N1 and N1/P2 peak to peak amplitudes between patients and controls. CONCLUSIONS: Our data revealed no general abnormality of the IDAP in patients with major depression in comparison to healthy control subjects. This result suggests that specific alterations of the IDAP are not to be expected in major depression in general, these may be confined to subgroups of depressed patients.

The intensity dependence of the auditory evoked N1 component as a predictor of response to Citalopram treatment in patients with major depression.

The intensity dependence of the auditory evoked N1 ERP component (IDAP) has been suggested as an indicator of central serotonergic neurotransmission with relevance to pharmacological treatment. We report the results of a study evaluating the IDAP in 16 in-patients fulfilling DSM-IV criteria for major depressive episode in the course of treatment with the SSRI Citalopram. Our data revealed a significant correlation between the intensity slopes of the N1 amplitude prior to Citalopram treatment and treatment response: patients with higher intensity slopes of N1 amplitude showed a significantly stronger decrease of HDRS-Score after Citalopram treatment than patients within the lower intensity slope ranges. Our results indicate an association of N1 amplitude intensity dependence with response to antidepressant treatment with Citalopram.

Safety and efficacy of combined clozapine-lithium pharmacotherapy.

Several case reports described neurotoxic side-effects in the course of a combined clozapine-lithium treatment. Here we report on the safety and efficacy of this combination in a sample of 44 hospital patients. Medical records were retrospectively audited and a subsample of 23 patients was re-assessed. Mean total duration of combined treatment was 23.5 months. The combination (indications: prophylaxis; treatment of affective symptoms or aggression/excitement; augmentation of neuroleptic efficacy) was rated effective in 84% and adverse events were reported in 64% of the patients. Notably, most of the adverse events were benign and transient. However, 8 patients (18%) developed transient neurological adverse events that were genuinely novel in only 3 patients (7%) and coincided with high dosage of medication or high plasma levels or serotonergic (antidepressant) co-medication. Our data suggest that combined clozapine-lithium treatment may appear to be safe and effective when administered within a moderate therapeutic dose range and without serotonergic co-medication or other substances interfering with clozapine metabolism.