Effects of Moclobemide on Event-related Potentials of Depressed Patients — a Preliminary Study (2003)

Abstract Objective: Moclobemide is a reversible inhibitor of monoamine oxidase-A and has become well established as an antidepressant, primarily because of its non-sedating effect and safety. This study was conducted to examine the effect of moclobemide on event-related potentials of depressed patients. Both P300 and contingent negative variation were tested. Patients and Methods: P300 was elicited using an auditory 'oddball' paradigm. Contingent negative variation was elicited using a click-flashing paradigm. Fifteen unmedicated patients who met DSMIV criteria for major depressive episode were examined. After initial event-related potential tests, they were administered moclobemide 150 mg/day. P300 and contingent negative variation were retested after 1 and 6 weeks of moclobemide treatment. The patients were also compared with 33 normal healthy controls. The N2 and P3 components of P300, and both the early and late contingent negative variation components were analysed. Results: Before medication, the depressed patients presented a longer P300 latency and lower contingent negative variation amplitudes than the controls. After 1 week of moclobemide treatment, although the patients were not yet showing signs of symptom remission, an amplitude increase in N2 of P300 and in both early and late contingent negative variation components was found. After 6 weeks of treatment with moclobemide, the patients' depressive symptoms have mostly remitted, and a recovery in the latency of P300 and in reaction time to contingent negative variation paradigm was observed, but there was no further amplitude increase in event-related potentials. Conclusion: While the amplitude increase in event-related potentials might be a direct effect of moclobemide on event-related potentials, the recovery in P300 latency and reaction time of contingent negative variation might be secondary to the remission of depressive symptoms. Key words: Contingent negative variation, Depression, Event-related potentials, Moclobemide, P300 Introduction Moclobemide is a reversible inhibitor of monoamine oxidase--A (RIMA). As a newer member of the monoamine oxidase inhibitor (MAOI) class, moclobemide is devoid of hepatic toxicity, and also has a very low liability for increasing the effect of dietary tyramine, so that strict diet restrictions may not be necessary. (1) The drug has become well accepted in the treatment of depression because of its non-sedating effect and safety. (2,3) Unique electrophysiological effects of moclobemide had been observed by some researchers, (4,5) who found that the drug could increase rapid eye movement (REM) sleep in patients with depression, throwing doubt on the assumption the reduction of REM sleep common many antidepressants was an important pharmacological requirement for therapeutic effects. To our knowledge, no study has yet examined the effect of moclobemide on event-related potentials (ERPs). The auditory evoked potential P300 and contingent negative variation (CNV) are commonly measured ERPs in psychiatry. (6,7) P300 has often been obtained using an 'oddball' paradigm in clinical studies. Two major endogenous components in P300 are N2 and P3. N2 is related to the automatic and controlled discriminating processing of stimuli, and P3 reflects the memory updating and attentional allocation aspects of information processing. CNV consists of 2 different components, an 'early' and a 'late' CNV. Early CNV is related to the orienting response and exhibits a rapid habituation. The late CNV is associated with motor preparation and stimulus anticipation. (8,9) Application of ERPs in psychopharmacological studies showed considerable promise. (10) ERPs seemed to be a sensitive and timely indicator in reflecting some of the pharmacological effects of psychotropic drugs (including antipsychotic agents, antidepressants, etc.) on the brain. ERPs are excellent in temporal resolution. …