A dissertation submitted to Faculty of Medicine in part fulfilment of the required for the degree of Master of Medicine in Psychiatry at the University of the Witwatersrand / Moclobemide is a reversible monoamine oxidase inhibitor. It is a short acting antidepressant, and previously studies were done comparing 300 to 600 mg dosages administered three times daily. Data on a twice daily dosage schedule is limited. This study compares the efficacy and tolerability of Moclobemide 150 mg twice daily as compared to two different three times a day schedules with total daily dosages of 300 to 450 mg respectively. Thirty one adult outpatients with major depressive disorder (as defined by DSM-IIIR) were included in this trial. It was controlled in a randomised double-blind manner. All treatments were found to be effective and no clinically significant differences between treatments could be demonstrated in this respect. Group 3 (150 mg b.d.) was found to be slightly more effective than the other two groups. Moclobemide was found to be effective at all dosage regimens with respect to treating co-morbid symptoms of anxiety and agitation. There were no differences between the groups with respect to type and frequency of adverse events. Overall tolerability was found to be good in all the treatment groups. Since the twice daily dosage is more convenient, it has been suggested that compliance will be enhanced on this regimen. The treatment response rates obtained confirm this conclusion. / IT2018

Deep brain stimulation (DBS) is currently being investigated as a therapy for treatment-resistant depression, with promising results. However, it is not clear whether or not DBS works via the same mechanisms as those induced by antidepressant medications. Processes currently implicated in antidepressant effects include neuroplastic changes and promotion of neurogenesis. We investigated the effects of chronic treatment with three different classes of antidepressants and DBS on markers of neuroplasticity (brain-derived neurotrophic factor, (BDNF), and phosphorylated cyclic-AMP regulatory element binding protein, (pCREB)) and neurogenesis (Ki-67, bromodeoxyuridine (BrdU) and doublecortin) in the rat hippocampus. No clear treatment effects were seen on BDNF, pCREB and Ki-67 levels. However all treatments caused increased levels of BrdU (range: 46%-96%) and doublecortin (8%-61%), although these effects were statistically significant only for DBS and amitriptyline, respectively. This overall pattern of results may suggest that diverse antidepressant treatments could possibly share common mechanisms involving cell survival and neuronal differentiation. Potentiated effects of DBS on cell survival may underlie its efficacy in treatment-resistant depression.

Deep brain stimulation (DBS) is currently being investigated as a therapy for treatment-resistant depression, with promising results. However, it is not clear whether or not DBS works via the same mechanisms as those induced by antidepressant medications. Processes currently implicated in antidepressant effects include neuroplastic changes and promotion of neurogenesis. We investigated the effects of chronic treatment with three different classes of antidepressants and DBS on markers of neuroplasticity (brain-derived neurotrophic factor, (BDNF), and phosphorylated cyclic-AMP regulatory element binding protein, (pCREB)) and neurogenesis (Ki-67, bromodeoxyuridine (BrdU) and doublecortin) in the rat hippocampus. No clear treatment effects were seen on BDNF, pCREB and Ki-67 levels. However all treatments caused increased levels of BrdU (range: 46%-96%) and doublecortin (8%-61%), although these effects were statistically significant only for DBS and amitriptyline, respectively. This overall pattern of results may suggest that diverse antidepressant treatments could possibly share common mechanisms involving cell survival and neuronal differentiation. Potentiated effects of DBS on cell survival may underlie its efficacy in treatment-resistant depression.