Psychotic Depression - Experimental Treatment Strategies

Experimental Treatment Strategies

The current treatments of PMD are reasonably effective but tend to carry a high side effect burden and may take a long time to work. Combination treatment with atypical antipsychotics and SSRIs tend to be associated with significant weight gain and sexual dysfunction. TCAs are lethal in overdose and some are associated with extra-pyramidal side effects including tardive dyskinesia. Finally, ECT has side effects of temporary cognitive deficits (e.g., confusion, memory problems), in addition to the burden of repeated exposures to general anesthesia.

Among the newer experimental treatments is the study of glucocorticoid antagonists, including mifepristone. These strategies may treat the underlying pathophysiology of PMD by correcting an overactive HPA axis. By competitively blocking certain neuro-receptors, these medications render cortisol less able to directly act on the brain.

Transcranial magnetic stimulation (TMS) is being investigated as an alternative to ECT in the treatment of depression. TMS involves the administration of a focused electromagnetic field to the cortex to stimulate specific nerve pathways. A number of early studies have shown promise of TMS in MDD with few side effects. TMS does not require anesthesia and has not been associated with significant cognitive deficits.

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