7. From healing the mind to repairing the brain
It is well-established that depression is associated with loss of dendritic spines and arborizations, loss of synapses, and diminishment of glial cells, especially in the hippocampus17 and anterior cingulate.18 Treating depression, whether pharmaceutical or somatic, involves reversing these changes by increasing neurotrophic factors, enhancing neurogenesis and gliogenesis, and restoring synaptic and dendritic health and cell survival in the hippocampus and frontal cortex.19,20 Treating depression involves brain repair, which is reflected, ultimately, in healing the mind.
8. From pharmacotherapy to neuromodulation
Although drugs remain the predominant treatment modality for depression, there is palpable escalation in the use of neuromodulation methods.
The oldest of these neuromodulatory techniques is electroconvulsive therapy, an excellent treatment for severe depression (and one that enhances hippocampal neurogenesis). In addition, several novel neuromodulation methods have been approved (transcranial magnetic stimulation and vagus nerve stimulation) or are in development (transcranial direct-current stimulation, cranial electrotherapy stimulation, and DBS).21 These somatic approaches to treating the brain directly to alleviate depression target regions involved in depression and reduce the needless risks associated with exposing other organ systems to a drug.
9. From monotherapy to combination therapy
The use of combination therapy for depression has escalated with FDA approval of adjunctive use of atypical antipsychotics in unipolar and bipolar depression. In addition, the landmark STAR*D study1 demonstrated the value of augmentation therapy with a second antidepressant when 1 agent fails. Other controlled studies have shown that combining 2 antidepressants is superior to administering 1.22
Just as other serious medical disorders—such as cancer and hypertension—are treated with 2 or 3 medications, severe depression might require a similar strategy. The field gradually is adopting that approach.
10. From cortical folds to wrinkles on the face
Last, a new (and unexpected) paradigm shift recently emerged, which is genuinely intriguing—even baffling. Using placebo-controlled designs, several researchers have reported significant, persistent improvement of depressive symptoms after injection of onabotulinumtoxinA in the corrugator muscles of the glabellar region of the face, where the omega sign often appears in a depressed person.23,24
The longest of the studies25 was 6 months; investigators reported that improvement continued even after the effect of the botulinum toxin on the omega sign wore off. The proposed mechanism of action is the facial feedback hypothesis, which suggests that, biologically, facial expression has an impact on one’s emotional state.
Big payoffs coming from research in neuroscience
These 10 paradigm shifts in a single psychiatric syndrome are emblematic of exciting clinical and research advances in our field. Like all syndromes, depression is associated with multiple genetic and environmental causes; it isn’t surprising that myriad treatment approaches are emerging.
The days of clinging to monolithic, serendipity-generated models surely are over. Evidence-based psychiatric brain research is shattering aging dogmas that have, for decades, stifled innovation in psychiatric therapeutics that is now moving in novel directions.
Take note, however, that the only paradigm shift that matters to depressed patients is the one that transcends mere control of their symptoms and restores their wellness, functional capacity, and quality of life. With the explosive momentum of neuroscience discovery, psychiatry is, at last, poised to deliver—in splendid, even seismic, fashion.