- Psychiatric Times Vol 27 No 4
- Volume 27
- Issue 4
Psychopharmacology: Controversies, Breakthroughs, and Tips
Available treatments are so robust that nearly one-third of patients with major depression will achieve full clinical remission with monotherapy.
The new decade brings exciting advances with all their attendant controversies to psychopharmacology. In this introduction to the Special Report, I review the controversies and breakthroughs and provide tips on how breakthroughs such as treatment customization can be used in clinical practice.
Controversies
In the February 27, 2010, edition of
Meanwhile, in the February 10, 2010, edition of
Which author is correct? Is our field moving in a direction of vague and undifferentiated diagnoses, as Shorter argues, or is the jury still out on the best way to define mental illnesses? Are those in the field taking a collective deep breath, as Carey indicates, before embarking on new ways of defining psychopathology?
Anyone who read the editorial
There may be controversy over the best way to measure clinical psychopathology (ie, should we rely on a categorical diagnostic system such as DSM-IV, use a dimensional approach like that used in the UCLA Family Study of Schizophrenia–related personality disorders,3 or should we employ a combination of the two?). However, there is no question that the evolution of psychiatric diagnosis into the mainstream of medical diagnosis will require an integration of clinical psychopathology with phenotypes based on molecular biology, genomic science, cognitive neuroscience, brain imaging, and psychopharmacology outcome research.
A stress variable composed of environmental factors that begin in utero (eg, malnutrition, infectious disease, immunological incompatibilities, psychological abuse, and physical trauma) and span an individual’s lifetime coupled with a family psychopathology variable will most likely be factored into these complex models. This hardly matches the world of “vague and undifferentiated diagnoses” painted by Shorter.
What does this have to do with psychopharmacology? Psychopharmacology in the 21st century will be aimed at phenotypes that define subgroups of mental illness by genomic fingerprint, RNA fingerprint, neurocognitive function, brain imaging, stress factors, familial aggregation of psychiatric disorders, and “good old DSM categories.” Let us take a look at some of the exciting progress that is being made.
Breakthroughs
Sibille and colleagues4 from the University of Pittsburgh and the Universit Franois-Rabelais, Tours, France, have conducted a large-scale study of gene expression of RNA from the amygdala of patients in whom DSM-IV major depression was diagnosed and who have a family history of major depression. The researchers also examined the large-scale gene expression of RNA from the amygdala of a mouse-model of depression.
The examination of gene expression in mice and humans allowed for the bidirectional confirmation of a phylogenetically conserved molecular signature of major depression, as expressed by RNA transcripts. The expression of specific RNA markers was reversed by fluoxetine administered in the mice. A network of 32 genes was identified, and it suggested that oligodendrocytes were negatively affected while neuronal structure and function were enhanced in the amygdala. This was theorized to be a reciprocal effect.
The study undertaken by Sibille and colleagues is an example of translational research at its best; it integrates genomic fingerprint, RNA fingerprint, stress factors, familial aggregation of psychiatric disorders, and DSM categories with medication responsiveness. One can imagine a day when a clinician, faced with a patient who has major depression, orders a genomic scan to identify single nucleotide polymorphisms that have resulted in an altered expression of a network of genes that underlie amygdala function. This genomic fingerprint combined with a familial his-tory of major depression and an environmentally imposed alteration in circadian rhythms (eg, a college student living in a dorm) will predict response to a certain medication. On the other hand, major depres-sion in patients who lack these characteristics will be predicted to be unresponsive to the same medication but instead be responsive to other treatments.
In another study, Harmer and colleagues5 from Warnerford Hospital and the department of psychiatry at the University of Oxford in the United Kingdom found that patients in whom DSM-IV major depression was diagnosed and who also had a phenotype defined by a negative bias in emotional information processing experienced amelioration of the negative bias 3 hours after receiving acute treatment with reboxetine, a selective norepinephrine inhibitor. The improvement in emotional processing was independent of changes in classic depression-rating scales. If this early response is found to predict the long-term effectiveness of antidepressants, not only can it be used to accelerate drug development but it presents another phenotype to be integrated into studies such as the one conducted by Sibille and colleagues. This study helps illustrate the importance of identifying phenotypes that go beyond DSM categories.
Addressing controversies and innovation in clinical practice
The quality of scientific evidence that supports the effectiveness of pharmacotherapies is robust and equal to that of treatment modalities in many other branches of medicine. The disorders that we treat may be umbrellas for many subtypes that will one day respond to individualized treatments. Until that day comes, evidence-based guidelines, such as the recently published 2009 Canadian Network for Mood and Anxiety Treatments
For now, available treatments are so robust that nearly one-third of patients with major depression will achieve full clinical remission with monotherapy. For the two-thirds whose condition does not respond to monotherapies, effective augmentation strategies are available. We can assure our patients that our treatments are well validated and that the scientific basis for behavioral disorders is on its way.
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