Neuroscience for Kids Website

Dr. Philip Grossi
Monday, 02 August 2010

Neuroscience for Kids is a great website for kids and adults.  It's laudable goal is to promote science and knowledge about neuroscience.  It is heavy with content and provides information about neuroanatomy, neurophysiology, neuropharmacology, special senses, mental illnesses, and sleep as well as providing interactive illusions and offline games.  They provide an event calendar and book reviews.  Great site!!

Generics vs. Branded Drugs

Dr. Philip Grossi
Monday, 02 August 2010

 When drug therapy is involved in treatment, a frequent conversation revolves around the use of generic drugs in place of the brand-name drug.  In the United States generics account for about 72% of the market and that is projected to rise to about 90% in the next six or seven years.  For most patients, generic substitution is acceptable and cost effective.  For particular circumstances switching to a generic or between generics may present problems of efficacy or tolerability. 

illustration to  generics vs branded drugs blogIn the United States the FDA reviews studies submitted by pharmaceutical companies and either authorizes of denies authorization to the company to market their drug for a particular purpose. In the case of generic authorization, the efficacy and safety of the molecule is a given and so  the FDA  only requires bioequivalence studies which must demonstrate that the generic product delivers 90% to 125% of the name brand drug. These studies typically have a small n and require a confidence interval of 90%. To say this another way, various pharmacokinetic parameters such as max concentration, time to max concentration, area under the curve, and absorption time fall within the 90% to 125% seen in the branded drug.  The FDA does not compare one generic to another but only to the branded drug.

In my office I routinely advise patients to avoid generic substitutes for Tegretol, Effexor, Parnate, Ritalin, and Lamictal (for the first prescription). I also advise patients to examine the prescription label for the name of the generic manufacturer.  It is common to discover that one generic product is less effective than another.  In those instances, this should be discussed with the pharmacist.

The ultimate resource for generic drugs is the Orange Book which is maintained and updated daily by the FDA.

The Future of Psychiatry

Dr. Philip Grossi
Wednesday, 21 October 2009

For my inaugural blog I have chosen an inherently risky topic which is the future of psychiatry. We call it the future because it is unknown.  What follows is an educated guess based on current knowledge, advances in technologies, and extant trends.

illustration to future psychiatry blogThe major psychiatric disorders of schizophrenia, bipolar disorder, autism, attention deficit hyperactivity disorder, obsessive-compulsive disorder are heterogeneous syndromes with extraordinarily varied phenotypic presentations.  Indeed they are so varied that any psychiatrist making such a diagnosis should present it as a probability and not as a Boolean, true/false diagnosis, but as a probability judgment by the psychiatrist.  The underlying genetics and cellular chemical cascades are largely unknown.  In addition it is becoming clear that these disorders are polygenetic, produce disruptions in chemical pathways in different neural circuits which in turn result in shared clinical symptoms that lead to the same or different clinical diagnoses. If this weren't daunting enough, recent work with copy number variations (CNV) in these disorders (Cook and Scherer, Neuron, 2008) and the increasing realization of the importance of epigenetic factors point to a prolonged research effort.  Gone are the days when the newly sequenced genome was thought by many to yield the answers to disease etiology within a decade.  Mother Nature is quite an adversary.

A law of technology is that people invariably overestimate the short term impact (as above), but underestimate the long term impact.  The research effort will proceed along two tracks: Genomics and Circuit Analysis.  Over the last ten years, the speed of sequencing DNA has increased 100,000 fold and the cost has fallen from about ten million to about $10,000.  This dramatic progress now allows researchers to sequence entire genomes for thousands of individuals and to use computational analysis to assess them.  Gone are the days of hypothesis-driven GWAS.  Many amplified or deleted segments of DNA are needed for nerve cell function and not other tissue types.  In a recent discussion Tom Insel, Director  NIMH, called attention to the fact that many of the mutations are seen only once and he referred to them as "private mutations."

Expert consensus now expects that many hundred mutations are involved in the disruption of neural circuits that produce psychiatric phenotypes.  Identifying the distribution, structure, function, and dysfunction of these neural circuits will be crucial in unraveling the mystery of psychiatric etiology.  Researchers Maybery, Shah, and Baxter have already added significantly in this area.  Recent advances in diffusion tensor imaging (DTI) allow better tracing of neural circuits and connections.  Other new strategies to study circuits include multiphoton imaging and calcium imaging.  At the animal level, knockout and knockin mice will be used to study psychiatric phenotypes as more genes are identified in human DNA of individuals with these disorders.

Lest we forget, these psychiatric phenotypes typically strike people early in life, are life-long, are often disabling, adversely influence interpersonal relationships, and generate an enormous cost to the society as a whole to say nothing of the enormous anguish draped over the sufferer.