Spring 2013 Maryland Psychiatrist
By Neil Sandson, MD
The Maryland Psychiatric Society hosted a conference at Sheppard Pratt on March 23, 2013 entitled “Psychopharmacology – Updates, Advances & New Information”, for which I was asked to give a presentation about new developments concerning atypical antipsychotic agents. So I pondered. It had been a while since the newest triad of atypicals (asenapine, iloperidone, and lurasidone, in generic alphabetical order) made their appearance, and long-acting injectable paliperidone isn’t news anymore. I’d heard that a promising glutamatergic agonist hadn’t panned out, so that wasn’t news either, at least not good news. I dug a little deeper and learned that in December 2012, the FDA approved loxapine (a typical antipsychotic, admittedly, but I was getting less choosy) inhalation powder for agitation in patients with schizophrenia and bipolar disorder. Visions of loxapine grenades lobbed by SWAT teams filled my mind, until I read further. Ah, it requires voluntary use of a hand-held inhalation device. Hmmm, you can only use it in a facility that is equipped to treat the possible life-threatening bronchospasm that could ensue. My enthusiasm was waning fast.
So I then did what I’ve learned to do since childhood when I got stuck — call someone smarter than I. Over the ensuing days, I talked to Scott Aaronson, Bob Buchanan, and one of my most cherished mentors, John Boronow. The comforting (for my ego) but disappointing news was that the reason I hadn’t heard much is that there wasn’t much to hear.
I then wondered if this situation applied to just atypicals, so I checked for all new, non-trivial (excluding silly stuff like low-dose doxepin for insomnia) FDA indications among antipsychotics (not already mentioned above), antidepressants, and mood stabilizers since January 2010. In chronological order, here’s what I found:
November 2010: Duloxetine approved for treatment of chronic musculoskeletal pain
January 2011: Vilazodone approved for treatment of Major Depressive Disorder
February 2011: Aripiprazole approved for maintenance treatment of bipolar I disorder as an adjunct to either lithium or valproate
April 2011: Paliperidone approved for treatment of schizophrenia in adolescents
April 2011: Lamotrigine (XR) approved for conversion to monotherapy for treatment of partial seizures in appropriate patients
So are we excited yet? No, me neither.
What’s going on? Are we running out of good pharmacologic ideas? Is the current economic and regulatory climate killing good research? Are we starting to encounter the limits of “business as usual”?
Regardless of the causes, signs of stagnation are evident. When I was a resident in the early 1990s (yes kids, there wasn’t texting then, we actually picked-up phones and talked to each other for minutes at a time!), there were some “hot” ideas floating around, such as tamoxifen for rapid cycling bipolar disorder, and repetitive transcranial magnetic stimulation (rTMS) was an emerging technology. A few years later, there was talk of mifepristone (also known as RU-486 or the “morning-after pill”) working within days for psychotic depression, vagal nerve stimulation (VNS), neuropeptides, substance P antagonists, and the like. VNS and rTMS have made it to the medical marketplace, but they haven’t exactly taken it by storm. Deep brain stimulation seems to be generating some interest, but we will have to wait and see, and it certainly doesn’t promise to be a readily available intervention in any case. The other stuff has sort of petered-out over time.
As many of you know, my personal coping strategy for not having much that’s NEW to do, has been to focus endlessly on what NOT to do, to the tune of drug-drug interactions. In the absence of new drugs, others have tried to create new drug combinations, pushing n! psychopharmacology to its rational limits, and regrettably beyond. What motivates such prescribing behaviors is the ever-present gap between our therapeutic hopes and the reality. For example` , antipsychotic polypharmacy, a practice with vast prevalence but scant supporting evidence, is an accurate barometer of our therapeutic desperation. Of course, as we all know, newer does not necessarily mean better, but our success rates with our array of medications are sufficiently modest that most psychiatrists are eager to try out the newest drug.
Of the hypotheses I ventured above, I actually think the most likely explanation is that we are truly approaching the limits of what pills can do. When you stop to think about it, taking pills for a psychiatric condition is a remarkably gross, non-specific, inelegant strategy. I would much rather micro-pipette stuff right where it needs to go, the liver and the blood-brain-barrier be damned, but we just aren’t there yet. Although interventions like rTMS and VNS haven’t revolutionized the treatment of mental illness, I think they are intriguing steps in more promising directions than drugs. That is where I think (hope) the future lies.
As my thoughts move in this direction, a delicious irony occurs to me. We already employ a remarkably elegant and targeted somatic intervention in the treatment of a broad array of mental illnesses. Efficacy rates can vary from modest to striking, and the side-effect burden is vastly less, or at least quite different, compared to medications. It takes longer to learn how to skillfully utilize this intervention than medications, but most practitioners regard the effort as more than worthwhile.
It’s called psychotherapy.
Dr. Neil Sandson is Clinical Associate Professor of Psychiatry at University of Maryland School of Medicine, and Staff Psychiatrist at Baltimore VA Medical Center.
Opinions expressed in the article are the author’s own, and do not necessarily reflect the opinions of the Editorial Advisory Board or the Maryland Psychiatric Society.