Introduction: Looking to the Future of Psychopharmacology

The focus of this Special Report is on some future-oriented aspects of psychopharmacology. First, it is an eclectic set of articles that cover treating resistant depression, using currently illegal drugs to treat psychiatric problems, and finally the potential of using vaccines to treat substance use disorders. Frankly, each of these topics can fill its own Special Report.

One of the considerations in a discussion of the ethics of psychopharmacology is the use of brand-name, expensive drugs versus generics. Sometimes the generics are not equal; there may be a 30% sway in bioavailability between the brand-name drug and available generics. The slow-release technology also differs from brand name to generics and allows for differential adverse-effect issues in practice. This must be weighed against the clear cost difference. Monotherapy approaches are the FDA norm and are speci-fied as first-line treatments in most guidelines. However, monotherapy does not often yield true remission of symptoms.

Polypharmacy certainly drives up cost and adverse effects, but it appears to be more of the norm in clinical practice despite a relative lack of empirical evidence that polypharmacy is inherently more effective. One could discuss off-label prescribing and the use of this rational polypharmacy approach. Does the FDA approval process that ultimately allows advertising provide enough evidence to move more risky drugs into early treatment phases in guidelines instead of using less risky agents that have less empirical data?

Should unipolar antidepressants be used in bipolar, depressed patients? There is an increased risk of manic escalation with formal antidepressants; however, they seem to be devoid of the risk of movement disorders and severe metabolic disor-ders that are possible adverse effects of the current bipolar depression–approved atypical antipsychotics. Perhaps we will find nonmonoamine, nonmania-escalating bipolar depression drugs in the research pipeline. In their article, Roger S. McIntyre, MD, and Danielle S. Cha review some novel approaches to the treatment of bipolar depression that include insulin sensitizers, anti-inflammatory agents, and glutamate-modulating drugs such as ketamine. Ketamine is a legally prescribed drug, but it also has street value and abuse potential. Investigators are looking into this product, and other glutamate modulators, for the treatment of resistant unipolar and bipolar depression.

The article by Daryl Shorter, MD, and Thomas R. Kosten, MD, deals with one of the most interesting advances in psychopharmacological approaches: a vaccine to treat substance use disorders. Simplistically, when we ingest or inject drugs, they enter our bloodstream and make their way across the blood-brain barrier where they cause addiction pathways to fire, allowing for reward pathways and behaviors to occur. A vaccine would allow antibodies in the patient’s system to bind to the addictive drug and mitigate the drug’s ability to cross the blood-brain barrier and, thus, reduce the addiction/reward pathway response in the CNS. This might promote less illicit drug use and help promote sobriety.

Upcoming in Part 2

In Part 2 of the Special Report coming in the May 2011 issue of Psychiatric Times,Michael C. Mithoefer, MD, reviews the evidence for another controlled substance that is not legally prescribed-MDMA (3,4-methylenedioxy-methamphetamine), or ecstasy. This Class I Drug Enforcement Administration drug was once considered for lower category III status. It promotes serotonergic facilitation, and phase 1 and 2 regulatory data are being collected. Findings from these studies on anxiety disorders indicate that MDMA may facilitate psychotherapeutic response. A whole special issue could be dedicated to illegal drugs or drugs of abuse that are used in psychopharmacology practice, ie, ketamine for depression, MDMA for anxiety, sodium oxybate (a GHB derivative) for anxiety and, of course, our currently widespread use of sedatives, hypnotics, and stimulants.

The availability of psychotropic medications has improved the lives of millions of patients with severe mental illness. However, the increased use of these medications has created ethical and societal concerns. Laura Roberts, MD, explores the issues associated with the greater reliance and application of psychotropic medications and the risks associated with their use, such as the reverse effects of some antidepressants on the pediatric population and the serious metabolic effects associated with atypical antipsychotics, as well as what some see as overprescription of psychotropic medications.