Trends in Psychopharmacology

Adjunct Professor of Psychiatry, University of California San Diego

Antidepressants

New psychopharmacologic treatments of interest include several late-stage products, most of which have mechanisms similar to products already on the market. In the area of depression, there are drugs that are active metabolites of known antidepressants (desvenlafaxine and radafaxine), and drugs that combine actions of known agents (ie, the “triple” reuptake inhibitors that block the transporters for serotonin, norepinephrine, and dopamine). Triple reuptake inhibitors may provide a therapeutic advance, especially for patients with symptoms hypothetically linked to dopamine, such as cognitive problems, sexual dysfunction, lack of motivation, and fatigue. Other agents in late-stage development for depression include a controlled-release formulation of the serotonin (5-HT)_1A partial agonist, gepirone, and an interesting dual-action agent, agomelatine, which combines agonist actions at melatonin 1 and 2 receptors with antagonist actions at 5-HT_2C receptors. Agents earlier in development for depression include the novel 3 agonists, neurokinin 2 antagonists, corticotropin releasing factor antagonists, vasopressin 1B antagonists, an injectable pentapeptide, nemifitide, and many more.

Antipsychotics

In the area of schizophrenia, late-stage products include new atypical antipsychotics, such as asenapine and iloperidone, as well as a novel dopamine partial agonist, bifeprunox. Agents earlier in development for schizophrenia include those working by non-dopaminergic mechanisms, such as 5-HT_2C agonists; glycine transport inhibitors that boost co-agonist glycine actions at N-methyl-D-aspartate glutamate receptors; positive allosteric modulators of N-methyl-D-aspartate as well as post-synaptic metabotrophic glutamate receptors; and antagonists of presynaptic metabotrophic glutamate autoreceptors. There are also a number of augmentation strategies for novel mechanisms to be added to atypical antipsychotics, including 5-HT_2A inverse agonists and 5-HT_1A antagonists.

Disclosure: Dr. Stahl is a consultant to, is on the speaker’s bureaus of, or receives grant/research support from Acadia, Amylin, AstraZeneca, Biolaunch, Biovail, Bristol-Myers Squibb, Boehringer-Ingelheim, Cephalon, CSC Pharmaceuticals, Cyberonics, Cypress, Eli Lilly, Epix, Forest, GlaxoSmithKline, Janssen, Neurocrine, Neuromolecular, Neuronetics, NovaDel, Novartis, Organon, Otsuka, Pfizer, Pierre Fabre, Sanofi, ScheringPlough, Sepracor, Solvay, Shire, Somaxon, Tetragenix, and Wyeth.