Psychiatry Prospects for 2015: Out With the Old, In With the New?

Nassir Ghaemi, MD, MPH


December 29, 2014

With the new year reviving old desires, one may wonder what, if anything, new will be in store for the practice of psychiatry. Will there be anything practice-changing?

More Meds

New medications are always the first question. I think there will be little that is new in terms of biological mechanisms for new drugs. Drugs that are in process tend to be refinements on current classes. This is not unimportant.

For instance, among our major antipsychotics, the majority have harmful cardiovascular effects, including anti-insulin and lipidogenic effects. This harmful impact increases the likelihood of diabetes, hypercholesterolemia, hypertension, and cardiovascular morbidity and mortality. Widely used agents, such as olanzapine and quetiapine, have these risks.

Because the antipsychotic market is now the biggest market for patented psychotropic drugs (most antidepressants are now generic), pharmaceutical companies still have an incentive to produce new agents for this market. To differentiate themselves, they are testing new agents to try to develop ones that do not have these harmful cardiovascular outcomes. The three newest antipsychotics— asenapine (Saphris®), lurasidone (Latuda®), and iloperidone (Fanapt®)—all are proven to be free of such risks.

Thus, although efficacy has not been improved, there are some benefits for safety. In the coming year, we can expect additional work along these lines, with perhaps another safer antipsychotic or two coming along.

Antidepressants are another story. Over a dozen agents that used to be blockbusters for pharmaceutical profits are still widely used, but are generic. A few new agents in recent years—such as desvenlafaxine (Pristiq®), vilazodone (VIIBRYD®), and vortioxetine (Brintellix®)—have added nothing to better efficacy, and nothing for more safety (unlike the new antipsychotics). Antidepressants were always relatively benign in terms of major medical complications, unlike antipsychotics, so it has been hard to differentiate newer drugs as safer.

Soon—perhaps this coming year, perhaps the next—there may be a new antidepressant with a new mechanism, finally. As opposed to just another serotonin or norephinephrine agonist, the US market has been waiting for something different, as exists with agomelatine in Europe. That agent is a melatonin agonist, and though it isn't any more effective than other antidepressants, it has a different mechanism, which may translate to different (not necessarily fewer) side effects.

For some reason, agomelatine has not been marketed in the United States, but makers of another melatonin receptor agonist, ramelteon (Rozerem), now marketed for insomnia, are trying to prepare the way for marketing that agent for depression in the United States. They seem to be targeting ramelteon for bipolar disorder, perhaps because no antidepressant is approved by the US Food and Drug Administration for this condition. Thus, instead of being the 20th agent for major depressive disorder, they want ramelteon to be the first for bipolar disorder.

Good luck to them. I'm skeptical that it'll work, because most previous data show that no antidepressant works for bipolar disorder (they have been repeatedly shown to be equivalent to placebo in the largest, best-designed trials, when added to standard mood stabilizers). If ramelteon fails in bipolar disorder, this would be unfortunate for practitioners who could use, as is the case in Europe, a new mechanism for managing non-bipolar depressive presentations.

"Addicted" to Amphetamines

It is worth noting that, on the basis of recent data, by far the most booming class of medication is amphetamines and stimulants, and the most rapidly increasing diagnosis is attention-deficit/hyperactivity disorder (ADHD), especially in adults. Even though amphetamines are among the oldest class of psychotropic drugs (marketed first in the 1930s for depression), and thus have been generic for decades, it has been a spectacular success of marketing that patented agents, such as Adderall XR® (amphetamine/dextroamphetamine) and Focalin® (dexmethylphenidate), are widely and increasingly used.

This is not something new that will happen in 2015, but it is the continuation of something new that has been happening in recent years: Clinicians are wildly addicted to adult ADHD and amphetamines. Whether this exuberance will prove to have been irrational is something we will learn, I think, in the not too distant future.


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