Antipsychotics and Kids: The Controversy Goes On and On

On December 4, 2009, the FDA approved the use of two more antipsychotic medications — Zyprexa and Seroquel — for treating schizophrenia and bipolar disorder in teens. Risperdal and Abilify are also specifically approved for the same use in this age group.

In association with the approval of Zyprexa and Seroquel, the FDA also stated it wants to know more about the risk of weight gain and diabetes in youth taking these drugs and other antipsychotics as well.

It has been clear for years that weight gain and other endocrine risks are associated with these medications, and their warning labels say so. Some evidence however, suggests that these issues are even more paramount in kids.

A study published in the November, 2009 issue of JAMA ( Journal of the American Medical Association) found that children and adolescents using antipsychotics gained significantly more weight over an 11-week period than comparable kids who weren’t taking the drugs. Those on Zyprexa demonstrated the most weight gain – 19 pounds – although weight gain was also associated with several others of these antipsychotics.

Zyprexa labeling does warn that youth are not only likely to gain weight, but are prone to gain more weight compared to adults taking the drug. But the labels for the other antipsychotics the FDA is investigating – Risperdal, Abilify, Geodon and Seroquel – don’t state whether children and teens are at higher risk than adults for weight gain. Frankly, I believe the reason for this is that Zyprexa clearly produces the most weight gain – regardless of age.

The safety conundrum associated with second-generation antipsychotic use in the treatment of schizophrenia and bipolar disorder in youth will linger until a new, safer generation of compounds is developed. These safer agents aren’t coming soon, as some big Pharma companies are planning to cut billions of dollars in annual research and development spending. When it comes to treating psychotic and bipolar disorders in children, I staunchly agree that the balance needs to favor minimizing risks. However, for children with serious and potentially dangerous behavioral problems such as severe aggression, violent outbursts and out-of-control tantrums, what other viable options are there outside of the use of these drugs? Mood stabilizers such as lithium and Depakote carry similar risks of marked weight gain, in addition to other debilitating side effects. Benzodiazepines are not approved for use in the pediatric population period, and carry the risk of potential abuse and dependence. Lastly, with many states experiencing severe cutbacks in mental health care services, there is a paucity of well trained, experienced behavioral specialists with the requisite skills for managing the above-mentioned behaviors in youth. And even if very capable behaviorists were in adequate supply, how on earth could the management of out-of-control behavior be successfully or even adequately facilitated in the absence of medication augmentation?

The bottom line is this: Don’t look for prescribers of these medications to change their prescription-writing habits anytime soon. Why? Because for children with serious and potentially dangerous behavioral problems associated with schizophrenia, bipolar disorder or other associated syndromes, physicians as a whole continue to conclude that the benefits of medication use typically outweigh the risks.

Saphris (asenapine): A New Entry Into the Ever-Growing Antipsychotic Mix

On August 14, 2009, the FDA approved Saphris (asenapine) as a new second-generation antipsychotic for the treatment of both schizophrenia and bipolar disorder. It is available only as a sublingual tablet, meaning that it is not effective if swallowed, and it must be left under the tongue to dissolve for it to be absorbed into the bloodstream. The available studies haven’t shown that Saphris (asenapine) provides any unique therapeutic advantage over other second-generation antipsychotics. The main contribution is that clinicians and patients will have yet another option, as if the clinical community needs another antipsychotic that is not special in any other way, and certainly not deserving of “novel” or “designer” drug status.

The manufacturer, Schering-Plough, is promoting the drug on the premise that it’s more effective at improving the negative and cognitive symptoms of schizophrenia compared to other atypical antipsychotics, and that Saphris (asenapine) has a better safety profile.

The safety profile issue has been used over and over before. While the drug demonstrated less weight gain compared to Risperdal ( risperidone) or Zyprexa (olanzapine), it has an elevated level (18%) of extrapyramidal symptoms (EPS) – comparable to first generation antipsychotics.

Schering-Plough’s specialty sales force is handling the detailing of Saphris (asenapine) – as opposed to its primary cast of sales representatives – targeting psychiatrists to prescribe this new antipsychotic.