Safety Watch

News, Developments and Perspectives

Orlaam Is Withdrawn

Suicide and Violence Issue

The public and political perceptions of drug safety are driven by drug withdrawals, just as fears about airline safety are stoked by the glare of media publicity surrounding a rare but tragic crash.

The safety withdrawal of Orlaam, however, occurred so quietly that press attention was almost non-existent. Only the 1999 withdrawal of GlaxoSmithKline's Raxar was achieved more stealthily. In the case of Raxar, the only mention was a press release on the company web site.

Roxane Laboratories' Orlaam (levomethadyl) is an opoid antagonist that is similar to methadone except that it carries additional safety risks of potentially lethal cardiac adverse effects. Like methadone, it is used for the treatment of narcotics addiction. Like several other withdrawn drugs (Propulsid, Seldane, Hismanal) it prolonged the QT interval which raises the risk of cardiac arrest. Orlaam was withdrawn in Europe in March 2001.

With very modest sales and a patient population of former narcotics addicts, Orlaam appears unlikely to trigger a pharmaceutical mass tort with thousands of lawsuits.

For more detail see the MedWatch notice and manufacturer's dear doctor letter.

The question whether antidepressant drugs can trigger suicide or violent behavior in some patients has been a hot button issue for more than a decade. The legal and scientific battle over the evidence has been celebrated and lengthy. The FDA, many practitioners and some juries have been successfully convinced that these highly popular drugs are not to blame, but rather the patients' underlying psychiatric illnesses accounted for numerous bizarre cases of murder and suicide.

Now, however, a series of events has reopened this emotion-laden issue. The first questions came as a result of a small study of 20 healthy volunteers conducted by British psychiatrist David Healy. Two reported suicidal impulses or feelings with Zoloft. The most compelling account came from the diary of a emergency room doctor in the study who detailed how close she came to succumbing to the impulse to crash her car into a bridge abutment.

Next came a $6.4 million jury verdict against Paxil in a case tried by Houston attorney Andy Vickery. The jury found Paxil played a role in motivating a 60-year-old Wyoming man to kill his wife, daughter, granddaughter and himself.

Finally, two antidepressants now carry warnings about the risk of suicide and violence when given to children. The British Medicines Control Agency has cautioned doctors not to give Paxil to children. In the United States, Wyeth has issued a similar warning about Effexor.

Case settlements are typically sealed. But it is likely that manufacturers are secretly paying substantial amounts in suicide and violence cases while publicly denying that their drugs could trigger such behavior. Drug safety recommendation: drug companies should be required to report drug case settlements to the Food and Drug Administration. Additional materials on antidepressant drugs....