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September 2010

Personalized Medicine
Even before genomic advances are ready for clinical use, "low-tech" aspects of personalized medicine can enhance psychiatric treatment.

Treating Patients with Schizophrenia: The Importance of Adherence
Antipsychotics can't work if patients don't take them. Nonadherance is a major cause of relapse among patients with schizophrenia.

Valproic Acid and Congenital Malformation
Exposure to valproic acid in the first trimester of pregnancy increases the risk of many congenital malformations in newborns.

In Brief
Bone Mineral Density Is Lower in Depressed than Nondepressed People; Few Adolescents Who Die by Suicide Have Had Recent Exposure to SSRIs

IV Ketamine Infusion Decreases Suicidal Ideation
In a study of treatment-resistant inpatients with major depressive disorder, a single IV infusion of ketamine rapidly decreased suicidal ideation.

SSRIs May Increase the Risk of Cataracts
In a pharmacoepidemiologic study, the use of selective serotonin reuptake inhibitor (SSRI) antidepressants was associated with a greater risk of cataracts among elderly patients.

IV Ketamine Infusion Decreases Suicidal Ideation

September 2010

The complex biological and psychosocial factors that lead some people to take their own lives remain mysterious. What is clear, however, is that suicide is prevalent, on the rise in certain groups (such as members of the active armed forces), and deeply disruptive to families and communities. Obviously, depressed patients are one group at high risk for suicide. How might physicians attenuate this risk?

In research that has received widespread attention, Zarate and others at the National Institute of Mental Health showed that an intravenous (IV) infusion of the N-methyl-D-aspartate (NMDA) antagonist ketamine produces a rapid antidepressant effect in patients with treatment-resistant major depressive disorder (MDD).1 This study, however, excluded patients with significant suicidal ideation. DiazGranados and colleagues have gone on to study the effects of a single IV ketamine infusion in treatment-resistant inpatients with MDD, who were enrolled regardless of severity of suicidal thinking.2 In addition to analyzing the effects of the infusion on depression symptoms, the authors also measured suicidal ideation.

Thirty-three patients received this open-label infusion of ketamine, 0.5 mg/kg over 40 minutes. Subjects with high baseline scores on a suicidal ideation scale showed a significant decrease in suicidal ideas within 230 minutes, with a mean time of only 44 minutes postinfusion. The size of the effect was substantial: d=2.36 (95% CI, 1.56–3.16) at 40 minutes and d=1.27 (95% CI, 0.62–1.92) at 230 minutes. Participants in the study had been ill, on average, for 26 years, and their current MDD episode had lasted a mean of approximately 8 years. More than half of the patients had a lifetime history of suicidal ideation, and 30% had previously attempted suicide.

The authors note their relatively small sample size and the open-label nature of their study. Nonetheless, these data support further research on modulating the glutamatergic system to attenuate suicidal thinking in depressed people.

1Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK: A randomized trial of an N-methyl-d-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 2006;63:856–864.

2DiazGranados N, Ibrahim LA, Brutsche NE, Ameli R, Henter ID, Luckenbaugh DA, Machado-Vieira R, Zarate CA Jr: Rapid resolution of suicidal ideation after a single infusion of an N-methyl-d-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry, in press.