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IN THIS ISSUE:
April 2007

Paliperidone (Invega)
Paliperidone (Invega), recently approved to treat schizophrenia, is similar to risperidone (Risperidone) in efficacy and adverse effects.

Methylphenidate for ADHD in Preschool Children
Low doses of methylphenidate (Ritalin and others) are effective and safe for preschool children with ADHD but may cause more side effects than in older children.

A Case of Wernicke's Encephalopathy
Wernicke's encephalopathy is caused by thiamine deficiency, usually due to alcoholism or malnutrition.

In Brief
Taste Altered in Mood Disorders; Reduced Gray Matter May Predict Schizophrenia; FDA Issues Methadone Alert

Two Ineffective Adjuncts for Mania
Olanzapine (Zyprexa) and topiramate (Topamax) add no therapeutic benefit as adjunctive treatments for bipolar disorder.

Schizophrenia, Substance Abuse, and Violence
Substance abuse increases the risk of violent behavior in people with schizophrenia.

In Brief

April 2007

A recent study found that taste function in humans is extremely plastic and is affected by changes in the serotonin and noradrenergic systems (TP Heath et al. J Neurosci 2006;26:12664-12671). In 20 healthy male subjects, the selective serotonin reuptake inhibitor paroxetine (Paxil and others) reduced taste thresholds for sweet by 27% and for bitter by 53%. The noradrenaline reuptake inhibitor reboxetine (not available in the United States) lowered taste thresholds to bitter by 39% and sour by 22%. In addition, the researchers found a significant positive correlation between mean trait baseline anxiety scores and mean baseline taste thresholds for bitter and salt. Their results may explain decreased appetite in anxious and depressed individuals and complaints of altered taste in some patients taking antidepressants.

Simple clinical and cognitive tests can predict which predisposed subjects will not develop schizophrenia but are not as good at predicting who will develop psychosis. D. E. Jon and others tested the theory that the onset of schizophrenia is preceded by a reduction in the brain's gray matter (BMC Med 2006;4:29). Sixty-five subjects with a family history of schizophrenia had two structural magnetic resonance imaging brain scans over about 1.5 years. Of individuals who showed a reduction over a certain threshold of gray matter in the inferior temporal gyrus, 60% went on to develop schizophrenia, while 92% of the individuals who did not experience these changes did not develop the disorder. The authors conclude that changes in grey matter can be used as part of a positive predictive test for schizophrenia and help physicians determine who would benefit from early interventions to help delay or attenuatethe disease.

Late last year, the US Food and Drug Administration (FDA) issued an alert about deaths, narcotic overdose, and serious cardiac arrhythmias in patients initiating methadone (Dolophine) treatment for pain control or switching to methadone after being treated for pain with other narcotics (US Food and Drug Administration Center for Drug Evaluation and Research web site. Available at http://www.fda.gov/cder/drug/infopage/methadone/default.htm. Accessed February 15, 2007). Methadone can have toxic cardiac effects, such as QT prolongation and torsade de pointes. With a duration of analgesic action of 4 to 8 hours but an elimination half-life of 8 to 59 hours, methadone can accumulate to toxic levels in the body if it is taken too often, if too much is taken, or if it is coadministered with certain other medicine or supplements. Physicians prescribing methadone should be familiar with the drug's toxic effects and pharmacological properties, carefully select doses for pain relief, slowly titrate to an analgesic effect, and closely monitor patients starting methadone treatment or receiving a change in dose. The 40-mg dispersible tablets, which are approved by the FDA only for detoxification and maintenance treatment of narcotic addiction, should not be prescribed for pain relief.

Heather S. Hopkins