Faculty Bibliography

Presents the case of lamotrigine-induced neutropenia. A 23-year-old woman was hospitalized with bipolar II depression. Her history was also remarkable for polysubstance abuse and eating disorder not otherwise specified. Two months previously, topiramate had been initiated, with which the patient had been partially compliant. On the first day of admission, topiramate 50 mg/day was initiated, then increased to 100 mg at bedtime on day 10. Subsequently, topiramate was decreased to 75 mg/day on day 15, then further decreased to 50 mg on day 26. Lamotrigine 12.5 mg at bedtime was added on day 15, then increased to 25 mg/day on day 19 and to 50 mg/day on day 26. A complete blood count (CBC) on day 2 was normal. A random CBC on day 29 revealed neutropenia, so topiramate 50 mg at bedtime and lamotrigine 50 mg/day, were discontinued. While there is no recommendation for regular monitoring of CBC in lamotrigine-treated patients, clinicians ought to be aware of the possibility of this uncommon but potentially serious adverse event.

Milnacipran is a cyclopropane derivative which acts by inhibiting norepinephrine and serotonin reuptake at presynaptic sites. Three women (aged 27, 27 and 29 years) with premenstrual dysphoric disorder (PMDD) and intolerant to selective serotonin reuptake inhibitors (SSRIs) were successfully treated with milnacipran. These cases suggest that milnacipran is an effective agent, with minimal side effects and a low propensity to cause drug-drug interactions, for SSRI intolerant PMDD.

Previous 'Psychopharmacology Reviews' columns have discussed emerging studies in psychopharmacogenomics, which correlate the variability of patient responses to psychotropic drugs to individual genetic differences. A recent report showed a 74-year-old patient with the cytochrome P450 (CYP) 2D6 *5/*10 genotype, associated with defective CYP 2D6 metabolism, which rendered him particularly susceptible to prominent risperidone induced extrapyramidal symptoms. With respect to risperidone, CYP 2D6-defective or poor metabolizers, such as the patient described above, are at increased risk for toxicity at conventional doses due to elevated serum levels of risperidone and of its principal metabolite, 9-hydroxyrisperidone. Conversely, in ultrarapid CYP 2D6 metabolizers, the concentrations of risperidone and of 9-hydroxyrisperidone will be very low. Accurately identifying these individuals would likely be of value to predict nonresponse with conventional risperidone doses, as well as to exclude questions of possible noncompliance.