Faculty Bibliography

Although numerous effective antidepressant medications are available, many patients suffer multiple episodes that are not adequately controlled with presently available therapies. Up to 1.5% of the general population is estimated to have chronic, severe depression. Approximately 30% of these patients are medically resistant to present treatments. As a result, combination treatments of ant/depressants with other medications, so-called augmentation strategies, are frequently employed for partial or nonresponders to various monotherapies, including serotonin reuptake inhibitors (SRIs). What follows is a report of the effectiveness of the oral form of the selective, irreversible monoamine oxidase (MAO)-B inhibitor selegiline in a patient with severe, refractory depression. (journal abstract)

Venlafaxine is a serotonin norepinephrine reuptake inhibitor widely used for the treatment of depression, generalized anxiety disorder, and social anxiety disorder, as well as a number of other psychiatric conditions for which serotonergic antidepressants are often employed. Reported side effects for venlafaxine include nausea, somnolence, insomnia, dizziness, constipation, sweating, anorexia, asthenia, nervousness, dose-dependent blood pressure elevation, increased urinary frequency, and sexual dysfunction. The following is a report of venlafaxine-induced rapid and severe edema, otherwise known as anasarca.

The following is a report of clozapine-induced pseudomembranous colitis occurring after 9 years of clozapine therapy. A 38-year-old woman with a 20-year history of organic brain syndrome secondary to chicken pox encephalitis presented with disorganized speech and behavior, aggressive episodes neglect of personal hygiene, and social withdrawal. The patient responded poorly and developed extrapyramidal side effects to various trials of conventional antipsychotics as well as to the atypical antipsychotic risperidone. In 1996, the patient was started on clozapine, which was gradually titrated to a dose of 350 mg/day. Throughout this time, she had no history of upper or lower gastrointestinal complaints. Clozapine was discontinued. Subsequently, the patient has remained psychiatrically stable on a regimen of the substituted benzamide D2 antagonist sulpiride 100 mg/day, sodium valproate 2400 mg/day, and fluvoxamine 25 mg/day. This appears to be the first published case of prolonged administration of clozapine resulting in pseudomembranous colitis, which is a gastrointestinal condition that often occurs without a background of chronic enteric disease and which has previously been associated with the use of antituberculous and antibiotic drugs but not neuroleptics.

Although most patients with depression ultimately respond to antidepressant therapy, >50% have inadequate response to an individual antidepressant trial. The desire to avoid adverse drug reactions is common among patients, and is an important determinant of drug selection among psychiatrists. However, since the major classes of antidepressants and antipsychotics appear to be comparable in efficacy, clinicians have little basis for selecting the most effective agent for an individual patient. Pharmacogenetics, often described as the study of genetic variation that explains differential response to medication, represents an important new avenue toward improving treatment outcomes. Genetic variation in drug-metabolizing enzymes has been recognized for decades. The main focus of current psychiatric pharmacogenetic testing is on the cytochrome P450 (CYP) 2D6 and, to a somewhat lesser extent, on the 2C19 genes. Data suggest that poor metabolizer status can be associated with an increased risk of adverse drug reactions with certain medications, and that ultra-rapid metabolizers may require higher-than-usual doses to achieve a therapeutic response. The importance of CYP enzymes in the metabolism of several antidepressant and antipsychotic drugs suggest that genetic variation may aid in medication selection or dosing. Advances in pharmacogenetic research may facilitate the development of personalized medicine in which genetic information can inform drug selection, leading to optimal drug effectiveness and minimal drug toxicity. In this monograph, David A. Mrazek, MD, provides an overview of the context of genetic testing in clinical psychiatric practice. Next, Jordan W. Smoller, MD, ScD, discusses some of the practical issues related to medication selection. Finally, Jose de Leon, MD, presents a comprehensive review of antidepressant and antipsychotic treatment based on drug metabolism, and reviews the available testing methods for CYP 2D6 and 2C19 genotypes. (journal abstract)

Venlafaxine is a serotonin norepinephrine reuptake inhibitor widely used for the treatment of depression, generalized anxiety disorder, and social anxiety disorder, as well as a number of other psychiatric conditions for which serotonergic antidepressants are often employed. Reported side effects for venlafaxine include nausea, somnolence, insomnia, dizziness, constipation, sweating, anorexia, asthenia, nervousness, dose-dependent blood pressure elevation, increased urinary frequency, and sexual dysfunction. The following is a report of venlafaxine-induced rapid and severe edema, otherwise known as anasarca

Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist approved for moderate-to-severe Alzheimer's disease. The NMDA receptor may be involved in the pathophysiology of schizophrenia, which is believed to be associated with excess production of glutamate in the brain and hyperexcitation of glutamate receptors, thereby allowing prolonged opening of calcium channels. Subsequently, an overabundance of calcium influx causes free-radical damage to the neuron and, eventually, neuronal death. Glutamatergic hyperfunction in the striatum may result in catatonia