Faculty Bibliography

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.

While the exact pathophysiology of tinnitus remains unknown, possible causes include cochlear deterioration; an extra-auditory response to respiratory, vascular, or muscular stimuli; a drug reaction; microvascular compression of the eighth cranial nerve; and turbulent flow in the ipsilateral internal carotid artery. Regardless of the cause, tinnitus may result in significant diminution of quality of life. Proposed treatments include retraining therapy, maskers, hyperbaric oxygen, carotid artery stenting, selective cochlear neurotomy, and biofeedback, as well as pharmacotherapy with antidepressants, benzodiazepines, lidocaine, the calcium channel blocker nimodipine, or botulinum toxin. The double-blind, placebo-demonstrates the effectiveness of the selective serotonin reuptake inhibitor (SSRI) sertraline for the treatment of severe tinnitus. The findings support a possible role for sertraline, and likely other SSRIs, for the treatment of refractory tinnitus.

Attention-deficit/hyperactivity disorder (ADHD) is a clinical disorder that may be confused with other medical and psychiatric conditions, due to overlapping symptoms. Often, symptoms suggestive of ADHD may be explained by other diagnoses. Medical 'mimics' one should consider when diagnosing a patient with ADHD include sleep deprivation, chronic and acute illness, medication effects, cognitive deficits, and other psychiatric disorders such as Asperger's syndrome, substance use disorders, and mood disorders. ADHD in both children and adults is also associated with academic performance problems, such as learning disabilities and executive functioning deficits. Learning disabilities such as math and spelling deficits are more common in children, although both age groups experience difficulties with reading and listening comprehension. Executive deficits in response inhibition and working memory have been demonstrated to be predictive of impairment in virtually every major life activity. Evaluation of both children and adults with ADHD requires screening for comorbid medical, psychiatric, and learning disorders; executive functioning; and history of school impairment. In this monograph, Russell A. Barkley, PhD, reviews the comorbidity of adult attention-deficit/hyperactivity disorder (ADHD) and learning and executive function disorders. Next, Timothy E. Wilens, MD, discusses differential diagnosis of ADHD as well as the prevalence of psychiatric comorbidity in adult ADHD. Finally, Lenard A. Adler, MD, reviews Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria for adult ADHD and reviews the diagnostic and symptom assessment instruments available for the evaluation of ADHD in this population. (journal abstract)

Priapism, characterized by abnormal, prolonged, painful erection of the penis, is a urologic emergency. If not treated within 4-6 hours, complications may occur, including difficulty urinating, urinary retention, impotence, cavernosa fibrosis, and gangrene. Even with surgery, approximately 40% to 50% of patients with priapism will become impotent. Priapism results from decreased venous outflow from the corpora cavernosa. This can be caused by physical obstruction of the venous system, blood dyscrasias that impede venous flow, solid tumors, trauma, spinal cord injuries, stroke, or blockade of postsynaptic alpha 1-adrenergic receptors that normally mediate sympathetically controlled detumescence of the penis or clitoris. In general, drug-induced priapism is believed to be mediated by the degree of aradrenergic antagonism. Opposing this tendency are anticholinergic effects. Thus, when a medication has more antiadrenergic than anticholinergic properties, it is more likely to be associated with priapism. Based on a review of available evidence, medication-induced priapism does not appear to correlate with either dose or length of treatment.

Anxiety disorders are common in depressed patients. Several studies of the full range of Diagnostic and Statistical Manual of Mental Disoroters-defined anxiety disorders in depressed psychiatric outpatients each found that when diagnoses are based on semi-structured diagnostic interviews >40% of the patients had a comorbid anxiety disorder. The recognition of comorbidity is not simply of academic interest, but it has important clinical significance. Epidemiological studies, such as the National Comorbidity Study, have demonstrated that depressed individuals with a history of anxiety disorders are at increased risk for hospitalization, suicide attempt, and greater impairment from the depression. The co-occurrence of anxiety disorders in depressed patients has been associated with a more chronic course of depression in psychiatric patients, primary care patients, and epidemiological samples. Recent research has suggested that clinicians underrecognize anxiety disorder comorbidity in depressed patients. The clinical significance of this underrecognition is highlighted by the finding that patients often want treatment to address their anxiety disorder comorbidity. When anxiety disorders are detected they often influence clinicians' selection of antidepressant medication, though some of clinicians' prescribing biases are not supported by empirical data. In this monograph, Iwona Chelminski, PhD, reviews the significance of anxiety in patients with depression as well as diagnostic instruments for recognizing this comorbidity. Next, Mark Zimmerman, MD, addresses the factors that affect the clinician's choice of antidepressant, focusing on the influence of comorbid anxiety. Finally, Sidney Zisook, MD, discusses the differential efficacy of antidepressants as well as the role of psychotherapy in patients with comorbid anxiety and depression. (journal abstract)

Previous 'Psychopharmacology Reviews' columns have discussed the use of lamotrigine for bipolar disorder, refractory unipolar depression, treatment-resistant schizophrenia, posttraumatic stress disorder, frontal lobe dementia, and post-stroke pathological laughing and crying. Lamotrigine is an anticonvulsant that blocks voltage-gated sodium channels where it inhibits the excessive release of the excitatory amino acids glutamate and gamma -aminobutyric acid. In addition to its actions on ion channels, lamotrigine weakly inhibits monoamine transporters. At a concentration of 100-1,000 mM, lamotrigine is an inhibitor of 5-hydroxytryptamine uptake in both rat and human tissues. At similar concentrations, lamotrigine also inhibits norepinephrine and dopamine uptake into rat brain synaptosomes. Now comes a report of a woman with bipolar disorder who developed hair loss as a side effect of lamotrigine. (journal abstract)

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)

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