Faculty Bibliography

Clozapine is a dibenzodiazepine derivative that has greater potency in blocking dopamine D1 compared with D2 receptors. Clozapine also has potent dopaminergic anti-D4, antiserotonergic, antimuscarinic, antiadrenergic and antihistamine effects and enhances dopamine release in the striatum. This article presents a report of clozapine induced eosinophilic colitis. A 45-year-old schizophrenic man suffered a psychotic decompensation in the setting of medication noncompliance. After reintroduction of haloperidol and risperidone, he developed neuroleptic malignant syndrome (NMS). Subsequently, he was treated with electroconvulsive therapy, concurrent with initiation of low dose clozapine, which was gradually increased. On day 14 of clozapine 200 mg/day, the patient developed a fever of 103.6degreesF and profuse bloody diarrhea. At this point, a diagnosis of clozapine-induced eosinophilic colitis was made, with clozapine discontinued. The next day, the patient's fever and diarrhea totally resolved.

Dry mouth is one of the most frequent side effects experienced by patients taking psychotropic drugs, particulary those with antimuscarinic and anticholinergic actions. The lack of saliva is annoying to patients, impairs their ability to chew and digest food, and is a contributor to dental morbidity, including caries and oral infection. Pilocarpine is a cholinergic muscarinic agonist that has been used to treat xerostomia induced in cancer patients by head and neck radiotherapy. In addition, in a recent placebo controlled study, doses of 20 mg/day were shown to be effective for the treatment of dry mouth and dry eyes in patients with Sjogren's syndrome.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening hematologic disorder. This article presents a report of TTP in association with the atypical neuroleptic, quetiapine. A 25-year-old African American man with a history of bipolar disorder and schizophrenia presented to the emergency room with 3 days of diffuse abdominal pain and red-colored urine. Five days earlier, he had been started on quetiapine 50 mg BID by his psychiatrist in the community. Previously, he had been taking lithium, without additional medications, for 2 years. A diagnosis of TTP was made, and plasmapheresis was started.

In addition to the psychological and medical health risks associated with lack of adequate sleep, effects of insomnia include impaired daytime functioning and decreased quality of life. Many patients experience delayed sleep onset, frequent awakenings, early waking, or nonrestorative sleep. Longitudinal data on insomnia indicate that the prevalence of persistent/chronic insomnia is high and appears to be characterized by multiple symptoms related to initiating or maintaining sleep. Physiologic studies indicate that short-term sleep restriction can cause physiologic problems that lead to long-term health consequences, such as high blood pressure, impaired glucose tolerance, and systemic inflammation. Epidemiologic studies have shown that sleep deprivation is independently associated with increased risk of cardiovascular disease, diabetes, obesity, and mortality. While the available agents are effective, those with a long half life may have carryover effects while short-acting agents may not provide enough sleep continuity. Pharmacologic therapies available for patients who suffer from insomnia include immediate-release nonbenzodiazepine hypnotics, which have a positive benefit/risk profile compared to the benzodiazepines. Modified-release (MR) formulations of these agents may offer the additional benefit of improving sleep continuity throughout the night without sacrificing the rapid elimination properties that minimize next-day residual effects. MR agents in development include zolpidem MR and indiplon MR.

Treatment options for epilepsy have increased in the last decade with the introduction of several new antiepileptic drugs (AEDs). As drug selection becomes more challenging, the use of evidence-based guidelines to aid in treatment decisions has become increasingly valued. The American Academy of Neurology's (A

The article presents a randomized, double-blind, placebo-controlled crossover trial of lamotrigine augmentation of clozapine in treatment-resistant, chronic schizophrenia. Thirty-four hospitalized, treatment-resistant chronic schizophrenic patients participated in this double-blind, placebo-controlled, 14-week, crossover trial in which lamotrigine 200 mg/day was gradually added to their ongoing clozapine treatment. Clinical assessments using the Positive and Negative Syndrome Scale (P

Anticonvulsant topiramate, oral hypoglycemic metformin, or the histamine H2 antagonist nizatidine, have been used to offset the weight gain associated with psychotropic medications. Weight gain is a significant problem with many of these medications, especially the atypical neuroleptics clozapine and olanzapine, which have also been associated with the development of elevated serum triglycerides and diabetes mellitus. Sibutramine, a medication approved by the Food and Drug Administration for the management of obesity, including weight loss and its maintenance, produces its effects by norepinephrine, serotonin, and dopamine reuptake inhibition, primarily via its secondary (Mi) and primary (M2) amine metabolites. Unlike many methamphetamine derivatives traditionally used for weight loss, it is not associated with abuse potential. The most common side effects associated with it include dry mouth, anorexia, headache, insomnia, and, in some patients, an increase in blood pressure and tachycardia due to anticholinergic activity. Adverse psychiatric effects reported postmarketing include psychosis, hypomania, and panic attacks. Now comes a randomized, double-blind, placebo-controlled trial of add-on sibutramine for olanzapine-induced weight gain. While the full findings of this study await publication, this early abstract indicates that addition of sibutramine may be a useful antidote to olanzapineinduced weight gain and perhaps even metabolic abnormalities.

In studies evaluating the safety of Selective serotonin reuptake inhibitors (SSRIs) during pregnancy, while no increase in major anomalies has been reported, several studies have found a greater risk of neonatal complications, including premature delivery, lower Apgar scores, and neurobehavioral effects, such as tremulousness, erratic motor activity, and underarousal. The article presents a case report of neonatal intracerebral hemorrhage in association with maternal use of paroxetine throughout pregnancy. Recently, there have been reports of neonatal intracerebral hemorrhage in association with maternal use of paroxetine throughout pregnancy. In evaluating the potential adverse effects of prenatal exposure to SSRIs and in deciding whether to use these medications during pregnancy, physicians and parents must balance these concerns against the seriousness of depression and its risks both to mother and baby, and should consider the effectiveness of other nonmedication treatments, such as psychotherapy. In the interim, clinicians who prescribe SSRIs during pregnancy ought to be aware of the possibility of precipitating bleeding in the neonate, particularly in patients who have a past personal or family history of bleeding. In all pregnant women taking SSRIs during pregnancy, consideration should be given to advising against concomitant use of aspirin, NSAIDs, or other medications which may impair clotting.

Selective serotonin reuptake inhibitors (SSRIs) are first-line treatments for depression due not only to their efficacy, but to their favorable side-effect profile and safety in overdose. Despite extensive use over the last 10-15 years, only isolated cases of liver injury have been seen with the use of fluoxetine, sertraline, paroxetine, fluvoxamine, and the serotonin-norepinephrine reuptake inhibitor venlafaxine. The article presents the first published case report of significant hepatotoxicity related to the SSRI citalopram. The temporal relation between hepatotoxicity and the introduction of citalopram, along with the resolution observed after drug iscontinuation, supports a diagnosis of citalopraminduced hepatocellular injury. Overall, the incidence of hepatoxicity occuring in relation to citalopram appears quite low. Nonetheless, in patients prescribed the drug, consideration ought to be given to periodic monitoring of liver function tests, particularly in those with liver disease.

The article presents a study indicating that the selective serotonin reuptake inhibitor (SSRI), paroxetine may be effective in the treatment of severe nondermatological pruritus. Twenty-six subjects (13 men and 13 women) with a mean of 65 years of age, most with malignant disease, were enrolled in this randomized, double-blind, placebo-controlled, crossover study of paroxetine and placebo. Seventeen subjects had solid tumors, four had hematological malignancies, and five had various nonmalignant or idiopathic conditions, such as osteoporosis, rheumatoid arthritis, or Parkinson's disease. The intensity of pruritus was measured subjectively with a numerical analogue scale. Two subjects dropped out of the study due to side effects of paroxetine, specifically severe nausea and vomiting. The study indicates that for some patients, paroxetine has beneficial effects in the treatment of severe pruritus of nondermatological origin. The investigators speculate that paroxetine's antipruritic activity may be due to modification of central opioid receptors involved in processing of itch signals.