Faculty Bibliography

Presents the case of diazepam-associated gynecomastia. An obese, 47-year-old man with an otherwise unremarkable medical history presented with breast enlargement that had first become apparent to him 2 months previously, which was 8 months after he had begun self-medicating with diazepam for anxiety. In his country, Serbia, diazepam is available over the counter. Initially, he took diazepam 5-10 mg on an as-needed basis. Dissatisfied with the results, he increased the dose to 10-30 mg/day. Two weeks prior to presentation, he had increased his dosage to 40-50 mg/ day. He denied being sedated or even feeling tired, instead reporting that over time he seemed to feel more nervous and aggressive, which in his view necessitated his increasing his dosage of diazepam. Three weeks after being advised to gradually taper off the diazepam, the patient described using the medication only occasionally, at a dosage of 5-15 mg/day. Over this period, while the patient's BMI decreased slightly, he experienced a significant breast dimension reduction, reaching near normal size, measured at 7.2 cm in width, 1.6 cm above the middle line of the chest. He also reported that he was less nervous and aggressive. Thus, given the widespread use of diazepam, as well as other benzodiazepines, it is important for clinicians to recognize that gynecomastia may sometimes be an adverse effect of this class of medications.

Presents the case of ifraconazole-tadafafil interaction resulting in priapism. A 56-year-old white man with erectile dysfunction (ED) but with an otherwise benign medical history had been using sildenafil 100 mg as needed, from 1999 to 2003, without adverse effects. In an effort to achieve improved and more sustained efficacy, he later switched to tadalafil 10 mg. He was not taking any concomitant medications and denied any undesirable side effects. In September 2003, due to recurrent onychomycosis of the foot, he started taking itraconazole 400 mg/day for 7 days/month. During the first day of monthly itraconazole therapy in October 2003, he took a dose of tadalafil. Within several hours, priapism occurred, lasting over 4 hours but without impeding urinary flow. However, upon use of sildenafil in the context of ongoing itraconazole therapy, he did not experience any recurrences of priapism. Given the potential seriousness of priapism, a medical emergency requiring prompt urological intervention to prevent complications such as impotence and gangrene, clinicians who prescribe tadalafil need to be aware of the potential for precipitating priapism in patients taking concomitant medications that inhibit cytochrome P450 3A4 (CYP).

Presents the case of adjunctive rivastigmine reducing the negative symptoms of schizophrenia. A 45-year-old Indian woman had residual schizophrenia of 6 years' duration. Despite treatment with risperidone 6 mg/day, over the prior 18 months, she had developed progressive passivity, lack of initiative, marked psychomotor' retardation, poverty of speech, and poor facial expression. With the support of her family, she maintained good compliance with risperidone, which completely controlled her positive symptoms. Subsequently, she began rivastigmine tartrate 1.5 mg twice daily, titrated to 6 mg/day after 2 months. She continued risperidone 6 mg/daily. A second evaluation, done after 4 weeks of drug therapy, showed 10% improvement in negative symptoms. After 6 months of combined drug treatment, the score had decreased by 41% from baseline. Neuropsychological testing revealed appreciably improved cognitive function that was directly related to the improvement in her quality of life. Additional studies with randomized, double-blind, placebo-controlled designs, are needed to more fully assess these treatments for this condition.

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.

Recognition and treatment of schizophrenia has largely focused on positive symptoms of the disorder, such as delusions, hallucinations, and disorganization. However, other important symptoms, such as depression, cognition, and social functioning, have not received comparable attention. Fifty percent of schizophrenic patients suffer from comorbid depression, which is a major risk factor for suicide in this population, while 10% to 25% suffer from comorbid obsessive-compulsive disorder. Cognitive deficits commonly observed in patients with schizophrenia include problems with concentration, attention, and memory, as well as problem-solving and verbal skills. These deficits are observed at early stages of the illness and can predict deficits in functional capabilities, such as occupational and social skills, educational attainment, and the ability to live independently. The severity of such impairments affects all patient in this population, including up to 10% of patients working full time and up to one third of those working part time. In light of the debilitating effects of depression, cognitive impairment, and other aspects of affective functioning on the quality of life of patients with schizophrenia, physicians need to partner with their patients to address these concerns and determine an appropriate treatment regimen. This can be done with simple functional-based cognitive questioning, the use of evidence-based psychosocial practices, and psychoeducation on the many pharmacotherapeutic options. It is recommended that depressive or suicidal symptoms of schizophrenia be treated with an antidepressant or mood stabilizer only if the symptoms have not subsided after treatment of the psychosis with an atypical antipsychotic. Additionally, relative to older medications, atypicals have demonstrated benefit in improving some of the cognitive impairments

Depression is a common, recurring illness that continues to be underdiagnosed and undertreated in both psychiatric and primary care settings. It is increasingly being recognized that painful physical symptoms, which commonly exist comorbid with depressive disorders, play a role in complicating diagnosis of depression. Patients tend to discuss physical pain with primary care physicians and emotional pain with psychiatrists, often oblivious to the fact that both may be aspects of one disorder. Those who present with somatic complaints are three times less likely to be accurately diagnosed than patients with psychosocial complaints. However, thorough evaluation of mood and anxiety disorders in primary care is sparse due to the limited time primary care physicians can spend with each patient. Better recognition and treatment of both physical and emotional symptoms associated with mood disorders may increase a patient's chance of achieving remission, which is the optimum therapeutic goal. Abnormalities of serotonin and noradrenaline are strongly associated with depression and are thought to play a role in pain perception. Brain-derived neurotrophic factor, which is increased with antidepressant treatment, appears to influence regulation of mood and perception of pain. Clinical evidence indicates that dual-acting agents may have an advantage in modulating pain over those agents that increase either serotonin or noradrenaline alone. The novel dual-acting agents, such as venlafaxine and duloxetine, are better tolerated than tricyclic antidepressants and monoamine oxidase inhibitors. These agents have demonstrated efficacy in depression and in diabetic neuropathic pain independently. Therefore, unless otherwise stated, all inferences to studies of pain in this monograph refer to neuropathic pain in nondepressed patients. (journal abstract)

This article discusses a report which suggests that topiramate may also be an effective agent for the treatment of nonparaphilic sexual addiction (T. W. Fong et al; see record 2005-11734-029). A 32-year-old man presented to the University of California, Los Angeles, Impulse Control Disorders Clinic requesting help with his 'addiction to sex.' Physically, prior to engaging in sexual behaviors, he experienced increased heart rate, nervousness, dry mouth, and nausea. Topiramate was started at 25 mg/day, then increased by 25 mg every 5 days to a total dose of 200 mg/day. For the first 4 weeks, there were no reductions in his sexual activities. At week 6, however, he described a noticeable cessation of the anticipatory physical sensations and a renewed sense of control. He was able to completely stop engaging in sexual behaviors. These results ought to be viewed as preliminary and require validation in larger, placebo-controlled trials. While the mechanism of action underlying these effects are not known, one possibility is that it may be related to disinhibition of GABA in the nucleus accumbens area, targeting the arachidonic acid cascade, which may be functionally hyperactive in patients with impulse-control disorders.

This article discusses a report of clozapine-induced allergic vasculitis (K. M. Penaskovic et al; see record 2005-08718-024). A 59-year-old schizophrenic man suffered from deafness, hypothyroidism, and tardive dyskinesia. Haloperidol was discontinued and clozapine initiated due to persistent extrapyramidal symptoms, tardive dyskinesia, and treatment-resistant psychotic symptoms. The patient developed a bilateral leg rash, characterized as a confluent, nonblanching, erythematous, elevated patch consistent with a palpable purpura. The rash continued to spread up his lower extremities but did not involve his palms or soles. The patient was discontinued with clozapine, and he improved with conservative management. The presentation and course of this patient, including the histopathologic findings, are consistent with a diagnosis of clozapine-induced leukocytoclastic vasculitis. The above case appears to be the first such published report of this reaction attributable to clozapine. In those treated with clozapine, the appearance of new-onset palpable purpura may be a sign of an allergic vasculitis.

This article discusses a report on the successful use of sodium valproate (VPA) for the treatment of catatonia in two brothers (I. Yoshida et al; see record 2005-11734-024). The first brother, 25 years of age, was diagnosed with catatonic schizophrenia, his acute phases were characterized by wandering with delusions, motor excitement, impulsivity, aggression, bizarre behavior, and negativism. VPA 600 mg/day was administered for the first time. Within 20 days, his psychotic symptoms disappeared. The second brother, now 23 years of age, also suffered from catatonic schizophrenia. VPA 600 mg/day was administered for the first time. Within 10 days, his psychotic symptoms disappeared. In both siblings, VPA exhibited robust acute and maintenance effects against catatonia.

This article discusses a report on risperidone-induced immunoallergic hepatitis (D. Esposito et al; see record 2005-12096-032). A 28-year-old man with paranoid schizophrenia experienced a recurrence of disordered thinking and auditory hallucinations after having been free of all medications for a period of 1 year. Subsequently, he was prescribed risperidone, which was titrated to a dosage of 8 mg/day over a period of 5 weeks. Seven weeks later, he developed elevated serum levels of aspartate aminotransferase, 83 U/L (normal 10-50), and alanine aminotransferase, 123 U/L (normal 10-60). The temporal sequence of events is consistent with risperidone-induced liver toxicity. More specifically, the presence of eosinophilia and high levels of anti-smooth-muscle antibodies suggest a risperidone-induced immunoallergic reaction.