Faculty Bibliography

Wagstaff et al (2003) have summarized case reports of statin-induced memory problems in patients treated with simvastatin. This article presents a report of new-onset cognitive difficulties in an older patient after initiation of simvastatin therapy. A 64-year-old white male presented with memory problems shortly after initiation of simvastatin therapy. The man had a history of bipolar disorder, characterized predominantly by depressive episodes, which had been stable over the past 2 years. At the time of presentation, the patient's medications included venlafaxine, quetiapine fumarate, simvastatin, terazosin, and carbamazepine extended-release. Simvastatin had been initiated by the patient's primary care physician for dyslipidemia. Within 1 week of starting simvastatin, the patient complained of additional memory problems. The temporal sequence of events supports a highly probable association between simvastatin and cognitive decline in this patient.

Attention-deficit/hyperactivity disorder (ADHD), once considered to be a childhood disorder, is diagnosed in similar to 7 million adults in the United States, as reported by The National Comorbidity Study. Although it is now recognized that ADHD often persists into adulthood, the current diagnostic criteria is geared toward symptom identification in children. Symptoms of inattention, impulsivity, and hyperactivity evolve over the life cycle and present differently in adults. Further complicating diagnosis is that ADHD is associated with multiple functional impairments and comorbid psychiatric disorders. The Multi-Modal Treatment Study of ADHD reported that only 32% of the study population had ADHD alone; 29% had ADHD plus oppositional defiant disorder and/or conduct disorder, 14% had ADHD plus anxiety or depression, and 25% had all three disorders. Optimal treatment utilizes a multimodal approach including behavioral treatments combined with pharmacologic treatment strategies. Food and Drug Administration-approved medications for ADHD include the stimulants and nonstimulants, although tricyclic antidepressants and bupropion are also commonly used. In this monograph, Craig L. Donnelly, MD, reviews the history of ADHD and discusses the pathophysiologic progression of childhood symptoms into those commonly exhibited by adults. Next, Frederick W. Reimherr, MD, reviews comorbidity of ADHD and describes the Utah Criteria as a method of diagnosing adults through recollection of childhood problems. Finally, Joel L. Young, MD, reviews treatment approaches to adult ADHD and its comorbid conditions.

BACKGROUND:Vagus nerve stimulation (VNS) alters both concentrations of neurotransmitters or their metabolites and functional activity of central nervous system regions dysregulated in mood disorders. An open trial has suggested efficacy. METHODS:This 10-week, acute, randomized, controlled, masked trial compared adjunctive VNS with sham treatment in 235 outpatients with nonpsychotic major depressive disorder (n = 210) or nonpsychotic, depressed phase, bipolar disorder (n = 25). In the current episode, participants had not responded adequately to between two and six research-qualified medication trials. A two-week, single-blind recovery period (no stimulation) and then 10 weeks of masked active or sham VNS followed implantation. Medications were kept stable. Primary efficacy outcome among 222 evaluable participants was based on response rates (>/=50% reduction from baseline on the 24-item Hamilton Rating Scale for Depression [HRSD(24)]). RESULTS:At 10-weeks, HRSD(24) response rates were 15.2% for the active (n = 112) and 10.0% for the sham (n = 110) groups (p = .251, last observation carried forward [LOCF]). Response rates with a secondary outcome, the Inventory of Depressive Symptomatology - Self-Report (IDS-SR(30)), were 17.0% (active) and 7.3% (sham) (p = .032, LOCF). VNS was well tolerated; 1% (3/235) left the study because of adverse events. CONCLUSIONS:This study did not yield definitive evidence of short-term efficacy for adjunctive VNS in treatment-resistant depression.

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.

Discusses the article 'Open-label Pilot Study of Ziprasidone for Refractory Generalized Anxiety Disorder' by S. H. Snyderman et al (see record 2005-11734-018). Thirteen adults (7 men, 6 women) with refractory generalized anxiety disorder (GAD) entered this 7-week ziprasidone monotherapy study. During the first week, all subjects received ziprasidone 20 mg/day. Subsequently, depending on response and tolerability, the dose could be increased in 20 mg/week increments to a maximum of 80 mg/week. The preliminary data from this short-term, open-label study suggest that ziprasidone at a dosage range of 20-80 mg/day may be of benefit to GAD patients who have not achieved sufficient improvement with serotonin reuptake inhibitors, buspirone, or benzodiazepines. Double-blind, placebo-controlled trials utitilizing a more stringent criterion for treatment resistance are needed to confirm these initial findings.

Depression affects 6.5 million of the 35 million Americans >=65 years of age. While depression usually begins earlier in life and recurs periodically, it can present for the first time in people 80-90 years of age as well. Depression throughout the lifespan has a genetic/biological component but is also very much affected by social environmental factors. As people age, demographic factors, social support, and negative life events remain important to overall mental health, while physical illness and disability begin to take on a much more prominent role. Depression in the elderly is associated with impairment, dependency, disability, and significant distress for the individual and their family. This population is likely to present with concomitant cognitive dysfunction and medical illness, which can complicate the identification and treatment of psychiatric conditions. Bereavement is almost universal in late life and is sometimes a deterrent to appropriate diagnosis and treatment of depression. Physical frailty and diminishing social resources further complicate the treatment of depression in the elderly. Elderly individuals respond well to standard pharmacotherapy and psychotherapy treatments for depression. However, due to the high rate of relapse of depression in this population, continuous treatment is often warranted. This monograph will review depression in the elderly in the context of social disruptions, such as bereavement, caregiver strain, interpersonal conflict, role transitions, and social isolation; late-onset vascular depression and cognitive impairment; and physical illness including disability.