Faculty Bibliography

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 (see record 2005-10992-010) 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 (see record 2005-10992-011); and physical illness including disability (see record 2005-10992-012); and treatment of late-life depression (see record 2005-10992-013).

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. Paper from this symposium are by M. K. Erman (see records 2005-10992-016 and 2005-10992-020), T. Young see records 2005-10992-017), S. R. Patel see records 2005-10992-018), and D. N. Neubauer see records 2005-10992-019).

Anticonvulsants are frequently used in the treatment of psychiatric conditions. In general, abrupt discontinuation of these drugs is contraindicated due to concerns about withdrawal symptoms. In a recent report, an 80-year-old woman developed delirium with focal brain splenial edema 8 days after having abruptly discontinued pregabalin, an analogue of gabapentin. While the causality is unsubstantiated at this point, the finding of focal brain edema in association with abrupt discontinuation of pregabalin ought to be a caution to clinicians about the importance of using tapering strategies when discontinuing pregabalin as well as other anticonvulsants.

Presents a report of a patient with epilepsy and testicular cancer in whom the chemotherapy agent, cisplatin, resulted in reduced levels and efficacy of valproic acid, culminating in a recurrence of severe, generalized, tonic-clonic seizures. Regardless of the mechanism of this interaction, clinicians who prescribe valproic acid ought to be aware of the possibility of cisplatin-induced reduction of serum valproic acid levels, and the associated loss of medication efficacy with reemergence of the underlying condition.

Reports the case of a 54-year-old woman with generalized anxiety disorder and complicated bereavement reaction who developed mirtazapine-induced arthralgia with an additional association to coagulopathy. While these side effects appear relatively uncommon, clinicians who prescribe mirtazapine ought to be aware of the possibility of their occurrence.

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Three cases are reported that documents patients with bipolar disorder (aged 31, 37 and 32 years) in whom mirtazapine was used successfully to treat acute neuroleptic induced akathisia. If these results are confirmed, it is likely that these effects derive principally from mirtazapine's blockade of 5-HT-sub(2A/2C) receptors, which may disinhibit dopamine release in nigrostriatal projections. Large scale, double-blind, placebo-controlled clinical trials are needed to further validate these findings.

Presents the case of gabapentin-induced dystonia. A 72-year-old woman complained of tremors of both arms. She had a history of depression and hypertension, the latter treated with amiloride 5 mg/ day plus hydrochlorothiazide 50 mg/day. She denied use of any other medications, and had been on an adequate low-sodium diet for the past 5 years. At the time of presentation, she presented with postural and intention tremor of both arms and cephalic resting tremor without other neurologic symptoms. An electrocardiogram did not show any rhythm disorders. Diagnosed with essential tremor, she was treated with propranolol 120 mg/day. However, symptomatic bradycardia made it necessary to withdraw the drug. Gabapentin was initiated, with slow dosage escalation, to 2,100 mg/day after 7 weeks of treatment. Shortly after starting the medication, the patient developed abruptly repetitive rotatory and sustained movements of the neck, as well as proximal contractions in the arms. She stopped gabapentin on her own, with resolution of the dystonic reaction. There was no family history of dystonia. Gabapentin was restarted at a lower dose than before and was titrated to a total of 1,800 mg/day in the sixth week. Subsequently, the patient developed a recurrence of her dystonic reaction. The case described is consistent with gabapentin-induced dystonia. However, conflicting data suggests that gabapentin may be efficacious in the treatment of some types of movement disorders but in other patients may actually precipitate movement disorders. Whether the outcome is a function of dosage used, individual predisposing factors, or some combination of factors at present is not known.

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).