Barbara R. Sommer

Comparison of Desipramine and Cognitive/Behavioral Therapy in the Treatment of Elderly Outpatients With Mild-to-Moderate Depression

The authors evaluated the efficacy of desipramine-alone, vs. cognitive/behavioral therapy-alone (CBT) vs. a combination of the two, for the treatment of depression in older adult outpatients. Patients (N=102) meeting criteria for major depressive disorder were randomly assigned to one of these three treatments for 16 to 20 therapy sessions. All treatments resulted in substantial improvement. In general, the CBT-Alone and Combined groups had similar levels of improvement. In most analyses, the Combined group showed greater improvement than the Desipramine-Alone group, whereas the CBT-Alone group showed only marginally better improvement. The combined therapies were most effective in patients who were more severely depressed, particularly when desipramine was at or above recommended stable dosage levels. The results indicate that psychotherapy can be an effective treatment for older adult outpatients with moderate levels of depression.

Folic Acid Supplementation in Dementia: A Preliminary Report

Recent work on high plasma homocysteine levels in patients at risk for developing Alzheimers disease has led to the hypothesis that folic acid supplementation might reduce risk in such patients. The authors report on the effects of folic acid 10 mg/day versus placebo on 11 patients (only 7 completers) with dementia and low-normal folic acid levels. This is the first study evaluating folic acid or placebo in patients with dementia. Subjects had low-normal baseline folic acid levels. The magnitude of change between baseline and second testing was not statistically significant between the 2 groups. However, there was a trend for the folate group to perform worse on two specific cognitive measures, suggesting a possible trend toward worsening of some cognitive abilities after the folic acid. The folic acid in very high doses was well tolerated. Larger studies are necessary before empirically administering folic acid to patients already suffering from dementia. (J Geriatr Psychiatry Neurol 2003; 16:156-159).

The efficacy, safety, and tolerability of donepezil for the treatment of young adults with Down syndrome

The objective of our study was to assess the efficacy and safety of donepezil in young adults with Down syndrome (DS) but no evidence of Alzheimer disease (AD). A 12‐week, randomized, double‐blind, placebo‐controlled study with a 12‐week, open‐label extension was conducted. The intervention consisted of donepezil (5–10 mg/day) in young adults (aged 18–35 years) with DS, but no AD. The primary measure was the Severe Impairment Battery (SIB) test and secondary measures were the Vineland Adaptive Behavior Scales (VABS), the Rivermead Behavioral Memory Test for Children, and the Clinical Evaluation of Language Fundamentals, Third Edition. At baseline, 123 subjects were randomly assigned treatment with donepezil or placebo. During the double‐blind phase, SIB scores improved significantly from baseline in both groups, with no significant between‐group differences. During the open‐label phase, SIB scores in the original donepezil group remained stable; the original placebo group showed an improvement similar to that seen in the double‐blind phase. VABS scores improved for donepezil, but not placebo, during the double‐blind phase (observed cases, P = 0.03; last observation carried forward, P = 0.07). Post hoc responder analyses were significant for donepezil using three of five response definitions (P ≤ 0.045). Adverse event rates were comparable to AD studies. In this first large‐scale, multicenter trial of a pharmacological agent for DS, donepezil appears safe. Efficacy interpretation was limited for the primary measure due to apparent learning/practice and ceiling effects. Outcomes in post hoc analyses suggested efficacy in some, but not all subjects, consistent with phenotypic variability of DS. Additional studies are required to confirm potential benefits of donepezil in this population.

RBC folic acid levels and cognitive performance in elderly patients: A preliminary report

The human brain contains large concentrations of folic acid (FA) (Reynolds 1976), and deficiencies of this vitamin may be associated with both neurological (Reynolds 1976; Shorvon et al. 1980) and psychiatric disorders (Camey 1979; Botez et al. 1982; Abou-Saleh and Coppen 1986). Furthermore, when severe enough to be associated with meg~ob~astic anemia, FA deficiency may also result in reversible dementia (Botez et al. 1982; Lishman 1978). The biochemical role of FA in cognitive function is unclear, but it is known that the vitamin is important in the synthesis of norepinephrine (NE), dopamine (DA), and serotonin (5HT) (Turner 1979). Specifically, FA may be required for tyrosine hydroxylase to act in the rate-limiting step of DA and NE synthesis (Turner 1979). A deficiency of FA in rats has also been associated with a decrease in brain 5-HT levels, implying a role for FA in the synthesis or metabolism of this monoamine as well (Botez et al. 1979). DA, NE, and 5-HT are all thought to be important modulators of attentional and higher order memory functions (Woikowitz et

Is dopamine administration possibly a risk factor for delirium

Objective We explored the possibility that the administration of intravenous dopamine increases the risk for delirium as manifested by need for haloperidol. Design This study was based on a retrospective analysis. To examine the contribution of dopamine in the prediction of need for haloperidol, a multivariate logistic regression model was used. Setting University hospital. Patients All inpatient admissions to Stanford University Hospital over a 1-year period (n = 21,844). Interventions None. Measurements and Main Results Dopamine administration was associated with nearly a tripling of the odds of subsequent need of the antipsychotic drug (chi-square = 108, df = 1, p = .0001, odds ratio = 2.89), even after intensive care unit admission and diagnostic related group weight were considered as indicators of severity of illness. Even when analysis was limited to patients seen in the intensive care unit setting (n = 3,308), dopamine administration remained a very strong risk factor for haloperidol and hence possibly for delirium. The increased risk of need for haloperidol in patients administered dopamine is evident in every age group after age 20. Conclusions The retrospective nature of this study, the inexact method to assess acuity, and, most of all, the use of haloperidol as an indicator of the presence of delirium preclude concluding that dopamine is directly a risk factor for delirium, much less a causal risk factor. However, the association is potent enough to suggest this possibility strongly and thus supports the need for prospective studies to examine the relationship between dopamine and delirium and to consider possible prophylactic treatment against delirium in those given dopamine.

Topiramate: Effects on cognition in patients with epilepsy, migraine headache and obesity

This paper reviews the clinical implications of topiramate (TPM)-induced cognitive deficits in patients with epilepsy, migraine headache, obesity, and in normal populations, followed by reviews of the literature describing the reversal of such deficits upon medication discontinuation. It also discusses animal investigations of TPM’s role of neuroprotection in brain injury. TPM’s most intolerable adverse effects (AEs) are on verbal fluency and reaction time, resulting in high discontinuation rates in patients taking it for epilepsy and migraine headache. However, because TPM is so effective in the treatment of epilepsy and migraine headache, its use is expected to continue. There appears to be greater tolerance of TPM’s cognitive AEs when it is used in the treatment of obesity, perhaps because of the lower doses required. Research attempting to predict the populations most vulnerable to the cognitive effects caused by TPM is ongoing. Studies suggest that one such population may include patients with a past psychiatric history. Slow titration and administration of the lowest possible doses may decrease risk of cognitive deficits.

Metabolism of thioridazine in the elderly

Metabolism of drugs may change with age. Yet, there are few studies that provide data to help define appropriate doses of neuroleptic drugs in the treatment of the elderly. To address this issue, we determined serum concentrations of thioridazine and its active metabolites, mesoridazine and sulforidazine, by high performance liquid chromatography in young adult (mean age, 28 +/- 7.6 years) and elderly (mean age, 76 +/- 7.7 years) patients after single 25-mg oral doses of thioridazine. At both times measured, 4 and 8 hours after dosing, the concentrations of parent compound and metabolites in serum were 1.5- to twofold higher, and side effects (especially postural hypotension and dry mouth) were more frequent and severe in the elderly patients. These results, along with those reported in a small number of studies of serum drug levels during extended treatment of the elderly, support the practice of using smaller doses of phenothiazine neuroleptics in older patients.

Quetiapine-induced extrapyramidal side effects in patients with Parkinson's disease: case report

Although quetiapine is the antipsychotic of choice for the psychosis associated with Parkinsons disease (PD) and often is also helpful for sleep, we report two cases of quetiapine-induced extrapyramidal side effects. The patients described were unusual in their frailty and severity of illness and may not represent the majority of patients with PD. (J Geriatr Psychiatry Neurol 2001; 14:99-100).

Review of topiramate for the treatment of epilepsy in elderly patients

Individuals over 65 years of age experience the new onset of seizures at a prevalence rate of roughly twice that of younger adults. Differences in physiology, need of concomitant medications, and liability for cognitive deficits in this population, make the choice of anticonvulsant drugs especially important. This paper reviews topiramate (TPM), a treatment for many types of seizures, with the above risks in mind. In particular, we discuss efficacy and pharmacokinetics with emphasis on the older patient, and adverse events in both the younger and older adult. With most studies of TPM-induced cognitive deficits having been performed in younger adults and volunteers, we discuss the implications for the older adult. Even in studies of younger individuals, up to 50% discontinue TPM because of intolerable cognitive deficits. Most studies find specific declines in working memory and verbal fluency. In conclusion, we give recommendations for use of this antiepileptic drug in this population.

Safety and efficacy of anticonvulsants in elderly patients with psychiatric disorders: oxcarbazepine, topiramate and gabapentin

Few controlled studies are available to guide the clinician in treating potentially assaultive elderly individuals with psychiatric disorders. Safety concerns limit the use of benzodiazepines and antipsychotic medications in the elderly individual, making anticonvulsants an attractive alternative. This paper reviews three specific anticonvulsants for this purpose: gabapentin, oxcarbazepine and topiramate, describing safety and efficacy in elderly patients with severe agitation from psychosis or dementia. Gabapentin, renally excreted, with a half-life of 6.5 – 10.5 h, may cause ataxia. Oxcarbazapine, hepatically reduced, may cause hyponatremia, and topiramate may cause significant cognitive impairment. Nonetheless, these are important medications to consider in the treatment of agitation.