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.

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.

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 Parkinson's 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.

Risperidone: clinical outcome predictors and cost-effectiveness in a naturalistic setting.

Although risperidone seems to be a safe and effective treatment for the management of psychotic symptoms, its acquisition cost is considerably higher than that of conventional antipsychotics, and its precise role in managing psychiatric illnesses has yet to be defined. The purpose of this investigation was to examine the relationship of patient demographic variables to therapeutic outcomes and to analyze the financial impact of risperidone on the treatment of psychotic symptoms. Subjects included in this 2-year, retrospective cohort, intent-to-treat analysis were all patients initiated on risperidone therapy at an inpatient psychiatric treatment facility. Clinical outcomes were assessed from the absolute change in hospitalized days, total number of psychotropic medications prescribed, and historic Clinical Global Impression severity scores. Logistic regression analysis was conducted to analyze the potential relationship to certain demographic variables to therapeutic response. The cost-benefit analysis compared the direct treatment costs incurred by the institution before and after risperidone initiation. Of the 66 patients originally started on risperidone, 57 completed a therapeutic trial. A clinical response was evident in 54 percent of these patients overall. Logistic regression analysis identified previous treatment intolerance and a negative history of substance abuse as predictive of therapeutic success with risperidone (p = .0006 and p = .01, respectively). Hospitalization rates declined by 43 percent among treatment responders and by 1.3 percent among nonresponders resulting in a net annual savings of $147,962. Risperidone may be efficacious in many patients who had previously failed antipsychotic trials. Patients who had been unable to tolerate traditional antipsychotics and those who lacked a documented history of substance abuse were uniquely responsive to risperidone treatment. The significant decline in hospitalized days that was observed among responsive patients seems to indicate that risperidone may be a cost-effective approach to the management of psychotic symptoms.

Syndrome of inappropriate antidiuretic hormone (SIADH) in an 80-year-old woman given clomipramine.

The author describes the syndrome of inappropriate antidiuretic hormone, with serum sodium decreasing from 137 mEq/L to 122 mEq/L in an 80-year-old woman prescribed clomipramine. The patient's delirium and serum sodium were slow to normalize, prolonging her hospital stay and delaying treatment of her depression.

Changes in tardive dyskinesia symptoms in elderly patients treated with ganglioside GM1 or placebo.

The unique role of ganglioside GM1 in neuronal plasticity led two centers, New York University and McLean Hospital, to study the effect of GM1 or placebo in patients with tardive dyskinesia. Results from the NYU cohort have already been published. We now present data from the entire cohort, allowing us to evaluate the effects of GM1 in the elderly compared to young adults. Subjects with tardive dyskinesia were randomly assigned to single-blind placebo injections for 1 week, followed by 1 month of double-blind intramuscular placebo or GM1 100 mg. The final sample included 29 patients: 12 younger than 55 years of age and 17 older. There was no GM1-versus-placebo difference observed in either age group, or in the total group. However, whether on placebo or GM1, repeated measures analysis of variance (RANOVA) found a significant difference in response between Abnormal Involuntary Movement Scale scores, taken baseline and week 4, in the elderly compared to young adults. Scores for the young adults show initial improvement then deterioration back to baseline, and those for the elderly show continuing improvement during the 4-week trial. The importance of the placebo effect in the elderly and its meaning for studies of GM1 in tardive dyskinesia are discussed.

Glycopyrrolate versus atropine in post-ECT amnesia in the elderly.

The neurotransmitter acetylcholine is important in memory function, and low brain concentrations may be associated with cognitive impairment. Our hypothesis was that atropine, a centrally acting anticholinergic drug known to cause amnesia, confusion, and delirium, may further exacerbate the amnesia and/or confusion resulting from electroconvulsive therapy (ECT) when used as a preanesthetic, and that the peripherally acting glycopyrrolate would by comparison decrease these side effects. We randomly administered glycopyrrolate versus atropine in equivalent doses as the preanesthetic agent to 20 consecutively admitted geriatric patients with major depression, for whom ECT was the clinical treatment of choice. Patients were matched for age, Hamilton Scale for Depression, and baseline performance on the Buschke Selective Reminding Task (BSRT). We found no significant difference in outcome between patients treated prior to ECT with atropine versus glycopyrrolate, as assessed by the above measures. We conclude from this study that atropine is no more deleterious to memory than is glycopyrrolate when given before ECT.

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.

Plasma levels of neuroleptic in patients receiving depot fluphenazine.

Depot forms of fluphenazine are frequently used in the outpatient treatment of psychiatric patients. To gather relevant data on pharmacokinetic characteristics of depot fluphenazines, the authors measured plasma levels of neuroleptic activity in 76 clinic patients on stable dosage regimens of fluphenazine decanoate or fluphenazine enanthate. Dose and plasma neuroleptic activity level were highly correlated for both forms of depot fluphenazine. Furthermore, the slope of the regression of log dose to the log plasma neuroleptic activity was the same for both drug forms. However, doses of enanthate twice those of decanoate were associated with the same mean plasma level of neuroleptic activity. Finally, while blood levels of drug overlapped markedly in cohorts of patients receiving different doses of depot medication, the assumption of recent studies that, on the average, patients in such cohorts have different blood and tissue levels of drug was confirmed.