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Biomedical subjects

L L Altshuler

Publications and source records attributed to L L Altshuler.

At least 55 records · Page 3Linked to original sources

Bipolar disorder in late life: a review.

Although there is a broad base of literature on depression among elderly patients and on mania in younger patients, there is a relative paucity of information on bipolar disorder in the elderly population. While the quantities of data reflect the relative prevalences of these illnesses, there is evidence to suggest that classification of mania in the elderly with respect to age of onset, natural course, family history, and pathophysiology may be useful in understanding the heterogeneous etiologies of this syndrome. This paper presents a review of the literature on the incidence and course of illness in late-life bipolar disorder. Further, dilemmas of diagnostic classification in relation to associated risk factors will be discussed.

Age of Onset↗

Course of mood and anxiety disorders during pregnancy and the postpartum period.

Because the onset of mood and anxiety disorders often occurs during the childbearing years, many women may be taking psychotropic medications for these disorders when they conceive. These medications easily diffuse across the placenta, and their impact on the fetus is of concern. But discontinuation may lead to relapse, in which case psychiatric symptoms may affect the fetus. Thoughtful treatment planning presents a dilemma to the clinician. Limited data suggest heightened vulnerability to relapse of mood and anxiety disorders in women during the postpartum period. Pregnancy appears to exacerbate symptoms of obsessive-compulsive disorder, while panic disorder patients may remain well after discontinuing medication. Future studies should address the prevalence and relapse rates of mood and anxiety disorders, particularly after medication discontinuation, among pregnant women.

Anxiety Disorders↗

Managing psychiatric medications in the breast-feeding woman.

Given the high risk of postpartum psychiatric problems, clinicians need to be prepared to appropriately manage the breast-feeding woman who needs psychotropics. These psychiatric researchers examine the issues and offer guidelines. Following childbirth, many women are at high risk for the onset or recurrence of psychiatric illness. Women who need psychopharmacologic treatment may wish to breast-feed their infants, but the data regarding the degree of drug passage to the infant and the subsequent effects of this exposure on infant growth and development are very limited, leaving clinicians with little guidance for responding in ways that protect the health and well-being of both mother and infant. In general, the less protein-bound, the more lipid-soluble, and the more weakly basic a drug is, the more likely it is to diffuse into breast milk. When a psychotropic medication is administered, the infant's clinical status and serum concentrations, including metabolite concentrations, should be closely monitored. Among the agents that have been the subject of at least limited studies in breast-feeding women are tricyclic antidepressants, selective serotonin reuptake inhibitors, benzodiazepines, and the mood stabilizers lithium, carbamazepine, and divalproex. This article examines the factors that influence infant exposure to psychotropic medication through breast-feeding and includes clinical guidelines for managing the breast-feeding woman on psychotropics as well as protecting and caring for her infant.

Breast Feeding↗

Pharmacologic management of psychiatric illness during pregnancy: dilemmas and guidelines.

OBJECTIVE: Given concerns about use of psychotropic medication during pregnancy, the authors reviewed the literature regarding the effects of prenatal exposure to psychotropic medications on fetal outcome. METHOD: A MEDLINE search of all articles written in English from 1966 to 1995 was performed to review information on the effects of psychotropic drug use during pregnancy on fetal outcome. Where sufficient data were available and when methodologically appropriate, meta-analyses were performed to assess risk of fetal exposure by psychotropic medication class. RESULTS: Three primary effects are associated with medication use during pregnancy: 1) teratogenicity, 2) perinatal syndromes (neonatal toxicity), and 3) postnatal behavioral sequelae. For many drug classes there are substantial data regarding risk for teratogenicity. Tricyclic antidepressants do not seem to confer increased risk for organ dysgenesis. The available data indicate that first-trimester exposure to low-potency phenothiazines, lithium, certain anticonvulsants, and benzodiazepines may increase the relative risk for congenital anomalies. However, the absolute risk of congenital malformations following prenatal exposure to most psychotropics is low. CONCLUSION: Exposure to certain psychotropic drugs in utero may increase the risk for some specific congenital anomalies, but the rate of occurrence of these anomalies even with the increased risk remains low. Use of psychotropic medications during pregnancy is appropriate in many clinical situations and should include thoughtful weighing of risk of prenatal exposure versus risk of relapse following drug discontinuation. The authors present disorder-based guidelines for psychotropic drug use during pregnancy and for psychiatrically ill women who wish to conceive.

Abnormalities, Drug-Induced↗

The relationship between antimanic agent for treatment of classic or dysphoric mania and length of hospital stay.

BACKGROUND: This retrospective study was conducted to evaluate the relationship between the mood-stabilizing agents lithium, carbamazepine, and divalproex sodium and time course of drug response as measured by length of hospital stay. METHOD: Seventy-eight patients were evaluated. Discharge date and length of hospitalization were obtained by review of the dictated discharge summary by investigators who were blind to medication status. Drug choice, including blood levels, was then identified as well as any adjunctive treatment. Statistical evaluation (SAS software) of time to improvement was conducted using nonparametric survival models. Possible confounding variables were assessed by parametric survival regression models and proportional hazards models. RESULTS: The individual survival curves of four major antimanic treatment groups revealed a significant difference by the second week of hospitalization in the divalproex sodium and the lithium/carbamazepine combination groups as compared with the lithium or carbamazepine groups (chi 2 = 13.83, df = 3, p = .003). The mean +/- SD length of stay was approximately 40% shorter for the divalproex sodium (10.2 +/- 2.0 days) and the lithium/carbamazepine combination (11.7 +/- 2.1 days) groups compared with the lithium alone (17.6 +/- 1.0 days) and the carbamazepine alone (18.1 +/- 3.0 days) groups. Regression analysis of possible confounding variables including adjunctive treatment (benzodiazepines and neuroleptics), severity of illness (number of years ill and previous hospitalizations), and discharge date revealed no statistically significant effect. CONCLUSION: Shortcomings of our study include those inherent in the design of a non-randomized, small naturalistic study and retrospective chart review. Our study does, however, suggest different drug response rates for the treatment of classic and dysphoric mania and warrants further controlled investigation.

Adult↗

Antidepressant-induced mania and cycle acceleration: a controversy revisited.

OBJECTIVE: The longitudinal course of 51 patients with treatment-refractory bipolar disorder was examined to assess possible effects of heterocyclic antidepressants on occurrence of manic episodes and cycle acceleration. METHOD: Using criteria established from life charts, investigators rated the patients' episodes of mania or cycle acceleration as likely or unlikely to have been induced by antidepressant therapy. Discriminant function analyses were performed to assess predictors of vulnerability to antidepressant-induced mania or cycle acceleration. Further, the likelihood of future antidepressant-induced episodes in persons who had had one such episode was assessed. RESULTS: Thirty-five percent of the patients had a manic episode rated as likely to have been antidepressant-induced. No variable was a predictor of vulnerability to antidepressant-induced mania. Cycle acceleration was likely to be associated with antidepressant treatment in 26% of the patients assessed. Younger age at first treatment was a predictor of vulnerability to antidepressant-induced cycle acceleration. Forty-six percent of patients with antidepressant-induced mania, but only 14% of those without, also showed antidepressant-induced cycle acceleration at some point in their illness. CONCLUSIONS: Mania is likely to be antidepressant-induced and not attributable to the expected course of illness in one-third of treatment-refractory bipolar patients, and rapid cycling is induced in one-fourth. Antidepressant-induced mania may be a marker for increased vulnerability to antidepressant-induced cycle acceleration. Antidepressant-induced cycle acceleration (but not antidepressant-induced mania) is associated with younger age at first treatment and may be more likely to occur in women and in bipolar II patients.

Adult↗

T2 hyperintensities in bipolar disorder: magnetic resonance imaging comparison and literature meta-analysis.

OBJECTIVE: Accumulating evidence suggests a greater number of T2 abnormalities in the brains of patients with bipolar I disorder. The authors sought to evaluate the presence of signal "hyperintensities" in both bipolar I and II subjects and systematically review the existing literature. METHOD: Magnetic resonance images of the brain were obtained prospectively for 29 patients with bipolar I disorder, 26 patients with bipolar II disorder, and 20 normal comparison subjects. The presence and location of signal hyperintensities in three brain regions (periventricular white matter, subcortical gray matter, and deep white matter) were evaluated. RESULTS: No significant differences were found between groups for the presence of subcortical gray or deep white matter hyperintensities. Periventricular hyperintensities were more common in bipolar I patients (62%) than in bipolar II patients (38%) and normal comparison subjects (30%). Within patient groups, medication use was not significantly different for those with or without the presence of white matter hyperintensities. The literature on bipolar disorder and signal hyperintensities is reviewed. A meta-analysis of the pooled data in the literature on bipolar illness and signal hyperintensities revealed that the odds of having a T2 hyperintensity are significantly greater for bipolar I than for normal comparison subjects. CONCLUSIONS: Having bipolar I disorder significantly increases the chance of having white matter changes in the brain. This study suggests that bipolar II patients may be more similar than bipolar I patients to comparison subjects on T2 measures. The possible pathophysiological significance of hyperintensities is discussed.

Adult↗

Breastfeeding and sertraline: a 24-hour analysis.

BACKGROUND: Few reports exist on the levels of antidepressants in breast milk or on observed behavioral effects, if any, of neonates who are breast-fed. Thus, a dilemma exists for women who would like to breast-feed but require psychotropic medications. METHOD: Analysis of sertraline levels was performed on eight samples of breast milk obtained over a 24-hour period, after 3 weeks of breastfeeding, from a lactating patient taking sertraline and nortriptyline. During this same 24-hour period, two serum samples each were taken from mother and child for analysis of sertraline and nortriptyline levels. After 7 weeks of exclusive breastfeeding, an additional serum sample was obtained from mother and child for analysis of sertraline levels. Drug metabolites were not measured. RESULTS: Breast milk levels of sertraline were lowest 1 hour before the ingestion of sertraline and highest 5 to 9 hours after ingestion of the drug. The infant's serum sertraline and nortriptyline levels were nondetectable. CONCLUSION: These data indicate that sertraline levels in breast milk vary substantially over 24 hours and appear to be lowest within the 2 hours before and 1 hour after ingestion of the medication, with the peak probably occurring between Hours 1 and 9 postingestion. However, the absence of detectable serum sertraline and nortriptyline levels in the infant suggests that if either medication is present in infant serum, its concentration would be extremely low. No abnormal occurrences have been noted in the development of the infant. It would be important in future studies to measure metabolites in addition to medication levels since the former have been associated with untoward events in an infant.

1-Naphthylamine↗

Lithium sustains the acute antidepressant effects of sleep deprivation: preliminary findings from a controlled study.

Early morning sleep deprivation (patient awake from 0200 to 2200 hours) produces a same-day antidepressant effect in approximately one-half of patients with major depression. Unfortunately, these antidepressant effects are short-lived and patients usually relapse to baseline depression levels within 48 hours. Recent work suggests, however, that the use of lithium with early morning sleep deprivation sustains this rapid antidepressant effect and makes it clinically useful. In a 30-day study, we compared the abilities of four different treatments (lithium plus early morning sleep deprivation, lithium plus a control sleep deprivation procedure, and desipramine with either of the two sleep manipulations) to induce a rapid (next-day) and sustained antidepressant response in 16 depressed patients. Lithium plus early morning sleep deprivation produced a quicker response than lithium with the control sleep deprivation, and the response was sustained for at least 30 days. In this design, however, lithium/early morning sleep deprivation was no faster than either of the two desipramine/sleep deprivation conditions in inducing remission. These results support the results of previous studies and suggest further investigation of this novel sleep/pharmacologic intervention is warranted.

Adult↗

Is there a role for neuroleptics in bipolar depression?

BACKGROUND: Lithium, carbamazepine, and valproic acid reduce relapse rates in most bipolar patients. However, some patients with bipolar illness fail to obtain antidepressant benefits from these medications, despite appropriate dosages of and duration on therapy with these drugs. METHOD: Three bipolar patients were followed in an open fashion on thymoleptic and neuroleptic medications. With discontinuation of neuroleptics, each patient relapsed into depression and was then restarted on neuroleptic treatment. RESULTS: These three patients responded rapidly to readministration of neuroleptics to their pharmacologic regimen. CONCLUSION: Some bipolar patients experience depressive relapse following neuroleptic discontinuation. With reinstitution of the neuroleptic, they show rapid improvement in mood.

Adult↗