Biomedical subjects

G S Sachs

Publications and source records attributed to G S Sachs.

At least 19 recordsLinked to original sources

PubMed2001

Effect of lithium on phosphoinositide metabolism in human brain: a proton decoupled (31)P magnetic resonance spectroscopy study.

BACKGROUND: The objective of our study was to evaluate whether lithium increases brain phosphomonoester (PME) levels in human subjects. METHODS: Proton decoupled (31)P magnetic resonance spectra were obtained from eight healthy volunteers before and after the administration of lithium carbonate, 450 mg b.i.d., for 7 and 14 days. RESULTS: Pairwise comparisons of the mole percent PME revealed a significant increase from baseline at day 7 and day 14 of lithium administration. CONCLUSIONS: An increase in PME concentration with 7 and 14 days of lithium administration in the human brain in vivo was observed. Because the inositol-1-monophosphate contributes to the PME peak, this result suggests that some of the initial actions of lithium may occur through a reduction of myo-inositol, which in turn may initiate a cascade of secondary changes at different levels of signal transduction process and gene expression in brain, effects that are ultimately responsible for the therapeutic benefits of lithium.

Adolescent↗

PubMed2001

31P Nuclear magnetic resonance spectroscopy findings in bipolar illness: a meta-analysis.

Published literature comparing 31P MR brain spectra of bipolar patients to healthy controls was evaluated, focusing on phosphomonoester (PME)/phosphodiester (PDE) resonance areas because these metabolites are related to membrane phospholipids and membrane defects in bipolar disorder have been suggested. Studies comparing PME and/or PDE values of bipolar subjects to values observed in healthy controls were reviewed. Data from the studies meeting our inclusion criteria (8 reports involving 139 bipolar and 189 comparison subjects) were grouped according to the mood state of the subjects. Meta-analyses of data were performed to compare PME and PDE levels of euthymic bipolar patients to healthy controls, as well as comparing PME levels during euthymia in bipolar subjects to values observed during manic and depressed states. The PME values of euthymic bipolar patients were found to be significantly lower than PME values of healthy controls. Depressed bipolar patients had significantly higher PME values in comparison to euthymic bipolar patients. No significant difference could be detected between the PDE values of bipolars and controls. This meta-analysis found support for trait- and possibly state-dependent abnormalities of membrane phospholipid metabolism, which may reflect a dysregulation in brain-signal transduction systems of relevance in bipolar illness.

Adult↗

PubMed2001

Administration of antidepressants. Single versus split dosing: a meta-analysis.

OBJECTIVE: To evaluate the literature comparing antidepressant effects of multiple daily dosing versus single daily dosing of antidepressants. METHOD: Studies comparing efficacy of single versus multiple daily dosing of antidepressants were reviewed. Data from the clinical trials meeting our inclusion criteria was subgrouped according to the half-life of the antidepressant drug studied. Meta-analyses were carried out to compare antidepressant efficacy of single versus multiple daily dosing overall and separately for the short, intermediate, and long half life antidepressant agent subgroups. RESULTS: The review process identified 22 studies comparing the therapeutic effect of antidepressants according to their dosing schedules. Although most studies used antidepressant medications with short half-lives, none found a significant difference in therapeutic efficacy. Furthermore, the improvement rates in depression scores in between the two groups were almost identical (SDD versus MDD). CONCLUSION: This meta-analytic approach found no advantage for multiple daily dosing and suggests that sustained therapeutic serum levels are not necessary for achievement of therapeutic activity. Antidepressant benefit may simply require a limited duration of exposure above the threshold serum level. Administration of antidepressants in single daily doses appears sufficient to perturb the physiological pathways associated with depression sufficiently to achieve an adaptive therapeutic response. Moreover, a single daily dosing regimen offers the potential advantages of simplicity, increased compliance, and reduced adverse effects, which in turn would increase the overall success rate in treatment of depression.

Antidepressive Agents↗

PubMed2001

Prenatal diagnosis of Bardet-Biedl syndrome by targeted second-trimester sonography.

Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by mental retardation, obesity, retinal degeneration, polydactyly and syndactyly, diabetes mellitus, hypogenitalism, renal dysplasia and short stature. Definitive molecular diagnosis for BBS is not currently available and counseling of affected families is based on the 25% recurrence risk consistent with autosomal recessive inheritance. Our case presents the first successful use of second trimester targeted sonographic anatomy scanning to prospectively identify a fetus affected with BBS, and indicates that ultrasound can be of critical importance in providing precise as well as timely prenatal diagnosis for families at risk for this serious disorder.

Adult↗

PubMed2001

Double-blind, placebo-controlled comparison of imipramine and paroxetine in the treatment of bipolar depression.

OBJECTIVE: This study compared the efficacy and safety of paroxetine and imipramine with that of placebo in the treatment of bipolar depression in adult outpatients stabilized on a regimen of lithium. METHOD: In a double-blind, placebo-controlled study, 117 outpatients with DSM-III-R bipolar disorder, depressive phase, were randomly assigned to treatment with paroxetine (N=35), imipramine (N=39), or placebo (N=43) for 10 weeks. In addition to lithium monotherapy, patients may have received either carbamazepine or valproate in combination with lithium for control of manic symptoms. Patients were stratified on the basis of trough serum lithium levels determined at the screening visit (high: >0.8 meq/liter; low: </=0.8 meq/liter). Primary efficacy was assessed by change from baseline in scores on the Hamilton Rating Scale for Depression and the Clinical Global Impression illness severity scale. RESULTS: Differences in overall efficacy among the three groups were not statistically significant. For patients with high serum lithium levels, antidepressant response at endpoint also did not significantly differ from placebo. However, both paroxetine and imipramine were superior to placebo for patients with low serum lithium levels. Compared to imipramine, paroxetine resulted in a lower incidence of adverse events, most notably emergence of manic symptoms. CONCLUSIONS: Antidepressants may not be useful adjunctive therapy for bipolar depressed patients with high serum lithium levels. However, antidepressant therapy may be beneficial for patients who cannot tolerate high serum lithium levels or who have symptoms that are refractory to the antidepressant effects of lithium.

Adult↗

PubMed2001

Citalopram as adjunctive therapy in bipolar depression.

BACKGROUND: The treatment of bipolar depression remains a major clinical challenge. The effectiveness and safety of adjunctive citalopram were evaluated in DSM-IV-diagnosed bipolar depressed patients in a 5-site study. METHOD: The treatment strategy consisted of an open-label add-on design in which patients received 8 weeks of acute treatment with citalopram adjunctive to their ongoing treatment with mood stabilizers. Ongoing treatment with 1 antipsychotic, 1 anxiolytic, and 1 hypnotic agent was permitted. Responders to the 8-week trial then received 16 weeks of additional treatment with citalopram. RESULTS: Forty-five subjects entered the trial; 12 dropped out before the end of the acute treatment phase. Of the 33 patients who completed the acute treatment phase, 64% (N = 21) were responders and 36% (N = 12) were nonresponders. In the continuation phase of the study, 14 patients achieved sustained remission, 3 patients did not achieve remission before completing 16 weeks of continuation treatment, 2 patients experienced a relapse, and 2 patients dropped out of the study and did not have a chance to remit. In spite of the extensive concomitant medication usage allowed in this study, citalopram treatment was well tolerated and the level of reported adverse events (including headache, nausea, diarrhea, and sexual dysfunction) relatively low. CONCLUSION: The high response rate, the high rate of sustained remission, and the low rate of adverse events strongly support the use of citalopram as a treatment for bipolar I or II depression. These findings should stimulate a controlled double-blind trial to demonstrate even more clearly the usefulness of this drug in the therapeutic regimen for bipolar disorder.

Adult↗

PubMed2001

Suicide prevention: increasing education and awareness.

Suicide is a serious and complex public health problem. Health care providers, including both psychiatrists and primary care physicians, are just beginning to understand the intricacies involved in suicide and its prevention. Suicide rates continue to rise, making the education of the public and physicians regarding awareness and prevention, recognition of a wide range of risk factors, and research into suicide prevention strategies very important.

Adolescent↗

PubMed2001

Integration of suicide prevention into outpatient management of bipolar disorder.

Suicide prevention is a critical objective in the treatment of bipolar disorder. This article describes practical mechanisms by which monitoring and management of suicide risk can be integrated into the routine care of patients with bipolar disorder. Suicide risk is assessed in terms of inclination (the drive to commit a self-destructive act) and opportunity (access to lethal means). Intervention strategies are adapted to the needs of bipolar patients across 3 phases of treatment: the acute episode; the continuation phase, when symptom reduction has occurred but adaptive recovery has not; and the maintenance phase, in which optimization of adaptive function and vigilance against impending relapse are paramount. Integration of suicide prevention into the outpatient management plan begins with a routine discussion of suicide risk at the initiation of a treatment relationship, even in the absence of other known risk factors. This discussion paves the way for ongoing assessment of suicidality. Just as the recommended routine monitoring of every euthymic bipolar patient includes at least some minimal assessment for prodromal symptoms of acute mania or depression, every clinical visit can include sufficient probes to determine the need for new interventions specific to suicide prevention. Ongoing assessment of risk and protective factors can be linked to a range of individualized interventions designed to meet the varying needs of patients over time. The intensity of monitoring and interventions reflects the clinician's knowledge of risk factors and may be life saving, but it is also important that patients and others involved in their care understand that monitoring cannot guarantee safety.

Adolescent↗

PubMed2000

Bipolar depression: pharmacotherapy and related therapeutic strategies.

The depressed phase of bipolar affective disorder is a significant cause of suffering, disability, and mortality and represents a major challenge to treating clinicians. This article first briefly reviews the phenomenology and clinical correlates of bipolar depression and then focuses on the major pharmacological treatment options. We strongly recommend use of mood stabilizers as the first-line treatment for the type I form of bipolar depression, largely because longer-term preventative therapy with these agents almost certainly will be indicated. Depressive episodes that do not respond to lithium, divalproex, or another mood stabilizer, or episodes that "breakthrough" despite preventive treatment, often warrant treatment with an antidepressant or electroconvulsive therapy. The necessity of mood stabilizers in the type II form of bipolar depression is less certain, aside from the rapid cycling presentation. Both experts and practicing clinicians recommend bupropion and the selective serotonin reuptake inhibitors as coequal initial choices, with venlafaxine and monoamine oxidase inhibitors, such as tranylcypromine, preferred for more resistant cases. The risk of antidepressant-induced hypomania or mania with concomitant mood stabilizer therapy is low, on the order of 5% to 10% during acute phase therapy. Additional therapeutic options and optimal durations of therapy also are discussed.

Acute Disease↗

PubMed2000

Bipolar disorder therapeutics: maintenance treatment.

Although most of the care received by bipolar patients occurs during the maintenance phase, relatively little empirical data is available to guide long-term treatment decisions. We review literature pertaining to key questions related to use of pharmacotherapy in the maintenance phase of bipolar disorder. The few double-blind trials with a reasonable sample size are restricted to bipolar I patients and address a modest range of questions mostly related to use of lithium. One rigorous multicenter trial found valproate to have prophylactic benefit. Other studies with valproate alone and in combination suggest efficacy equivalent to lithium and perhaps greater than carbamazepine. Data available for combination treatment are sparse but moderately encouraging. Maintenance treatment with standard antidepressant medications appears destabilizing for some bipolar patients, particularly following a mixed episode. Although some bipolar patients may benefit from combined treatment with a mood stabilizer and a standard antidepressant medication, current knowledge does not allow confident selection of the bipolar patients who might benefit. Clozapine and perhaps other atypical antipsychotics are promising options for maintenance treatment but have not been evaluated in double-blind trials. The numerous other agents used in maintenance treatment are primarily adjuncts to lithium, valproate, or carbamazepine, and information about them is largely anecdotal and uncontrolled. Study design for maintenance trials remains an imperfect art. Conclusions must be drawn cautiously, given the limited generalizability of study designs that accession samples enriched with presumed treatment responders, randomize patients after brief periods of partial remission, abruptly taper prior treatment, make no attempt to distinguish relapse from recurrence, use no formal outcome assessments, or report hospitalization as the only outcome criterion.

Antidepressive Agents↗

PubMed2000

Pramipexole augmentation in the treatment of unipolar and bipolar depression: a retrospective chart review.

OBJECTIVE: To assess the effectiveness and safety of pramipexole as an adjunctive medication in refractory bipolar and unipolar depression in a naturalistic setting. METHODS: Retrospective chart review by psychiatrists on staff at a university hospital identified all patients who had received pramipexole. Response was based on moderate to marked improvement in the Clinical Global Impression-Improvement (CGI-I) scale. RESULTS: Pramipexole (mean dose 0.70 mg/d, mean duration 24.4 weeks) was effective in 6/12 (50.0%) of patients with bipolar depression, and 8/20 (40%) of patients with unipolar depression, mean duration of follow-up of 24.4 weeks. One case of transient hypomania was noted. Eight patients discontinued pramipexole due to lack of response and four due to side effects. CONCLUSIONS: Pramipexole, used as an adjunct to antidepressants or mood stabilizers, appeared to be effective and safe in the treatment of unipolar and bipolar depression. These uncontrolled, retrospective, naturalistic pilot data require confirmation by controlled research before conclusions can be made.

Adult↗

PubMed2000

The treatment of bipolar depression.

OBJECTIVES: The treatment of the depressed phase of bipolar disorder is understudied and remains a common clinical dilemma for clinicians. Compared to the manic phases, episodes of bipolar depression are more frequent and of longer duration, yet the literature on this problem is minimal. The few methodologically sound studies find that treatment effective for unipolar depression are also efficacious for bipolar depression. However, standard antidepressant agents may cause acute mania or a long-term worsening of bipolar illness. This paper reviews the available literature on the treatment of bipolar depression and offers recommendations for clinical management. METHODS: A literature search was conducted using keywords 'bipolar disorder', 'depression', 'drug therapy', 'antidepressants', 'lithium', and 'anticonvulsants'. RESULTS: If effectively treated by lithium, patients are spared the risk of antidepressant-induced mania. If lithium is not sufficient treatment for acute depression, the combination of lithium and a standard antidepressant appears to reduce the risk of affective switch, as well as the induction of a long-term rapid-cycling course. Additionally, tapering antidepressant medication after periods of sustained remission can be beneficial in limiting the risk of affective switch and acceleration of the cycle rate. CONCLUSIONS: Doctors must be cautious in prescribing antidepressants for bipolar depression. Use of antidepressants alone should be avoided.

Anticonvulsants↗

PubMed2000

Ovarian function before and after salpingectomy in artificial reproductive technology patients.

To determine the effect of the removal of the tube on ovarian function we studied 52 artificial reproduction technology cycles in 26 women before and after undergoing laparoscopic salpingectomy for ectopic pregnancy. Ovarian response was measured by the duration and quantity of human menopausal gonadotrophins used in the cycle, the pre-ovulatory concentrations of oestradiol, the number of oocytes retrieved, and the quality of the embryos. All parameters were compared between cycles carried out before and after salpingectomy as well as between affected and unaffected sides. Our findings show no significant difference in any of the parameters studied. We conclude that laparoscopic salpingectomy does not abate ovarian response in artificial reproduction technology cycles that follow the procedure.

Adult↗

PubMed2000

Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire.

OBJECTIVE: Bipolar spectrum disorders, which include bipolar I, bipolar II, and bipolar disorder not otherwise specified, frequently go unrecognized, undiagnosed, and untreated. This report describes the validation of a new brief self-report screening instrument for bipolar spectrum disorders called the Mood Disorder Questionnaire. METHOD: A total of 198 patients attending five outpatient clinics that primarily treat patients with mood disorders completed the Mood Disorder Questionnaire. A research professional, blind to the Mood Disorder Questionnaire results, conducted a telephone research diagnostic interview by means of the bipolar module of the Structured Clinical Interview for DSM-IV. RESULTS: A Mood Disorder Questionnaire screening score of 7 or more items yielded good sensitivity (0.73) and very good specificity (0.90). CONCLUSIONS: The Mood Disorder Questionnaire is a useful screening instrument for bipolar spectrum disorder in a psychiatric outpatient population.

Adolescent↗

PubMed2000

Comorbidity of attention deficit hyperactivity disorder with early- and late-onset bipolar disorder.

OBJECTIVE: The relationship between attention deficit hyperactivity disorder (ADHD) and earlier age at onset of affective illness was examined in probands with a history of bipolar disorder. METHOD: The authors assessed 56 adult bipolar subjects. Those with a history of childhood ADHD (N=8) were age and sex matched with bipolar subjects without a history of childhood ADHD (N=8). RESULTS: The age at onset of the first affective episode was lower for the subjects with bipolar disorder and a history of childhood ADHD (mean=12.1 years, SD=4.6) than for those without a history of childhood ADHD (mean=20. 0 years, SD=11.3). CONCLUSIONS: ADHD in children of bipolar probands might identify children at highest risk for development of bipolar disorder.

Adolescent↗

PubMed2000

A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder.

BACKGROUND: Our purpose was to evaluate the overall efficacy and tolerability of novel antipsychotic medications for patients with bipolar disorder type I. METHOD: A retrospective study of the Massachusetts General Hospital Bipolar Clinic database was carried out to identify 50 consecutive treatment trials in patients with DSM-IV bipolar disorder type I who had received adjunctive treatment with risperidone, olanzapine, or clozapine, along with standard mood stabilizers. The treatment charts of those patients (N = 42) were reviewed for details of adverse effects, tolerability, and efficacy of medication. RESULTS: Overall results indicated equivalent efficacy in novel antipsychotic treatments according to change in Clinical Global Impressions scale score. Levels of extrapyramidal symptoms were similar in all groups and occurred in 12/42 patients (28.6%). Prolactin-related side effects were not observed in any patients. There were no cases of affective switch or worsening of mania. Substantial weight gain of more than 10 lb (4.5 kg) was significantly greater in patients treated with olanzapine. CONCLUSION: These results suggest that the efficacy and tolerability of risperidone, olanzapine, and clozapine are similar in patients with bipolar disorder. One major differentiation factor of these drugs appears to be weight gain, particularly between olanzapine and risperidone. This may, in part, also be related to the need to use mood-stabilizing agents, like lithium or divalproex sodium, which may potentiate the weight-gain effect of novel antipsychotics.

Adult↗

PubMed2000

A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder. Lamictal 614 Study Group.

BACKGROUND: Patients with rapid-cycling bipolar disorder are often treatment refractory. This study examined lamotrigine as maintenance monotherapy for rapid-cycling bipolar disorder. METHOD: Lamotrigine was added to patients' current psychotropic regimens and titrated to clinical effect during an open-label treatment phase. Stabilized patients were tapered off other psychotropics and randomly assigned to lamotrigine or placebo monotherapy for 6 months. Time to additional pharmacotherapy for emerging symptoms was the primary outcome measure. Secondary efficacy measures included survival in study (time to any premature discontinuation), percentage of patients stable without relapse for 6 months, and changes in the Global Assessment Scale and Clinical Global Impressions-Severity scale. Safety was assessed from adverse event, physical examination, and laboratory data. RESULTS: 324 patients with rapid-cycling bipolar disorder (DSM-IV criteria) received open-label lamotrigine, and 182 patients were randomly assigned to the double-blind maintenance phase. The difference between the treatment groups in time to additional pharmacotherapy did not achieve statistical significance in the overall efficacy population. However, survival in study was statistically different between the treatment groups (p = .036). Analyses also indicated a 6-week difference in median survival time favoring lamotrigine. Forty-one percent of lamotrigine patients versus 26% of placebo patients (p = .03) were stable without relapse for 6 months of monotherapy. Lamotrigine was well tolerated; there were no treatment-related changes in laboratory parameters, vital signs, or body weight. No serious rashes occurred. CONCLUSION: This was the largest and only prospective placebo-controlled study of rapid-cycling bipolar disorder patients to date; results indicate lamotrigine monotherapy is a useful treatment for some patients with rapid-cycling bipolar disorder.

Adolescent↗

PubMed2000

Clinical and sonographic fetal weight estimates in active labor with ruptured membranes.

OBJECTIVE: To determine and compare the accuracy of clinical and sonographic estimates of fetal weight (EFW) in active labor with ruptured membranes. STUDY DESIGN: Clinical and sonographic EFWs were obtained on 107 term patients in active labor, with cervical dilatation of 4 cm or more and ruptured membranes. Accuracy of birth weight was determined by calculating percentage error, absolute percentage error and ratio of estimates within 10% of actual birth weight for all stages of labor. Statistical analysis was by paired t test, Wilcoxon sign test, chi 2 test and Mann-Whitney U test; P < .05 was considered significant. RESULTS: Absolute percentage errors were lower by the sonographic method at all stages. Except for the second stage of labor, the rates of birth weight +/- 10% were higher with the sonographic method than with the clinical method (83.17% vs. 60.75% and 84.9% vs. 63.44%, respectively). Estimations performed in the first stage were more accurate than in the second stage with both methods (absolute error of 7.82 +/- 5.5 vs. 12.38 +/- 4.9 for clinical and 5.44 +/- 5.99 vs. 9.08 +/- 3.19 for sonographic). CONCLUSION: During active labor with ruptured membranes, sonographic EFWs are more accurate than clinical estimations. The accuracy of both methods is reduced during the second stage of labor.

Adult↗