PubMed Health⌕ Search

Biomedical subjects

C A Zarate

Publications and source records attributed to C A Zarate.

At least 19 recordsLinked to original sources
PubMed2004

Emerging experimental therapeutics for bipolar disorder: insights from the molecular and cellular actions of current mood stabilizers.

Bipolar disorder afflicts approximately 1-3% of both men and women, and is coincident with major economic, societal, medical, and interpersonal consequences. Current mediations used for its treatment are associated with variable rates of efficacy and often intolerable side effects. While preclinical and clinical knowledge in the neurosciences has expanded at a tremendous rate, recent years have seen no major breakthroughs in the development of novel types of treatment for bipolar disorder. We review here approaches to develop novel treatments specifically for bipolar disorder. Deliberate (ie not by serendipity) treatments may come from one of two general mechanisms: (1) Understanding the mechanism of action of current medications and thereafter designing novel drugs that mimics these mechanism(s); (2) Basing medication development upon the hypothetical or proven underlying pathophysiology of bipolar disorder. In this review, we focus upon the first approach. Molecular and cellular targets of current mood stabilizers include lithium inhibitable enzymes where lithium competes for a magnesium binding site (inositol monophosphatase, inositol polyphosphate 1-phosphatase, glycogen synthase kinase-3 (GSK-3), fructose 1,6-bisphosphatase, bisphosphate nucleotidase, phosphoglucomutase), valproate inhibitable enzymes (succinate semialdehyde dehydrogenase, succinate semialdehyde reductase, histone deacetylase), targets of carbamazepine (sodium channels, adenosine receptors, adenylate cyclase), and signaling pathways regulated by multiple drugs of different classes (phosphoinositol/protein kinase C, cyclic AMP, arachidonic acid, neurotrophic pathways). While the task of developing novel medications for bipolar disorder is truly daunting, we are hopeful that understanding the mechanism of action of current mood stabilizers will ultimately lead clinical trials with more specific medications and thus better treatments those who suffer from this devastating illness.

Antimanic Agents↗
PubMed2004

Emerging experimental therapeutics for bipolar disorder: clues from the molecular pathophysiology.

Bipolar affective disorder (manic-depressive illness) is a common, severe, chronic, and often life-threatening illness, associated with significant comorbidity. The recognition of the significant morbidity and mortality of patients with bipolar disorder, as well as the growing appreciation that a high percentage of patients respond poorly to existing treatments, has made the task of discovering new therapeutic agents, that are both efficacious and have few side effects increasingly more important. Most recent agents introduced into the pharmacopeia for the treatment of bipolar disorder have been anticonvulsants and atypical antipsychotics. We propose that novel treatments developed specifically for bipolar disorder will arise from (1) understanding more precisely the molecular mechanisms of treatments that are clearly efficacious or (2) developing medications based on the knowledge obtained of the underlying pathophysiology of bipolar disorder. Knowledge with regard to the underlying pathophysiology of bipolar disorder is increasing at a rapid pace, including alterations in intracellular signaling cascades as well as impairments of cellular plasticity and resilience in critical neuronal circuits. We propose that therapeutics designed to enhance cellular plasticity and resilience and that counter maladaptive stress-responsive systems may have considerable utility for the treatment of bipolar disorder. Therapeutic strategies designed to address cellular resilience and plasticity include the regulation of neurotrophic pathways, glucocorticoid signaling, phosphodiesterase activity, and glutamatergic throughput and mitochondrial function. While the task of developing novel medications for bipolar disorder is truly daunting, these and similar approaches will ultimately lead to better medications for the millions who suffer from this devastating illness.

Antimanic Agents↗
PubMed2001

Cycling into depression from a first episode of mania: a case-comparison study.

OBJECTIVE: The characteristics of patients who cycle from mania to major depression and the frequencies of these cycles remain poorly understood. METHOD: This study compared 28 patients with a first episode of mania who cycled into a major depressive episode without recovery from their index episode and 148 patients with first-episode mania who did not cycle into depression. Patients were given extensive assessments at baseline and 6-, 12-, and 24-month follow-ups. Comparisons between the two groups were made on demographic variables, clinical ratings, and outcome variables. RESULTS: Approximately 16% of the patients with a first episode of mania cycled into major depression. Patients who cycled into depression were more likely to have higher depressive scores at admission and tended to have the mixed subtype of bipolar disorder. CONCLUSIONS: Patients with first-episode mania who score high for depression at admission may be at greater risk of cycling into a major depressive episode.

Adult↗
PubMed2000

First-episode schizophreniform disorder: comparisons with first-episode schizophrenia.

BACKGROUND: Schizophreniform disorder remains poorly understood and has been reported probably to be a heterogeneous group of psychotic disorders. METHOD: This study compared first-episode schizophreniform disorder (N=12) and schizophrenia (N=18) patients. The authors propose that schizophreniform disorder has a different type of onset and outcome than schizophrenia. Patients were given extensive assessments at initial evaluation, 6 month follow-up, and 24 month follow-up. Comparisons between the two groups were made on type of onset, demographic, clinical ratings and outcome variables. RESULTS: Patients with schizophreniform disorder compared to patients with schizophrenia were more likely to have an acute onset (P=0.003), and have recovered by 6 months (P=0.03). However, there were no differences in outcome at 24 months. Furthermore, all schizophreniform cases except for two were re-diagnosed at 24 months as having schizophrenia. CONCLUSIONS: The findings suggest that the initial differences of schizophreniform disorder compared to schizophrenia were not apparent at 24 months follow-up. Schizophreniform disorder did not emerge as a highly distinctive and stable form of psychosis that merits a diagnostic classification separate from schizophrenia.

Adult↗
PubMed2000

Functional impairment and cognition in bipolar disorder.

Bipolar disorder is a common, chronic and severe mental disorder, affecting approximately 2% of the adult population. Bipolar disorder causes substantial psychosocial morbidity that frequently affects the patient's marriage, children, occupation, and other aspects of the patient's life. Few studies have examined the functional impairment in patients with affective illness. Earlier outcome studies of mania reported favorable long-term outcomes. However, modern outcome studies have found that a majority of bipolar patients evidence high rates of functional impairment. These low reports of functional recovery rates are particularly surprising. The basis for such limited functional recovery is not entirely clear. Factors associated with functional dysfunction include presence of inter-episode symptoms, neuroleptic treatment, lower social economic class, and lower premorbid function. Cognitive dysfunction, a symptom domain of schizophrenia, has been identified as an important measure of outcome in the treatment of schizophrenia. Recently, there has been some suggestion that there may be impaired neuropsychological performance in euthymic patients with recurring mood disorders. Whether impaired neuropsychological performance in associated with the functional impairment in bipolar patients who have achieved syndromal recovery is an intriguing question. The literature on functional impairment and cognition in bipolar disorder is reviewed.

Adult↗
PubMed2000

Antipsychotic drug treatment in first-episode mania: a 6-month longitudinal study.

OBJECTIVE: To determine the use of antipsychotics during and following inpatient treatment of patients with a first-episode of mania. METHOD: The 198 subjects available for analysis were 129 consecutively hospitalized first-episode manic patients and 69 nonaffective psychotic patients assessed at admission and at 6-month follow-up postdischarge. Comparisons between the groups were made on frequency, type, and doses of antipsychotics prescribed during and after hospitalization in relation to clinical status. RESULTS: First-episode manic patients were given lower mean +/- SD daily doses of antipsychotics than nonaffective psychotic patients at discharge (163 +/- 132 mg chlorpromazine equivalents [CPZe] vs. 224 +/- 167 mg CPZe, p = .0102), at 6-month follow-up (109 +/- 167 mg CPZe vs. 260 +/- 178 mg CPZe; p = .0001), and if recovered (110 +/- 174 mg CPZe vs. 265 +/- 207 mg CPZe, p = .0014). At 6-month follow-up, 31 (24%) of 129 manic and 24 (35%) of 69 nonaffective psychotic patients continued to receive antipsychotics (NS). There was no difference between the groups in the time to discontinuation of antipsychotic agents. The mean time to drug discontinuation in manic patients was 98 days. CONCLUSION: (1) Antipsychotic doses at discharge and at 6-month follow-up were much lower in manic than in nonaffective psychotic patients, although there was no significant difference in the proportion of patients who continued to receive them 6 months after discharge. (2) The time to discontinuation was independent of clinical outcome. In those who discontinued the antipsychotic agent, the time to discontinuation was more rapid in the manic group than in the nonaffective psychotic patients.

Adult↗
PubMed2000

Clinical predictors of acute response with quetiapine in psychotic mood disorders.

BACKGROUND: In controlled studies of patients with schizophrenia, the atypical antipsychotic quetiapine, 300 mg/day, has been shown to be as effective in the treatment of positive and negative symptoms as haloperidol. However, little is known about the efficacy of quetiapine in patients with psychotic mood disorders. The purpose of this study was to assess the efficacy of quetiapine in the treatment of psychotic mood disorders in comparison with nonaffective psychotic disorders and identify clinical factors associated with quetiapine response. METHOD: In a naturalistic setting, by reviewing medical records, we assessed response to quetiapine and factors associated with response to quetiapine in 145 consecutive patients newly treated with the drug at a nonprofit academic psychiatric hospital. These patients had received a discharge diagnosis of bipolar disorder (manic, mixed, or depressive type), major depression with psychotic features, schizophrenia, schizoaffective disorder (bipolar or depressive type), delusional disorder, or psychosis not otherwise specified (NOS) according to DSM-IV criteria. RESULTS: Patients with a diagnosis of bipolar disorder, manic, mixed, or depressed and schizoaffective disorder, bipolar type displayed higher response rates (> 74%) compared with patients with schizophrenia. However, this finding did not achieve statistical significance. A diagnosis of major depression with psychotic features (p = .02) and longer duration of illness (p = .03) were associated with less chance of responding. CONCLUSION: Quetiapine may be a useful alternative or adjunctive treatment for patients with bipolar and schizoaffective disorders.

Adult↗
PubMed2000

Antipsychotic drug side effect issues in bipolar manic patients.

While the efficacy of antipsychotics as a maintenance treatment for bipolar patients has not been systematically studied, these drugs are commonly used in the long-term treatment of bipolar patients, and it is not unusual for a bipolar patient to be taking 3 to 4 medications, including antipsychotics. Conventional antipsychotics may be comparable to lithium for acute mania, but have limitations when used in the long-term treatment of bipolar disorder. Their adverse effects, which include extrapyramidal side effects, tardive dyskinesia, weight gain, sedation, and sexual dysfunction, often lead to non-compliance; their use may have a negative impact on the overall course of illness; and they may not be as effective as lithium in treating the core manic symptoms over the long term. Atypical antipsychotics may prove useful for bipolar patients who require antipsychotic treatment because of their favorable side effect profile, thymoleptic properties, and positive effect on overall functioning.

Antipsychotic Agents↗
PubMed1999

The adverse effect profile and efficacy of divalproex sodium compared with valproic acid: a pharmacoepidemiology study.

BACKGROUND: Divalproex sodium has been reported to be better tolerated than valproic acid. To our knowledge, no study has examined whether significant differences in the tolerability and efficacy exist between these preparations in psychiatric patients. The objective of the present study was to compare the tolerability and efficacy of divalproex sodium with those of valproic acid in psychiatric inpatients. METHOD: Information gathered retrospectively from the medical records of 150 patients treated with divalproex sodium was compared with that of 150 patients treated with valproic acid. These medical records were photocopied, and any mention of divalproex sodium or valproic acid treatment was concealed. A series of demographic and clinical characteristics were compared. RESULTS: Patients treated with divalproex sodium compared with patients treated with valproic acid were less likely to have gastrointestinal side effects (14.7% vs. 28.7%, p = .003), specifically anorexia (6.0% vs. 14.7%, p = .012), nausea or vomiting (6.7% vs. 16.7%, p = .007), and dyspepsia (11.3% vs. 22.0%, p = .013). Divalproex sodium-treated patients compared with valproic acid-treated patients were less likely to have discontinued their medication because of side effects (4.0% vs. 12.7%, p = .0066). Twelve (63.2%) of 19 patients who discontinued valproic acid because of gastrointestinal side effects were subsequently treated with divalproex sodium, of whom only 2 continued to have gastrointestinal side effects. There were no differences in efficacy between the 2 drugs. CONCLUSION: Divalproex sodium was better tolerated than valproic acid in inpatients with a variety of diagnoses and taking concomitant medications. Patients treated with divalproex sodium compared with patients treated with valproic acid were less likely to experience gastrointestinal side effects and to have discontinued their medication because of an adverse event.

Adolescent↗
PubMed1998

Clinical predictors of acute response with olanzapine in psychotic mood disorders.

BACKGROUND: In controlled studies of patients with schizophrenia, the atypical antipsychotic olanzapine has been shown to be more effective in the treatment of positive and negative symptoms compared with haloperidol at doses of 10 mg/day. However, little is known about the efficacy of olanzapine in patients with psychotic mood disorders. The purpose of this study was to assess the efficacy of olanzapine in the treatment of these psychotic mood disorders in comparison with nonaffective psychotic disorders and to identify clinical factors associated with olanzapine response. METHOD: In a naturalistic setting, by reviewing medical records, we assessed response to olanzapine and factors associated with response to olanzapine in 150 consecutive patients newly treated with the drug at a nonprofit academic psychiatric hospital. RESULTS: Patients displaying a moderate-to-marked response to olanzapine were more likely to be younger; be female; receive a diagnosis of bipolar disorder; and have a shorter duration of illness, shorter length of stay prior to olanzapine, and longer duration of trial. CONCLUSION: Olanzapine may be a useful alternative or adjunctive treatment for patients with bipolar disorder.

Adolescent↗
PubMed1998

Antipsychotic agents and bipolar disorder.

Antipsychotic agents have been used commonly in the treatment of bipolar disorder. This article reviews the evolution of the use of antipsychotic agents and their role in the acute and maintenance treatment of bipolar disorder. The focus is on neuroleptic drugs, the atypical antipsychotic drugs (risperidone and clozapine), and two fo the new atypical antipsychotic drugs that were recently approved.

Acute Disease↗
PubMed1997

Shifts in hospital diagnostic frequencies: bipolar disorder subtypes, 1981-1993.

Annual rates of bipolar and schizoaffective disorder (SA) subtypes from 1981 to 1993 at a private university psychiatric hospital were reviewed. Annual total diagnostic rates for all bipolar disorders (BPD) remained constant between 1981 and 1993, (22%), while the frequency of SA rose 6-fold, from 1.4% to 8.7%. Rates of BPD, not otherwise specified increased 7-fold, while that for the other BPD subtypes fell in the same period of time. Several factors may have influenced these trends including changes in diagnostic criteria used, treatment-oriented diagnostic bias and indirect effects of sharply falling length of stay.

Bipolar Disorder↗
PubMed1997

Combined valproate or carbamazepine and electroconvulsive therapy.

This pharmacoepidemiological study was undertaken to determine if the combination of electroconvulsive therapy (ECT) and the anticonvulsants valproate (VPA) or carbamazepine (CBZ) is safe and efficacious. The charts of seven patients receiving ECT and VPA or CBZ (ECT-anticonvulsant group) concurrently between May 8, 1989, and May 9, 1993, were reviewed to determine the indication for each treatment, the number and type of ECT treatments, the seizure duration, adverse events, and the efficacy of the combination. The ECT-anticonvulsant group was compared to patients not treated with anticonvulsants (ECT-alone group) to determine if there were any differences in the two groups. Three patients had a marked clinical improvement, two a moderate response, one a minimal response, and one no response. The ECT-AC group, compared to the control group, had a shorter duration of seizures when unilateral treatments were used. However, there were no differences in the other variables compared. One patient had moderate confusion, and the other mild confusion and hypomania. This small case series suggests that the combination of ECT and anticonvulsants is safe and may be considered in patients for whom prophylaxis with anticonvulsant drugs is planned. Further controlled studies are needed to confirm our findings.

Adult↗