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Biomedical subjects

C L Bowden

Publications and source records attributed to C L Bowden.

At least 37 records · Page 2Linked to original sources
PubMed1999

Mania: gender, transmitter function, and response to treatment.

Noradrenergic and GABA systems may be involved in mania, but there is little information about relationships between the function of these systems and response to specific antimanic treatments. We investigated relationships between indices of catecholamine or GABA system function, pretreatment mania severity and antimanic response to divalproex, lithium, or placebo. Plasma GABA and urinary excretion of catecholamine metabolites were measured before randomization to lithium, divalproex or placebo in patients hospitalized for manic episodes. Severity of mania was evaluated using the Manic Syndrome, Behavior and Ideation and Mania Rating Scale scores from the SADS-C. Multiple regression analysis showed that pretreatment plasma GABA was related to severity of manic symptoms. This relationship seemed stronger in women. Multiple regression analysis showed that pretreatment levels of urinary MHPG correlated with improvement in manic syndrome scores. These data suggest that GABA and norepinephrine may be related to different aspects of the manic state and to its pharmacologic sensitivity.

Adult↗
PubMed1999

Psychomotor performance and monoamine function in bipolar and unipolar affective disorders.

BACKGROUND: Affective disorders are associated with prominent psychomotor abnormalities that may be related to changes in arousal or motivation due to altered catecholamine function. METHODS: We investigated relationships between performance on psychomotor tests of motor speed (reaction time and tapping speed) and visual tracking (trail making and dot placement) and catecholamine system function including cerebrospinal fluid (CSF) or urinary concentrations of catecholamines or their metabolites. Subjects were medicine-free inpatients with unipolar depression or with manic, depressive, or mixed episodes of bipolar disorder, and healthy controls matched by gender and stratified by age. RESULTS: Unipolar and bipolar depressed patients were impaired in motor speed, dexterity, and visual tracking, whereas manic and mixed patients did not differ from controls. Tapping speed correlated positively with CSF 3-methoxy-4-hydroxyphenylglycol in healthy controls and with CSF homovanillic acid in bipolar depressed subjects. Increased catecholamine function correlated with slowing in all other measures for patients with bipolar disorder. Relationships between catecholamines and psychomotor function were weaker in unipolar depressed subjects. Psychomotor function was related to severity of depression in bipolar, but not in unipolar, patients. CONCLUSIONS: These data suggest that catecholamine systems are associated with increased arousal and psychomotor impairment in patients with bipolar disorder. Similar behavioral changes have different neurotransmitter relationships in unipolar disorder.

Adult↗
PubMed1999

The efficacy of lamotrigine in rapid cycling and non-rapid cycling patients with bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) who have rapid cycling features are often treatment refractory. Clear and conclusive evidence regarding effective treatments for this group is not available. METHODS: Patients with diagnoses of refractory bipolar disorder who were currently experiencing manic, mixed, depressive, or hypomanic episodes were treated with lamotrigine as add-on therapy (60 patients) or monotherapy (15 patients). We compared the efficacy of lamotrigine in the 41 rapid cycling and 34 non-rapid cycling patients with BD. RESULTS: Improvement from baseline to last visit was significant among both rapid cycling and non-rapid cycling patients for both depressive and manic symptomatology. For patients entering the study in a depressive episode, improvement in depressive symptomatology was equivalent in the two groups. Among patients entering the study in a manic, mixed, or hypomanic episode, those with rapid cycling improved less in manic symptomatology than did non-rapid cycling patients. Among rapid cycling patients with initial mild-to-moderate manic symptom severity, improvement was comparable to that in non-rapid cycling subjects; however, the subset of rapid cycling patients with severe initial manic symptomatology had little improvement in mania. Rapid cycling patients had earlier onset and more lifetime episodes of mania, depression, and mixed mania. CONCLUSIONS: Lamotrigine was generally effective and well tolerated in this group of previously non-responsive, rapid cycling bipolar patients.

Activity Cycles↗
PubMed1999

Lamotrigine in the treatment of bipolar depression.

Several case reports and open studies have reported the efficacy of lamotrigine in bipolar depression. A randomised placebo-controlled 7-week study comparing two doses of lamotrigine with placebo in 195 patients with moderate to severe bipolar depression has now been completed. Lamotrigine was superior to placebo after 3 weeks as assessed by changes in the Montgomery-Asberg Depression Rating Scale (MADRS). A response, defined as more than 50% improvement on the MADRS occurred in 56 and 48% of the lamotrigine 200 and 50 mg/day groups, respectively, compared with 29% for placebo (P<0.05). There was no evidence that lamotrigine destabilised mood or precipitated mania. Tolerability was good and there were no cases of serious rashes. Preliminary results from an ongoing study also indicate that lamotrigine is more effective than gabapentin in bipolar depression. In conclusion, lamotrigine is effective in alleviating bipolar depression, without causing mood destabilisation. Slow dosage escalation yields good tolerability.

Acetates↗
PubMed1999

Spectrum of activity of lamotrigine in treatment-refractory bipolar disorder.

OBJECTIVE: New mood stabilizers are needed that possess efficacy for all phases of bipolar disorder. This study was designed to provide preliminary evidence for the safety and efficacy of a new anticonvulsant, lamotrigine, in adult patients with bipolar disorder who had been inadequately responsive to or intolerant of prior pharmacotherapy. METHOD: A 48-week, open-label, prospective trial was conducted in 75 patients with bipolar I or bipolar II disorder. Lamotrigine was used as adjunctive therapy (N = 60) or monotherapy (N = 15) in patients presenting in depressed, hypomanic, manic, or mixed states. RESULTS: Of the 40 depressed patients included in the efficacy analysis, 48% exhibited a marked response and 20% a moderate response as measured by reductions in 17-item Hamilton Depression Rating Scale scores. Of the 31 with a hypomanic, manic, or mixed state, 81% displayed a marked response and 3% a moderate response on the Mania Rating Scale. From baseline to endpoint, the depressed patients exhibited a 42% decrease in Hamilton depression scale scores, and the patients presenting with hypomania, mania, or a mixed state exhibited a 74% decrease in Mania Rating Scale scores. The most common drug-related adverse events were dizziness, tremor, somnolence, headache, nausea, and rash. Rash was the most common adverse event resulting in drug discontinuation (9% of patients); one patient developed a serious rash and required hospitalization. CONCLUSIONS: These open-label data provide preliminary evidence that lamotrigine may be an effective treatment option for patients with refractory bipolar disorder; however, potential benefits must be weighed against potential side effects, including rash.

Adult↗
PubMed1999

Differential effect of number of previous episodes of affective disorder on response to lithium or divalproex in acute mania.

OBJECTIVE: The authors investigated the relationship between number of lifetime episodes of affective disorder and the antimanic response to lithium, divalproex, or placebo. METHOD: The subjects were 154 of the 179 inpatients with acute mania who entered a 3-week parallel group, double-blind study. The primary efficacy measure was the manic syndrome score from the Schedule for Affective Disorders and Schizophrenia. The relationship between improvement and number of previous episodes was investigated by using nonlinear regression analysis. RESULTS: An apparent transition in the relationship between number of previous episodes and response to antimanic medication occurred at about 10 previous episodes. For patients who had experienced more episodes, response to lithium resembled the response to placebo but was worse than response to divalproex. For patients who had experienced fewer episodes, however, the responses to lithium and divalproex did not differ and were better than the response to placebo. This differential response pattern was not related to rapid cycling or mixed states. CONCLUSIONS: A history of many previous episodes was associated with poor response to lithium or placebo but not to divalproex.

Acute Disease↗
PubMed1999

A double-blind placebo-controlled study of lamotrigine monotherapy in outpatients with bipolar I depression. Lamictal 602 Study Group.

BACKGROUND: More treatment options for bipolar depression are needed. Currently available antidepressants may increase the risk of mania and rapid cycling, and mood stabilizers appear to be less effective in treating depression than mania. Preliminary data suggest that lamotrigine, an established antiepileptic drug, may be effective for both the depression and mania associated with bipolar disorder. This is the first controlled multicenter study evaluating lamotrigine monotherapy in the treatment of bipolar I depression. METHODS: Outpatients with bipolar I disorder experiencing a major depressive episode (DSM-IV, N = 195) received lamotrigine (50 or 200 mg/day) or placebo as monotherapy for 7 weeks. Psychiatric evaluations, including the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), Mania Rating Scale, and the Clinical Global Impressions scale for Severity (CGI-S) and Improvement (CGI-I) were completed at each weekly visit. RESULTS: Lamotrigine 200 mg/day demonstrated significant antidepressant efficacy on the 17-item HAM-D, HAM-D Item 1, MADRS, CGI-S, and CGI-I compared with placebo. Improvements were seen as early as week 3. Lamotrigine 50 mg/day also demonstrated efficacy compared with placebo on several measures. The proportions of patients exhibiting a response on CGI-I were 51%, 41%, and 26% for lamotrigine 200 mg/day, lamotrigine 50 mg/day, and placebo groups, respectively. Adverse events and other safety results were similar across treatment groups, except for a higher rate of headache in the lamotrigine groups. CONCLUSION: Lamotrigine monotherapy is an effective and well-tolerated treatment for bipolar depression.

Adult↗
PubMed1998

Bupropion slow-release response in depression: diagnosis and biochemistry.

BACKGROUND: Bupropion has been previously shown to be particularly beneficial in bipolar and atypical depression. Previous research has supported a possible association of response to plasma levels and to changes in plasma homovanillic acid (HVA). These findings were here extended to bupropion slow-release (SR), a formulation with slower release kinetics. METHODS: Forty-one patients with major depressive disorder (DSM-III-R) completed 8 weeks of a fixed dose of 300 mg/day in two doses/day. Clinical outcome measures were the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). Biological parameters included plasma HVA and 3-methoxy-4-hydroxyphenyl-glycol (MHPG), as well as a final measurement of plasma bupropion and its metabolites. RESULTS: Response to bupropion SR differed among the three groups: results for change in HDRS and in BDI were greater in the bipolar and atypical than in the "typical" depressed patients. Mean change in HDRS was, respectively, of 15.6, 17.1, and 7.6 (F = 5.57, p < .01); mean change in the BDI, 21.1, 16.9, and 7.3 (F = 3.32, p < .05). Threobupropion levels correlated with HDRS scores (r = .47, p = .02, n = 23); plasma HVA and MHPG increased significantly (t = 2.31, p = .03; t = 2.15, p = .04, n = 17). Bipolar depressed patients' improvement in HDRS was related to increases in MHPG (r = .87, p = .01) and in HVA (r = .70, p = .08). CONCLUSIONS: This fixed-dose study indicates that there may be specific benefits for bupropion SR in atypical and bipolar depression, and that these benefits may be related also to plasma levels and biochemical changes in catecholamines. Due to the small sample size, replication is of key importance.

Adult↗
PubMed1998

New concepts in mood stabilization: evidence for the effectiveness of valproate and lamotrigine.

Recognition of limited overall benefits from lithium in bipolar disorder, with even greater disadvantages in more severe forms of the disease, has spurred interest in alternative therapies. A long history of development of evidence for the utility of valproate has culminated in well-designed, placebo-controlled studies that establish the efficacy of the divalproex form of valproate in acute mania. Generally positive, but as yet not conclusive, studies indicate continued benefits in prophylactic treatment of bipolar disorder. The spectrum of efficacy of valproate is somewhat broader than that of lithium, extending to patients with certain more severe forms of the illness; e.g., mixed manics. Pretreatment plasma GABA activity was positively correlated with magnitude of improvement in manic symptomatology with divalproex. The evidence of comparable clinical benefits for lithium and valproate has stimulated studies that indicate overlapping effects on specific G protein-linked signal transduction for lithium and valproate, but not for carbamazepine. The possibility that additional antiepileptic drugs might have efficacy in bipolar disorder has encouraged early clinical studies with several newer antiepileptic drugs. Preliminary evidence for the efficacy of one of these, lamotrigine, has been presented.

Affect↗
PubMed1998

Key treatment studies of lithium in manic-depressive illness: efficacy and side effects.

Lithium is the most extensively studied single psychopharmacologic agent. This review summarizes efficacy results of key studies in manic-depressive illness, the increasingly practical findings regarding predictors of response, and the implications of the increasingly better understood adverse effect profile of lithium. A recent well-designed study confirms earlier studies regarding the marked effectiveness of lithium in alleviation of acute mania. Early maintenance studies of marked superiority of lithium over placebo have been countered by recent open reports of lesser effectiveness. A recent randomized study provides support for the efficacy of lithium in maintenance therapy, but a satisfactory assessment of the effectiveness of lithium for maintenance and its optimal role requires further study. Many of the adverse effects of lithium can be addressed by dosage reduction, use of sustained-release lithium, or combination therapy.

Acute Disease↗
PubMed1997

Depression during mania. Treatment response to lithium or divalproex.

BACKGROUND: Little information exists from controlled studies about clinical characteristics that predict treatment response in mania. The presence of depressive symptoms during manic episodes may be associated with poor response to psychopharmacological treatments. This is an investigation of the relation between depressive symptoms and treatment response in acute manic episodes. METHODS AND DESIGN: In a parallel-group, double-blind study, 179 patients hospitalized for acute manic episodes were randomized to receive divalproex sodium, lithium carbonate, or placebo (ratio, 2:1:2). The study was carried out at 9 academic medical centers. Patients had comprehensive evaluations of behavior and symptoms before and during 3 weeks of treatment. The primary outcome measure, change in mania factor scores derived from the Schedule for Affective Disorders and Schizophrenia: Change Version, was compared in patients with and without depressive symptoms at baseline according to nurse- or physician-rated scales. RESULTS: Depressive symptoms were associated with poor antimanic response to lithium and with better response to divalproex. This was not due to differences in overall severity of illness, substance abuse, gender, age, or history. CONCLUSIONS: These data suggest that even a modest level of pretreatment depression-related symptoms is a robust predictor of lithium nonresponse, and is associated with better response to divalproex. Although their overall efficacy in acute mania is similar, lithium and divalproex may be most effective in clinically and biologically distinct groups of patients.

Adult↗
PubMed1997

Effect size of efficacy measures comparing divalproex, lithium and placebo in acute mania.

Effect size (ES) is a statistical concept that can be used to improve the interpretation of results from psychopharmacological studies. ES may aid interpretation of results when sample size is unbalanced or small or when units or levels of baseline measures differ across items. Usually, an investigator can define a threshold value for a clinically meaningful ES based on published data and clinical judgment or by resorting to conventions, e.g., a medium ES = 0.5 S.D., which can usually be discerned by the trained clinician. In the present study, we apply ES analysis to results from a study comparing the effectiveness of divalproex (DIVAL), lithium (LI), and placebo (PLA) in hospitalized, acutely manic patients. One hundred seventy-six patients were randomly assigned to DIVAL, LI, or PLA in a 2:1:2 ratio, with drug administered in a double-blind, parallel group design for 21 days. The primary efficacy measure was the Mania Rating Scale from the Schedule for Affective Disorders and Schizophrenia, composed of the Manic Syndrome Score (MSS) from items that are relatively specific to the manic state, and the Behavior and Ideation Score (BIS), which reflects severe but nonspecific psychopathology. Improvement of the MSS after 5 days of treatment was difficult to interpret based on percentage change (DIVAL = 19%, LI = 13.5%, PLA = 8.5%). However, the corresponding effect sizes of 0.79, 0.55, and 0.35 indicated a medium to marked ES for DIVAL, a medium ES for LI, and a small ES for PLA at this early point in treatment. Similarly, the ES for change on the MSS at the end of treatment indicated a large, readily observable improvement with both DIVAL (ES = 1.01) and LI (ES = 0.79) vs. an ES of 0.37 for PLA. ES analysis also indicated that the BIS is a less robust indicator of change to either drug. The ES at the end of treatment for the BIS was 0.67 for DIVAL-, 0.62 for LI-, and 0.25 for PLA-treated patients.

Adolescent↗
PubMed1997

Schizophrenia, psychosis, and cerebral spinal fluid homovanillic acid concentrations.

Neuroleptic drugs block brain dopamine receptors and are effective in treating psychoses of diverse origins. This finding has become a cornerstone of the dopamine theory of schizophrenia, but clinical studies relating schizophrenia, per se, to brain dopamine metabolism have ranged from controversial to negative. This article presents new evidence that cerebrospinal fluid levels of the dopamine metabolite homovanillic acid are related to the severity of psychosis in schizophrenia. These results support the concept that homovanillic acid levels in cerebrospinal fluid vary as a function of psychosis rather than being related to the diagnosis of schizophrenia per se.

Adult↗
PubMed1997

Desipramine versus phenelzine in recurrent unipolar depression: clinical characteristics and treatment response.

We compared desipramine with phenelzine in a double-blind, parallel-groups study of 43 outpatients with recurrent unipolar depression. Response to the two drugs was similar, with an overall average reduction in scores on the Hamilton Rating Scale for Depression of about 50% over 6 weeks. Improvement was negatively correlated with initial severity of depression, especially in patients treated with desipramine. Response to desipramine was better in patients with moderate to severe stressors and no previous hospitalizations. Response to either treatment was better in patients whose course consisted of recurrent depressions with a stable baseline, even if the baseline was dysthymic.

Adolescent↗
PubMed1997

Clonazepam in the treatment of panic disorder with or without agoraphobia: a dose-response study of efficacy, safety, and discontinuance. Clonazepam Panic Disorder Dose-Response Study Group.

In this multicenter, parallel-group, placebo-controlled, fixed-dose study, the efficacy, safety, dosing characteristics, and discontinuation of clonazepam were analyzed in patients with panic disorder. Four hundred thirteen patients were randomly assigned to receive placebo or one of five fixed daily doses of clonazepam (0.5 mg, 1.0 mg, 2.0 mg, 3.0 mg, and 4.0 mg). After 3 weeks of dose escalation, the fixed dose was given for 6 weeks (the dose-maintenance phase) and then was tapered during a 7-week discontinuance phase. The completion rates for the dose-maintenance phase ranged from 59 to 85% for the clonazepam groups (74% for the placebo group). Efficacy measurements at the end of the dose-maintenance phase indicated clinical improvement in all treatment groups but with a clear differentiation of the four higher doses of clonazepam from the 0.5-mg dose and placebo. The minimum effective dosage, as determined by the Williams' test, was 1.0 mg daily. Dose-response analysis showed that daily dosages of 1.0 mg and higher were equally efficacious in reducing the number of panic attacks. All treatments were well tolerated. Somnolence and ataxia were reported more often by patients in the 3.0- and 4.0-mg groups; depression, dizziness, fatigue, and irritability, although not showing dose-relatedness, were reported by more patients taking clonazepam than placebo. During the discontinuance phase, most patients worsened from their condition at the end of the dose-maintenance phase but did not revert to that at baseline. In addition, with the tapering schedule chosen for this study, patients in all treatment groups tolerated the discontinuance of clonazepam. Daily doses of 1.0 to 2.0 mg of clonazepam offered the best balance of therapeutic benefit and tolerability.

Adolescent↗