zimeldine and Bipolar-Disorder

Cerebrospinal fluid concentrations of the norepinephrine metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), and the dopamine metabolite, homovanillic acid, were measured in depressed patients before and after treatment with three putatively specific antidepressants. The expected specificity of action on these three neurotransmitter metabolites was not observed. Desipramine hydrochloride, a norepinephrine uptake inhibitor, reduced 5-HIAA as well as MHPG concentrations; zimeldine hydrochloride, a serotonin uptake inhibitor, reduced MHPG as well as 5-HIAA concentrations; and clorgyline, a selective monoamine oxidase type A inhibitor, which might be predicted to most affect 5-HIAA, dramatically reduced MHPG, moderately reduced homovanillic acid, and only modestly reduced 5-HIAA concentrations.

Topics: Adolescent; Adult; Aged; Bipolar Disorder; Clorgyline; Depressive Disorder; Desipramine; Female; Glycols; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Male; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Propylamines; Serotonin; Zimeldine

A double-blind comparison of zimeldine, a selective 5-HT reuptake inhibitor, and nomifensine, a noradrenaline and a dopamine reuptake inhibitor, was carried out in 43 inpatients with a scheduled treatment period of 6 weeks. All patients were diagnosed as definite major depressive disorder according to Research Diagnostic Criteria (RDC), and the WHO International Classification of Diseases (ICD-9). The antidepressive efficacy was evaluated by a 10-item subscale of the Comprehensive Psychopathological Rating Scale (CPRS), a clinical global impression (CGI) scale and a self-rating scale (VAMS). Side effects were recorded, and anticholinergic effect was evaluated by parotid saliva volume measurement. No statistically significant differences in efficacy or profile between the two drugs were demonstrable. With the exception of increased sweating in the zimeldine group there were no statistically significant differences in side effects.

Topics: Bipolar Disorder; Clinical Trials as Topic; Depressive Disorder; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Isoquinolines; Nomifensine; Psychiatric Status Rating Scales; Psychotic Disorders; Zimeldine

Effects of five antidepressant treatments--clorgyline, desipramine hydrochloride, electroconvulsive treatment, lithium carbonate, and zimelidine hydrochloride--on urinary outputs of dopamine, dihydroxyphenylacetic acid, and homovanillic acid (HVA) were investigated in unipolar and bipolar depressed patients. Clorgyline and lithium carbonate, which stabilized mood in bipolar patients, reduced the urinary output of HVA and whole-body dopamine turnover. Electroconvulsive treatment and zimelidine were without major effects, whereas desipramine had variable effects on these indexes of dopamine metabolism. Three patients, two receiving desipramine and one receiving clorgyline, who had increased HVA output during the drug treatments, became severely agitated and delusional.

Topics: 3,4-Dihydroxyphenylacetic Acid; Adult; Antidepressive Agents; Bipolar Disorder; Brompheniramine; Clorgyline; Depressive Disorder; Desipramine; Dopamine; Electroconvulsive Therapy; Female; Homovanillic Acid; Humans; Male; Middle Aged; Zimeldine

The efficacy of zimeldine in preventing depressive episodes in recurrent major depressive disorders was evaluated in a randomized, placebo-controlled study involving 40 patients. The intended study period was 18 months. The results showed zimeldine to be significantly more effective than placebo, both in terms of preventing recurrence (t-test: P less than 0.001) and the withdrawal rate (Cox's test: P less than 0.01). Adverse symptoms for zimeldine did not differ from placebo. There were no noteworthy changes in clinical chemistry, blood pressure, ECG and pulse rate.

Topics: Adult; Aged; Bipolar Disorder; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Compliance; Recurrence; Zimeldine

Zimeldine, imipramine and placebo were studied in a randomized, double-blind, parallel group comparison of 119 patients with primary affective disorders. These out-patients were between 18 and 65 years of age and all received placebo single-blind during an initial 3-7-day washout period. During the subsequent 6-week double-blind period, patients were titrated from 50 mg b.d. to 150 mg b.d. with zimeldine, a potent and selective inhibitor of 5-HT reuptake, with imipramine, an inhibitor of noradrenaline and 5-HT reuptake, or with a corresponding number of placebo capsules. The zimeldine treatment group had significantly lower mean HAM-D scale total scores than the placebo and imipramine groups at week 4 and last available assessment. There was a significantly greater proportion of patients showing an improvement of 50% or more in HAM-D score, among the zimeldine group than in the placebo group at week 4, and among the imipramine group at weeks 4, 6 and last available assessment. The Clinical Global Impression (CGI) scales and the 56-item Hopkins Symptom Check-list (HSCL-56) self-rating inventory both showed significantly more improvement in the zimeldine patients than in the placebo or the imipramine patients. Fewer zimeldine patients reported adverse experiences than imipramine patients. Dry mouth was the most frequently reported adverse experience, occurring significantly more often in the imipramine group than the zimeldine or the placebo groups; significantly more zimeldine than placebo patients reported dry mouth. Headache was the only other adverse experience which occurred more often in the zimeldine than in the placebo group. The imipramine group had consistently higher mean pulse rates than the other two groups, and postural hypotension was also more common in the imipramine group.

Topics: Adolescent; Adult; Aged; Bipolar Disorder; Blood Pressure; Body Weight; Clinical Trials as Topic; Depressive Disorder; Double-Blind Method; Headache; Humans; Imipramine; Middle Aged; Placebos; Psychiatric Status Rating Scales; Pulse; Zimeldine

A comparative evaluation of zimelidine, a potent and selective serotonin (5-HT) uptake inhibitor, and desipramine, a potent noradrenaline (NA) uptake inhibitor, was carried out in a 4-week randomized, double-blind study in 65 hospitalized patients with endogenous depression. For evaluation of the clinical effect, Hamilton Rating Scale for depression (HRS) and a 14-item scale chosen from the Comprehensive Psychopathological Rating Scale (CPRS) were used. The concentration of drug in plasma was determined on the same days as the clinical ratings. There were no significant difference in the overall therapeutic effect between the two drugs. However, zimelidine had significantly better effect on anxiety. Although both agents were well tolerated, the zimelidine-treated patients reported significantly less severe anticholinergic side effects. Body weight did not change significantly in either treatment group. In the total material ther were no significant correlation between plasma concentrations of zimelidine, norzimelidine and desipramine and the amelioration score of either HRS and CPRS.

Topics: Adult; Aged; Antidepressive Agents; Bipolar Disorder; Brompheniramine; Depressive Disorder; Desipramine; Double-Blind Method; Female; Humans; Male; Middle Aged; Norepinephrine; Psychiatric Status Rating Scales; Pyridines; Serotonin; Zimeldine

Depressed patients, who did not respond after 4 weeks treatment with zimelidine 100 mg b.i.d. (five patients) or desipramine 75 mg b.i.d. (11 patients) in a double-blind randomized study were crossed over, after 1 placebo week, to 4 weeks of treatment with the other drug. The three zimelidine non-responders who responded to desipramine were significantly more retarded compared with eight desipramine non-responders who responded to zimelidine. It was observed that two patients with bipolar depression developed mania during crossover treatment with desipramine, while two patients with bipolar depression who were treated with zimelidine during the second treatment period did not show any symptoms of mania. Three patients who were non-responders during both treatment periods had lower plasma concentration of the drugs compared with respective responding groups.

Topics: Antidepressive Agents; Bipolar Disorder; Brompheniramine; Depressive Disorder; Desipramine; Double-Blind Method; Female; Humans; Male; Middle Aged; Norepinephrine; Pyridines; Serotonin; Zimeldine

Metabolism, synthesis rates, and pharmacokinetics of major metabolites of endogenous norepinephrine were investigated in 38 drug-free depressed patients receiving a low monoamine diet on a closed ward. In a group of 21 patients, plasma and cerebrospinal fluid (CSF) concentrations of 3-methoxy-4-hydroxyphenyl-glycol (MHPG) correlated positively, but not significantly. In two groups of eight patients each, effects of desipramine and zimelidine on the central production rate of MHPG were examined using CSF and urine data. Both desipramine and zimelidine significantly reduced the central production rate of MHPG.

Topics: Adult; Aged; Bipolar Disorder; Depressive Disorder; Desipramine; Female; Glycols; Humans; Kinetics; Male; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Zimeldine

Somatostatin is a hypothalamic tetradecapeptide with many central nervous system actions. We investigated a potential role for altered somatostatin activity in affective disorder by measuring somatostatin in the cerebrospinal fluid (CSF) of 47 patients with affective disorder and of 39 normal volunteers. Medication-free depressed patients showed significantly lower levels of CSF somatostatin than normal volunteers (p less than .001) or patients during the improved state (p less than .01). Somatostatin levels were significantly and inversely correlated with duration of sleep on the night of the lumbar puncture (p less than .05). Treatment with carbamazepine reduced CSF somatostatin (p less than .01) in contrast to the absence of effect of imipramine, desmethylimipramine, and lithium carbonate and the significant increase in CSF somatostatin seen in a small group of patients treated with zimelidine. The implications of these findings with respect to attempts to explore the neurobiology of depression are discussed.

Topics: Bipolar Disorder; Carbamazepine; Depressive Disorder; Desipramine; Humans; Imipramine; Lithium; Lithium Carbonate; Somatostatin; Zimeldine

A small group of patients who had been successfully treated with lithium for a number of years were treated with zimeldine in order to determine whether this antidepressant could be substituted for lithium in patients with a bipolar affective illness. The proposed treatment period of 6 months was not reached by any patient due to depression, hypomania, mania or unusual adverse symptoms. The results of this pilot study suggest that bipolar patients being treated with lithium should not then be treated by antidepressants including those which are potent and selective inhibitors of 5-HT uptake.

Topics: Adolescent; Adult; Aged; Bipolar Disorder; Female; Humans; Male; Middle Aged; Zimeldine