zimeldine and Obsessive-Compulsive-Disorder

Reports of the antiobsessional efficacy of clomipramine have led to a "serotonin hypothesis" of obsessive-compulsive disorder (OCD). To test this hypothesis, 16 outpatients with DSM-III OCD were studied using several measures of serotonergic function. Platelet 3H-imipramine binding and serotonin uptake were not significantly different between the OCD patients and a normal, age-matched control group. The level of the metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) was significantly higher in a small cohort of obsessionals compared with healthy volunteers, possibly reflecting increased brain serotonin turnover. In a direct test of the role of serotonin uptake in clomipramine's antiobsessional effects, the serotonin uptake inhibitor zimelidine was compared with the noradrenergic uptake inhibitor desipramine in a double-blind, controlled study. Zimelidine reduced CSF 5-HIAA, but was clinically ineffective in this group. Desipramine had weak but significant clinical effects. Nonresponders to zimelidine or desipramine improved significantly during a subsequent double blind trial of clomipramine. These findings demonstrate that pharmacological blockade of serotonin reuptake alone is not sufficient for an antiobsessional response.

Topics: Adult; Blood Platelets; Central Nervous System; Clinical Trials as Topic; Desipramine; Female; Humans; Hydroxyindoleacetic Acid; Male; Obsessive-Compulsive Disorder; Serotonin; Zimeldine

Six patients suffering from obsessive compulsive neurosis were randomly allocated into two groups of three patients each and commenced on either imipramine, a noradrenaline re-uptake inhibitor, or zimelidine, a serotonin re-uptake inhibitor. After 4 weeks, the group on zimelidine showed significant reduction of obsessional symptoms as compared to the other group. The response was rapid and sustained over a period of two months.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Imipramine; Male; Obsessive-Compulsive Disorder; Random Allocation; Zimeldine

Nearly every category of psychotropic drug has been investigated in an attempt to find a pharmacologic treatment for obsessive compulsive disorder (OCD). This study reviews published trials from the English literature in which tricyclic antidepressants, monoamine oxidase inhibitors, neuroleptics, benzodiazepines, and other agents were employed for treatment of OCD. Weaknesses in the current methodology including diagnosis, measurement of severity and criteria for improvement have contributed to invalid conclusions about drug treatment and efficacy. It appears that OCD is an etiologically heterogeneous disorder with a complex differential diagnosis. For the clinician, a major conclusion drawn from this review is that no agent emerges as a drug of choice. Although clorimipramine, the most actively investigated agent, shows some promise, it has not been conclusively demonstrated that other, more readily available heterocyclic agents are less effective. Furthermore, when other disorders co-exist, such as panic disorder, alternative agents may prove as effective.

Topics: Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Double-Blind Method; Humans; Lithium; Monoamine Oxidase Inhibitors; Obsessive-Compulsive Disorder; Psychotropic Drugs; Zimeldine

Six patients with Obsessive-Compulsive Disorder (DSM III) were treated in an open uncontrolled trial with Zimeldine, for 8 weeks. All six patients had cognitive deficits before treatment. Five patients improved on the clinical symptoms. Four of these showed pronounced amelioration of their cognitive deficits.

Topics: Adult; Female; Humans; Male; Obsessive-Compulsive Disorder; Psychological Tests; Zimeldine