A double blind study in out-patients with primary non-agitated depression treated with imipramine in combination with placebo, diazepam or dixyrazine

Sixty-three out-patients suffering from primary non-agitated depression were included in a double-blind, between-patient randomized study. All patients were treated with imipramine (100-200 mg-day) combined with either placebo, diazepam (10 mg/day) or dixyrazine (50 mg/day) for 8 weeks. The clinical efficacy assessed with a subscale of CPRS was significantly (p1 less than or equal to 0.05) better for the imipramine-dixyrazine combination than for the imipramine-diazepam or imipramine-placebo combination. Serum concentration of imipramine was significantly higher (p1 less than or equal to 0.05) in the group treated with dixyrazine than in the other two groups. Further, serum concentration of imipramine in the diazepam group was significantly lower (p1 less than or equal to 0.05) than in the placebo group. At the end of the study, 67% in both the placebo and the diazepam group and 86% in the dixyrazine group were practically symptom-free.     

Neuropharmacological and physiological validation of a computer-controlled two-compartment black and white box for the assessment of anxiety

1. 1. The two-compartment black and white box first described by Crawley and Goodwin (1980) has been used to study anti-anxiety properties of drugs but has not been validated.

2. 2. An automated test system and validation of the protocol for the evaluation of compounds with anxiolytic or anxiogenic potential is described.

3. 3. The box is partitioned into black and white sections with an interconnecting opening and is equipped with micro-switch photoelectric controls (light source and photorecciver) and an interface connected to the menudriven computer during anxiety testing.

4. 4. Plasma corticosterone levels in naive mice maintained on a reversed L:D cycle was significantly reduced following restricted exposure to the brightly lit white section but not in the red-illuminated black section.

5. 5. The optimal structural configuration in different test situations was found to be a square rather than a round box.

6. 6. Under normal conditions, mice spend about 60% of the time in the dark compartment so that the exploratory activities and time spent in the white section are taken as a measure of anxiety.

7. 7. Compounds examined included the reference anxiolytic diazepam, nicotine, naloxone, MDL 72222, ICS 205 930 and buspirone, all of which increased mouse exploratory activities in the white section. PTZ, β-CCP, morphine and amphetamine increased exploration in the black compartment and reduced exploration in the white area.

8. 8. Fluphenazine and imipramine had no specific effects on anxiety responding, although the cataleptogenic effect of fluphenarinc was apparent.

9. 9. Daily repeated testing was possible with a maximum of up to four trials a week using naive animals during the 5-min test session.

10. 10. The results suggest that the rapid and automated test system for the assessment of changes in measures of anxiety is not only valid for large scale evaluation of compounds but could be used to elucidate mechanisms of drug action and the CNS pathways linked with anxiolysis and/or anxiogenesis.

Serotonergic interhemispheric asymmetry: gender difference in the orbital cortex

The asymmetry of tritiated imipramine (IMI) binding sites (which are associated with serotonergic mechanisms) were investigated in the orbital frontal cortex in 6 women and men who died of natural causes, and who did not have a history of mental disorders. There was significant interhemispheric asymmetry in both sexes, higher Bmax on the right side compared with the left. The Bmax values of IMI binding in the right orbital cortex in women were significantly higher than in men. Our preliminary findings--gender difference of serotonergic mechanisms in some area of the human brain--are in accordance with the observed gender differences in a variety of serotonin-regulated behaviors (sexual behavior, aggression and impulse control), and serotonergic mental disorders (eating disorders, suicidal behavior, anxiety disorders and depression).     

Efficacy of venlafaxine treatment in depressed patients with psychomotor retardation or agitation: A metaanalysis

A meta-analysis was performed to assess the effectiveness of the novel antidepressant venlafaxine in depressed patients with psychomotor retardation and/or agitation [respective baseline item score greater than zero on the Hamilton Rating Scale for Depression (HAM-D)]. Data from five comparable placebo-controlled double-blind studies (n = 1122) were analysed; in two of them venlafaxine was also compared with imipramine. Separate analyses were performed on data from psychomotor retarded and agitated patients by using a one-way analysis of covariance (HAM-D total score during therapy, dependent variable; baseline HAM-D total score, covariate; therapy, factor). The overall pool of venlafaxine-treated patients showed a significantly greater decline in total HAM-D score than did the placebo-treated patients. Venlafaxine-treated patients with retardation showed a significantly greater decline in total HAM-D scores than did placebo- and imipramine-treated patients, starting at weeks 3 and 4, respectively. Venlafaxine-treated patients with agitation showed a significantly greater decline in total HAM-D scores than did placebo-and imipramine-treated patients, starting at weeks 2 and 1, respectively. In conclusion, venlafaxine is effective in depressed patients whether or not they have symptoms of psychomotor retardation or agitation.     

Alexithymia as a predictor of treatment response in post-traumatic stress disorder

Fifty-seven veterans with post-traumatic stress disorder (PTSD) completed the Alexithymia Provoked Response Questionnaire (APRQ) upon entering an 8-week randomized trial comparing phenelzine, imipramine, and placebo. Low alexithymia on the APRQ significantly predicted improvement on the avoidance items of the Impact of Events Scale (IES) particularly among patients treated with placebo, but was not associated with changes in the intrusion items of the scale.     

Panic disorder: response to sodium lactate and treatment with antidepressants

Effective drugs for mental disorders have been found by serendipitous findings not supported by knowledge of psychopharmacology. Drug are assigned labels, such as "antidepressant" without knowledge that such a label delimits the utility of such agents. Many double-blind controlled studies have shown that imipramine effectively ameliorates panic attacks and agoraphobia. Epidemiological data show a relationship between Panic Disorder and Depression. Relatives of probands with Major Depression plus an Anxiety Disorder were at greater risk for both Major Depression and for an Anxiety Disorder. Panic Disorder, as a subcategory of Anxiety Disorder was associated with the greatest increased risk. Intravenous sodium lactate reliably produces anxiety attacks clinically indistinguishable from those occurring in Panic Disorder, in subjects with that disorder. Panic Disorder is characterized by response to imipramine, an epidemiological link to Affective Disorder, and is similar to panic induced by infusion of sodium lactate.     

dl-Phenylalanine versus imipramine: A double-blind controlled study

Summary In a double-blind study,dl-phenylalanine (150–200mg/24h) or imipramine (150–200mg/24h) was administered to 40 depressed patients (20 patients in each group) for 30 days.Diagnoses were established according to the International Classification of Diseases (ICD). The AMP system, the Hamilton Depression Scale and the Bf-S self rating questionnaire (von Zerssen et al., 1974) were used to document psychopathological, neurologic, and somatic changes.Twenty-seven patients (14 on imipramine, 13 on phenylalanine) completed the 30-day trial. No statistical difference could be found between these two drug treatment groups (Student'st-test) using the Hamilton Depression Scale and the Bf-S self rating questionnaire. Ratings for anxiety were significantly lower in the imipramine group on days 10 and 20, but not on day 30; in addition, sleep disturbances were more influenced by imipramine on days 1, 5, and 10, but not on days 20 and 30.Separate analysis of psychopathological syndromes as somatic depressive syndrome and retarded depressive syndrome did not show a group difference (0.05 level of significance using a two-way analysis of variance).It is concluded thatdl-phenylalanine might have substantial antidepressant properties. However, certain methodological considerations still warrant a careful interpretation.     

Binding of perazine to α1-acid glycoprotein

Summary The high-affinity binding of perazine to human serum-protein (non-albumin binding) was previously investigated by gel-chromatography. The immunoelectrophoretic identification of the binding agent as ₁-acid glycoprotein is described here. It was demonstrated by equilibrium dialysis that the average free fraction of³H-perazine added to 22 sera from patients before neuroleptic treatment was 3.67±0.42%, and that there was a significant correlation between the ₁-acid glycoprotein content and the free fraction in these serum samples. This result is in accordance with what others have found for impramine. It is suggested that the nature of this binding should be studied in more detail, since specific binding to ₁-acid glycoprotein may be related to the receptor binding of perazine and possibly other drugs.A preliminary summary of the present findings appeared in Naunyn-Schmiedebergs Arch Pharmacol 307 (Suppl) R 70 (1979)     

Chronic administration of imipramine decreases freezing time in rats genetically predisposed to catalepsy

The effects of acute and chronic imipramine treatment on the degree of catalepsy were compared in GC rats genetically predisposed to catalepsy. We recorded the time over which the rats remained in a vertical position they were placed. As differentiated from acute treatment, chronic administration of imipramine dose-dependently decreased the time of freezing in GC rats.Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 138, No. 10, pp. 450–453, October, 2004     

甘草和五味子对大鼠肝微粒体CYP450诱导作用的研究

目的：考察甘草和五味子对大鼠肝微粒体CYP450的诱导作用及其对丙咪嗪体外代谢的影响。方法：大鼠分别给予甘草或五味子的水提物连续3d或6d，然后制备肝微粒体并测定其CYP450的水平；以丙咪嗪为底物，采用体外温孵法，用HPLC测定丙咪嗪及其主要代谢物的量以考察其代谢情况。结果：给予中草药的大鼠肝微粒体CY P450水平均显著增加，其对丙咪嗪的体外代谢速率显著加快。结论：研究显示甘草和五味子对大鼠CYP450有诱导作用，且与剂量或诱导时间有关。