http://repub.eur.nl/res/aut/13917/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/29495/ 2008-12-01T00:00:00Z http://repub.eur.nl/res/pub/15997/ 2008-04-01T00:00:00Z The purpose of the present study is to compare the efficacy of imipramine in the treatment of psychotic versus nonpsychotic depression. Previous studies report varying results of monotherapy with antidepressants in psychotic depression. Because psychotic depression is seriously underinvestigated, performing a post hoc analysis of randomized clinical trials consisting of both psychotic and nonpsychotic depressed patients may contribute to the discussion on the optimal treatment of depressed patients with mood-congruent psychotic features. A total of 112 patients diagnosed with major depression (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) (40 with psychotic depression and 82 without psychotic features) received treatment with imipramine for 6 weeks after a washout period of 7 days. Imipramine doses were adjusted to attain a predefined fixed plasma level. Treatment response was assessed with the Hamilton Rating Scale for Depression (HAM-D). A logistic regression analysis showed a significantly larger reduction in HAM-D score in the sample with psychotic features compared with the nonpsychotic sample (regression coefficient, -3.47; SE, 1.7; P = 0.04). According to the primary outcome criterion, that is, the change in HAM-D score, imipramine was significantly more effective in the sample with psychotic depression compared with the nonpsychotic depressed patients. The contradiction between our results and those of several previous studies may be due to the fixed plasma level dosing of imipramine refraining from concurrent psychotropic medication or limiting our patient sample to patients with mood-congruent psychotic features http://repub.eur.nl/res/pub/35940/ 2007-06-30T00:00:00Z The efficacy of the addition of lithium to an established course of antidepressant treatment can be explained by a synergistic effect of the two drugs on central 5-HT neurotransmission. In the present study we investigated the effect of lithium addition on the 5-HT concentration in plasma and platelets and the concentration of 5-HIAA. Thirty-nine depressed inpatients who fulfilled the DSM-IV criteria for major depressive disorder and who did not respond to monotherapy with either imipramine or fluvoxamine participated in this study. Concentration of 5-HT in both plasma and platelets did not change significantly during lithium addition. The 5-HT ratio (plasma concentration/platelet concentration) shows a small non-significant increase after 3 weeks lithium addition. The mean concentration of 5-HIAA shows a significant increase during lithium addition; with no difference between the imipramine and the fluvoxamine sample. The increments in 5-HIAA concentration during lithium addition are indicative of an increased 5-HT turnover. http://repub.eur.nl/res/pub/10786/ 2007-04-01T00:00:00Z http://repub.eur.nl/res/pub/35958/ 2007-04-01T00:00:00Z http://repub.eur.nl/res/pub/13537/ 2004-11-01T00:00:00Z OBJECTIVE: This study was designed to compare the efficacy of two two-phase pharmacological treatment strategies for inpatients with DSM-IV major depressive disorder. METHOD: During phase I, patients participated in a double-blind study of the effects of imipramine versus fluvoxamine, with final evaluation of response 4 weeks after patients attained the target plasma level. In phase II, for patients without treatment response or with partial response in phase I, lithium was added to imipramine or fluvoxamine. Final evaluation of response was made 3 weeks after the patients attained the target plasma level of lithium (0.6-1.0 mmol/liter). RESULTS: One hundred thirty-eight patients were enrolled in the study. At the end of phase I, remission, defined as a final Hamilton Depression Rating Scale score < or =7, was achieved by 16 (23%) of 70 imipramine-treated patients and 10 (15%) of 68 fluvoxamine-treated patients. At the end of phase II, 41 (59%) of 70 imipramine-treated patients versus 27 (40%) of 68 fluvoxamine-treated patients qualified for remission, a significant difference in favor of the imipramine strategy. Only a small minority of both groups received concomitant medication. In both phase I and phase II, the discontinuation rate was low (5% and 10%, respectively). CONCLUSIONS: Imipramine with subsequent lithium addition is superior to a similar strategy with fluvoxamine for treatment of severely depressed inpatients. Both strategies were well tolerated. http://repub.eur.nl/res/pub/26122/ 1977-06-10T00:00:00Z The pleasant effects of opium were already known 6000 years ago and opium has been used for medical purposes for at least 3500 years. Opium, and its r.1ain constituent morphine, evoke a feeling of well-being and always relieve pain of any origin, in other words, a perfect analgesic and euphoric drug. However, there are unpleasant repercussions. Thus, the pleasant effects are followed by a period of dysphoria. With the first, moderate dose of opiate this rebound is not important. But euphoric and analgesic effects disappear with repeated administration unless the dose is steadily increased. When the opiate is withcirawn after repeated administration of high doses, the dysphoric rebound wi 11 gain dangerous proportions and this is one of the reasons for continued (addicted) use of the opiate. Thus, the perfect analgesic and euphoric drug produces a perfect dependence. One of the most important stimuli to the promotion of research into the mechanism of action of opiates is the desire to control opiate-dependence. Such control would help two groups of users: those who need a strong analgesic would not necessarily become dependent and those who become dependent would not necessarily always need opiates. The acute effects of morphine are highly interrelated phenomena such as analgesia and euphoria, while dependence is ascribed to an adaptation of the cells of the body. In order to relate or dissociate these effects of opiates it is necessary to analyse the eel lular and molecular events related to the acute effects of the opiate. If these cellular and molecular events are the same as those underlying opiate-dependence, it will not be possible to dissociate the analgesic and euphoric effects of opiates from their ability to produce dependence. However, if it appears that differences do exist between the mechanism of these two opiateinduced phenomena then control of opiate-dependence may be possible. In the experiments described here, the effects of acute morphine administration on dopaminergic neurons in the rat were investigated. Dopamine is an important neurotransmitter in 1 imbic and extrapyramidal brain areas and plays an important role in the integration of emotional responses. Furthermore, the analgesic and rewarding (euphoric?) properties of morphine have been related inter alea to interactions with dopaminergic systems. An attempt has been made to analyse molecular mechanisms involved in the action of morphine on dopaminergic neurons in different brain areas and to analyse the relation of both these actions and behavioural responses to acute morphine administration.