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Biomedical subjects

G Bertschy

Publications and source records attributed to G Bertschy.

At least 37 records · Page 2Linked to original sources
PubMed1998

A double-blind double-dummy study of citalopram comparing infusion versus oral administration.

BACKGROUND: This study compares antidepressant efficacy and tolerability of citalopram given either orally or as a slow drop infusion. METHODS: Citalopram (40 mg/day) was administered double-blindly as tablets or slow-drop infusion during the first 10 days and then open, orally, up to treatment Day 42. RESULTS: In 60 moderately to severely depressed patients, the Hamilton depression total score (17-items) at baseline was 23.9 and 23.6 in the active infusion (n = 30) and active tablet (n = 30) group, respectively. These scores dropped in both groups to 15.6 and 16.9 on Day 10, and to 10.3 and 10.2 on Day 42. Response rates (delta Hamilton > or = 50%) amounted to 33.3% and 17.9% on Day 10, and 66.2% and 63.3% on Day 42, without a relevant group difference in citalopram plasma concentration. CONCLUSION: Slow-drop infusion with citalopram shows a similar risk/benefit relationship to oral citalopram. The design of this study allowed us to evaluate pharmacological but not psychological factors which may contribute to response to slow-drop infusion.

Administration, Oral↗
PubMed1997

Antidepressant treatment before hospitalization for major depression: often prescribed, often undertitrated.

Fifty-three patients hospitalised for major depression were given a semi-structured interview to collect data allowing to consider the question of treatment in the period preceding hospitalisation. Twenty-one patients were discarded because they did not consult any physician (n = 5) or because they did it too late ( n = 11) or for they reached the threshold of major depression too late to allow sufficient time for efficacy of the treatment (n = 5). There remained a subsample of 20 potentially treatable patients. The majority of them refused their treatment (17%), were given no antidepressant treatment (14%) or at an insufficient dose (41%). If they received a sufficient dose, it was too lately (3%) or it was a maintenance therapy, which had not been modified in spite of a recurrence (14%), and finally only 10% of the potentially treatable patients could be considered as adequately treated, from a psychopharmacological point of view.

Adult↗
PubMed1997

The association carbamazepine-mianserin in opiate withdrawal: a double blind pilot study versus clonidine.

Our clinic has fortuitously developed the therapeutic use of the association of mianserin (maximum daily dose 90 mg) and carbamazepine (maximum daily dose 400 mg) in opiate withdrawal management. If animal studies have suggested efficacy of mianserin in such indication, no human studies have been performed. To test the efficacy of such an association, a comparison was made to clonidine (maximum daily dose 0.600 mg) in a one week treatment period according to a double blind pilot study design. Thirty-two patients were included (16 in each treatment group). The two treatments did not differ in the intensity of the withdrawal, according to the rate of retention in treatment and symptoms, and the psychic distress which were auto-evaluated every other day with the Opiate Withdrawal Questionnaire and several Visual Analog Scales (VAS). The clonidine group, however, scored significantly higher (P < 0.05) on the VAS rating of the global feeling of satisfaction on the last day. The patients in the mianserin group fortuitously had a moderately lower number of daily heroin intakes but there was no significant correlation between this variable and the global OWQ scores on Days 1, 3, 5 and 7. Given the size of the groups, we cannot conclude that the association carbamazepine-mianserin is as effective as clonidine, but a real effectiveness is probable. A study versus placebo would be necessary to draw more definitive conclusions.

Adult↗
PubMed1997

Fluvoxamine and fluoxetine do not interact in the same way with the metabolism of the enantiomers of methadone.

Six and seven addicts treated with racemic methadone (MTD) were comedicated with fluvoxamine (FLV) and fluoxetine (FLX), respectively. The plasma concentrations of both (R)- (the active enantiomer) and (S)-MTD were increased by FLV, whereas only (R)-MTD concentrations were increased by the addition of FLX. This suggests that cytochrome P450IID6 (CYP2D6), an enzyme that is strongly inhibited by FLX, preferentially metabolizes (R)-MTD, whereas CYP1A2, which is strongly inhibited by FLV, metabolizes both enantiomers. The choice of a selective serotonin reuptake inhibitor in depressive addicted patients treated with MTD and the possible use of FLX or FLV to potentiate the effects of MTD in some cases of therapeutic failure are discussed.

Fluoxetine↗
PubMed1997

Long-term treatment of depression: is there a use for depot antidepressants?

Depot neuroleptics have been widely introduced for long-term treatment of schizophrenia. The question of whether depot antidepressants should be developed for the treatment of chronic depression and for the prophylaxis of recurrent depression is addressed. This approach seems to be indicated in patients showing poor compliance to oral antidepressive medication and in patients suffering from secondary depression and who are already receiving depot antipsychotics, but it is also indicated in subgroups of patients who, for social, cultural or personality reasons, have problems with regard to a regular and long-term intake of oral medication. Before the development of depot antidepressants is initiated, the ethical issues relating to this form of medication should be discussed. Technically, the preparation of depot forms may represent a serious challenge. Depot antipsychotics are all esters of hydroxylated neuroleptics and long-chain fatty acids. Potential candidates for antidepressants are venlafaxine, flesinoxan and E-10-OH-nortriptyline. The possibility of developing forms for transdermal application is also discussed. In conclusion, clinical considerations support the idea of the usefulness of a depot preparation for antidepressants but ethical and technical aspects should not be neglected.

Administration, Cutaneous↗
PubMed1996

Non-response to citalopram in depressive patients: pharmacokinetic and clinical consequences of a fluvoxamine augmentation.

The effect of comedication with fluvoxamine on the plasma concentrations of the enantiomers of citalopram and its metabolites in dextromethorphan/mephenytoin phenotyped patients pretreated with citalopram (CIT) was studied: seven female patients (45.1 +/- 13.9 years) suffering from a major depressive episode [ICD-10: F32.2 (n = 3 patients), F33.2 (n = 2), F32.10 (n = 1) or F32.11 (n = 1)], who were non-responders to a 3-week treatment with 40 mg/day CIT (From day-21 to day 0) (day 0: MADRS score > or = 12), were co-medicated for another 3 weeks with fluvoxamine (50 mg/day from day 1-7, 100 mg/day from day 14-21). All patients were extensive metabolizers of mephenytoin (CYP2C19) and dextromethorphan (CYP2D6), except one patient, who had a genetic deficiency of CYP2D6. There was a significant increase of the plasma concentrations of S- and R-citalopram from day 0 (27 +/- 14 micrograms/l and 55 +/- 23 micrograms/l, respectively) to day 21 (83 +/- 38 micrograms/l and 98 +/- 44 micrograms/l, respectively), after addition of fluvoxamine (P < 0.02, for each comparison), and the mean ratio S/R-citalopram increased from 0.48 to 0.84. S-Citalopram inhibits more potently 5-HT uptake than R-citalopram: therefore, fluvoxamine increases the pharmacologically more active S-citalopram with some stereoselectivity. According to a previous in vitro study, this pharmacokinetic interaction occurs on the level of CYP2C19, but also of CYP2D6 and CYP3A4 which, in contrast to CYP1A2, contribute to the N-demethylation of citalopram and which are stereoselectively inhibited by fluvoxamine. All but one patient showed clinical improvement by a decrease of the MADRS score by at least 50% and a final score < or = 13 (mean +/- SD: day 0:30.6 +/- 9.2; day 21:11.0 +/- 6.5). Some patients showed minor symptoms, such as nausea and tremor, but the combined treatment was generally well tolerated.

Adult↗
PubMed1996

Risperidone and reversible neutropenia: a negative rechallenge.

After 6 weeks of a risperidone rechallenge therapy (2-4 mg/day), no hematological abnormalities were observed in a 26-year-old schizophrenic woman. Two years previously after 9 days of risperidone therapy (2-6 mg/day), the same patient had developed a reversible neutropenia during a cold.

Adult↗
PubMed1996

Fluoxetine addition to methadone in addicts: pharmacokinetic aspects.

We report nine cases where fluoxetine (FX) (20 mg/day) was added to maintenance treatment with methadone (MTD) (dose range: 30-100 mg) in addicts with affective disorders. MTD plasma levels were measured before and after treatment with FX under steady-state conditions. Among the nine patients, two also received fluvoxamine (FLVX) at different times. Although it is possible that in some patients a moderate FX-MTD interaction occurs, resulting in increased plasma levels of MTD, this interaction is certainly less marked than that between FLVX and MTD and unlikely to have clinical consequences.

Adult↗
PubMed1995

Methadone maintenance treatment: an update.

Available data (this review includes old major articles and recent articles) show that, although results are heterogeneous, methadone maintenance treatments (MMTs) have a real efficiency not only to reduce illicit opiate abuse (50-80% of patients under MMT did not use heroin in the preceding month) but also to reduce criminality, HIV risks and mortality, and to improve social rehabilitation, without inducing other alternative substance abuse. A minority of patients (perhaps 5-20%) stay on MMT on a very long-term basis (more than 10 years). Efficiency of MMTs are rather poorly related to patients' variables, with the exception of a moderately deleterious effect of a low age at onset of opiate dependence, a precocious or high involvement in criminality and an abuse of non-opiate drugs. On the other hand, variables related to treatment play a more important role in explaining heterogeneity of results. Optimal daily dose, high quality of medical and psycho-social services, clear orientation towards social rehabilitation and treatment retention (to allow a sufficient duration of treatment) and slow detoxification regimen of well-stabilized patients are all factors contributing to better results.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Fluvoxamine and fluoxetine: interaction studies with amitriptyline, clomipramine and neuroleptics in phenotyped patients.

The in vivo pharmacokinetic interaction between two selective serotonin reuptake inhibitors (SSRI) (fluvoxamine, fluoxetine) and tricyclic antidepressants (TCAs) (amitriptyline, clomipramine) or neuroleptics (haloperidol, cyamemazine, levomepromazine, propericiazine) was assessed in 29 in-patients. They were phenotyped twice with dextromethorphan and mephenytoin: first in steady state conditions while under treatment with TCAs or neuroleptics; and also 10 days after an associated treatment with fluvoxamine (150 mg day(-1)) or fluoxetine (20 mg day(-1)). A clear and statistically significant increase in the mean urinary metabolic ratio (MR) of dextromethorphan/dextrorphan and in the mean mephenytoin S/R ratio (S/R) was seen with the fluvoxamine and fluoxetine treatment. The mean MR increased from 0.13 to 0.27 (P<0.01) with fluoxetine and from 0.34 to 0.84 with fluvoxamine (P<0.05). The (dextromethorphan) 'extensive metabolizer' phenotype switched to the 'poor metabolizer' phenotype in six patients by the 10-day fluoxetine treatment, and in two patients by the fluvoxamine treatment. The mean S/R increased from 0.24 to 0.34 (P<0.05) with fluoxetine, and from 0.33 to 0.58 (P<0.002) with fluvoxamine. These results are in agreement with the observed modification of TCA plasma levels after the SSRI association. During fluvoxamine treatment, amitriptyline and clomipramine plasma levels (P<0.06 both) tendentially increased, and those of demethylclomiprarnine decreased (P<0.06). Fluoxetine addition lead to a significant increase (P<0.02) of the desmethylclomipramine plasma levels. Fluvoxamine induced a moderate augmentation of the plasma levels of haloperidol and its reduced metabolite and no change in the plasma levels of cyamemazine and levomepromazine. But patients treated with neuroleptics are to few to draw any firm conclusion. This study suggests, that fluoxetine and fluvoxamine differ in their interaction with the metabolism of some other basic psychotropic drugs, by a mechanism which implies CYP2D6 and CYPmeph and possibly other isoformes of cytochrome P-450. Moreover, the interactions produced varied with the TCA prescribed.

Adult↗
PubMed1994

[Sensitization and training of physicians in the field of drug addiction: the example of a program in Vaud].

In the canton of Vaud general practitioners and internists from the private sector play a great role in the care for addict patients. Their interventions may also contribute to a decrease of risk factors as they work with families, children and adolescents. To help them to do better and in order to have more collaborators in this field, the University Department of Adult Psychiatry of Lausanne and the Department of Public Health of Vaud have developed a two-year program: the Program of Prevention and Physicians Postgraduate Training in the field of Addiction. The paper presents the different ways of interventions being selected, the first result concerning the program's activities, including a few remarks, and the role of the general practitioner.

Education, Medical, Continuing↗
PubMed1994

Probable metabolic interaction between methadone and fluvoxamine in addict patients.

We report five cases where fluvoxamine (FLVX) was added to maintenance treatment with methadone (MTD) in addict patients with affective disorders. In view of the implication of FLVX in several metabolic drug interactions, MTD plasma levels were measured before and after treatment with FLVX. A slight increase (approximately 20% of the MTD plasma level/dose ratio) occurred in two cases. In the remaining three patients, the interaction was more pronounced (40-100% increase of the MTD plasma level/dose ratio), with clinical manifestations of opiate withdrawal after stopping FLVX therapy in one case. Caution is needed when starting or stopping treatment with FLVX in patients receiving maintenance treatment with methadone.

Adult↗
PubMed1993

Minor and clinically non-significant interaction between toloxatone and amitriptyline.

The possibility of a pharmacokinetic interaction between amitriptyline and toloxatone (a new MAOI-A) has been studied in 17 depressed in-patients. Amitriptyline and its demethylated and hydroxylated metabolites in blood and urine were measured at steady state after the administration of amitriptyline with and without toloxatone in steady state. The metabolic status of patients was determined using the dextromethorphan phenotyping test. There was only a minor pharmacokinetic interaction between amitriptyline (AMT) and toloxatone, with a small increase in the AMT/NT (nortriptyline) plasma ratio: 0.68 before and 0.78 after toloxatone. The urinary excretion and plasma levels of AMT and its metabolites were not affected by the co-therapy. Three of the patients were poor metabolisers, but this did not predict the magnitude of the drug interaction. The interaction does not justify plasma level monitoring of amitriptyline as the change in pharmacokinetics was so small.

Adult↗