First Experiences in Combination Therapy Using Olanzapine with SSRIs (Citalopram, Paroxetine) in Delusional Depression

König, Frank; Hippel, Cathrin; T, Petersdorff; Neuhöffer-Weiss, M.; Wolfersdorf, Manfred; Kaschka, Wolfgang P.

doi:10.1159/000054886

Cited by 21 publications

(6 citation statements)

References 19 publications

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“…It is commonplace to co-administer antipsychotics and antidepressants, and generally, no clinical problems have been associated with simultaneous administration of P-gp substrates. For example, combination of the P-gp substrates olanzapine and citalopram has not resulted in problems (König et al, 2001). On the other hand, Pgp substrates/inhibitors binding at sites different from those occupied by CsA and NT, might exert a larger effect on P-gp transport of Risp.…”

Section: Discussionmentioning

confidence: 99%

P-glycoprotein interaction with risperidone and 9-OH-risperidone studiedin vitro, in knock-out mice and in drug-drug interaction experiments

Ejsing¹,

Pedersen²,

Línnet

2005

Hum. Psychopharmacol. Clin. Exp.

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The drug transporter P-glycoprotein (P-gp) influences drug distribution across the blood-brain barrier (BBB) by actively extruding drugs into the neural capillaries. Several psychotropic drugs, including nortriptyline (NT) and risperidone (Risp), are substrates of P-gp. Here we compared the in vitro P-gp interactions of Risp and its major metabolite, 9-OH-Risperidone (OH-Risp), with their distribution over the BBB in P-gp knock-out mice and in rats where P-gp was inhibited. K(m) and V(max) were determined by an in vitro ATPase assay, and V(max)/K(m) ratios of 2.7 and 0.5 were recorded for Risp and OH-Risp, respectively, suggesting that Risp is a better substrate for P-gp than OH-Risp. In Mdr1a (-/-) knock-out mice, the brain-serum ratios of both Risp and OH-Risp were more than ten times those of control mice (14 and 11, respectively). When P-gp was inhibited with cyclosporine A (CsA) in Wistar rats, the effect was an order of magnitude less than that observed for the knock-out mice experiments (1-1.5 times the controls), and co-administration of NT had no effect. In conclusion, both Risp and OH-Risp interact with P-gp in vitro, and P-gp has a profound effect on Risp and OH-Risp distribution over the BBB, as is evident from the knock-out mice experiments. Drug-drug interaction effects in relation to P-gp, however, appear to be more limited.

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Section: Discussionmentioning

confidence: 99%

P-glycoprotein interaction with risperidone and 9-OH-risperidone studiedin vitro, in knock-out mice and in drug-drug interaction experiments

Ejsing¹,

Pedersen²,

Línnet

2005

Hum. Psychopharmacol. Clin. Exp.

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“…The disorders with the higher number of papers were obsessive compulsive disorder (17 papers) [10,19,23,27,31,32,40,41,50,54,56,60,62,72,75,85,105], depression (16 papers) [34,43,47,48,61,68,70,77,84,91,94,97-99,103,107], pervasive developmental disorder (15 papers) [14-18,22,28,30,38,39,42,49,52,63,66] and Tourette's syndrome (10 papers) [12,13,25,55,64,71,73,92,102,108]. …”

Section: Resultsmentioning

confidence: 99%

Off-label indications for atypical antipsychotics: A systematic review

Fountoulakis

Nimatoudis

Iacovides

et al. 2004

Ann Gen Hosp Psychiatry

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“…In schizophrenia patients, double blind olanzapine (but not haloperidol) was superior to placebo in attenuating comorbid anxiety and depression (5). Also, in psychotic depression studies, open adjunctive olanzapine yielded substantial improvement in 18 of 26 (69%) (21) and 10 of 15 (67%) patients (22). The latter response rate was superior to four of 15 (27%) seen with other antipsychotics.…”

Section: Discussionmentioning

confidence: 96%

Olanzapine in diverse syndromal and subsyndromal exacerbations of bipolar disorders

et al. 2002

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First Experiences in Combination Therapy Using Olanzapine with SSRIs (Citalopram, Paroxetine) in Delusional Depression

Cited by 21 publications

References 19 publications

P-glycoprotein interaction with risperidone and 9-OH-risperidone studiedin vitro, in knock-out mice and in drug-drug interaction experiments

P-glycoprotein interaction with risperidone and 9-OH-risperidone studiedin vitro, in knock-out mice and in drug-drug interaction experiments

Off-label indications for atypical antipsychotics: A systematic review

Olanzapine in diverse syndromal and subsyndromal exacerbations of bipolar disorders

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