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Dive into the research topics where Harm J. Gijsman is active.

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Featured researches published by Harm J. Gijsman.


Journal of Clinical Psychopharmacology | 1998

Pharmacokinetic and pharmacodynamic profile of oral and intravenous meta-chlorophenylpiperazine in healthy volunteers

Harm J. Gijsman; Joop M. A. van Gerven; Marjo C. Tieleman; Rik C. Schoemaker; M. S. M. Pieters; Michel D. Ferrari; Adam F. Cohen; Godfried M.J. Van Kempen

meta-Chlorophenylpiperazine (mCPP) is a compound that is frequently used in challenge tests of the serotonergic system. Its human pharmacology is largely unexplored. The objective of this study was to investigate the pharmacokinetic and pharmacodynamic profile of mCPP. Eight female and six male healthy volunteers were included in a randomized, double-blind, double-dummy, three-way crossover design of single-dose intravenous (0.1 mg/kg), oral (0.5 mg/kg), and placebo treatment, with 24-hour follow-up. mCPP showed a large variability in clearance (11-92 mL/hr) and bioavailability (14-108%). Two female subjects dropped out because of headache and dysphoria. During the 27 occasions in which mCPP was administered, autonomic physical symptoms were observed in 23 subjects and disturbances of mood in 6 subjects. Oral and intravenous mCPP caused sudden increases in cortisol levels, prolactin levels, and total scores of the Body Sensation Questionnaire. Administration of mCPP also led to concentration-dependent increases of saccadic peak velocity and adaptive tracking performance and to a decrease of electroencephalographic occipital theta activity. No clinically relevant effects on electrocardiogram, temperature, and blood pressure were found. In conclusion, it is doubtful whether mCPP is a useful compound for challenge tests in view of the large pharmacokinetic variability after intravenous and oral administration. The effects of mCPP are consistent with disinhibition of the central nervous system.


Journal of Clinical Psychopharmacology | 2002

Placebo-controlled comparison of three dose-regimens of 5-hydroxytryptophan challenge test in healthy volunteers

Harm J. Gijsman; Joop M. A. van Gerven; Marieke L. de Kam; Rik C. Schoemaker; M. S. M. Pieters; Margo Weemaes; Roel de Rijk; Jeroen van der Post; Adam F. Cohen

Single-dose administration of 5-hydroxytryptophan (5-HTP) is regularly used as a challenge test of the serotonergic system. The use of 5-HTP has been limited by an apparent small window between the occurrence of neuroendocrine endpoints and the occurrence of side effects. Therefore, many dosing strategies have been tried with and without concurrent administration of carbidopa, a peripheral inhibitor of the decarboxylation from 5-HTP to serotonin. The aim of the current study was to assess the relation between pharmacokinetics and pharmacodynamics of 5-HTP. Twelve healthy male volunteers were included in a placebo-controlled, randomized, four-way crossover, double-blind, single-dose investigation of oral 5-HTP with or without coadministration of carbidopa. The four dose regimens were placebo, 5-HTP 100 mg, 5-HTP 200 mg, and 5-HTP 100 mg with coadministration of carbidopa 100 mg and 50 mg at 3 hours before and 3 hours after the administration of 5-HTP, respectively. The last regimen resulted in a doubling of the elimination half-life, an apparent clearance at least 14 times smaller, and a 15.4 times greater area under the curve compared with 5-HTP 100 mg without carbidopa. Furthermore, it was the only regimen to induce a significant change in cortisol and prolactin. It did not induce any change in subjective psychologic symptoms or cardiovascular parameters, but it was the only regimen to induce some nausea in three participants. The authors conclude that this regimen of 5-HTP 100 mg plus carbidopa is a relatively simple, effective, and tolerable challenge of the presynaptic serotonergic system. Further increase of the dose of 5-HTP might improve the size of the effect on endpoints as long as the tolerability remains good.


Journal of Psychopharmacology | 2008

Pharmacology of rising oral doses of 5-hydroxytryptophan with carbidopa

Ljca Smarius; G. Jacobs; Dhm Hoeberechts-Lefrandt; Ml de Kam; J. P. Van Der Post; R.H. de Rijk; J. van Pelt; Rik C. Schoemaker; Frans G. Zitman; Jma van Gerven; Harm J. Gijsman

5-hydroxytryptophan (5-HTP) is a direct 5-hydroxytryptamine (5-HT) precursor used to assess central serotonergic function. Its use has been limited by a narrow window between neuroendocrine changes and side effects, and variable kinetics related to inconsistent administration modes. By combining 5-HTP with carbidopa (CBD), increased bioavailability for brain penetration and decreased peripheral side effects would be expected, due to reduced peripheral decarboxylation of 5-HTP to 5-HT. A doubleblind, placebo-controlled, single rising dose, four-way crossover trial with placebo randomisation was performed in 15 healthy male volunteers to investigate the neuroendocrine dose–response relationship at various 5-HTP levels; the tolerability and subjective effects of oral 5-HTP at 100, 200 and 300mg combined with CBD and the pharmacokinetic properties of the 5-HTP/CBD-challenge. Dose-dependent increases in average cortisol concentrations were observed. Mean response (area-under-the-curve) over the first 4 hours (SD): 172.0 nmol/L (22.3) for placebo, 258.3nmol/L (72.6) for 100mg, 328.47nmol/L (84.6) for 200mg and 387.3nmol/L (82.4) for 300mg 5-HTP. Similar dose-dependent increases for prolactin were seen while adreno-corticotrophic hormone response was more variable. 5-HTP kinetics were adequately described using a one-compartment model with first-order absorption and a lag time (mean oral clearance 28 L/h interindividual coefficient of variation 31%). Nausea and vomiting occurred dose-dependently as most frequent side effects, resulting in dose-related dropout of 6.6% at 100mg and 45.5% at 300mg 5-HTP. Orally administered 5-HTP combined with CBD is an effective serotonergic challenge test, exhibiting dose-related plasma concentrations and neuroendocrine responsiveness. Frequent occurrence of nausea and vomiting limits the applicability of this challenge at 5-HTP doses above 100mg


Human Psychopharmacology-clinical and Experimental | 2000

Estimation of plasma serotonin using isopycnic centrifugation.

Harm J. Gijsman; Robbert-Jan Verkes; Jolanda C. M. Schouten-Verhagen; Rik C. Schoemaker; Joop M. A. van Gerven; Roel de Rijk; Godfried M.J. Van Kempen

The valid measurement of the concentration of serotonin (5‐HT) in blood plasma is important when using the platelet as a model for the serotonergic neuron. The assay is hampered by the release of 5‐HT by (residual) platelets during the preparation for assay. We developed an isopycnic method that separates cells gently and completely from plasma by centrifuging a diluted Percoll density‐gradient to which whole blood was added. In this study this method was compared with the usual differential centrifugation method. The isopycnic method on average resulted in nine times lower levels of plasma 5‐HT. This difference was linearly related to the number of residual platelets in plasma after differential centrifuging. The proportion of intra‐individual variation decreased three‐fold. Therefore, the use of a Percoll density‐gradient may lead to a more precise and more accurate estimate of the level of plasma 5‐HT. Copyright


American Journal of Psychiatry | 2004

Antidepressants for bipolar depression: A systematic review of randomized, controlled trials

Harm J. Gijsman; John Geddes; Jennifer M Rendell; Willem A. Nolen; Guy M. Goodwin


Psychopharmacology | 2001

Cognitive performance and serotonergic function in users of ecstasy.

R.J. Verkes; Harm J. Gijsman; M. S. M. Pieters; Rik C. Schoemaker; Saco de Visser; Monique Kuijpers; Ed J. M. Pennings; Dick de Bruin; Govert Van de Wijngaart; Joop M. A. van Gerven; Adam F. Cohen


British Journal of Psychiatry | 2003

Effects of a branched-chain amino acid drink in mania

Antonina Scarnà; Harm J. Gijsman; S.F.B. McTavish; Catherine J. Harmer; P J Cowen; Guy M. Goodwin


Psychopharmacology | 2002

A dose-finding study on the effects of branch chain amino acids on surrogate markers of brain dopamine function.

Harm J. Gijsman; Antonina Scarnà; Catherine J. Harmer; Sarah F. B. McTavish; John Odontiadis; P J Cowen; Guy M. Goodwin


Cochrane Database of Systematic Reviews | 2003

Olanzapine alone or in combination for acute mania

Jennifer M Rendell; Harm J. Gijsman; Paul K Keck; Guy M. Goodwin; John Geddes


Cochrane Database of Systematic Reviews | 2006

Risperidone alone or in combination for acute mania.

Jennifer M Rendell; Harm J. Gijsman; M S Bauer; G M Goodwin; Gr Geddes

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Willem A. Nolen

University Medical Center Groningen

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