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Reactivity of serotonin in whole blood: relationship with drug response in obsessive-compulsive disorder
Psychiatry of Northern Dalecarlia, Mora Hospital, Mora, Sweden; Karolinska Institutet, Division of Psychiatry, Danderyd Hospital, Danderyd, Sweden.ORCID iD: 0000-0001-6726-7787
Department of Neuroscience, Division of Psychiatry, Uppsala University, Uppsala, Sweden.ORCID iD: 0000-0002-3587-6075
Department of Clinical Pharmacology, Lund University, Lund, Sweden.
Department of Clinical Pharmacology, Lund University, Lund Sweden; Department of Neuroscience and Locomotion, Division of Psychiatry, Linköping University Hospital, Linköping, Sweden.
2001 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 49, no 4, 360-368 p.Article in journal (Refereed) Published
Abstract [en]

Background: Obsessive-compulsive disorder responds almost only to potent serotonin reuptake inhibitors. Previous studies have suggested a relation between serotonergic function and clinical outcome in serotonin reuptake inhibitor treatment of obsessive-compulsive disorder.

Methods: In a randomized, double-blind trial, comparing clomipramine, paroxetine, and a placebo in obsessive-compulsive disorder, serotonin levels in whole blood (WB-5-HT) were measured at baseline, after 1 week, and after 4 weeks of treatment and related to clinical outcome in 36 patients.

Results: In patients treated with serotonin reuptake inhibitors there was a pronounced decrease of WB-5-HT, variable after 1 week and uniformly maximal after 4 weeks. The decrease of WB-5-HT after 1 week of serotonin reuptake inhibitor treatment correlated negatively with clinical outcome after 12 weeks (r = -.61, p =.0006); hence, patients with slower WB-5-HT reactivity eventually responded better to treatment. Baseline WB-5-HT, but not WB-5-HT reactivity, was related to season. Depression, autistic traits, and previous serotonin reuptake inhibitor treatment predicted nonresponse.

Conclusions: A fast decrease of WB-5-HT was associated with poor clinical outcome. This may be related to faster serotonin efflux from platelets, which has previously been linked to autism. Further studies are necessary to identify the underlying mechanism and discern whether serotonin reuptake inhibitor-induced WB-5-HT decrease is clinically useful.

Place, publisher, year, edition, pages
New York, USA: Elsevier, 2001. Vol. 49, no 4, 360-368 p.
Keyword [en]
Obsessive-compulsive disorder, serotonin, kinetics, serotonin reuptake inhibitors, autism, prediction of response, randomized controlled trial
National Category
Medical and Health Sciences Psychiatry Neurology
Identifiers
URN: urn:nbn:se:oru:diva-50184DOI: 10.1016/S0006-3223(00)00956-2ISI: 000167183100007PubMedID: 11239907Scopus ID: 2-s2.0-0035865647OAI: oai:DiVA.org:oru-50184DiVA: diva2:925968
Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2016-09-02Bibliographically approved
In thesis
1. Obsessive-compulsive disorder, serotonin and oxytocin: treatment response and side effects
Open this publication in new window or tab >>Obsessive-compulsive disorder, serotonin and oxytocin: treatment response and side effects
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Obsessive-compulsive disorder (OCD), with a prevalence of 1-2 %, frequently leads a chronic course. Persons with OCD are often reluctant to seek help and, if they do, their OCD is often missed. This is unfortunate, since active treatment may substantially improve social function and quality of life. Serotonin reuptake inhibitors (SRIs) have welldocumented efficacy in OCD, but delayed response may be problematic. Methods to predict response have been lacking. Because SRIs are effective, pathophysiological research on OCD has focussed on serotonin. However, no clear aberrations of serotonin have been found, thus other mechanisms ought to be involved.

Our aims were to facilitate clinical detection and assessment of OCD, to search for biochemical correlates of response and side-effects in SRI treatment of OCD and to identify any possible involvement of oxytocin in the pathophysiology of OCD.

In study I, we tested in 402 psychiatric out-patients the psychometric properties of a concise rating scale, “Brief Obsessive Compulsive Scale” (BOCS). BOCS was shown to be easy to use and have excellent discriminant validity in relation to other common psychiatric diagnoses.

Studies II-V were based on 36 OCD patients from a randomised controlled trial of paroxetine, clomipramine or placebo. In study II, contrary to expectation, we found that the change (decrease) of serotonin in whole blood was most pronounced in non-responders to SRI. This is likely to reflect inflammatory influence on platelet turnover rather than serotonergic processes within the central nervous system.

In studies IV-V, we found relations between changes of oxytocin in plasma and the anti-obsessive response, and between oxytocin and the SRI related delay of orgasm, respectively. In both cases, the relation to central oxytocinergic mechanisms is unclear. In males, delayed orgasm predicted anti-obsessive response.

Place, publisher, year, edition, pages
Örebro: Örebro university, 2016. 133 p.
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 148
Keyword
Adverse effects, Obsessive-compulsive disorder, Orgasm, Oxytocin, Randomised controlled trial, Rating scale, Response prediction, Serotonin, Serotonin uptake inhibitors, Sexual function
National Category
Psychiatry Family Medicine
Research subject
Psychiatry
Identifiers
urn:nbn:se:oru:diva-51438 (URN)978-91-7529-153-6 (ISBN)
Public defence
2016-09-26, Campus USÖ, hörsal C3, Södra Grev Rosengatan, Örebro, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2016-07-25 Created: 2016-07-25 Last updated: 2016-09-05Bibliographically approved

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