Long-term sertraline treatment and peripheral biochemical markers in female depressed patients Nela Pivac a , Dorotea Mu ¨ck-S ˇ eler a, * , Marina S ˇ agud b , Miro Jakovljevic ´ b , Maja Mustapic ´ a , Alma Mihaljevic ´-Peles ˇ b a Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, Rud c er Bos ˇkovic ´ Institute, P.O. Box 180, HR-10002 Zagreb, Croatia b University Psychiatric Clinic, Clinical Hospital Centre Zagreb, Zagreb, Croatia Accepted 22 April 2003 Abstract Serotonergic system is implicated in the pathogenesis of depression. Peripheral biochemical markers, platelet serotonin (5-HT) and platelet monoamine oxidase (MAO) activity were determined spectrofluorimetrically at baseline and after 4 and 24 weeks of sertraline (a selective serotonin reuptake inhibitor (SSRI)) treatment in 15 female nonsuicidal, nonpsychotic patients with major depression and compared with 15 drug-free healthy women. The aim of the study was to determine the effects of 4 and 24 weeks of sertraline treatment on platelet 5- HT concentration and platelet MAO activity in depressed patients subdivided according to the treatment response into remitters, responders and nonresponders after 4 and 24 weeks of sertraline treatment based on the 70%, 50 – 69% and < 49% reductions in baseline Montgomery – Asperg Depression Rating Scale (MADRS) scores, respectively. Platelet 5-HT concentration was significantly lower in all depressed patients at baseline than in healthy subjects. Among patients, platelet 5-HT concentration or platelet MAO activity did not differ before treatment. There was no significant correlation between MADRS scores and peripheral biochemical markers. The limitation of the study was in a small number of patients, but its advantage was in a long-term (24 weeks) follow-up of both patients and healthy controls. Our results show that long-term sertraline treatment induced remission and response in 87% patients, decreased platelet 5-HT concentration after 4 and 24 weeks of treatment and decreased platelet MAO activity after 24 weeks and suggest that pretreatment values of platelet 5-HT and platelet MAO might not predict therapeutic outcome to sertraline treatment in female depressed patients. D 2003 Elsevier Science Inc. All rights reserved. Keywords: Blood platelets; Major depression; Monoamine oxidase; Remission; Response and nonresponse; Serotonin; Sertraline 1. Introduction Sertraline, a naphthylamine derivative, is a selective serotonin reuptake inhibitor (SSRI) that causes a dose- related inhibition of serotonin (5-hydroxytryptamine, 5- HT) uptake into platelets (Sanchez and Hyttel, 1999). It has clear antidepressive and anxiolytic properties (Ander- son, 2000). Recommended starting dose is 50 mg/day, which should not exceed 200 mg/day (Licht and Qvitzau, 2002). Sertraline is slowly absorbed after the oral adminis- tration, with peak plasma concentrations at 6–8 h and elimination half-life at about 26 h (MacQuin et al., 2001). Steady state is reached after 7 days of treatment (Warring- ton, 1991). Its clinical effects are apparent after repeated treatment, paralleling the adaptive changes in the sensitivity of serotonergic autoreceptors (Stahl, 1998; Sanchez and Hyttel, 1999). Neuroendocrine effects have been reported after long-term sertraline treatment (S ˇ agud et al., 2002). Alterations in serotonergic transmission have been found in depression (Stahl, 1985; Roy and Linnoila, 1988; Maes and Meltzer, 1995), and 5-HT has been shown to affect a wide range of physiological (cardiovascular, respiratory and thermoregulatory) and behavioral (circadian rhythm, sleep – wake cycle, appetite, aggression, sexual behavior, sensory motor reactivity, pain sensitivity and learning) functions disturbed in depression (Stahl, 1998), anxiety disorders, schizophrenia and eating disorders (Lucki, 1998). Since 0278-5846/03/$ – see front matter D 2003 Elsevier Science Inc. All rights reserved. doi:10.1016/S0278-5846(03)00105-2 Abbreviations: ACD, acid citrate dextrose; CGI-I, Clinical Global Impression of Improvement Scale; CGI-S, Clinical Global Impression of Severity Scale; MADRS, Montgomery – Asperg Depression Rating Scale; MAO, monoamine oxidase; SSRI, selective serotonin reuptake inhibitor; 5- HT, 5-hydroxytryptamine, serotonin. * Corresponding author. Tel.: +385-1-4571-207; fax: +385-1-456- 1010. E-mail address: seler@rudjer.irb.hr (D. Mu ¨ck-S ˇ eler). www.elsevier.com/locate/pnpbp Progress in Neuro-Psychopharmacology & Biological Psychiatry 27 (2003) 759 – 765