Emin Önder

Clinical and pharmacologic risk factors for neuroleptic malignant syndrome and their association with death

Aim:  The aim of the present study was to evaluate demographics, clinical features, psychiatric diagnoses and prognosis of neuroleptic malignant syndrome (NMS) reported in Turkey, and to assess their association with mortality.

Faster response in depressive patients treated with fluoxetine alone than in combination with buspirone

BACKGROUND The aim of this study was to compare the antidepressant efficacy of standard dose, dose optimization of antidepressant drug and buspirone augmentation strategies. METHODS 120 outpatients with a DSM-IV diagnosis of unipolar depression were randomised to 12-weeks of open label treatment with fluoxetine 20 (flx20) or 40 mg (flx40) daily or fluoxetine 20 mg plus buspirone 20 mg daily (flx20-plus-buspirone). The severity of depression was assessed by Hamilton Depression Rating Scale (HDRS). Response was defined as a 50% or greater reduction of the baseline HDRS total score. A response, which began at any time of the study and was maintained until the last visit, was defined as a sustained response. RESULTS The proportion of responders was not significantly different among the treatment groups at the endpoint. Survival analysis showed, however, a significant faster response in the patients treated with flx20 or flx40 alone than flx20-plus-buspirone. The mean times to onset of a sustained response were 33, 24 and 40 days, respectively. LIMITATIONS The lack of treatment-resistant group is a methodological limitation of this study. CONCLUSIONS Adding buspirone to fluoxetine in the treatment of major depressive disorder may delay the time to onset of antidepressant efficacy. In order to accelerate and maximise the clinical response in depressive patients, clinician should prefer to optimize the fluoxetine dose instead of in combination with buspirone.

Fluoxetine once every third day in the treatment of major depressive disorder

Fluoxetine and its active metabolite norfluoxetine have long half-lives. We postulate that, owing to the long elimination half-life and the time to reach steady-state level in plasma is nearly four weeks, patients diagnosed with major depressive disorder might be treated with fluoxetine taken once every third day, after being treated initially during 4 weeks with daily doses of fluoxetine. In this open label, 12-weeks, randomized, prospective study, patients diagnosed with DSM-IV major depressive disorder were randomly assigned into 1 of 3 treatment groups. Thirtyfour patients took 20 mg and 32 patients took 40 mg of fluoxetine daily throughout the study. Twenty-nine patients had been taking 20 mg of fluoxetine daily for 4 weeks of the study initially, and then were switched to 20 mg fluoxetine once every third day regime. The severity of depression was assessed by Hamilton Depression Rating Scale (HDRS) and Clinical Global Impressions- Severity Scale (CGI-S). Response was defined as a 50% or greater reduction of the baseline HDRS total score. After defining a strict criterion of relapse, time to relapse was estimated using survival analyses (Kaplan-Meier method). The repeated measures analysis of variance (ANOVA) of HDRS found a significant time effect (F = 464.04, df = 1.00, p < 0.001), but no significant group effects (F = 0.84, df = 2.00,p = 0.433) from baseline through week 12. The proportion of responders was not significantly different between the treatment groups at the endpoint. Survival analyses showed, however, a significant delayed mean time to relapse in patients treated with 40 mg of fluoxetine daily compared to either patients treated with 20 mg of fluoxetine daily or 20 mg fluoxetine once every third day. The mean times to relapse were 79.8, 70.8, and 70.5 days, respectively. Fluoxetine was associated with some adverse events in 46.3% of patients. The most frequently occurring adverse event was insomnia. It is proposed that either every third day or daily dosing with the same dose of fluoxetine could treat the patients with major depressive disorder during the acute and continuation period of treatment. Nevertheless, higher daily dose of fluoxetine has a reduced relapse rate compared to that of the lower daily dose.

Neurotrophic factors and hippocampal activity in PTSD

Although numerous studies have investigated the neurotrophic factors and hippocampal activity in posttraumatic stress disorder (PTSD) separately each other, it is unclear whether an association between neurotrophic factors and hippocampal activity is present. The aim of this study was to evaluate the functional changes in hippocampus before and after treatment with escitalopram and to associate these changes with peptides related to neuronal growth in patients with chronic PTSD and trauma survivors without PTSD. Fifteen earthquake survivors with chronic PTSD and thirteen drug naïve trauma exposed individuals without PTSD underwent fMRI scans in a block design. Serum levels of Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) were measured before and after 12 weeks treatment with escitalopram. Baseline median serum level of NGF was significantly lower in patients with chronic PTSD than trauma survivors; however, 12 weeks of treatment with escitalopram significantly increased it. Higher activation was found both in left and right hippocampus for chronic PTSD group than trauma survivors. Treatment with escitalopram was significantly associated with suppression of the hyperactivation in left hippocampus in patients with chronic PTSD. Bilateral hyperactivation in hippocampus and lowered NGF may associate with neurobiological disarrangements in chronic PTSD. Treatment with escitalopram was significantly associated with both improvement in the severity of PTSD symptoms and biological alterations. Patients diagnosed with PTSD may have further and complicated deteriorations in hippocampal networks and neurotransmitter systems than individuals who had not been diagnosed with PTSD following the same traumatic experience.