The effects of amitriptyline, citalopram and reboxetine on autonomic nervous system

RATIONALE: In therapeutic use, amitriptyline, reboxetine and citalopram have all been associated with apparent anticholinergic-like side effects (dry mouth, constipation, etc.), despite the very low antimuscarinic activity of reboxetine and citalopram in vitro. OBJECTIVES: We hypothesised that the spectral analysis of heart rate variability (HRV) might detect differences between amitriptyline, citalopram and reboxetine in their anticholinergic activities following a single peroral administration. METHODS: In this double-blind, cross-over study, amitriptyline (75 mg), citalopram (20 mg), reboxetine (4 mg) and placebo were randomly given at 1-week intervals to eight healthy male volunteers. Drug and catecholamine concentrations in plasma were determined repeatedly. The drug effect was assessed with periodic recordings of electrocardiogram (ECG) and blood pressure, and with measurements of salivary secretion. The ECG recordings were subjected to spectral analysis of HRV, in which the high frequency (HF) power of R-R interval (RRI) variability was supposed to reflect cardiac parasympathetic tone. RESULTS: Reboxetine increased heart rate and blood pressure and reduced the HF power of RRI and 3,4-dihydroxyphenylglycol (DHPG) plasma concentrations. Amitriptyline diminished salivary secretion and had a prominent sedative action. Measurements after citalopram did not differ significantly from placebo. CONCLUSIONS: Reboxetine, despite its low antimuscarinic activity in vitro, had distinct effects on the HF power of RRI, consistent with anticholinergic activity in vivo. Amitriptyline had a measurable anticholinergic effect in the salivary glands, but, surprisingly, not in the heart. We suggest that the sedative effect of amitriptyline could alter cardiac sympathovagal balance and, therefore, counteract the anticholinergic drug effect.     

Prediction of the response to citalopram and reboxetine in post-stroke depressed patients

Rationale and objective Depression is a significant complication of stroke. The effectiveness of antidepressant drugs in the management of post-stroke depression (PSD) has been widely investigated. However, the choice of antidepressant drug is critically influenced by its safety and tolerability and by its effect on concurrent pathologies. Here we investigate the efficacy and safety of a selective serotonin reuptake inhibitor (SSRI), citalopram, and a noradrenaline reuptake inhibitor (NARI), reboxetine, in post-stroke patients affected by anxious depression or retarded depression.Methods This was a randomized double-blind study. Seventy-four post-stroke depressed patients were diagnosed as affected by anxious or retarded depression by using a synoptic table. Randomisation was planned so that 50% of the patients in each subgroup were assigned for 16 weeks to treatment with citalopram and the remaining 50% were assigned to treatment with reboxetine. The Beck Depression Inventory (BDI), the Hamilton Depression Rating Scale (HDRS) and a synoptic table were used to score depressive symptoms.Results Both citalopram and reboxetine showed good safety and tolerability. Citalopram exhibited greater efficacy in anxious depressed patients, while reboxetine was more effective in retarded depressed patients.Conclusions Citalopram or other SSRIs and reboxetine may be of first choice treatment in PSD because of their good efficacy and lack of severe side effects. In addition, PSD patients should be classified according to their clinical profile (similarly to patients affected by primary depression) for the selection of SSRIs or reboxetine as drugs of choice in particular subgroups of patients.     

甲磺酸瑞波西汀与氢溴酸西酞普兰治疗迟缓性抑郁的随机双盲对照研究

目的 比较甲磺酸瑞波西汀与氢溴酸西酞普兰治疗迟缓性抑郁症的疗效和安全性.方法 将59例迟缓性抑郁症患者随机分为Ⅰ组(n=29)和Ⅱ组(n=30).Ⅰ、Ⅱ组治疗分别使用甲磺酸瑞波西汀和氢溴酸西酞普兰,两组疗程均为6周.使用汉密尔顿抑郁量表(HAMD)于治疗前及治疗第1、2、4、6周末各评定1次临床疗效;通过不良反应量表(TESS)、实验室检查、生命体征等观察药物安全性.结果 治疗6周后,甲磺酸瑞波西汀组HAMD总分减分值为(18.48±6.38),氢溴酸西酞普兰组为(11.60±4.46),两组差异有统计学意义(P＜0.001).两组总有效率差异有统计学意义(82.8%与56.7%,P＜0.05),而不良反应差异无统计学意义.结论 甲磺酸瑞波西汀治疗迟缓性抑郁症的疗效优于氢溴酸西酞普兰,是一种安全有效的抗抑郁药物.     

<Emphasis Type="SmallCaps">L</Emphasis>-5-Hydroxytryptophan induced increase in salivary cortisol in panic disorder patients and healthy volunteers

BACKGROUND: Hypersensitivity of brain serotonin receptors has been proposed as a causal mechanism in the pathophysiology of panic disorder. This theory can be tested, using serotonergic stimulation of the HPA axis. Up to now, plasma cortisol has generally been used as the outcome measure in such studies. Assessment of salivary cortisol is a non-invasive alternative to measure HPA axis activity.METHOD: Salivary cortisol levels were measured in 24 panic disorder patients and 24 healthy volunteers, following ingestion of 200 mg L-5-hydroxytryptophan or placebo.RESULTS: A significant rise in cortisol was observed in both patients and controls following ingestion of L-5-hydroxytryptophan. No such effects were seen in the placebo condition.CONCLUSION: The results show that L-5-hydroxytryptophan stimulated salivary cortisol is a useful probe of serotonin function in healthy volunteers as well as panic disorder patients, and provide some evidence against a serotonin receptor hypersensitivity in panic disorder.     

Four days of citalopram increase suppression of cortisol secretion by prednisolone in healthy volunteers

Rationale Chronic antidepressant treatment increases glucocorticoid-mediated negative feedback on the hypothalamic-pituitary-adrenal (HPA) axis, and thus reduces HPA axis activity, in depressed patients and healthy controls. In contrast, acute antidepressant treatment induces an activation of basal HPA axis activity.Objectives We examined the effects of 4 days of treatment with the selective serotonin reuptake inhibitor, citalopram, on basal salivary cortisol and on suppression of salivary cortisol by prednisolone.Methods We used a single-blind, placebo-controlled, repeated-measure design. Salivary cortisol was measured from 0900 to 1700 hours. In the first phase of the study, basal salivary cortisol secretion was measured on 2 study days, before and after 4 days of treatment with citalopram (orally, 20 mg/day). In the second phase, salivary cortisol secretion after suppression by prednisolone (5 mg, given at 2200 hours the night before) was measured on 2 study days, again before and after 4 days of treatment with citalopram (orally, 20 mg/day). Eight volunteers participated to the study.Results Citalopram increased basal salivary cortisol in the morning (0900–1100 hours) by approximately 47% (P=0.003). Moreover, citalopram increased suppression by prednisolone in the morning (0900–1100 hours): suppression was approximately 22% before citalopram and 45% after citalopram (P=0.05).Conclusions Citalopram increases glucocorticoid-mediated negative feedback on the HPA axis after as little as 4 days of treatment. This effect could be due to an increased function of the corticosteroid receptors. Our findings further support the notion that one of the mechanisms by which antidepressants exert their therapeutic effects is by normalizing HPA axis hyperactivity in depressed patients.     

Psychosocial environment and health: methodological variability of the salivary cortisol measurements

Salivary cortisol offers a novel approach to understand the relationship between psychosocial environment and health. This study examines the intra-individual relationships among indicators of the cortisol circadian rhythm and investigates the influence of determinants affecting the day-to-day variability of the cortisol measures. Over three weekdays, 87 healthy subjects (63 females and 24 males) collected saliva samples at seven time points to assess the cortisol awakening response (CAR), and to evaluate the post morning cortisol profile. The generalized estimating equations method was used to explore the relations between repeated cortisol measures and potential determinants (sociodemographic, health, and sampling factors) influencing salivary cortisol levels. Younger age, being smoker, and sampling on a working day were associated with higher at awakening and total cortisol excretion in the morning period. Higher overall cortisol excretion and cortisol increase in the first hour of the day were found for adherents to sampling procedure. Higher educational level was found associated with greater total cortisol excretion in the morning and post morning period, while a flatter diurnal slope was found in smokers. Results are consistent with the knowledge that the circadian cortisol rhythm is differentially determined by situational factors and that results obtained in the early morning hour are of crucial importance corroborating the evidence that the CAR is a highly state-dependent phenomenon. These data indicate that many confounding factors need to be controlled when using salivary cortisol as biomarker of the mind-health interrelationship.     

Differential effects of reboxetine and citalopram on hand-motor function in patients suffering from major depression

Rationale Motor dysfunctions might be a more common side effect of serotonergic than noradrenergic antidepressants. However, the effects of antidepressants on motor function in depression have rarely been analyzed systematically. Computerized methods allow the objective registration of drug-induced motor dysfunction and were applied in this study.Objectives To examine the effects of a selective noradrenaline re-uptake inhibitor (NARI) (reboxetine) and a selective serotonin re-uptake inhibitor (SSRI) (citalopram) on hand-motor function in patients with major depression.Methods Different types of hand movements (drawing of circles and handwriting probes) were recorded and analyzed in 16 acutely depressed inpatients receiving citalopram (30–60 mg/day) and 12 acutely depressed inpatients treated with reboxetine (4–8 mg/day), using a digitizing tablet for the analysis of movement dynamics. Both groups were comparable regarding mean age (42–43 years), gender, handedness (preponderance of right-handers) and the mean baseline HAMD score (about 27). Five kinematical parameters reflecting velocity, regularity and degree of automation of hand movements have been computed.Results Reboxetine had significantly more favorable effects on fine motor function (increased velocity of rapid hand movements) in depressed patients than citalopram. These differences became obvious when patients conducted more complex tasks and are not explained by differential antidepressant effects.Conclusions Our findings are in line with the hypothesis that SSRI tend to have small, but more pronounced negative effects on motor function than NARI.     

Acute citalopram administration produces correlated increases in plasma and salivary cortisol

RATIONALE: Intravenous administration of the selective serotonin (5-HT) re-uptake inhibitor, citalopram, increases plasma cortisol. This would be expected to produce a parallel increase in salivary cortisol concentration. OBJECTIVE: To find out whether IV citalopram produces correlated increases in plasma and salivary cortisol levels. METHODS: Twelve healthy volunteers were tested on two occasions receiving either citalopram (10 mg IV) or saline in a double-blind, randomised, cross-over design. Plasma and salivary cortisol levels were measured before and for 150 min after each infusion. RESULTS: Relative to placebo, citalopram significantly increased cortisol levels in both plasma and saliva. The size of the increases in plasma and saliva cortisol correlated significantly with each other. CONCLUSIONS: Monitoring changes in salivary cortisol might be a valid and acceptable means of measuring 5-HT-mediated cortisol release.     

Adaptation of DELFIA cortisol kit for determination of salivary cortisol concentration

Salivary cortisol concentration seems to be an excellent indicator of the biologically active plasma cortisol level because of the nearly absence of corticoid-binding proteins in saliva. With regard to the easy, noninvasive, and stress-free nature of saliva sampling, this parameter greatly facilitates studies of the HPA (hypothalamus-pituitary-adrenocortical) axis, especially in children. A commercially available TR-FIA (time-resolved fluoroimmunoassay), the DELFIA (dissociation-enhanced lanthanide fluoroimmunoassay) method, proposed for plasma and urine cortisol analyses, was adapted for salivary cortisol measurement by means of simple modifications of the assay protocol. The sensitivity was determined to be 0.53 nmol/L. The intra- and interassay coefficients of variation ranged from 5.5 to 8.2 % and from 6.0 to 10.4 %, respectively. The present findings suggest that the DELFIA procedure provides a reliable, sensitive, and convenient alternative procedure to the assay for salivary cortisol.     

The effects of reboxetine on autonomic and cognitive functions in healthy volunteers

RATIONALE: Though reboxetine, a selective noradrenaline reuptake inhibitor, causes autonomic and cognitive adverse events there is a paucity of appropriately designed studies on the cognitive and autonomic effects of the drug in the literature. OBJECTIVE: To compare the effects of reboxetine on cognitive and autonomic functions with those of placebo in healthy humans. METHOD: A randomised, double-blind, crossover study of 12 healthy male volunteers aged 25 (21-27; median, range) years. Subjects orally received 4 mg reboxetine and placebo twice daily for periods of 14 days each with at least 14 days in between. Vasoconstrictory response of cutaneous vessels (VR) and skin conductance response (SCR) following sudden deep breath were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. RESULTS: Reboxetine decreased SCR and prolonged the dilation phase of VR (P<0.05). It did not affect cognitive functions such as flicker fusion frequency, choice reaction, memory and psychomotor coordination but increased slow beta (beta1) power density in the qEEG. Tiredness (n=12), dry mouth (n=9), delayed urination (n=3) and constipation (n=1) were noted with reboxetine. CONCLUSION: Sustained peripheral and/or central sympathetic activation accounts for the prolongation of VR. The decrease of SCR and typical side effects suggest a relevant antimuscarinic drug action. Chronic administration of reboxetine at therapeutic doses causes autonomic dysfunction and subjective sedation but does not impair cognitive and psychomotor abilities in healthy humans.     

夜间两不同时间点唾液皮质醇检测结果分析

目的比较分析夜间23：00与24：00唾液皮质醇检测结果,以判断能否将午夜唾液皮质醇提前至23：00采集,用于临床库欣综合征的筛查诊断。方法对健康人群组（NS组）108例,库欣综合征（CS）高危人群组（NCS组）50例,库欣综合征患者（cs组）7例,分别于夜间23：00与24：00采集唾液,用酶联免疫吸附分析法（ELISA）检测唾液皮质醇。结果三组受试者夜间23：00与24：00唾液皮质醇检测结果分别为：Ns组：（2．01±O．91）ng/m1,（1．96±0．85）ng／ml;NCS组：（3．55±1．73）ng／ml,（3．81±1．49）ng／ml;CS组：（12．63±6．14）ng／ml,（10．98±3．98）ng／ml;三组组内两时间唾液皮质醇检测结果差异均无统计学意义（P均〉0．05）,呈良好的直线相关（r=0．924,P〈0．001）;三组组间两时间唾液皮质醇检测结果差异均有统计学意义（P均〈0．001）,cs组明显高于NS组和NCS组,NCS组高于NS组;23：00和24：00唾液皮质醇ROC曲线下面积分别为：0．995、0．996,对cs的诊断准确性较高。结论夜间唾液皮质醇浓度是筛查、诊断cs的一个方便、敏感指标;23：00唾液皮质醇浓度与24：00的接近,在23：00采集唾液可以满足临床库欣综合征的筛查诊断要求。     

An integrated model for the effect of budesonide on ACTH and cortisol in healthy volunteers

AIMS: Budesonide, a glucocorticosteroid, is used as a first-line treatment for asthma. The aim of the study was to develop a PK/PD model for the effect of budesonide on ACTH and cortisol. METHODS: The modelling data were generated by conducting a single-blind, randomized, placebo-controlled cross-over study. Ten healthy volunteers inhaled placebo (Placebo Turbohaler) and 1600 microg budesonide (Pulmicort Turbohaler), with a wash-out period of 7 days between treatments. Baseline concentrations of cortisol and ACTH were measured after placebo treatment and concentrations of cortisol, ACTH and budesonide were assessed after budesonide treatment. A one-compartment disposition model was used for budesonide disposition. Based on indirect response models, two types of models, distinguishing between production driven by a sum of cosine functions and production driven by surges, were used in parallel to describe the data. RESULTS: The surge-based approach was the most appropriate, based on goodness-of-fit, objective function values and number of parameters. The surge-based model that integrated both ACTH and cortisol data was chosen as the final model. The estimated half-lives of endogenous ACTH and cortisol were 9 and 113 min, respectively. The budesonide and ACTH concentrations producing 50% of the maximal response (IC(50) and A(50)) were 0.325 microg l(-1) and 4.96 pmol l(-1). CONCLUSIONS: The present PK/PD model of the effect of budesonide on ACTH and cortisol can serve as a tool for further understanding of the hypothalamic-pituitary-adrenal (HPA) axis and be useful in the development of drugs interacting with the axis.     

唾液皮质醇与血浆皮质醇、尿游离皮质醇测定的相关性分析及其临床价值

目的探讨正常人唾液皮质醇、血浆皮质醇和24 h尿游离皮质醇三者之间的相关性。方法选择30例健康受试者同时检测唾液皮质醇、血浆皮质醇和24 h尿游离皮质醇。男子组和女子组各15例。采用化学发光技术测定,唾液标本采用唾液收集器收集,血标本为血浆,24 h尿液标本用硼酸防腐。结果唾液皮质醇和血浆、24 h尿液皮质醇在正常男女组之间均无显著性差异（P＆gt;0.05）,唾液皮质醇与血浆皮质醇（r=0.91）、唾液皮质醇与24 h尿游离皮质醇（r=0.95）,均存在显著的相关性。结论唾液皮质醇可作为库欣氏综合征的筛查指标。     

Acute reboxetine administration increases plasma and salivary cortisol

We investigated the effect of a single oral dose of the selective noradrenaline reuptake inhibitor, reboxetine (4 mg), on plasma and salivary cortisol in 24 healthy volunteers in a randomized, placebo-controlled, parallel-group design. Reboxetine significantly increased both plasma and salivary cortisol, although the correlation between the responses in plasma and saliva was modest. Our results are consistent with previous neuroendocrine challenge studies showing that potentiation of brain noradrenaline function stimulates the hypothalamic-pituitary-adrenal axis. Reboxetine-induced salivary cortisol release appears to be a simple and relatively non-invasive test of hypothalamic noradrenaline function. However, placebo-controlled, within-subject designs are likely to yield a more valid measure of noradrenaline-mediated cortisol release.     

Time course of hypothalamic-pituitary-adrenocortical axis activity during treatment with reboxetine and mirtazapine in depressed patients

Rationale In healthy subjects, cortisol and ACTH secretion are acutely stimulated by reboxetine and inhibited by mirtazapine. However, it was not investigated so far whether reboxetine and mirtazapine may also differ in their impact on hypothalamic-pituitary-adrenocortical (HPA) axis activity in depressed patients and whether these effects are related to clinical outcome.Objectives In the present study, we investigated the impact of 5-week treatment with reboxetine or mirtazapine on the combined dexamethasone suppression/corticotropin releasing hormone (DEX/CRH) test results in depressed patients.Methods Forty drug-free patients suffering from a major depressive episode (Diagnostic and Statistical Manual of Mental Disorders-IV criteria) were treated with either reboxetine (8 mg/day; n=20) or mirtazapine (45 mg/day; n=20) for 5 weeks. Before, after 1 and 5 weeks of therapy, the DEX/CRH test was performed and cortisol and ACTH concentrations were measured.Results During reboxetine treatment, a gradual and significant reduction in HPA axis activity as measured by the DEX/CRH test was seen, which was most pronounced after 5 weeks of treatment. In contrast, mirtazapine significantly reduced the cortisol and ACTH concentrations during the DEX/CRH test within 1 week. However, after 5 weeks of mirtazapine treatment, the cortisol and ACTH responses to the DEX/CRH test partially increased again both in responders and nonresponders.Conclusions This is the first study demonstrating differential effects of various antidepressants on the time course of serial DEX/CRH test results in depressed patients.     

Neuronal effects of acute citalopram detected by pharmacoMRI

Rationale Serotonin (5-hydroxytryptamine, 5-HT) is implicated in the aetiology and treatment of a variety of psychiatric disorders. A limitation of research has been the necessity to use indirect measures of 5-HT function. Method We describe a method of analysing pharmacoMRI data using SPM and apply it to the direct i.v. infusion of selective 5-HT reuptake inhibitor, citalopram, in 12 healthy volunteers. Scanning took place on a 1.5-T Philips MRI scanner. Results Areas implicated in depression and its treatment were observed to have increasing signal with respect to time. These areas included the caudate, the amygdala, the hippocampus, the striatum and the thalamus. Conclusion Direct pMRI using i.v. citalopram opens new ways of investigating 5-HT mechanism in depression and its treatment.     

Contrasting Fos expression induced by acute reboxetine and fluoxetine in the rat forebrain: neuroanatomical substrates for the antidepressant effect

Rationale Antidepressants preferentially facilitating serotonin seem to be particularly effective for treating the anxiety and aggressive component of the depressive syndrome, whereas those with a noradrenergic profile seem to be more effective in reducing psychomotor retardation, although their overall antidepressant effects are about the same. However, the mechanism of this difference remains unknown.Objectives To investigate the neural substrate for the different therapeutic efficacies of fluoxetine and reboxetine, we examined the regional Fos immunoreactivity (Fos-ir) induced by the two agents.Methods Male Wistar rats (290–330 g) were given a subcutaneous injection of fluoxetine (5 or 10 mg/kg), reboxetine (5 or 10 mg/kg) or saline. Two hours later, rats were perfused through the ascending aorta and their brains were processed for Fos immunohistochemistry. Fos-ir was quantified by counting the number of Fos-ir-positive nuclei in six areas of the forebrain.Results The shell of the nucleus accumbens was the only region in which both fluoxetine and reboxetine equally increased Fos-ir expression. Fluoxetine particularly induced Fos-ir in the central nucleus of the amygdala. In contrast, reboxetine induced Fos-ir in the cingulate cortex area 3 and the lateral orbital cortex.Conclusions These results suggest that the shell region may be one possible target for the antidepressant effects of fluoxetine and reboxetine. Furthermore, the difference in their clinical effects may depend on their different target sites of action.     

Transfer of reboxetine into breastmilk, its plasma concentrations and lack of adverse effects in the breastfed infant

Objective To investigate the transfer of reboxetine into milk, the absolute and relative infant doses via milk and to assess plasma concentrations and adverse unwanted effects in the breastfed infant.Methods Multiple samples of blood and milk were obtained over a dose interval at steady-state from four women who were taking reboxetine for postnatal depression. Drug concentrations in plasma and milk were measured by high performance liquid chromatography and milk/plasma ratio (M/P), absolute infant dose and relative infant dose were estimated by standard methods. Their four, breastfed, infants were also examined clinically, and a blood sample was taken for drug analysis.Results The median (range) dose taken by the women was 6 (4-10) mg/day. There was no significant difference in reboxetine concentration between paired fore-and hind-milk samples. The mean (95% CI) M/P was 0.06 (0.03, 0.09). Absolute infant dose was 1.7 (0.7, 2.4) μg/kg/day for reboxetine while the relative infant dose was 2.0% (1.3, 2.7%). Three of the infants met normal developmental milestones and no adverse effects were seen in any infant. The fourth infant had developmental problems that were not associated with the maternal reboxetine therapy. The concentrations of reboxetine in plasma from the four infants were <4 μg/l, 2.6 μg/l, 2.3 μg/l and 5 μg/l, respectively.Conclusion The study suggests that reboxetine use by lactating women is safe for the breastfed infant. Nevertheless, our study had only four mother/baby pairs, and each decision to breastfeed should always be made on the basis of an individual risk/benefit analysis.     

Methadone patients exhibit increased startle and cortisol response after intravenous yohimbine

Brain noradrenergic systems have been shown to be altered in opioid dependence and to mediate aspects of opioid withdrawal. Pre-clinical and clinical studies by others have shown that yohimbine, which increases noradrenergic activity, also increases both baseline and fear enhancement of the magnitude of the acoustic startle response (ASR). In a separate report from this experiment, it was shown that yohimbine produced opioid withdrawal-like symptoms, including anxiety, in clinically stable methadone-maintained patients and also produced elevations in the norepinepherine (NE) metabolite, 3-methoxy-4 hydroxyphenethyleneglycol (MHPG), and cortisol serum levels. The current study reports the effects of intravenous yohimbine hydrochloride, 0.4 mg/kg versus saline (double-blind), on ASR magnitude, plasma MHPG, and cortisol levels in eight methadone-maintained patients and 13 healthy subjects in a double-blind fashion. Yohimbine increased startle magnitude in both groups. There was no basal (placebo day) difference between the startle response of the two groups, but methadone patients had a larger startle magnitude increase in response to yohimbine than healthy controls. Methadone-maintained patients had lower baseline plasma levels of MHPG and similar baseline plasma cortisol levels compared with normal subjects. Yohimbine caused significant elevation in cortisol and MHPG in both groups. Methadone-maintained subjects had higher elevations in cortisol levels and MHPG (methadone main effect) levels in response to yohimbine. However, when MHPG levels were corrected for baseline differences by analysis of covariance (ANCOVA), the yohimbine effect, but not the methadone effect remained statistically significant. These results are consistent with the previous report and support the hypothesis that abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis and of noradrenergic mechanisms of stress response persist in opioid-agonist maintenance. The ASR effect extends the previous report and provides an additional objective measure for perturbation of noradrenergic and stress responses in these patients.     

Neuroendocrine effects of ipsapirone on the hypothalamic-pituitary adrenal axis: CRF,ACTH and cortisol in healthy volunteers

Summary The neuroendocrine effects (changes in plasma CRF, ACTH and cortisol) of single and multiple (t.d.s. for 2 days) doses of ipsapirone (BAY Q 7821) 5 and 10 mg have been investigated in 6 healthy male volunteers. The study followed a balanced complete block, placebo-controlled and double blind design with two baseline phases (pre and post-treatment). Volunteers were investigated on identical days during 5 successive weeks.The results do not show a specific effect of ipsapirone on the hypothalamic-pituitary-adrenal axis when doses in the range of 5–30 mg per day were given.