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Biomedical subjects

I Berlin

Publications and source records attributed to I Berlin.

At least 19 recordsLinked to original sources
PubMed2005

[Nicotine replacement therapies during pregnancy: what do we know about the balance between benefits and risks?].

Maternal smoking during pregnancy induces obstetrical and fetal complications but also has an impact on newborns, infants, children and adults. Nicotine replacement therapies are authorized during pregnancy in France, the purpose being to reduce fetal exposure to toxic compounds in tobacco smoke. However, it is not proven that nicotine replacement therapy is harmless to the fetus and to date, no study has demonstrated any beneficial effect in terms of abstinence. It is suggested that benefit and risks of nicotine replacement therapies during pregnancy should be evaluated.

Animals↗
PubMed2005

Identification of factors associated with impaired hypoglycaemia awareness in patients with type 1 and type 2 diabetes mellitus.

OBJECTIVES: To assess clinical factors associated with impaired hypoglycaemia awareness (HA). METHODS: Survey of 241 type 1 and type 2 diabetic patients hospitalised in a diabetes department for a diabetes education program. Demographic, diabetes and psychiatric characteristics and subjective hypoglycaemic symptoms were recorded by a self-report questionnaire. RESULTS: Age and body mass index (BMI) was greater and glycated haemoglobin was lower in diabetic patients reporting impaired HA, however, these latter differences became not significant when age was included as a covariate. There were significantly more current smokers among those with impaired HA and controlling for age accentuated this difference. Current treatment by insulin was not associated with impaired HA. Backward stepwise logistic regression showed that type 2 diabetic patients were twice as likely to have impaired HA than type 1 diabetic patients (OR = 2.195, 95% CI: 1.017-4.734, P = 0.04). Moreover, higher age, current smoking and type 2 diabetes interacted significantly in increasing the likelihood of impaired HA. Among those with impaired HA more patients experienced drowsiness and nervousness and less patients reported tremor during the hypoglycaemic episodes. No other symptoms were associated with impaired HA. CONCLUSION: Type 2 diabetic patients, whether on insulin or not, and especially if they are of advanced age and if they smoke, are at increased risk of impaired HA.

Alcohol Drinking↗
PubMed2004

Efficacy of bupropion and predictors of successful outcome in a sample of French smokers: a randomized placebo-controlled trial.

BACKGROUND: Previous published studies assessed the efficacy of bupropion in smoking cessation only in North American populations of smokers. Results of therapeutic drug trials are not always directly applicable in other populations. AIMS: To confirm the efficacy of bupropion in smoking cessation in European smokers. DESIGN: A multi-centre, randomized, double-blind placebo-controlled trial. SETTING: Seventy-four smoking cessation out-patient clinics in France. PARTICIPANTS: The study included 509 smokers motivated to quit smoking. Intervention Subjects were randomized to either slow-release bupropion 150 mg b.i.d. (B) or to placebo (Pl) in a 2 : 1 ratio, treated for 7 weeks, and followed-up for 26 weeks. MEASUREMENTS MAIN OUTCOME MEASURE: 6 months' point prevalence abstinence, determined by self-report and expired air carbon monoxide measurement. SECONDARY OUTCOME MEASURES: weeks 4-7 and weeks 4-26 continuous abstinence rates, craving, withdrawal symptoms, weight and cigarette consumption in smokers unable to quit. Adverse events were recorded systematically. FINDINGS: Six months' point prevalence abstinence rates were 31% and 16%[odds ratio = 2.3, confidence interval (CI) 95%: 1.4-3.7] in the B and Pl groups, respectively. Continuous abstinence rates were 41% (B) and 21% (P) with OR = 2.5 (CI 95%: 1.6-3.9) for weeks 4-7, and 25% (B) and 13% (P) with OR = 2.2 (CI 95%: 1.3-3.6) for weeks 4-26, respectively. Craving decreased significantly more with B than with Pl during treatment period, but there was no difference for total withdrawal symptoms score. Abstinent subjects gained significantly less weight at week 7 with B than with Pl. Low level of nicotine dependence, high motivation, absence of smoking-related disease, long duration of previous quit attempts, male gender, low level of current alcohol problems and living as a couple were predictive of successful cessation. With the exception of marital status, no interaction was observed between any of these predictive factors and the efficacy of bupropion. More of those who continued smoking in the B group than the P group reduced their consumption by at least 50%. CONCLUSIONS: Sustained-release bupropion is efficacious as an aid to smoking cessation in European smokers. No outcome predictors were identified that might indicate that certain subgroups of smokers would benefit more than others from treatment with bupropion.

Adult↗
PubMed2003

Psychological stress and cortisol secretion in anhedonic alcoholic men.

We investigated plasma cortisol in a psychological stress paradigm in seven weaned anhedonic alcoholics in comparison with seven age-matched healthy controls. Alcoholics had significantly higher mean plasma cortisol at baseline and no increase following a psychological stress paradigm. Anhedonic alcoholics judged the experimental situation less agreeable than controls. Anhedonic alcoholics may have blunted cortisol response to psychological stress.

Adult↗
PubMed2001

Differential abnormalities in plasma 5-HIAA and platelet serotonin concentrations in violent suicide attempters: relationships with impulsivity and depression.

Brain serotonergic systems may participate in the regulation of mood, impulsivity and aggressive behavior. Because some monoaminergic mechanisms seem to be similar in the central nervous system and peripheral tissues, we tested whether serotonergic or dopaminergic biochemical parameters in peripheral venous blood are related or not to violent suicide behavior.We simultaneously studied plasma serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and platelet 5-HT content in patients within 3 days following a violent suicide attempt and in matched healthy controls. We examined their relationship with depression and impulsivity. Twenty seven drug-free suicide attempters and controls were included. Plasma 5-HIAA and platelet 5-HT concentrations were lower in suicide attempters than in controls. Fifteen patients were classified as impulsive (I), including all patients suffering from personality disorder and alcohol abuse, and 12 as non impulsive (NI), mostly melancholics. MADRS scores were similar in both I and NI suicide attempters. When controlling for age, plasma 5-HIAA was lower in I than in NI suicide attempters or controls; these findings are similar to those we observed recently with CSF 5-HIAA in I and NI violent suicide attempters. Contrarily, platelet 5-HT levels were lower in NI than in I patients or controls. Plasma HVA was not associated with suicide behavior. Plasma 5-HIAA concentration was inversely associated with the degree of impulsivity and platelet 5-HT with the intensity of depression. This study indicates that each peripheral serotonergic index is specifically related to a distinct clinical feature and shows differential alteration according to the impulsivity group. In I and NI drug-free violent suicide attempters an inverse figure between plasma 5-HIAA and platelet 5-HT data was observed indicating a non parallelism between these two peripheral variables. Further prospective studies are needed to investigate whether these peripheral serotonergic parameters may be used as helpful early predictors of violent suicide behavior.

Adolescent↗
PubMed2001

Pharmacodynamics and pharmacokinetics of single nasal (5 mg and 10 mg) and oral (50 mg) doses of ephedrine in healthy subjects.

OBJECTIVE: To determine the cardiovascular, subjective effects and potential of abuse liability of single dose (-) ephedrine (E) administered orally (50 mg) or intranasally (10 mg and 5 mg). METHODS: Sixteen healthy Caucasian men with no history of drug/alcohol/nicotine abuse or dependence received intranasal single doses of E 5 mg, 10 mg and oral doses of 50 mg and placebo in a double-blind, double-dummy, crossover study. Dependent measures included assessment of subjective feelings by Addiction Research Centre Inventory (ARCI). Profile of Mood States (POMS). visual analogue scales (VAS); "drug liking", "any drug effect", subjective quality of sleep and blood pressure and heart rate. Plasma E concentrations were also determined. RESULTS: (-) E increased supine systolic, diastolic blood pressure (P < 0.01). Changes in supine systolic blood pressure (areas under the 8 h of the experimental sessions) were -59 +/- 47 mmHgh with placebo, -59 +/- 57 mmHg-h with E5 mg by the nasal route, -18 +/- 48 mmHg x h with E 10 mg by the nasal route and 13 +/- 58 mmHgh with E 50 mg by the oral route (P<0.001). (-) E-induced orthostatic hypotension (P < 0.01) (maximal systolic blood pressure drop: E 50 mg 14 +/- 10 mmHg, P < 0.03; E 10 mg 11 +/- 6 mmHg, P = 0.08 compared with placebo) and resulted in decreased tiredness (placebo -2 +/- 39 mm x h, E 5 mg -17 +/- 39 mm x h, E 10 mg -30 +/- 42 mm x h, E 50 mg -24 +/- 35 mm x h; P < 0.03). E did not modify ARCI subscales--in particular the "amphetamine" subscale--but showed a tendency for drug liking (P= 0.09). On the "any drug effect" questionnaire, subjects could identify drug effect (P=0.007). Maximal plasma E concentration (Cmax) and areas under the curves for up to 8 h were proportional to the doses. Elimination half-life was approximately 6 h. A clockwise hysteresis was observed for systolic blood pressure in all but one subject with E 50 mg by the oral route. CONCLUSION: E even at low doses and by the nasal route can decrease tiredness in healthy persons; this is accompanied by a substantial increase in blood pressure and orthostatic hypotension exposing individuals in case of intensive physical exercise to cardiovascular risks. No clear evidence of abuse liability in healthy drug naive subjects was observed.

Administration, Intranasal↗
PubMed2001

Monoamine oxidases and tobacco smoking.

Although nicotine has been identified as the main ingredient in tobacco responsible for aspects of the tobacco dependence syndrome, not all of the psychopharmacological effects of smoking can be explained by nicotine alone. Accumulating preclinical and clinical evidence has demonstrated that smoking also leads to potent inhibition of both types (A and B) of monoamine oxidase (MAO). Smokers have 30-40 % lower MAOB and 20-30 % lower MAOA activity than non-smokers. Reduced MAO activity in smokers has been shown by direct measures (platelets, positron emission tomographic studies) or by indirect measures (concentration of monoamine catabolites in plasma or CSF). We examine the hypothesis that chronic habitual smoking can be better understood in the context of two pharmacological factors: nicotine and reduced MAO activity. We speculate that MAO inhibition by compounds found in either tobacco or tobacco smoke can potentiate nicotine's effects. Based on this concept, more effective anti-smoking drug strategies may be developed. As a practical consequence of tobacco smoke's MAO-inhibitory properties, comparative psychiatric research studies need to screen and control for tobacco use.

Animals↗
PubMed2001

Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone.

OBJECTIVE: To assess, in depressed patients, the clinical benefit of mianserin augmentation of fluoxetine or the the benefit of switching treatment from fluoxetine to mianserin. METHOD: In a 6-week double-blind study we compared the therapeutic efficiency and tolerance of mianserin 60 mg/day (N = 34), mianserin 60 mg/day plus fluoxetine 20 mg/day (N = 32) and continuing fluoxetine 20 mg/day (N = 38) in patients with major depression who did not respond to previous fluoxetine treatment. RESULTS: Intent-to-treat analysis showed that at week 6 the decrease in the Hamilton Depression rating scale score was significantly (P < or = 0.03) greater in the mianserin plus fluoxetine group when compared to the fluoxetine group (effect size 0.665). Switching from fluoxetine to mianserin gave intermediate results. Mianserin augmentation of fluoxetine was well tolerated. CONCLUSION: Mianserin augmentation of fluoxetine in patients non-responders to fluoxetine 20 mg/day increases response to treatment and is well tolerated.

Adult↗
PubMed2001

Correlates of expired air carbon monoxide: effect of ethnicity and relationship with saliva cotinine and nicotine.

AIMS: To assess the accuracy of expired air carbon monoxide (CO) measurement vs. saliva cotinine and nicotine and to estimate the degree of misclassifications of smoking status as a function of ethnicity. DESIGN AND MEASUREMENTS: Comparison for accuracy of expired air CO, saliva nicotine and cotinine in simultaneously collected specimens. SETTING: Outpatient clinic of a clinical research ward. PARTICIPANTS: 228 current African-American and Caucasian cigarette smokers. RESULTS: Expired-air CO concentration was significantly associated with saliva cotinine, but not with saliva nicotine. Saliva cotinine but not expired CO or saliva nicotine showed a significant between-ethnic difference when adjusted for number of cigarettes smoked and for time since last cigarette. Agreement between expired air CO and saliva cotinine was substantial at expired CO < or = 8 ppm but only moderate at < or = 10 ppm. False negative rates were twice as high at < or = 10 ppm than at < or = 8 ppm at each saliva cotinine cut-off tested. At saliva cotinine of < or = 15 ng/ml, more African-Americans were classified as false negative. CONCLUSIONS: Expired CO is strongly associated with saliva cotinine but not with saliva nicotine. Despite this association, misclassifications for no smoking are frequent if true classification is based on saliva cotinine. False negative results occur more frequently in African-Americans.

Adolescent↗
PubMed2000

Low serum cholesterol in violent but not in non-violent suicide attempters.

Many previous studies have suggested that low or lowered serum cholesterol levels may increase the risk of mortality not due to somatic disease: principally, suicide and violent death. Because violent death is rare, some studies have investigated afterwards the relation between cholesterol levels and either suicide attempts in psychiatric populations or violence in criminally violent populations. However, none of these studies have compared cholesterol levels in violent and non-violent suicide attempters. The blood of 25 consecutive drug-free patients following a violent suicide attempt and of 27 patients following a non-violent suicide attempt by drug overdose was drawn in the 24 h following admission. Patients with a diagnosis of alcohol abuse and with cholesterol-lowering therapy were excluded. Age, sex, body mass index, psychiatric diagnosis and the physical conditions of the suicide attempt were investigated. Thirty-two healthy subjects were used as a control group. There were no differences between the groups in age, frequency of psychiatric diagnoses or body mass index. There was more women in the group of non-violent suicide attempters than in that of violent suicide attempters (P<0.001). In analyses controlling for sex and age, the serum cholesterol concentration was 30% lower (F(2,82)=15.8; P<0.0001) in the group of violent suicide attempters (147+/-54 mg/dl) than in the group of non-violent suicide attempters (209+/-38 mg/dl) or control subjects (213+/-46 mg/dl). Our results showed that low serum cholesterol level is associated with the violence of the suicide attempt and not with the suicide attempt itself. Further investigations are necessary to determine the usefulness of this easily accessible parameter as a potential risk indicator for violent acts such as violent suicidal behavior in susceptible individuals.

Adult↗
PubMed2000

Sensitive determination of ephedrine and norephedrine in human plasma samples using derivatization with 9-fluorenylmethyl chloroformate and liquid chromatography.

A high-performance liquid chromatography procedure for the determination of ephedrine and norephedrine using fluorimetric detection in plasma samples is described. A double liquid-liquid extraction was performed, followed by derivatization with 9-fluorenylmethyl chloroformate. The extracts were chromatographed with a 5-microm C18 (150x4.6 mm I.D.) column using a mobile phase composed of acetonitrile and water (52:48; v/v). The excitation and emission wavelengths were respectively 264 nm and 313 nm. Calibration curves were linear over the range 0 to 300 ng/ml for each analyte. The specificity of the method was demonstrated with several FMOC-reacting drugs. The limits of quantification are similar to those obtained with the reference method: 2 ng/ml for ephedrine and 5 ng/ml for norephedrine. This method has been successfully applied to the determination of ephedrine and norephedrine plasma levels after administration of low doses of ephedrine to healthy subjects.

Chromatography, High Pressure Liquid↗
PubMed2000

The diagnostic value of electron microscopy in human immunodeficiency virus-positive patients with gastrointestinal disease.

BACKGROUND: Our aim was to determine the diagnostic value of electron microscopy in evaluating the etiology of gastrointestinal disease in patients infected with the human immunodeficiency virus (HIV). METHODS: A retrospective review of electron microscopic and light microscopic results of all HIV-positive patients with gastrointestinal and liver diseases was made during a 3-year period from June 1995 to June 1998. RESULTS: A total of 145 HIV-positive patients had their electron microscopy specimens reviewed. Of these, 136 were investigated for diarrhea, and the other 9 for increased liver enzymes. Twenty-seven of the 145 (18.6%) HIV-positive patients had a pathogen identified by electron microscopy, compared with only 13 of 145 (9%) identified by light microscopy (P < 0.005). The sensitivity of light microscopy for detecting opportunistic pathogens was 68%. Twenty-one of the 27 (77.8%) patients diagnosed by electron microscopy had microsporidiosis, and the most commonly diagnosed species was Enterocytozoon bieneusi. Light microscopy failed to identify 12 cases of microsporidiosis and 2 cases of leishmaniasis. CONCLUSIONS: Electron microscopy contributes substantially to the identification of pathogens in HIV-positive patients. Light microscopy failed to identify one of every two pathogens diagnosed by electron microscopy.

Adult↗
PubMed2000

Anal carcinoma: a 15-year retrospective analysis.

BACKGROUND: Using a 15-year experience in two teaching hospitals to illustrate the clinicopathologic, treatment and survival characteristics of cloacogenic and squamous cell carcinoma of the anus. METHOD: A retrospective analysis over a 15-year period from St Vincent's Hospital (SVH) and the Catholic Medical Center (CMC) in New York City. The patients in the study all had a diagnosis of either squamous or cloacogenic cell carcinoma of the anus. RESULTS: Cloacogenic and squamous cell carcinoma accounted for 2.5% of all large bowel cancers. In the population sample, 28/92 (30.4%) were of the cloacogenic type and 64/92 (69.6%) were of the squamous cell type. The male-to-female ratio was 1:1.5 in those with cloacogenic cancer and 1.8:1 in those with squamous cell carcinoma. The mean age of presentation was 57 +/- 2.8 years for the squamous cell carcinoma patients and 66.3 +/- 3.4 years in those with cloacogenic carcinoma (P < 0.02); 3/28 (10.7%) of patients with cloacogenic cancer were human immune deficiency virus (HIV) positive while 15/64 (23.4%) of the squamous cell cancer patients were HIV positive. The most common clinical presentation in both groups were rectal bleeding, pain, constipation and the presence of an anal mass. Of patients with squamous cell cancer 25% had evidence of infection with the human papilloma virus (HPV) while none of those with cloacogenic cancer had evidence of HPV infection (P < 0.0005). The treatment modality and survival were similar in both histologic groups. The most important factors that affect survival in both groups are female sex and stage of disease. CONCLUSION: Cloacogenic and squamous cell carcinoma account for only a small proportion of large bowel cancers. The squamous cell type is the more common type and presents at a younger age in both sexes. The squamous cell type is also more common in males and is associated with human papilloma and HIV infection. Treatment modality and survival is, however, similar in both histologic variants of anal cancer.

Adult↗
PubMed2000

Platelet monoamine oxidase B activity is inversely associated with plasma cotinine concentration.

Cigarette smoke but not nicotine inhibits irreversibly platelet monoamine oxidase B (MAO-B) activity. Current smokers have decreased platelet MAO-B activity which normalizes when smokers quit. Normalization of platelet MAO-B activity probably depends on platelet turnover. Platelet MAO-B activity has been found to be correlated with plasma thiocyanate concentration. The aim of this study was to investigate in smokers whether platelet MAO-B activity is related to plasma cotinine concentration, an indirect index of use of smoked tobacco. We determined simultaneously plasma cotinine concentration and platelet MAO-B activity in 85 cigarette smokers [mean (+/- SD) age 39 +/- 8.8 years, 55 men]. Platelet MAO-B activity was lower in male than in female smokers (14.1 +/- 7.9 versus 17.8 +/- 7.2 nmol/h/10(9) platelets, p = 0.03). Platelet MAO-B activity correlated positively with age (r = 0.26, p = 0.01) and inversely with plasma cotinine concentration (r = -0.32, p = 0.002) but not with number of cigarettes smoked or with Fagerström Tolerance Questionnaire score. Multiple linear regression analysis showed that 49% of the age-adjusted variance in platelet MAO-B activity (R2 = 0.489, p < 0.0001) was explained by plasma cotinine concentration (p < 0.001) and gender (p = 0.037). It was concluded that platelet MAO-B activity in smokers is inversely associated with plasma cotinine level, an index of smoked tobacco use. Further studies are needed to investigate whether measurement of platelet MAO-B activity can be used as a long-term index of tobacco use and smoke exposure.

Adult↗
PubMed2000

African-American teen smokers: issues to consider for cessation treatment.

Previous reports have indicated ethnic differences in both tobacco-related morbidity and treatment outcome for smoking cessation among adults. We assessed smoking-related characteristics in African-American and non-African American teenagers applying to a cessation trial. 115 teens (15.9 +/- 1.8 years, 68% females, 27% African-American) responded via telephone to media ads. Self-reported sociodemographic, medical and smoking-related data were obtained to determine pre-eligibility for a full intake screen prior to trial participation. Compared to non-African American, African American teen applicants were older (16.4 +/- 1.7 years versus 15.6 +/- 1.6; p = 0.015), had lower Fagerström Test for Nicotine Dependence (FTND) scores (5.3 +/- 2.3 versus 6.1 +/- 1.8; p = 0.018, ANOVA controlling for age) and smoked fewer cigarettes on the weekend (27 +/- 16 versus 38 +/- 17; p = 0.001). African American teens reported similar duration of smoking (3.3 +/- 1.4 versus 3.1 +/- 1.5 years) and time elapsed between first cigarette ever smoked and daily smoking (0.7 +/- 0.9 versus 0.6 +/- 0.7 years). African American and non-African American teens had similar motivation to quit scores and frequency of reported health problems (e.g., asthma, psychiatric conditions). These data suggest that cessation treatment programs designed for African American youth should include lower Fagerstrom-defined levels, and possibly other criteria for tobacco dependence. These observations also highlight the importance of ethnocultural issues in treatment research programs.

Adolescent↗
PubMed1999

Propranolol in hypoglycaemia unawareness.

The effect of propranolol on the occurrence of hypoglycaemic symptoms was assessed in insulin-dependent diabetic patients with hypoglycaemia unawareness. A double-blind, randomised parallel group study (2:1 fashion) was conducted over 4-week period. The propranolol group (n = 9) received 20 mg (week 1 and 2) and 30 mg (week 3 and 4) twice daily, and the other group (n = 5) a matched placebo for 4 weeks. Patients included had experienced at least two severe hypoglycaemic episodes (coma or seizures) during the previous year, which were characterised by a lack of adrenergic symptoms and required the assistance of another person. The mean number of hypoglycaemias during the study period was similar in both groups (placebo: 13 +/- 2 propranolol: 11 +/- 1), whereas the number of totally asymptomatic hypoglycaemias (< 0.6 g/l) was lower on propranolol than on placebo (3 +/- 1 vs 8 +/- 3, NS) and the number of symptomatic hypoglycaemias was higher (7.2 +/- 2 vs 4.6 +/- 1, NS). Subjective evaluation of treatment by the investigators showed 0/5 successes in the placebo group and 5/9 in the propranolol group (chi2 = 4.32, p = 0.038). The main advantage of propranolol over placebo was an increased incidence of sweating. The ratio [number of hypoglycaemias with sweating/total number of hypoglycaemias] being higher with propranolol (0.28 +/- 0.08 vs 0.06 +/- 0.02, p = 0.06). This pilot study suggests that beta-blockers may be useful in restoring adrenergic symptoms during hypoglycaemia in insulin-dependent diabetic patients without warning symptoms of hypoglycaemia. This beneficial effect seems to be predominantly related to an increase in hypoglycaemia-induced sweating. A larger study is needed to confirm or invalidate these preliminary results.

Adrenergic beta-Antagonists↗
PubMed1998

Blunted 5-HT1A-receptor agonist-induced corticotropin and cortisol responses after long-term ipsapirone and fluoxetine administration to healthy subjects.

OBJECTIVES: To assess whether acute 5-hydroxytryptamine-1A (5-HT1A)-receptor-mediated corticotropin, cortisol, and temperature responses are maintained after 3 weeks of treatment with controlled-release (CR) ipsapirone and fluoxetine compared with placebo and whether changes are reversible after cessation of treatment. METHODS: This was a randomized parallel-group study. Ten healthy subjects received ipsapirone CR or fluoxetine, and eight received placebo in a double-blind manner. An ipsapirone challenge test with 20 mg ipsapirone immediate-release formulation (IR) was performed before treatment (day 0) and after 20 days of treatment with placebo, 80 mg/day ipsapirone CR, or 20 mg/day fluoxetine (day 21). From day 22 to day 34 all subjects received placebo in a simple-blind manner. A third ipsapirone challenge test was performed on day 35. RESULTS: Before treatment, resting plasma corticotropin and cortisol concentrations and increases in plasma corticotropin and cortisol concentrations after challenge with 20 mg ipsapirone IR were similar for the three groups. After 20 days of treatment, plasma corticotropin and cortisol concentrations were similar before challenge, but ipsapirone IR-induced increases in plasma corticotropin and cortisol concentrations were significantly lower in both the ipsapirone CR group (corticotropin, 6.5 +/- 2 pg/ml; cortisol, 1.5 +/- 0.7 micrograms/dl) and fluoxetine group (corticotropin 4.4 +/- 2 pg/ml; cortisol 1.5 +/- 0.7 micrograms/dl) compared with placebo (corticotropin, 34 +/- 14 pg/ml; cortisol, 5.8 +/- 2 micrograms/dl, mean +/- SEM). After 2 weeks of placebo administration, plasma corticotropin and cortisol responses to ipsapirone IR again became identical in all three groups. Plasma ipsapirone concentrations were similar in all groups during each challenge. The hypothermic response to ipsapirone IR showed no difference before treatment, at the end of the treatment period, or 2 weeks after cessation of treatment. Long-term administration of antidepressants to the healthy subjects did not lead to any serious adverse effects. CONCLUSIONS: Long-term administration of fluoxetine and ipsapirone did not influence resting plasma corticotropin and cortisol concentrations in the morning. Stimulation of corticotropin and cortisol release by a selective 5-HT1A-agonist is reduced with long-term administration of these serotoninergic antidepressants. This subsensitivity of postsynaptic 5-HT1A-receptors is reversible.

Adrenocorticotropic Hormone↗