[Pharmacokinetic and pharmacodynamic effects of psychotropic medications: Differences between sexes].

The gender based or gender sensitive pharmacology is a new research area. Differences among sexes are observed in several parameters of their pharmacokinetic which may relate to alteration of their pharmacodynamic as well. Most psychotropics are given per os, and the greater part of their absorption takes place in the small intestine. Premenopausal women have slower gastric emptying times and lower gastrointestinal blood flow which probably reduces the extent of drug absorption. The distribution of drugs is influenced by the relative lower body mass index, the lower blood volume and flow and the greater percentage of body fat of women. Further, the elimination and renal clearance is reduced in women and the hepatic metabolism differ between sexes. Besides, women differ from men in physiological conditions which may have an impact on the psychotropic medication and dosage required for efficacy and response. Women are exposed to monthly hormonal fluctuations (menstruation), pregnancy, puerperium, menopause and use of contraceptives or synthetic hormonal replacement therapies. Throughout of these conditions changes may occur in total body water, in renal clearance, cardiovascular and autoimmune system, which may cause fluctuations in the activity of the psychotropics, changes in the central neurotransmitters, in the number and sensitivity of the receptors, and the general metabolism as well. Despite the fact that women are the primer consumers of psychotropic medication, taking more psychotropics as well as more multiple medications than men, little attention has been paid to sex differences in psychopharmacology. Till recently women were under-represented or excluded from most of the pharmacological clinical trials. The treatment guidelines for psychotropic medication are based on studies verified and investigated almost exclusively in men. Results from such studies were generalized and recommended for use in the clinical practice without any critique and justification between the sexes. In conclusion, women compared to men, tend to have a greater bioavailability and slower elimination of drugs leading to higher concentrations of free circulating drugs in serum and causing more side effects and adverse reactions to the psychotropic medication than men do. In general, women require lower doses of antidepressants, antipsychotics and benzodiazepines than men. For safety and efficacy reasons and despite the fact that research is still being carried out to determine the exact differences in pharmacodynamic of several psychotropics between genders, the clinician must be aware of the reported effect of the recommended medications on serum levels and organ tissues both for men and women.

Religiosity dimensions and subjective health status in Greek students.

The quest for existential meaning constitutes a universal phenomenon traditionally manifested in official religions (religiosity) or personal modes of transcendence (spirituality). Religiosity and spirituality have been found to be associated with a variety of mental health and illness parameters. In the last decades there is an increasing number of publications with interesting results on the relationship between religiosity and mental health, both on a theoretical and a clinical level. Recent research suggests the presence of clinically important interactions between religious beliefs and mental health, although the exact nature of the associations remains unclear. The aim of the present study is to investigate subjective health status in relation to specific dimensions of religiosity and spirituality in Greek students; 202 students of the faculty of Theology of the University of Athens were interviewed using the Brief Multidimensional Measurement of Religiousness/Spirituality (BMMRS), which assesses the dimensions of "daily spiritual experiences", "meaning", "values/beliefs", "forgiveness", "private religious practices", "religious/spiritual coping", "religious support", "religious/ spiritual history", "commitment", "organizational religiousness", and "religious preferences". Subjective health status was measured by the General Health Questionnaire (GHQ-28) which examines four areas of health in the following sub-scales: (a) somatic symptoms, (b) anxiety and insomnia, (c) social dysfunction and (d) severe depression. Pearson correlations coefficients and linear regression analyses were used to estimate the associations of GHQ-28 subscales with religiosity dimensions. High scores in each dimension of BMMRS corresponded to a low level of religiosity. The dimension of "daily spiritual experiences" was positively correlated with the subscales of anxiety/ insomnia, social dysfunction and severe depression, while the dimension of "values/beliefs" with social dysfunction and severe depression and the dimension of "forgiveness" with all GHQ-28 subscales. The "organizational religiousness" dimension was positively correlated with anxiety/ insomnia, while overall self-ranking with social dysfunction and severe depression. Additionally, the dimension of "meaning" had a negative correlation with somatic symptoms. Moreover, in the multiple linear regression analyses, "meaning" was independently negative associated with somatic symptoms (p=0.032), whilst "daily spiritual experiences" were positively associated with anxiety/insomnia (p=0.023). Also, "values/beliefs and the overall self-ranking were positively associated with social dysfunction (p=0.026), (p=0.01) and "daily spiritual experiences", "values/beliefs", "forgiveness", as well as the overall self-ranking with severe depression (p=0.03), (p=0.01), (p=0.017), (p=0.009). Certain religiosity dimensions ("daily spiritual experiences", "values/beliefs", "forgiveness" and "organizational religiousness") were correlated with lower morbidity, in accordance to previous reports in different populations, whereas "meaning" was correlated with more somatic symptoms.

Myocarditis after administration of clozapine.

OBJECTIVE: Clozapine is an atypical antpsychotic medication with established efficacy in patients diagnosed of resistant schizophrenia. However, clozapine has multiple side effects. Cardiac complications such as myocarditis and cardiomyopathy have always been related with treatment with clozapine. METHODS: A 42 year old Caucasian male, with history of schizophrenia developed a acute myocarditis after commencement of clozapine. RESULTS: The patient recovered with intensive medical support. The symptoms occurred approximately 20 days after starting clozapine. CONCLUSIONS: Myocarditis is an ingreasingly recognized complication associated with clozapine. Use of clozapine must be based on a balance of its risks and benefits on an individual basis which for the most part defines its use in treatment refractory schizophrenia. Appropriate monitoring of adverse events is an essential part of the clinical usage of clozapine and should be charted for at least two years.

Protracted acute stress reaction following an earthquake.

OBJECTIVE: To verify the official criteria of ICD-10 diagnosis of acute stress reaction (ASR) among earthquake victims. METHOD: Data on psychosocial variables and the diagnosis of ASR were collected from 91 subjects. RESULTS: The diagnosis of ASR was made in 70% of the sample. However, the restrictive duration criterion (i.e. symptoms not exceeding the first 48 h) was fulfilled only in 10%; in the remaining 60% the symptoms lasted for about another week. Thus, 60% of the sample constituted a group with protracted ASR (PASR) and 40% a group without it (n-PASR). Medical history was more frequent among PASR than n-PASR; PASR showed higher anxiety levels (both pre- and post-disaster) than n-PASR; finally, the persistence of ASR related positively to the fear of death at the time of the earthquake and pre-disaster anxiety levels. CONCLUSION: As in the vast majority of earthquake victims the ASR is protracted beyond 48 h, a revision of ICD-10 guidelines should be considered.

Melatonin response to clonidine administration in depression: indication of presynaptic alpha2-adrenoceptor dysfunction.

BACKGROUND: The aim of this study was to investigate alpha2-adrenoceptor sensitivity in depression, by using melatonin response to clonidine administration as an index of alpha2-adrenoceptor functioning. METHOD: 35 depressed subjects and 41 healthy controls were assessed for overnight urinary melatonin pre- and post-administration of oral clonidine. RESULTS: Administration of clonidine significantly reduced melatonin concentrations in depressed patients but not in control subjects. LIMITATION: A single oral dose (0.15 mg) of clonidine was administered. CONCLUSIONS: Further indication is provided for presynaptic alpha2-adrenoceptor dysfunction in depression with the application of an alternative pharmacological challenge method.

Relapse prevention in schizophrenia: attitudes of neurologists-psychiatrists.

The overall high relapse rates observed in schizophrenia are attributed to several causes. One important factor influencing satisfactory prevention of relapse is the lack of consistent treatment strategies among medical doctors, especially neurologists-psychiatrists. Nearly one-third of the members of the Hellenic Society of Neurology and Psychiatry were asked to fill in anonymously a structured questionnaire on their treatment attitudes and prescribing tactics regarding schizophrenic patients both after the first schizophrenic episode and after multiple episodes. The majority of Greek neurologists-psychiatrists seem to adopt prescribing habits that approximate the current international standards for prevention of schizophrenic relapse. Their attitudes regarding the treatment and prevention of relapse for the first schizophrenic episode and first relapse are determined from multiple factors. These are: the expected relapse rates after the first episode, the expected prevalence of extrapyramidal side effects following a long-term neuroleptic treatment, the patient's expected treatment compliance after the first episode, the doctor's experience with treating schizophrenics, and lastly the knowledge of current literature on the topic. These results point to the need for continuing education, especially of the younger mental health professionals and those working in the private sector, addressing the issue of the actual risk of developing side effects from the treatment. In due course, benefits could result for everyday psychiatric practice and the patients' compliance with treatment.

Sleep spindle incidence dynamics: a pilot study based on a Markovian analysis.

Results are reported, based on 5 healthy subjects, concerning patterns in the dynamics of the sequential arrangement of spindles in human stage 2 sleep. Specifically, the conditional probability of incidence of successive spindle lengths and successive inter-spindle intervals is investigated. The results show that successive spindle lengths may be statistically independent. However, their distribution (histogram) may be similar for two different stage 2 periods, one in the first third and another in the second third of the night sleep record. In contrast to the finding about spindle lengths, results show that successive inter-spindle intervals may not be statistically independent. Furthermore, the overall dynamics of the sequential arrangement of inter-spindle intervals may be similar for the two sleep periods. These findings are discussed in the context of the "sleep maintenance" role of spindles.

Normative melatonin excretion: a multinational study.

The present study on overnight urinary melatonin was conducted on the most geographically dispersed population to date, over a 1 year period, also covering a broad age range (18-62 years). An inverse relationship between melatonin and age, as well as between melatonin and weight was observed for both genders. Females as a whole, had higher melatonin values than males. Furthermore, the excretion of melatonin exhibited a bimodal distribution, distinguishing two groups of individuals: low and high melatonin excretors. The cut-off point was set at 0.25 nmol/l for ages up to 40 years and at 0.20 nmol/l for subjects above this age. Since melatonin may be involved in several physiological and pathological processes, it could be of importance to detect the type of melatonin excretion that prevails in various conditions, using a simple noninvasive procedure such as the overnight urinary measurement. For that purpose, this large sample could serve as a worldwide reference databank across different ages and locations.

Growth hormone secretion during sleep in male depressed patients.

1. Growth hormone (GH) secretion during sleep was studied in ten male patients with major depression according to DSM III and eight normal controls. 2. Samples were collected through a continuous blood withdrawal pump while sleep was recorded in the laboratory. 3. The results showed a marked decrease in the GH secretion mainly during the first three hours of sleep in depressed patients as compared to normal controls. DST and TRH tests were also administered to the same patients but no correlation was observed between a positive test and a blunted GH secretion, suggesting that the various neuroendocrinological disturbances do not coexist in all depressed patients. 4. This disturbance in GH secretion during sleep, along with reduced slow wave sleep (SWS), gives support to the theory that GHRH is the common stimulus of SWS and GH release and that the ratio of GHRH and its counterpart CRH plays a major role in the pathophysiology of disturbed endocrine activity during sleep in depression.

Low and high melatonin excretors among healthy individuals.

To meet the need of establishing firm normative data regarding the secretion/excretion of human melatonin, nighttime urinary melatonin of 16 healthy volunteers was measured in samples collected monthly over a period of 1 year. Low melatonin excretors (N = 8) were distinguished from high melatonin excretors (N = 8), based on a cut-off mean melatonin value of 0.25 nmol/l. There was no overlap in any of the monthly melatonin values between the two groups, while their annual rhythms of melatonin excretion were not different in shape. Since no obvious factors (age, sex, height, weight, etc.) were responsible for the observed differences, the distinction between low and high nocturnal excretion and by inference secretion of melatonin most likely reflects genetically determined variable levels of the noradrenergic secretory drive and/or variable N-acetyltransferase/hydroxyindole-O-methyltransferase enzymatic activity during the night.

An experimental antidepressant increases REM sleep.

1. An experimental antidepressant was studied through sleep laboratory recordings, psychoendocrinological tests and clinical measurements in terms of its efficacy, side effects and effects on sleep. 2. The design included a four-week drug administration period, preceeded and followed by a one week placebo period. 3. In the presence of antidepressant efficacy, the drug did not disturb sleep induction and maintainance. 4. The only effect on sleep stages was an increase of REM sleep during the short-term drug administration period which is contrary to the REM supressant effect of most antidepressants. 5. This finding suggests that REM supression and antidepressant efficacy are not necessarily related. 6. Further, given that the only known action of the drug is its inhibitory effect on GABAergic transmission, one can speculate that GABA mechanisms may be involved in REM sleep modulation.

Behavioral side effects of triazolam in psychiatric inpatients: report of five cases.

Triazolam was administered to five psychiatric inpatients for a two-week period. This period was preceded by a one-week placebo baseline and followed by another week of placebo administration. All conditions were double blind. By the second week of active drug administration, psychopathology greatly intensified across all of the patients with the emergence of anxiety, memory impairment, confusion, paranoid ideation, and hallucinations. The drug-induced behavioral changes persisted during the initial withdrawal period, but then gradually subsided. Also following drug withdrawal, four patients showed a marked worsening of their sleeplessness for several nights.