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

Seasonal pattern of melatonin excretion in humans: Relationship to daylength variation rate and geomagnetic field fluctuations

In order to investigate the influence of various environmental parameters on melatonin excretion, the night-time urinary melatonin excretion of 16 healthy volunteers was measured in samples collected monthly over a period of one year. No significant interindividual differences were detected in the monthly rate of change of melatonin excretion. A seasonal bimodal pattern did, however, emerge. Peak values were observed in June and November. In these months a combination of high daylength stability and low values of the vertical component of the geomagnetic field was recorded. Trough values were found in April and August-October when low daylength stability was combined with high values of the vertical component of the geomagnetic field. We propose that the daylength variation rate, and the fluctuations of the vertical component of the geomagnetic field, interact to induce the changes in melatonin secretion which signalize the different seasons in humans

The relationship between forgivingness, mental health and psychotherapy

Forgivingness occupies a prominent place in religions as well as in various philosophical systems of ethics and can be defined as the free, personal distancing from feelings of rage and resentment toward a person or persons having committed an injustice. The main psychological function of forgiveness consists in allowing for the replacement of negative emotions by positive ones, such as generosity, goodness, compassion, empathy, or even love toward the offender. It must be emphasized that forgiveness is independent from reconciliation, and it is not simply a form of tolerance, justification, oblivion, underestimation, denial or amnesty. Intrapsychic processes are sufficient and necessary for the genesis of forgiveness, although it is likely that these are also influenced by complex interpersonal events. Current research identifies various dimensions of forgiveness, which must be distinguished from each other, as they differ both on the level of causes, as well as on that of effects. The observation that forgiveness has a positive effect on mental health is not new, it is, however, only recently that comprehensive theories have been constructed and scientific research has been developed regarding the relationship between forgiveness and psychopathology. Over the recent years, there has been an increasing number of studies affirming the beneficial effects of forgiveness on a broad spectrum of aspects of mental health and well-being, despite the lack of complete clarification of underlying mechanisms. The positive connection between forgiveness and mental health could be mediated through direct or indirect mechanisms interacting not only on a biological level, but also in the psychological and social realm of human existence. One direct way could be the avoidance of ruminative thoughts reinforcing and maintaining negative emotions such as resentment, hatred, anger, anxiety and fear. Moreover, forgiveness cultivates empathy and promotes altruistic forms of behavior, facilitating the preservation of relationships and protecting from prolonged distress. An indirect mechanism could involve various forms of health behavior, interpersonal functionality and social supportive networks, factors universally accepted as contributing to mental health. Owing to the positive influence of forgiveness on health issues, various modes of intervention have been proposed and implemented using forgiveness either independently or from within the conceptual framework of specific psychotherapeutic methods. The aim of these interventions is to express negative emotions, to liberate the subject from the vicious circle of rumination, and to overcome resentment in a positive way. Thus, there is an obvious need to further promote forgivingness as a subject of psychological and psychiatric research, and to foreground findings and possible clinical psychotherapeutic applications

Posttraumatic stress disorder in outpatients with depression: Still a missed diagnosis

Comorbidity between major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) is a well-established fact but has been studied little among MDD patients and even less among outpatients. We assessed the prevalence and characteristics of comorbid MDD-PTSD patients in a sample of MDD outpatients in an effort to elucidate possible causes of MDD-PTSD comorbidity. A semistructured clinical interview was applied to 101 outpatients with MDD. Sociodemographic factors, psychiatric history, the presence of PTSD, and MDD-PTSD comorbidity were recorded. The prevalence of MDD-PTSD comorbidity was 38.6%, with 26.7% suffering currently from PTSD. The average duration of PTSD was 16 years, and in most cases (79.5%) PTSD started earlier than or simultaneously with MDD. Only 28.8% of patients with PTSD had a documented diagnosis in their medical record. The most significant factors predicting MDD-PTSD comorbidity were found to be chronic depression, a history of prolonged or repeated trauma, male gender, a younger age at onset of psychological symptoms, lower education, and a lower level of functioning. Our findings indicate that MDD-PTSD comorbidity still remains an overlooked fact. Prolonged trauma seems to be a major risk factor for MDD-PTSD comorbidity, predisposing subjects to PTSD and later on or simultaneously to comorbidity with MDD

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 excreters (N = 8) were distinguished from high melatonin excreters (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

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