Testosterone deficiency and mood in aging men: pathogenic and therapeutic interactions.

In contrast to women, men do not experience a sudden cessation of gonadal function comparable to menopause. However, there is a progressive reduction in hypothalamic-pituitary-gonadal (HPG) function in aging men: testosterone (T) levels decline through both central (pituitary) and peripheral (testicular) mechanisms and there is a loss of the circadian rhythm of T secretion. In cohorts of men 75 years of age, mean plasma T levels are 35% lower than comparable young men, and more than 25% of men over 75 appear to be T-deficient. Such age-associated T deficiency, which has been termed 'andropause', is thought to be responsible for a variety of symptoms experienced by elderly men, such as weakness, fatigue, reduced muscle and bone mass, impaired haematopoiesis, oligospermia, sexual dysfunction, depression, anxiety, irritability, insomnia and memory impairment. However, it has been difficult to establish correlations between these symptoms and plasma T levels. Nevertheless, there is some evidence that T replacement leads to symptom relief, particularly with respect to muscle strength, bone mineral density, and haematopoiesis. Studies to date on the specific association between psychiatric symptoms, such as depressed mood, and T levels have been methodologically flawed. Overall, data suggest that although hypogonadism is not central to major depressive disorder (MDD), HPG hypofunction may have aetiological importance in mild depressive conditions, such as dysthymia.     

Low testosterone levels in elderly men with dysthymic disorder

OBJECTIVE: A decline in hypothalamic-pituitary-gonadal (HPG) axis function is often seen in elderly men, and dysthymic disorder is common. Symptoms of both HPG axis hypofunction and dysthymic disorder include dysphoria, fatigue, and low libido. The authors compared total testosterone levels in three groups of elderly men. METHOD: Total testosterone levels were measured in subjects who met DSM-IV criteria for major depressive disorder (N=13) or dysthymic disorder (N=32) and a comparison group (N=175) who had participated in an epidemiological study of male aging and had scored below the median on the Center for Epidemiologic Studies Depression Scale, a well-validated, self-report depression symptom inventory. RESULTS: There were no differences among the three groups in measured demographic variables, including age and weight. Median testosterone levels varied for those with dysthymic disorder (295 ng/dl), major depressive disorder (425 ng/dl), and no depression (423 ng/dl). A test for differences in central tendency showed a statistically significant difference among the three groups. Post hoc pairwise comparisons revealed statistically significant differences between those with dysthymic disorder and those with major depressive disorder and no depression. CONCLUSIONS: Total testosterone levels were lower in elderly men with dysthymic disorder than in men with major depressive disorder and men without depressive symptoms. Dysthymic disorder in elderly men may be related to HPG axis hypofunction.     

Plasma testosterone levels in patients with combat-related posttraumatic stress disorder

BACKGROUND: An abnormal level of androgens has been reported in various psychiatric disorders and the important role of androgens in the regulation of human sexuality, aggression, cognition, emotions and personality have been described. Previous studies in the area of stress and the hypothalamic-pituitary-gonadal (HPG) system in humans indicate that circulating testosterone levels are suppressed by physical and psychological stress. However, there is also evidence that plasma levels of testosterone can increase during potentially stressful events and may be elevated in combat-related posttraumatic stress disorder (CR-PTSD) in comparison with normal subjects and major depressive disorder patients. METHODS: The aim of the present study was to examine the possible involvement of the HPG system in chronic untreated CR-PTSD. To this end, we assessed the morning plasma levels of testosterone and cortisol in never-treated chronic CR-PTSD outpatients compared with normal healthy controls. RESULTS: There were no statistically significant differences between the CR-PTSD patients and healthy control subjects in morning plasma testosterone (547.8 +/- 152.2 ng/dl vs. 565.6 +/- 122.4 ng/dl; p = 0.7) and cortisol (19.0 +/- 8.5 microg/dl vs. 15.4 +/- 5.1 microg/dl; p = 0.1) levels. However, a significant correlation between plasma testosterone level and avoidance symptom scores of the Impact of Events Scale (IES) was found in the CR-PTSD patients (r = 0.43, p < 0.05). CONCLUSIONS: The findings of plasma testosterone levels comparable with normal controls in CR-PTSD patients may indicate that the previously described reduction in testosterone levels in normal subjects under stressful conditions may reflect the acute stress response of the HPG axis, in contrast to an adaptation of the HPG axis under chronic psychological stress.     

Suicide attempt by jumping: A study of gonadal axis hormones in male suicide attempters versus men who fell by accident

Low plasma total testosterone (T) levels may influence the sense of well-being and produce depressive symptomatology, increasing the risk of suicide. In a previous study, we reported reduced serum T levels in male psychiatric patients after a suicide attempt. The reduction was more pronounced in subjects who used violent attempt methods, and we discussed the possible influence of stress of hospitalization, serious medical condition and treatment. In order to minimize the influence of such factors, we compared in this study the levels of plasma sex hormones of 15 psychiatric patients (10 suffering from schizophrenia and 5 from depression) who had attempted suicide by jumping with those of a group of 18 male subjects who were hospitalized after accidentally falling from a high height. Compared with a healthy control group of 40 males, both accident and attempt groups had lower T levels. The attempt group showed a trend toward lower T levels compared with levels in the accident group. In the accident group, luteinizing hormone (LH) levels were elevated compared with levels in healthy controls, indicating a normal function of the hypothalamic-pituitary-gonadal (HPG) axis. This was not the case for the attempt group, where low T levels were not accompanied by increases in LH. Cortisol and prolactin were similarly elevated in both patient groups, but were not related to the low T levels. The results indicate that male psychiatric patients who attempt suicide by violent methods may have low total plasma T levels, possibly due to a dysfunction of the HPG axis at the hypothalamic-pituitary level. Monitoring HPG axis function in future studies could prove to be a predictor of suicide at least for male psychiatric attempters, and could lead to preventive strategies.     

Total testosterone, androgen receptor polymorphism, and depressive symptoms in young black and white men: the CARDIA Male Hormone Study

Androgen receptor (AR) CAG repeat length (RL) might modify the relationship between endogenous testosterone (T) and depressive symptoms in men on average over age 50 years. We hypothesized that CAG RL modifies the association between T and depressive symptoms in 525 black and 721 white men under age 40 years participating in the CARDIA Male Hormone Study. We assessed cross-sectional associations of quartiles of total and bioavailable T and tertiles of CAG RL with depressive symptoms, defined as Center for Epidemiologic Studies Depression Scale (CES-D) score > or=16, in 1995-1996. The interaction of CAG RL and total T on depressive symptoms was statistically significant for blacks, whites, and both groups combined. In the combined analysis, the odds ratios (OR) (95% confidence intervals (CI)) across the quartiles of total T were 1.00, 0.17 (95% CI=0.07-0.43), 0.31 (95% CI=0.14-0.70), and 0.49 (95% CI=0.22-1.09) for the shortest RL group. The interaction of CAG RL and bioavailable T on depressive symptoms was statistically significant for black men only, and nonsignificant in a combined analysis. For black men in the shortest RL group, the ORs for the quartiles of bioavailable T were 1.00, 0.41 (95% CI=0.16-1.05), 0.10 (95% CI=0.03-0.38), and 0.35 (95% CI=0.14-0.90). In other CAG groups, there were no relationships of total or bioavailable T with depressive symptoms. CAG RL might modify the association between endogenous total and bioavailable T and depressive symptoms in younger black men. Clinical trials assessing the effects of T replacement therapy on depressive symptoms in hypogonadal men should consider including CAG RL in their design and/or analysis.     

Depressive symptoms may explain elevated plasma levels of homocysteine in females with eating disorders

Elevated plasma homocysteine levels have been found in different psychiatric disorders, including major depression and eating disorders. The aim of the present study was to evaluate whether presence of depression or depressive symptoms is associated with elevated homocysteine levels in patients with eating disorders. Total plasma homocysteine levels were assessed in 44 females with anorexia nervosa (n = 21) or bulimia nervosa (n = 23). Comorbid major depressive disorder (MDD) was diagnosed according to DSM-IV criteria using a semi-structured interview (SCID-I). Furthermore, depressive symptoms were assessed using Beck's depression inventory (BDI). Presence of MDD was not associated with elevated homocysteine levels (t-test: T = 0.42; df = 42; P = 0.68). However, self-rated presence of clinically relevant depressive symptoms (BDI score18) was associated with elevated homocysteine (T = -2.8; df = 42; P = 0.008). Presence of depressive symptoms may explain elevated homocysteine levels previously reported in patients with eating disorders or vice versa. Longitudinal studies are needed to unravel this hen or egg problem.     

Body mass index, waist circumference, waist-hip ratio and depressive symptoms in Chinese elderly: a population-based study

BACKGROUND: Studies that investigated the relationship between obesity and depressive symptoms in the elderly have generated conflicting findings, partly because of the use of body mass index (BMI) alone to measure obesity in the elderly. The use of BMI fails to account for varying proportions of muscle, fat and bone, and few studies have used other measures of central obesity, such as waist-hip ratio (WHR) and waist circumference (WC). OBJECTIVES: We examined whether individually BMI, WHR and WC were consistently associated with depressive symptoms in the elderly. METHODS: Analysis of cross-sectional data of 2604 community dwelling Chinese elderly aged 55 and above, including socio-emotional characteristics, self-rated health and functional status, anthropometric measurements and Geriatric Depression Scale (15 items, GDS-15). RESULTS: There was a negative trend in the prevalence of depressive symptoms (GDS > or =5) across increasing BMI categories: 16.9% in low BMI, 14.2% in normal weight, 12.1% in moderate to high BMI. The associations for moderate to high BMI (OR, 0.77; p = 0.04) relative to normal BMI, were statistically significant after controlling for confounding variables. However, no consistent trends in the prevalence of depressive symptoms and OR's were observed for increasing WHR and WC categories. CONCLUSION: Our results suggest that waist-hip and circumference measures of central obesity did not support an inverse relationship of obesity and depressive symptoms. An inverse relationship of BMI with depressive symptoms may indicate greater physiologic and functional reserve from greater muscle mass that protects against depressive symptoms.     

Plasma interleukin-6 is associated with psychological coronary risk factors: moderation by use of multivitamin supplements

The current study examined the relation of plasma IL-6 to anger, hostility, and severity of depressive symptoms as a function of multivitamin supplement use in 96 healthy, nonsmoking men (aged 18-46). Plasma IL-6 was independently associated with anger, hostility, and severity of depressive symptoms, as well as with a composite factor score, but only among nonusers. Among users, these associations were not significant. Multivitamin use was associated with lower plasma IL-6 levels, but only among men with high composite factor scores. Statistical adjustments for age, body mass index, resting diastolic blood pressure, fasting total cholesterol, high-density lipoprotein cholesterol, alcohol use, exercise frequency, and educational level did not alter these results. These data suggest that plasma IL-6 is elevated among healthy men characterized by a propensity for anger, a hostile disposition, and greater severity of depressive symptoms and that multivitamin supplements could ameliorate plasma IL-6 levels among these men.     

Lower TSH and higher T4 levels are associated with current depressive syndrome in young adults

OBJECTIVE: The relationship of individual thyroid function indices to depression in those without a history of prior thyroid dysfunction is uncertain. METHOD: We examined the relationship between thyroid-stimulating hormone (TSH) and thyroxine (T4) levels and current or lifetime history of depressive symptoms using information from 6869 participants, aged 17-39 years, in the Third National Health and Nutrition Examination Survey without history of thyroid-related illness. RESULTS: We found that lower TSH and higher T4 levels were associated with current depressive syndrome in men, but only higher T4 levels correlated with current depressive syndrome in women. Lifetime depressive syndrome was associated with neither TSH level nor T4 levels in men or women. CONCLUSION: These findings suggest that transient or 'state dependent' changes are associated with depression in those without a history of thyroid illness. Further studies to discern whether these depression-associated changes represent distinct endophenotypes of depression should be encouraged.     

Depressive symptoms and bone mineral density in older men

Most studies examining the relation between depression and bone mineral density (BMD) have been limited to psychiatric patients or to community-dwelling, older women. We conducted a cross-sectional and prospective cohort study to determine whether depressive symptoms are associated with low BMD in community-dwelling, older men. We recruited 515 men 50 years of age or older from population-based listings of age-eligible men. Participants completed the Geriatric Depression Scale (short form) and were considered depressed if they scored 6 or more out of 15 possible points. BMD was measured in the spine and hip using dual energy x-ray absorptiometry in all participants, and again an average of 3.6 years later in a random subset of 100 participants. The prevalence of depressive symptoms (GDS = 6) was 3.1% (16 of 515). We found no difference in mean BMD or mean percent change in BMD per year of the hip and lumbar spine in men who had 6 or more depressive symptoms compared with men who reported 5 or fewer symptoms of depression. These findings suggest that depressive symptoms are not associated with BMD in community-dwelling, older men.     

Associations between sex steroid hormone levels and depressive symptoms in elderly men and women: results from the Health ABC study

INTRODUCTION: Sex steroid hormone levels decline with age and in some studies this decline has been linked with depressive symptoms. This study investigates the association between total testosterone, free testosterone, and DHEAS levels with depressive symptoms in a well-functioning elderly population. METHODS: Data are from 2855 well-functioning elderly men and women, 70-79 years of age, participating in the Health, Aging, and Body Composition study. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression scale. Total testosterone, free testosterone, and DHEAS levels were assessed after an overnight fast. RESULTS: In men and women, DHEAS levels and depressive symptoms were inversely associated after adjustment for covariates (men: beta=-0.059, p=0.03, women: beta=-0.054, p=0.05). In addition, free testosterone levels in women, but not in men, were inversely associated with depressive symptoms (adjusted beta=-0.079, p=0.004). Men, but not women, in the lowest total testosterone quartile reported significantly more depressive symptoms than men in the other total testosterone quartiles (adjusted beta=-0.166, p=0.04). DISCUSSION: Our study is consistent with the idea that testosterone and DHEAS levels may play a role in mechanisms underlying depressive symptoms in old age.     

Pituitary volume mediates the relationship between pubertal timing and depressive symptoms during adolescence

Early timing of puberty (i.e., advanced pubertal maturation relative to peers) has been linked to the onset of depressive symptoms during the early adolescent phase. However, the precise neurobiological mechanisms linking early pubertal timing to adolescent depressive symptoms are not clear. We investigated whether the volume of the pituitary gland, a key component of the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-adrenal (HPA) axes, mediated the relationship between pubertal timing and depressive symptoms in 155 adolescents (72 females) both cross-sectionally and longitudinally. At baseline (M age 12.7, SD 0.5 years), early pubertal timing predicted larger pituitary gland volume and higher depressive symptoms (especially for girls), but there was no mediation effect. Longitudinally, however, larger pituitary gland volume at baseline was found to mediate the relationship between early pubertal timing and increased depressive symptoms over time (M follow-up period=2.57 years, SD=0.26) for both boys and girls. Our findings suggest that neurobiological mechanisms are partly responsible for the link between early pubertal timing and depressive symptoms in adolescents. We speculate that an enlarged pituitary gland in adolescents with early pubertal timing might be associated with hyperactivation of the hormonal stress response, leading to increased susceptibility to environmental stressors, and subsequent development of depressive symptoms. Given the well-established relationship between increasing depressive symptoms in adolescence and later disorder, these findings have implications for targeted prevention and early intervention strategies for depressive disorders in adolescence.     

Neuroendocrine aspects of primary endogenous depression VIII. Pituitary-gonadal axis activity in male patients and matched control subjects

To determine the extent of hypothalamo-pituitary-gonadal (HPG) axis dysfunction in endogenous depressed men, we measured nocturnal and diurnal serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), and estradiol (E2) concentrations, and their responses to gonadotropin releasing hormone (LHRH) and dexamethasone administration, in 16 Research Diagnostic Criteria primary, definite endogenous male depressives and 16 individually matched male normal controls. Compared to their controls, the patients showed no differences in basal nocturnal or diurnal gonadotropin or gonadal steroid hormone concentrations, and no differences in hormone concentrations either post-LHRH or post-dexamethasone. Age was negatively correlated with baseline serum T in the patients but not in the controls, and it was modestly positively correlated with baseline serum LH in both groups of subjects. In the patients, the presence of DSM-III melancholia was modestly negatively correlated with baseline and post-LHRH concentrations of both LH and FSH and was positively correlated with baseline serum T, but it bore no relation to serum E2. None of the other subject characteristics or specific dimensions of depressive symptomatology were significantly related to the HPG axis measures. The HPG axis measures also were unrelated to pre- and post-dexamethasone cortisol concentrations in both groups of subjects. The results of this study suggest that, in contrast to the hypothalamo-pituitary-adrenal cortical and thyroid axis abnormalities frequently found in endogenous depressives, HPG axis function in male depressives is relatively normal.     

Sociodemographic and Personal Factors Related to Depressive Symptomatology in the Mexican Population Aged 12 to 65

Objective: To describe the prevalence of depressive symptoms in the Mexican population, aged 12 to 65 years, by identifying the main related socio-demographic and personal factors. Methods: Data are drawn from the National Survey on Addictions 2008 (ENA 2008), a random, probabilistic, multistage study. A randomly selected sub-sample of 22,962 persons answered the section on depressive symptomatology, measured with the Center for Epidemiologic Studies Depression Scale (CES-D). Results: The total prevalence for depressive symptomatology was 5.1%; the prevalence was 7.5% for women and 2.5% for men. For women, more evidence of depressive symptoms was seen in the central region, whereas for men, symptoms were homogeneous across the country. Factors related to the presence of depressive symptoms include being divorced (in women) or widowed (in men), having lower educational attainment, perceiving one's place of residence as unsafe, displaying alcohol abuse or dependence, being a regular drug consumer (in men) and having been sexually abused (males and females). Conclusions: The regional distribution of depressive symptomatology in women indicates the need for region-specific prevention programs that take into account the different social problems that affect women's emotional well-being. More research is also needed to support the early identification and intervention of men suffering from depression.     

Plasma adiponectin elevation in elderly individuals with subsyndromal depression

Adiponectin, one of the adipokines, has believed to play a role in developing of depression, but the relationship between plasma adiponectin and depressive disorder is still unclear. To investigate the association between plasma adiponectin and depressive disorders, we measured plasma adiponectin concentrations in 785 randomly sampled elderly Koreans including 41 patients with major depressive disorder (MDD), 46 with minor depressive disorder (MnDD), and 61 with subsyndromal depression (SSD). Plasma adiponectin levels were different among the diagnostic groups (df=3, F=4.928, P=0.002). The plasma adiponectin level in the SSD patients was higher than in the non-depressed controls (NC) (12.48 ± 8.38 μg/ml versus 9.27 ± 6.21 μg/ml, P=0.001, Tukey's post hoc comparison). However, plasma adiponectin levels in the MnDD and MDD patients were comparable with those found in the NC (P>0.1, Tukey's post hoc comparison). The elevation of plasma adiponectin in the SSD patients remained significant in men (P=0.002, Tukey's post hoc comparison) but not in women. In the subjects without MDD and MnDD, plasma adiponectin level was positively correlated with the Hamilton Depression Rating Scale score (r=0.156, P<0.001) and the Geriatric Depression Scale (r=0.117, P=0.002). When men and women were analyzed separately, these significant correlations were confined to men. Circulating adiponectin concentration may play a role in compensation on process for depressive mood.     

Plasma testosterone in male patients with Huntington's disease: relations to severity of illness and dementia

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms and by a progressive loss among other, of dopaminergic receptors in striatum, cortex, and hypothalamus. Central dopaminergic activity has been implicated in the regulation of sex hormones. Several features of testosterone deficiency, such as reduced muscle mass, depressive mood, and cognitive impairment, are often present in HD patients, but data on their testosterone levels are lacking. We assessed plasma levels of testosterone, LH, and FSH in 42 male patients with HD, confirmed by molecular genetic analysis, and searched for differences from age-matched healthy male subjects and for relations to CAG repeat number, age, age range, 26 to 76 (mean, 50.7 +/- 12.3) years; duration of illness range, 1 to 23 (mean, 6.7 +/- 6.3) years; and CAG repeat numbers from 40 to 65 (45.1 +/- 3.8). Disease symptomatology was assessed using the Unified Huntington's Disease Rating Scale. Testosterone and LH levels of the patients were significantly lower compared to the levels of 44 age-matched (mean age, 48.9 +/- 13.0, range, 26-76 years) healthy men. Severity of illness was negatively related to plasma testosterone levels. Further, low testosterone levels were associated with dementia but not with depression or psychotic features. Clinical studies with selected HD patients are needed to evaluate possible beneficial effects of androgen substitution therapy on cognitive functions, depression, muscle mass and strength, general well-being, and, eventually, neuroprotective effects.     

Safety and efficacy of testosterone gel 1% augmentation in depressed men with partial response to antidepressant therapy

The current study evaluates the efficacy and safety of testosterone (T) gel 1% augmentation on depressive symptoms and quality of life in treatment-resistant, depressed, hypogonadal men older than 50 years of age who are receiving antidepressants. The authors hypothesized that T augmentation would improve depressive symptoms and quality of life. Eighteen hypogonadal men entered the study who had had an adequate trial of antidepressant therapy and had significant depressive symptoms. Participants were continued on their antidepressant and were randomized to receive either placebo or active T gel (5 g) to be applied once a day. Participants were tested on 6 occasions: screening visit, an initial session (pretreatment), at 6 and 12 weeks during the first treatment condition, and at 18 and 24 weeks during the crossover condition. The authors found a significant improvement in depressive symptoms from baseline to 12 weeks of testosterone treatment. However, a statistical difference between placebo and testosterone treatment phases was not demonstrated. The limitations of the study, including the chronicity and severity of patients' depression, variability in T levels, and a small sample size, probably influenced the ability to detect a discernable difference. Nevertheless, the study shows that T gel augmentation may be helpful in hypogonadal males with depression.     

Luteinizing hormone levels are positively correlated with plasma amyloid-beta protein levels in elderly men

Dysregulation of the hypothalamic pituitary gonadal (HPG) axis during aging has been associated with increased risk of cognitive decline and developing dementia. Compared to controls, men with Alzheimer's disease (AD) have been shown to have lower serum testosterone levels and higher serum luteinizing hormone (LH) levels. As serum free testosterone concentration is negatively correlated with LH in older men, the independent contributions of these hormones to the pathogenesis of AD warrants further clarification. To explore this notion, we measured plasma amyloid-beta (Abeta), serum testosterone, serum LH and other biochemical parameters in 40 cognitively normal elderly men. Multiple linear regression analysis revealed that serum LH concentration is the only parameter that significantly correlates with plasma Abeta levels in these men (r=0.5, p=0.041). These results suggest that increased serum LH concentration, rather than lower serum free testosterone, is associated with the accumulation of Abeta in plasma. Larger, longitudinal human studies are needed to determine the significance of LH in the pathogenesis of AD.     

The influence of depressive symptomatology and perceived stress on plasma and salivary oxytocin before, during and after a support enhancement intervention

Oxytocin (OT) activity increases in response to stress as well as to warm social contact. Subclinical depression is associated with higher stress but less reward from social contacts. The present investigation was intended to examine whether husbands and wives with high depressive symptomatology scores have increased plasma and salivary OT that may be mediated partly by higher perceived stress, and also to assess whether an intervention to convey partner support through "warm touch" may reduce effects of depressive symptoms on OT. In this study, 34 healthy married couples (n=68) ages 20-39 provided self reports of depressive symptoms (CESD) and stress (Perceived Stress Scale) before being randomly assigned to a 4-week intervention study enhancing partner support through "warm touch", or to a "behavior monitoring" control group. Plasma oxytocin levels were obtained pre- and post-intervention, while salivary oxytocin was taken at home during week 1 and week 4. Results revealed that subjects with higher depressive symptoms scores had higher plasma OT levels at pre-intervention, and higher salivary OT levels at home during week 1 (p<.05). Plasma OT results were moderated by gender such that plasma OT levels were highest among females high in depressive symptomology. Higher perceived stress was also linked to both higher depressive symptomatology (r=+65, p<.0001) and plasma OT (p< .05) and a significant mediator. During the intervention, salivary OT remained elevated among subjects high in depressive symptomatology in the control group but not the intervention group. At post-intervention, plasma OT levels in subjects with vs. without depressive symptomatology no longer differed. Results indicate that subclinical depression is associated with elevated plasma and salivary OT levels, which may be mediated in part by increased stress. OT differences linked to subclinical depression were minimized by the warm touch intervention.     

Parasuicide and psychotropic medication: Clinical data and drugs used for overdose in 202 parasuicides

We have earlier reported on medications used for overdose in 812 consecutive parasuicides. Different studies have found some kind of depression in 30–80% of parasuicides. Therefore, we then interpreted our finding that only 5% used antidepressants for overdoses as a possible indicator of underprescribing of these drugs in suicidal patients. In this study based on an extensive interview of 202 hospitalized parasuicides (69% psychiatric in-patients), we found that women used antidepressants and anxiolytics relatively more frequently for overdose (11% and 21%) than did men (3% and 8%), younger persons used more frequently analgesics (25%), and elderly more frequently hypnotics (75% in men above 75 years of age, and 57% in women above 75). Interestingly, those who took antidepressants in overdose reported lower suicide intent, while those who took anxiolytics reported more depressive symptoms. It is concluded that depressive syndromes frequently includes symptoms of anxiety and that such patients should be treated with antidepressants and not with anxiolytics alone.