Erectile dysfunction (ED) is commonly associated with depressed mood and diminished quality of life (QoL), but few studies have investigated the causal associations involved. Therefore, we evaluated the correlation between several measures of mood, QoL, and sexual function in a retrospective analysis of a sample of depressed men (n=152), with ED enrolled in a clinical trial of sildenafil citrate (VIAGRA®). Strong correlations were observed at baseline among measures of erectile function (EF), mood, and overall QoL. Significant treatment effects were observed on all three domains, with significant interactions between changes in mood and QoL. Based on multiple regression and path analysis, a model was developed in which EF changes were associated with improved mood and quality of sexual life, which resulted in improved partner satisfaction, family life, and overall life satisfaction. These data suggest that QoL changes associated with ED therapy may be mediated by changes in sexual function, mood, and family relationships.

The International Consensus Group on Depression and Anxiety held the meeting “Focus on Depression and Anxiety Disorders in General Medicine,” October 7–8, 1999, in Funchal, Madeira. The Consensus Meeting was supported by an unrestricted educational grant from SmithKline Beecham Pharmaceuticals. Reprint requests to: James C. Ballenger, M.D., Medical University of South Carolina, Department of Psychiatry and Behavioral Sciences, 171 Ashley Ave., Charleston, SC 294250742. severe depression develop more severe cardiovascular disease, but there are data showing that patients with more severe anxiety develop more severe cardiovascular disease. In a large study of male health care professionals, Kawachi et al. showed an association between panic phobic symptoms and an excess risk of sudden cardiovascular death. Anxiety disorders, such as panic disorder and phobic disorder, often start early in life and develop chronically. They frequently lead to secondary depression and are a risk factor for the development of cardiovascular disease and for later sudden cardiac death. The presence of an anxiety disorder can bring people into a high-risk group at an earlier age in their life. Depression is not only a risk factor for cardiovascular disease but is also a strong predictor of mortality in patients with manifest ischemic heart disease. Among survivors of acute myocardial infarction, the increased risk of cardiovascular mortality is not restricted to patients with major depression but also extends to those patients with subsyndromal depressive symptoms. At 18 months after myocardial infarction, the mortality rate is reported to be the same in depressed patients who failed to meet full criteria for major depression as in those meeting criteria for major depression (17%). Vulnerability to cardiovascular risk increases with age in depressed patients, and it is most significant in the population aged over 60 years, which is the most rapidly growing segment of the world population. For example, a significant and substantial excess risk of death, myocardial infarction, or stroke in hypertensive patients aged over 70 years has been associated with an increase in depressive symptoms over time. Also, elderly men (aged over 70 years) newly diagnosed with depression are reported to be almost twice as likely to have a cardiovascular event as men without a history of depression. It is accepted clinical practice that primary care physicians will consider risk factors for coronary artery disease when evaluating patients aged over 40 years and will intervene to decrease cardiovascular risk if they find hypertension, elevated cholesterol, or obesity. We feel strongly that depression and anxiety should be included in this model. D population, individuals suffering from depression have an increased risk of sudden cardiovascular death, and the risk is highest in the presence of concomitant cardiovascular disease. Similarly, patients with cardiovascular disease suffer from major depression more frequently than expected. More than 20% of subjects with angiographic evidence of coronary heart disease have concomitant major depression. Also, up to 20% of survivors of recent acute myocardial infarction meet diagnostic criteria for major depression, and the presence of depression i associated with an increased 6-month mortality, compared with nondepressed survivors. At our consensus meeting on depressive and anxiety disorders in general medicine, the International Consensus Group on Depression and Anxiety reviewed depression, anxiety, and the cardiovascular system from the perspectives of both the cardiologist and the psychiatrist. This article sets forth our views on the management of comorbid depression and anxiety in the cardiovascular patient on the basis of the current state of knowledge and identifies areas of further research.

OBJECTIVE:Depressed men commonly have erectile dysfunction, and men with erectile dysfunction are frequently depressed. Since the etiologic and modulatory relationships between depression and erectile dysfunction have been poorly characterized, a 12-week, randomized, double-blind, placebo-controlled trial was conducted at 20 urologic clinics to evaluate the effects of sildenafil treatment in men with erectile dysfunction and mild-to-moderate comorbid depressive illness.METHOD:Men (N=152, mean age=56 years) with erectile dysfunction for > or =6 months (mean=5.7 years), a DSM-IV diagnosis of depressive disorder not otherwise specified, and a Hamilton Depression Rating Scale score > or =12 (mean at baseline=16.9) were randomly assigned to flexible-dose treatment with sildenafil citrate or matching placebo. Interviewer-rated and self-report instruments were used to assess changes in sexual function, depressive symptoms, and quality of life. Conservative criteria were used to classify erectile dysfunction treatment response and nonresponse.RESULTS:Sildenafil was strongly associated with erectile dysfunction treatment response. Fifty-eight men met the conservative criteria for response (48 given sildenafil, 10 given placebo), and 78 men did not respond (18 given sildenafil, 60 given placebo). Mean decreases of 10.6 and 2.3 in Hamilton depression scale scores were seen in treatment responders and nonresponders, respectively; 76% of treatment responders showed a > or =50% decline in Hamilton depression scale score versus 14% of nonresponders. Quality of life was similarly improved in treatment responders.CONCLUSIONS:Sildenafil is efficacious for erectile dysfunction in men with mild-to-moderate depressive illness. Improvement of erectile dysfunction is associated with marked improvement in depressive symptoms and quality of life.

Background: Testosterone (T) level declines progressively with age. Psychiatric symptoms of T deficiency (e.g., dysphoria, fatigue, irritability, low libido) are also symptoms of depression, and appear to be variably expressed.Methods: We assessed independent measures of hypothalamic-pituitary-gonadal axis functioning, i.e., total T level and androgen receptor (AR) CAG repeat length (CAG RL), a genetic trait market- associated with AR function; and depression (diagnosed by above-threshold score on the Center for Epidemiologic Studies-Depression Scale [CES-D]) in 1000 men (mean age = 62.6 years; SD = 8.3) who participated in the Massachusetts Male Aging Study.Results: There were 110 (11%) men with "depression" (CES-D score greater than or equal to 16) in the analysis sample. Neither total T level nor CAG RL was associated with depression in bivariate analyses. Among men with shorter CAG RLs, the percentage of men with depression was 21.6% in the lowest subgroup of total T (defined by quintiles) and 4.2% in the highest subgroup of total T. This was confirmed in simple logistic regression models with depression as the dependent variable and continuous total T as the predictor, run separately within the three CAG RL subgroups: depression was significantly and inversely associated with total T in men with shorter CAG RLs but not in men with moderate and longer CAG RLs.Conclusions: CAG isotype, a genetic trait marker of androgen receptor function, may mediate the expression of the central nervous system effects of T deficiency in men. Biol Psychiatry 2001;50:371-376 (C) 2001 Society of Biological Psychiatry.

BACKGROUND:Symptoms of male hypogonadism include low libido, fatigue, and dysphoria and are alleviated with testosterone replacement. The prevalence of major depressive disorder (MDD) in hypogonadal men is not known, nor is the antidepressant efficacy of testosterone replacement in depressed, hypogonadal men.METHOD:A 6-week double-blind, placebo-controlled clinical trial was conducted in 32 men with DSM-IV MDD and a low testosterone level, defined as total serum testosterone < or = 350 ng/dL. Patients were randomly assigned to receive weekly 1-mL intramuscular injections of either testosterone enanthate, 200 mg, or sesame seed oil (placebo). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression (HAM-D).RESULTS:Thirty patients were randomly assigned to an intervention; 13 received testosterone, and 17 received placebo. Mean +/- SD age was 52+/-10 years, mean testosterone level was 266.1+/-50.6 ng/dL, and mean baseline HAM-D score was 21+/-8. All patients who received testosterone achieved normalization of their testosterone levels. The HAM-D scores decreased in both testosterone and placebo groups, and there were no significant between-group differences: reduction in group mean HAM-D score from baseline to endpoint was 10.1 in patients who received testosterone and 10.5 in those who received placebo. Response rate, defined as a 50% or greater reduction in HAM-D score, was 38.5% (5/13) for patients who received testosterone and 41.2% (7/17) for patients who received placebo. Patients receiving testosterone had a marginal but statistically significant improvement in sexual function (p = .02).CONCLUSION:In this clinical trial with depressed, hypogonadal men, antidepressant effects of testosterone replacement could not be differentiated from those of placebo.

OBJECTIVETransthyretin plays an important role in the transport and distribution of thyroid hormone in the central nervous system (CNS). This study replicated and extended to patients with nonrefractory depressive illness a pilot study indicating that patients with refractory major depression have significantly lower levels of CSF transthyretin than do healthy comparison subjects.METHODLumbar punctures were performed in drug-free subjects with DSM-III-R major depression (N = 18), DSM-III-R bipolar disorder, depressed phase (N = 1), and healthy comparison subjects (N = 24). CSF concentrations of transthyretin, determined by a quantitative dot-immunobinding assay, of the depressed patients and comparison subjects were compared by analysis of covariance (ANCOVA). The relationship between CSF transthyretin levels and Hamilton Depression Rating Scale scores was determined in a subset of the depressed patients.RESULTSCSF concentrations of transthyretin were significantly lower in the depressed patients than in the comparison subjects by ANCOVA. Within the depressed group there was no significant overall correlation between CSF transthyretin levels and Hamilton depression scale scores, but there was a significant inverse correlation in male depressed patients (N = 8) between CSF transthyretin concentrations and Hamilton depression scores.CONCLUSIONSLower CSF transthyretin concentrations in depressed patients may reflect either a stable trait in this population or a state change secondary to depression or other factors. Lower CSF transthyretin concentrations may result in altered CNS thyroid hormone homeostasis. Such alteration could account for certain mood and neurovegetative symptoms of depression and might contribute to failure of standard antidepressant treatment.

BACKGROUND The morbidity and mortality caused by tricyclic antidepressant (TCA) overdose are well recognized. Among newer antidepressants, the selective serotonin reuptake inhibitors (SSRIs) are thought to be safer in overdose. This study was designed to describe the signs, symptoms, and mortality associated with SSRI overdose. METHOD English-language articles identified through MEDLINE (1985 through 1997), and case reports from the American Association of Poison Control Centers (AAPCC) (1987 through 1996) and United States Food and Drug Administration (FDA) adverse event database (through 1997) that describe findings of fatal and nonfatal overdoses involving SSRIs alone or in combination with other ingestants were reviewed. RESULTS SSRI antidepressants are rarely fatal in overdose when taken alone. During the 10 years that SSRI antidepressants have been marketed, there have been remarkably few fatal overdoses reported in the literature or to the AAPCC or FDA involving ingestion only of an SSRI. Moderate overdoses (up to 30 times the common daily dose) are associated with minor or no symptoms, while ingestions of greater amounts typically result in drowsiness, tremor, nausea, and vomiting. At very high doses (> 75 times the common daily dose), more serious adverse events, including seizures, electrocardiogram (ECG) changes, and decreased consciousness may occur. SSRI overdoses in combination with alcohol or other drugs are associated with increased toxicity, and almost all fatalities involving SSRIs have involved coingestion of other substances. CONCLUSION The SSRI antidepressants are far safer than the TCAs in overdose. There is no apparent difference among SSRIs with respect to overdose safety.

The efficacy of psychoanalysis and long-term psychotherapy remains a fundamentally unresolved issue for lack of methodologically sound studies. This article reviews the shortcomings of prior long-term treatment research, and presents a rationale and justification of the importance of more rigorous outcome studies. An emphasis on process research is premature when efficacy remains uncertain. The modern reconceptualization of psychotherapy in terms of hermeneutic theory is discussed in relation to the empirical model. Although historically the hermeneutic perspective has served to repudiate positivism, the hermeneutic and empirical (but not positivistic) approaches to understanding information actually share common priorities. The clearest of these is that the process is ultimately evaluated and validated by the produced effect. It is argued that the recasting of psychoanalytic technique and theory according to aesthetic and pragmatic principles is not inconsistent with contemporary outcome research paradigms so long as the professed treatment objective is clearly specified in verifiable terms. The specific methodologic problems involved in extending the successful short-term psychotherapy research model to psychoanalysis are discussed. An overview of the major components of the Columbia feasibility study currently underway is presented. Finally, a number of assessment domains-for which reliable and validated instruments exist-that are thought to be relevant to outcome are reviewed.

Hostility and anger have been attributed as psychosocial risk factors for coronary heart disease. Heightened cardiovascular reactivity (CVR), and poor recovery, to provocative stressors are thought to hasten this risk.To examine the relationship between hostility and anger inhibition (AI), and the moderating situational influences of harassment and evaluation, in predicting CVR and recovery to mental arithmetic (MA) stress using a multiple regression approach.48 male undergraduate students engaged in the following 3 minute tasks during recording of the electrocardiogram, impedance cardiography, and blood pressure: baseline, MA, and evaluation. Hostility and AI were assessed with the Cook-Medley Hostility Scale and the Speilberger Anger In subscale, respectively.An interaction between hostility and AI showed high diastolic blood pressure reactivity to the MA task among hostile anger inhibitors. Harassment did not modify this effect. However, harasser evaluation predicted prolonged systolic blood pressure (SBP) responding among men scoring high in AI, and facilitated SBP recovery among those scoring low on AI.The findings highlight the interactive influences of AI and hostility in predicting CVR to stress and underscore the importance of recovery assessments in understanding the potentially pathogenic associations of these constructs.

: Though analytic process is a core concept in psychoanalysis, no consensus definition or reliable method of assessment currently exists. This paper reviews clinical definitions of analytic process and concludes that analytic process is comprised of free association, resistance, interpretation and working through. Psychoanalytic outcome research suggests that analytic process develops in only 40 per cent of analyses. Though the presence of analytic process is highly correlated with therapeutic benefit, significant numbers of analytic patients (50 per cent) achieve good outcome despite the fact that an analytic process never developed in treatment. A review of process research on the components of analytic process suggests that a variety of measures already exist for free association, resistance, and interpretation. As in the clinical literature, working through is less well defined and studied. Although several researchers have assessed analytic process using a variety of techniques, these clinically defined component measures of analytic process have not yet been synthesised into a comprehensive scale. Such a measure of analytic process would have the benefit of being easily applied to an adequate sampling of session material and would result in a judgement about the presence and quality of analytic process. A consensus definition and the development of a reliable method to assess analytic process will be of use in clinical, educational and research settings as well as in attempts to define and quantify psychoanalytic treatment.

This paper describes a study to assess the feasibility of applying the methodology and instruments used in brief-term psychotherapy outcome research to long-term psychodynamic psychotherapy and psychoanalysis.

Some depressed patients may suffer from restricted central hypothyroidism, which could occur if levels of the thyroid hormone transport protein transthyretin were low. CSF transthyretin was measured in eight inpatients with refractory major depression and nine neurological patients. The depressed patients had significantly lower transthyretin levels than the comparison subjects, suggesting that central hypothyroidism, with normal peripheral thyroid concentrations, could occur in some depressed patients.

IN 1977, we first reported the antiarrhythmic effect of imipramine hydrochloride.1Prior to that time, physicians generally believed that the tricyclic antidepressants (TCAs) caused arrhythmia. That belief stemmed from the propensity of overdoses of these drugs to provoke arrhythmias.2However, it subsequently became apparent, both from our studies3-6and the work of others,7that at plasma concentrations therapeutic for depression,8TCAs suppress arrhythmias, and their cardiac effects closely resemble those of class I antiarrhythmic drugs.9,10Until recently, it was our belief that depressed patients with preexisting arrhythmias would benefit from the antiarrhythmic effect of TCAs.11,12Unfortunately, recent studies indicate that this opinion may need to be revised. Ventricular premature depolarizations (VPDs) are a well-documented risk factor for sudden death after myocardial infarction (MI)13,14and the assumption had been that drugs that suppress VPDs would reduce this associated mortality. However, in 1983, Furberg