A randomized, prospective pilot study of patient expectancy and antidepressant outcome.

BACKGROUND: This study is a randomized, prospective, investigation of the relationships between clinical trial design, patient expectancy and the outcome of treatment with antidepressant medication. Method Adult out-patients with major depressive disorder (MDD) were randomized to either placebo-controlled (PC, 50% probability of receiving active medication) or comparator (COMP, 100% probability of receiving active medication) administration of antidepressant medication. Independent-samples t tests and analysis of covariance (ANCOVA) were used to determine whether the probability of receiving active medication influenced patient expectancy and to compare medication response in the PC v. COMP conditions. We also tested the correlations between baseline expectancy score and final improvement in depressive symptoms across study groups. RESULTS: Subjects randomized to the COMP condition reported greater expectancy of improvement compared to subjects in the PC condition (t = 2.60, df = 27, p = 0.015). There were no statistically significant differences in the analyses comparing antidepressant outcomes between subjects receiving medication in the COMP condition and those receiving medication in the PC condition. Higher baseline expectancy of improvement was correlated with lower final depression severity scores (r = 0.53, p = 0.021) and greater improvement in depressive symptoms over the course of the study (r = 0.44, p = 0.058). CONCLUSIONS: The methods described represent a promising way of subjecting patient expectancy to scientific study. Expectancy of improvement is affected by the probability of receiving active antidepressant medication and seems to influence antidepressant response.

Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients.

BACKGROUND: Age of onset may affect clinical features and prognosis in elderly patients with major depression (MDD), but there is a lack of such data in elderly patients with dysthymic disorder (DD) and systematic comparisons of late onset MDD and DD have not been conducted. METHODS: In a Late Life Depression Clinic, patients > or = 60 years old who met DSM-III-R or DSM-IV criteria for MDD or DD were studied. The 24-item Hamilton Rating Scale for Depression (HRSD) and SCID-P were completed, family history was obtained, and medical illnesses were assessed. RESULTS: In the total sample (n=370; 211 MDD and 159 DD), compared to early onset patients, late onset (onset > or =60 years) patients had a higher rate of cardiovascular disease (chi(2)=4.12, df=1, P<0.05), lower rate of anxiety disorder (chi(2)=4.19, df=1, P<0.05), and a lower rate of family history of affective disorder (chi(2)=9.37, df=1, P<0.002). Late onset DD patients were more likely to have cardiovascular disease than early onset DD patients (chi(2)=5.63, df=1, P<0.02), but the rate of cardiovascular disease did not differ between late and early onset MDD patients (chi(2)=0.35, df=1, P<0.6). Late onset MDD patients were less likely to have a family history of affective disorder than early onset MDD patients (chi(2)=10.71, df=1, P<0.001). Prevalence of anxiety disorders did not differ between the early and late onset MDD patients (chi(2)=0.07, df=1, P<0.79), but was more common in the early onset DD compared to the late onset DD patients (17.98% versus 4.29%, chi(2)=6.98, df=1, P<0.01). Late onset DD did not differ from late onset MDD in the rates of cardiovascular disease, anxiety disorders, and family history of affective disorder. Excluding patients with double depression (n=32) did not alter the cardiovascular or family history findings, but the difference in anxiety disorders between early and late onset DD patients was no longer significant. LIMITATIONS: Academic clinic sample results may not generalize to community populations. CONCLUSIONS: In the elderly, late-onset DD is typically different from early onset DD. Cerebrovascular disease appears to play a role in the etiology of late onset DD. The similarities between late onset DD and late onset MDD suggest a single condition along a continuum.

Quality of life, mood, and sexual function: a path analytic model of treatment effects in men with erectile dysfunction and depressive symptoms.

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.

Treatment of erectile dysfunction in men with depressive symptoms: results of a placebo-controlled trial with sildenafil citrate.

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.

Testosterone level, androgen receptor polymorphism, and depressive symptoms in middle-aged men.

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 marker 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 > or = 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.

Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial.

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.

Suicide: what is in the clinician's mind?

The assessment and treatment of the suicidal patient challenge all clinicians, regardless of training or theoretical orientation, to draw upon their knowledge and judgment to formulate the best treatment plan possible. As great as the influence of demographics, genetics, and psychobiology are, what is in the mind of the clinician, whether it is anxiety, confidence, knowledge, or uncertainty, will determine the fate of the suicidal patient.

Sexual dysfunction and depression.

Sexual functioning is generally impaired during depression. Interest in the relationship between sexual dysfunction and depression has risen substantially, prompted primarily by 1) the 1998 Food and Drug Administration approval of sildenafil citrate as the first oral therapy of erectile dysfunction, and 2) the widespread clinical use of selective serotonin reuptake inhibitors, which prominently impair orgasm, and possibly libido and arousal. In this paper, we first review the phenomenology of sexual dysfunction and important contributing factors, such as age and illness, and then focus on the clinical assessment and therapeutic interventions used for sexual dysfunction in depressed individuals.

ECT in bipolar and unipolar depression: differences in speed of response.

OBJECTIVES: There is sparse evidence for differences in response to electroconvulsive therapy (ECT) between patients with bipolar or unipolar major depression, with virtually no information on speed of response. We contrasted a large sample of bipolar (BP) and unipolar (UP) depressed patients in likelihood and rapidity of clinical improvement with ECT. METHODS: Over three double-blind treatment protocols, 228 patients met Research Diagnostic Criteria for UP (n = 162) or BP depression (n = 66). Other than lorazepam PRN (3 mg/day), patients were withdrawn from psychotropics prior to the ECT course and until after post-ECT assessments. Patients were randomized to ECT conditions that differed in electrode placement and stimulus intensity. Symptomatic change was evaluated at least twice weekly by a blinded evaluation team, which also determined treatment length. RESULTS: Patients with BP and UP depression did not differ in rates of response or remission following the ECT course, or in response to unilateral or bilateral ECT. Degree of improvement in Hamilton Rating Scale for Depression scores following completion of ECT was also comparable. However, BP patients received significantly fewer ECT treatments than UP patients, and this effect was especially marked among bipolar ECT responders. Both BP I and BP II patients showed especially rapid response to ECT. CONCLUSIONS: The BP/UP distinction had no predictive value in determining ECT outcome. In contrast, there was a large effect for BP patients to show more rapid clinical improvement and require fewer treatments than unipolar patients. The reasons for this difference are unknown, but could reflect a more rapid build up of anticonvulsant effects in BP patients.

The Columbia Supervision Project: data from the dyad.

Anonymous questionnaires were sent to all candidates and supervisors at the Columbia University Center for Psychoanalytic Training and Research (hereafter "Columbia"). Questions focused on the four domains most emphasized in the literature on supervision: logistical issues; the "teach or treat" question; the evaluatory function of the supervisor; and the affective experience of supervision. By coding the questionnaires, anonymity of respondents was maintained while allowing for a matched pair of analyses of supervisors and supervisees. Return rate was over 85 percent. In general, rates of satisfaction with supervision were high, and candidates and supervisors agreed on such issues as the "teach or treat" question, as well as the technical and theoretical frame of reference of the supervisor. However, there were striking disagreements between candidates and supervisors as to the role of the supervisor, what candidates find useful in supervision, the evaluatory function, and the relation between supervision and progression to graduation. Although 50 percent of candidates reported anxiety about receiving credit for cases, this was not routinely discussed in supervision, and the supervisory relationship itself was not discussed in over 50 percent of dyads. Despite high overall satisfaction ratings, 25 percent of candidates said they wished they had a different supervisor for the case, and 75 percent believed that a candidate who asked to switch supervisors would be labeled problematic. In contrast, over 75 percent of supervisors reported that switching supervisors carries no stigma. In a follow-up study conducted one year later, many candidates reported that they feared reprisals for switching, and some reported that their training analysts advised against "rocking the boat." Candidates felt that participating in the study emboldened them to think more openly about supervision and in some cases to make changes.

ECT and onset of action.

Although there is a long-standing clinical belief that electroconvulsive therapy (ECT) is the fastest available treatment for depression, ECT has not been compared directly with drug therapy. For this reason, it is impossible to say whether ECT treatment actually works faster than standard medications. Studies comparing various modalities of ECT have highlighted several factors that should be considered in any assessment of differential onset of antidepressant effect. First, patients are heterogeneous; that is, given any treatment or mode of treatment, some patients will respond, and some will not. Second, the choice of statistical method can significantly affect the interpretation of comparative onset data. Third, improved onset of action sometimes is achieved at the expense of tolerability. Thus, accelerating the onset of therapeutic response should not be an end in itself.

An ideal trial to test differential onset of antidepressant effect.

Although various published clinical studies have suggested that some antidepressants may have a more rapid onset of therapeutic effect than others, none of these trials was adequately designed to measure differential time to onset of effect. Thus, existing data do not support claims that one drug reduces the symptoms of depression faster than another. In this article, we propose a study that would be ideal for measuring comparative onset of antidepressant effect. The key features of this ideal trial include (1) a prospective definition of early onset of action, (2) increased frequency of assessment, (3) a data-analytic approach capable of capturing the dynamic nature of symptomatic change, and (4) various strategies to minimize bias and heterogeneity of response.

Depression, anxiety, and the cardiovascular system: the psychiatrist's perspective.

It is becoming clear that the comorbidity of depression and cardiovascular disease does not occur by chance but rather is an inevitable consequence of the relationship between the conditions. Depression in patients with cardiovascular disease is a significant risk factor for developing symptomatic and fatal ischemic heart disease. Moreover, depressed patients have a higher than expected rate of sudden cardiovascular death. Therefore, appropriate treatment of patients with depression and cardiovascular disease cannot be restricted to considerations of either depression or cardiovascular disease in isolation. The tricyclic antidepressants (TCAs) have various effects on the cardiovascular system, including Type IA antiarrhythmic activity that has been associated with an increased risk of mortality in post-myocardial infarction patients. The selective serotonin reuptake inhibitors (SSRIs) are not associated with adverse cardiac effects. The SSRI paroxetine was compared with a therapeutic level of the TCA nortriptyline in a randomized, controlled study and demonstrated a benign cardiovascular profile, while the TCA induced a significantly higher rate of serious adverse cardiovascular events. On the basis of this favorable cardiovascular profile, the SSRIs should therefore be the preferred choice for the treatment of most patients with comorbid depression and cardiovascular disease. Investigation of putative pathophysiologic mechanisms linking depression and cardiovascular mortality, such as the role of platelet activation, will form the basis for further investigation of antidepressant treatments in order to establish if the antidepressants have a beneficial effect on the prognosis of cardiovascular diseases.

The relationship between depression and erectile dysfunction.

Normal sexual function is a biopsychosocial process; sexual dysfunction almost always has organic and psychologic components, and it requires multidisciplinary, goal-directed evaluation and treatment. Factors such as aging, declining testosterone levels, medical illness, certain medications, and comorbid depressive illness can contribute to sexual dysfunction. Erectile dysfunction (ED) is the most common male sexual dysfunction encountered in the clinical setting. Comorbidity between ED and depressive illness is high, but the causal relationship is unclear, and likely bidirectional. In this article, we review the existing literature on the relationship between depression and ED.

Regional cerebral blood flow in mood disorders, V.: Effects of antidepressant medication in late-life depression.

Twenty elderly outpatients with major depression were treated with either nortriptyline or sertraline. Resting regional cerebral blood flow (rCBF) was assessed by the planar (133)Xenon inhalation technique after a medication washout and following 6- 9 weeks of antidepressant treatment. At baseline, the depressed sample had reduced rCBF in frontal cortical regions when compared with 20 matched normal-control subjects. After treatment, Responders and Nonresponders differed in the expression of a specific topographic alteration, with Responders manifesting reduced perfusion in frontal regions. These findings are consistent with this group's previous report of reduced rCBF after response to electroconvulsive therapy (ECT) and suggest a common mechanism of action.

Patient-therapist match: revelation or resistance?

Patient-therapist match is a relatively new yet frequently invoked concept within psychoanalysis. Despite Freud's appreciation of the influence of the analyst's past to his or her work within the analytic setting, psychoanalysts have historically held varied opinions about the degree to which the analyst's personality and conflicts affect the analytic process. As analysis was reconfigured as a two-person system, attention focused on the fit between patient and analyst. The literature on patient-therapist match is reviewed, and the conclusion reached that this intuitively appealing concept suffers from a lack of rigorous definition and operationalization. Many authors invoke match in ways that imply that it is real, static, external to the domain of analytic inquiry, and unaffected by analytic process. In its present form, the concept of patient-therapist match obstructs rather than facilitates analytic exploration and obscures rather than clarifies what happens between analyst and analysand in psychoanalysis. By suggesting that match exists as a reality outside the domain of transference and countertransference, analysts may overlook the importance of psychoanalytic technique in creating a sense of match. Analysts may attribute stalemated or limited analyses to a bad match, rather than tenaciously exploring the transference-countertransference configurations that remain at the heart of analytic work.

Can we do psychoanalytic outcome research? A feasibility study.

Despite the widespread use of long-term psychodynamic treatments, methodologically rigorous outcome studies have not been conducted. The authors describe the results of a feasibility study designed to (1) investigate whether patients in psychodynamic treatment, including psychoanalysis, could be recruited and retained as research subjects, (2) determine patient and therapist compliance with self-report measures, rater-administered structured interviews and session audiotaping and (3) obtain pilot data on changes in these measures after one year of treatment. Nine patients entering psychoanalysis and fifteen entering psychodynamic psychotherapy were studied at baseline, six months and one year. Major findings were as follows: (1) recruitment rates were 27% (psychoanalysis) and 83% (psychotherapy), (2) all patients who remained in treatment remained in the research protocol, (3) drop-out rates among research participants and non-participants were equivalent, (4) current Axis I (usually affective or anxiety) disorders were found in over 60% of patients, (5) Axis II disorders in the absence of current Axis I disorders were rare, (6) despite a small number (N) of participants, significant positive change was demonstrated on a variety of measures after one year. Results suggest that it is possible to demonstrate a therapeutic effect of psychodynamic treatments, including psychoanalysis, but changing negative clinical perceptions of research is necessary if methodologically rigorous outcome studies are to be possible in the future.