Wilma Harrison

Gender differences in chronic major and double depression.

BACKGROUND While the sex difference in prevalence rates of unipolar depression is well established, few studies have examined gender differences in clinical features of depression. Even less is known about gender differences in chronic forms of depression. METHODS 235 male and 400 female outpatients with DSM-III-R chronic major depression or double depression (i.e., major depression superimposed on dysthymia) were administered an extensive battery of clinician-rated and self-report measures. RESULTS Women were less likely to be married and had a younger age at onset and greater family history of affective disorder compared to men. Symptom profile was similar in men and women, with the exception of more sleep changes, psychomotor retardation and anxiety/somatization in women. Women reported greater severity of illness and were more likely to have received previous treatment for depression with medications and/or psychotherapy. Greater functional impairment was noted by women in the area of marital adjustment, while men showed more work impairment. LIMITATIONS Since our population consisted of patients enrolling in a clinical trial, study exclusion criteria may have affected gender-related differences found. CONCLUSIONS Chronicity of depression appears to affect women more seriously than men, as manifested by an earlier age of onset, greater family history of affective disorders, greater symptom reporting, poorer social adjustment and poorer quality of life. These findings represent the largest study to date of gender differences in a population with chronic depressive conditions.

Platelet/Endothelial Biomarkers in Depressed Patients Treated With the Selective Serotonin Reuptake Inhibitor Sertraline After Acute Coronary Events. The Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART) Platelet Substudy

Background—Depression after acute coronary syndromes (ACSs) has been identified as an independent risk factor for subsequent cardiac death. Enhanced platelet activation has been hypothesized to represent 1 of the mechanisms underlying this association. Selective serotonin reuptake inhibitors (SSRIs) are known to inhibit platelet activity. Whether treatment of depressed post-ACS patients with SSRIs alters platelet function was not known. Accordingly, we serially assessed the release of established platelet/endothelial biomarkers in patients treated with sertraline vs placebo in the Sertraline AntiDepressant Heart Attack Randomized Trial (SADHART). Methods and Results—Plasma samples (baseline, week 6, and week 16) were collected from patients randomized to sertraline (n=28) or placebo (n=36). Anticoagulants, aspirin, and ADP-receptor inhibitors were permitted in this study. Platelet factor 4, &bgr;-thromboglobulin (&bgr;TG), platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane B2, 6-ketoprostaglandin F1a, vascular cell adhesion molecule-1, and E-selectin were measured by ELISA. Treatment with sertraline was associated with substantially less release of platelet/endothelial biomarkers than was treatment with placebo. These differences attained statistical significance for &bgr;TG (P =0.03) at weeks 6 and 16 and for P-selectin (P =0.04) at week 16. Repeated-measures ANOVA revealed a significant advantage for sertraline vs placebo for diminishing E-selectin and &bgr;TG concentrations across the entire treatment period. Conclusions—Treatment with sertraline in depressed post-ACS patients is associated with reductions in platelet/endothelial activation despite coadministration of widespread antiplatelet regimens including aspirin and clopidogrel. The antiplatelet and endothelium-protective properties of SSRIs might represent an attractive additional advantage in patients with depression and comorbid coronary artery and/or cerebrovascular disease.

Age of onset in chronic major depression: relation to demographic and clinical variables, family history, and treatment response

BACKGROUND The clinical and etiological significance of the early-late onset distinction in chronic major depressive disorder was explored. METHOD Subjects were 289 outpatients with DSM-III-R chronic major depression drawn from a multi-site study comparing the efficacy of sertraline and imipramine in the acute and long-term treatment of chronic depression. Patients received comprehensive evaluations using semi-structured interviews and rating scales. RESULTS Early-onset chronic major depression was associated with a longer index major depressive episode and higher rates of recurrent major depressive episodes, comorbid personality disorders, lifetime substance use disorders, depressive personality traits, and a history of psychiatric hospitalization. In addition, more early-onset patients tended to have a family history of mood disorders. The early-late onset distinction was not associated with differences in symptom severity, functional impairment, or treatment response. LIMITATIONS Family members were not interviewed directly; there were a large number of statistical comparisons; and interrater reliability of the assessments was not evaluated. CONCLUSIONS Early-onset chronic major depression has a more malignant course and is associated with greater comorbidity than late-onset chronic major depression.

Daily Record of Severity of Problems (DRSP): reliability and validity

SummaryThe Daily Record of Severity of Problems (DRSP) form was developed to aid in the diagnosis and evaluation of DSM-IV Premenstrual Dysphoric Disorder (PMDD). The reliability and validity of the procedure was tested in two studies. Study A included 27 subjects who ranged from having few or no premenstrual problems to those who met criteria for PMDD. Study B included 243 subjects, all of whom met criteria for PMDD. Individual items and Summary Scores had high test–retest reliability in both studies. Internal consistency of Summary Scores was also high in both studies. Summary Scores had moderate to high correlations with other measures of severity of illness. In addition, items and Summary Scores have been shown to be sensitive to change and to treatment differences in Study B. The DRSP provides sensitive, reliable, and valid measures of the symptoms and impairment criteria for PMDD.

An open-label preliminary trial of sertraline for treatment of major depression after acute myocardial infarction (the SADHAT Trial) ☆ ☆☆ ★

BACKGROUND Depression occurs frequently in patients with acute myocardial infarction and is associated with increased mortality rates. It is not known whether serotonin reuptake inhibitors would be safe and effective for patients with depression after myocardial infarction and whether such treatment would reduce mortality rates. METHODS AND RESULTS We conducted a multicenter, open-label, pilot study of sertraline treatment in patients with major depressive disorder identified 5 to 30 days after admission for acute myocardial infarction. Outcome measures included cardiovascular and hemostatic function, adverse events, and mood ratings. Twenty-six patients were enrolled in the study. During treatment there were no significant changes in heart rate, blood pressure, cardiac conduction, or left ventricular ejection fraction, and there was a trend toward reduced ventricular ectopic activity. There were no changes in coagulation measures. Bleeding time increased in 12 patients, decreased in 4 patients, and was unchanged in 2 patients. Three (12%) patients withdrew from treatment prematurely because of adverse events. Significant improvements in mood ratings occurred over the course of treatment. CONCLUSIONS Sertraline treatment was associated with clinical improvement and was well tolerated in >85% of the patients in this open-label treatment trial for patients with major depression after myocardial infarction. These results encourage further controlled trials to establish the effects of treatment for this high-risk population.

Provocation of panic with carbon dioxide inhalation in patients with premenstrual dysphoria.

The effects of double breath inhalation of a 35% CO2 mixture in oxygen and placebo air inhalation were compared in 14 women seeking treatment for marked premenstrual dysphoric changes who did not have panic disorder and 12 control women. The first exposure to CO2 inhalation induced a panic attack reaction (severe subjective anxiety with autonomic symptoms) in 9 of 14 women with premenstrual dysphoria but none of the controls. Neither patients nor controls panicked in response to the air inhalation. Control subjects experienced mild anxiety and/or somatic symptoms after CO2 inhalation, but these did not resemble panic attacks and were clearly different from the response of the patient group.

Effects of Antidepressant Medication on Sexual: Function

There has been little systematic study of the types of sexual dysfunction produced by antidepressant medication or of the frequency with which this type of adverse effect occurs. The authors report results of a double-blind study in which the effects of imipramine, phenelzine, and placebo on specific aspects of sexual function were assessed in depressed outpatients before and after 6 weeks of treatment. Both active treatments were associated with a high incidence of adverse changes in sexual function and produced significantly more adverse effects on sexual function than placebo. Orgasm and ejaculation were impaired to a greater extent than erection. Adverse sexual function changes secondary to antidepressant medication occurred frequently in both men and women, although men reported a higher incidence. Antidepressant-related sexual dysfunction may be of clinical importance for medication compliance in view of current recommendations that antidepressants be administered for longer periods as maintenance therapy or for prophylaxis.

Characteristics of Women Seeking Treatment for Premenstrual Syndrome

Controversy has developed about the existence of a relatively discrete condition of severe premenstrual dysphoric changes in the absence of underlying mental disorder (late luteal phase dysphoric disorder). With careful screening and evaluation, women with this disorder can be identified. In this study, women who sought treatment for premenstrual syndrome were divided into two groups: individuals who experienced mood and behavior changes and impaired social functioning that were limited to the premenstrual period (n = 86), and women with persistent mental disorders who experienced exacerbation or complication of symptoms during the premenstrual period (n = 54). These groups were compared with a control group of women who had no significant premenstrual changes and no current mental disorder (n = 61). Most of the differences between subjects seeking treatment and controls that were not attributable to premenstrual changes were accounted for by the women with persistent mental disorders.

How blind is blind? Assessment of patient and doctor medication guesses in a placebo-controlled trial of imipramine and phenelzine

The purpose of the double blind is to protect the internal validity of a clinical trial by preventing knowledge of treatment conditions from influencing outcome or its assessment. We studied medication guesses of 137 depressed patients and/or their doctors at the end of a 6-week randomized trial of placebo, imipramine, and phenelzine. Overall, 78% of the patients and 87% of the doctors correctly distinguished between placebo and active medication. Clinical outcome, treatment condition, and their interaction each contributed to guessing accuracy, while medication experience and side effects assessed only in week 6 did not. Accuracy was high, however, even when cases were stratified for clinical outcome, indicating that other cues were available to the patients and doctors. These may include patterns and timing of side effects and clinical response not detectable in this end-point analysis.

Effect of concurrent anxiety on response to sertraline and imipramine in patients with chronic depression

Anxiety commonly complicates the clinical presentation of depression and has been associated with poorer long‐term outcome, but little information is available on the clinical correlates, and comparative effect on treatment response, of subsyndromic or secondary anxiety. Patients diagnosed with chronic major or double depression were randomized to 12 weeks of double‐blind treatment with either sertraline or imipramine in a 2:1 ratio. A high anxiety subgroup was operationally defined by a HAM‐D anxiety/somatization factor score ≥ 7. The effect of study treatment was measured utilizing the HAM‐D, CGI, HAM‐D anxiety/somatization factor, as well as a quality of life measure (Q‐LES‐Q) and a measure of psychosocial functioning (the MOS‐SF‐36). Two hundred nine patients were treated with imipramine and 426 patients were treated with sertraline. Thirty‐six percent of the total met criteria for the high anxiety subgroup. According to Kaplan‐Meier probability estimates, patients with significant concurrent anxiety symptoms were more likely to respond by 12 weeks (66.4%) than those without significant anxiety symptoms (54.2%). There was no significant difference in response rates for sertraline vs. imipramine. Both drugs were effective at treating high baseline levels of anxiety, with 60% of sertraline patients and 58% of imipramine patients having 50% or greater reduction from baseline in HAM‐D anxiety/somatization factor scores, and only 4.6% and 9.9%, respectively, reporting treatment‐emergent worsening in anxiety at study endpoint. Despite the chronicity of depressive illness, acute treatment with both sertraline and imipramine significantly improved psychosocial and quality of life measures. High baseline levels of anxiety did not reduce overall antidepressant response but did somewhat delay the onset of response to sertraline or imipramine in patients with chronic depression. Depression and Anxiety 13:18–27, 2001.