Carol Fairchild

Which depressions respond to placebo

This descriptive study of 55 outpatients with unipolar major depression compared placebo responders (n = 21) and placebo nonresponders (n = 34) with respect to demographic, diagnostic, history of illness and symptomatic features of the current episode of depression. Placebo responders were significantly more likely to be nonendogenous and were more likely to meet criteria for another Research Diagnostic Criteria diagnosis. Additionally, placebo responders were characterized by a shorter length of illness and reported a lower level of depressive symptomatology on the Beck Depression Inventory and the Carroll Rating Scale. Clinician-rated depressive symptom severity (e.g., Hamilton Rating Scale for Depression, Covi Global Anxiety Scale, and Raskin Depression Rating Scale) and demographic variables did not differentiate placebo responders from nonresponders. These data suggest candidates for antidepressant treatment and implications for antidepressant drug trials.

TRH-induced prolactin release is blunted in females with endogenous unipolar major depression.

Twenty-five women with unipolar primary major depressive disorder (20 endogenous, 5 nonendogenous) and 20 female control subjects were studied with the thyrotropin-releasing hormone stimulation test (TRH-ST). Prolactin (PRL) levels were measured before and after TRH administration for patients and control subjects. For patients, thyrotropin (thyroid-stimulating hormone; TSH) levels were measured from the same serum specimens as PRL levels, and the 1 mg dexamethasone suppression test (DST) was performed. Patients with endogenous depression (ED) had significantly lower maximal serum PRL levels (max PRL) following TRH, and a significantly reduced increase over basal serum PRL (delta max PRL) compared to normal controls (NC). Nonendogenous depressed (NED) patients did not differ significantly from the ED or NC groups on either of these measures. For the ED group, delta max PRL was inversely correlated with severity of depressive symptomatology. Basal PRL levels did not differentiate the depressed subgroups (ED, NED) from each other or from the NC group. Depressed patients with blunted delta max PRL values tended to have blunted delta max TSH values and vice versa. Almost all patients with blunting of either delta max PRL or delta max TSH were also DST nonsuppressors; conversely, only about half (7 of 12) of patients who were DST nonsuppressors had either blunted delta max PRL or delta max TSH. Patients with clinical diagnoses of melancholia or psychotic features were significantly more likely to have blunted delta max PRL values than patients without these diagnoses. A disturbance of central noradrenergic function could explain these findings.

Free triiodothyronine (T3) and thyroxine (T4) in a group of unipolar depressed patients and normal subjects

We examined levels of free triiodothyronine (fT3) and free thyroxine (fT4) in serum from a group of 32 patients with unipolar major depression and 46 normal control subjects using the Amerlex (Amersham, Arlington Heights, IL) RIA procedures for these hormones. Free T3 levels were significantly lower (p less than 0.004) in the depressed patients as a group (5.02 +/- 1.01 pmol/L, mean +/- SD) than in the normal control subjects (5.74 +/- 1.23 pmol/L). Free T3 levels were lower (p less than 0.01) in depressed men (5.25 +/- 1.43 pmol/L) when compared with male control subjects (6.46 +/- 1.01 pmol/L). Depressed women (4.78 +/- 0.60 pmol/L) also had lower T3 levels than did the female control subjects (5.09 +/- 1.06 pmol/L), but the difference was not statistically significant. Lower fT3 levels were also observed in melancholic depressed patients when compared with nonmelancholic depressed patients or when compared with normal control subjects. No differences in fT4 were observed between groups in this study.

The effect of dosage on the dexamethasone suppression test in normal controls

A sample of 23 drug-free, normal adult subjects, aged 23 to 50 years, received 1 mg dexamethasone p.o. at midnight. Serum cortisols were obtained at 0800h, 1600h, and 2330h pre- and postdexamethasone. Only 1 of these 23 subjects (4.3%) evidenced nonsuppression, as defined by any postdexamethasone serum cortisol value of greater than 4.0 micrograms/dl. A dose of 0.75 mg dexamethasone was administered to 23 drug-free, normal adult subjects, 20 of whom participated in the above 1 mg trial. Six of these 23 (26.1%) showed nonsuppression at a threshold of 4.0 micrograms/dl. Another 11 normal adults who were taking various prescription medications (e.g., sympathomimetics, nasal decongestants, birth control pills, thyroid hormones) or who were suffering from untreated upper respiratory infections, venereal infections, or allergies were tested with 1 mg of dexamethasone. In this sample, 7 of 13 (53.8%) showed nonsuppression. These findings suggest that: (1) 1 mg of dexamethasone is the lowest effective dose that can be used in diagnostic testing for melancholic depression; (2) a false-positive response to the dexamethasone suppression test (DST) may occur with infections, allergies, or possibly with certain prescription medications. Further studies of the effects of illness and/or medications on DST responses are needed.

Withdrawal syndrome following cessation of guanabenz therapy.

A withdrawal syndrome consisting of nervousness, palpitations, diaphoresis, and insomnia appeared in three patients within 16--48 hours following discontinuation of guanabenz, a new centrally acting antihypertensive agent. A similar syndrome of sympathetic overactivity has been described with abrupt withdrawal of clonidine. Three of four patients treated with 48 mg/day but none of 20 other patients treated with 32 mg/day or less guanabenz developed this syndrome. None of the three patients developed hypertensive crisis, though one had a modest rise in the blood pressure above baseline levels. It is concluded that guanabenz therapy should not be discontinued abruptly and that, when possible, the dosage should be limited to less than 48 mg/day.

Renin classification for diuretic and beta-blocker treatment of black hypertensive patients

Renin classification has been proposed to guide initial treatment of hypertensive patients with diuretics vs beta-blockers. Most previous studies evaluating this issue have utilized patient populations that were white or predominantly white. Black hypertensives have been noted to differ from white hypertensives in several respects. To evaluate the clinical utility of renin classification in black hypertensives, we compared the blood pressure response of low vs normal renin patients during double-blind treatment with either hydrochlorothiazide or beta blocker (metoprolol or oxprenolol). Hydrochlorothiazide a significantly (P less than 0.05-0.01) larger blood pressure fall than beta-blocker, though there was no difference in the response of low vs normal renin patients. Thus, renin classification does not appear to guide initial selection of diuretic vs beta blocker therapy of black hypertensives, and diuretic therapy is more effective.

The thyrotropin-releasing hormone stimulation test: A methodological study

Abstract Repeated thyroid-stimulating hormone (TSH) determinations were carried out for 90 or 180 minutes following thyrotropin releasing hormone (TRH) stimulation in 160 euthyroid psychiatric patients, most of whom had a symptomatic affective disorder. The purpose was to determine which of the simple TSH measurements from the TRH stimulation test (TRH-ST) yield(s) the most accurate index of pituitary TSH reserves and to clarify the relationship between the various TRH-ST methods reported in the literature. The area beneath the 180 minute TSH response curve, the best available parameter of pituitary TSH stores, was calculated and compared to simple indices of absolute TSH level and increase from 0 minute baseline. Fourteen parameters of the TSH response were determined; TSH 0, TSH 15, TSH 30, and TSH 45 represent the absolute levels at 0, 15, 30, and 45 minutes after TRH administration, respectively. TSH Max is the maximum TSH level attained after TRH infusion among all TSH measures. Δ TSH measures are the increase in TSH relative to baseline. The Δ Max TSH and Δ TSH 30 were highly correlated with the ideal index of pituitary TSH reserve (0 – 180 minute area). Subjects were classified as either blunted or normal over a broad range of Δ Max TSH criteria or thresholds. The number of misclassified subjects (false positives) at each criterion was counted for each of the seven possible combinations of Δ TSH 15, Δ TSH 30, and/or Δ TSH 45. The simplest index which produced the smallest number of false positives was Δ TSH 30 whereas Δ Max TSH (15, 30, and 45) produced no false positives. Overall, Δ TSH 30 was a very good simple index of pituitary TSH stores. This may be the preferred index when economy of time, expense, or blood samples is desired. However, it results in 5–7% false positives, which will compromise specificity somewhat. The preferred simple index of pituitary TSH reserves when accuracy is of highest priority is Δ Max TSH (15, 30, and 45). These data reveal that the TRH-ST can be simplified to include only four TSH levels: TSH 0, TSH 15, TSH 30, and TSH 45.

Dexamethasone suppression test status does not predict differential response to nortriptyline versus amitriptyline.

Thirty-five (35) inpatients with nonpsychotic major depression were randomly assigned to either amitriptyline or nortriptyline on a double-blind basis, following a 4- to 10-day placebo run-in period. Thirty-two patients completed at least 3 weeks of active medication. The 1.0-mg dexamethasone suppression test (DST) was performed before treatment. Twelve of 32 patients were DST nonsuppressors. Both medications were equally effective. Pretreatment DST status failed to predict overall response to both medications combined. DST status also did not predict differential medication response. These data argue, along with several other studies, that pretreatment DST status may be of limited value in selecting a particular tricyclic antidepressant compound.

Effect of Guanabenz and Hydrochlorothiazide on Blood Pressure and Plasma Renin Activity

Abstract: Patients with mild to moderate essential hypertension were treated with guanabenz plus placebo (26 patients) or guanabenz plus hydrochlorothiazide (26 patients) for one year. Ambulatory plasma renin activity was determined during placebo treatment, after four weeks and one year of treatment with the study drugs, and one month after discontinuation of guanabenz while continuing the same hydrochlorothiazide dosage. Treatment with guanabenz plus hydrochlorothiazide proved more satisfactory than treatment with guanabenz plus placebo in that fewer patients were treatment failures, a smaller dosage of guanabenz was required, better control of supine blood pressure was achieved, and no increase in guanabenz dosage was needed to maintain chronic blood pressure control. Drowsiness, dry mouth, and dizziness were the side effects noted most commonly. Plasma renin activity was not significantly suppressed by chronic guanabenz therapy. Thus, guanabenz is an effective new antihypertensive that provides optimal blood pressure control when used with a diuretic.