Prediction of steady-state imipramine and desmethylimipramine plasma concentrations from single-dose data.

Tricyclic antidepressant plasma levels were measured in patients and healthy subjects after a single dise of desmethylimipramine (DMI) or imipramine (IMI) and after chronic dosing to steady states. Tricyclic plasma levels measured 24 hr after the single oral dose correlated with steady-state plasma levels. In patients receiving DMI there was a correlation (r = 0.97, n = 10) between 24-hr and steady-state DMI levels, while in normal subjects receiving IMI the correlation was r = 0.92 (n = 20) between 24-hr and steady-state total tricyclic levels (IMI plus its metabolite, DMI). These results suggest the possibility that after a test dose of tricyclic antidepressant, a patient may be put on a "therapeutic" dosage regimen without delay.

DST and TRH stimulation test in mood disorder subtypes.

Both the dexamethasone suppression test (DST) and the thyrotropin-releasing hormone (TRH) stimulation test have been reported to be useful in subtyping some depression diagnoses. Whether the DST discriminates delusional from nondelusional depression remains controversial, but this possibility has not been studied for the TRH test. The authors evaluated DST and TRH test results in 29 depressed hospitalized patients; both tests significantly discriminated patients with nonendogenous depression from those with endogenous depression. Furthermore, postdexamethasone cortisol levels but not the change in thyroid-stimulating hormone discriminated the patients with endogenous delusional depression from those with endogenous nondelusional depression.

Toward a rational pharmacotherapy of depression.

The authors review several approaches that show promise for predicting which antidepressant medication will be best for a particular patient and for achieving maximum benefit from each drug. These include delineation of clinical and historical characteristics associated with response to various drugs, use of psychological tests, assessment of biochemical and electroencephalographic parameters, evaluation of mood response to amphetamine, determination of acetylator status, and measurement of plasma tricyclic levels and degree of inhibition of platelet monoamine oxidase. The authors believe that the use of these approaches may improve our ability to help depressed patients.

How are depression and bulimia related?

The idea that bulimia may be related to affective illness was encouraged by early reports of a high prevalence of clinical depression in bulimic patients as well as a high lifetime prevalence of depression in the families of these patients. More recent evidence suggests, however, that bulimia and major depression are distinct entities. The authors review clinical data, family studies, pharmacotherapy, and the neurobiology of bulimia and discuss the nature of the relationship between depression and bulimia.

Affective disorder in the families of women with normal weight bulimia.

The authors determined the lifetime prevalence of affective disorder in the first- and second-degree relatives, excluding children, of 27 bulimic women who had never had anorexia nervosa and 27 women with no history of an eating disorder. Family diagnoses were made blind to the proband's diagnosis. The prevalence of affective disorder was 9% in the relatives of the bulimic probands and 10% in the relatives of the control probands, a nonsignificant difference. These findings are in contrast to reports of an increased prevalence of affective disorder in the relatives of patients with anorexia nervosa.

Drug combinations in the treatment of refractory depression: a review.

The authors critically review several drug combinations that may be of promise in the management of depressions that do not respond to treatment with a single drug. These include the use of tricyclic antidepressants with monoamine oxidase inhibitors (MAOI's), L-triiodothyronine (T3), methylphenidate, lithium carbonate, L-tryptophan, reserpine, and neuroleptics; MAOI's with lithium and L-tryptophan; and L-tryptophan with allopurinol. The authors stress the need for further double-blind, controlled studies to evaluate the safety and efficacy of these combinations.

Withdrawal symptoms during the course of imipramine therapy.

The authors describe 2 cases in which withdrawal symptoms occurred during the course of imipramine therapy, after the patients had failed to take a single daily dose of medication. They note that similar withdrawal symptoms have been noted upon discontinuation of imipramine and its derivatives desipramine and chlorimipramine, but have not--with one exception--been reported in association with other tricyclics.

Intraoperative examination of the sentinel lymph node for breast carcinoma staging.

Intraoperative pathologic examination of the sentinel lymph node (SLN) draining a primary breast carcinoma allows an SLN-positive patient to undergo complete axillary lymphadenectomy as part of the same surgical procedure. However, the optimal technique for rapid SLN assessment has not been determined. We reviewed our results with imprint cytology (IC) and frozen section (FS) examination of SLNs from 278 patients. Compared with H&E-stained paraffin sections, IC and FS had an overall accuracy of 93.2%. The false-reassurance rate (false-negative results/all negative results) was 8.4%. It correctly identified 98% of macrometastases but only 28% of micrometastases. There were no false-positive results. Compared with paraffin-section cytokeratin immunohistochemistry results, the IC-FS false-reassurance rate increased to 25.8%. The false-reassurance rate decreased with smaller primary tumor size (T1 vs T2/3) and ductal type, smaller diameter of the SLN (< or = 2.0 cm), and greater pathologist experience. IC combined with 2-level FS reliably identifies SLN macrometastases but commonly fails to detect SLN micrometastases. If SLN micrometastasis is used to determine the need for further lymphadenectomy, more sensitive intraoperative methods will be needed to avoid a second operation.

2-Hydroxydesipramine and desipramine plasma levels: how are they related to antidepressant response?

Thirty-six outpatients aged 20 to 51 with RDC primary major depressive disorder (MDD) completed a 5-week trial of desipramine following a week of single-blind placebo. Five had a past history of hypomanic disorder. For all but one patient, daily dosage at bedtime was constant for the final 4 weeks, with a mean (S.D.) of 168.1 (46.5) mg. Plasma samples drawn at the three final weekly visits were assayed by high-performance liquid chromatography for 2-hydroxydesipramine (2-OH-DMI) and desipramine. Mean (S.D.) plasma levels were 59.8 (30.0) ng/ml for 2-OH-DMI and 142.9 (138.6) ng/ml for desipramine. Thirteen patients (36%) had a final 17-item Hamilton depression rating < and = 6 and were classified as responders. According to receiver operating characteristics analysis, patients with plasma 2-OH-DMI levels > and = 58 and < 92 ng/ml had a greater likelihood of responding than those with lower or higher levels (p = 0.005, Fisher's exact test), while patients with plasma desipramine levels > and = 64 ng/ml were more likely to respond than those with lower levels (p = 0.032, Fisher's exact test). Results using an alternate response criterion were similar. These findings suggest that in desipramine-treated outpatients with primary MDD the relationship between therapeutic response and plasma levels is curvilinear for 2-OH-DMI and linear for desipramine.

Serum and red cell folate concentrations in outpatients receiving lithium carbonate.

We measured serum and RBC folate levels in 17 outpatients taking lithium for the prophylaxis of recurrent major affective disorder. In contrast to a previous report, we found no evidence for low folate concentrations or for any significant correlation between folate levels and affective morbidity.

Depression in the elderly.

Depression in the elderly can be difficult to diagnose but often responds well to treatment. In treating late-life depression, we have the satisfaction not only of relieving our patients' distress but very likely of prolonging their lives as well.