A.L.C. Pottash

The TRH test in the diagnosis of major and minor depression.

Abstract (1) The effect of TRH on TSH and GH release was studied in 144 consecutive psychiatric admissions. The magnitude of the TSH response to TRH differentiated unipolar from clinically similar and dissimilar groups. (2) Of 41 patients with unipolar depression, 31 had a ΔTSH of ≤7 μI.U./ml while only 1 of 12 bipolar and 0 of 10 minor depressive patients had a ΔTSH of ≤7 μI.U./ml. (3) A ΔTSH of ≤7 μI.U./ml is a frequent finding in unipolar depression and infrequently associated with other psychiatric diagnoses. (4) The data reported support the hypothesis that patients with a ΔTSH of ≤7 are unipolar depressives. (5) Six of 12 bipolar and 17 of 41 unipolar depressives had a GH response to TRH while none of the patients with a minor depression had a significant GH response. These data suggest that major and minor depressions can be separated on the basis of the TRH-induced GH response test. (6) The magnitude of the TRH-induced TSH response and the presence of a pathological GH response may be extremely useful in differentiating manics from schizophrenics and other similarly appearing patient groups. (7) The TRH test is useful in clinical differential diagnosis of dysphoric states and as a confirmatory laboratory test for major depressive disease and unipolar depression.

TRH-induced TSH response in unipolar, bipolar, and secondary depressions: Possible utility in clinical assessment and differential diagnosis

Abstract (1) The effect of TRH on TSH and GH release was studied in 32 depressed patients. (2) Patients were diagnosed as having a primary (unipolar or bipolar) or secondary depression and rated with Hamilton ratings at the time of TRH testing. (3) The magnitude of the TRH-induced TSH responses significantly differentiated unipolar and bipolar depressed patients who had similar symptoms, cortisol secretion, and Hamilton ratings. (4) GH responses to TRH were only observed in primary affective, depressed patients. (5) The fact that bipolar depressives had augmented TSH responses while unipolar patients had blunted TSH responses supports the clinical differentiation of these patients and suggests that different neurobiological factors may be involved in these clinically similar states. TRH-induced TSH response may ‘switch’ from augmented to blunted as the patients clinical state changes from depressed to manic. (6) The neural mechanism mediating these TRH test data is difficult to discern on the basis of current studies reported in the literature.

Relationship of Thyrotropin-releasing hormone test and dexamethasone suppression test abnormalities in unipolar depression

The thyrotropin-releasing hormone (TRH) test and the dexamethasone suppression test (DST) were administered to 50 inpatients with unipolar depression. Of the patients tested, 64% had a blunted thyroid-stimulating hormone (TSH) response to TRH and 50% failed to suppress on the DST. There was no significant association between these two abnormalities by chi-square test. This lack of association suggests that the blunted TSH response to TRH is not an artifact of hypothalamic-pituitary-adrenal hyperactivation. The TRH test and the DST complemented each other as biological markers for active unipolar depression: 30% of the patients were identified by both tests, 34% by the TRH test only, 20% by the DST only, and 16% by neither test. The two tests may be useful in developing a nosology for major unipolar depression that is based on both descriptive and neurobiological information.

Evaluating depression in alcoholics.

The persistence of untreated depression was evaluated in 49 severely depressed alcoholics. After 2 weeks of sobriety, 80% of patients with initial major depression by Research Diagnostic Criteria were no longer depressed. These patients improved without antidepressant medications, suggesting the need for a 2-week period of sobriety before psychopharmacotherapy for depression is instituted. Many severe depressions in actively drinking or recently sober alcoholics may represent alcohol-induced organic affective syndromes which, unlike major depressive illness, remit spontaneously with sobriety.

Drug Abuse and Bipolar Disorders

Abuse of multiple substances can coexist in many patients who present with symptoms indistinguishable from any Bipolar Disorder. Failure to recognize and treat this coexistent substance abuse may preclude the proper management of the bipolar disorder.

The thyrotropin-releasing hormone test in the diagnosis of unipolar depression

The establishment of criteria for a blunted thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) may prove useful in distinguishing patients with major unipolar depression from patients with nonmajor depressions and controls. To this end, we administered the TRH test to a group of depressed, euthyroid inpatients diagnosed by Research Diagnostic Criteria and 20 normal volunteer controls. The mean maximal TSH response (delta TSH) to infusion of 500 micrograms of TRH of 7.3 +/- SD 4.6 microIU/ml in the 105 patients with major depressive disorder, primary unipolar subtype was significantly lower than that of 13.4 +/- SD 4.4 in the 20 controls and 10.9 +/- SD 4.4 in the 40 patients with nonmajor depressions. The differences were not explainable by differences in baseline thyroid function, age, or sex. When a delta TSH less than or equal to 7.0 microIU/ml was used as a diagnostic test for unipolar depression, the sensitivity of the TRH test was 56%, the specificity 93%, and the predictive value 91%. These results suggest that the TRH test may be useful in confirming the diagnosis of major unipolar depression and hence identifying patients likely to respond to antidepressant medications or electroconvulsive therapy.

Efficacy of clonidine in opiate withdrawal: A study of thirty patients

In a placebo-controlled, double-blind crossover trial, clonidine caused a marked and significant reduction of objective signs and subjective symptoms of opiate withdrawal in thirty hospitalized opiate addicts. In an open trial of clonidine in opiate withdrawal, clonidine was found to suppress opiate withdrawal signs and symptoms, allowing all of the patients to detoxify successfully from chronic opiate addiction. Clonidine was demonstrated to reverse and suppress the signs, symptoms, and effects associated with opiate withdrawal. These data support a release from chronic opiate-induced noradrenergic inhibition producing noradrenergic hyperactivity as the pathophysiological substrate for opiate withdrawal. Clonidine replaces opiate-mediated inhibition with alpha-2 mediated inhibition of noradrenergic nuclei.

The thyroid-stimulating hormone response to thyrotropin-releasing hormone in mania and bipolar depression

The release of thyroid-stimulating hormone (TSH) from the pituitary after infusion of 500 microgram of thyrotropin-releasing hormone (TRH) was decreased (p < 0.01) in manic patients and increased (p < 0.01) in bipolar depressed patients compared to a control group of patients with personality disorders. These results suggest that the TRH test may be useful in the diagnosis of psychiatric disorders and in the prediction of response to pharmacotherapy. We discuss the role of central monoaminergic systems in changes in the TSH response to TRH.

Psychiatric Complications of Antihypertensive Medications

Psychiatric complications of antihypertensive medications have been identified in the literature primarily in case reports. Most other studies to date have suffered from major design flaws. Side effects seriously complicate the treatment of hypertensive patients and no doubt decrease compliance. There are significant interactions between psychotropic medications and antihypertensive drugs. The literature is reviewed, and the implications for clinical practice of psychiatric side effects of antihypertensive treatment and of psychotropic-antihypertensive interactions are discussed.

Thyroid-stimulating hormone response to thyrotropin-releasing hormone in unipolar depression before and after clinical improvement

Fourteen patients with unipolar depression who had a blunted thyroid-stimulating hormone (TSH) response to infusion of 500 micrograms of thyrotropin-releasing hormone (TRH) and who showed marked clinical improvement after pharmacotherapy and/or electroconvulsive therapy had the TRH test repeated after improvement. The mean (+/- SD) maximal TSH response to TRH (delta TSH) increased significantly from 4.0 +/- 1.9 to 9.1 3.5 micro IU/ml. The number of patients with delta TSH less than 7.0 micro IU/ml increased significantly from 0 to 9 of 14 after improvement. Eleven of the patients were followed for 5 to 19 months, and none showed clear relapse. The results suggest that the blunted TSH response to TRH has features of both a state marker for active unipolar depression and a trait marker for vulnerability to this illness, and support the suggestion that the TRH test may be useful in diagnosis and treatment planning.