In a series of 39 patients with major depression, 16 were found to have delta thyroid-stimulating hormone (TSH) results greater than 20, suggestive of subclinical hypothyroidism. The two groups of patients did not differ in severity of depression (Beck Depression Inventory), in subclinical symptoms of mood disorder (the General Behavior Inventory), in family history of depression, or in family history of thyroid disorder. Thyroid hormone treatment alone was given to 8 of these 16, all of whom had full remissions (p = 0.004). Six-month follow-up data indicated that these remissions were maintained, while thyroid function measures were significantly improved. Depressed patients who have thyroid insufficiency as determined by delta TSH results may respond to treatment with thyroid hormone, without need for antidepressants.

Twelve young adults meeting DSM-III-R criteria for cocaine dependence were administered single oral dose of the dopamine agonist bromocriptine and the noradrenergic tricyclic desipramine within 72 hours of hospital admission using a double-blind, random assignment, crossover design. Self-ratings of drug craving, depressed mood, and energy showed reduced craving after administration of both medications, but improvement in depressed mood and energy only after bromocriptine. Implications or these findings for understanding the neuro-chemistry of cocaine dependence, as well as for treatment of cocaine withdrawal in the clinical setting are discussed.

An 8-week open, non-randomized study compared the dopamine-specific antidepressant, bupropion, to the serotonin-specific antidepressant, fluoxetine. Of the 57 patients, 10 met DSM-IIIR criteria for bipolar depression. The other 47 met DSM-IIIR criteria for major depressive disorder. Of these, 23 were subclassified as “atypical” whereas 24 were “typical” based on sleep and appetite patterns. In bipolar patients, depression (as indicated by fall in Beck Depression Inventory [BDI] score) improved significantly in eight of nine patients following administration of bupropion (the mean fall = 16.3 [p < 0.003]). In atypical depression patients, depression as measured by BDI improved significantly after bupropion, but not after fluoxetine. Significant improvement was seen following bupropion in 9 of 14, but only in 2 of 9 following fluoxetine. In typical depression, BDI dropped 6.0 (p = 0.09) after bupropion, and 11.8 (p = 0.002) after fluoxetine. Significant improvement was seen after bupropion in 2 or 1...

Thyroid tests, especially the TRH test, can aid psychiatrists in the same way that laboratory tests are used in other medical specialties. Such tests augment clinical judgment and provide information about possible primary thyroid disturbances. The TRH test has the added value of prognostic significance when repeated after a course of treatment. Thyroid tests may also identify subgroups of depressed patients who can benefit from thyroid hormone replacement or who require T3 potentiation of tricyclics, as well as those patients with bipolar illness who are hypothyroid and may be at risk for rapid cycling.

The aim of this paper is to review and explore the psychopharmacology of cocaine from two divergent points of view - the chronic user and the laboratory. Cocaine's behavioral effects will be correlated with neurophysiological, neurochemical events, and reports by users of consequences of chronic use. These studies and reports when pieced together offer considerable promise in the development of a natural history of compulsive cocaine use. Additional neurochemical and neurophysiological research investigations are needed to allow for the development of non-addicting treatmetns for detoxification (a la clonidine) and prophylaxis (a la naltrexone). In the absence of these data cocaine treatment programs have been developed borrowing heavily from self help, contingency contracting and inpatient programs for working addicts.

The aim of this paper is to review and explore the psychopharmacology of cocaine from two divergent points of view--the chronic user and the laboratory. Cocaine's behavioral effects will be correlated with neurophysiological, neurochemical events, and reports by users of consequences of chronic use. These studies and reports when pieced together offer considerable promise in the development of a natural history of compulsive cocaine use. Additional neurochemical and neurophysiological research investigations are needed to allow for the development of non-addicting treatments for detoxification (à la clonidine) and prophylaxis (à la naltrexone). In the absence of these data cocaine treatment programs have been developed borrowing heavily from self help, contingency contracting and inpatient programs for working addicts.

This chapter focuses on the studies of dopamine hypothesis of schizophrenia. The group of disorders known collectively as schizophrenia continues to be a critical problem for modern psychiatry and accounts for large expenditures by society and tragedy for many families. The predominant hypothesis for a neurochemical defect in schizophrenia is the dopamine (DA) hypothesis of schizophrenia, which suggests that there is an excess of DA neuronal activity in specific brain areas in schizophrenic patients. Such excess DA activity could occur through increased presynaptic DA release via increased DA synthesis and/or faulty negative feedback regulation, or through supersensitive postsynaptic DA receptors. The DA hypothesis of schizophrenia is supported by indirect pharmacologic evidence. Drugs such as amphetamine and methylphenidate, which increase central DA function, in high and long-term doses, can produce a paranoid schizophrenic-like syndrome in normal subjects. These drugs also exacerbate positive symptoms, that is, hallucinations, delusions, in schizophrenic patients.

It is well documentedl.2 that hypothyroidism can produce signs and symptoms of depression. It has also been shown3.4 that several grades of hypothyroidism exist, and they can be assessed by a thorough thyroid examinationS and by measurement of triiodothyronine (T3), thyroxine (T.), thyroid-stimulating hormone (TSH), and TSH response induced by thyrotropin-releasing hormone (TRH).3.4 Lithium is known6 to cause hypothyroidism, which may first become evident by the increased TSH response to TRH.3.4·7 Linstedt and associates8 have reported a 20% prevalence rate of lithium-induced hypothyroidism in women, using the criterion of elevated TSH and clinical signs and symptoms, with one third of the patients developing hypothyroidism during the first year of treatment. Since patients taking lithium are usually those with recurring depression, bipolar or unipolar, it is conceivable that depression in such patients could be induced or exacerbated by subclinical (grade 3-discussed later) hypothyroidism secondary to lithium. The differential diagnosis of depressed mood and lack of energy in a depressed patient treated with lithium thus should

The authors emphasize the favorable response of most patients with major depression to appropriate pharmacotherapy, and present a decision-tree approach to the pharmacotherapy of major depression. Also discussed are use of contemporary clinical nosology and neuroendocrine diagnostic tests to identify candidates for pharmacotherapy and/or ECT, use of secondary tricyclics because of their lower incidence of side-effects, monitoring plasma levels of antidepressants to achieve therapeutic levels, and potentiating tricyclic nonresponders with T3 or lithium.

The thyrotropin-releasing hormone (TRH) test may be useful in differentiating major depressive disorders from other psychiatric and medical conditions that can be associated with depressed mood. Clinical experience with euthyroid patients with major unipolar depression or non-major depression and with normal controls indicates that a blunted thyroid-stimulating hormone (TSH) response to 500 μg of TRH can potentially aid the clinician in diagnosis, choice of treatment, and prognosis in patients with affective illnesses. Further research on optimal utilization of TRH test abnormalities in affective disorders is needed, along with better understanding of the mechanisms of these abnormalities.

Plasma cortisol levels of 28 hospitalized patients meeting Research Diagnostic Criteria for major or nonmajor (minor or intermittent) depression were significantly higher than those of eight normal subjects. In contrast, plasma beta-endorphin immunoreactivity was significantly lower in patients with nonmajor depression than in those with major depression or in normal subjects. A low ratio of plasma beta-endorphin to cortisol immunoreactivity was found to characterize patients in both groups. Through the use of only this ratio, a post-hoc analysis identified 25 depressed patients and seven controls. These findings have implications for psychiatric diagnosis and the involvement of the endogenous opioid system in the pathogenesis of depression.

The authors examined the relationship between both pre-dexamethasone 8:00 AM serum cortisol level and the dexamethasone suppression test (DST) with urinary 3-methoxy-4-hydroxyphenyl glycol (MHPG) excretion in a group of fifteen men and fourteen women with unipolar depression. No significant difference was found between the mean MHPG excretion for either male or female DST suppressors or non-suppressors. No significant correlation was found between the pre-dexamethasone 8:00 AM serum cortisol level and urinary MHPG. These results do not support the hypothesis that DST non-suppression in depression is related to central noradrenergic deficiency.