Primary affective disorder, clinical state change, and MHPG excretion: a longitudinal study.

Urinary 3-methoxy-4-hydroxyphenethylene glycol (MHPG) excretion, which is thought to reflect CNS norepinephrine metabolism, has been shown to be significantly decreased in some depressed patients. Although there is consensus that urinary MHPG excretion varies directly with mood in rapidly cycling bipolar patients, there is little information on longer term state changes, such as those that accompany recovery from depression. Ten female patients with diagnoses of primary affective disorder were studied initially during an inpatient hospitalization and restudied at least ten months after discharge. Five healthy female comparison subjects were also studied over a similar interval of time. During the baseline period, the patient sample excreted less MHPG than did the comparison group. Improvement in clinical state from a seriously depressed baseline was associated with a significant increase in MHPG excretion, while the patients with recurrences of depression showed no change and continued to excrete less MHPG than the comparison subjects. These results suggest that urinary MHPG excretion may represent an index of psychobiological state in depressive patients.

State anxiety, physical activity, and urinary 3-methoxy-4-hydroxyphenethylene glycol excretion.

Measurement of urinary 3-methoxy-4-hydroxyphenethylene glycol (MHPG) levels has been suggested as possibly being important in elucidating the role of central noradrenergic function in affective illnesses. The influence on urinary MHPG excretion of the state variables of physical activity and stress has not been clearly defined in previous studies. During a baseline medication-free period, 24 hospitalized depressed female patients underwent a five-day protocol including an eight-hour period of either enhanced or restricted activity. Throughout the protocol, independent measurements of telemetered mobility and stale anxiety were obtained. There were no significant effects of physical activity on urinary MHPG levels. Furthermore, baseline urinary MHPG levels and baseline state anxiety did not covary significantly. However, within-individual analyses yielded a highly significant relationship between changes in urinary MHPG levels and changes in state anxiety. The data suggested that those patients with lower baseline MHPG levels were those more prone to experience increased anxiety under environmentally "activating" circumstances.

Plasma free and conjugated MHPG in psychiatric patients. A pilot study.

Measures of plasma 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) may be useful for investigating noradrenergic function in certain behavioral and physiologic states. Serial plasma and urine samples were obtained from a diagnostically heterogeneous group of ten psychiatric inpatients over a three- to five-day period. The plasma samples were assayed for free and total MHPG and the urine samples for total MPHG. The variance between patients in both plasma free and conjugated MHPG was markedly greater than the variance within patients. The test-retest reliability for free plasma MHPG in both AM vs PM values within and across study days was also significant for both free and conjugated MHPG even though the AM plasma free MHPG values were significantly greater than the PM values. No significant correlations were found between plasma free and conjugated MHPG or between urinary total MHPG and plasma free MHPG.

Exacerbation of psychosis by tricyclic antidepressants in delusional depression.

The authors describe three patients with delusional unipolar depression whose delusional thinking worsened markedly following administration of tricyclic antidepressant drugs. The patients had met Research Diagnostic Criteria for major depressive episode and had no evidence of schizophrenia or mania. Since tricyclic antidepressants are known to exacerbate psychosis in schizophrenic patients, it is sometimes suggested that the exacerbation of psychotic thinking in depressed patients indicates schizophrenia. The authors suggest that such an exacerbation does not in itself indicate schizophrenia but may occur in patients with an affective disorder who are prone to depressive delusions. The authors discuss the use of antipsychotic medication in this patient group and present a neurochemical hypothesis to explain the interaction of the drug with the illness, which results in exacerbation of psychotic thinking.

Urinary 3-methoxy-4-hydroxyphenylglycol and psychiatric diagnosis.

The authors examined the quantities of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the urine of 11 schizophrenic female patients, 14 primary affective disorder (depressed type) female patients, and 10 healthy comparison women. The primary affective disorder patients had significantly less MHPG in their urine than did the comparison subjects. The schizophrenic patients when compared with the healthy subjects or the depressed patients did not excrete significantly different amounts of MHPG in urine. The variance in MHPG in schizophrenic patients was quite large; some had very low urinary MHPG. There was a significant positive correlation between agitation and urinary MHPG for schizophrenic but not depressed patients. The authors discuss theoretical and practical implications of these findings.

Plasma cortisol and beta-endorphin immunoreactivity in nonmajor and major depression.

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.

Specificity of the TRH test for major depression in patients with serious cocaine abuse.

The authors administered the thyrotropin-releasing hormone (TRH) test to 17 patients with severe cocaine abuse and without major depression. The results suggest that the test is not specific for major depression when serious cocaine abuse is present.

Treatment of outpatients with borderline personality disorder.

Outpatient treatment of patients with borderline personality disorder is sometimes more difficult and more challenging than inpatient treatment. Because symptoms are frequently less florid and more variable in the outpatient, diagnostic evaluation must proceed at a slower pace. Diagnostic distinctions among patients with borderline personality disorder are based on whether the predominant symptoms displayed are "affective," "schizotypal," or "impulse-disordered." Outpatient evaluation requires a keen sensitivity to the presenting problems and the ability to assign priorities to treatment issues. Pharmacotherapy can be of advantage in treating outpatients with borderline personality disorder, but care must be taken in selecting appropriate drugs and dosage and in communicating to the patient what can be expected during therapy. Borderline patients with impulse-control disorders, especially substance abuse, cannot be treated effectively with individual psychotherapy alone. Although many creative and articulate psychodynamic formulations of borderline personality disorder have been proposed, an initial "cognitive" approach to psychotherapy combined with pharmacotherapy can be effective in alleviating acute symptoms, and more psychodynamic approaches can be employed when the patient is better equipped to use them.

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.

Evidence for an endorphin dysfunction in methadone addicts: lack of ACTH response to naloxone.

Chronic exogenous opiate administration might be responsible for the acute and protracted abstinence syndrome by producing a prolonged decrease in the availability of endogenous opioids (endorphins). However, the hypothesis that potent exogenous opiates may have anti-endorphin effects has been difficult to test. We have been investigating this hypothesis with neuroendocrine test paradigms which have provided preliminary evidence of anti-endorphin effects for chronic methadone. Naloxone-induced ACTH response data from chronic methadone addicts offers preliminary support for the hypothesis that chronic exogenous opiate administration has anti-endorphin effects. The subjects were 7 male methadone addicts who had been addicted to greater than or equal to 40 mg of methadone and 7 male healthy opiate-naive volunteers. Naloxone failed to produce a significant increase in ACTH in methadone addicts while opiate-naive normal volunteers demonstrated a significant naloxone-induced release of ACTH. Five of the seven methadone addicts ahd no demonstrable ACTH response to naloxone. These impaired naloxone response data reported here for recently detoxified addicts suggest that chronic methadone administration comprises the functional integrity of the endorphin system. Prolonged abstinence, post-detoxification depression and other affective symptoms which contribute to relapse may result from a prolonged endorphin derangement.

The TRH test and urinary MHPG in unipolar depression.

Twenty-five men and 26 women with major unipolar depression were evaluated by the TRH test and urinary MHPG excretion. A significant positive correlation between TSH response to TRH and urinary MHPG was found in the men, though not in the women. These findings suggest that at least for depressed men, central norepinephrine deficiency may be the neurobiological substrate of blunted TSH responses to TRH.

Single-dose bromocriptine reverses cocaine craving.

Thirteen hospitalized cocaine addicts complaining of cocaine craving were given a single dose of bromocriptine, a dopamine agonist, in a randomized, double-blind, placebo-controlled study design. Compared to placebo, bromocriptine caused a significant reduction in craving ratings. These data suggest that bromocriptine may be effective as a new, nonaddictive pharmacological treatment for cocaine addicts and support the notion that functional dopamine depletion occurs with chronic cocaine use. Open trials indicate that low-dose bromocriptine may be useful in cocaine detoxification.

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.

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.

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