Donald R. Sweeney

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.

Bromocriptine treatment for cocaine abuse: the dopamine depletion hypothesis.

The authors review the evidence that cocaine exerts its rewarding effects through the acute activation of dopamine (DA) pathways in the brain. Chronic cocaine administration is hypothesized to lead to DA depletion, which results in cocaine craving and cocaine abstinence states. Treatment of these states with bromocriptine, a DA antagonist, appears to have efficacy with acute and maintenance trials, and may represent a new adjunctive treatment for cocaine abuse. DA antagonists appear to exacerbate cocaine craving, which is consistent with the DA depletion hypothesis of chronic cocaine abuse. Theoretical issues relating to drug addiction and endogenous reward centers are discussed.

ECSTACY: A Review of MDMA and MDA

The Drug Enforcement Administration classified the drug methylenedioxymeth-amphetamine, MDMA, also known as Ecstacy, as a Schedule I controlled substance on July 1, 1985. The controversy surrounding the classification of MDMA is related to the question of its efficacy as an adjunct to psychotherapy and the larger issue of how to regulate the production and use of designer drugs. The authors review the literature on MDMA and its predecessor, MDA, a substance that differs from MDMA by one methyl group.

ANTIMANIC, ANTIDEPRESSANT, AND ANTIPANIC EFFECTS OF OPIATES: CLINICAL, NEUROANATOMICAL, AND BIOCHEMICAL EVIDENCE

These clinical data may offer some support for the hypothesis that opiates have antidepressant, antimanic, and antipanic effects. This hypothesis should be studied directly by double-blind studies of the effects of exogenous and synthetic endogenous opioid peptides in patients with major depressive illness, panic and anxiety states, schizophrenia, and schizo-affective illness. These clinical data support our studies in nonhuman primates and man which suggest a common LC or NE hyperactivity may underly both drug withdrawal and spontaneous panic states. Whether endorphin deficiency or derangements account for the postulated NE hyperactivity needs additional study and we will discuss our preliminary work later. Failure of endorphins to terminate bursts in LC firing rate and NE release may be responsible for both of these types of panic states. In addicts, this mechanism could exist prior to opiate use, or abuse of potent exogenous endorphinomentic compound may cause an endorphin-abnormality. Both of these possibilities would be compensated by continuous opiate maintenance. Methadone maintenance is a complicated psychiatric, psychological, and social phenomenon. Further studies are necessary to evaluate the role of opiate maintenance in treating or suppressing the emergence of underlying psychopathology. Previous psychiatric hospitalization or treatment for a schizophrenic or affective illness may contraindicate absolutely the use of clonidine or other rapid detoxification methods. These data suggest the possibility of substituting a nonaddicting psychotropic medication for opiates in some patients who are self-medicators. The clinical data support other data suggesting the potential antipsychotic, antidepressant, and antianxiety/antipanic effects of the endogenous opioids, endorphins, and exogenous opioids, endorphins, and exogenous opiates. These and other data suggest potential utility for opioid agonists and endorphin testing in psychiatric treatment and diagnosis.

Opiate detoxification with lofexidine

Abstract Noradrenergic neuronal hyperactivity is the final common pathway responsible for the signs and symptoms of opiate withdrawal in man. We have used this NE hyperactivity hypothesis to explain a large body of preclinical and clinical research and in screening potential antiwithdrawal treatments for clinical use. While the efficacy of clonidine in human opiate withdrawal offered strong support for the LC disinhibition or NE hyperactivity hypothesis on the basis of the known effects of low dose clonidine on the LC and NE activity, it was only one test of the hypothesis. More recently, we have suggested that lofexidine, an imidazoline derivative which is a structurally related analogue of clonidine, may be the ideal non-opiate antiwithdrawal agent for outpatients. We have recent data from 15 male chronic methadone addicts which demonstrates potent antiwithdrawal activity for lofexidine and offers additional support for the NE hyperactivity hypothesis of opiate withdrawal. Lofexidine significantly reduced withdrawal signs and symptoms. Systolic and diastolic blood pressure were not significantly decreased and remained in the normal range. The effects of clonidine and now lofexidine in opiate withdrawal support the NE hyperactivity hypothesis and suggest these medications reverse opiate withdrawal by replacing opiate-mediated inhibition with alpha-2 adrenergic inhibition of NE activity.

Plasma Levels of Tricyclic Antidepressants in Panic Disorder

Five patients with panic disorder were placed on low doses of imipramine. All patients had shown dramatic improvement after three weeks of treatment, when plasma levels of imipramine and desipramine were measured. Plasma levels corresponded to the low doses being administered. This result implies that the mechanism of action of tricyclic antidepressants is different in patients with panic disorder than in patients with depressive disorder.

Cannabis diagnosis of patients receiving treatment for cocaine dependence

In three separate samples using DSM-III-R criteria for substance dependence in 232 inpatients and 51 outpatients, we confirm the clinical suspicion that many cocaine dependents qualify for the diagnosis of cannabis dependence. As many as 53% of cocaine dependents diagnosed by DSM-III-R criteria have the concurrent diagnosis of cannabis dependence. The reports regarding cannabis dependence among cocaine dependents are few and inconclusive. The diagnosis of cannabis dependence in cocaine dependents has important consequences on etiology, prognosis, and treatment.

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.

Multifocal Neurological Impairment Caused by Infection-Induced Rise in Blood Lithium and Amitriptyline

We present the case of a thirty-eight-year-old woman who developed a febrile illness which was associated with a rise of blood lithium and amitriptyline, and subsequently suffered permanent neurological impariment, implicating CNS dysfunction at several levels. Medical, laboratory, radiological and neuropsychological findings are described, and the attribution of the syndrome is discussed. It is crucial to emphasize that the authors are not challenging the frequently useful combination of lithium and antidepressants. Rather, we urge psychiatrists to be vigilant when such patients develop febrile illnesses.