Brain functions and psychiatric disorders. A clinical view.

Psychiatric disorders are viewed as brain disorders affecting five circuits of the brain: the brainstem, the hypothalamus, the motor striatum, the limbic system (ventral striatum), and the neocortex. This five-circuit model combines neuroscientific, psychopharmacologic, evolutionary, introspective, and behavioral data. The article presents a broad speculative overview of some brain functions and dysfunctions relevant for clinicians.

Differential effect of amitriptyline and bupropion on primary and secondary depression: a pilot study.

In a prospective, controlled, double-blind study, 37 patients with major depressive disorder were subclassified into primary depression (N = 25) and secondary (N = 12) depression and treated with either amitriptyline (primary depressives N = 13, secondary depressives N = 6) or bupropion (primary depressives N = 12, secondary depressives N = 6). A differential response to the novel antidepressant bupropion was observed between the two diagnostic subgroups, but no differential response to amitriptyline was observed; patients with primary depression and secondary depression responded equally well to amitriptyline but not to bupropion. Our results provide pharmacological evidence supporting the usefulness of this subclassification of depression.

Evaluation of sexual dysfunction.

Sixteen analogue scales were designed to measure drug- and illness-related changes in three dimensions of sexual function: interest, arousal, and performance. An orthogonal principal component factor analysis confirmed the three clinical factors. Retest reliability ranged between .80 and .94. Normals (N = 30) reported significantly better functioning than did psychiatric outpatients (N = 30).

Effect of buspirone on sexual dysfunction in patients with generalized anxiety disorder.

After 4 weeks' treatment with buspirone, sexual function was normalized in 8 of 10 patients with generalized anxiety disorder. Nine of the patients had reported decreased sexual function before treatment. Buspirone appears to offer a clinical advantage over existing anxiolytics, which are usually associated with impairment of sexual function.

Refractory migraine headache controlled with alprazolam: case report.

A woman with major depressive disorder and refractory, incapacitating migraine headaches responded to alprazolam in a double-blind, placebo-controlled study. Migraine, but not depression, recurred following tapering of the drug, suggesting efficacy of alprazolam for control of refractory migraine.

Tricyclic-induced electroencephalogram abnormalities and plasma drug concentrations.

In a double-blind study of 34 randomly assigned depressed inpatients, antidepressant-induced electroencephalogram (EEG) abnormalities were compared in amitriptyline-treated versus bupropion-treated patients. Drug-free baseline EEGs plus one or more repeat EEGs under pharmacokinetic steady state conditions were obtained. Of the 34 patients, eight developed EEG abnormalities. Seven were on amitriptyline and one was on bupropion (chi 2 = 13.77, df = 3, p less than 0.01). All but one of the amitriptyline-treated patients with EEG abnormalities had plasma concentrations above its therapeutic range (150 to 250 ng/ml), whereas all with normal EEGs were within or below this range.

Evaluation of bupropion hydrochloride: the first of a new class of atypical antidepressants.

Bupropion hydrochloride is a new antidepressant that differs clinically and pharmacologically from the tricyclic antidepressants and the monoamine oxidase inhibitors. Pharmacokinetically, bupropion is an intermediate-lived drug with a half-life of about 12 hours. Its antidepressant activity in man has been demonstrated in double-blind, placebo and active drug-controlled studies. Onset of antidepressant action occurs in one to three weeks. Bupropion has a greater effect on the neuronal reuptake of dopamine than of other biogenic amines. At a recommended dose of 450-600 mg/day, the side effect profile of bupropion also distinguishes it from other antidepressants. It does not bind to cholinergic receptors in vitro at clinically relevant concentrations and does not produce appreciable autonomic side effects. The exception is dry mouth, which is reported in 13% of patients. The mechanism underlying this effect is unclear. Bupropion is devoid of cardiovascular effects (e.g., impaired intracardiac conduction, reduced myocardial contractility, decreased peripheral resistance, orthostatic hypotension) in both human and animal studies. The drug is nonsedating and antagonizes the effects of commonly used sedatives, such as alcohol and diazepam. It does not produce weight gain. In susceptible patients, activating effects can occur. Given this profile, bupropion should be less toxic than conventional antidepressants when taken in overdoses; however overdose experience with the drug is limited.

Long-term efficacy and safety of bupropion.

Bupropion is a novel, structurally unique (single ring) compound, radically different from tricyclic antidepressants in its pharmacologic profile. In a random assignment, double-blind, long-term follow-up study of 60 depressed in- and outpatients (DSM-III criteria) in eight centers, the antidepressant actions of bupropion and amitriptyline were compared. Bupropion was as effective as amitriptyline in reducing depressive symptoms over a 6-month period, as measured by Hamilton depression and anxiety scales and Clinical Global Impression scores. Unlike amitriptyline, bupropion did not increase uric acid or cholesterol levels, and was not associated with weight gain. Bupropion was better tolerated than amitriptyline, the most commonly prescribed antidepressant.

Electromyogram processing for sleep research.

A computer method for quantifying the submental electromyographic surface interference pattern (EMG) during sleep and wakefulness by amplitude envelope measurement for consecutive 2-sec intervals is described. The method is largely insensitive to electrocardiogram (EKG) artifact. Though this algorithm was developed as part of a program to detect electroencephalographic (EEG), electrooculographic (EOG), tonic and phasic EMG changes during sleep, the method is applicable by itself wherever the envelope width of the EMG interference pattern is of interest. The results obtained correlate well with visual estimates of the amplitude envelope of the raw EMG. It offers increased speed, accuracy and reproducibility compared to visual EMG evaluation and enables a high degree of information extraction. The simplicity of the algorithm permits implementation and on-line processing on a small laboratory computer.

Plasma indolethylamine-n-methyltransferase activity and growth hormone level during sleep: a pilot study.

Polygraphic recordings and sequential growth hormone (GH) samplings were performed in eight healthy adult males. In the plasma samples from seven of the subjects, indolethylamine-N-methyltransferase (INMT) activity was also determined. Five of eight subjects showed significant fluctuation in plasma GH level, and six of seven subjects showed significant fluctuation in plasma INMT activity level. There were also significant positive correlations between plasma GH and INMT activity level during the second episode of NREM sleep stage 1 and during the third episode of NREM sleep stage 2. A significant negative correlation between plasma GH and INMT activity level during the seventh episode of sleep stage 2 and during the fifth episode of post sleep-onset wake was found. In view of a previous finding that INMT activity in the serum of psychiatric patients is positively correlated with severity of delusions, the observation that NREM sleep is associated with mental activity characterized by repetitive thoughts, and the result that GH level in plasma is increased in NREM sleep early at night, our present findings suggest the hypotheses that increased plasma INMT activity during sleep is indicative of both increased INMT activity in the central nervous system (CNS) and the activation or maintenance of NREM mental activity during sleep. Additional research will be needed in order to validate our observations and test these hypotheses.