Biomedical subjects
Publications and source records attributed to M R Liebowitz.
Six patients developed symptoms of pyridoxine deficiency while taking phenelzine. All had low pyridoxine levels, five being abnormally low. In all patients, symptoms responded to the addition of pyridoxine while continuing the antidepressant.
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The ability of sodium lactate to precipitate panic attacks in vulnerable individuals has been repeatedly demonstrated, although its mechanism of action is unknown. Pitts and McClure hypothesized that the panicogenic effect of sodium lactate was due to its induction of a peripheral hypocalcemia via the complexing of infused lactate ions with extracellular ionized calcium. In the current study, serial ionized calcium measurements during lactate infusion are assessed for 22 panic patients who panicked during infusion, 11 panic patients who did not panic during the procedure, and 6 normal controls. Intravenous sodium lactate infusion was found to be associated with a significant decrease in ionized calcium in all groups. No specific association was found between the rate or magnitude of decrease in ionized calcium and the occurrence of a panic attack during the infusion.
Urinary phenylacetic acid (PAA) excretion was found to be decreased in a group of chronic schizophrenic patients, particularly in a nonparanoid subtype. No significant change in PAA excretion was observed in a group of 21 unipolar depressed patients. Urinary PAA was studied following the administration of phenylethylamine, monoamine oxidase inhibitors, a dopa decarboxylase inhibitor, a low phenylalanine diet, and phenylalanine loads in several groups of psychiatric patients and normal volunteers. While Phenylethylamine ingestion increased urine PAA, inhibition of both phenylethylamine metabolism and synthesis failed to alter urine PAA. These studies suggest that urine PAA is primarily derived from phenylalanine transamination or pathways not involving monoamine oxidase or both. The observed decrease in PAA excretion in some schizophrenic patients may reflect an alteration in this pathway. The high phenylethylamine excretion previously reported in some chronic schizophrenic patients is not directly related to the observed low PAA excretion. Therefore measurement of urine PAA is not expected to be useful in assessing any phenylethylamine abnormalities in psychiatric disorders. The possible contribution of reduced phenylalanine transamination and its subsequent increased availability for the possible synthesis of phenylethylamine in schizophrenia is discussed.
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The efficacy of desipramine for mild depression was tested in a double-blind, placebo-controlled study of outpatients with scores below 19 on the Hamilton Rating Scale for Depression (HAM-D). Of 103 such patients, 23 dropped out and 16 improved during a ten-day placebo period. Among 64 patients completing the randomized portion of the study, significantly more improved with desipramine that with placebo. The Research Diagnostic Criteria (RDC) category of major depressive disorder largely accounted for the drug-placebo response difference found for the entire sample. Patients with intermittent depressive disorder improved significantly less frequently with desipramine than patients with major depressive disorder. Independent of RDC diagnosis, severity of illness correlated with outcome. Thus, patients with pretreatment HAM-D scores at or above the median demonstrated significant drug effect, while patients with lower pretreatment HAM-D scores did not.
Many clinical and theoretic attempts have been made to link anxiety disorders and the beta-adrenergic nervous system. Six patients with panic disorder, who had panic attacks produced by sodium lactate infusions, were given repeated lactate infusions that were immediately preceded by intravenous administration of propranolol hydrochloride. In all cases, propranolol pretreatment infusion failed to prevent panic attacks, anxiety, tachycardia, and increased systolic BP during the lactate infusion.
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New uses are still being discovered for a number of psychotropic agents that have been available for some time. Among the more important recent discoveries are the efficacy of the tricyclic antidepressants for panic disorder and agoraphobia with panic attacks; the use of the monoamine oxidase inhibitors for the above disorders and for atypical depression and hysteroid dysphoria; the use of propranolol for anxiety disorders and for uncontrollable violent outbursts; the antianxiety and antipanic effects of clonidine; and the usefulness of lithium in treating schizophrenia and schizoaffective disorder and for emotionally unstable character disorders. In addition to strengthening the therapeutic armamentarium, the author says, the discovery of new drug response patterns helps generate or strengthen hypotheses about the pathophysiology of various psychiatric disorders.
The urinary excretion of some important phenylethylamines, catecholamines, their metabolites, amphetamine, and methamphetamine were measured in parkinsonian patients on Sinemet (L-dopa plus carbidopa, a peripheral dopadecarboxylase inhibitor) and depressed patients after chronic (-) deprenyl treatment. Deprenyl was efficiently metabolized to amphetamine and methamphetamine. It increased the excretion of phenylethylamine and of m- and p-tyramine, and reduced the output of norepinephrine metabolites, but failed to alter the excretion of dopamine-deaminated metabolites. These changes were attributed more to amphetamine and methamphetamine than to inhibition of monoamine oxidase type B. Sinemet treatment alone increased the excretion of dopamine, 3-methoxytyramine, and their respective deaminated metabolites, 3, 4-dihydroxyphenylacetic acid and homovanillic acid. It is concluded that conversion of deprenyl to amphetamine and methamphetamine may contribute to some of the therapeutic benefits of deprenyl.
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Clinical lore suggests that monoamine oxidase inhibitors (MAOIs) are not effective in endogenous depression. A review of previous placebo-controlled trials of MAOI in patients with endogenous depression neither refutes nor confirms their utility in this patient group. We present patients in the depressive phase of bipolar illness refractory to treatment with tricyclics who have responded to MAOI. These open trials require confirmation in controlled studies. Bipolar illness may be a heterogeneous disorder. Presence or absence of X-linkage, low platelet MAO, or response to MAOI may indicate different forms of the disorder.
Recent advances in our understanding of and ability to treat panic disorders and various types of phobia have been reviewed. A case of agoraphobia was presented in detail to illustrate clinical issues and serve as a basis for discussing differential diagnosis. The presence or absence of spontaneous panic attacks has crucial implications for classifying phobic states. Data and speculations concerning the pathophysiology of agoraphobia, social phobia and simple phobia were also presented. Finally, a variety of pharmacological and behavioral treatment approaches, some solidly established, other still investigational, were discussed.
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Severe depersonalization at times constitutes a chronic and disabling syndrome for which there is no generally established etiology or treatment. Two cases in which young female patients with severe depersonalization became floridly manic in response to stimulant and antidepressant drug treatment are reported, and the clinical and theoretical implications of these phenomena are discussed.