Phenelzine and amitriptyline in the treatment of depression. A comparison of present and past studies.

We present the results of a direct comparison of pheneizine sulfate and amitriptyline hydrochloride therapy in 105 depressed patients. We believe this is the first definitive double-blind controlled clinical trial of a monoamine oxidase inhibitor and a tricyclic antidepressant in the outpatient setting. The results show both antidepressants to be effective, with the similarities between the two exceeding the differences. Both drugs had marked antidepressant and antianziety effects. Phenelzine tended to exert a stronger antianxiety action; amitriptyline was more effective in reversing weight loss and improving sleep. The incidence of two side effects, sedation and orthostatic hypotension, was almost identical. Dry mouth was more prevalent with amitriptyline. We discuss the indications for the differential clinical use of both drugs in depressed outpatients.

Clinical pharmacology of phenelzine.

There is renewed interest in the clinical pharmacology of phenelzine sulfate and other monoamine oxidase (MAO) inhibitors. Newer clinical and analytic techniques recently have been applied to investigations of this class of drugs in man. The results show that drugs such as phenelzine are effective in nonendogenous depression and phobic disorders. Clinical response to phenelzine is related to platelet MAO inhibition and dosage per unit body weight. High percent MAO inhibition in platelets at two weeks is associated with greater improvement after a six-week course of treatment. Our data show that a safe, effective phenelzine dose in 1 mg/kg body weight per day. These results have delineated the pharmacologic and therapeutic effects of phenelzine and support a continuing role for MAO inhibitors in psychopharmacology.

A multiple-dose, controlled study of phenelzine in depression-anxiety states.

In a double-blind, controlled experiment, 62 outpatients with symptoms of depression with anxiety were selected for treatment with phenelzine sulfate, 60 mg daily, phenelzine sulfate, 30 mg daily, or placebo for six weeks. Forty-nine patients (79%) completed the experiment. Phenelzine sulfate, 60 mg daily, was significantly more effective than placebo in relieving symptoms of both depression and anxiety. Phenelzine sulfate, 30 mg daily, did not differ from the placebo. Only phenelzine sulfate, 60 mg daily, resulted in a median inhibition of platelet monoamine oxidase that exceded 80%. The results confirm a previous study that found phenelzine to be effective in the treatment of outpatients with depressive-anxiety states. Drug dosage is an important variable influencing clinical outcome in this patient group.

A comparison of standard alternating current and low-energy brief-pulse electrotherapy.

This study compares a low-energy brief-pulse stimulus (LEBS) with a conventional a-c sine wave stimulus in terms of electrical paramenters, efficiency in producing seizures, and clinical outcome on a variety of standard behavioral measures. The results show the LEBS to require equal voltage, less current, and only one-half the total energy to produce clinically manifest convulsions. There was no apparent difference between methods on any outcome measure. The Halstead-Reitan Neuropsychological Test Battery showed as many patients impaired prior to ECT as following treatment. Implications for ECT practices are discussed.

Portable electromyograph monitoring of unilateral ECT.

The authors describe a portable electromyograph (EMG) designed for use in monitoring unilateral ECT. Administration of muscle relaxants in conjunction with ECT often makes it difficult to determine that an adequate response has been elicited. The authors feel that this adaptation of the EMG provides a useful and easy means of monitoring the presence, bilateralism, and length of the seizure.

Relationship between age and tricyclic antidepressant plasma levels.

Older depressed patients treated with imipramine or amitriptyline developed higher steady-state plasma levels of imipramine, desipramine, and amitriptyline. In imipramine-treated patients this finding was associated with a decreased rate of drug elimination from plasma. These findings provide at least a partial explanation for the increased susceptibility of the older patient to tricyclic antidepressant side effects and also provide a pharmacological rationale for use of lower dosages in this age group.

Plasma tricyclic drug levels in amitriptyline-treated depressed patients.

In a double-blind phenelzine controlled clinical trial, 49 depressed outpatients were treated with a fixed dose of amitriptyline (AMI) 150 mg/day for 6 weeks. No significant relationships were found between steady-state plasma levels of AMI and its metabolite, nortriptyline, at 4 weeks and therapeutic response at 6 weeks or side effects. In the patient subgroup with more severe endogenous symptoms, there was a general trend for a weak positive association between AMI plasma levels and clinical improvement. Plasma tricyclic determinations appear to have little if any predictive value for antidepressant effect in outpatients treated with AMI.

Use of MAOI antidepressants.

The monoamine oxidase inhibitors (MAOIs) exert significant antidepressant, antianxiety and antiphobic effects. They are safe, provided the patients are carefully selected for treatment and are given instructions on incompatible foods and drugs that must be avoided. The MAOIs represent effective alternatives to the tricyclic antidepressants. Phenelzine is an excellent agent for treating ambulatory patients with neurotic depression and those with agoraphobia and social phobias.

Neuropsychological effects of electroconvulsive therapy.

Although ECT as the treatment of choice for psychotic depression has been in use for many years, little is known about the neocortical residual of such treatments inferred from behavioral measures. The major portion of the literature has been concerned with inferred or observed changes in affective state. The present study compared pre- and posttreatment performances on the Halstead-Reitan neuropsychological battery of 20 patients who were receiving ECT from two different machines. Most Ss gave indicators of cerebral impairment prior to treatment when performance of one side of the body was contrasted with performance of the other side. After treatment, there was an increased number of Ss who evidenced signs consistent with damage to the right cerebral hemisphere. Some concern was raised that a large number of patients who eventually are subject ot ECT because of depression behave in this way because of an undiagnosed neocortical dysfunction. There is some suggestion that the effect of the procedure is to either create or intensify a right hemisphere focus as inferred from behavioral measures.