Search

Objective: The purpose of this study was to compare the effectiveness and tolerability of tranylcypromine and combination treatment with extended-release venlafaxine and mirtazapine in patients with treatment-resistant major depression whose current depressive episode had not responded adequately to treatment in three prior prospective medication trials. Method: Adult outpatients with nonpsychotic major depressive disorder who had not achieved remission or had withdrawn from treatment because of intolerance in three previous prospective medication trials were randomly assigned to receive open-label treatment with either tranylcypromine (N=58) or extended-release venlafaxine plus mirtazapine (N=51). The primary outcome measure was whether patients achieved remission, which was defined as a score ≤7 at exit on the 17item Hamilton Depression Rating Scale (HAM-D). The HAM-D was administered by telephone by raters to whom treatment was masked. Results: Remission rates were not significantly different between the two treatment groups (6.9% for the tranylcypromine group and 13.7% for the venlafaxine plus mirtazapine group). The mean daily dose at exit for tranylcypromine was 36.9 mg (SD=18.5); for venlafaxine, 210.3 mg (SD=95.2); and for mirtazapine, 35.7 mg (SD=17.6). Tranylcypromine was associated with significantly less symptom reduction and greater attrition due to intolerance. Conclusions: Remission rates were modest for both the tranylcypromine group and the extended-release venlafaxine plus mirtazapine group, and the rates were not statistically different between groups. The lower side effect burden, lack of dietary restrictions, and ease of use of venlafaxine and mirtazapine suggest that this combination may be preferred over tranylcypromine for patients with highly treatment-resistant depression who have not benefited adequately from several prior treatments.

Objective Few trials of monoamine oxidase inhibitors (MAOIs) in tricyclic-resistant depression have had double-blind conditions. In the authors' previous double-blind comparison of tranylcypromine and imipramine in anergic bipolar depression, tranylcypromine was significantly more effective. This investigation was a crossover study of nonresponders in the initial study. Method The subjects were 16 outpatients with anergic bipolar depression. Fourteen had not responded to 4 weeks of treatment with at least 30 mg/day of tranylcypromine or 150 mg/day of imipramine, and two patients were crossed over because of intolerable side effects from the initial drug. The crossover medication was prescribed as in the initial double-blind study. Results Twelve patients were crossed over from imipramine to tranylcypromine; nine of them responded to tranylcypromine. Highly significant improvements were documented on the Hamilton, Beck, and Pittsburgh Reversed Vegetative Symptom Scales. Four patients were switched from tranylcypromine to imipramine, but only one responded. Conclusions The high rates of response to tranylcypromine in both the initial and crossover double-blind studies document the efficacy of MAOI treatment for anergic bipolar depression. Moreover, the results further illustrate the utility of MAOIs in tricyclic-resistant depressions.

M ost contemporary psychiatric literature describing the longterm treatment of bipolar illness emphasizes the benefit of pharmacotherapy. Although reference may be made to the need for concomitant psychotherapy (1–3), the techniques and problems in integrating these two therapeutic approaches are seldom discussed. The following case report, describing the treatment of a woman with bipolar disorder, illustrates problems common to the management of bipolar disorder and the usefulness of psychotherapy in the following aspects of treatment: 1) establishing a therapeutic alliance, 2) helping the patient overcome denial of illness, 3) addressing issues in transference and countertransference, 4) balancing therapeutic drug doses and side effects, and 5) encouraging significant others to provide ongoing mental status information.

Twelve inpatients with major depression refractory to at least two controlled antidepressant trials had tranylcypromine added to ongoing lithium treatment. Eleven patients showed reliable improvement in nurses' depression ratings compared with a prior trial of lithium added to an antidepressant that was not a monoamine oxidase inhibitor (MAOI). Eight patients were blindly judged much or very much improved, and all 12 patients improved sufficiently to be discharged. Preclinical studies of conjointly administered lithium and MAOIs suggest that central serotonergic pathways may mediate this robust clinical effect.

Eight patients with hypersomnolent, anergic major depression benefited markedly from treatment with relatively high doses of phenelzine or tranylcypromine but experienced intense afternoon somnolence and disrupted sleep. Reducing the dose of monoamine oxidase inhibitor (MAOI) or substituting isocarboxazid sometimes provided relief, but altering the schedule of drugs or meals did not. Bedtime sedation alleviated the disrupted sleep but had little effect on daytime somnolence. The mechanism underlying this side effect is unknown; sleep deprivation, narcolepsy, or hypotension does not account for it. Patients given an MAOI should be assessed for this disturbance and cautioned to avoid risk of injury when it occurs.

This investigation examines the effects of tranylcypromine on the uptake, release, and metabolism of intracisternally administered tritiated norepinephrine (norepinephrine-H3) in rat brain. The findings suggest that, in addition to being a potent inhibitor of the enzyme monoamine oxidase, tranylcypromine discharges norepinephrine extraneuronally onto receptors and possibly also inhibits the neuronal reuptake of this amine. These neuropharmacological effects of tranylcypromine may possibly account for the greater clinical efficacy of tranylcypromine in the treatment of some depressed patients and the higher incidence of hypertensive cerebrovascular reactions when this drug is compared with other monoamine oxidase inhibitors.

The authors gave 1,223 courses of antidepressant medication, and in 692 courses MAO inhibitors were used. Prior to Sept. 7, 1963, 8.4% of patients receiving MAO inhibitors experienced acute hypertensive crises featured by intense occipital headache and palpitation. After Sept. 7, 1963, patients receiving MAO inhibitors were advised not to eat cheese and the incidence of acute reactions fell to 3.3%. Of the 8 reactions in the latter series, 5 followed the ingestion of cheese, despite our warning, 2 followed the taking of cream in fairly large quantity and one occurred immediately after drinking 17 oz. of draught beer on an empty stomach after sunbathing. The highest incidence of these reactions occurred with tranylcypromine, but nevertheless this drug is being used more frequently than any other MAO inhibitor and is regarded as indispensible in the treatment of depressive illness. Acute vascular crises, when they occur, are immediately relieved with intravenous phentolamine, but where the associated cervic...

Two Alzheimer's patients with disabling depression failed to respond to standard antidepressants but improved with a monoamine oxidase inhibitor. The author points out that the cholinergic system is involved in Alzheimer's symptoms and that demented patients have high monoamine oxidase levels.

To prevent any aggravation of underlying anxiety or agitation during antidepressant therapy, trifluoperazine was given with tranylcypromine to 40 newly admitted depressed patients. Response to therapy was measured by improvement in mood and change in motor activity. Twenty-four patients showed an excellent response and were discharged within one to 3 months after admission. Ten patients showed moderate improvement; 6 had not improved 6 months after admission.

In correspondence with the Smith Kline & French Labs., the following additional data obtained by them are of interest. On single dose oral administration to mice no evidence of an increase or decrease in toxicity was obtained with combinations of tranylcypromine, amobarbital and d-amphetamine. In a limited amount of clinical work in man a combination of tranylcypromine (10 mg.), amobarbital (65 mg.) and d-amphetamine (2.5 mg.) produced in only a few cases drowsiness, sedation or confusion.

Six months of clinical experience with a new antidepressant medication, Parnate (tranylcypromine), indicates that this compound is a very effective monoamine oxydase inhibitor. It appears to act fairly rapidly in a wide variety of depressive states and in this examiner's hands seemed to effect remission in several very refractory depressive illnesses. It would appear to be indicated in the treatment of any form of depression and warrants trial in some long depressive illnesses which had been nonresponsive to other therapies.