MAOI treatment response: multiaxial assessment.

While studying the effectiveness of the MAOI isocarboxazid for the treatment of depression, we noted that many patients experienced a reduction of symptoms without equivalent improvement in other areas of their lives. We evaluated four outcome areas: symptoms, work, family functioning and social functioning. After 6 weeks on medication, symptoms improved the most, significantly more so than the other three areas. For the group of patients who completed 24 weeks on medication, all four outcome areas were further improved compared to the 6-week levels, with the improvement in work functioning reaching statistical significance. We conclude that the assessment of treatment outcome is more complex than the simple measurement of symptom reduction, and that different outcome areas are likely to improve at different rates and to different extents.

Long-term amitriptyline in chronic depression.

Medication was discontinued under a placebo-controlled, double-blind, six-month protocol with 17 chronically depressed patients who had been taking an average daily dose of 138 mg amitriptyline (AMI) for an average of 3.7 years. Only one of nine patients became depressed on active medication, while of the 15 patients receiving a placebo trial, 11 had a depressive recurrence at an average time of 9.3 weeks. These 11 were subsequently restarted on AMI, and responded similarly to the way in which acutely depressed patients respond, although the patients showed either a need for less AMI or decreased symptoms, compared to entry. Tolerance did not develop to anticholinergic side-effects during long-term medication. Twelve of the 15 patients on placebo showed a withdrawal reaction during the first few weeks of tapered AMI discontinuation which could be distinguished from recurrence of depression. This study suggests that the majority of patients on long-term antidepressant will suffer a recurrence of depressive symptoms when the medication is discontinued.

Assessing treatment response to the monoamine oxidase inhibitor isocarboxazid.

The response to the MAOI isocarboxazid was investigated in a two-phase protocol. Phase 1 was a double-blind, placebo-controlled study; Phase 2 was an open active medication trial for Phase 1 placebo patients who still met symptom criteria. In Phase 1, 60 male outpatients were randomly divided into placebo or active medication groups. Mean platelet MAO inhibition was 86% by Week 1, while significant symptomatic improvement was not seen until Week 3. In Phase 2, 16 of the symptomatic placebo patients were given an open trial on isocarboxazid; thus, 43 patients received a trial of active medication. Separation of responders (N = 26) from nonresponders (N = 17) by discriminant function analysis using 3 entry variables (platelet MAO activity, standing diastolic blood pressure, and psychomotor irregularity) accounted for 28% of the variance, with correct classification of 32 of the 43 patients.

Recurrence of depression after discontinuation of long-term amitriptyline treatment.

In this study 10 of 17 patients receiving long-term amitriptyline treatment (average duration: 3.7 years, average dose: 138 mg) had their medication tapered and discontinued under double-blind conditions. Eight became depressed within 3 to 15 weeks. None of the 7 control subjects became depressed during the 6 months of the study. Those who became depressed also showed psychomotor retardation and sleep disturbance. Relief of longstanding anticholinergic side effects followed medication discontinuation. Some patients whose amitryptyline was discontinued experienced a mild withdrawal syndrome within the first 2 weeks, consisting of irritability, dream and sleep disturbance, and restlessness during the first few weeks.

Monoamine oxidase inhibitor-responsive depression.

Double-blind, placebo-controlled trials have documented the efficacy of some monoamine oxidase (MAO) inhibitors in treating certain depressed patients. This preliminary report of a 6-week, double-blind, placebo-controlled study of the MAO inhibitor isocarboxazid (Marplan) examines the time course of platelet MAO inhibition and treatment response, and describes symptoms that distinguish markedly improved from slightly improved responders. Thirty male outpatients, ages 28-64, randomly divided into placebo (n = 15) and active medication (n = 15) groups, were followed weekly. Medication was started at 20 mg daily and increased to achieve 90% platelet MAO inhibition. Data were analyzed for 24 patients who completed at least 3 weeks of the study. A clinician's global change rating at the study's conclusion showed that 12 of 13 patients (92%) in the active medication group improved, while 3 of 11 (27%) patients in the placebo group improved. Significant symptomatic improvement occurred in the active treatment group by week 3. Trends suggest that anxiety improved first (week 2), followed by depression (week 3), and finally cognitive outlook (week 6). Only minimal difficulties were observed with orthostatic hypotension, hypertensive crises, or other side effects. At baseline, the only significant difference between the markedly improved and slightly improved groups was greater psychomotor retardation in the markedly improved group. Trends suggest that the markedly improved group showed less depression, anxiety, sleep disturbance, and weight loss, fewer gastrointestinal complaints, and more helplessness and worthlessness.

Platelet MAO and amitriptyline treatment.

Some tricyclic antidepressants have been reported to inhibit monoamine oxidase (MAO) activity in vitro in addition to blocking the reuptake of norepinephrine and/or serotonin. While the inhibition of MAO is reversible, platelet MAO activity in depressed patients responding to amitriptyline treatment has been reported to be reduced after drug treatment. In a reverse design, we measured platelet MAO activity and drug levels in patients chronically being treated with amitriptyline and again 2 and 4 weeks after stopping the medication. Although tricyclic drug concentrations were initially within the therapeutic range and undetectable on placebo treatment, platelet MAO activities were unchanged.