Craig D. Turnbull

A comparison of inpatients with primary unipolar depression and depression secondary to anxiety

Retrospective comparisons between primary unipolar depression and depression secondary to anxiety in 65 inpatients revealed a number of differences. Secondary depression was associated with a significantly higher incidence of neurotic traits in childhood, chronic unhappiness, and unsupportive family. Tricyclic antidepressants and ECT were both more effective in primary depression, and some secondary depressives became worse on ECT. When primary depression was sub‐divided into familial, nonfamilial and spectrum types, the greatest differences were noted between familial and secondary depressions. In the former group a more stable life style was noted. Secondary and spectrum types differed on only two variables and several similarities were noted. Platelet monoamine oxidase activity was significantly higher in secondary depression.

Isocarboxazid: Efficacy and tolerance

In a double-blind study, isocarboxazid was found to have greater efficacy than placebo. Patients with weight gain, increased appetite, and increased sleep responded particularly well, with a rapid onset of improvement that was apparent by one week. Their response to placebo was poor. Using a flexible dose, the modal range was 30-60 mg per day. Higher doses were poorly tolerated. At the doses used, side effects were generally mild, the most common being dizziness and myoclonus.

An evaluation of two doses of isocarboxazid in depression

Two fixed doses of isocarboxazid were studied over a 4-week period in depressed in-patients. Thirty-five patients completed treatment, 20 of whom received 30 mg isocarboxazid per day, and 15 of whom received 50 mg isocarboxazid per day. No overall difference between the two doses was observed. When patients were subdivided into melancholia/endogenous depression or non-melancholia/non-endogenous depression, the higher dose exerted significantly greater antidepressant effects in the latter groups. Diagnostic type is considered to be an important variable in studies of dose-effect relationships with antidepressant drugs. The side effects of isocarboxazid at the two doses studied did not differ materially, although there was a suggestion of greater anticholinergic effect at 50 mg.

DEPRESSIVE ILLNESS AND PLACEBO RESPONSE

Fifty-three depressed inpatients received placebo treatment as part of a multicenter double-blind placebo-controlled study of an investigational antidepressant, bupropion. Groups of placebo responders and nonresponders were identified based on percentage change on the Hamilton Depression Scale and validated against the Clinical Global Impression Scale. Although the diagnostic and demographic features of responders and nonresponders were generally similar, some differences emerged. Placebo nonresponders were more often associated with male gender, lack of college education, diagnosis of manic-depressive illness and greater lack of insight at baseline. Placebo responders largely consisted of females with a diagnosis of depressive neurosis. When the individual symptoms as measured by the Hamilton Depression Scale were examined, the nonresponders showed improvement only in psychological symptoms (i.e., lack of interest, guilt, and suicide). The responders showed consistent improvement in most symptoms except middle insomnia, loss of weight, and diurnal mood change. These results suggest that depressions of an endogenous nature are unlikely to respond to placebo and when they do respond, the vegetative symptoms are least likely to improve.

The effects of isocarboxazid on blood pressure and pulse

In a fixed-dose inpatient study, isocarboxazid produced a dose-related lowering of systolic blood pressure at weeks 2 and 4. Systolic blood pressure was also lowered by the drug in a placebo-controlled outpatient study. The magnitude of these reductions was considerable, reaching an average of 14.6 mm in inpatients who received a 50-mg dose, and 18.7 mm in outpatients. There was no evidence for a dose-related orthostatic effect, and greater orthostasis relative to placebo was found only at week 3 in the outpatient study. Significant bradycardia was produced by isocarboxazid in outpatients at weeks 2, 3, and 4 relative to placebo, but no dose-related effect was found among inpatients. Inpatients with a baseline systolic orthostatic drop of greater than or equal to 10 mm showed a significantly better response to isocarboxazid than did those with an orthostasis of less than 10 mm. The theoretical significance of these findings is discussed.

A comparison of phenelzine and imipramine in depressed inpatients

Phenelzine and imipramine were compared double-blind, in 43 depressed inpatients. A placebo week preceded drug treatment; this allowed early identification of placebo responders who did not therefore enter the study. After three weeks treatment, the two drugs were equally effective on Hamilton, Beck and SCL-90 measures of depression and anxiety. On the the SCL-90 scales of hostility and paranoia imipramine was more effective; in some patients phenelzine was associated with increased hostility. Measurement of MAO inhibition and plasma tricyclic levels indicated that adequate doses were generally used - (mean 81 mg/day phenelzine and 144 mg/day imipramine).