Brit.J. Psychiat.(1979), 134,572—81

Depressive

Classification and Prediction to Pheneizine

By E. S. PAYKEL, SUMMARY

R. R. PARKER,

A variety

of

R. J. J. PENROSE

depressive

classifications

of Response and E. R. RASSABY were

used

to

predict response to four weeks' treatment with phenelzine. Better response was found in outpatients rather than inpatients, in atypical depressives, in less severe depressives with a pattern of anxiety and other

neurotic

symptoms,

and

agitated. The findings, although the concept of a specific clinical

in groups

The precise place of monoamine oxidase (MAO) inhibitors in the treatment of depression is still open to debate. Although placebo controlled trials show evidence of efficacy (Tyrer, 1976), some large-scale studies have been negative (Medical Research Council, 1965; Greenblatt et al, 1964; Raskin et al, 1974; Overall ci al, 1962). A probable reason for this is that MAO inhibitors are only effective in certain specific syndromes.

A considerable

body

characterized

as hostile

a little patchy, gave clear support group responsive to MAO inhibitors.

of psychiatric

opinion holds the view that the best response is in atypical or neurotic depressions and phobic anxiety states (Sargant, 1961; Tyrer, 1976). However, there have been comparatively few studies which have used statistical methods to examine the features which predict response to MAO inhibitors. The task is made more complex by the confused state of the nosology of depression, in which a number of competing classifications have been developed in the last 10—15 years (Kendell, 1976). Neurotic depressives tend not to emerge as a single group (Kendell, 1976; Paykel, 1971), but appear heterogeneous and may be further divisible. It is not clear to what extent patients responsive to MAO inhibitors form a sub-group separate from the remainder of neurotic depressives. This paper will report a study of a varied sample of depressed patients treated with phenelzine. Prediction of outcome was exa

mined, lapping Subjects

and

to

using a number of different but over clinical classifications of depression.

Methods

Subjects were 64 depressed patients, aged 18—70, treated at St George's Hospital or Springfield Hospital, London. The depression was of at least two weeks' duration and suffi ciently severe to reach a rating of 7 or more on a scale (range 3—15) made by summing separate ratings of 1—5for verbal report of depression, depressed appearance and secondary symptoms of depression (Raskin ci al, 1970). Patients with mixed depression and anxiety or phobic states were included, but otherwise those in whom the depression appeared secondary to another syndrome were excluded. Also excluded were those who were alcoholic, mentally handi capped, brain damaged, or too unreliable to co operate; and those who showed evidence of hypertension, liver disease or other physical disease contraindicating use of an MAO inhibitor. The sample was moderately heterogeneous. Thirty-five patients (55 per cent) were treated as out-patients, 11 as day-patients, and 18 as in-patients. Fifty-two (81 per cent) were female, and 12 male. The mean age was 36.8 years (SD = 14.2); the median length of illness six months. Thirty-two (50 per cent) had previously suffered from depression, but 572

573

E. S. PAYKEL, R. R. PARKER, R. J. J. PENROSE AND E. R. RASSABY none had experienced manic illness.

a clear previous

attack

of

greater

Treatment Patients

were

treated

for four

weeks

with

phenelzine, 30 mg daily in the first week, 45 mg daily in the second week, and 60 mg daily in the third and fourth weeks. A final dose of 45 mg was permitted

if side-effects

were severe

or

the response already adequate. Five patients completed only three weeks' treatment. Patients were questioned as to the extent to which they failed to take tablets and only 5 per cent acknowledged taking less than 75 per cent of the prescribed dose in any one week. No other medication was allowed, except night sedation with a benzodiazepine. An additional 15 patients entered the study, but dropped out, the majority (13) in the first week. Reasons for dropout were: failure to take medication or to re-attend 6; possible side effects 4; worsening 2; other reasons 3. There were no hypertensive crises during the study, although two patients experienced anxiety after eating

contraindicated

foods.

Outcome measures Assessments were made immediately treatment and weekly thereafter. Four

iatrists

treated

the patients

before psych

and were trained

beforehand in the use of the rating instruments, until satisfactory concordance was achieved.

The assessment instruments were the Clinical Interview for Depression (Paykel et al, 1970); the Brief Psychiatric Rating Scale (BPRS) (Overall

and Gorham,

1962);

a 7-point

scale of

global severity of illness; the 13-point three-area depression

rating

scale

great

improved

used

as

moderately,

improved

a

little, no change, and three similar points for worsening). In addition, details of psychiatric and social history at initial interview.

were recorded

systematically

The outcome measures were the changes in scores from initial to final rating on the global illness scale, the three-area depression scale, and on

total

Interview

scores

for

the

for Depression;

BPRS

and

together

Clinical

with

the

improvement.

On average, the improvement over judgement of global rated as improved a study,

sample showed moderate the four weeks. On the change, 43 per cent were great deal at the end of the

27 per cent improved

moderately,

16 per

cent improved a little, 6 per cent showed no change, and 8 per cent were worse. Predictor analyses The predictor fications

variables

of depression

in the literature

comprised

which

classi

had been reported

to be related

to outcome

of

antidepressant treatment. For categorical (typo logical) predictors, analysis of covariance was

used to correct for differences between duals in initial scores, since higher severity

in psychiatry

usually

predicts

indivi initial

greater

improvement but a higher final score. For continuous predictors, correlational analyses were employed, using partial correlation to correct for initial level. A separate set of multiple regressional analyses between predictor variables and outcome measures was also undertaken, but will not be presented. Multiple correlations were mostly not significant,

in contrast

to the

findings

to be

presented for classifications. After initial level, the only individual variable contributing con sistently to prediction was the number of previous depressive episodes, probably a non specific reflection of worse outcome where illness is chronic. The predictor findings presented in this paper remained significant when

inclusion

criterion (Raskin et al, 1970); and a 7-point global judgement of overall change (improved a deal,

judgement of global change at the final rating. In all these measures higher scores indicated

number

of previous

depressive

episodes

was held constant by analysis of co-variance partial correlation in a further set of analyses.

or

Results Classzficatoiypredictors Table I summarizes the classifications used in predictor analyses, and their utility as pre dictors. Four classificatory systems gave sig nificant prediction; the first two were categorical, the others dimensional. Several classifications failed to predict outcome, including those directly related to the psychotic-neurotic dis

574

DEPRESSIVE

CLASSIFICATION

AND PREDICTION

tinction and the admixture of phobic symptoms. The significant predictors will be presented first. Overall's typology Overall ci al (1966) used a statistical classi fying procedure to derive three types of de pressive disorder: retarded, anxious, and hostile, and in a subsequent development a fourth group, agitated depression. Retarded depressives responded better to tricyclic anti depressants, anxious depressives to pheno thiazines (Overall ci al, 1966; Hollister et al, 1966, 1967). Patients were assigned to the four groups on TABLE I Classificatory predictors examined

significant

predictionOverall Significant predictionNo typologyFour-group typologyTreatment settingNies-Robinson

Analytic

Cluster

diagnosisindexFactor diagnosticPsychotic-Neurotic dimension

TO PHENELZINE

the basis of initial BPRS rating profiles. Find ings are shown in Table II. After adjustment for initial scores, differences on two outcome measures were significant, with the others showing similar although non-significant trends. Hostile depressives showed the best outcome, closely followed by agitated depressives. Anxious depressives were intermediate in outcome and retarded depressives clearly came off worst. Treatment setting Review of controlled trials suggested differ ences by treatment setting, with better response among out-patients. Out-patients are likely to show different characteristics to in-patients and treatment setting was therefore regarded as a classificatory category. Outcome was examined in three settings: in-patient, day hospital, and out-patient. Findings are shown in Table III. There was a consistent trend across outcome measures, reaching significance on two of them, for in-patients to do worst and out-patients best, with day patients closely comparable to out-patients. @1Vies-Robinsondiagnostic index

Endogenous-NeuroticSeverityDepressed dimensionsFactor vs. AnxiousPhobic

OF RESPONSE

In a controlled trial of phenelzine, Robinson ci al (1974) developed a dimensional diagnostic index of atypical and typical depression, depending on a weighted combination of symptom and history variables. The present study used different rating scales, but the items

symptoms

Past PresentAnergia

TABLE II Overall typology: mean change scores after adjustmentfor initial level by analysis of covariance measureRetarded(N

valueGlobal Outcome .39Threeillness scale1

= .331

10)Anxious (N = 28)Agitated (N = 13)Hostile (N = 12)F .571

.862

.201

scale2.433.894.524.682.28BPRStotal—0.010.550.730.684.725*Clinicalinterviewtotal0.791.151.381.401.73Global area depression

change'4.605.856.006.423.13* No adjustment * **

p