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Persistence of a drug-personality interaction in psychiatric outpatients
J. psychiat.
Rer.,
1970,
Vol.
PERSISTENCE
7, pp. 299-305.
Pergamon
Press.
Printed
in Great
Britain.
OF A DRUG-PERSONALITY IN PSYCHIATRIC
INTERACTION
OUTPATIENTS*
DOUGLAS M. MCNAIR, SEYMOURFISHER, CAROL SUSSMAN,LEO F. DROPPLEMAN and RICHARD J. KAHN Psychopharmacology
Laboratory,
Division
of Psychiatry,
Boston, (Received (Revised
Boston University
School of Medicine,
Massachusetts 25 November 24 February
1968) 1970)
CLINICAL drug trials with psychiatric outpatients usually span brief time periods. Investigators rarely follow up such trials. Apparently only one previous study reported an objective and comprehensive follow-up of a clinical trial of mild tranquilizers.1 Unfortunately it used different measures during the clinical trial and at follow-up, and psychiatric status for the two periods could not be compared. This paper reports a follow-up four months after the end of a double-blind trial of diazepam (Valium).a-4-t The 2-week trial indicated that a personality characteristic (Acquiescence) and medication had significant joint, or interactive, effects upon outcome. Patients had been classified as High or Low Acquiescers by their frequency of agreement with 35 glib generalizations from the Bass Social Acquiescence Scale.5$ After twa weeks of treatment Low Acquiescers had improved more on drug than on placebo, while High Acquiescers had improved more on placebo than on drug. Figure 1 depicts the interaction pattern on a typical criterion. The research questions in the follow-up phase concerned: (1) the persistence of the medication-personality interaction; (2) the effects of the clinical trial upon subsequent treatment and clinical progress.
MEANING
OF ACQUIESCENCE
The Bass Scale purportedly measures social acquiescence or conformity. Our evidence and that of others6 suggests that it may not. High Acquiescers have given more problems than low scorers in adhering to research protocols and in volunteering for studies. Unpublished * This investigation was supported by a research grant from the National Institute of Mental Health (MH 08954). The authors are particularly grateful to Jacob Swartz, M.D., Director, Psychiatry Clinic, University Hospital, for administrative help and support and to Mrs. Elizabeth Nikula for her overall supervision of most of the details of data processing and computer analyses. t Hoffman-La Roche Laboratories, Inc., Nutley, N. J. generously supplied all medication. 1 The Bass Scale was abbreviated and used with permission of the author and publisher, Psychological Test Specialists. 299
DOUGLASM. MCNAIR et al.
300
PRE-TX
2 WKS
LOW ACQUIESCERS
PRE-TX
HIGH
2 WKS
ACQUIESCERS
FIG. 1. Treatment group means on the Tension-Anxiety Mood Scale before and after two weeks of treatment.
work by our Laboratory indicates that the Bass correlates only mildly-to-moderately with the acquiescence response set measured by the MMPI and similar inventories. Bass scores appear to relate consistently and inversely to education. In the above diazepam study, however, a reanalysis of the 2-week results indicated the drug-personality interaction was not attenuated by statistically removing the influence of education. Other unpublished work by this Laboratory with college and medical students, where education was held constant, verified the important influence of Acquiescence in drug studies. In the diazepam study, another correlate of the Bass (r = 0.30) was degree of somatic distress. Does the Bass then indirectly measure patient somatization? Neither during the control phase nor in the present follow-up could the confounding of Acquiescence with somatization be untangled. Statistically removing the effects of one measure from the other either removed the interaction or suggested a triple order interaction of drug, somatization and Acquiescence. A subsequent study using a different drug7 replicated the Acquiescence by medication interaction in a sample where Acquiescence was not confounded with somatization. The issue was not fully resolved, however, because of the small N involved in that study. For the above reasons, we prefer at present not to attach to the High and Low Acquiescer labels any meaning beyond a tendency to indulge in glib generalizations. Further work on this problem is in progress.
METHOD
Patients and treatment groups The follow-up sample included 44 (73 per cent) of 60 outpatients who completed the diazepam study. All patients in the clinical drug trial were new admissions to the Psychiatry Clinic at Boston University Medical Center. They met fairly standard screening criteria for
PERSISTENCE OF A DRUG-PERSONALITY INTERACTIONIN PSYCHIATRICOUTPATIENTS
301
trials of anti-anxiety drugs. These criteria and the drug trial are described elsewhere.2 The follow-up sample did not differ significantly from the original sample in average age (29-30 years), in education (some college), or in proportions of women (66 per cent) and whites (86 per cent). After participating in the drug trial, each patient either was referred for additional psychiatric treatment or was discharged. At the same time a re-evaluation was scheduled for 16 weeks later (actual follow-up time averaged 18 weeks later). This period allowed most patients to complete 12 hr of time-limited psychotherapy, the most frequent disposition, before the re-evaluation. Each of the four treatment subgroups to be studied at follow-up originally comprised 15 patients. The groups were: 1. HA-D: High Acquiescers (Bass Score > 15) treated with diazepam (5 mg., t.i.d.). 2. LA-D: Low Acquiescers (Bass Score < 14) treated with diazepam. 3. HA-P: High Acquiescers treated with placebo. 4. LA-P: Low Acquiescers treated with placebo. Procedure
The research social worker (SW), blind to medication and Acquiescence type, interviewed the therapists of patients who had received psychiatric treatment after the clinical trial. This interview covered : (a) kind and length of treatment; (b) degree and kind of effects attributed to the clinical drug trial; (c) degree of improvement during post-trial treatment. Next the SW interviewed the patients, at their homes when feasible, at the Clinic when not. The principal aims were to readminister the patient measures used during the trial and to elicit and to rate the patients’ impressions of their treatment during the trial. Measures
The measures are described elsewhere.2 In addition to the Bass, those referred to here are: 1. Global Improvement Ratings. 2. Hopkins Symptom Distress Scales.8 a. Anxiety b. Depression c. Somatic 3. Psychiatric Outpatient Mood Scales (POMS).g a. Tension-Anxiety b. Depression-Dejection c. Anger-Hostility d. Fatigue e. Vigor-Activity . RESULTS
Acquiescence
AND
DISCUSSION
and attrition
Table 1 shows by subgroup the number of follow-up participants and refusers. attriters had moved either to places too distant for inclusion or to points unknown.
Seven Nine
302
DOUGLAS M. MCNAIR
et al.
patients either refused to participate or repeatedly failed to show for scheduled follow-up interviews. Refusal was unrelated to medication or to the drug-personality interaction, but refusal was related to Acquiescence type. Eight of the nine refusers were High Acquiescers (x2 = 5.44, p <0*02). TABLE 1.
FOLLOW-UP PARTICIPATIONAND POST-TRIALTREATMENT HA-D
Response
HA-P
LA-D
LA-P
to follow-up (N)
Participated
10
10
11
13
Moved
1
1
4
1
Refused
4
4
0
1
100
93
93
93 43
Post-trial
therapy recommended
Termination
(per cent)
33
21
7
Above md. interviews (per cent)
rate (per cent)
70
50
55
38
Post-trial
50
20
27
23
drugs (per cent)
Post-trial treatment A carry-over effect.
Table 1 also presents data which demonstrate a carry-over effect of the drug trial upon subsequent treatment. Additional treatment, usually timelimited psychotherapy, was the recommended disposition for nearly all cases. The premature termination rate (‘no show’ or termination after one session) clearly indicated that the drugpersonality interaction carried over into the immediate post-trial period. The two groups, HA-D and LA-P, that reacted least favorably to the trial phase had significantly more terminators (interaction F = 444, df = 1,53, p ~0.05) than did the other two groups. Noteworthy, though not significant, is the fact that the HA-D group which had the poorest reaction to the trial, received the most drug and psychotherapy during the post-trial period.* Additional improvement. Change between the end of the drug trial and follow-up was evaluated by correlated t tests. The total sample showed significant additional improvement on Global Ratings (t = 5.32, p < O.OOl), Depression Symptoms (t = 2.65, p
of the personality-medication
interaction
Did the initial treatments have different long-range effects ? More specifically, did the drug-personality interaction persist four months after the clinical trial? Testing this hypothesis involved 2 x 2 (medication-by-Acquiescence) analyses of covariance of five patient * Further evidence of the poor response of High Acquiescers to mild tranquilizers was that the five HA-D patients who received post-trial psychotropics did not improve between the end of the trial and follow-up, whereas the five who received no additional medication did improve.
PERSISTENCE OF A DRUG-PERSONALITYINTERACTIONIN PSYCHIATRICOUTPATIENTS
303
follow-up measures controlled for pretreatment scores. The measures, all of which had shown a significant drug-personality interaction at two weeks were: Somatic, Anxiety and Depression Symptoms, Tension-Anxiety Mood and Depression Mood. There was evidence that the effects of the medication-personality combination on Depression Symptoms persisted four months later (interaction F = 4.53, df = 1,40, p t0.05). Figure 2 illustrates for Depression Symptoms the relative status of the four treatment groups at three times: pretreatment, after two weeks, and at follow-up. Prior to treatment, the HA groups reported slightly less distress from Depression Symptoms, but there was no warning of the interaction shown at two weeks and sustained at follow-up. Low Acquiescers who received diazepam during the clinical trial reported progressively more improvement than those who received placebo. Just as clearly, the High Acquiescers who had received placebo during the trial reported more improvement at the end of the trial
PRE-TX
2 WKS
20 WKS
LOW ACQUIESCERS FIG. 2.
Group means on Depression
PRE-TX
2 WKS
20 WKS
HIGH ACQUIESCERS Symptoms
at three times-follow-up
sample.
and at follow-up than High Acquiescers who had received the active drug. The interaction pattern, though somewhat attenuated, remained present four months after the drug trial ended. Graphs similar to Fig. 2 for three other criteria, Somatic Distress, Anxiety Symptoms and Depression Mood, showed similar patterns of change over time. Graphically, the interaction pattern of group means at follow-up appeared only slightly attenuated compared with two weeks. However, with these slight attenuations and the reduced sample size plus the somewhat larger within group variation, the statistical tests did not approach significance except for a trend on Somatic Distress (F = 1.72, p <0.20). The Tension-Anxiety measure yielded no suggestion that the interaction persisted, nor were any tests for the separate effects of Acquiescence or medication significant.
304
DOUGLASM. MCNAIR et al.
A selected subsample. A subsample was selected to control for two factors in addition to medication and Acquiescence: treating doctor and patient sex. Nine doctors in the clinical trial treated either two HA or two LA women, with one patient in each pair on each medication. In terms of significance levels and variance predicted, these 18 patients showed a much stronger medication-personality interaction during the drug trial than did the total sample. Five of these pairs (three HA and two LA) returned at follow-up, and covariance analyses for correlated groups indicated highly significant (p ~0.01) drug-personality interactions for Somatic Symptoms, Depression Symptoms and Tension-Anxiety Mood, and significant interactions (p <0.05) for Anxiety Symptoms and Depression Mood. In spite of the very small N, these interactions appeared to reflect persistence of the interaction seen during the trial, rather than to arise from such misleading factors as pretreatment or variance differences. Graphs of the criterion scores for this subsample were similar to Fig. 2. The two main differences were that: (1) the interactions in the subsample were amplified rather than attenuated at follow-up; (2) the HA-D and LA-P groups in the subsample showed more disturbance at followup than at pretreatment. The data on these five pairs, then, strongly suggest that the Acquiescence-medication interaction may prove to be of considerable magnitude and importance when obscuring influences are controlled. Bias. Tests of the persistence hypothesis may have been biased in opposite directions by two influences : a refuser bias and a terminator bias. While not statistically significant, these possible biases suggest caution in interpreting the findings. In the HA-D group, follow-up refusers (Table 1) tended to be some of the poorer responders to the clinical trial. In the HA-P group, refusers tended to be among the better responders. Such a sampling bias probably acted to attenuate the interaction pattern at follow-up by reducing the contrast between the two HA groups. Premature terminators who returned for the follow-up reported more disturbance than patients who completed their post-trial therapy. There were more such terminators in the LA-P group (46 per cent) than in the LA-D group (9 per cent), suggesting a bias toward exaggeration of the drug-personality interaction. The net effect of these and other unknown sources of bias is impossible to estimate accurately, and replication is crucial.
CONCLUSIONS
AND
SUMMARY
This follow-up study re-evaluated four small groups of psychiatric outpatients who, four months earlier, had completed a double-blind trial of diazepam. A drug-personality interaction demonstrated during the 2-week trial was that High Acquiescer-Placebo and Low Acquiescer-Diazepam groups improved significantly more than High Acquiescer- Diazepam and Low Acquiescer-Placebo groups. The follow-up data supported two principal conclusions about the long-range combined effects of medication and personality: (1) they can modify patients’ reactions to subsequent treatment; (2) they also can endure for a considerable period. Thus, the same two groups who improved most during the clinical trial significantly less often prematurely quit their subsequent therapy and, further, they maintained their significantly greater symptomatic improvement four months later. As a whole, the follow-up sample reported significant additional improvement after the
PERSISTENCEOF A DRUG-PERSONALITY INTERACTION IN PSYCHIATRIC OUTPATIENTS
305
drug trial. The patients, their post-trial therapists and an independent social worker considered both the medication and other aspects of participation in the drug trial to have benefited subsequent therapy. Another finding was that High Acquiescers refused the follow-up request significantly more often than Low Acquiescers, reinforcing previous doubts that High Acquiescers are conformers. Some potential biasing and confounding influences upon the results are discussed, and the need is stressed for replication and for further studies of the mechanism of the drug-personality interaction.
REFERENCES
5.
ROTH, I., RHUDICK, P. J., SHASKAN, D. A., SLOBIN, M. S., WILKINSON, A. E. and YOUNG, H. H. Long-term effects on psychotherapy of initial treatment conditions. J. osychiat. Res. 2. 283, 1962. McNA~R, D., KAHN, R.-J.: DROPPL&AN, L. F. and FISHER, S. Compatibil&y, acquiescence and drug effects. Neuropsychopharmacology 5, 536, 1967. FISHER, S. The placebo reactor: Thesis, antithesis, synthesis, and hypothesis. Dis. ner. Syst. 28, 510, 1967. MCNAIR, D. M., KAHN, R. J., DROPPLEMAN, L. F. and FISHER, S. Patient acquiescence and drug effects. In Non-specific Factors in Drug Therapy, RICKELS, K. (Ed.), pp. 59-12. Thomas, Springfield, Illinois, 1968. BASS, B. Development and evaluation of a scale for measuring social acquiescence. J. abnorm. Sot.
6.
SCHUYZ, R. E. and FOSTER, R. J. A factor
Psychol. 53, 296, 1956. Educ. psychol. Measur. 23,435, I.
MCNAIR,
D.,
FISHER, S., KAHN,
intensive outpatient 8. 9.
treatment.
analytic
study
of acquiescent
and extreme
response
set.
1963. R. J. and
DROPPLEMAN, L. F. A drug-personality
interaction
in
Archs. gen. Psychiat. 22, 128, 1970.
PARLOFF, M. B., KELMAN, H. C. and FRANK, J. D. Comfort, effectiveness and self-awareness as criteria of improvement in psychotherapy. Am. J. Psychiat. 111, 343, 1954. MCNAIR, D. M. and LQRR, M. An analysis of mood in neurotics. J. abnorm. Sot. Psychol. 69,620, 1964.
Rer.,
1970,
Vol.
PERSISTENCE
7, pp. 299-305.
Pergamon
Press.
Printed
in Great
Britain.
OF A DRUG-PERSONALITY IN PSYCHIATRIC
INTERACTION
OUTPATIENTS*
DOUGLAS M. MCNAIR, SEYMOURFISHER, CAROL SUSSMAN,LEO F. DROPPLEMAN and RICHARD J. KAHN Psychopharmacology
Laboratory,
Division
of Psychiatry,
Boston, (Received (Revised
Boston University
School of Medicine,
Massachusetts 25 November 24 February
1968) 1970)
CLINICAL drug trials with psychiatric outpatients usually span brief time periods. Investigators rarely follow up such trials. Apparently only one previous study reported an objective and comprehensive follow-up of a clinical trial of mild tranquilizers.1 Unfortunately it used different measures during the clinical trial and at follow-up, and psychiatric status for the two periods could not be compared. This paper reports a follow-up four months after the end of a double-blind trial of diazepam (Valium).a-4-t The 2-week trial indicated that a personality characteristic (Acquiescence) and medication had significant joint, or interactive, effects upon outcome. Patients had been classified as High or Low Acquiescers by their frequency of agreement with 35 glib generalizations from the Bass Social Acquiescence Scale.5$ After twa weeks of treatment Low Acquiescers had improved more on drug than on placebo, while High Acquiescers had improved more on placebo than on drug. Figure 1 depicts the interaction pattern on a typical criterion. The research questions in the follow-up phase concerned: (1) the persistence of the medication-personality interaction; (2) the effects of the clinical trial upon subsequent treatment and clinical progress.
MEANING
OF ACQUIESCENCE
The Bass Scale purportedly measures social acquiescence or conformity. Our evidence and that of others6 suggests that it may not. High Acquiescers have given more problems than low scorers in adhering to research protocols and in volunteering for studies. Unpublished * This investigation was supported by a research grant from the National Institute of Mental Health (MH 08954). The authors are particularly grateful to Jacob Swartz, M.D., Director, Psychiatry Clinic, University Hospital, for administrative help and support and to Mrs. Elizabeth Nikula for her overall supervision of most of the details of data processing and computer analyses. t Hoffman-La Roche Laboratories, Inc., Nutley, N. J. generously supplied all medication. 1 The Bass Scale was abbreviated and used with permission of the author and publisher, Psychological Test Specialists. 299
DOUGLASM. MCNAIR et al.
300
PRE-TX
2 WKS
LOW ACQUIESCERS
PRE-TX
HIGH
2 WKS
ACQUIESCERS
FIG. 1. Treatment group means on the Tension-Anxiety Mood Scale before and after two weeks of treatment.
work by our Laboratory indicates that the Bass correlates only mildly-to-moderately with the acquiescence response set measured by the MMPI and similar inventories. Bass scores appear to relate consistently and inversely to education. In the above diazepam study, however, a reanalysis of the 2-week results indicated the drug-personality interaction was not attenuated by statistically removing the influence of education. Other unpublished work by this Laboratory with college and medical students, where education was held constant, verified the important influence of Acquiescence in drug studies. In the diazepam study, another correlate of the Bass (r = 0.30) was degree of somatic distress. Does the Bass then indirectly measure patient somatization? Neither during the control phase nor in the present follow-up could the confounding of Acquiescence with somatization be untangled. Statistically removing the effects of one measure from the other either removed the interaction or suggested a triple order interaction of drug, somatization and Acquiescence. A subsequent study using a different drug7 replicated the Acquiescence by medication interaction in a sample where Acquiescence was not confounded with somatization. The issue was not fully resolved, however, because of the small N involved in that study. For the above reasons, we prefer at present not to attach to the High and Low Acquiescer labels any meaning beyond a tendency to indulge in glib generalizations. Further work on this problem is in progress.
METHOD
Patients and treatment groups The follow-up sample included 44 (73 per cent) of 60 outpatients who completed the diazepam study. All patients in the clinical drug trial were new admissions to the Psychiatry Clinic at Boston University Medical Center. They met fairly standard screening criteria for
PERSISTENCE OF A DRUG-PERSONALITY INTERACTIONIN PSYCHIATRICOUTPATIENTS
301
trials of anti-anxiety drugs. These criteria and the drug trial are described elsewhere.2 The follow-up sample did not differ significantly from the original sample in average age (29-30 years), in education (some college), or in proportions of women (66 per cent) and whites (86 per cent). After participating in the drug trial, each patient either was referred for additional psychiatric treatment or was discharged. At the same time a re-evaluation was scheduled for 16 weeks later (actual follow-up time averaged 18 weeks later). This period allowed most patients to complete 12 hr of time-limited psychotherapy, the most frequent disposition, before the re-evaluation. Each of the four treatment subgroups to be studied at follow-up originally comprised 15 patients. The groups were: 1. HA-D: High Acquiescers (Bass Score > 15) treated with diazepam (5 mg., t.i.d.). 2. LA-D: Low Acquiescers (Bass Score < 14) treated with diazepam. 3. HA-P: High Acquiescers treated with placebo. 4. LA-P: Low Acquiescers treated with placebo. Procedure
The research social worker (SW), blind to medication and Acquiescence type, interviewed the therapists of patients who had received psychiatric treatment after the clinical trial. This interview covered : (a) kind and length of treatment; (b) degree and kind of effects attributed to the clinical drug trial; (c) degree of improvement during post-trial treatment. Next the SW interviewed the patients, at their homes when feasible, at the Clinic when not. The principal aims were to readminister the patient measures used during the trial and to elicit and to rate the patients’ impressions of their treatment during the trial. Measures
The measures are described elsewhere.2 In addition to the Bass, those referred to here are: 1. Global Improvement Ratings. 2. Hopkins Symptom Distress Scales.8 a. Anxiety b. Depression c. Somatic 3. Psychiatric Outpatient Mood Scales (POMS).g a. Tension-Anxiety b. Depression-Dejection c. Anger-Hostility d. Fatigue e. Vigor-Activity . RESULTS
Acquiescence
AND
DISCUSSION
and attrition
Table 1 shows by subgroup the number of follow-up participants and refusers. attriters had moved either to places too distant for inclusion or to points unknown.
Seven Nine
302
DOUGLAS M. MCNAIR
et al.
patients either refused to participate or repeatedly failed to show for scheduled follow-up interviews. Refusal was unrelated to medication or to the drug-personality interaction, but refusal was related to Acquiescence type. Eight of the nine refusers were High Acquiescers (x2 = 5.44, p <0*02). TABLE 1.
FOLLOW-UP PARTICIPATIONAND POST-TRIALTREATMENT HA-D
Response
HA-P
LA-D
LA-P
to follow-up (N)
Participated
10
10
11
13
Moved
1
1
4
1
Refused
4
4
0
1
100
93
93
93 43
Post-trial
therapy recommended
Termination
(per cent)
33
21
7
Above md. interviews (per cent)
rate (per cent)
70
50
55
38
Post-trial
50
20
27
23
drugs (per cent)
Post-trial treatment A carry-over effect.
Table 1 also presents data which demonstrate a carry-over effect of the drug trial upon subsequent treatment. Additional treatment, usually timelimited psychotherapy, was the recommended disposition for nearly all cases. The premature termination rate (‘no show’ or termination after one session) clearly indicated that the drugpersonality interaction carried over into the immediate post-trial period. The two groups, HA-D and LA-P, that reacted least favorably to the trial phase had significantly more terminators (interaction F = 444, df = 1,53, p ~0.05) than did the other two groups. Noteworthy, though not significant, is the fact that the HA-D group which had the poorest reaction to the trial, received the most drug and psychotherapy during the post-trial period.* Additional improvement. Change between the end of the drug trial and follow-up was evaluated by correlated t tests. The total sample showed significant additional improvement on Global Ratings (t = 5.32, p < O.OOl), Depression Symptoms (t = 2.65, p
of the personality-medication
interaction
Did the initial treatments have different long-range effects ? More specifically, did the drug-personality interaction persist four months after the clinical trial? Testing this hypothesis involved 2 x 2 (medication-by-Acquiescence) analyses of covariance of five patient * Further evidence of the poor response of High Acquiescers to mild tranquilizers was that the five HA-D patients who received post-trial psychotropics did not improve between the end of the trial and follow-up, whereas the five who received no additional medication did improve.
PERSISTENCE OF A DRUG-PERSONALITYINTERACTIONIN PSYCHIATRICOUTPATIENTS
303
follow-up measures controlled for pretreatment scores. The measures, all of which had shown a significant drug-personality interaction at two weeks were: Somatic, Anxiety and Depression Symptoms, Tension-Anxiety Mood and Depression Mood. There was evidence that the effects of the medication-personality combination on Depression Symptoms persisted four months later (interaction F = 4.53, df = 1,40, p t0.05). Figure 2 illustrates for Depression Symptoms the relative status of the four treatment groups at three times: pretreatment, after two weeks, and at follow-up. Prior to treatment, the HA groups reported slightly less distress from Depression Symptoms, but there was no warning of the interaction shown at two weeks and sustained at follow-up. Low Acquiescers who received diazepam during the clinical trial reported progressively more improvement than those who received placebo. Just as clearly, the High Acquiescers who had received placebo during the trial reported more improvement at the end of the trial
PRE-TX
2 WKS
20 WKS
LOW ACQUIESCERS FIG. 2.
Group means on Depression
PRE-TX
2 WKS
20 WKS
HIGH ACQUIESCERS Symptoms
at three times-follow-up
sample.
and at follow-up than High Acquiescers who had received the active drug. The interaction pattern, though somewhat attenuated, remained present four months after the drug trial ended. Graphs similar to Fig. 2 for three other criteria, Somatic Distress, Anxiety Symptoms and Depression Mood, showed similar patterns of change over time. Graphically, the interaction pattern of group means at follow-up appeared only slightly attenuated compared with two weeks. However, with these slight attenuations and the reduced sample size plus the somewhat larger within group variation, the statistical tests did not approach significance except for a trend on Somatic Distress (F = 1.72, p <0.20). The Tension-Anxiety measure yielded no suggestion that the interaction persisted, nor were any tests for the separate effects of Acquiescence or medication significant.
304
DOUGLASM. MCNAIR et al.
A selected subsample. A subsample was selected to control for two factors in addition to medication and Acquiescence: treating doctor and patient sex. Nine doctors in the clinical trial treated either two HA or two LA women, with one patient in each pair on each medication. In terms of significance levels and variance predicted, these 18 patients showed a much stronger medication-personality interaction during the drug trial than did the total sample. Five of these pairs (three HA and two LA) returned at follow-up, and covariance analyses for correlated groups indicated highly significant (p ~0.01) drug-personality interactions for Somatic Symptoms, Depression Symptoms and Tension-Anxiety Mood, and significant interactions (p <0.05) for Anxiety Symptoms and Depression Mood. In spite of the very small N, these interactions appeared to reflect persistence of the interaction seen during the trial, rather than to arise from such misleading factors as pretreatment or variance differences. Graphs of the criterion scores for this subsample were similar to Fig. 2. The two main differences were that: (1) the interactions in the subsample were amplified rather than attenuated at follow-up; (2) the HA-D and LA-P groups in the subsample showed more disturbance at followup than at pretreatment. The data on these five pairs, then, strongly suggest that the Acquiescence-medication interaction may prove to be of considerable magnitude and importance when obscuring influences are controlled. Bias. Tests of the persistence hypothesis may have been biased in opposite directions by two influences : a refuser bias and a terminator bias. While not statistically significant, these possible biases suggest caution in interpreting the findings. In the HA-D group, follow-up refusers (Table 1) tended to be some of the poorer responders to the clinical trial. In the HA-P group, refusers tended to be among the better responders. Such a sampling bias probably acted to attenuate the interaction pattern at follow-up by reducing the contrast between the two HA groups. Premature terminators who returned for the follow-up reported more disturbance than patients who completed their post-trial therapy. There were more such terminators in the LA-P group (46 per cent) than in the LA-D group (9 per cent), suggesting a bias toward exaggeration of the drug-personality interaction. The net effect of these and other unknown sources of bias is impossible to estimate accurately, and replication is crucial.
CONCLUSIONS
AND
SUMMARY
This follow-up study re-evaluated four small groups of psychiatric outpatients who, four months earlier, had completed a double-blind trial of diazepam. A drug-personality interaction demonstrated during the 2-week trial was that High Acquiescer-Placebo and Low Acquiescer-Diazepam groups improved significantly more than High Acquiescer- Diazepam and Low Acquiescer-Placebo groups. The follow-up data supported two principal conclusions about the long-range combined effects of medication and personality: (1) they can modify patients’ reactions to subsequent treatment; (2) they also can endure for a considerable period. Thus, the same two groups who improved most during the clinical trial significantly less often prematurely quit their subsequent therapy and, further, they maintained their significantly greater symptomatic improvement four months later. As a whole, the follow-up sample reported significant additional improvement after the
PERSISTENCEOF A DRUG-PERSONALITY INTERACTION IN PSYCHIATRIC OUTPATIENTS
305
drug trial. The patients, their post-trial therapists and an independent social worker considered both the medication and other aspects of participation in the drug trial to have benefited subsequent therapy. Another finding was that High Acquiescers refused the follow-up request significantly more often than Low Acquiescers, reinforcing previous doubts that High Acquiescers are conformers. Some potential biasing and confounding influences upon the results are discussed, and the need is stressed for replication and for further studies of the mechanism of the drug-personality interaction.
REFERENCES
5.
ROTH, I., RHUDICK, P. J., SHASKAN, D. A., SLOBIN, M. S., WILKINSON, A. E. and YOUNG, H. H. Long-term effects on psychotherapy of initial treatment conditions. J. osychiat. Res. 2. 283, 1962. McNA~R, D., KAHN, R.-J.: DROPPL&AN, L. F. and FISHER, S. Compatibil&y, acquiescence and drug effects. Neuropsychopharmacology 5, 536, 1967. FISHER, S. The placebo reactor: Thesis, antithesis, synthesis, and hypothesis. Dis. ner. Syst. 28, 510, 1967. MCNAIR, D. M., KAHN, R. J., DROPPLEMAN, L. F. and FISHER, S. Patient acquiescence and drug effects. In Non-specific Factors in Drug Therapy, RICKELS, K. (Ed.), pp. 59-12. Thomas, Springfield, Illinois, 1968. BASS, B. Development and evaluation of a scale for measuring social acquiescence. J. abnorm. Sot.
6.
SCHUYZ, R. E. and FOSTER, R. J. A factor
Psychol. 53, 296, 1956. Educ. psychol. Measur. 23,435, I.
MCNAIR,
D.,
FISHER, S., KAHN,
intensive outpatient 8. 9.
treatment.
analytic
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