mechanisms of the placebo effect

7/28/2019 Mechanisms of the Placebo Effect

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P S Y C H O L O G I C A L B U L L E T I NVol. 53, No. 4, 1956

PSYCHOTHERAPY AND THE PLACEBO EFFECTD A V I D ROSENTHAL

National Institute of Mental HealthA N D JEROME D . FRANK

School of Medicine, Johns Hopkins UniversityI t is by now generally recognizedt h a t all f o r m s o f psychotherapy yieldsuccessful results with some p a t i e n t san d that these successes depend to anu n d e t e r m i n e d ex t en t o n factors com-m o n t o m a n y types of re lat ionship

between p a t i e n t a n d therapist . T h i sposes a k n o t t y problem f o r propo-n e n t s of v a r i o u s specif ic forms of psy-chotherapy w h o a r e convinced thattheir successes result f r o m theirp a r t i c u l a r t h e o r y o r t e c h n i q u e a n dwish to convince others of this. A s aresul t , problems of research designin p s y c h o t h e r a p y have been receivingm o r e and more cr i t ical a t tent ion inrece nt years , especial ly w ith refe renceto controls (6, 11, 20, 23, 24, 25, 27,31, 34, 35, 38, 39).Certain general aspects of th e psy-c h o t h e r a p e u t i c relat ionship seem verys i m i l a r to those responsible for the so-cal led placebo effect , which is wellk n o w n to investigators of the thera-p e u t i c efficacy of m e d i c a t i o n s . T hep u r p o s e of this pa per is to describethe placebo effect , discuss some of i tsi m p l i c a t i o n s for the e v a l u a t i o n o fpsychotherapy, a nd make some rec-o m m e n d a t i o n s c o n c e r n i n g r e s e a r c hdesign in p s y c h o t h e r a p y based onthese considerations.

T H E P L A C E B O E F F E C TW e h a v e no w part icipated in twosep arat e investigations of the effec-tiveness o f d r u g s on the s y m p t o m a t i cdistress o f p s y c h i a t r i c o u t p a t i e n t s(14, 22). B oth s tudies involved thea d m i n i s t r a t i o n o f a placebo, a n i n e r ta g e n t o u t w a r d l y i n d i s t i n g u i s h a b l ef r om the agent being tes ted, as wel l

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a s d r u g s . T he physician never knewwhether h e w a s g i v i n g the p a t i e n td r u g o r placebo. T he p at i en t s weretold t h a t a n e w m e d i c i n e ha d b e c o m eavailable which, i t was t h o u g h t ,m i g h t h e l p t h e m . T he physiciansra t ed s y m p t o m s o n a 4 - p o i n t scale o fdistress, with high reliabili ty. I nboth studies a signif icant r e d u c t i o n o fdistress accom panied the taking ofplacebos, as shown in T a b l e 1.T h i s p h e n o m e n o n o c c u rs w i t h g r e a tr e g u l a r i t y , n o t only with respect tothe k i n d s o f s y m p t o m s u s u a l l y a s s o -ciated with psychologic illness, b u twith others as well . F o r e x a m p l e , i na s t u d y o f vaccines for the c o m m o ncold, there was f o u n d a r e d u c t i o n i nthe n u m b e r of yearly colds of 55 percent among those given vaccine a n dof 61 per cen t a m o n g a control groupw ho received in ject ions of isotonicsodium chloride solut ion (4) . H i ll is(15) f o u n d placebos as effective asother agents in inhibi t ing the coughreflex. Wolf and P i n s k y (37) studiedmedical outpat ients suf fe r i n g f r o mpeptic u lcer , migraine, muscle ten-sion, headache, a nd t i g h t m u s c l e s inthe extremities. A ll were also tensea n d anxious. Twenty to thir ty p e rcent fel t be t te r while takin g placebos .L a s a g n a et al. (19) gave 1 m l. ofsaline b y s u b c u t a n e o u s i n j e c t i o n tosurgical pa tients suffer ing from s t e a d y ,severe wound pains a n d f o u n d that30 to 40 per cent reported a satis-f a c t o r y relief of pa in . In a s tudy byJellinek (18) 60 per cent of 199 s u b -jects with chronic headaches receivedrelief f r o m a placebo on one or m o r eoccasions.


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PSYCHOTHERAPY AND THE PLACEBO EFFECT 2 95T A B L E 1S Y M P T O M D I S T R E S S B E F O R E E X P E R I M E N T S A N D A F T E R A T R I A L O N P L A C E B O S

Mean distress scoresS t u d y N D r u g tested

Before A f t e r Signif icanceexperiment placebo of difference1st study2 nd s t u d y 1716 MephenesinReserpine 25.583 4 . 0 6 15.882 4 . 6 9 .01.0 2

The p l a c e b o effect is not alway sfavor able , b u t m a y also resul t i n un -desirable , distressful react ions. A sfa r b a c k as 1933, Diehl (3) using lac-tose placebos as a control fo r a varietyof me di c a t i on s t a ke n b y m o u t h ,f o u n d that some of his subjects re-ceiving placebos developed nausea,faintness, a n d di a rrhe a . Some t i me sthis "toxic response" to placebos m a yeven attain ma j or propor t i on s . Wolfand Pi n s ky (3 7 ) tell of one patientw ho ha d "ove rwhe l mi n g we a kn e s s ,palpitation, and nausea within I Smi n ut e s of t a ki n g he r tablets." I nanother, "a dif fuse itchy e ry t he ma -tous m a c u l o p a p u l a r r a s h d e v e l o p e daf ter te n days of taking pills. A skinconsultant considered the e r u p t i o n tobe t y pi c a l de rma t i t i s me di c a me n t os a .A f t e r use of the pills w as stopped, th ee r u p t i o n qui c kl y cleared." A t h i r dpatient developed epigastric pain fol-lowed b y wa t e ry di a r rhe a , ur t i c a r i a ,and angioneurotic edema of the l ipswithin ten m i n u t e s o f t a ki n g he r pills.O n e o f o u r o w n patients , who hadbeen tolerat ing a chronic syphilo-p h o b i a fa ir ly we l l, b e c a m e a c ut e l yagitated shortly after placebo inges-t ion , b e m o a n i n g w h a t the pills ha ddone to h i m , and required hospitaliza-tion s hor t l y t he re a f t e r .Wolf a nd Pinsky (37) f o u n d thatp l a c e b o s p r o d u c e d m o r e i m p r o v e -m e n t in s ub j e c t i ve t ha n ob j e c t i vem a n i f e s t a t i o n s o f anxiety a nd t e n -sion, but object ive changes also oc-c ur . I n o u r second study (22) , 6 9p er c e n t o f o u r patients showed d e-

creased blood pressure a nd p u l s ere a di n gs fol lowing placebo, 19 percent showed increased blood pres-s u r e , a nd 25 per cent showed a rise inpulse rate. Wolf (36) demonstratedclearly a n d c o n v i n c i n g l y that a c t u a lend-organ changes can follow placeboa d m i n i s tr a t i o n . T h is d e m o n s t ra t io nwas made in a series of studies on then o w - c el eb ra te d T o m , a h u m a n s u b -ject wi t h a large gastric f istula, inw h o m i t was possible to observe d i-rectly the g a str ic m u c o u s m e m b r a n e ,correlating changes in color and t u r -g i d i t y w i t h s i m u l t a n e o u s m e a s u r e -m e n t s o f gastric secretion and m o t o ra c t i v i t y .The placebo effect m a y a c t u a l l yreverse the n o r m a l p h a r m a c o l o g i ca c tion of a dru g. F or e xa m pl e , W ol freports that Tom was repeatedlygiven P r o s t i g m i n e , w h i c h i n d u c e dabdominal cramps, diarrhea, as wella s h y p e r a e m i a , h y p e r s e c r e t i o n , a n dhy pe rm ot i li ty of t he s t om a c h. S ub -s e q u e n t l y , the s a me re s pon s e o c -c u r r e d n o t only to tap w a t e r a n d lac-tose capsules, b u t also t o a t r o p i n es u l f a t e w h i c h u s u a l l y has an inhibit-ing effect 011 gastric f u n c t i o n . Apregnant pat ient with excessive vom-iting showed th e u s u a l response o fnausea a n d v o m i t i n g to ipecac. Thesem a n i f e s t a t i o n s w e r e a c c o m p a n i e d b ycessation of n o r m a l g a s t r i c c o n t r a c -t ions. W hen ipecac was givent h r o u g h a t ub e wi t h s t ron g a s s ura n c ethat it woul d re l i e ve he r v o m i t i n g ,gastric contractions were resumed atthe same interval after ingest ion o f


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2% DAVW KOSENTHAL AND JRROMF. D. FRANKthe d r u g that t h e y w o u l d n o r m a l l yh a v e c e a s e d , a n d he r n a u s e a a n dv o m i t i n g w e r e relieved.T he p l a c e b o ef fect , in shor t , c a nbe quite p o w e r f u l . I t can signifi-c a n t l y m o d i f y the pat ient ' s physio-logical fu nc t io nin g, even to the ex-tent o f r e v e r s i n g the n o r m a l p ha rm a -cological act ion o f d r u g s ; a n d , as willb e d is c u s s e d b e l o w , i t m a y b e e n d u r -i n g . P l a c e b o effects c a n n o t b e dis-missed a s s u p e rf ic ia l o r t r a n s i e n t .They oft e n i n v o l v e a n increased senseof we ll -be ing in the p a t i e n t and ar em a n i f e s t e d p r i m a r i l y by relief fromthe p a r t i c u l a r s y m p t o m a t i c d i s t r e s sfor w h i c h the p a t i e n t e x p e c t s a n d re -ceives t r e a t m e n t . T h u s , t he reliefof a n y p a r t i c u l a r c o m p l a i n t b y agiven m edicat ion is not suff iciente v i d e n c e for the specific effect of them e d i c i n e o n this c o m p l a i n t u n l e s s itcan be sh ow n that the relief is noto b t a i n e d a s a placebo effect .

I M P L I C A T I O N S O F T H E P L A C E B OE F F E C T F O R R E S E A R C H I NP S Y C H O T H E R A P YT he g i v i n g of a n y m e d i c a t i o n m a yh a v e c e r t a i n m e a n i n g s for a p a t i e n tin t e r m s ot his r e l a t i o n s h i p to hisph y s ic ia n w h i c h m a y be ne f i t his c o n -d i t i o n ir respective of the p h a r m a -cological act ion of the d r u g . For e x -a m p l e , i t m a y r e l ieve the a n x i e t y re -s u l t i n g f r o m th e distr ess cau sed b yhis illness (10), W olf believes theef fects o f placebos on his p a t i e n t s"depended fo r their force on the con-vict ion o f t h e p a t i e n t that this or thateffect w o u l d result." T he degr ee oft h e p a t i e n t ' s c o n v i c ti o n m i g h t b e e x -

pected to be influenced by his previ-o u s exper iences with doctor s , hisc on f i de n c e in his p h y s i c i a n , his su g-ge s t ib i l i ty , t h e s u g g e s t ib i l it y - e n h a n c -in g aspects of the s i t u a t i o n in whichthe t h e r a p e u t i c a g e n t is being a d -m i n i s t e r e d , and his f a i th in or f e a r o ft h e t h e r a p e u t i c a g e n t i tsel f . T h e s e

attitudes are obviou sly r e levant topsychother apy.Psychotherapists have theories o fp e r s o n a l i t y a n d p s y c h o t h e r a p y a n dplan their therapeutic actions in thebelief that these are the a c t i v e a g e n t swhich pr odu ce the desired results.A n y f a v o r a b l e c h a n g e s in p a t i e n t sc o n s e q u e n t to a c o u r s e o f psychother -apy tend to be c i ted as evide nce forthe val idi ty of the theor y o f p e r s o n -a l i t y a n d n e u r o s i s w h i c h u n d e r l i e ther a t i o n a l e of the p s y c h o t h e r a p y . I nview of the above discu ssion i t m aywell b e that the efficacy of a n y p a r -t i c u l a r s e t o f t h e r a p e u t i c o p e r a t i o n slies i n t h e i r a n a l o g y t o a p l a c e b o i nthat t h e y e n h a n c e th e ther apis t ' sa n d p a t i e n t ' s c o n v i c t i o n that s o m e -thing u s e f u l is being done. Patientse n t e r i n g p s y c h o t h e r a p y h a v e v a r i o u sdegrees of belief in its efficacy, andthis m a y b e a n i m p o r t a n t f a c t o r inthe results o f t h e r a p y , b u t this ha sn o t b e e n s t u d i e d , t o o u r k n o w l e d g e .W e k n o w that the authoritarian at-t i t u d e o f th e p h y s i c i a n c a n p r o d u c ethis convict ion in som e pat ients .A t fi rs t g l a n c e the a t t i t u d e s f o u n dby F iedler (8, 9) to c h a r a c t e r i z e ex-pe rie n c e d p s y c h o t h e r a p i s t s , v i z . feel-i n gs o f e m p a t h y f o r and closeness tothe p a t i e n t , a n u n d e m a n d i n g a t t i -t u d e , s e c u r i t y , a n d t h e a b i l i t y t o " u n -d e r s t a n d " the p a t i e n t , s e e m d i a -m e t r i c a l l y o p p o s e d to the a u t h o r i t a r -ia n attitude. I t m a y b e , h o w e v e r ,that the t h e r a p e u t i c efficacy o f theseattitudes l ies pr imarily in their abil-i ty to increase the c o nf id e nc e of cer-tain patients in the ability of thet h e r a p i s t to h e l p t h e m . L a ck o f s u c hconfidence may be one of the reasonsw hy p a t i e n t s o f l o w e r socioeconom icstatus f a r e less well in p s y c h o t h e r a p yt h a n p a t i e n t s h i g h e r in this scale (16,29) , a t a l k i n g t h e r a p y s e e m i n g to beb e y o n d t he i r c o m p r e h e n s i o n a n d c o n -t r a r y to their concept ion of the doc-t o r - p a t i e n t r e l a t i o n s h i p .


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PSYCHOTH ERAPY AND THE PLACEBO EFFECT 2 9 7I n this connect ion, th e role o f s u g -gestion in p s y c h o t h e r a p y ha s b e e ne m p h a s i z e d fo r years , especia l ly intherapies utilizing hypnosis, but sug-

gestion effects h a v e b e e n t h o u g h tb y m a n y s i n c e F r e u d t o b e supe r f i c i a land transitory. W e know of no ex-p e r i m e n t a l s t u d y w h i c h d e m o n s t r a t e sthat t h e r a p e u t i c effects based on i n -sights or perceptual reorganization,w hi ch m ay a lso be su gg ested , a re lesssuperf icial or less t ransi tory.It may be pointed out parentheti-cally that c o n v i c t i o n of the h e l p f u l -ness o f therapy need not be e q u a t e dw i t h " m o t iv a t i o n f o r therapy," w h i c hw as invest igated by G r u m m o n (13)a n d D y m o n d ( 5 ) a n d f o u n d to havel i t t le re la t ionship to success in psy-c h o t h e r a p y . P a t i e n t s a r e o f t e n s u f -f iciently distressed to be s t r o n g l ym o t i v a t e d to r e c e i v e h e l p , y e t h a v elittle f a i t h that a p r o c e d u r e s u c h a sp s y c h o t h e r a p y c a n h e lp t h e m .T he s imi lar i ty of the forces o p e r a t -in g in psychotherapy and the placeboeffect m a y a c c o u n t for the high c o n -sistency o f i m p r o v e m e n t , rates f o u n dwith various therapies , f ro m thatc o n d u c t e d b y p h y s i c ia n s w i t h o u t p s y-chiatr ic t ra ining to intensive psycho-analysis (7). This e x p l a n a t i o n g a i n sp l a u s i b i l i t y f r o m the f a c t that re -p o r t e d i m p r o v e m e n t rates f o r vari-ou s series of neurotics treated by dif -f e r e n t f o r m s o f psychotherapy hovera r o u n d 6 0 p e r cent (1). This is thesame as that reported for the placeboef fect in il lnesses in w h i c h e m o t i o n a lc o m p o n e n t s m a y p l a y a m a j o r r o l esuch as "colds" (3) and headaches(18).T o show that a specific form o ft r e a t m e n t p r o d u c e s m o r e t h a n a n o n -specific placebo effect it m u s t beshown that its effects a re s t r o n g e r ,last longer, or a re q u a l i t a t i v e l y d i f -f e r e n t f r o m t h o s e p r o d u c e d by thea d m i n is t ra t io n o f placebos, o r that ita f f e c ts d i f f e re nt t y p e s o f pat ients .

O u r k n o w l e d g e of a l l these mattersis still f r a g m e n t a r y , b u t s om e b e g i n -nings have b e e n m a d e .With respect to the strength andq u a l i t a t i v e n a t u r e of the effects o ft h e r a p y , o ne l ine o f e n d e a v o r ha sbeen to study the physiologicalc ha n ge s o c c u r r i n g d u r i n g p s y c h o -t h e r a p y . S in c e p h y s i o l o g i c a l m e a s -u r e s u s u a l l y u s e d to provide evidenceo f resistance or f r u s t r a t i o n ( 2 6 , 33) ors i m i l a r psychological states d u r i n gpsychotherapy (28) m ay also be in-f l u e n c e d b y t h e p l a c e b o e f f e c t , o n ec a n n o t c o n c l u d e that d e m o n s t r a t i o no f such physiological changes im pl iesa g r e a t e r depth o f t h e r a p y or a m o r ep r o f o u n d r e o r g a n i z a t i o n of the p e r -s o n a l i t y , u n l e s s we a re wil l ing toe q u a t e the placebo e f f e c t w i t h s u c hr e o r g a n i z a t i o n .W i t h r e s p e c t to the d u r a t i o n o fi m p r o v e m e n t , if it c o u l d be s h o w nthat the placebo ef fect is of shorterd u r a t i o n t h a n c h a n g e s specific to agiven p s y c h o t h e r a p y , t hi s w o u l d p r o -vide o ne k i n d o f e v i d e n c e f a v o r i n gthat t h e o r y o f p s y c h o t h e r a p y . A sfar as we k n o w , no s t u d y o f the l imitsof d u r a t i o n of the placebo ef fect hasbeen m a d e . O u r e x p e r i m e n t w i t hm e p h e n e s i n vs. placebo covered f o u r

t wo-we e k p e r io d s . F i g u r e 1 s ho w sthe c u r v e s f o r both agents for theeight weeks.F i g u r e 1 shows that the greatestdecrease in distress f o l lo wing place-bos was f e l t d u r i n g the first two-weektr ia l per iod. A f t e r that, a s l ight butstat ist ical ly i ns i g ni f i cant rise in dis-tress occurred; and, at the end ofe i g h t weeks, the placebo effect w a sa b o u t a s great a s a f t e r tw o weeks.U n f o r tu n a t e ly , o u r data y i e l d e d n oi n f o r m a t i o n o n h o w m u c h l o n g e r itm i g h t h a v e e n d u r e d . I f the effect isa n a l ogous t o t he relief o f pain bypl a c e b os in p a t i e n t s w i t h s u r g i c a lw o u n d s , w e s h o u l d e x p e c t it e v e n t u -ally to d i m i n i s h . L a s a g n a el al. (19)


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298 DAVID ROSENTHAL AND JE RO M E D. FRANK

O(T )830UJQ ZO

PLACEBOSA A E P H E N E S I N

W E E K SF I G . 1. E F F E C T S O F M E P H E N E S I N A N DP L A C E B O O N S Y M P T O M A T I C D I S T R E S S O V E R A N

8 - W E E K P E R I O D .Total p a t i e n t s = 1 7 . A t the 2-, 4 -, 6-, a n d8-week i nt ervals , ^ V for placebo =11, 6, 10,an d 7 respectively, while N fo r m e p h e n e s i n= 6 , 11, 7, and 10 respectively. For t he 2-and 4-week per i ods, th e dosage o f m e p h e n e s i nwas 3 gm s. per da y; for t he 6- and 8-weekperi ods, 9 g m s . per day.

f o u n d t h a t a s p l a c e b o t h e r a p y o f s u c hp a t i e n t s c o n t i n u e d t h e relief e x-p e r i e n c e d de c re a s e d.A l t h o u g h the n u m b e r o f p a t i e n t sis to o s m a l l to j u s t i f y a n y c o n c l u s i o n s ,it is i n t r i g u i n g that the first dose o fm e p h e n e s i n s e e m e d to c o u n t e r a c t thep l a c e b o ef fect . I n t h e s t u d y w i t hr e s e r p i n c ( 2 2 ) , th e o n l y p a t i e n t s w hofa i led to show a pl a c e b o e f f e c t w e r et hos e who ha d re c e i ve d re s e rpi n c pre -vi ous l y . It ma}' be that any d i s c o m -f o r t p r o d u c e d b y a p h a r m a c o l o g i -c a l ly a c t i ve a ge n t t e n ds to c o u n t e r a c tt h e e m o t i o n a l state re s pon s i b l e for apl a c e b o ef fect in s us c e pt i b l e pa t i e n t s .A n a lo g o u s ly , a n a c t i v i t y by the ps y -c h o t h e r a p i s t w h i c h d i s t u r b s t h e p a -tient m a y c o n c e i v a b l y c o u n t e r a c tthe pl a c e b o ef fect o f p s y c h o t h e r a p yw i t h certain pat ients .I t w o u l d a l s o b e h e l p f u l to k n o w ifp a t i e n t s c o u l d b e d i f f e r e n t i a t e d a c -c o r d i n g t o a t t r i b u t e s w hi c h pre d i s -posed t h e m to a posit ive or n e ga t i vepl a c e b o effect . I f p a t i e n t s w h o i m -p r o v e d w i t h a p a r t i c u l a r f o r m o f ps y -c hot he ra py we re a l l kn own t o b e

posit ive placebo reactors , then theimprovement c oul d not be attributedto the specif ic form o f t r e a t m e n t . I f ,h o w e v e r , they w e r e k n o w n not to beposit ive p lacebo reactors , then anyd e m o n s t r a t e d i m p r o v e m e n t w o u l dc o n s t i t u t e e v i d e n c e of efficacy specificto the f o r m o f p s y c h o t h e r a p y .T h e r e is l i t t l e k n o w n , h o w e v e r ,w i t h regard to the attributes o fpl a c eb o re a c t ors . L a s a gn a et al. (19)h a v e m a d e the first attempts to in-vestigate this p r o b l e m and r e p o r ts o m e a t t i t u d e s and Rors c ha c h c a t e -gories w h i c h d i f f e r e n t i a t e d their re -a c t ors ( J V = 1 1 ) f r o m their n o n r e -actors ( 7 V = 1 6 ) . H o w e v e r , o n l y 1 4p e r c e n t o f t he i r pa t i e n t s we re c on -sistent reactors , i .e . , showed the ef -f e c t wi t h e ve ry p l a c e b o dos e , a n d 3 1p e r c e n t we re c on s i s t e n t n on re a c t ors ,while 55 p er cent showed the e f f e c to n s ome oc c a s i on s b ut n ot on ot he rs .This contrasts with the findings ofJ e l l i n e k (18) w hose pa t ients w ithh e a d a c h e w e r e , for the m o s t p a r t ,c i t h e r in the a l w a y s -r e li e v e d g r o u p o rt h e n e v e r - r e li e v e d g r o u p , w i t h o n l y as m a l l p e r c e n t a g e o f p a t i e n t s s h o w i n gi n c o n s i s t e n c y o f r e s p o n s e . T h e a p -p a r e n t c o n t r a d i c t i o n i n f i n d i n g s m a yp e r h a p s r e s u l t f r o m the d i f f e r e n c e inthe c a u s e of the p a i n in the two serieso r f r o m other fac tors . I n any case i ti n d i c a t e s that the p r o b l e m is a c o m -plex o n e n e e d i n g m u c h m o r e s t u d y .I n th e l i g h t o f these c o n s i d e r a t i o n s ,a n y m e t h o d o f d e m o n s t r a t i n g thes p e c i f ic i ty o f r e s p o n s e t o a g i ve n t y peof p s y c h o t h e r a p y w o u l d h a v e to p r o -v i d e a n a d e q u a t e c o n t r o l d e s ig n . A sfar a s w e k n o w , the s t u d y w h i c h ha sp a i d c l os e s t a t t e n t i on t o t he que s t i onof c o n t r o l s in re s e a rc h in ps y c hot he r-apy is that o f Roge rs and his col-l e a g u e s ( 3 1 ) . T h e y e m p l o y e d tw o d i f -f e r e n t k i n d s o f c o n t r o l g r o u p s . O n ew a s a g r o u p o f n on c l i e n t s w ho we res i m p l y gi ve n a battery o f tests b e for ea n d a f t e r specified t i m e p e r io d s . T h e


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PSYCHOTH ERAPY AND THE PLACEBO EFFECT 2 9 9other wa s a g r o u p o f cl ients w ho we rere qui re d t o wa i t a specified period oft i m e b e for e b e g i n n i n g t h e r a p y . Thisg r o u p was tested at the b e g i n n i n gand end of the wait period, at the endof t h e r a p y , and a f t e r a f o l l o w - u p p e-riod.T h e s e p r o c e d u r e s d o n o t c on t rolfor the pl a c e b o ef fect since nei therc on t rol group wa s b e i n g s ub j e c t e dto any s pe c ia l pro c e du re s w hi c h c oul dp r o d u c e a reasonable expectancy inc o n t r o l s u b j e c t s that c e r t a i n c ha n ge ss h o u l d o c c u r . T he e x p e r i m e n t a lg r o u p , howe ve r , c oul d b e expectedto anticipate certain effects m e r e l y a sa consequence o f participating in thec l i e n t - t he ra p i s t i n t e rvi e ws . T he re -f o r e , e ve n t hough fa vora b l e c ha n ge sc o u l d be d e m o n s t r a t e d in their cli-e n t s , the q u e s t i o n o f whether thesewere placebo effects could not beanswered f r o m such research designunless addit ional information wereprovi de d.I f we do not c on t rol for nonspecif icfa c tors like the pl a c e b o ef fect , w ec a n n o t k n o w w h e t h e r effects pre -dicted f r om a theory lead to or resultf r o m i m p r o v e m e n t b a s e d on the n o n -specific ef fect . B u t l e r a nd H a i g h ( 2 ) ,for e x a m p l e , r e p o r t a n increased cor-r e l a t i o n of perceived self with idealself following c l i e n t -c e n t e re d therapy.T h e i m p l i c i t i n f e r e n c e is that thespecific therapeutic method leads tothis increased correlat ion w h i c h , int u r n , c o n t r i b u t e s to a m e l i o r a t i o n o fdisability and distress.It is c on c e i va b l e , t hough, that as aresult of a nonspecific placebo effectthe c l i e n t feels less disabled a nd dis-tressed w h i c h , in t urn , l e a ds him todescribe himself a s m o r e like his idealself. Rogers' (30) findings of greatere mot i on a l maturity in successfullytreated cases m a y b e similarly ex-pl a i n e d, c l i e n t s feeling less disableda n d distressed d u e t o a nonspecificplacebo response and b e ha vi n g c on -

sequently in ways which are less anx-i e t y -de t e rmi n e d a n d whi c h a re s e e na s m o re m a tu r e b y others .W e w o u l d p ro p o se that the fol low-ing cond itions are optimal in planningre s e a rc h i n ps y c hot he ra py :1. A theory of personality and psy-chological distress (neu rosis , m ala d-j u s t m e n t , etc.).2. Predict ions of effects in the pa-t ient o r c l i e n t c on s e que n t to ps y c ho-therapy, in accord with the theory.3 . De m on s t ra t i on of a re l a t i on s hi pb e t we e n the pre di c t e d effects a n ds o m e cri terion of i m p r o v e m e n t .4 . D e m o n s t r a t i o n that the pre -dicted effects a nd their relationshipto the i m p r o v e m e n t c r i t e r i o n a r e n o td u e p r i m a r i l y to the pa t i e n t ' s c on vi c -tion that t he ra py will h e l p h i m . Thiswill pe rmi t gre a t e r co nf i d ence thatthe relat ionship f o u n d is specific tothe t h e r a p e u t i c t e c h n i q u e d e r i v e dfrom the theory.Ide a l l y , t he s e c on di t i on s s houl dob t a i n b ot h for proc e s s a n d out c omeresearch. There s e e ms to be g e n e r a la g r e e m e n t w i t h r e g a r d to the f irsttw o c on di t i on s a l t hough M a c k i n n o n(21) ha s s ome re s e rva t i on s a b outb e g i n n i n g wi t h a t he ory ra t he r t ha na h u n c h . G o r d on et al. (12) havec o m e to q u e s t i o n the t h ir d c o n d i t i o n ,at least with respect to a "global"cr i ter ion o f i m p r o v e m e n t .The f o u r t h condition has not beenm et in any research o f which we ar ea wa re . I t i s not possible to set up ane x p e r i m e n t precisely analogous toc ompa r i s on of a me di c a t i on wi t h aplacebo because there is no such thingas inert psychotherapy in the sensethat pl a c e b os a r e p h a r m a c o l o g i c a l l yi n e rt . H o w e v e r , i t m a y b e possible tos t u d y the possible specific effects o fa ny pa r t i c ul a r form o f therapy by theu s e o f a m a t c h e d c o n t r o l g r o u p p a r -t icipat ing in an a c t i v i t y re ga rde d a st h e r a p e u t i c a l l y i n e r t f r o m the s t a n d -p o i n t of the t he ory of the t h e r a p y


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300 DAVID ROSENTHAL AND JEROME D. FRANKb e in g s t u d i e d . That i s , i t woul d n otb e expected to p r o d u c e the effectspre di c t e d by the t he ory . T he"pl a c e b o ps y c hot he ra py " in thissense would b e a n a l o g o u s to placebosin that it w o u l d b e a d m i n i s t e r e dun de r c i rc ums t a n c e s and by personss u c h t h a t the p a t i e n t s w o u l d e x p e c tto be helped by it.L e t u s s a y that o u r theory is p s y -c h o a n a l y t i c a n d o u r pre di c t e d effectis an increased correlation betweent he mora l va l ue s of t he pa t i e n t a n dthe therapist (superego identi f ica-t ion ) a n d that w e also expect an as-socia t ion between the increased cor-relation and a criterion o f i mprove -m e n t ( 3 2) . A c c o r d in g to the t h e o r y ,there is no reason to believe that con-trol pa t i e n t s re c e i vi n g, f o r e x a m p l e ,r e laxat ion t he ra py (1 7 ) will s how theincreased correlat ion o f m o r a l v a l u e swi t h t he i r t he ra pi s t ' s mora l va l ue s ,nor should they show as m u c h or asl a s t i n g i m p r o v e m e n t as the pa t i e n t sr e c e i v i n g ps y c hoa n a l y t i c t he ra py o fe q u a l l e n g t h . S u c h a d e s ig n w o u l dc o n s t i t u t e a f a i r test of the hypothesisbased on the theory. In comparatives t u d i e s w h e r e o ne type o f ps y c hot he r-a py i s t es te d a ga i n s t a n ot h e r , d i f -fe r e n c e s f o u n d b e t we e n t he m in pre-dicted effects o r a m o u n t , n a t u r e , a n dd u r a t i o n o f i m p r o v e m e n t w o u l d no tbe e xpl a i n a b l e as placebo effects , ifthe condition could be met that pa-t ients ha d e q u a l f a i t h in the efficacyof the therapies and therapists towhich they are assigned.

S U M M A R Y A N D C O N C L U S I O N ST he l i t e r a t u r e o n th e t h e r a p e u t i c

efficacy of d r u g s c o m p a r e d w i t hplacebos is briefly reviewed, and i tsre l e va n c e fo r re s e a rc h in p s y c h o t h e r -a p y c on s i de re d. I t is c o n c l u d e d thati m p r o v e m e n t un de r a s pe c i a l for mof ps y c hot he ra py c a n n ot be t a ke n asevidence for: (a) correctness of thet h e o r y o n w h i c h it is b a s e d ; or ( b )efficacy of the specific t e c h n i q u e u s e d ,un le s s i m p r o v e m e n t c a n b e s h o w n tob e gre a t e r t ha n o r q u a l i ta t iv e l y d i f -ferent from that produced by thepa t i e n t s ' f a i t h in the efficacy o f th etherapist a n d h i s t e c h n i q u e " t h eplacebo e ffe c t . " T h i s effect m a y b et h o u g h t of as a nonspecific f o r m o fpsychotherapy and it may be q u i t ep o w e r f u l in that i t m a y p r o d u c e e n d -orga n c ha n ge s a n d rel ief f ro m distressof c o n s i d e r a b l e d u r a t i o n .T o show that a specific f o r m o fpsychotherapy based o n a t he ory o fpe rs on a l i t y a n d n e uros i s produc e sresults not attributable to the non-specific pl a c e b o ef fect it is not s u f f i -c i e n t to c o m p a r e its re s ul t s wi t hchanges in pa t i e n t s re c e i vi n g n ot r e a t m e n t . T he o n l y a d e q u a t e c o n -trol w o u l d b e another f o r m o f therapyin whi c h pa t i e n t s ha d e q u a l f a i t h , sothat the pl a c e b o e f f e c t ope ra t e de q u a l l y i n b o t h , b u t w h i c h w o u l d n o tb e e xpe c t e d b y t he t he ory of t he ra pybeing studied to p r o d u c e the s a m e e f-fects. W e n e e d t o l e a r n m o r e a b o u tthe nature of the placebo e f f e c t , thecondit ions giving r ise to i t , and thea t t r i b u t e s o f pa t i e n t s mos t s us c e pt i -ble o r re s i s t a n t to it so that w e m a yobtain a b e t t e r u n d e r s t a n d i n g of therole of nonspecific factors in psycho-t he ra py .

R E F E R E N C E S1. A P P E L , K. E . , L H A M O N , W . T., M Y E R S ,J. M., & H A R V E Y , W . A . L o n g termpsychotherapy. I n Psychiatric treat-ment. Proc. Ass. Res. Nerv. Ment. Dis.Dec. 14, I S , 1951, N ew York. Balti-m o r e : W i ll ia m s & Wilkins, 1953, 21-34.2. B U T L E R , J. M ., & H A I G H , G . V . Changes

iu the relat ion between self-con cep tsand ideal concepts consequent uponclient-centered c o u n s e l in g . I n C . R .Rogers & Rosalind F . Dy r a o n d (E d s . ) ,Psychotherapy and personality change,C h ic a g o : U n i v e r. of C h i c a g o P r e s s ,1954. P p. 55-75.


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PSYCHOTHERAPY AND THE PLACEBO EFFECT 3013 . D I E H L , I I . S . M e d i c a l treatment of thec o m m o n cold. /. Amer. Med. Ass.,1933, 101, 2042-2045.4. D I E H L , H. S., B A K E R , A . B . , & C O W A N ,D. W. C old vacci nes, f u r t h e r e v a l u a -

t i on. /.Amer. Med. Ass., 1940, 115,593-594.5. D Y M O N D , R O S A L I N D F. A d j u s t m e n tc h a n g e s in the a b s e n c e o f p s y c h o t h e r -a p y . /. consult. Psychol., 1955, 19,103-107.6. EDWARDS, A . L ., & C R O N B A C I I , L . J .E x p e r i m e n t a l desi gn fo r research inp s y c h o t h e r a p y . J. din. Psychol., 1952,8, 51-59.7. E Y S E N C K , H . J . T h e effects o f psycho-t he r ap y A n e v a l u a t i o n . J. consult.Psychol., 1952, 16, 319-324.8. F I E D L E R , F. E. The c o n c e p t of the i dea lt h e r a p e u t i c r e l a t i o n s h i p . /. consult.Psychol., 1950, 14, 239-245.9 . F I E D L E R , F . E . A c o m p a r i s o n o f t hera-peut i c re la t i onshi ps in p s y c h o a n a l y t i c ,n o n d i r e c t i v e , a n d A d l e ri an t h e r a p y ./.consult. Psychol, 1950, 14, 436-445.1 0 . F R A N K , J. D. Psychotherapeutic aspectsof s y m p t o m a t i c t r e a t m e n t . Amer. J.Psychiat., 1946, 103, 21-25.11. G R E E N H I L L , M. H., F O R D , L . S., O L S O N ,W . C . , R Y A N , W . C., W H I T M A N , S., &S K E E L S , H. M. Evaluation in mentalhealth, B e th e s cl a : N a t io n a l I n s t i t u t e o fM e n t a l H e a l t h , 1 95 5.12 . G O R D O N , T ., G R U M M O N , D. L ., R O G E R S ,C . R . , & S E E M A N , J , Developi ng a pro-g r a m o f research in p s y c h o t h e r a p y . I nC. R. Rogers & Rosal i nd F. D y m o n d( E d s . ) Psychotherapy an d personalitychange. C h ic a g o : U n i v e r . o f C hi cagoPress, 1954. Pp. 12-34.1 3 . G R U M M O N , D. L . P ersonal i t y changes asa f u n c t i o n o f t i m e in p e r s o n s m o t i v a t e dfor therapy. In C. R. Rogers & Rosa-l ind F. D y m o n d (Eds.), Psychotherapyan d personality change. C h i c a g o :U n i v e r. o f C h i c a g o Press, 1954, 238-255.1 4 . H A M P S O N , J. L., R O S E N T H A L , D., &F R A N K , J. D. A c o m p a r a t i v e s t u d y o fth e effects o f m e p h e n e s i n a nd placeboo n t h e s y m p t o m a t o l o g y o f a m i x e dg r o u p o f p s y c h i a t r i c o u t p a t i e n t s . Bull.Johns Hopkins Hasp., 1954, Q S , 170-177.15. H I L L I S , B . R . T h e assessment o f c o u g h -s u p p r e s s i n g d r u g s . Lancet, 1952, 1,1230-1232.

16. I M B E R , S . D ., N A S H , E . H., & S T O N E ,A . R . Social class and d u r a t i o n o fp s y c h o t h e r a p y . /. din. Psychol., inpress.

1 7. J A C O B S O N , E . Progressive relaxation.C h ic a g o : U n i v e r . o f C h i c ag o Press,1938.1 8. J E L L I N E K , E . M . C l in i c a l tests o n c o m -parative effectiveness o f analgesi c drugs.Biometrics Bull, 1946, 2, 87.19 . L A S A G N A , L., M O S T E L L E R , F., F E L S I N G E R ,J. M., & B E E C H E R , H . K . A s tu d y o fthe placebo response . Amer. J. Med.,1954, 16, 770-779.2 0. L E B O , D . T h e p r e s e n t s t a t u s o f researcho n n o n d i r e c t i v e p l a y therapy. J. con-sult. Psychol, 1953, 17, 177-183.2 1 . M A C K I N N O N , D . W . Fact a n d f a n c y inpersonal i t y research. Amer. Psychol.1953, 8, 138-145.22. M E A T H , J . A . , F E L D B E R G , T . M ., R O S E N -T H A L , D., & F R A N K , J. D. A c o m p a r a -t i v e s t u d y o f reserpi ne a nd placebo int he t r e a t m e n t o f p s y c h i a t r ic o u t p a -tients. ( U n p u b l is h ed m a n u s c r i p t . )2 3. M O R S E , P . W . A p r o p o s e d t e c h n i q u e fo rt he e v a l u a t i o n o f p s y c h o t h e r a p y . Amer.J. Orthopsychiat., 1953, 4, 716-731.2 4 . M O S A K , H . H . Problems in the d ef i ni t i o na nd m e a s u r e m e n t o f success in p s y c h o -therapy. L. W. Wolff & J. A. Preckcr:Sitccess in psychotherapy. New Y o r k :G r i m e & Stratton, 1952, 1-25.25. M O W R E R , O . H . (Ed.). Psychotherapy:theory and research. N e w York:Ronald, 1953.2 6 . M O W R E R , O . H ., L I G H T , B . H., L U R I Z ,Z ., & Z E L E N Y , M . P . T e n s i o n c h a n g e sd u r i n g p s y c h o t h e r a p y , w i t h s p e c i a lr ef er ence to resistance. In O. H.M o w r e r ( E d . ) Psychotherapy: theoryand research. N e w Y o r k : R o n a l d , 19 53 ,Pp. 546-640.

27. O B E R N D O R F , C . P . , G R E E N A C R E , P H Y L L I S ,& K U B I E , L . S y m p o s i u m on the e v a l u a -t ion of t h e r a p e u t i c r e s u l t s . Int. J.Psychoanal, 1948, 29, 7-33.28. O ' K E L L Y , L. I. Physi ologi ca l changesd u r i n g p s y c h o t h e r a p y . In O. H.M o w r e r ( E d . ) l^sychotherapy: theoryand research. N e w Y o r k : R o n a ld1953, 641-656.2 9 . R E D L I C H , F . C., H O L L I N G S H E A D , A . B .,R O B E R T S , B . I I . , R O B I N S O N , H . A .,F R E E D M A N , L . Z ., & M Y E R S , J . K .S o c i a l s t r u c t u r e a n d p s y c h i a t r i c d i s -orders. Amer. J. Psychiat., 1953, 109,7 2 9 - 7 3 4 ,3 0 . R O G E R S , C . R . C h a n g e s in the m a t u r i t yof b e h a v i o r as re la t ed to t h e r a p y . InC. R. R o g e r s & R o s a l i n d F. D y m o n d( E d s . ) Psychotherapy an d personalitychange. C h ic a g o: U n i v e r . of C h i c a g oPress, 1954. Pp. 215-237.31. R O G E R S , C . R., & DY M O N D , R O S A L I N D F .


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302 DAVID RO SENTIIAL AND JEROME D. FRANK(Eels.) Psychotherapy anil personalitychange. Chicago: Univcr. o f ChicagoPress, 1954.3 2 . R O S E N T H A L , D. Changes in some moralvalues f o l l o w i n g psychotherapy. /.consult. Psychol., 1955, 19, 431-436.33. T H E T F O R D , W. N. An objective measure-ment o f frustration tolerance in evaluat-in g psychotherapy. I n W . Wol f f &J. A. Precker, Success in psychotherapy.N e w York: Grime & Stratton, 1952,26-62.

3 4 . T H O R N E , F . C . Rules o f evidence in theevaluation of the effects o f psycho-therapy. /. din. Psychol., 1952, 8,38-41.

3 5 . W A T S O N , R . I., M E N S C H , I . , & G I L D E A ,E . F . T h e evaluation of the ef f ect s o fpsychotherapy III. Research design.

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Received July 22, 1055

mechanisms of the placebo effect

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