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Journal of Neurology, Neurosurgery, and Psychiatry, 1973, 36, 925-935

Does levodopa alter depression and psychopathologyin Parkinsonism patients?'

GAYLE G. MARSH AND CHARLES H. MARKHAM

From the Departments ofPsychiatry and Neurology, UCLA Centre for the Health Sciences,The Neuropsychiatric Institute, Los Angeles, California, U.S.A.

SUMMARY Twenty-seven Parkinsonism patients and 31 controls, matched for age and verbal IQ,were tested on an objectively scored personality test (Minnesota Multiphasic Personality Inventory)at the beginning of the patients' levodopa therapy and three months later. Patients, but not thecontrols, were retested after 15 months of levodopa treatment. The patients, all ofwhom were intactintellectually, obtained MMPI scores indicating moderate depression before beginning levodopatreatment. There was no test evidence to indicate that levodopa significantly increased or decreasedthe amount of depression in the patients after three or 15 months of levodopa. The patient group,however, significantly increased their Index of Psychopathology (Ip) score after 15 months of levo-dopa but not after three months.

Mild to severe emotional symptoms are notunusual in patients with Parkinson's disease(Patrick and Levy, 1922; Jackson et al., 1923;Mjones, 1949; Warburton, 1967; Mindham,1970). Jackson and his associates (1923) graphi-cally described the emergence of severe emotionaldisorders in Parkinsonism patients who wereoften found to experience emotional symptomsbefore motor symptoms by months or years. In1958, Schwab and England included psycho-logical disorders as part of the symptomatologyof Parkinson's disease-for example, changes inpersonality, depression, agitated states, excessiveanxiety, mental disorganisation and impairment,confusion, dementia, and psychotic symptoms,such as pathological suspiciousness, hallucina-tions, and delusions.

Transitory emotional disturbances similar tothose symptoms described above have beenobserved in patients with Parkinson's diseaseduring levodopa treatment. These disturbancesrange from agitation, restlessness, and depressionto suicide attempts and overt psychosis withhallucinatory activity (Yahr et al., 1968;Barbeau, 1969; Calne et al., 1969; Cotzias et al.,1969; Klawans and Garvin, 1969; Cherington,1 Studies performed in the Department of Neurology with partialsupport from the Lawrence Harvey Fund.

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1970; Jenkins and Groh, 1970a, b; McDowellet al., 1970; Mawdsley, 1970; Treciokas et al.,1970; Damasio et al., 1971). In most cases,lowering the levodopa dosage eliminated theadverse emotional reactions. However, in a fewcases, levodopa had to be discontinued beforethe emotional side-effects subsided. Sacks et al.(1970) found demented patients with Parkinson'sdisease to be severely affected emotionally bylevodopa. Damasio et al. (1971) report that 13 oftheir 15 patients who developed or increasedtheir psychiatric symptoms had a previoLlspsychiatric history. Chronic schizophrenicpatients after being placed on levodopa for drug-induced Parkinsonism deteriorated further intheir mental status (Tobias and Merlis, 1970).

In addition to the observations describingadverse emotional side-effects due to levodopa,Barbeau (1969) and Yahr et al. (1969) alsoobserved an alleviation of depression in manypatients who had been apathetic and depressedbefore levodopa treatment. Wagshul and Daroff(1970) found depressive reactions in only two of125 patients treated with levodopa, one ofwhomhad a history of previous depressive episodes.Because not all patients with Parkinson's diseaseexperience distressing emotional side-effects fromlevodopa, it is conceivable that the reported

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Gayle G. Marsh and Charles H. Markham

clinical observations of emotional abnormalitiesduring levodopa treatment relate to exacerbationsof pre-existing emotional malfunctioning such as

Barbeau (1969) and Tobias and Merlis (1970)have suggested rather than to the emergence of anew emotional disorder.

In all the studies mentioned above, emotionalfunctioning of the patients has been evaluated atthe time of the studies by clinical assessment or byretrospective study of medical records. Bothmethods are subjective in nature and may in-advertently reflect an interviewer's bias.The present study, which is part of a larger

study (Marsh et al., 1971), was undertaken toinvestigate the short-term and long-term effectsof levodopa on the emotional functioning ofParkinsonism patients with attention being givento the assessment of depression and psychoticideation in the patients. Because of the subjectivenature of the clinical observations which oftencontain observer bias, a personality test withobjective test scores was selected to replace thecommonly used clinical judgments as measures ofthe various facets of emotional functioning. The

TABLE 1DESCRIPTIVE CHARACTERISTICS OF THE

PARKINSONISM PATIENTS AND CONTROL SUBJECTS

Parkinsonism patients Control subjects)(22 males; 5 females) (13 males; 18 females)

Range Mean SD Range Mean SD

Age (yr) 44-71 58-11 6-65 42-71 57 00 8 75VerbalIQ* 91-138 111-11 11-92 92-137 113-58 10-68Educ. level

(yr) 8-23 14-37 3 96 6-18 12-35 2 60L-dopa med.

(mth) (g)3 2-9 4-44 1-5515 2-7 4-14 1-30

* Satz and Mogel abbreviated WAIS (1962).

test was administered to the patients beforelevodopa therapy. All patients were retestedtwice, after approximately three months of levo-dopa therapy and again after 15 months. Agroup of control subjects was included in thestudy. The purpose of this control group was todetermine whether any changes in test scoresoccurred as a function of repeated administrationof the test over time.

TABLE 2ANTIPARKINSONISM MEDICATION BEING TAKEN

Patient Daily medication (mg) Daily medication (mg) Daily medication (mg)pre-test (3 mth) (IS mth)

1 None None None2 Procyclidine 20 Same Same

Trihexyphenidyl 4 Same f None3 Benztropine 3 Same None

Amantadine 300 Same Amantadine 2004 None None None5 Benztropine I Same Same6 Benztropine 4 Same Same7 Procyclidine 10 Same SameAmantadine 2008 Benztropine 4 Same Same9 Procyclidine 5 Same Same10 Ethopropazine 100 Same Sameil Procyclidine 5 Same Same12 Trihexyphenidyl 15 Same Trihexyphenidyl 1213 f Trihexyphenidyl 6 1 Same I Same1 Amantadine 200 VSame lSame14 None None Trihexyphenidyl 415 Benztropine 2 Same None~Amantadine 10016 Benztropine 6 None None

f Benztropine I Same 4 Same17 V Trihexyphenidyl 2 Same Same18 fJChlorophenoxamine 150 None None

Benztropine 3 {None None19 Trihexyphenidyl 6 {None f None

Amantadine 6 Same VSame20 Chlorophenoxamine 150 None None21 Benztropine 2 Same Same22 None None Trihexyphenidyl 623 Ethopropazine 200 Same Same24 Benztropine 2-5 Benztropine 05 Benztropine 125 Amantadine 200 None None26 Biperiden 10 Biperiden 10 None

f Biperiden 20 IBiperiden 10 INone27 \ Amantadine 200 None XNone

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Does levodopa alter depression andpsychopathology in Parkinsonism patients?

METHODS

The patient group included 22 males and five femaleson levodopa therapy for Parkinson's disease betweenJuly 1969 and June 1970. They ranged in age from44 to 71 years with a mean age of 58-1 1, and SD of+6 65 years (Table 1). All patients obtained verbalintelligence scores in the average to superior rangewith a mean IQ of 111 11 (which places them at the75th percentile of their age group) and an SD of 11 -92.Educationally, they scored above average: meanyears of education were 14-37; SD 3-96. By thepatients' own accounts, the onset of the disease begannine months to 34 years before levodopa therapy.

Eight patients had had cryothalamotomy per-formed: three on the left, three on the right, and twobilaterally. All cryothalamotomies had been per-formed 10 months to two years before psychologicaltesting. Twenty-three of the 27 patients had beentaking anticholinergic anti-Parkinsonism medica-tions initially. In some cases, after approximatelythree months of levodopa, some of these anti-cholinergic medications were decreased in dosage ordiscontinued for a brief period of time (Table 2).After 15 months of levodopa therapy, the amount ofanticholinergic medications in addition to levodopawas again approximately the same as the pretestlevel. The level of levodopa dosage was about thesame after three months (ranging from 2 to 9 g witha mean of 4-44 ± 1-55 g) and 15 months (ranging from2 to 7 g with a mean level of 4-14± 1-30 g).The patients had general physical and neurological

examinations at one to three month intervals through-out the study. On each patient the examinationswere performed by the same neurologist. Thepatients' neurological state was graded in a number ofways (Treciokas et al., 1971; McDowell and Mark-ham, 1971). One of these was the following overallassessment of the stages of Parkinson's disease:(1) unilateral involvement only; (2) bilateral in-volvement; (3) first evidence of impaired postural andrighting reflexes by examination or by history of poorbalance, falling, etc., disability mild to moderate;(4) fully developed severe disease, disability marked;(5) confinement to bed or wheelchair. A category (0)denoting no discernible motor involvement wasadded at the time of retest to describe the patientswho had complete reversal of their motor symptoms.

CONTROL GROUP The controls were employees orvolunteer workers at UCLA Hospital, physiotherapypatients without central nervous system disease, orrelatives of the Parkinsonism patients. Thirteenmales and 18 females comprised the control groupand ranged in age from 42 to 71 years, mean age of57-0 years, ± 8 75 (Table 1). The two groups were

comparable in age and verbal IQ. The patient grouphad completed more years of formal schooling thanthe control group and contained a larger proportionof males. The greater number of females in thecontrol group may have biased this group towardelevated scores on emotional and physical symptoms,since women in our culture tend to admit morereadily to physical and emotional symptoms thanmen.

PERSONALITY TEST The shortened version of theMinnesota Multiphasic Personality Inventory(MMPI) consisting of 447 statements relating to theindividual's physical status, physical symptoms,morale, attitudes, and beliefs was selected as the testinstrument (Dahlstrom and Welsh, 1960). TheMMPI is a true-false personality questionnaire whichoffers objective test scores on characteristicsassociated with the individual's emotional function-ing. The assumption underlying the test is thatindividuals similar to each other in important aspectsof their personality and behaviour answer thequestions in a similar manner.The MMPI consists of three validity scales and 10

clinical scales. These scales were derived empirically(Dahlstrom and Welsh, 1960) on the basis of beingable to differentiate specific patient groups fromnormal groups. Although the MMPI is interpretedby profile analysis (configuration of the elevatedscales' scores) and not by a score on a single scale, abrief description of the individual scales is givenbelow to acquaint the reader with the diversity ofemotional pathology measured by the test. Thesescale descriptions are based on those of Dahlstromand Welsh (1960) and Good and Brantner (1961).

In general, standard scores on all the scales in therange from 45-55 are within normal limits andindicate that the individual is able to functioneffectively emotionally and to respond to stress with-out crippling neurotic defenses or psychotic de-compensation. As the standard scores increase andapproach 70 and above, the individual is usuallyfound to have an emotional disorder. The nature ofthe disorder is predicted by the profile or pattern ofthe elevated scores. Although a score of 65 and aboveis usually considered to be indicative of emotionalsymptomatology, the seriousness of an elevatedscore is determined not only by the height of theelevation but also by the nature of the scale. Forexample, a score of 65 on scale 5 (the scale measuringmasculinity and femininity) for a college-educatedmale is a relatively benign finding, but a score of 65on scale 6 (Paranoia scale) is suggestive of a moderateamount of suspiciousness, distrust, and possiblyparanoid ideation.The three validity scales (L, F, and K) assess the

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PRE TEST

POST TEST70

50 /= X -----

30

I I 1 1 1 1L F K Hs D Hy Pd Mf Pa Pt Sc Ma Si Es

FIG. 1. Control subjects' mean MMPI scale scores (pre-test and three months post-test).

subject's test-taking attitudes and give informationabout the validity of his test. The Hypochondriasis orHy scale indicates the presence of physical com-plaints and concern over physical health; the De-pression or D scale (depression and general adjust-ment); the Hysteria or Hs scale (somatic complaintsin response to stress and denial of personal diffi-culties); the psychopathic deviate or Pd scale(disregard of social customs and mores, emotionalshallowness, impulsive actions, and difficulties withauthority figures); the Masculinity-femininity or Mfscale (indicates masculine or feminine interestpatterns); the Paranoia or Pa scale (heightenedsuspiciousness, ideas of reference, persecutory orgrandiose self-concepts, and paranoid ideation); thePsychasthenia or Pt scale (anxiety, worry, fears,excessive vacillations in decision-making, concentra-tion difficulties, and obsessive-compulsive tend-encies); the Schizophrenia or Sc scale (bizarre andunusual thoughts or behaviour, and psychoticthinking); the Hypomania or Ma scale (emotionalelation and/or instability, psychomotor excitementand flight of ideas); and Social Introversion-Extroversion or Si scale (social uneasiness andavoidance of other people); the Ego Strength or Es

scale (good physical functioning, spontaneity,ability to share emotional experiences, good reality-testing, feeling of personal adequacy).

PROCEDURE The MMPI was answered by allpatients (except two, see below) before beginninglevodopa and after taking levodopa for approximatelythree months and again after approximately 15months. These two patients answered the MMPIafter being on 0 5 g levodopa per day for six and fourdays, respectively. There is little likehood that sobrief a period of time on the medication could haveinfluenced the patients' emotional or physicalfunctioning. A control group of subjects answeredthe MMPI twice with a three month interval interven-ing between the two testings. The controls were notretested after 15 months.

RESULTS

Both the Parkinsonism and control groups'MMPI mean scores remained stable (Figs 1 and2). Differences between test and retest scores forthe two groups were analysed by t tests for eachgroup separately.

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Hs D Hy Pd M t Pa Pt Sc Ma Si Es

FIG. 2. Parkinsonism patients' mean MMPI scale scores (pre-L-dopa, three months, and 15months post-L-dopa).

VALIDITY SCALE There were no significantdifferences between the two groups on theValidity Scales; scores are diagnostically withinnormal limits and indicate that the subjects' testresults are valid. The control group's mean

scores on all MMPI scales fell well within thenormal range and did not change significantly onretest (Table 3). This test-retest stability suggeststhat any changes observed in the patients' group'sscores reflect actual changes rather than test-retest artefact.

RESULTS OF PATIENTS' SCALE SCORES AFTER THREE

AND 15 MONTHS OF LEVODOPA None of thepatients' 14 scale scores changed significantlyfrom pretest to three-month or 15-month post-test (Table 4) even though the patients demon-

TABLE 3CONTROL SUBJECTS' MMPI SCALES MEAN SCORES

Mean T scores SD

Initial AJfer t Initial AfterScale test 3 mth test test 3 mth

L 49 7 49-1 0-48 5 8 5 2F 54-3 53-1 0-61 6-8 7-9K 53-9 54-8 0-42 8-7 9-4Hs 52-5 50 5 0 79 10-6 8 5D 57-3 55 8 0-54 10-9 11-2Hy 55 0 54-5 0-20 9.1 8-6Pd 53-9 52-1 0-81 9-0 9-2Mf 59-6* 55-4* 1-01 10-4 11.0Pa 53-9 51-8 0 94 6-8 10-0Pt 52-6 50 1 1*02 10-1 9-3Sc 51-3 51-6 1-09 10-2 8-6Ma 540 51-7 093 90 9-8Si 54-2 52-9 055 8-7 9.3Es 57-3 57-2 0-04 10-5 10.1

* Based on 13 control males.

PRE L-DOPAAFTER 3 MONTHSPOST L-DOPAAFTER 15 MONTHS.

I . . _ . . .. . .. . . _

L F K

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930 Gayle G. Marsh and Charles H. Markham

TABLE 4PARKINSONISM PATIENTS MEAN MMPI SCALES SCORES

MMPI Mean Tscores t SD Mean Tscore, t SDscale test test --

Pre- After Pre- After After AfterL-dopa 3 rnth L-dopa 3 mth 15 ,nth 15 mth

L 527 515 074 6-1 60 520 039 6-2F 53 7 54 8 0-71 4 9 6-1 56 7 1-71 6 9K 55 5 55-8 0-11 8 7 10-2 55-8 0 12 9-4Hs 70-2 72 9 0 72 11 8 15 5 73-7 1-21 14 2D 81-3 79 4 0 50 14-4 14-4 83-3 0-46 16 6Hy 697 71-7 0-60 11-2 13-2 72 1 0-72 11-7Pd 57-3 56 3 0-37 9.1 10 5 55-9 0 45 13-1Mf 54.5* 58.6* 1-43 9.4 9.5 55-6* 0 70 10 8Pa 53-3 54 0 0 27 9 7 9-6 55 7 0.91 9 7Pt 63-7 62 1 0 54 10-2 11-7 66 0 0 58 16-0Sc 637 628 0-32 9-2 107 667 100 134Ma 51-2 51-3 0-02 9.4 96 508 019 7-9Si 61-0 61-3 0-12 9.1 87 626 070 86Es 44 0 47 5 1-39 9 7 8-7 45-1 0 40 8 9

* Based on 22 males with Parkinsonism.

TABLE 5PARKINSONISM AND CONTROL GROUPS MEAN SCALES SCORES

MMPI Initial sinean scores t 3-nionth mnean scores tscale - test test

Parkinsonisin Control Parkinsonism Control

L 527 49.7 191 51-5 491 162F 53-7 54.3 0 39 54-8 53 1 0 92K 55 5 53*9 0 70 55 8 54-8 0-39Hs 70-2 52 5 5-98t 72 9 50.5 6 68tD 81-3 57-3 7 07t 79-4 55 8 6.89tHy 69-7 55 0 5 43t 71-7 54-5 5-78tPd 57-3 53.9 1-43 56 3 52 1 1 61Pa 53-3 539 0-27 540 51 8 085Pt 63-7 526 4-15t 62-1 50.1 4-28tSc 63-7 513 4-87t 628 516 435tMa 51-2 540 1-15 51-3 517 0-16Si 61-0 54-2 2-90* 61 3 529 3-55tEs 44 0 57-3 501t 47.5 57-2 3-93t

* P<0-01.t P<0-001.

strated significant improvement in their motor Brantner, 1961). The control group scored wellfunction. within normal limits on all scales.

DIFFERENCES IN MMPI SCALE SCORES BETWEENPATIENT AND CONTROL GROUP On initial testingand after three months, the patient group scoredsignificantly higher than the control groups onseven of the 13 MMPI scales (Table 5), Hs, D,Hy, Pt, Sc, Si, and Es. On all these elevatedscales, the scores are diagnostically as well asquantitatively significant in the range indicatingmild to moderate emotional disturbance(Dahlstrom and Welsh, 1960; Good and

MMPI PROFILE INTERPRETATIONS The controlgroup's MMPI profile is within normal limitson all the subtest scores, indicating that thecontrol subjects as a group had no seriousneurotic or psychotic pathology that wasinterfering with their daily living (Fig. 1).

In contrast, the patient group's elevated profile(Fig. 2) suggests considerable maladjustmentwith complaints of physical illness, depression,and hopelessness which would appear to be to a


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large extent a reality-based response to theprogressively debilitating nature of Parkinson'sdisease. The patient group's post-test MMPIprofiles do not deviate enough from their pretestMMPI profile to justify separate interpretations.The following description therefore is char-acteristic of the profiles. Elevated profiles of thistype have been associated with personality traitsof tension, worrying, a pessimistic outlook,thoughts about death and suicide, loss ofefficiency, feelings of apathy, inadequacy, self-doubt, marked self-depreciation, health worries,and loss of initiative.The Depression scale remained unchanged in

TABLE 6PARKINSONISM PATIENTS' MEAN SCORES

ON DISABILITY RATINGS

Stages of Pre-L-dopa After 3 mth After 15 mth*Parkinson's disease

0 0 5 61 5 15 152 13 5 33 7 2 24 2 0 05 0 0 0

Mean 2-22 1 15 1-04SD 0 85 0-82 0-82

* One patient had not been evaluated clinically after 15 months oflevodopa treatment.

TABLE 7a. FREQUENCY OF MMPI PROFILE TYPES IN PARKINSONISM AND CONTROL GROUPS

Profile tvpe Parkinsonisnm patients Controls

Pre-levodlopa 3 mth 15 inth Pre-test 3 mth

1. Normal depressed 10 7 5 8 92. Normal nondepressed - 1 1 20 203. Abnormal depressed 10 10 12 2 14. Abnormal nondepressed 7 9 9 1 1

b. MMPI PROFILE: COMBINED PROFILE CLASSIFICATIONS

1 and 2 ((Normal) 10 8 6 28 293 and 4 (Abnormal) 17 19 21 3 2

spite of the fact that the patients showed muchimprovement in their physical state. Thisimprovement is shown in the shift of all patientsto a less severe stage of Parkinson's disease(Table 6). The pre-levodopa mean stage ofParkinson's disease was 2-22; after three months,the mean rating was 115 (P<001); after 15months of levodopa therapy, the mean stage was1'04 (P < 0O01). There was no significant differencebetween the patients' improvement in motorability after three and 15 months of levodopatherapy (t=0-49; 0O6<P<0-7).

ADDITIONAL ANALYSIS OF PATIENTS DEPRESSION

SCALE Changes in patients' Depression sub-group categories after three and 15 monthsBecause the Parkinsonism patients' highest score

occurred on the Depression scale, a more

detailed analysis of this scale is included below.Although the patients as a group did notsignificantly change their mean Depression scalescore over the 15 months of levodopa therapy, it

is possible that a subgroup significantly changedtheir individual Depression scores. Anothermethod of analysing the MMPI profiles is tocategorize them individually into diagnostic sub-groups measuring the degree of depression and/or emotional abnormality present in eachpatient. Gilberstadt and Farkas (1961) developedthis method of analysing MMPI profiles whichoffers more detailed analysis of each patient'sMMPI pattern than do group mean score

TABLE 8PARKINSONISM PATIENTS' AND CONTROLS' INDEX

OF PSYCHOPATHOLOGY (Ip) MEAN SCORES

Parkinsonism Controls

Mean SD Mean SD

Pre-levodopa 2-89 1-22 2-13 1-26After 3 mth 2-96 1-40 2-03 1-35After 15 mth 3-37 1-57 - -

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comparisons. Their method involves examiningthe configuration of the scales' scores andcategorizing each individual MMPI profile intoone of the four following categories: (1) anMMPI profile with not more than 1 scale over70, D greater than 60 is categorized as normaldepressed; (2) an MMPI profile with not morethan 1 scale over 70, and D less than 60 is anormal nondepressed one; (3) an MMPI profilewith 2 or more scales over 70, and D greater than80 is an abnormal depressed one; (4) an MMPIprofile with 2 or more scales over 70, and D lessthan 80 is an abnormal nondepressed one. Thismethod which places emphasis on one's score onthe D scale is particularly relevant in examiningthe MMPI profiles of the Parkinsonism patients,since their Depression scale score was theirhighest mean score. Table 7a gives the distributionof Parkinsonism patients and normal controls onthese four MMPI categories.

EFFECTS OF LEVODOPA ON THE PARKINSONISMPATIENTS GILBERSTADT-FARCAS CATEGORIESAlthough more Parkinsonism patients werecategorized as abnormal depressed and abnormalnondepressed after being on levodopa, theincrease was not statistically significant ;2 afterthree months, X2= 217, P<0 50; after 15months, x2= 3 52, P < 0 30).

COMPARING PATIENTS' AND NORMALS' GILBER-STADT-FARKAS' SUBGROUPS In categorizing theMMPI test profiles into the four categoriesdenoting normal and abnormal depressed andnondepressed subjects, the distributions of thetwo groups were found to be reliably differentboth for pretest (X2=29X87, P<0.001) and forthree month post-test (X2 = 31 03, P < 0-001). Oninspecting Table 7a, it is apparent that moreParkinsonism patients were classified in theabnormal depressed and abnormal nondepressedcategories than were the controls. To illustratemore clearly the significant difference betweenthe Parkinsonism and control subjects' MMPIclassification, the four Gilberstadt and Farkas'categories were recombined into two categories:normal (combining categories 1 and 2) andabnormal (combining categories 3 and 4).

2 G-test was the statistical test used in analysis of these data (Sokal& Rohlf, 1969).

Table 7b compares the Parkinsonism and controlgroups on the number of normal and abnormalprofiles. The Parkinsonism patients obtainedmore abnormal profiles than the controls at pre-test (X2=2l185, P<0 001) and at three monthpost-test (X2 = 31.61, P < 0'001).

LEVODOPA S INFLUENCE ON DEGREE OF PSYCHO-PATHOLOGY The Index of Psychopathology (Ip)score was calculated for each Parkinsonismpatient in order to obtain an objective measureof the amount of psychopathology in eachpatient's pre-levodopa, three-month levodopa,and 15-month levodopa MMPIs. The Ip scorewas developed by Sines and Silver (1963) andMeier and French (1965) in an attempt toquantify the concept of degree of psycho-pathology as reflected in the MMPI Pa(Paranoia) and Sc (Schizophrenia) scale scoreelevations and is based on the followingregression equations:

Ip = 0- 1OPa+ 0-06Sc -6.26 (males)Ip = 0-08Pa+ 0 10Sc-7-36 (females)

An individual with a high Ip score is one whohas endorsed many items on these scales indicat-ing oversensitivity, suspiciousness, ideas ofreference and persecution, bizarre and unusualthoughts and behaviour.

INFLUENCE OF LEVODOPA ON PARKINSONISMPATIENTS' IP MEAN SCORES The patients' mean Ipscore did not increase significantly after being onlevodopa for three months (Table 8), t=0-28,P < 0 50, after 15 months of levodopa treatment,however, the Ip score increased significantly(Table 8) indicating an increase in the amount ofpsychopathology after 15 months of levodopa,t=1-83, P=0.05. The increase in the Psycho-pathology Index score occurred after the patientshad been on levodopa over three months, sincethere is a significant increase in Ip score from thethree month to 15 month interval.

COMPARISON BETWEEN PARKINSONISM PATIENTSAND CONTROLS PSYCHOPATHOLOGY INDEX SCORESThe patients obtained significantly higher Ipmean scores than the normals at the time of theinitial test, t=2-33; P=0-01; and after thepatients had been taking levodopa for threemonths, t=2-57, P<0-01 (Table 8).

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DISCUSSION

One of the noteworthy findings in the study isthe presence of moderate depression inParkinsonism patients before levodopa therapythat is apparently resistant to the influence ofimproved motor functioning after three or 15months of levodopa treatment. The patient'sDepression scale score did not change signi-ficantly, even though clinically they had improvedin motor ability. These data do not lend supportto the observation (Yahr et al., 1969) thatdepression is alleviated by levodopa in manyParkinsonism patients. These authors observedtheir patients over a one year interval. In thepresent study, retesting occurred after three and15 months of levodopa therapy. The discrepancybetween the present findings of moderatedepression in Parkinsonism patients beforelevodopa therapy as well as afterward andCherington's clinical observation (1970) thatlevodopa produces depression in someParkinsonism patients indicates the need forfurther research in this area. The research shouldinclude a more thorough evaluation and moredetails about the patient's history in relation tohis past emotional functioning.Although the patients in the present study did

not increase their Depression score significantly,the findings do not rule out the possibility thatlevodopa may exacerbate a pre-existing de-pressive reaction in individual patients with a

psychiatric history of depressive reactions. Therewere no detailed psychiatric histories taken of thepatients in the present study.The finding that Parkinsonism patients remain

moderately depressed in spite of significantimprovement in their motor functioning afterlevodopa treatment suggests that the depressionis probably not a reactive one related to impairedphysical functioning.That the Parkinsonism patients' mean Psycho-

pathology Index (Ip) score increased significantlyafter 15 months of levodopa treatment lendssupport to the clinical observations of Sacks et al.(1970), Tobias and Merlis (1970), and Damasioet al. (1970, 1971) that levodopa exacerbatespsychotic symptoms in demented and schizo-phrenic patients and in patients with a previouspsychiatric history. The present study's patientgroup was relatively intact emotionally before

levodopa therapy and the increase in theirpsychopathology score appears to reflect theemergence ofsome borderline psychotic thinking,but no actual psychosis.The one Parkinsonism patient excluded from

the present study who resembled the dementedpatients of Sacks and his associates did notcomplete his MMPI test. Although he scored inthe average range on his verbal intelligence test,his daily behaviour suggested the confusion andmemory loss that is associated with organicbrain syndrome. It is unfortunate that therewere no MMPI test scores on this patient.

Observations by Duvoisin and Katz (1968)assign a prominent role to the anticholinergicdrugs in the emergence of psychiatric symtomsin some patients. They have described typicalsymptoms arising from the anticholinergicsyndrome that are very similar to those ascribedto levodopa, such as confusion, agitation,hallucinations, stupor, delirium, and psychoticthinking. Duvoisin and Katz have reported thatanticholinergic intoxication occurs with ap-preciable frequency in patients with extra-pyramidal disease who are being treated with anyof the standard anticholinergic medications andresponds readily to physostigmine therapy.

In the present study, patients were maintainedon relatively mild dosages of anticholinergicmedications which probably did not interferewith their emotional functioning. Becauseanticholinergic medications are often prescribedin conjunction with levodopa, further research onpatients being maintained on higher dosages ofanticholinergic medications may help resolvesome of the conflicting reports oflevodopa effectson emotional disturbances in Parkinsonismpatients.The Parkinsonism patients scored highest on

scales D (Depression), Hs (Hypochondriasis),and Hy (Hysteria). These three scales havefrequently been found elevated in the test profilesofneurological patients and have been interpretedas reflecting a depressive reaction in patientswith physical symptoms of a chronic nature.However, in interpreting the present MMPIprofiles of the patients with Parkinson's disease,it is not possible to delineate the aetiology of thepatients' depression from psychological testresults. The depression may be reactive in natureor endogenous in the sense of having an organic

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basis, or a combination of a reactive-endogenousdepression.The patients' moderately to severely elevated

scores on these scales suggest a pervasive mal-adjustment with a preoccupation with physicalfunctioning and feelings of hopelessness. Sad-ness, moodiness, irritability, tension, worry,and pessimism are all indicated. Indecision andinability to get started are to be expected. Thepatients' self-esteem and self-initiative appear tohave been undermined and replaced by feelingsofinadequacy and self-doubt. Socially introvertedbehaviour and social withdrawal are alsoindicated and suggest an inability to feel com-fortable in the presence of other people. Thepatients' reality-testing appears to be fairlyintact and indicates they are aware of theirimpaired functioning.The MMPI profile interpretation corroborates

much of the clinical description of emotionalsymptoms found in patients with Parkinson'sdisease mentioned in the above research,especially that of Jackson et al. (1923). Theobjective data from the MMPI test results lendsupport to Jackson and his associates' contentionthat emotional symptomatology is a frequentsymptom of Parkinson's disease.

Drugs used in the study were Akineton bi-periden), Artane (trihexyphenidyl HCI),Cogentin (benztropine mesylate MSD), Kema-drin (pro-cyclidine hydrochloride), Parsidol(ethopropazine), Phenoxene (chlorophenox-amine), and Symmetrel (amantadine HCI).

We are indebted to Dr. Alexander Caldwell,Assistant Clinical Professor, Department ofPsychiatry, Neuropsychiatric Institute, UCLA,for his valuable suggestions and advice on theMMPI interpretations. Mrs. F. C. Wang was ofgreat service to the study in constructing theFigures and with the statistical analyses of thedata.

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