- Email: [email protected]
Fluphenazine Enanthate and Fluphenazine Decanoate: A Comparative Study in Chronic Schizophrenic Outpatients
Fluphenazine Enanthate and Fluphenazine Decanoate: A Comparative Study in Chronic Schizophrenic Outpatients A. KESKI1'ER, M.D., T.M. ITIL, M.D.,
AND
•
Various studies have demonstrated the clinical merits of long-acting phenothiazines (fluphenazine enanthate and fluphenazine decanoate) in the maintenance and treatment of psychotic patients. I ••. \".\"... A single parenteral administration of either compound has a duration of efficacy up to three weeks. Comparative studies of the enanthate and decanoate forms of fluphenazine show that although both drugs were quite similar, the decanoate form had a longer duration of action and produced less extrapyramidal symptoms than the enanthate form."",t:I, .. The aim of the present study \Vas to compare the efficacy, tolerance and duration of action of both depot forms of fluphenazine in a schizophrenic outpatient population. :\IATERIAL A1'D METHOD From 24 chronic schizophrenic outpatients who were heing treated with fluphenazine decanoate, 18 were included in this study. There were 15 female and three male patients ranging in age from 26 to 51 years with an average of 35.5 years. The length of psychiatric illness was six to 26 years with an average of 12.8 years. Since their release from the hospital they have been followed up as outpatients from 1.6 to 4.1 years with an average of 2.2 ycars prior to this study. Schizophrenic diagnostic subgroup numbers
From the Department of Psychiatry at the Missouri Institute of Psychiatry, University of Missouri School of Medicine, St. Louis, Missouri. Supported in part by USPHS-MH-1l381, the Psychiatric Research Foundation of Missouri and by Squibb Institute for ~fedical Research, New Bmns.wick, New Jersey. ~2
J. M. C. HOLDEN, M.D., M.R.C.P., D.P.\1. were: paranoid, ten; hebephrenic, four; chronic undifferentiated, two; simple, one; and catatonic, one. As reported elsewhere," these patients had received daily oral fluphenazine HCl for an average of six weeks in order to establish a baseline prior to fluphenazine decanoate (FD) I.M. administered at two-week intervals. Individual doses of FD approximated that of the daily oral fluphenazine and ranged from 2.5 mg. to 75 mg. (0.1 cc to 3 cc) per injection. This initial treatment with FD lasted from 12 to 48 weeks with an average of 42 weeks. On a single blind basis, fluphenazine decanoate was then replaced hy fluphenazine enanthate (FE) at equal dosage and administered at the same intervals. Changes in subsequent dosage depended on each individual patient's clinical condition. Those patients receiving an antiparkinson medication ( procyclidine or benztropine) were maintained on it throughout the study and the dosage was increased if clinically indicated. All patients attended the research outpatient clinic regularly every two weeks for the first eight weeks for clinical assessments and injections. After eight weeks, some of the patients were visited every two weeks at their home by the research nurse for the administration of the drug. A seven-point rating scale similar to BPRSII (1 indicating no sign of mental illness to 7 indicating that the patient is extremely ill), was rated monthly for the global clinical evaluations. Psychopathological and druginduced psychosomatic changes were evaluated monthly, using Missouri Institute of Psychiatry rating scales" of 70 and 40 items respectively. The ratings were completed by Volume X
FLUPHENAZINE-KESKINER ET AL TABLE I.
Flu. Enanthate Treatment Period Antiparkimon Med. F.E. (Daily) I.M./q.2 Wk p. B"
Flu. Docanoate Treatment Period Antiparkinson Med. F.D. (Daily) p. B" I.M./q.2 Wk
.
Ran~e
j"
.Avera~e
26.9
Number 01 Patients
18
!
(GROUP) AVERAGE DOSAGE VARIATION
2.5-75
5-15
6
8
6
2.5-75 28.5
6
9
6
15
18
13
S-20
• = Procyclidine
•• = Benztropine
the same psychiatrist throughout the whole study period. Laboratory examinations were carried out at regular monthly intervals for CBC, alkaline phosphatase, SCOT, BUl\', bilirubin, thymol turbidity and urinalysis. EKC's and resting EEG's wcre also performed monthly. RESULTS
All 18 patients completed a mlmmum of 12 weeks of FE treatment. The dosage variation for both drugs shows that (Table I) the last FD dosage ranged from 2.5 to 75 mg. with a group average of 26.9 mg. per single injection. The dose range of FE at the 12th week of treatment was 2.5 mg. to 75 mg. with a group average of 28.5 mg. per single injection and this was about 1.5 mg. higher than the decanoate dosage. During the first eight weeks of FE treatment, five patients reported that "the effect of the 'shots' didn't seem to last" until their next injection was due. In threc of these patients the dosage of the enanthate had to be increased because of signs of deterioration in their condition. One patient required temporary re-hospitalization in order to prevent relapse. Of the 13 patients requiring antiparkinson medication (procyclidine) during decanoate treatment, in two the dosage was increased during the period on the enanthate. Two more patients were started on procyclidine during enanthate therapy, bringing the number of patients receiving procyclidine to 15 during enanthate treatment. The average procyclidine dosage was 1 mg. higher for the group on enanthate than decanoate treatment. January-Ft'brnary 1969
Clinical Evaluation.-Using the seven-point global behavior rating scale, the last scores of the FD period were compared with the scores of the fourth, eighth and 12th week of FE treatment period (Table II). Four of the patients showed higher scores on enanthate, particularly at the eighth week of treatment. Friedman two-way analysis of variance of the scores for all periods on both drugs, however, was not significantly different. PSlJchopathological Evaluation. -Some of the patients reported feelings of "uneasiness and excitability" on the enanthate. Tendency to withdrawal and preoccupation, suspiciousness and poor judgment, were observed as the early signs of clinical deterioration. However, the analysis of variance in the 70 individual symptom scores of the last decanoate treatment to the fourth, eighth and 12th week of FE treatment did not reveal TABLE II. GLOBAL EVALUATION (18 PATIENTS)
Flu. Decanoate
42 Weeks
Score
e
ill !~
'"
~.~ 80
.!It c:lllo
I 2
Treatment Periods Flu. Enanthate 4th Wk 8th WIt 12th WIt
8 8
3 4 5
8 6
..
6 8
3 I
5 9
.
6 7
--------------_._--Tww>way analysis variance :
~o
significant difference.
43
PSYCHOSO~IATICS
Symptoms
TABLE III. I:-ICIDENCE OF SECO:-iDARY EFFECTS (No. of Patients) Flu. Enan. Treatment Flu. Deea. Treatment Slight Moderate Slight Moderate
Hyperkineosia
4
2
Tremor Akathisia
4
4
6
4
5
Dystonia Rigidit'l' Parkinoonoid Am>earanee
I
I
3
I
c-N~aus=ea-:.-V,;.,;o=DlJ=.·t::.;in""g,--
4 5
I
~I,-
I 2
~
2
Weakn..., :..:A::::ch:.:e:;.. ••Pa:.=in=.
--:.'--
2
~.~
Two.. way analY'!'is variance
No significant clifferenee.
statistically significant differences between any of the periods. Secondary EfJects.-The quality of extrapyramidal symptoms during enanthate treatment were similar to those of FD period and were controlled with antiparkinson medication (Table III). However, there was a slight increase in the frequency of akathisia and muscle rigidity during enanthate treatment. Occasional nausea and vomiting as well as complaints or dizziness, aches and pains were also reported more frequently on the enanthate. However, analysis of variance of 40 drug-induced psychosomatic symptoms did not reveal any significant differences hetween the two compounds.
EKG Findings.-In two patients, nonspecific T-\Vave changes were noted. In one there was bradycardia; and in one, sinus arrhythmia was reported during enanthate treatment. Subsequent records were within normal limits. These changes were transient. Laboratory Findings.-Of the various blood tests performed during the enanthate periods, a slight increase in WBC was reported in four patients at eight weeks and in seven patients at 12 weeks, ranging from 10,300 to 15,500 WBC. Subsequent counts later returned to within normal limits. There were no other laboratory deviations of note. Acceptance of Parenteral Medication.Since all 18 patients had previously taken the daily oral tablet form of fluphenazine, an inquiry was made to obtain their reaction to, and possible preference for the parenteral 14
2
form. Eight thought that the injections helped them to a greater extent, six felt that the pills were more helpful and four were undecided. In the preference of tablets to injections the group was equally divided, nine to nine. The main objections to the injections were the need for frequent visits and dislike for the injections. On the other hand, half of the patients preferring the injection felt that they "don't have to worry anymore about taking their medicine." Sixteen stated that they had regularly taken their tablets in the past, and two said that they had not done so. When the alternative of receiving their injection at home and coming to the hospital for follow-up only every two to three months was offered, 14 answered "yes" for continuation of the injections and four said "no." Fourteen thought that the injections were safer, two answered "no" and two were undecided. DISCUSSION AND CONCLUSIOl'
In this study, our findings are in agreement with other comparative studies.""·I:<.t.t Both forms of fluphenazine are effective as longacting preparations (two weeks or longer) and are useful agents in maintenance treatment. The results of the comparative study of FD and FE treatment did not show statistically significant differences between the two forms in regard to efficacy in the maintenance treatment of chronic schizophrenic outpatients. However, as with other investigators, we noticed some minor clinical differences between the enanthate and decanoate forms of fluphenazine. FE was observed to have a shorter duration of effect than decanoate in Volwne X
FLUPHENAZINE-KESKINER ET AL
28 percent of our patients. The early signs of deterioration were a tendency to withdrawal. suspiciousness, excitability and poor judgment. The required dosage for the maintenance of the improvement was slightly higher for the enanthate. Side effects for both compounds were similar. However, the incidence of akathisia and muscle rigidity was slightly higher with the enanthate. The number of patients requiring antiparkinson medication was also higher (15 for FE vs. 13 for FD). The relatively wide margin of the dosage range (2.5 mg. to 75 mg. per injection) for both forms of fluphenazine indicates the necessity for determining the individual maintenance dosage for each patient. One interesting finding was the attitude and the acceptance of parenteral medication. The majority were tolerant and satisfied with this type of treatment. The main objection was the necessity for frequent visits to the hospital for injections. However, in the majority of patients, the inconvenience of frequent visits to the hospital can be avoided by traveling clinics, visiting nurses and close contact with family physicians. This could lead to further family and home treatment programs of psychiatric patients. On the other hand, in-patients who have proved to be reliable in taking their medication regularly, the daily oral form of the compound should be made available if requested. Treatment with depot phenothiazines does not remove the need for daily oral medication of antiparkinson compounds,4 but we found that patients become easily reconciled to their need for antiparkinson medication, when they omit the drug and rapidly develop extrapyramidal symptoms. This study, as well as previous reports indicate that with these long-acting forms of fluphenazine we now have effective therapeutic agents in the treatment of psychotic patients. Both FD and FE are not only important contributions to the management of floridly psychotic patients, but more important aid in the maintenance treatment phase of hospitalized as well as outpatient populations. Serious side effects are rare under supervised conditions; we arc in agreement with Simpson'" that this should not be an objection for the use of these compounds. January-February 1969
ACKNOWLEDGMENT
We would like to thank J. G. Sedivy, M.S., for the statistical analysis, and J. Townsend, R.N., and N. Todt, R.N., for their valuable assistance. REFERENCES
1. BlacWy, P. H.: Depot fluphenazine enanthate treatment of outpatient schizophrenics. }. New Drugs, 5: 114-116, 1965. 2. Bucci, L., Fuchs, M., Simeon, J., and Fink, M.: Depot fluphenazine in the treatment of psychosis in a community mental health clinic, In Press, 1968. 3. ltil, T., and Keskiner, A.: Psychopathological and psychosomatic rating scale. Mo. P.R.F. Publ., 12, 1966. 4. Keskincr, A., Simeon, J., Fink, M., and Itil, T.: Long acting phenothiazine (fluphenazine decanoate) treatment of psychosis. Arch. Gen. Psychiat., 18:447-481, 1968. 5. Keskincr, A., Holden, J. ~1. C., and !til, T. ~I.: Maintenance treatment of schizophrenic outpatients with a depot phenothiazine. PsyclIOSOmotics, 9:166-171, 1968. 6. Kinross-Wright, J., Vogt, A. H., and Charalampous, K. D.: A new method of drug therapy. Amer. }. Psychiat., 119:779-780, 1963. 7. Kline, M. S., and Simpson, G. ~I.: A long acting phenothiazine in office practice. Amer. }. Psychiat., 120: 1012-1014, 1964. 8. Kurland, A. A., and Richardson, J. H.: A comparative study of two lon~ acting phenothiazine preparations, fluphenazine enanthate and fluphenazine decanoate. Psyc/wpharmacologia, 9:320327, 1966. 9. Laian, R. J., High, J. P., and Burke, J. C.: The prolonged action of fluphenazine enanthate in oil after depot injection. Int. }. Neuropsychiat., 1:300-306, 1965. 10. Lambert, P. A., Midenet, M., ~1idenet, Mme. J., Marcou, G., and Bouchardy, J.: Perspective Nouvelles OHertes par un Neuroleptique Injectable Retard L'Enanthate de Fluphenzine. Ann. Medicopsychol., 124 annee, I 702-707, 1966. 11. Overall, J. E., and C.orham, D. R.: Brief psychiatric rating scale. Psyc1lOlogical Reports, 10: 799-812, 1962. 12. Pollack, S. L., Tourlentes, T. T., and Zocchi, A. F.: Clinical trial of fluphenazine enanthate-a long acting injectable tranquilizer. Amer. }. Psyclliat., 121:73-74, 1964. 13. Sanseigne, A. J., Yale, H. L., Hess, S. M., Burke, J. C., and Horovitz, Z. P.: New concept in phenothiazine therapy: Fluphenazine enanthate and fluphenazine decanoate. Agressologle, IX., 309-313, 1968. 14. Simp90n, G. M., Amin, ~I., Kunz, E., and MeCaHerety, F. V.: Studies on a second long acting fluphenazine. Amer. }. Psychiat., 121:784-787, 1965. 15. Simpson, G. ~1.: Side effects of phenothiazines. Brit. }. Psychiat., 113:331, 1967. Missouri IIl$Utute of Psychiatry Unkiersity of Missouri School of Medicine St. Louis, Missouri 45
AND
•
Various studies have demonstrated the clinical merits of long-acting phenothiazines (fluphenazine enanthate and fluphenazine decanoate) in the maintenance and treatment of psychotic patients. I ••. \".\"... A single parenteral administration of either compound has a duration of efficacy up to three weeks. Comparative studies of the enanthate and decanoate forms of fluphenazine show that although both drugs were quite similar, the decanoate form had a longer duration of action and produced less extrapyramidal symptoms than the enanthate form."",t:I, .. The aim of the present study \Vas to compare the efficacy, tolerance and duration of action of both depot forms of fluphenazine in a schizophrenic outpatient population. :\IATERIAL A1'D METHOD From 24 chronic schizophrenic outpatients who were heing treated with fluphenazine decanoate, 18 were included in this study. There were 15 female and three male patients ranging in age from 26 to 51 years with an average of 35.5 years. The length of psychiatric illness was six to 26 years with an average of 12.8 years. Since their release from the hospital they have been followed up as outpatients from 1.6 to 4.1 years with an average of 2.2 ycars prior to this study. Schizophrenic diagnostic subgroup numbers
From the Department of Psychiatry at the Missouri Institute of Psychiatry, University of Missouri School of Medicine, St. Louis, Missouri. Supported in part by USPHS-MH-1l381, the Psychiatric Research Foundation of Missouri and by Squibb Institute for ~fedical Research, New Bmns.wick, New Jersey. ~2
J. M. C. HOLDEN, M.D., M.R.C.P., D.P.\1. were: paranoid, ten; hebephrenic, four; chronic undifferentiated, two; simple, one; and catatonic, one. As reported elsewhere," these patients had received daily oral fluphenazine HCl for an average of six weeks in order to establish a baseline prior to fluphenazine decanoate (FD) I.M. administered at two-week intervals. Individual doses of FD approximated that of the daily oral fluphenazine and ranged from 2.5 mg. to 75 mg. (0.1 cc to 3 cc) per injection. This initial treatment with FD lasted from 12 to 48 weeks with an average of 42 weeks. On a single blind basis, fluphenazine decanoate was then replaced hy fluphenazine enanthate (FE) at equal dosage and administered at the same intervals. Changes in subsequent dosage depended on each individual patient's clinical condition. Those patients receiving an antiparkinson medication ( procyclidine or benztropine) were maintained on it throughout the study and the dosage was increased if clinically indicated. All patients attended the research outpatient clinic regularly every two weeks for the first eight weeks for clinical assessments and injections. After eight weeks, some of the patients were visited every two weeks at their home by the research nurse for the administration of the drug. A seven-point rating scale similar to BPRSII (1 indicating no sign of mental illness to 7 indicating that the patient is extremely ill), was rated monthly for the global clinical evaluations. Psychopathological and druginduced psychosomatic changes were evaluated monthly, using Missouri Institute of Psychiatry rating scales" of 70 and 40 items respectively. The ratings were completed by Volume X
FLUPHENAZINE-KESKINER ET AL TABLE I.
Flu. Enanthate Treatment Period Antiparkimon Med. F.E. (Daily) I.M./q.2 Wk p. B"
Flu. Docanoate Treatment Period Antiparkinson Med. F.D. (Daily) p. B" I.M./q.2 Wk
.
Ran~e
j"
.Avera~e
26.9
Number 01 Patients
18
!
(GROUP) AVERAGE DOSAGE VARIATION
2.5-75
5-15
6
8
6
2.5-75 28.5
6
9
6
15
18
13
S-20
• = Procyclidine
•• = Benztropine
the same psychiatrist throughout the whole study period. Laboratory examinations were carried out at regular monthly intervals for CBC, alkaline phosphatase, SCOT, BUl\', bilirubin, thymol turbidity and urinalysis. EKC's and resting EEG's wcre also performed monthly. RESULTS
All 18 patients completed a mlmmum of 12 weeks of FE treatment. The dosage variation for both drugs shows that (Table I) the last FD dosage ranged from 2.5 to 75 mg. with a group average of 26.9 mg. per single injection. The dose range of FE at the 12th week of treatment was 2.5 mg. to 75 mg. with a group average of 28.5 mg. per single injection and this was about 1.5 mg. higher than the decanoate dosage. During the first eight weeks of FE treatment, five patients reported that "the effect of the 'shots' didn't seem to last" until their next injection was due. In threc of these patients the dosage of the enanthate had to be increased because of signs of deterioration in their condition. One patient required temporary re-hospitalization in order to prevent relapse. Of the 13 patients requiring antiparkinson medication (procyclidine) during decanoate treatment, in two the dosage was increased during the period on the enanthate. Two more patients were started on procyclidine during enanthate therapy, bringing the number of patients receiving procyclidine to 15 during enanthate treatment. The average procyclidine dosage was 1 mg. higher for the group on enanthate than decanoate treatment. January-Ft'brnary 1969
Clinical Evaluation.-Using the seven-point global behavior rating scale, the last scores of the FD period were compared with the scores of the fourth, eighth and 12th week of FE treatment period (Table II). Four of the patients showed higher scores on enanthate, particularly at the eighth week of treatment. Friedman two-way analysis of variance of the scores for all periods on both drugs, however, was not significantly different. PSlJchopathological Evaluation. -Some of the patients reported feelings of "uneasiness and excitability" on the enanthate. Tendency to withdrawal and preoccupation, suspiciousness and poor judgment, were observed as the early signs of clinical deterioration. However, the analysis of variance in the 70 individual symptom scores of the last decanoate treatment to the fourth, eighth and 12th week of FE treatment did not reveal TABLE II. GLOBAL EVALUATION (18 PATIENTS)
Flu. Decanoate
42 Weeks
Score
e
ill !~
'"
~.~ 80
.!It c:lllo
I 2
Treatment Periods Flu. Enanthate 4th Wk 8th WIt 12th WIt
8 8
3 4 5
8 6
..
6 8
3 I
5 9
.
6 7
--------------_._--Tww>way analysis variance :
~o
significant difference.
43
PSYCHOSO~IATICS
Symptoms
TABLE III. I:-ICIDENCE OF SECO:-iDARY EFFECTS (No. of Patients) Flu. Enan. Treatment Flu. Deea. Treatment Slight Moderate Slight Moderate
Hyperkineosia
4
2
Tremor Akathisia
4
4
6
4
5
Dystonia Rigidit'l' Parkinoonoid Am>earanee
I
I
3
I
c-N~aus=ea-:.-V,;.,;o=DlJ=.·t::.;in""g,--
4 5
I
~I,-
I 2
~
2
Weakn..., :..:A::::ch:.:e:;.. ••Pa:.=in=.
--:.'--
2
~.~
Two.. way analY'!'is variance
No significant clifferenee.
statistically significant differences between any of the periods. Secondary EfJects.-The quality of extrapyramidal symptoms during enanthate treatment were similar to those of FD period and were controlled with antiparkinson medication (Table III). However, there was a slight increase in the frequency of akathisia and muscle rigidity during enanthate treatment. Occasional nausea and vomiting as well as complaints or dizziness, aches and pains were also reported more frequently on the enanthate. However, analysis of variance of 40 drug-induced psychosomatic symptoms did not reveal any significant differences hetween the two compounds.
EKG Findings.-In two patients, nonspecific T-\Vave changes were noted. In one there was bradycardia; and in one, sinus arrhythmia was reported during enanthate treatment. Subsequent records were within normal limits. These changes were transient. Laboratory Findings.-Of the various blood tests performed during the enanthate periods, a slight increase in WBC was reported in four patients at eight weeks and in seven patients at 12 weeks, ranging from 10,300 to 15,500 WBC. Subsequent counts later returned to within normal limits. There were no other laboratory deviations of note. Acceptance of Parenteral Medication.Since all 18 patients had previously taken the daily oral tablet form of fluphenazine, an inquiry was made to obtain their reaction to, and possible preference for the parenteral 14
2
form. Eight thought that the injections helped them to a greater extent, six felt that the pills were more helpful and four were undecided. In the preference of tablets to injections the group was equally divided, nine to nine. The main objections to the injections were the need for frequent visits and dislike for the injections. On the other hand, half of the patients preferring the injection felt that they "don't have to worry anymore about taking their medicine." Sixteen stated that they had regularly taken their tablets in the past, and two said that they had not done so. When the alternative of receiving their injection at home and coming to the hospital for follow-up only every two to three months was offered, 14 answered "yes" for continuation of the injections and four said "no." Fourteen thought that the injections were safer, two answered "no" and two were undecided. DISCUSSION AND CONCLUSIOl'
In this study, our findings are in agreement with other comparative studies.""·I:<.t.t Both forms of fluphenazine are effective as longacting preparations (two weeks or longer) and are useful agents in maintenance treatment. The results of the comparative study of FD and FE treatment did not show statistically significant differences between the two forms in regard to efficacy in the maintenance treatment of chronic schizophrenic outpatients. However, as with other investigators, we noticed some minor clinical differences between the enanthate and decanoate forms of fluphenazine. FE was observed to have a shorter duration of effect than decanoate in Volwne X
FLUPHENAZINE-KESKINER ET AL
28 percent of our patients. The early signs of deterioration were a tendency to withdrawal. suspiciousness, excitability and poor judgment. The required dosage for the maintenance of the improvement was slightly higher for the enanthate. Side effects for both compounds were similar. However, the incidence of akathisia and muscle rigidity was slightly higher with the enanthate. The number of patients requiring antiparkinson medication was also higher (15 for FE vs. 13 for FD). The relatively wide margin of the dosage range (2.5 mg. to 75 mg. per injection) for both forms of fluphenazine indicates the necessity for determining the individual maintenance dosage for each patient. One interesting finding was the attitude and the acceptance of parenteral medication. The majority were tolerant and satisfied with this type of treatment. The main objection was the necessity for frequent visits to the hospital for injections. However, in the majority of patients, the inconvenience of frequent visits to the hospital can be avoided by traveling clinics, visiting nurses and close contact with family physicians. This could lead to further family and home treatment programs of psychiatric patients. On the other hand, in-patients who have proved to be reliable in taking their medication regularly, the daily oral form of the compound should be made available if requested. Treatment with depot phenothiazines does not remove the need for daily oral medication of antiparkinson compounds,4 but we found that patients become easily reconciled to their need for antiparkinson medication, when they omit the drug and rapidly develop extrapyramidal symptoms. This study, as well as previous reports indicate that with these long-acting forms of fluphenazine we now have effective therapeutic agents in the treatment of psychotic patients. Both FD and FE are not only important contributions to the management of floridly psychotic patients, but more important aid in the maintenance treatment phase of hospitalized as well as outpatient populations. Serious side effects are rare under supervised conditions; we arc in agreement with Simpson'" that this should not be an objection for the use of these compounds. January-February 1969
ACKNOWLEDGMENT
We would like to thank J. G. Sedivy, M.S., for the statistical analysis, and J. Townsend, R.N., and N. Todt, R.N., for their valuable assistance. REFERENCES
1. BlacWy, P. H.: Depot fluphenazine enanthate treatment of outpatient schizophrenics. }. New Drugs, 5: 114-116, 1965. 2. Bucci, L., Fuchs, M., Simeon, J., and Fink, M.: Depot fluphenazine in the treatment of psychosis in a community mental health clinic, In Press, 1968. 3. ltil, T., and Keskiner, A.: Psychopathological and psychosomatic rating scale. Mo. P.R.F. Publ., 12, 1966. 4. Keskincr, A., Simeon, J., Fink, M., and Itil, T.: Long acting phenothiazine (fluphenazine decanoate) treatment of psychosis. Arch. Gen. Psychiat., 18:447-481, 1968. 5. Keskincr, A., Holden, J. ~1. C., and !til, T. ~I.: Maintenance treatment of schizophrenic outpatients with a depot phenothiazine. PsyclIOSOmotics, 9:166-171, 1968. 6. Kinross-Wright, J., Vogt, A. H., and Charalampous, K. D.: A new method of drug therapy. Amer. }. Psychiat., 119:779-780, 1963. 7. Kline, M. S., and Simpson, G. ~I.: A long acting phenothiazine in office practice. Amer. }. Psychiat., 120: 1012-1014, 1964. 8. Kurland, A. A., and Richardson, J. H.: A comparative study of two lon~ acting phenothiazine preparations, fluphenazine enanthate and fluphenazine decanoate. Psyc/wpharmacologia, 9:320327, 1966. 9. Laian, R. J., High, J. P., and Burke, J. C.: The prolonged action of fluphenazine enanthate in oil after depot injection. Int. }. Neuropsychiat., 1:300-306, 1965. 10. Lambert, P. A., Midenet, M., ~1idenet, Mme. J., Marcou, G., and Bouchardy, J.: Perspective Nouvelles OHertes par un Neuroleptique Injectable Retard L'Enanthate de Fluphenzine. Ann. Medicopsychol., 124 annee, I 702-707, 1966. 11. Overall, J. E., and C.orham, D. R.: Brief psychiatric rating scale. Psyc1lOlogical Reports, 10: 799-812, 1962. 12. Pollack, S. L., Tourlentes, T. T., and Zocchi, A. F.: Clinical trial of fluphenazine enanthate-a long acting injectable tranquilizer. Amer. }. Psyclliat., 121:73-74, 1964. 13. Sanseigne, A. J., Yale, H. L., Hess, S. M., Burke, J. C., and Horovitz, Z. P.: New concept in phenothiazine therapy: Fluphenazine enanthate and fluphenazine decanoate. Agressologle, IX., 309-313, 1968. 14. Simp90n, G. M., Amin, ~I., Kunz, E., and MeCaHerety, F. V.: Studies on a second long acting fluphenazine. Amer. }. Psychiat., 121:784-787, 1965. 15. Simpson, G. ~1.: Side effects of phenothiazines. Brit. }. Psychiat., 113:331, 1967. Missouri IIl$Utute of Psychiatry Unkiersity of Missouri School of Medicine St. Louis, Missouri 45