A Study of the Clinical Outcome of Patients with Profound Mental Retardation Gradually Withdrawn from Chronic Neuroleptic Medication

Annals of Clinical Psychiatry 1995;7(4):155-160.

Running Head: Neuroleptic Withdrawal in Mental Retardation

Philip B. May Jr., M.D. Clinical Associate Professor of Medicine and Pediatrics UMDNJ-Robert Wood Johnson Medical School New Brunswick, NJ Attending Physician, UMDNJ-Robert Wood Johnson Medical School Department of Internal Medicine, Developmental Medicine Clinic, Physician Specialist Hunterdon Developmental Center Clinton, NJ

Eric B. London, M.D. Clinical Assistant Professor of Psychiatry UMDNJ-Robert Wood Johnson Medical School Piscataway, NJ, Medical Director, Advanced Psychological Assessments Freehold, NJ

Thomas Zimmerman, M.D. Assistant Professor of Neurology UMDNJ-Robert Wood Johnson Medical School New Brunswick, NJ

Robert Thompson, M.A. Staff Psychologist Hunterdon Medical Center

Terri Mento, A.B. Administration, Hunterdon Developmental Center

Scott Spreat, Ed.D. Program Director Woodland Center for Langhorne, PA

Communications regarding this manuscript should be sent to: Philip May, M.D. Hunterdon Developmental Center, Box 4003 Clinton, NJ 08809, Phone: 908-735-4031 Fax: 908-730-1311
ABSTRACT:In a naturalistic study of 23 severely and profoundly mentally retarded adult male patients undergoing slow "diagnostic" neuroleptic taper, it was determined that at least 60% could eventually be managed without psychoactive medication. However, most of these demonstrated a remarkably long, but nonetheless transient, period of worsening. This suggests that behavioral deterioration during drug reduction trials does not always indicate a need for chronic neuroleptic maintenance since these behaviors may return to baseline without pharmacological intervention. On the other hand 40% demonstrated persistent (greater than 2 years) behavioral worsening. Those individuals who demonstrated persistent deterioration had been generally well-controlled on neuroleptics, were somewhat older, and receiving a higher baseline dose. Most of these persistently worsened subjects currently require some type of psychoactive medication (although only two have been returned to neuroleptics).

INTRODUCTION: For many years and until relatively recently, maladaptive behaviors encountered in the severely and profoundly mentally retarded were managed outside the mainstream of clinical practice (1). In the 1970's the federal Intermediate Care Facility (ICF/MR) Program was implemented and provided for an improved staff/client ratio and reevaluation of treatment modalities. As surveys emerged which documented the high prevalence of neuroleptic drug use in patients with mental retardation (2), the appropriateness of the use of this class of medication to treat behavioral problems of the mentally retarded came under question. Reports of efforts to reduce neuroleptic medication use in residential facilities for the mentally retarded revealed that medication could often be reduced or eliminated at times without untoward conseguences (3). Federal mandates subsequently were developed which required yearly "diagnostic" efforts to reduce or eliminate medication so that it could be determined which patients still required pharmacotherapy. However, it became apparent that some mentally retarded patients develop severe behavioral syndromes when chronically administered neuroleptic medication was reduced and/or eliminated (4-7). As has been reported by others (4,6,7) the problem confronting the psychiatrist and/or developmental medicine specialist was the distinction of those emergent behaviors representing a transient "withdrawal" phenomenon from those that are symptoms of a neuropsychiatric condition or "psychosis" which had been controlled by the medication. There are few studies which attempt to address this problem, in fact it is not generally appreciated that severe behavioral symptoms which emerge during neuroleptic dosage reduction can be transient. If symptoms do not appear during drug taper, the usual clinical practice is to reintroduce the drug, often at doses higher than the original (4). In his retrospective study of predominately mild/moderate mentally retarded patients, Luchins, et al attempted to determine which patients could be successfully weaned from neuroleptics (4). He found that a psychiatric diagnosis of "psychosis" (usually schizophrenia) was correlated with an inability to be successfully withdrawn from neuroleptics. He also found that the use of "alternative" medication (lithium, carbamazapine, buspirone, propranolol) was positively associated with successful neuroleptic reduction.

In a series of 38 mentally retarded individuals Gaultieri, et al noted behavioral deterioration in 24% which lasted up to 4 months and then returned to baseline (5). Syzmanski has observed transient behavioral deterioration which usually remits by 4 months, but can last as long as one year in some patients (8). These studies suggest therefore, that it is possible for transient maladaptive behaviors to persist for an extended period following neuroleptic reduction in some individuals and that clinicians should take this phenomenon into consideration before reintroducing medications, even though behavioral deterioration has occurred.

The study reported here suggests that behavioral deterioration seen in profoundly retarded individuals being tapered from neuroleptic medication is "transient" more freguently than is generally appreciated. Lack of appreciation of the transient nature of behavioral deterioration may be related to the prolonged nature of the transiency in some cases and also possibly to deficient knowledge of alternative ways to manage the emergent behaviors. Attempts to differentiate transient "withdrawal" phenomena from neuropsychiatric disease/psychosis are discussed.

METHODS: Twenty-three adult male residents of Hunterdon Developmental Center, a 650 bed state ICF/MR facility in Clinton, NJ, were studied. The mean age was 42 years with range of 24-62 years. I.Q.'s were determined by the Slosson Intelligence Test. All patients fell into the severe/profound range (less than 40). All were generally healthy and fully ambulatory. All had received neuroleptic medication (thioridazine) for at least ten years. AIMS testing was routinely performed on all patients on a quarterly basis. None demonstrated tardive dyskinesia at the beginning of the study. Six patients had seizure disorders (complex partial with secondary generalization) and were receiving anti-epileptic medication (tegretol, dilantin, phenobarbital) during the study period.

Clinical evaluation determined that there was little or no documented evidence that chronically administered thioridazine was indeed efficacious in these individuals. Because of possible negative effects on cognition as well as the risk of long term tardive dyskinesia (5), it was decided to initiate a gradual taper process for predominately "diagnostic" purposes. Thioridazine was usually tapered at a rate of 10% of the original dose every three months, thus it took most patients two to three years to be removed completely (See figures 1-3 below). Data was collected for at least one year after thioridazine was discontinued. In all cases data was recorded by direct care staff and evaluated by a psychologist (RT). Numbers shown in the figures represent mean frequency of behavior (B) or mg. of thioridazine (T) for each quarter (3 months).

RESULTS: Overall thioridazine was reduced from a total congregate starting dose of 8750 mg/day in 1989 to 0 mg/day by 1992. Total freguency of destructive behaviors rose from a baseline established in 1989 of 882 incidents per month average, to 1,113 per month average in 1990 and then decreased to 746 average per month during 1993. Coincident with this rise and subsequent fall in destructive behaviors, the use of mechanical restraints (as an indirect measure of severity) increased from an average of 25 times/month to 91 per month and then decreased to an average of 18 times/month during 1993. Individual patterns of behavior fell into three groups. There were no significant differences of age or I.Q. between the three groups.

Group one, which consisted of nine individuals, demonstrated a transient worsening and then return to baseline (SEE BELOW).

GROUP 1: TRANSIENT WORSENING OF BEHAVIOR AS THIORIDAZINE WAS TAPERED.

Group two, which consisted of five individuals, demonstrated a progressive decrease in maladaptive behaviors (SEE BELOW).

GROUP 2: PROGRESSIVE IMPROVEMENT OF BEHAVIOR AS THIORIDAZINE WAS TAPERED.

Group three, which consisted of nine individuals, demonstrated persistent worsening of behavior that lasted for more than two years (SEE BELOW).

GROUP 3: PERSISTENT WORSENING OF BEHAVIOR AS THIORIDAZINE WAS REDUCED.

Detailed tables which provide specific demographic freguencies of target behaviors, and doses of Thioridazine are available from the authors on request.

Patient demographics and clinical variables for the three groups are shown in table 1(SEE BELOW)

TABLE 1	GROUP 1 (TRANSIENT WORSENING)	GROUP 2 (PROGESSIVE IMPROVEMENT)	GROUP 3 (PERSISTENT WORSENING)
Age(range)	39 (31-48)years	43 (34-54)years	45(30-63)years
Mean initial dose of thioridazine(mg/day)	328 mg/day (range 75-773)	195 mg/day (range 50-400)	374 mg/day (range 142-775)
Baseline frequency of behavior(incidents/month)	19 (range 0-98)	63 (range 3-111)	1 (range 0-4)
Frequency of assaults as target behavior	50% (5/9)	40% (2/5)	78% (7/9)
Frequency of epilepsy and anti-epileptic medication.	22% (2/9)	20% (1/5)	33% (3/9)
Current psychoactive medication	None	None	78%(7/9)

There were no significant differences of age or I.Q. between the three groups; however, group 3 (persistant) patients tended to be older and received a slightly higher initial dose of thioridazine. There were too few subjects in each group to achieve statistical significance. In addition, the frequency of assaults (as the measured target behavior) as well as epilepsy (partial complex with secondary generalization) in all cases was slightly higher in group 3. It is interesting to note that the initial baseline frequency of behavior was much lower for the patients who eventually developed persistant behavior problems. In other words these group 3 individuals were apparently "well controlled" by the thioridazine in contrast to groups 1 and 2 patients who had higher baseline behaviors but eventually did better or no worse following discontinuation of the drug.

DISCUSSION: An increased awareness of the negative consequences of chronic neuroleptic use has stimulated a reconsideration of this practice in individuals with severe and profound mental retardation. This has led to attempts to wean individuals from these drugs when indications for their use were unclear (6). While some individuals are able to be weaned without difficulty, others have demonstrated marked deterioration when neuroleptics are withdrawn (4-7). The management of those individuals who demonstrate deterioration is usually to reintroduce the drug, at times a dose higher than the original (4). The study reported here suggests that reintroduction of the drug may not always be necessary since behavioral deterioration seen in 78% (18/23, groups 1 and 3) was transitory half the time (group 1). Others have noticed this phenomenon (5,8). It is also important to note that maladaptive behavior frequency actually improved in twenty-two percent (5/23, group 2) of those who underwent neuroleptic taper. For the group 1 patients, the period of behavioral worsening lasted from as little as 6 months to as long as 21 months before return to baseline. These behaviors were managed primarily by redirection and restraint (as previously mentioned), but we subsequently learned that environmental changes (e.g. to a less noisy or crowded area) may obviate the need for even mechanical restraint. It is therefore important to explore the use of alternativesto neuroleptics in the management of behavioral problems which arise in those profoundly retarded individuals being weaned from neuroleptics. Transient behavior problems may resemble psychiatric syndromes, thus making it difficult to ascertain whether they represent a "withdrawal" state or a bona fide psychiatric disorder. The temporary use of "alternatives" (redirection, environmental changes, the use of carbamazapine, valproic acid, propranaolol, clonidine, etc. ) thus might provide the possibility for symptoms to resolve without chronic pharmacological intervention. Those individuals who demonstrate persistent severe behavior problems (group 3) require careful neuro-psychiatric evaluation and most likely will require a specific psychotherapeutic agent. However many who are tapered will improve without the use of psychoactive medication (14/23 or 61% in our study) (groups 1 & 2) and even those with persistent behavior problems can, infrequently be managed nonpharmacologically with behavioral and environmental techniques (2 patients in group 3). The explanation for the syndromes of "progressive improvement" (group 2) and "transient worsening" (group 1) is unclear. The patients in group 2 might have been experiencing neuroleptic induced akathisia while those in group 1 may have been better able to respond to behavioral programs once the neuroleptic was removed. Alternatively those in group 1 may have been demonstrating a prolonged but transient "cholinergic supersensitivity" (9) adrenergic rebound (10), neuroleptic-induced supersensitivity psychosis (11), or tardive akathisia (5) as has been previously suggested. The emergent behavioral symptoms varied from patient to patient and included slapping, hair pulling, rectal picking, head banging, rumination, tantrums, and assaults. Therefore, in patients with profound mental retardation the symptoms that appear during withdrawal of chronic neuroleptic use are nonspecific and may reflect a general state of agitation secondary to decreased sedation, or as was found in the "persistant" group, symptoms of an underlying neuropsychiatric disorder. There were insufficient numbers of patients in our study to be conclusive about which patients can or cannot be readily tapered from neuroleptics; however, the data suggest adult male profoundly retarded individuals who are older, have a seizure disorder, have a low frequency of aberrant (especially assaultive) behavior while receiving a relatively large dose of neuroleptic may be appropriately treated with neuroleptics. We are still in the process of evaluating those patients who have persistant behavior problems following elimination of thioridazine, and will report the long term follow-up of this group at a future date. At the present time thioridazine has been reinitiated in two patients. Others in group 3 are undergoing trials of alternative medications (table 1). In conclusion, our study is consistent with the study previously reported by Luchins et al (4) in that patients who are accurately diagnosed as "psychotic" will likely benefit from psychoactive medication. The clinical challenge encountered with the profoundly retarded is the achievement of an accurate psychiatric diagnosis. Perhaps neuroradiological (12-14) and psychoneuroendocrinological (15-17), biological markers may help provide the necessary diagnostic precision.

REFERENCES:

l. Nelson R., Crocker A. The Medical Care of Mentally Retarded Persons in Public Residential Persons in Public Residential Facilities. N. Ena. J. Med. 1978; 299: 1039-1044.

2. Hill B., Balow E., Bruininks R. A National Study of Prescribed Drugs in Institutions and Community Residential Facilities for Mentally Retarded People. Psychopharm. Bull. 1985; 21: 279-284.

3. Poindexter A: Psychotropic drug patterns in a Large ICF/MR facility: A ten year experience AM. J. on Ment. Retard. 1989; 93: 624-626.

4. Luchins D., Dojka D., Hanaran P.. Factors Associated with Reduction in Antipsychotic Medication Dosage in Adults with Mental Retardation. Am. J. on Ment. Retard. 1993; 98: 165- 172.

5. Gaultieri, C.T., Schroeder S., Hicks R., Quade D.. Tardive Dyskinesia in young Mentally Retarded Individuals. Arch. Gen. Psych. 1986; 43: 335-340.

6. Fielding L., Murphy R., Reagan M., Peterson T.. An Assessment Program to Reduce Drug Use with the Mentally Retarded. Hosp. & Comm. Psvchiatry 1980; 31: 771-773.

7. Heistad G., Zimmerman R., Doebler M. Long Term Usefulness of Thioridazine for Institutionalized Mentally Retarded Patients. Am. J. of Ment. Def. 1982; 87: 243-251.

8. Szymanski L., Crocker A. Mental Retardation In: Kaplan H., Sadock S. (eds) Comprehensive Textbook of Psychiatrv Baltimore, Wilkins and Wilkins, 1989; 1728-1771.

9. Luchins D., Freed W., Wyatt R. The Role of Cholinergic Supersensitivity in the Medical Symptoms Associated with Withdrawal of Antipsychotic Drugs Am. J. Psych. 1980; 137: 1395-1398.

10. Sovner R. Thioridazine Withdrawal-Induced Behavioral Deterioration Treated with Clonidine: Two Case Reports. Mental Retardation 1995; 33: 221-225.

11. Chouinard G., Jones B., Neuroleptic-Induced Supersensitivity Psychosis: Clinical and Pharmacological Characteristics. Am. J.Psychiatry 1980; 1937: 16-21.

12. May P., Zimmerman T., Thompson R., London E., Tannenbaum L., Spreat S. Significance of Ventricular Enlargement in Individuals with Profound Mental Retardation and Severe Abnormal Behavior, J. of Neuropsychiatry & Clinical Neurosci. 1995; 7: 405-406.

13. Woods B., Brenna S., Todd D., Young T., Panzarino P. MRI Abnormalities in Major Psychiatric Disorders: An Exploratory Comparative Study. J. of Neuropsychiatry and Clin. Neurosci. 1995; 7: 49-53.

14. Andreasen., Flashman L., Flaum M., Arndt S., Swayze V., O'Leary D., Ehrhardt J., Yuh W. Regional Brain Abnormalities in Schizophrenia Measured with Magnetic Resonance Imaging JAMA 1995; 272: 1769-1763.

15. Coryell W., Tsuang D. Hypothalamic-Pituitary-Adrenal Axis Hyper-Activity and Psychosis. Am. J. Psvchiatry 1992; 149: 1033-1039.

16. May, P., Thompson R., Mento T. Serum Prolactin Levels May Predict an Undesirable Outcome to Neuroleptic Reduction in Profoundly Retarded Adults AM. Assoc. on Mental Retard. (ReQion 9Ji Annual Meetinq 1991 (Oct.), Princeton, N.J.

17. Coccaro, E. The Biology of Aggression, Scientific American Science and Medicine. 1995; 2: 38-47.