(Ind. J. Paed. (1993): (60), 3, 423) 

Usha P. Dave, Vijaysingh Chauvan and Jyoti Dalvi,
Centre of Research in Mental Retardation (CREMERE),
V.D. Indian Society for Mentally Retarded, Bombay, India. 

It is important to control abnormal behaviour, hyperactivity and improve cognition in mentally retarded children (MRC), which would help in their education, training and subsequent rehabilitation. Recently it has become known that amongst other side-effects, protracted use of anti-convulsant medication induces cognitive and behavioural dysfunction, which is a major problem in mentally retarded epileptics. In a placebo-controlled study, we confirmed the efficacy of a herbal preparation, BR-16A (Mentat) in controlling such behavioural and cognitive deficits in 40 mentally retarded children. The efficacy of this remedy was further evaluated in 19 MRCs with epilepsy. Twelve patients had generalised seizure, 4 with partial and 3 with mixed seizure pattern. In spite of the usual antiepileptic treatment, the frequency of seizures ranged from 1 to 7 attacks in periods from 1 week to 1 year. With the active drug Mentat, it was possible to note a reduction in seizure frequency. Patients with higher frequency responded better. There was no further increase in the dosage of antiepileptic drugs. There was significant control of other abnormal behaviour as shown by reduction in rating score on the Children’s Behavioural Inventory test. Mentat was effective in controlling abnormal behaviour, especially hyperactivity and incongruous behaviour in mentally retarded children with and without epilepsy. 

Key words: BR-16A (Mentat), Mental retardation, cognition, hyperkinetism. 

Mental retardation is a multidimensional condition and symptoms range from mild to severe. It may present as a specific disorder or may occur in combination with other disorders. More than 6.8 million persons suffer from mental retardation (IQ<70) in the USA¹. In India its number is estimated to be 18 million. 

The degree of mental retardation varies and the level of impairment is classified as per W.H.O. classification². Retarded children learn at a slower rate than normal children and are less capable of mastering abstract and complex concepts. Besides cognitive deficits, associated abnormal behaviour, especially restlessness, hyperactivity, distractibility, aggressiveness and destructive nature are the major complicating factors often interfering with educational and training activities of mentally retarded individuals. 

The treatment approach is the simultaneous application of pharmacological, psychological and behavioural therapies. 

Amphetamine has been shown to be effective in hyperactive normal children^3,4, regardless of the basic aetiological factors involved. While the short-term pharmacological effects of stimulants on the symptoms of hyperactive children are well established, their long-term effects are not so well known⁵. In addition, the use of such drugs might prove harmful in mentally retarded children who manifest different genetic and environmental or unknown causative factors responsible for the basic pathology. BR-16A (Mentat) is a complex herbal preparation prepared as per the knowledge of Ayurvedic science and contains ingredients like Ashvagandha, Malkangni, Mandookaparni, Shankhpushpi and Jalbrahmi^6-11, which are of known value in the management of nervous disorders. 

Initially 19 mentally retarded children fulfilling DSM III-R criteria in the age range of 1-18 years were enrolled in a double-blind, placebo-controlled study. The degree of mental retardation ranged from dull normal (IQ=70-90) to severe retardation (IQ<35). A detailed birth history and family history were recorded and detailed neurological and other necessary investigations were done. Amidst different cognitive deficits and abnormal behaviour, hyperactivity from mild restlessness to severe aggressiveness and anger outbursts were the main criteria for selection. Prior to the treatment, the IQ was assessed using the standard battery of psychological tests appropriate for the age. Details of the cognitive function and behavioural abnormality were assessed using the Children’s Behavioural Inventory (CBI)¹². The children were randomly allocated to 2 groups of ten each to receive either the active drug of placebo in the dose of 2 tsp. three times a day. The initial dose of 1 tsp. was stepped up to a maximum of 2 tsp. at the end of 6 weeks in those cases where the desired therapeutic effect was not observed. At the end of 12 weeks, the assessments were done once again and the code was opened. 

Since at the end of 12 weeks, there was significant improvement seen with the active drug and not with the placebo, it was decided to conduct a further open controlled study with the active drug only in other children. All the patients receiving placebo were switched over to the active drug treatment. A further 40 patients were enrolled, out of which 19 patients also had a history of seizures. Thus a total of 59 patients received treatment for 1 year and assessments were done at 6 months and 1 year. None of the patients received any minerals or vitamin supplements. Nineteen patients having a history of epilepsy received antiepileptic drugs (Table 1). The monthly follow-up was maintained during which clinical and behavioural observations were made. 

In the initial double-blind, placebo-controlled study of 19 patients, significant improvement was noted in the group receiving the active drug as compared to the placebo group, as well as in the pretreatment score (student’s ‘t’ tests) (Table 2). In the later phase of the study, where a total of 60 patients received the drug for one year, significant improvement was noted in both the groups, i.e. in patients with and without epilepsy, at 6 months and 12 months (Figure 1) and there was no statistical difference between the groups. In 40 cases (without epilepsy) of mild to severe mental retardation including dull normal cases, more than 75% improvement was noted in 23, >50% improvement in 8 and >25% in 2 children. The effect was more evident in severely retarded children. The degree of improvement was the same in epileptic children, i.e. more improvement was evident in severely retarded children although epileptic. 

The subset group of anger, hostility and incongruous behaviour describes hyperkinetic and aggressive behaviour in terms of verbal and physical attitudes. Improvement in these areas was reflected in increased concentration and attention span during educational activities (Figure 2).

The subset group of conceptual functioning includes the developmental part of speech, its disturbance and memory functions. Striking improvement was observed in the majority of cases (Figure 3).

The subset group of perceptual dysfunction, lethargy and dejection indicates cognitive function. Significant improvement was noticed with >75% of total improvement. The subset group of physical complaints, fear and worry remained unaffected. These scores were initially low and were present only in the mildly retarded group. 

Incongruous ideation and self-depreciation were noticed. It improved on treatment, reflecting a change in respective subset scores. The development in overall understanding was especially in the severely retarded group which was mainly visible in their obeying simple verbal commands and appropriate response to the same. It was possible to train 12 out of 17 children in toilet habits. As a result, such cases could be brought into a group educational programme from an individual training set-up. The sleep cycle was regulated in hyperactive children.

No side-effects of any kind were reported. However, two children had diarrhoea and passed green coloured stools, similar to the colour of the drug. They also did not show any change in their cognition on behaviour parameters and ultimately the drug was stopped. Two other patients dropped out due to irregular follow-up.

There are no suitable remedies available for mentally retarded children with emotional and behavioural problems. The emphasis of therapy in most conditions is to achieve symptomatic control. The psychotropic drugs have little role in the general treatment programme of mentally retarded children.

Many major tranquillisers are often used in maximal doses for a long period especially in the institutionalized population. Side-effects are common with high dosages of these agents Unmanageable behaviour disorders are helped with major tranquilizers but with decrease in cognitive learning performance¹³. Mentat is a balanced formulation of herbal remedies which chiefly contains CNS-active Ayurvedic drugs (Medhya-rasayan-dravya) shown to be effective in various disorders, mental disability and poor memory^14,15.

The results of this study clearly bring out the remarkable improvement on the CBI rating scale in mentally retarded children. Improvement in hyperactivity and aggressiveness, as indicated by significant reduction in the respective subset scores, emphasises the efficacy of Mentat in behavioural dysfunction. Substantial changes in the score points meant for conceptual days function indicated developmental progress in the areas of cognitive function.

The absence of any deterious effects on performance and learning abilities of subjects treated for a period of one year reflected the safety of the treatment in mental retardation. Sedation or drowsiness, characteristic side-effects of major tranquilisers, was not reported.

Cognitive dysfunction resulting from prolonged use of antiepileptic drugs has been reported¹⁶. With Mentat treatment, marked improvement was noted in children on anti-epileptic therapy. The frequency of seizures diminished especially in patients having attacks more frequently (Table 3).

A noteworthy feature was better response in the moderate to severely retarded group. Two patients with only 25% improvement constituted the severely retarded group. Two mentally retarded children who showed no progress had either associated neurotic features or unknown genetic causes.

The biochemical and molecular events linked with higher brain functions like memory, learning and intelligence still remain unravelled; so also the neurochemical basis of hyperkinetism and other associated abnormal behaviour. It is probable that several interdependent neurotransmitters and peptide systems may be involved. Endorphins playing a role in emotion, behaviour and a variety of mental disorders is a probable hypothesis^17,18. The cholinergic system also extends to the process of learning and memory¹⁹. The cognitive improvement with Mentat could be the effect of the drug on the underlying memory processes and related biochemical features. Mentat probably influences the interaction between various transmitter systems.

As the clinical efficacy in a condition like hyperkinetism has been demonstrated, studies are warranted for elucidating the molecular basis for its efficacy, which may shed more light on the aetiology of the condition.

The authors wish to thank The Himalaya Drug Co. for samples of BR-16A (Mentat) used in the trial.

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