Drugs are widely used in mental retardation. Besides being used for disorders which are simply more frequent in this population, such as epilepsy, Gilles de la Tourette syndrome, and psychosis, drugs play a part in the management of a wide range of symptomatology which includes aggression, self-injury, social withdrawal, compulsive routines, outbursts of distress, and social withdrawal. About one-third of the people in institutions are on neuroleptics and a further third are on antiepileptics. As discharge to the community does not bring much change, the figures probably reflect the nature of these populations as much as that of the institutions.
The presence of mental retardation lends its own emphasis to prescribing.
!. Non-compliance usually results from an unpalatable formulation or a carer's prejudice rather than forgetfulness.
2. Coexistent disorders, such as epilepsy, constipation, and cerebral palsy, can make a patient more vulnerable to adverse effects.
3. Cerebral dysfunction may cause more frequent atypical responses, sensitivity being either increased or decreased to various aspects of the drug's effect. Most responses are dose-specific paradoxical effects, and therapeutic windows are frequent and, as frequently, forgotten. Prescribing details are subject to revision and should be checked with a formulary.(8) However, treatment should be started at a lower dosage and increased more gradually than recommended for the rest of the population. The unexpected should be expected so that, besides the routine warning of adverse effects, carers should have someone to contact if they are in any doubt about the drug's effects.
4. Evidence of efficacy is anecdotal, with trials being mostly small, open, and uncontrolled, but providing some justification for almost any neuropharmacological adventure.
These are used frequently and for a variety of symptoms despite a shortage of consistent, demonstrable, and specific effects. For example, although a series of studies have shown haloperidol to be effective in autism, the response can be in any of a variety of areas including decreases in anger or overactivity, a reduction in the frequency and intensity of outbursts, and improved discrimination learning.(9) The recent proliferation of neuroleptics has been driven by a search for greater effectiveness together with a reduced risk of adverse effects and has been steered by the theoretical clinical attributes of various neuroreceptor systems. Neuroleptics largely block dopaminergic transmission. Animal work suggests that self-injury might be the result of D ! supersensitivity. Fluphenazine, which predominantly affects D!
transmission, was effective in open trial.(!0) Clozapine, also very effective for self-injury but limited by its propensity for marrow toxicity, has a broad affinity for both serotoninergic and dopaminergic receptors. A stream of anecdotal reports indicate risperidone, blocking both D 2 and 5-HT2 receptor sites, to be effective in aggression, social withdrawal, and attention-deficit hyperactivity disorder. Other drugs are being evaluated; unwanted weight gain will restrict the use of olanzepine, another drug with a broad receptor affinity that includes both D 2 and 5-HT2 sites. As more neuroleptics are released the clinical relevance of such subtyping remains to be confirmed.
The prevalence of tardive dyskinesias depends on dose and duration. Although cerebral dysfunction may be a predisposing factor, it may also be that it identifies a group of people who, starting at an earlier age, have been on neuroleptics longer. The risk may be increased further by female sex and perinatal complications, but more general conclusions are limited by the size and selection of the groups surveyed. (!!,)
Depression, once noticed and identified, is as treatable as in the normal population. Obsessive-compulsive symptomatology is frequent and responsive to the drugs augmenting serotoninergic transmission. The use of the selective serotonin reuptake inhibitors and lithium is being extended beyond the management of apparently compulsive acts of violence and self-injury to include bouts of non-specific distress. A small study has shown clomipramine to be effective, (12> but the evidence for the value of the newer selective serotonin reuptake inhibitors is still based on open series.
The serotoninergic system appears to be central to a wide number of vegetative functions suggesting a potential for these drugs in appetite disorders such as the compulsive search for food and lack of satiety of Prader-Willi syndrome.
Propranolol and nadolol limit the autonomic response to anxiety and the propensity to panic. They have a particular place where acute anxiety underlies aggression as, for example, in someone with autism who lashes out or flees when feeling crowded. They are non-sedative but can cause lethargy and even depression.
There is a widespread re-evaluation of the place of attention deficit-hyperactivity disorder, its prevalence, and management. There is a general unsubstantiated belief that it is more intractable the greater the degree of mental retardation. Methylphenidate and amphetamine remain the standard treatments, but amantadine might be more effective and less toxic.(l3> When effective, stimulants can produce a global improvement in behaviour that includes appetite, sleep, and mood, even though anorexia, insomnia, and depression head the list of potential adverse effects.
Several antiepileptic drugs have been used to treat the episodic dyscontrol syndrome—sudden outbursts of rage which have an organic, possibly epileptic, basis. A retrospective study found carbamazepine to be effective although this may simply be the result of better control of clinical epilepsy. ^i15,' Aggression has a large variety of causes and, after the exclusion of physical discomfort, the primary approach is psychological. However, lithium has shown to be effective in reducing outbursts of aggression, particularly where there is irritability and explosiveness. (!,6)
Early congenital opioid excess might underlie both autism and its frequent associate, an indifference to pain. On this theoretical basis, naltrexone is used both for autism and for repetitive self-injury, the latter possibly representing excessive self-stimulation. Blocking endorphin receptors, the ability of naltrexone to effect a sustained reduction in repetitive self-injury contrasts with the deterioration induced by its predecessor, naloxone. (!7> However, naltrexone, a long-acting compound, probably withholds the self-stimulatory reward consistently whereas the short-acting nature of naloxone allows intermittent reward, reinforcing self-stimulation as effectively as a fruit machine reinforces gambling.
Where autism shows any response it is to a very low dosage (0.5 mg/kg/day), a window in a therapeutic U-curve. (!8) Subsequent trials failed to confirm this, but a substantially higher dosage was used. By contrast, if self-injury responds, it is to a higher dosage (100 mg/day), a response that is neither straightforward nor consistent and appears to be delayed and incremental, the response rate improving even 2 years after starting treatment. (19)
For a few, a strong sexual drive overrides the teaching, training, and psychological therapies which are the main approach to sexual offending. An anti-libidinal agent can supplement the other approaches, reducing the drive to a level where it is under the patient's control. The sensitivity of this area makes it especially important that the patient, the family, and the carers are all part of any decision to use medication.
Cyproterone acetate, a steroid analogue which reduces testosterone levels, and medroxyprogesterone acetate are the most frequently used. (20) The former can affect growth and should not be used in anyone under 18 years of age. Although not licensed for this use, goserilin offers a third choice where the others have failed. The efficacy of benperidol, a neuroleptic, is in doubt.
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