Mental Retardation - Treatment

Treatment of mental retardation

Psychopharmacotherapy of mental retardation is entering a new era, characterized by improved diagnostics, understanding of its pathogenetic mechanisms, and expansion of therapeutic possibilities.

The examination and treatment of children and adults with mental retardation must be comprehensive and take into account how the individual learns, works, and how his or her relationships with others are developed. Treatment options include a wide range of interventions: individual, group, family, behavioral, physical, occupational, and other types of therapy. One of the components of treatment is psychopharmacotherapy.

The use of psychotropic drugs in mentally retarded individuals requires special attention to legal and ethical aspects. In the 1970s, the international community proclaimed the rights of mentally retarded individuals to receive adequate medical care. These rights were set out in the "Declaration of the Rights of Disabled Persons". The Declaration proclaimed "the right to adequate medical care" and "the same civil rights as other people". According to the Declaration, "persons with disabilities should be provided with qualified legal assistance if it is necessary for the protection of these persons".

The proclamation of the right of mentally retarded persons to adequate medical care implied close control over possible excesses in the application of restrictive measures, including in connection with the use of psychotropic drugs to suppress unwanted activity. Courts are generally guided by the provision that physical or chemical restraint measures should be applied to a person only when "violent behavior, injury, or suicide attempt occurs or is seriously threatened." In addition, courts usually require "an individual assessment of the possibility and nature of violent behavior, the likely effect of drugs on the individual, and the possibility of alternative actions of a less restrictive nature" - in order to confirm that the "least restrictive alternative" has been implemented. Thus, when deciding to use psychotropic drugs in mentally retarded persons, the possible risks and expected benefits of such a prescription should be carefully weighed. The protection of the interests of a mentally retarded patient is carried out through the use of an “alternative opinion” (if the anamnestic data indicate the absence of criticism and the patient’s preferences) or through the so-called “substituted opinion” (if there is some information about the individual’s preferences in the present or past).

In the last two decades, the doctrine of the "least restrictive alternative" has become relevant in connection with the data of studies on the use of psychotropic drugs in mentally retarded patients. It turned out that psychotropic drugs are prescribed to 30-50% of patients placed in psychiatric institutions, 20-35% of adult patients and 2-7% of children with mental retardation observed on an outpatient basis. It was found that psychotropic drugs are more often prescribed to elderly patients, persons to whom more severe restrictive measures are applied, as well as patients with social, behavioral problems and sleep disorders. Gender, level of intelligence, the nature of behavioral disorders did not affect the frequency of use of psychotropic drugs in mentally retarded individuals. It should be noted that although 90% of mentally retarded individuals live outside psychiatric institutions, systematic studies of this contingent of patients are extremely rare.

Psychotropic drugs and mental retardation

Since people with mental retardation are often prescribed psychotropic drugs, and often a combination of them, to control their behavior over a long period, it is extremely important to consider the short-term and long-term effects of these drugs in order to choose the safest ones. First of all, this concerns neuroleptics, which are especially often used in this category of patients and often cause serious side effects, including irreversible tardive dyskinesia. Although neuroleptics allow controlling inappropriate behavior by suppressing behavioral activity in general, they are also able to selectively inhibit stereotypes and autoaggressive actions. Opioid antagonists and serotonin reuptake inhibitors are also used to reduce autoaggressive actions and stereotypes. Normotimic drugs - lithium salts, valproic acid (depakine), carbamazepine (finlepsin) - are useful in correcting cyclic affective disorders and outbursts of rage. Beta-blockers, such as propranolol (Anaprilin), can be effective in treating aggression and disruptive behavior. Psychostimulants - methylphenidate (Ritalin), dextramphetamine (Dexedrine), pemoline (Cylert) - and alpha2-adrenergic agonists, such as clonidine (Clonidine) and guanfacine (Estulic), have a positive effect in treating attention deficit hyperactivity disorder in people with mental retardation.

Combined treatment with neuroleptics, anticonvulsants, antidepressants and normotimics is fraught with problems associated with pharmacokinetic and pharmacodynamic interactions. Therefore, before prescribing a combination of drugs, the doctor should inquire about the possibility of drug interactions in reference books or other sources of information. It should be emphasized that patients often take unnecessary drugs for a long time, the withdrawal of which does not have an adverse effect on their condition, but allows them to avoid the side effects of these drugs.

Neuroleptics. Many psychotropic drugs have been used to suppress destructive actions, but none of them have been as effective as neuroleptics. The effectiveness of neuroleptics can be explained by the role of hyperactivity of the brain's dopaminergic systems in the pathogenesis of autoaggressive actions. Clinical trials of chlorpromazine (chlorpromazine), thioridazine (sonapax), and risperidone (rispolept) have demonstrated the ability of all these drugs to inhibit destructive actions. Open trials of fluphenazine (moditen) and haloperidol have also demonstrated their effectiveness in correcting autoaggressive (self-harming) and aggressive actions. However, aggressiveness may not respond to neuroleptic treatment to the same extent as self-harming actions. Perhaps, internal, neurobiological factors are more important in autoaggressive actions, while aggressiveness depends more on external factors.

The main danger in using neuroleptics is the relatively high frequency of extrapyramidal side effects. According to various studies, approximately one or two thirds of patients with mental retardation show signs of tardive dyskinesia - chronic, sometimes irreversible orofacial dyskinesia, usually associated with long-term use of neuroleptics. At the same time, it has been shown that in a significant proportion (in some studies, in a third) of patients with mental retardation, violent movements resembling tardive dyskinesia occur in the absence of neuroleptic therapy. This indicates that this category of patients is characterized by a high predisposition to the development of tardive dyskinesia. The likelihood of developing tardive dyskinesia depends on the duration of treatment, the dose of the neuroleptic, and the age of the patient. This problem is especially relevant due to the fact that approximately 33% of children and adults with mental retardation take neuroleptics. Parkinsonism and other early extrapyramidal side effects (tremor, acute dystonia, akathisia) are detected in about a third of patients taking neuroleptics. Akathisia is characterized by internal discomfort, forcing the patient to be in constant motion. It occurs in about 15% of patients taking neuroleptics. The use of neuroleptics carries the risk of neuroleptic malignant syndrome (NMS), which is rare but can lead to death. Risk factors for NMS are male gender, the use of high-potency neuroleptics. According to a recent study, the mortality rate among mentally retarded individuals with the development of NMS is 21%. In cases where patients with mental retardation are prescribed neuroleptics, a dynamic assessment of possible extrapyramidal disorders is mandatory before and during treatment using special scales: Abnormal Involuntary Movement Scale (AIMS), Dyskinesia Identification System Condensed User Scale (DISCUS), Acathisia Scale (AS). Atypical neuroleptics such as clozapine and olanzapine are less likely to cause extrapyramidal side effects, but their effectiveness in mentally retarded individuals must be confirmed in controlled clinical trials. It should also be recalled that although clozapine is an effective neuroleptic, it can cause agranulocytosis and epileptic seizures. Olanzapine, sertindole, quetiapine and ziprasidone are new atypical neuroleptics that will undoubtedly be used in the future to treat mentally retarded patients. patients, as they are safer than traditional neuroleptics.

At the same time, an alternative to neuroleptics has recently appeared in the form of selective serotonin reuptake inhibitors and normothymic agents, but their use requires a more precise identification of the structure of mental disorders. These drugs can reduce the need for neuroleptics in the treatment of self-harming actions and aggression.

Normotimic agents. Normotimic agents include lithium, carbamazepine (finlepsin), and valproic acid (depakine). Severe aggression and self-harming actions are successfully treated with lithium even in the absence of affective disorders. Lithium use has led to a decrease in aggressive and autoaggressive actions, both according to clinical impressions and according to the results of assessment scales, in almost all clinical trials. Other normothymic agents (carbamazepine, valproic acid) can also suppress self-harming actions and aggression in individuals with mental retardation, but their effectiveness must be verified in clinical trials.

Beta-blockers. Propranolol (anaprilin), a beta-adrenergic receptor blocker, can reduce aggressive behavior associated with increased adrenergic tone. By inhibiting the activation of adrenoreceptors by noradrenaline, propranolol reduces the chronotropic, inotropic, and vasodilator effects of this neurotransmitter. Inhibition of physiological manifestations of stress can itself reduce aggression. Since the blood level of propranolol in patients with Down syndrome was higher than usual, the bioavailability of the drug in these patients may be increased for certain reasons. Although the ability of propranolol to successfully suppress impulsive outbursts of anger in some mentally retarded individuals has been reported, this effect of propranolol should be confirmed in controlled trials.

Opioid receptor antagonists. Naltrexone and naloxone are opioid receptor antagonists that block the effects of endogenous opioids and are used in the treatment of self-aggression. Unlike naltrexone, naloxone is available in a parenteral form and has a shorter T1/2. Although early open-label studies of opioid receptor antagonists demonstrated a reduction in self-aggression, subsequent controlled trials showed that their efficacy was no greater than placebo. The potential for dysphoria and negative results of controlled studies do not allow this class of drugs to be considered the treatment of choice for self-aggression. However, clinical experience shows that these agents may be useful in some cases.

Selective serotonin reuptake inhibitors. The similarity of autoaggressive actions with stereotypies may explain the positive response of some patients to selective serotonin reuptake inhibitors, such as clomipramine (Anafranil), fluoxetine (Prozac), fluvoxamine (Fevarin), sertraline (Zoloft), paroxetine (Paxil), citalopram (Cipramil). Self-harm, aggression, stereotypies, and behavioral rituals may decrease under the influence of fluoxetine, especially if they develop against the background of comorbid compulsive actions. Similar results (reduction of autoaggressive, ritual actions, and perseverations) were obtained with the use of clomipramine. Double-blind trials will determine whether these agents are useful in all patients with autoaggressive actions or whether they help only in the presence of comorbid compulsive/perseverative actions. Since these agents are capable of causing excitation, their use may be limited to the treatment of this syndrome.

Mental retardation and affective disorders

Recent advances in the diagnosis of depression and dysthymia in mentally retarded individuals allow these conditions to be treated with more specific agents. However, the response to antidepressants in mentally retarded individuals is variable. Dysphoria, hyperactivity, and behavioral changes often occur with antidepressants. In a retrospective review of the response to tricyclic antidepressants in mentally retarded adults, only 30% of patients showed a significant positive effect, with symptoms such as agitation, aggression, self-harm, hyperactivity, and irascibility remaining largely unchanged.

The response to normothymic drugs in cyclic affective disorders in patients with mental retardation was more predictable. Although lithium is known to disrupt sodium transport in nerve and muscle cells and affect catecholamine metabolism, the mechanism of its action on affective functions remains unclear. When treating with lithium, the level of this ion in the blood should be regularly monitored, a clinical blood test and a study of thyroid function should be performed. One placebo-controlled and several open studies of the effectiveness of lithium in bipolar disorder in individuals with mental retardation have yielded encouraging results. Side effects of lithium preparations include gastrointestinal disorders, eczema, and tremors.

Valproic acid (Depakine) and divalproex sodium (Depakote) have anticonvulsant and normothymic effects, which may be due to the drug's effect on GABA levels in the brain. Although cases of liver toxicity with valproic acid have been reported, they have usually occurred in early childhood, during the first six months of treatment. However, liver function should be monitored before and regularly during treatment. The positive effect of valproic acid on affective disorders, aggression, and self-harm in mentally retarded individuals has been shown to occur in 80% of cases. Carbamazepine (Finlepsin), another anticonvulsant used as a normothymic agent, may also be useful in the treatment of affective disorders in mentally retarded individuals. Since aplastic anemia and agranulocytosis may develop when taking carbamazepine, clinical blood tests should be monitored before prescribing the drug and during treatment. Patients should be warned of early signs of toxicity and hematological complications such as fever, sore throat, rash, mouth ulcers, bleeding, petechial hemorrhages, or purpura. Despite its antiepileptic activity, carbamazepine should be used with caution in patients with polymorphic seizures, including atypical absences, since the drug can provoke generalized tonic-clonic seizures in these patients. The response to carbamazepine in mentally retarded individuals with affective disorders is not as predictable as the response to lithium and valproic acid.

Mental retardation and anxiety disorders

Buspirone (Buspar) is an anxiolytic drug that differs in its pharmacological properties from benzodiazepines, barbiturates, and other sedatives and hypnotics. Preclinical studies show that buspirone has a high affinity for serotonin 5-HT1D receptors and a moderate affinity for dopamine D2 receptors in the brain. The latter effect may explain the occurrence of restless legs syndrome, which sometimes occurs soon after the start of treatment with the drug. Other side effects include dizziness, nausea, headache, irritability, and agitation. The effectiveness of buspirone in the treatment of anxiety in mentally retarded individuals has not been subjected to controlled trials. However, it has been shown that it can be useful in autoaggressive actions.

Mental retardation and stereotypes

Fluoxetine is a selective serotonin reuptake inhibitor effective in depression and obsessive-compulsive disorder. Since fluoxetine metabolites inhibit CYP2D6 activity, combination with drugs that are metabolized by this enzyme (e.g., tricyclic antidepressants) may cause side effects. Studies have shown that the steady-state concentration of imipramine and desipramine in the blood after adding fluoxetine increases 2-10-fold. Moreover, since fluoxetine has a long half-elimination period, this effect may occur within 3 weeks after its withdrawal. The following side effects are possible when taking fluoxetine: anxiety (10-15%), insomnia (10-15%), changes in appetite and weight (9%), induction of mania or hypomania (1%), epileptic seizures (0.2%). In addition, asthenia, anxiety, increased sweating, gastrointestinal disorders including anorexia, nausea, diarrhea, and dizziness are possible.

Other selective serotonin reuptake inhibitors (SSRIs) - sertraline, fluvoxamine, paroxetine, and the nonselective inhibitor clomipramine - may be useful in the treatment of stereotypy, especially when there is a compulsive component. Clomipramine is a dibenzazepine tricyclic antidepressant with specific antiobsessional activity. Clomipramine has been shown to be effective in the treatment of rage outbursts and compulsive ritualistic behaviors in adults with autism. Although other SSRIs may also have a positive effect on stereotypy in mentally retarded patients, controlled studies are needed to confirm their effectiveness.

Mental retardation and attention deficit hyperactivity disorder

Although it has been known for some time that almost 20% of children with mental retardation have attention deficit hyperactivity disorder, it is only in the last two decades that attempts have been made to treat it.

Psychostimulants. Methylphenidate (Ritalin) is a mild stimulant of the central nervous system. It selectively reduces the manifestations of hyperactivity and attention deficit in individuals with mental retardation. Methylphenidate is a short-acting drug. Its peak activity in children occurs after 1.3-8.2 hours (on average after 4.7 hours) when taking a slow-release drug or after 0.3-4.4 hours (on average after 1.9 hours) when taking a standard drug. Psychostimulants have a positive effect on patients with mild to moderate mental retardation. At the same time, their effectiveness is higher in patients with impulsivity, attention deficit, behavioral disorder, impaired motor coordination, perinatal complications. Due to the stimulating effect, the drug is contraindicated in cases of severe anxiety, mental stress, and agitation. In addition, it is relatively contraindicated in patients with glaucoma, tics, and those with a family history of Tourette syndrome. Methylphenidate may slow the metabolism of coumarin anticoagulants, anticonvulsants (such as phenobarbital, phenytoin, or primidone), as well as phenylbutazone and tricyclic antidepressants. Therefore, the dose of these drugs should be reduced if they are prescribed together with methylphenidate. The most common adverse reactions with methylphenidate are anxiety and insomnia, both of which are dose-dependent. Other adverse effects include allergic reactions, anorexia, nausea, dizziness, palpitations, headache, dyskinesia, tachycardia, angina, cardiac arrhythmia, abdominal pain, and weight loss with prolonged use.

Dextramphetamine sulfate (d-amphetamine, dexedrine) is a dextrorotatory isomer of d, 1-amphetamine sulfate. The peripheral action of amphetamines is characterized by an increase in systolic and diastolic blood pressure, a weak bronchodilator effect, and stimulation of the respiratory center. When taken orally, the concentration of dextramphetamine in the blood reaches a peak after 2 hours. The half-elimination period is approximately 10 hours. Drugs that increase acidity reduce the absorption of dextramphetamine, and drugs that reduce acidity enhance it. Clinical trials have shown that dextramphetamine reduces the manifestations of ADHD in children with mental retardation.

Alpha-adrenergic receptor agonists. Clonidine (clonidine) and guanfacine (estulic) are alpha-adrenergic receptor agonists that are successfully used to treat hyperactivity. Clonidine, an imidazoline derivative, stimulates alpha-adrenergic receptors in the brainstem, reducing sympathetic system activity, reducing peripheral resistance, renal vascular resistance, heart rate, and blood pressure. Clonidine acts quickly: after oral administration, blood pressure decreases within 30-60 minutes. The concentration of the drug in the blood reaches its peak within 2-4 hours. With prolonged use, tolerance to the drug develops. Sudden withdrawal of clonidine can lead to irritability, agitation, headache, tremors, which are accompanied by a rapid rise in blood pressure and an increase in the level of catecholamines in the blood. Since clonidine can provoke the development of bradycardia and atrioventricular block, caution should be exercised when prescribing the drug to patients taking digitalis preparations, calcium antagonists, beta-blockers that suppress the function of the sinus node or conduction through the atrioventricular node. The most common side effects of clonidine include dry mouth (40%), drowsiness (33%), dizziness (16%), constipation (10%), weakness (10%), sedation (10%).

Guanfacine (Estulic) is another alpha2-adrenergic agonist that also reduces peripheral vascular resistance and slows heart rate. Guanfacine effectively reduces the manifestations of ADHD in children and can specifically improve the function of the prefrontal regions of the brain. Like clonidine, guanfacine enhances the sedative effect of phenothiazines, barbiturates, and benzodiazepines. In most cases, the side effects caused by guanfacine are mild. These include dry mouth, drowsiness, asthenia, dizziness, constipation, and impotence. When choosing a drug for the treatment of ADHD in children with mental retardation, the presence of tics is not so often an issue; in this category of patients, they are more difficult to recognize later than in normally developing children. However, if a patient with intellectual disability has tics or a family history of Tourette syndrome, alpha2-adrenergic agonists should be considered the drugs of choice for the treatment of ADHD.