Mental retardation: treatment

Treatment of mental retardation

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

Research and treatment of children and adults with mental retardation should be comprehensive and take into account how this individual learns, works, how his relationships develop with other people. Medical options include a wide range of interventions: individual, group, family, behavioral, physical, labor 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 the mentally retarded to receive adequate medical care. These rights were set forth in the Declaration of the Rights of Persons with Disabilities. The Declaration proclaimed "the right to adequate medical care" and "the same civil rights as other people". According to the Declaration, "Disabled persons should be provided with qualified legal assistance if it is necessary to protect these persons".

The proclamation of the right of mentally retarded persons to adequate medical care presupposed 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 repression measures should be applied to a person only if "there is a serious threat of violent behavior, trauma or suicide attempt". In addition, courts usually require "an individual assessment of the possibility and nature of violent behavior, the likely effect of drugs on this individual and the possibility of alternative actions that are less restrictive" - in order to confirm that the "least restrictive alternative" has been implemented. Thus, when deciding whether to use psychotropic drugs in mentally retarded individuals, the possible risk and the intended use of such an appointment should be carefully weighed. The protection of the interests of the mentally retarded patient is achieved through the involvement of an "alternative opinion" (if the anamnestic data indicate that the patient has no criticism and preferences) or through the so-called "substituted opinion" (if there is some information about the individual's preferences in the present or in the past).

In the last two decades, the doctrine of the "least restrictive alternative" has become relevant in connection with research data on the use of psychotropic drugs in mentally retarded patients. It turned out that psychotropic medications are prescribed by 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 has been established that psychotropic drugs are more often prescribed for elderly patients, for persons who are subjected to more severe restrictive measures, as well as for patients with social, behavioral problems and sleep disorders. Sex, the level of intelligence, the nature of behavioral disorders did not affect the frequency of use of psychotropic drugs in mentally retarded persons. It should be noted that although 90% of mentally retarded persons live outside of 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 for controlling their behavior for a long time, and often a combination thereof, it is extremely important to take into account the short-term and long-term effects of these remedies - in order to choose the safest ones. Primarily this applies to neuroleptics, which are especially often used in this category of patients and often cause serious side effects, including irreversible tardive dyskinesia. Although antipsychotics allow you to control inadequate behavior by suppressing behavioral activity in general, they are also able to selectively inhibit stereotypes and autoaggressive actions. To reduce auto-aggressive actions and stereotypy, opioid antagonists and serotonin reuptake inhibitors are also used. Normotimicheskie means - lithium salts, valproic acid (depakin), carbamazepine (finlepsin) - are useful in the correction of cyclical affective disorders and outbursts of rage. Beta-adrenoblockers, for example, propranolol (anaprilin), are effective in the treatment of aggression and destructive behavior. Psychostimulants - methylphenidate (ritalin), dextramphetamine (dexedrine), pemoline (cilert) - and alpha2-adrenoreceptor agonists, for example clonidine (clonidine) and guanfacine (estulik), have a positive effect in treating people with mental retardation of attention deficit hyperactivity disorder .

Combined treatment with neuroleptics, anticonvulsants, antidepressants and normotimics is fraught with problems associated with pharmacokinetic and pharmacodynamic interaction. Therefore, before prescribing a combination of drugs, the physician should inquire about the possibility of drug interaction in reference books or other sources of information. It should be emphasized that often patients take unnecessary drugs for a long time, the cancellation of which does not adversely affect their condition, but avoids the side effects of these medicines.

Neuroleptics. Many psychotropic agents were used to suppress destructive actions, but none of them was as effective as neuroleptics. The effectiveness of neuroleptics can be explained by the role of hyperactivity of dopaminergic brain systems in the pathogenesis of autoaggressive actions. Clinical trials of chlorpromazine (aminazine), thioridazine (sonapax), risperidone (rispolept) demonstrated the ability of all these drugs to contain destructive effects. Open trials of fluphenazine (moditene) and haloperian also demonstrated their effectiveness in correcting autoaggressive (self-damaging) and aggressive actions. Nevertheless, aggressiveness can not react to the same extent as self-damaging actions, for treatment with neuroleptics. Perhaps, with autoaggressive actions, internal, neurobiological factors are more important, whereas aggressiveness is more dependent on external factors.

The main danger with the use of neuroleptics is a relatively high incidence of extrapyramidal side effects. According to various studies, approximately one-third or two-thirds of patients with mental retardation show signs of tardive dyskinesia - chronic, sometimes irreversible orofacial dyskinesia, usually associated with prolonged intake of neuroleptics. At the same time, it was shown that a significant part (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 for this category of patients there is 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, the age of the patient. This problem is especially relevant in connection with the fact that approximately 33% of children and adults with mental retardation are taking antipsychotics. Parkinsonism and other early extrapyramidal side effects (tremor, acute dystonia, akathisia) are detected in about a third of patients taking antipsychotics. Akathisia is characterized by internal discomfort, causing the patient to be in constant motion. It occurs in about 15% of patients taking antipsychotics. The use of neuroleptics carries the risk of a malignant neuroleptic syndrome (NSA), which is rare but can lead to death. Risk factors ZNS - male sex, the use of high-potential neuroleptics. According to a recent study, mortality among the mentally retarded in the development of the NSA is 21%. In cases where neuroleptic drugs are prescribed for patients with mental retardation, a dynamic evaluation of possible extrapyramidal disorders prior to treatment and during treatment with special scales is required: Abnormal Involuntary Movement Scale (AIMS), Dyskinesia Identification System Condensed User Scale - DISCUS, Acathisia Scale (AS) Scales: Atypical antipsychotics such as clozapine and olanzapine, are less likely to cause extrapyramidal side effects, but their effectiveness in the mentally retarded It should also be noted that although clozapine is an effective antipsychotic, it can cause agranulocytosis and epileptic seizures.Olanzapine, sertindole, quetiapine and ziprasidone are new atypical antipsychotics that in the future will no doubt be used to treat mentally retarded patients, because they are safer than traditional antipsychotics.

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

Normotimicheskie means. Normotimics include lithium preparations, carbamazepine (finlepsin), valproic acid (depakin). Expressed aggressiveness and self-damaging effects are successfully treated with lithium even in the absence of affective disorders. The use of lithium led to a reduction in aggressive and autoaggressive actions, both from the clinical impression and the results of scoring scales, in almost all clinical trials. Other normotimic agents (carbamazepine, valproic acid) can also suppress self-injurious actions and aggressiveness in persons with mental retardation, but their effectiveness should be checked in clinical studies.

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

Opioid receptor antagonists. Naltrexone and naloxone - opioid receptor antagonists, blocking the effects of endogenous opioids - are used in the treatment of autoaggressive actions. Unlike naltrexone, naloxone is released in the form for parenteral administration and has a shorter T1 / 2. Although early open trials of opioid receptor antagonists demonstrated a decrease in autoaggressive actions, in subsequent controlled trials their efficacy did not exceed the placebo effect. The possibility of developing dysphoria and negative results of controlled studies do not allow considering this class of drugs to be a means of choice for autoaggressive actions. But, as the clinical experience shows, in some cases, these funds can be useful.

Inhibitors of serotonin reuptake. The similarity of autoaggressive actions with stereotypes can explain the positive reaction of a number of patients to serotonin reuptake inhibitors, such as clomipramine (anaphranil), fluoxetine (prozac), fluvoxamine (feravin), sertraline (zoloft), paroxetine (paxil), citalopram (cipramil). Self-harm, aggression, stereotypes, behavioral rituals can 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 clomipramine. Tests with double-blind control will determine whether these drugs are useful in all patients with autoaggressive actions or whether they help only in the presence of comorbid compulsive / perseverative actions. Since these drugs are capable of causing excitation, their use can be limited only by the treatment of this syndrome.

Mental retardation and affective disorders

The latest advances in the diagnosis of depression and dysthymia in mentally retarded individuals make it possible to treat these conditions with more specific means. Nevertheless, the response to antidepressants in mentally retarded individuals is variable. With the use of antidepressants, dysphoria, hyperactivity, and behavioral changes often occur. In a retrospective review of the response to tricyclic antidepressants in mentally retarded adults, only 30% of patients had a significant positive effect, with symptoms such as agitation, aggression, self-damaging actions, hyperactivity, and temper, left largely unchanged.

More predictable was the response to normotimic drugs in cyclical affective disorders in patients with mental retardation. Although it is known that lithium disrupts sodium transport in nerve and muscle cells and affects the metabolism of catecholamines, the mechanism of its action on affective functions remains unclear. When treating with lithium drugs should regularly monitor the level of this ion in the blood, conduct a clinical blood test and study the function of the thyroid gland. One placebo-controlled and several open studies of the effectiveness of lithium in bipolar disorder in persons with mental retardation have yielded promising results. Side effects of lithium drugs include gastrointestinal disorders, eczema, trembling.

Valproic acid (depakin) and divalproex sodium (depakot) have a pronounced seizure and normotime effect, which may be due to the effect of the drug on the level of GABA in the brain. Although cases of toxic effects of valproic acid on the liver have been described, they were usually observed in early childhood, during the first six months of treatment. Nevertheless, before the start and regularly during treatment, it is necessary to monitor liver function. It is shown that the positive effect of valproic acid on affective disorders, aggressiveness and self-damaging actions in mentally retarded individuals is manifested in 80% of cases. Carbamazepine (finlepsin) - another anticonvulsant, used as a normotime agent, can also be useful in treating affective disorders in mentally retarded individuals. Since aplastic anemia and agranulocytosis may develop with carbamazepine, blood test should be monitored prior to prescribing and during treatment. Patients should be warned about early signs of intoxication and hematological complications such as fever, sore throat, rashes, mouth sores, bleeding, petechial hemorrhage or purpura. Despite anti-epileptic activity, carbamazepine should be used with caution in patients with polymorphic seizures, including atypical absences, since in these patients the drug is capable of provoking generalized tonic-clonic seizures. The reaction to carbamazepine in mentally retarded individuals with affective disorders is not as predictable as the response to lithium and valproic acid preparations.

Mental retardation and anxiety disorders

Buspirone (buspar) - an anxiolytic agent, differing in 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 modest affinity for the dopamine D2 receptor in the brain. The latter effect can explain the appearance of restless legs syndrome, which sometimes occurs soon after the beginning of treatment with the drug. Other side effects include dizziness, nausea, headache, irritability, agitation. The effectiveness of buspirone in the treatment of anxiety in mentally retarded individuals has not been subjected to controlled trials. Nevertheless, it is shown that it can be useful in autoaggressive actions.

Mental retardation and stereotypes

Fluoxetiv is a selective serotonin reuptake inhibitor, effective in depression and obsessive-compulsive disorder. Because fluoxetine metabolites inhibit the activity of CYP2D6, a combination with drugs that are metabolized by this enzyme (eg, tricyclic antidepressants) can lead to side effects. Studies have shown that a stable concentration of imipramine and desipramine in the blood after the addition of fluoxetine increases 2-10 times. Moreover, since fluoxetine has a long semi-elimination period, this effect can appear within 3 weeks after its elimination. When taking fluoxetine, the following side effects are possible: anxiety (10-15%), insomnia (10-15%), change 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 - sertraline, fluvoxamine, paroxetine and a nonselective clomipramine inhibitor - may be useful in the treatment of stereotypes, especially in the presence of a compulsive component. Clomipramine is a dibenzazepine tricyclic antidepressant with a specific anti-obsessive effect. It has been shown that clomipramine is effective in the treatment of outbreaks of rage and compulsive ritualized actions in adults with autism. Although other serotonin reuptake inhibitors are also likely to have a positive effect on stereotypes in mentally retarded patients, controlled studies are needed to confirm their effectiveness.

Mental retardation and attention deficit with hyperactivity

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

Psychostimulants. Methylphenidate (Ritalin) - a mild stimulant of the central nervous system - selectively reduces the manifestations of hyperactivity and impaired attention in persons with mental retardation. Methylphenidate is a short-acting drug. The peak of its activity occurs in children after 1.3-8.2 hours (an average of 4.7 hours) when taking the drug with sustained release or after 0.3-4.4 hours (an average of 1.9 hours) with reception of a standard drug. Psychostimulants have a positive effect in patients with mild and moderate mental retardation. At the same time, their effectiveness is higher in patients with impulsivity, attention deficit disorder, behavioral disorder, impaired coordination of movements, perinatal complications. Because of the stimulating effect, the drug is contraindicated in cases of severe anxiety, mental stress, agitation. In addition, it is relatively contraindicated in patients with glaucoma, tics, and streets with indications of Tourette's syndrome in a family history. 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, if they are prescribed together with methylphenidate, must be reduced. The most frequent adverse reactions with methylphenidate are anxiety and insomnia, both of which are dose-dependent. Other side effects include allergic reactions, anorexia, nausea, dizziness, palpitation, headache, dyskinesia, tachycardia, angina, cardiac rhythm abnormalities, abdominal pain, weight loss with prolonged admission.

Dextramphetamine sulfate (d-amphetamine, dexedrine) is the dextrorotatory isomer of d, 1-amphetamine sulfate. Peripheral action of amphetamines is characterized by an increase in systolic and diastolic arterial pressure, a weak bronchodilator action, 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, strengthen it. Clinical trials have shown that dextramphetamine reduces the occurrence of DVN in children with mental retardation.

Agonists of alpha-adrenergic receptors. Clonidine (clonidine) and guanfacine (estulik) are agonists of a-adrenergic receptors, which are successfully used in the treatment of hyperactivity. Clonidine, an imidazoline derivative, stimulates a-adrenergic receptors in the brain stem, reducing the activity of the sympathetic system, reducing peripheral resistance, renal vessel resistance, heart rate, and blood pressure. Clonidine acts quickly: after taking the drug inside, the blood pressure decreases after 30-60 minutes. The concentration of the drug in the blood reaches a peak after 2-4 hours. With prolonged reception, tolerance to the action of the drug develops. Sudden abolition of clonidine can lead to irritability, agitation, headache, trembling, which are accompanied by a rapid rise in blood pressure, an increase in the level of catechol-mines in the blood. Since clonidine can provoke the development of bradycardia and atrioventricular blockade, caution should be exercised when administering the drug to patients taking digitalis preparations, calcium antagonists, beta-blockers that suppress the function of the sinus node or conduct through the atrioventricular node. The most frequent side effects of clonidine are dry mouth (40%), drowsiness (33%), dizziness (16%), constipation (10%), weakness (10%), sedation (10%).

Guangficin (estulik) is another alpha 2-adrenergic agonist, which also reduces peripheral vascular resistance and reduces the heart rate. Guangfincin effectively reduces the manifestation of DVG in children and can specifically improve the function of the prefrontal parts of the brain. Like clonidine, guanfacin increases the sedative effect of phenothiazines, barbiturates and benzodiazepines. In most cases, the side effects caused by guanfacin are easy. These include dry mouth, drowsiness, asthenia, dizziness, constipation and impotence. When choosing a drug for the treatment of DVG in children with mental retardation, the presence of tics does not affect so often, in this category of patients they are more difficult to recognize later than in normally developing children. Nevertheless, if a patient with mental retardation has tics or indications of cases of Tourette's syndrome in a family history, alpha2-adrenoreceptor agonists should be considered the drugs of choice for the treatment of DVG.