**5. Non-medical treatment of ASD patients**

**4.5. Sleep disorders**

644 Recent Advances in Autism Spectrum Disorders - Volume I

& Ferri, 2010).

Aggressiveness Irritability elf-injury

Hyperactivity Inattention

Repetitive behavior Stereotypies

Other disruptive behaviors

Sleep disorders can be identified years before an unequivocal diagnosis of autism. Not infrequently, we face with sleep complaints in very young babies who lately will develop the whole clinical picture compatible with ASD. By the other hand, sleep disorders occur more frequently in ASD patients compared with developing children (Benvenuto et al., 2012; Miano

Sleep disorders tend to be under-recognized valued in the ASD patient group, probably because they can be considered less disabling than aggression and repetitive behaviors; however, ongoing abnormal sleep patterns are very disruptive to the overall quality of family life and interfere with patient daytime functioning. Parents frequently ask for medication and then physicians are confronted with the lack of FAD-approved treatments for this problem

Before use of medication, is important to ensure appropriate sleep hygiene as well as to use behavioral intervention. Pharmacology is recommended only when psychosocial treatments fail. Melatonin administration in ASDs is reported to be safe, well tolerated and efficient in improving sleep parameters and daytime behavior, and in decreasing of parental stress

> Large scale double blind RCT Large scale double blind RCT

Large scale double blind RCT\*\* Large scale double blind RCT\*\*

Large scale double blind RCT\*\* Large scale double blind RCT\*\*

Small open label reports

Double blind RCT Small open label reports Small open label reports

Crossover RCT Crossover RCT

RCT RCT

RCT

RCT RCT

**Core symptoms Medications Level of evidence**

Risperidone\* Aripiprazole\* Olanzapine Clozapine Ziprazidone Valproic acid Topiramate

Metilfenidate Atomoxetine Risperidone\* Aripiprazole\* Guanfacine Clonidine

Risperidone\* Aripiprazole\* Fluoxetine Valproic acid

\*FDA-approved medications for ASD children; \*\*Secondary analysis; RCT = randomized controlled trials

Sleep disorders Melatonin RCT

**Table 2.** Psychopharmacological treatment in ASD patients

(Kaplan & McCracken, 2012; Weinssman & Bridgemohan, 2012).

(Malow et al., 2011; Rossignol & Frye, 2011).

The treatment of ASD evolves professionals coming from different area and usually is characterized by comprehensive and intense programs encompassing both patients and families. Early identification is critically important to ensure that families have the op‐ portunity to reap the many unique benefits that may arise from early intervention ef‐ forts. For example, intervention efforts that occur early during a child's development may have the advantage of increasing brain plasticity, which may enhance outcomes (LeBlanc & Gillis, 2012).

In our experience, children with low intensity ASD treats, when early-treated can eventually get out from de ASD diagnosis when accessed by CARS, a rating scale of autism symptoms (Gottfried & Riesgo, 2011).

The non-medical intervention programs are directed to the core social, communication and cognitive issues in autism. The objectives of each one program are selected according with the specific abilities and difficulties as well as the actual neurodevelopmental phase of the ASD patient. As a result, this kind of intervention needs to be customized (Dawson & Burner, 2011; LeBlanc & Gillis, 2012).

In general, the following types of therapy can be used both isolate or in different combi‐ nations: behavioral, occupational, speech therapy as well as psychopedagogic therapy. Although the non-medical treatments for ASD patients can be different from each other, they usually had the same goals, such as to give the child the best degree of independ‐ ent functioning as well as to improve quality of life from the patient and family (Myers & Johnson, 2007).

There is a consensus that facing a suspicious case of ASD in children the treatment must be promptly initiated, independently of the type of non-medical treatment, because of the brain plasticity in the developing child (LeBlanc & Gillis, 2012; Lord & McGee, 2001).

Besides the large number of non-medical type of treatment, there are some of them with good level of evidence. According with the National Autism Center's Standard Report, after a systematic review of literature available from 1957 to 2007, at least 11 treatment methods for ASD were considered with good level of evidence.

Additionally, there are some problems in evaluating the efficacy of non-medical treatments in ASD patients. For example, the small sample sizes, the different methodologies, the difficulty in the outcome measures, etc.

#### **5.1. Behavioral treatment**

The therapies involving behavioral and educational strategies are the main components of the non-medical treatments of ASD children. The only psychoeducational treatment that meets the criteria as well-established and efficacious intervention for ASD to date is the behavior treatment (Dawson & Burner, 2011; LeBlanc & Gillis, 2012).

There is consensual that behavioral therapy must be intensive with at least 25 hours per week, all year long. There are two main types of behavioral treatments: interventionists and non-interventionists. Among the first group of available therapies, there are three principal methods: a) Applied Behavior Analysis (ABA); b) Treatment and Educational of Autistic and related Communication-handicapped Children (TEACCH); c) developmen‐ tal/relationship-based therapy (Floortime). Some of these strategies use combinations of different models and are denominated integrative models. To date, there is no evidence that integrative models are better than the original models (Weinssman & Bridgemohan, 2012). By the other side, one example of non-interventionist behavioral therapy is the Picture Exchange Charts System (PECS).

**Psychoeducational**

Interventional Models

Parental role

**treatments Example Effectiveness**

Well established Insufficient evidence to recommend one over another

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Insufficient evidence to recommend one over another

> Inconsistent results Small size studies

ABA\* TEACCH Denver model Floortime

Specific behaviors Focal behavior intervention Well established Communication PECS Promising results Social skills instruction Promising results

> Parent-mediated intervention programs

ingly, more than 70% of ASD patients are treated by CAM (Rossignol, 2009).

therapies; they are well accepted methods treating this group of patients.

Sensory integration therapy Inconsistent results Occupational therapy Little research

Complementary and alternative medicine (CAM) encompasses different kinds of medical and healthcare systems, practices, and products usually not considered to be a part of the conven‐ tional medicine. There are several proposed CAM systems to treat ASD children, but to date still without recognized efficacy by FDA. As a result, they are considered "off label". Interest‐

It is important to note that the definition of CAM is slightly different when used in ASD when compared with other medical disorders. That difference is due the fact of many of the psy‐ choeducational therapies used in ASD children, although not considered conventional medical

In terms of scientific support, there are three main groups of CAM: a) promising treatments; b) treatments with some degree of scientific evidence; c) treatments with no scientific proved

These types of treatment showed the highest level of evidence and include music therapy, naltrexone, and acetyl-cholinesterase inhibitors (Rossignol, 2009). Concerning music therapy, there is evidence that it is able to improve social interaction as well as communication skills (Gold et al., 2006; Kim et al., 2008). Our group conducted a RCT using music therapy in ASD patients and we identified the promising effect of this treatment (Gattino et al., 2011). There is

Integrative Models Focal behavior intervention

\*Suggested by Autism Center Guidelines

efficacy to date (Rossignol, 2009).

*5.2.1. Promising CAM*

**Table 3.** psychoeducational treatment of ASD patients

**5.2. Complementary and alternative therapies**

#### *5.1.1. ABA (Applied Behavior Analysis)*

Aims to teach the absent child skills through the introduction of these skills in stages. Usually, each one of the skills is individually showed, presenting it coupled with an indication or instruction. When necessary, any support that is offered should be removed as soon as possible. (Ospina et al., 2008; Warren et al., 2011). In the clinical setting, we have identified problems in terms of improvement from the classroom as well as a trend to overestimate the efficacy of ABA.

#### *5.1.2. Treatment and Educational of Autistic and related Communication-handicapped Children (TEACCH)*

Use structured activities and environment to help ASD patients to improve compromised area. The model is adapted to each one child and addresses environment organization as well as predicable routines in order to adapt the environment to make it easier for the child to understand it, and understand what is expected of her. TEACCH programs are usually given in a classroom, but can also be made at home. Parents work with professionals as co-therapists for techniques that can be continued at home. It is used by psychologists, special education teachers, speech therapists and trained professionals (Myers & Johnson, 2007).

#### *5.1.3. Floortime*

The main objective is to teach fundamental skills expected to the level of development which were not acquired in a given ASD patient age, but to date the efficacy evidences are still inconclusive (Ospina et al., 2008). Our group is conducting an evidence-based research to find out if this treatment is reliable.

#### *5.1.4. Picture Exchange Communication System (PECS)*

This non-interventionist behavioral therapy enables non-verbal children to communicate by using figures. PECS can be used at home, in the classroom or in several others envi‐ ronments (Bondy & Frost, 2001). A meta-analysis showed that PECS is a promising inter‐ vention (Ganz et al., 2012).


**Table 3.** psychoeducational treatment of ASD patients

#### **5.2. Complementary and alternative therapies**

Complementary and alternative medicine (CAM) encompasses different kinds of medical and healthcare systems, practices, and products usually not considered to be a part of the conven‐ tional medicine. There are several proposed CAM systems to treat ASD children, but to date still without recognized efficacy by FDA. As a result, they are considered "off label". Interest‐ ingly, more than 70% of ASD patients are treated by CAM (Rossignol, 2009).

It is important to note that the definition of CAM is slightly different when used in ASD when compared with other medical disorders. That difference is due the fact of many of the psy‐ choeducational therapies used in ASD children, although not considered conventional medical therapies; they are well accepted methods treating this group of patients.

In terms of scientific support, there are three main groups of CAM: a) promising treatments; b) treatments with some degree of scientific evidence; c) treatments with no scientific proved efficacy to date (Rossignol, 2009).

#### *5.2.1. Promising CAM*

There is consensual that behavioral therapy must be intensive with at least 25 hours per week, all year long. There are two main types of behavioral treatments: interventionists and non-interventionists. Among the first group of available therapies, there are three principal methods: a) Applied Behavior Analysis (ABA); b) Treatment and Educational of Autistic and related Communication-handicapped Children (TEACCH); c) developmen‐ tal/relationship-based therapy (Floortime). Some of these strategies use combinations of different models and are denominated integrative models. To date, there is no evidence that integrative models are better than the original models (Weinssman & Bridgemohan, 2012). By the other side, one example of non-interventionist behavioral therapy is the

Aims to teach the absent child skills through the introduction of these skills in stages. Usually, each one of the skills is individually showed, presenting it coupled with an indication or instruction. When necessary, any support that is offered should be removed as soon as possible. (Ospina et al., 2008; Warren et al., 2011). In the clinical setting, we have identified problems in terms of improvement from the classroom as well as a trend to overestimate the

*5.1.2. Treatment and Educational of Autistic and related Communication-handicapped Children*

teachers, speech therapists and trained professionals (Myers & Johnson, 2007).

Use structured activities and environment to help ASD patients to improve compromised area. The model is adapted to each one child and addresses environment organization as well as predicable routines in order to adapt the environment to make it easier for the child to understand it, and understand what is expected of her. TEACCH programs are usually given in a classroom, but can also be made at home. Parents work with professionals as co-therapists for techniques that can be continued at home. It is used by psychologists, special education

The main objective is to teach fundamental skills expected to the level of development which were not acquired in a given ASD patient age, but to date the efficacy evidences are still inconclusive (Ospina et al., 2008). Our group is conducting an evidence-based research to find

This non-interventionist behavioral therapy enables non-verbal children to communicate by using figures. PECS can be used at home, in the classroom or in several others envi‐ ronments (Bondy & Frost, 2001). A meta-analysis showed that PECS is a promising inter‐

Picture Exchange Charts System (PECS).

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*5.1.1. ABA (Applied Behavior Analysis)*

efficacy of ABA.

*(TEACCH)*

*5.1.3. Floortime*

out if this treatment is reliable.

vention (Ganz et al., 2012).

*5.1.4. Picture Exchange Communication System (PECS)*

These types of treatment showed the highest level of evidence and include music therapy, naltrexone, and acetyl-cholinesterase inhibitors (Rossignol, 2009). Concerning music therapy, there is evidence that it is able to improve social interaction as well as communication skills (Gold et al., 2006; Kim et al., 2008). Our group conducted a RCT using music therapy in ASD patients and we identified the promising effect of this treatment (Gattino et al., 2011). There is a comprehensive RCT been done testing the efficacy of music therapy in ASD patients (Geretsegger et al., 2012).

world. Another critical problem in terms of psychopharmacotherapy is the paucity of well-conducted RCT, as pointed before in this chapter, especially in the table 2. To date, there are only two FDA-approved antipsychotic medications for ASD in children: risperi‐

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Risperidone was approved by FDA in 2006. The usual dose varies from 1 to 3mg/day. In our practice, 3mg/day of risperidone seems to be the cutoff dose in terms of seizure susceptibility. We have identified patients who experienced seizures with doses higher than 3mg/day.

Because of ASD patients are almost twenty times more prone to have epilepsy when compared with normally developing children, and because of many of the drugs used in autism can decrease the seizure threshold in susceptible children, it is important to assure that there is a

The clinical approach includes a general management as well as two types of not excluding treatment strategies: one with medication and another without medication. From the clinical

In the clinical practice, numerous types of treatment have been proposed and there is ur‐ gent need to choose any one of them in short period of time. Searching literature, a lack of well conducted RCT was identified. As a result, caution is the best form to approach

Future perspectives in the treatment of ASD probably will include immunomodulation, quantic biochemistry, stem cell therapy and other forms of approach after careful RCT attesting

1 Translational Research Group in Autism, (UFRGS) Federal University of Rio Grande do

2 Child Neurology Unit, HCPA (Clinical Hospital of Porto Alegre), UFRGS, Porto Alegre,

3 Neuroglial Plasticity Laboratory, Department of Biochemistry, Postgraduate Program of

Biochemistry, Institute of Basic Health Sciences, UFRGS, Porto Alegre, RS, Brazil

Aripiprazole was FDA-approved in 2009 and the daily dose is up to 15mg.

previous normal EEG before prescribing psychopharmacotherapy.

point of view, these two types of treatment are, in fact, complementary.

Rudimar Riesgo1,2, Carmem Gottfried1,3 and Michele Becker1,2

**7. Conclusions and future remarks**

done and aripiprazole.

ASD cases.

its efficiency.

RS, Brazil

**Author details**

Sul, Porto Alegre, RS, Brazil

#### *5.2.2. CAM with little evidence*

This group of therapies may include the use of carnitine, ocytocin, vitamin C, tetrahydrobiop‐ terin, adrenergic alfa-2 agonists, hyperbaric oxygen therapy, immune-modulatory treatment, and anti-inflammatory treatment (Rossignol 2009). Caution is needed with the hyperbaric oxygen therapy because of the potential adverse effects, such as barotrauma, reversible myopia, oxygen toxicity, and seizures (Weinssman & Bridgemohan, 2012).

#### *5.2.3. CAM with no proved efficacy to date*

Several of the proposed CAM for ASD had no proved efficacy to date, for example: use of carnosine, multi-vitamin and mineral complexes, piracetam, omega-3 fatty acids, selective diets, vitamin B6, magnesium, chelation, cyproheptadine, glutamate antagonists, acupunc‐ ture, auditory integration training, massage, neuro-feedback, and others (Rossignol, 2009).
