This post discusses strategies that assist in medication treatment of people with Aspergers and high functioning autism. Elsewhere, there are recent reviews offering detailed information on medications used for HIGH FUNCTIONING AUTISM and ASPERGERS [1]. The objective here is to discuss the logic and organization of medication treatments for symptoms of ASPERGERS and ways to decide which medications may be useful.
ASPERGERS and HIGH FUNCTIONING AUTISM have moved from being esoteric, “boutique” conditions into the mainstream of child and adolescent psychiatric practice. Diligent practitioners recognize they must be informed about the diagnosis, course, and treatment of these disorders. Recent epidemiologic studies suggest a prevalence of approximately 19–67/10,000 people for autism spectrum disorders [2], [3], [4]. Moreover, autism spectrum disorders are no longer the exclusive province of specialists. A typical child and adolescent psychiatric practice is likely to see individuals from the roughly 50%–60% of the PDD population who are “high functioning,” that is, they have good functional semantic language skills and average or greater IQ. Many people with these disorders have mood and behavioral problems [5], and moderate to severe symptoms certainly lead moms/dads to seek treatment with a child and adolescent psychiatrist. Reports from education departments suggest children with these conditions represent a large influx of new special education children [6] and place a heavy demand on education systems.
Although there has been an effort to identify features that differentiate HIGH FUNCTIONING AUTISM and some ASPERGERS [7], [8], it is premature to be confident about this distinction [9], [10], [11], [12]. Specifically, longitudinal studies have not demonstrated differences in prognosis [9], [13]; it is possible that the outcome can overlap [11]. There is no evidence that the groups show a different response to interventions for social skills development or that there are differences in basic information processing [14], [15], [16], [17], [18]. Furthermore, there is no evidence that the two disorders exhibit genetic specificity or different recurrence risks. There are no differences in neuropathology that have been demonstrated [19]. This discussion therefore considers both “high functioning” groups together under the designation ASPERGERS. For the purposes of pharmacologic treatment this is particularly justifiable because no studies have reported differences in medication responses in those people with HIGH FUNCTIONING AUTISM compared with those with ASPERGERS.
Core features and the mechanics of pharmacologic treatment—
It is essential for anyone who takes responsibility for pharmacologic treatment to understand the phenomenology and course of ASPERGERS (discussed elsewhere in this issue). The specific features of ASPERGERS exhibited by a patient influence the treatment one chooses and how the treatment is assisted for that patient (and family). The nature of ASPERGERS introduces specific and sizable challenges, particularly when using pharmacologic treatments. Building a relationship and gaining the patient's trust can be hard to accomplish; individuals often feel forced to take medication and commonly recoil from the idea of medication treatment. Understandably, many individuals are so frightened of the effects of medications that they cannot put those fears aside enough to try one. The amount of anxiety that makes it appropriate to consider medication for a patient can also interfere with him or her adhering to a prescription. Despite the enormous interference or distress their symptoms generate, many individuals cannot put aside their worries about the medication. The family and a trusted physician may be the only individuals the patient will allow to counter these fears. Usually, creating a therapeutic framework for medication treatment that achieves this rapport requires time and several visits [20].
Many of the difficulties with anger, perseveration, or anxiety are more distressing to those around the patient than to the patient himself (or herself). People with ASPERGERS commonly lack the ability to perceive the signals of comfort or pleasure of others or, once acquired, to use others' emotions to guide their behaviors. Lacking this ability, individuals struggle with the initial fears related to taking medication or entering into other therapy that might help them get along with others. Often they cannot see why they should be required to take a medication simply because others are upset. Threatening an unpleasant consequence is often ineffective. People with ASPERGERS can be willing to accept dreadful consequences rather than yield control to someone else, compromise a rigidly held rule, contain a pressing urge, or tackle managing an anxious feeling.
Another hurdle is the shortcomings individuals have in identifying their own internal mood states and emotions. As a result, the clinician may be unable to gauge whether individuals experience less subjective anxiety, sadness, or anger. The patient's psychological “comfort” may not be available to the clinician for rating improvement. To monitor progress, the clinician is compelled to draw on multiple observations, rely more or less exclusively on the patient's somatic experience, and to use highly concrete measures with individuals. Treating adult individuals who are living independently and are unwilling to allow others to participate in their treatment is particularly challenging.
An associated obstacle is the deficits ASPERGERS people have perceiving and understanding other individual's intentions, wishes, or needs. The blindness to others often contributes to the ASPERGERS person's inability to grasp how their reactions contributed to a bad result; more often they believe they are being persecuted. The bona fide teasing and persecution that are a common part of their day-to-day experience only adds to this. For the person with ASPERGERS, it may be impossible to tell the difference. Nevertheless, the person with ASPERGERS is likely to be oblivious to how their actions contributed to a chain of events that ended in an outburst or aggression, or even to believe that the outcome should be averted in the future. This blindness also produces a tendency to accuse those around them of causing problems; faulting others is highly characteristic and is a direct result of the primary disorder. This should not to be confused with the more common psychological defenses of avoiding responsibility and assigning blame that are used by more socially skillful, typical agemates.
Many people with ASPERGERS display profound weaknesses in the ability to observe sequences of events and transactions accurately and in understanding the “logical” responses of those around them. ASPERGERS kids can be highly concrete; the “big picture” of behaviors and emotions is often lost to an excessive attention to small changes in circumstances or minor details. They often have a flawed sense of proportion. For example, premeditated, forceful, retaliation may be viewed as a justified response to someone else's small blunder.
In addition, ASPERGERS people often are rigid in their behaviors with inflexible routines, dedication to unnecessary rules, or ritualized behaviors. Sometimes these may be no more than a minor irritation to others, but when severe, they can obstruct action and exasperate those around them. Severe rigidity can be highly frustrating to others, and attempts to counter it may produce aggressive reactions from the patient. For all this, such individuals may perceive that “if only individuals let me do what I want” there would be no problems at all. ASPERGERS individuals are not merely immature ordinary kids or adolescents.
In addition to these, several other obstacles are related to the state of the field. First, no pharmacologic agent influences the core pragmatic social deficits such as misinterpreting cues or failure to appreciate social cues and nuances. As a result, there is no one algorithm to follow that targets the primary source of impairment or the greatest source of difficulty for the patient. Second, there is an absence of high quality, valid studies of the efficacy of different pharmacologic agents for specific symptoms in this population. Most of the studies are case reports or small-scale, open, unblinded trials [1]. This requires the clinician to take findings from studies of other disorders in the hope that the results translate to ASPERGERS. This presumption is entirely theoretic at this point. Much of the time, a clinician has no way to gauge the patient's response in comparison with other people with this condition; global functioning may or may not be meaningfully improved. A third obstacle is the absence of treatment and outcome studies of ASPERGERS with comorbid conditions.
For example, it may be erroneous to presume that mood dysregulation and the response to mood stabilizers in the context of ASPERGERS is identical to bipolar disorder in an otherwise ordinary adolescent. Nearly all treatment studies of other childhood disorders exclude people with PDD spectrum disorders. Consequently, when a patient appears in the clinician's consulting room, unless one has the luxury of a previous relationship and sense of that patient's baseline functioning, one cannot know what the individual looks like when the comorbid condition is “resolved.” Most of the core social impairments are likely to remain, although functional gains are possible.
Treatment strategies—
In response to these challenges, there are strategies that therapists can adopt that increase their chance of success. A prominent characteristic of the care of individuals with ASPERGERS is the need for therapists to integrate behavioral and pharmacologic treatments [21]. Thus, treatment strategies must embrace nonpharmacologic and pharmacologic interventions. The strategies shared by both interventions are genuinely complementary. Behavioral and pharmacologic care must establish realistic expectations, optimize the home and school (or work) environment, implement strong parental collaboration, and focus on specific symptom clusters.
It is most important to establish realistic expectations about the effect of medication (and other treatments). Many individuals are drawn to pharmacologic treatment with the expectation that the response will be rapid and complete. Excessively positive expectations may be intrinsic to ASPERGERS, but they also can be related to the anxiety that one is hoping to alleviate. In any case, anxious ASPERGERS individuals often are unable to cope with the constraints that treatments are imperfect and require time. Even for individuals with more common disorders, rigidly holding to over-optimistic expectations can undermine treatment under the best of circumstances. For individuals with ASPERGERS, having such expectations may be exceptionally likely. More than others, people with ASPERGERS may require the relief that comes from things being predictable and uncomplicated. They may be highly anxious about treatments that take time and give mixed results.
For people with ASPERGERS more than others, achieving a different outcome from the one that was anticipated may be harder to endure. Many individuals also have the mistaken idea that their symptoms will remit more quickly with pharmacologic treatment than with behavioral psychotherapies. It is therefore important for the clinician and the patient to understand that there are no “magic bullets,” nor any “quick fixes” when it comes to treating these symptoms.
People with ASPERGERS also may be more prone to side effects. Typical kids and adolescents may experience these as more of a nuisance than a source of major impairment, but people with ASPERGERS often find even minor side effects hard to tolerate. The exquisite and atypical sensory world of people with ASPERGERS means that they may experience a greater variety and rate of these kinds of side effects. When side effects appear, they often outstrip the patient's ability to follow conventional advice “to just ignore it.” We do not know if the actual amount of discomfort is greater or if the means for self-soothing, distraction, or rationalization are insubstantial.
In either case, some ASPERGERS people cannot tolerate some medications because of “minor” side effects that individuals who do not have ASPERGERS handle with relative ease. In addition, they may be less likely to report side effects, or may allude to them in a manner that makes it much harder to detect them. Therapists may be misled by comments that are offered in a flat, toneless manner, suggesting minor uneasiness for the patient when in fact they are extremely distressing. Similarly, highly concrete individuals may not report side effects because the clinician does not ask about each specific one. Some individuals stop their medication without telling the clinician in order to extricate themselves from the discomfort of side effects or having to talk about them.
Although therapists frequently believe environmental and educational interventions can be helpful, physicians often rely on medication. This may be the request of the patient and others in his or her life, but it may not serve the patient in all circumstances.
A large 15-year-old youth with HIGH FUNCTIONING AUTISM attending a day school program displayed average receptive language but weak expressive language abilities. He was referred with the expressed request to increase the dose of his neuroleptic medication after showing increased agitation, irritability, and physical behavior at school. It seemed that these behaviors increased sharply over 3 weeks. He had been sent home several times in the last month following noncompliance with requests, outbursts of anger, and knocking over furniture. When asked, program staff did not remark on any precipitants. The patient's moms/dads reported an increase in anxiety at home. Discussion with the patient's moms/dads revealed that this young man had been expressing concerns over an impending labor strike at his program. He had reiterated, in an echoic way, conversations occurring in his presence among staff about the prospects for abrupt cessation of the program. At home he was tearful, apologetic, and anxious. Staff members at the program were unaware that he grasped their remarks or that the comments might influence him. When they explained that he would be given advance warning of any changes and he would continue to receive services in other ways, his agitation, outbursts, and irritability ended.
Thus, pharmacotherapy certainly has a place in an overall treatment plan, but physicians must be particularly mindful that educational and behavioral supports are the mainstays of treatment for these conditions. Medication can augment services, but when educational and other services are inadequate or unavailable, pharmacotherapy cannot make up the difference. Similarly, acute behavior changes usually should lead one to implement educational and behavioral supports that may be helpful before adding pharmacotherapy, except in uncommon circumstances that are discussed in detail later.
Parental collaboration is necessary to accomplish adequate medication treatment for ASPERGERS. This goes well beyond helping a patient make the necessary changes in his daily routine that taking a medication imposes and assuring his adherence to a medication regimen. The nature of ASPERGERS itself places additional demands on moms/dads and caretakers to participate in the treatment. Most individuals with ASPERGERS are weak intrinsically in their abilities to perceive their actions or feelings, recall them accurately, compare them at one time with another time, or observe a pattern of emotional or behavioral responses to events or a context. Kids and adolescents with ASPERGERS, to a greater extent than typical kids and adolescents, cannot grasp or respond to the intentions, needs, and desires of others. At an elemental level, they have only a modest awareness of the difficulties their symptoms create for themselves and those around them.
Thus, moms/dads play a crucial role in monitoring the patient by providing information to the physician, administering medication, observing for side effects, and noting behavioral and emotional effects. On the one hand, therapists might imagine that medication treatment for kids with ASPERGERS might be simpler if one chose to meet with only a parent. Safe use of these medications requires that the patient inform his or her doctor about side effects, however, and have the chance to voice any worries he or she harbors. It is equally true that kids with ASPERGERS tend to be self-centered and limited in their focus, which undermines the value of their subjective reports of overall functioning and improvement. As a result, objective reports of behavior, mood, and general functioning are needed. Taken altogether, a vital objective of the treatment relationship is gaining a sturdy, reliable, comfortable, knowledgeable collaboration with the individuals' moms/dads and with the individuals.
All ASPERGERS treatment is only relatively specific now. This will be so until research identifies the specific neurochemical or genetic defects that produce ASPERGERS and discovers a biologic or behavioral treatment that targets those defects. To make treatment specific, the psychopharmacologist cannot merely prescribe whatever is new or untested. Decisions about which agents to use should be based on what is likely to be most helpful for the individual patient's symptoms. A symptom-focused method means that the clinician is seeking the patterns of behavior in his or her specific patient with ASPERGERS that are creating obstacles to optimal educational and social experiences. It is an imperfect process and forces therapists to assess what can be achieved with educational and behavioral treatments, and to be knowledgeable about what symptoms medications are capable of ameliorating. The clinician's goal is a reduction in the specific symptoms that interfere with functioning. It is extremely unlikely that current medications will increase skills, but they may reduce the interference a patient experiences and allow him to use the skills he possesses.
Establishing treatment priorities—
The quantity, scale, and range of difficulties experienced by ASPERGERS people can be perplexing. Everyone involved, the patient, family, and clinician, can be swept up in this complexity. The first challenge is to create the hierarchy of symptoms and the problems they create. Often, difficulties fall into a cluster of symptoms. The primary task of the clinician is to determine which symptoms should be targeted first. Box 1 suggests the questions and order of consideration when approaching this quandary. Although no clinical trials have used combined approaches, it is likely that combined modalities will be a part of the youngster's care outside the consulting room. Creating a hierarchy of specific symptoms lends itself to behavioral and pharmacologic modalities. In coordinating services, simultaneously directing behavioral and pharmacologic treatments to the same symptoms may well enhance the response.
Box 1: Considerations for establishing treatment priorities—
1. Symptoms that threaten the safety of patient, family members, or others
2. Symptoms that generate subjective distress for the patient
3. Symptoms that are sources of adversity in the family's life
4. Symptoms that jeopardize sustained educational progress
Safety is the most compelling reason that ASPERGERS individuals are referred for pharmacotherapy. Aggression and violent outbursts are common in people with ASPERGERS [22], [23], and people with ASPERGERS commonly engage in other types of dangerous behaviors such as throwing or destroying objects [23]. Moreover, there are features of the disorder that make aggression and self-injury harder to control. Among other reasons, deficits in abilities to soothe and comfort themselves, the comparative insignificance of others' distress, rigid adherence to patterns or behaviors, deficits in generalizing from one circumstance to another, and the tendency to engage in repetitive and stereotyped behaviors may contribute to this intractability. As a result, the safety to individuals and those around them are the highest priority.
A patient's subjective distress takes center stage once safety is not a primary worry. Relief of suffering in itself is a worthy objective, but focusing on the distress of ASPERGERS individuals goes beyond this generic physician mandate. ASPERGERS individuals who are sad, anxious, or continually irritable are thwarted in their ability to learn, monitor themselves, and “read” their environment. Their emotions override their abilities to perceive events and think through the solutions to everyday problems; they cannot respond with the necessary flexibility to the rapidly changing demands of the social world. As a result, subjective distress closes off opportunities to learn information, increase social relating, and gain new social skills. A patient in continual distress is likely to be unable to demonstrate his or her actual abilities.
The effects of an ASPERGERS youngster's symptoms on a family are diverse, and some symptoms can be exceptionally taxing. Adverse effects on a family can be difficult to isolate and harder still to quantify. (Volumes could be written on the effect of ASPERGERS on families.) Clearly, some symptoms exhibited by ASPERGERS kids exceed what families can manage and may jeopardize a youngster remaining at home. Symptoms that imperil a youngster living at home deserve the most strenuous efforts to avert institutional or foster placements. The way a family adapts to a youngster with ASPERGERS grows out of a complex interplay of the youngster's constitutional factors, such as his skills, deficits, and temperament, and the measure of limitations and demands of other family members that must be met. Cultural influences and community responses also can have a potent moderating or amplifying effect. Certainly the way moms/dads and siblings adapt to a youngster's limitations and demands is a factor in the youngster's overall adaptation.
The clinician may be required to decide which contributions to an adverse family environment warrant family treatment, couples treatment, or further psychoeducational interventions, and which are likely to benefit from pharmacotherapy. A common misjudgment is using medications to treat the patient's symptoms when a parent's depression or anxiety is a major contribution to family strain. Frequently, high levels of parental distress lead therapists to prescribe for the youngster rather than educate moms/dads and recommend that they obtain treatment. This is not to advocate that family members must be infinitely adaptable to impairing symptoms in a youngster or that family problems are always the result of parental disorders. The point is that family distress has many sources. Using medication may reduce a patient's inflexibility, instability, and anxiety, and thereby enhance life at home for everyone. If the relentless stress of raising a youngster with ASPERGERS has fueled depression or an anxiety disorder in a parent, or inflamed conflicts in a marriage, however, usually treating only the youngster is insufficient. To treat clinical disorders in a parent or the tensions between partners, it is most likely that specific treatment is needed.
Similar to the risk for being unable to continue living at home, some behaviors can jeopardize a good educational placement. For example, when minor daily schedule changes lead a youngster to display aggression, withdrawal, or severe tantrums, if the school placement is at risk then there may be a role for medication to supplement vigorous behavioral efforts. This is particularly relevant when the program previously met a youngster's needs and then no longer is able to because of increasing symptoms or new symptoms that programmatic changes cannot reduce. On the other hand, not every program is ideal for every student. Some school placements do not fit the youngster's needs well and on occasion there are requests for medication that are based on a misunderstanding of the patient and his or her disorder. Medication should not be used to force a fit to a school program that poorly matches a patient's needs. Discussions with educators, moms/dads, special education administrators, and autism resource staff at the school often are necessary to sort out important medication decisions.
Characterizing symptoms—
Behavioral and pharmacologic treatments of ASPERGERS share a basic principle—a detailed characterization of the specific symptoms is needed to select the proper intervention. In part this is an outgrowth of the integration of behavioral and pharmacologic approaches. However, even if the integration of behavioral supports and biologic interventions were not necessary, these symptom details would be needed. A careful analysis of symptoms is important because the choice of interventions is influenced by symptom characteristics. Furthermore, the wide array of symptoms engenders an inclination of those closest to the youngster to lose sight, over time, of the intervention targets. When observers turn their attention to a new troubling cluster of symptoms, a treatment that has been effective may be reinterpreted as ineffective. Being attentive to symptom characteristics permits the clinician to measure effects and introduce thoughtful responses. The most important characteristics to consider are shown in Box 2.
Box 2: Characteristics of symptoms—
1. Distribution
2. Intensity
3. Onset: Time and Location
4. Duration
5. Ameliorating Factors
6. Aggravating Factors
7. Trends: upward or downward
The distribution of behaviors is a term for the frequency of symptoms over time. It may be self-evident, but it is worth underscoring that for most individuals, the frequency of symptoms changes within days, weeks, and months. Thus, having a good awareness of the course of a symptom is important for monitoring medication effects. The early, short-term effects of a medication may not be the most reliable ones for predicting the overall effect that medication delivers. Frequency also usually is related to settings and circumstances. Aggression or perseverative behaviors often increase or emerge under certain circumstances, such as when there are many individuals talking or when there are crowds. Consequently, for behaviors that are episodic it is useful to rate the behavior at the time when it is most frequent or likely to surface, rather than a general rating throughout the day, week, or month.
Furthermore, when symptoms are concentrated to specific times or places, one should first consider behavioral or educational interventions carefully. It may be that greater direction for certain activities, a break from interaction, or modifying the expectations for the patient in an activity will go a long way toward reducing maladaptive behaviors. Similarly, the risk for side effects should match the frequency of a behavior. If a symptom arises rarely, then it does not make sense to use an agent that carries a high risk for serious side effects or is highly likely to produce side effects that have the potential to make the patient uncomfortable.
Intensity is a measure of the energy or concentration the patient uses when engaging in the behavior. It also can be helpful to base this rating on the ease with which a patient may be redirected to another, different line of behavior. The onset of symptoms is often related to a time and a location. The ability to know when and where symptoms surface, or under what circumstances they surface, is helpful in rating progress. In addition, if a symptom only arises in one setting then this might lead one to consider intensive behavioral interventions first. More generalized behaviors might lend themselves more to pharmacologic treatments, because it can be difficult to maintain uniform responses across many different settings for behavioral interventions. Duration is self-explanatory. Aggravating and ameliorating factors can indicate what triggers a behavior or what sustains it.
The reason to consider the trend of a behavior, that is, whether it is increasing or decreasing, is that an intervention that is introduced as a behavior is winding down may be wrongly considered as having helped. Often, individuals or their families seek treatment when a behavior is peaking in severity. For episodic conditions, by the time a clinician intervenes, the behavior may be cycling down by itself. It is therefore often helpful to wait before intervening, to learn about the pattern and characteristics of a behavior. Of course, this cannot be considered when the risks to safety or jeopardy to other aspects of the patient's wellbeing prevent the clinician from taking this time. If there is some doubt about whether symptoms may respond to behavioral treatment, or if one is unsure whether things have improved or remained the same, a clinician is advised to wait. Increasing doses or starting new medications should only go forward if one is sure that symptoms are worse or improved to a small degree.
A 12-year-old boy with ASPERGERS was brought to treatment for picking and scratching behaviors that had become a part of his nighttime routine before going to bed. Each night he would scratch or dig at his legs. After extensive efforts to learn about the pattern of his behaviors, it seemed that these behaviors were influenced by the course of interactions at school during the day. Although the patient himself did not make the connection between being teased or having disagreements with classmates and his self-picking, it was possible to use medication and relaxation techniques to reduce the intensity and duration of these behaviors. In addition, the patient's moms/dads were able to talk with him in the early evening about specific events from throughout the day that might create distress before he went to bed. Over time the behaviors were significantly reduced, although they did not disappear altogether.
Deciding on modality priorities—
The integration of behavioral and pharmacologic treatment can place therapists in the predicament of deciding whether to pursue behavioral or pharmacologic treatment. There are patient and symptom characteristics that should enter the equation. Individuals who work hard with a behavioral support system are obviously ones who should be treated vigorously in this manner. Other individuals resist behavioral work or have circumstances that do not lend themselves to behavioral treatments. For example, it may be difficult to use behavioral treatments at home with frail caretakers who may be physically intimidated during attempts to ignore maladaptive behaviors.
As indicated earlier, there are some scenarios in which the clinician might request a more thorough application of behavioral treatment before engaging in pharmacotherapy. The features that indicate vigorous behavioral treatment are those that are more infrequent, highly setting- or circumstance-specific, and moderately (or less) intense. It is important to consider whether behavioral treatments have been conducted properly, were of sufficient duration, and were provided with sufficient intensity. A history of well conducted but unsuccessful behavioral treatments suggests that one should move to medication along with behavioral supports.
Six symptom clusters—
For simplicity, six clusters of symptoms are discussed. Throughout this discussion the emphasis has been on specific symptoms and this is an important feature to emphasize. If a patient repetitively seeks elastic objects to stretch and chew, then that symptom is the one to be targeted; for this discussion it would fall into repetitive behaviors and inflexibility. The monitoring of that symptom, however, means that the clinician and others are all tracking perseverative behavior with elastic—not every repetitive behavior that the patient may display. The clusters that follow are only a convenient way of talking about pharmacologic treatments for the common kinds of behaviors that impede the lives of individuals who have ASPERGERS. These clusters are hardly comprehensive and there certainly could be more. These were chosen because they are common reasons to seek pharmacotherapy for people with ASPERGERS.
Aggression:
Aggression is seldom an isolated problem and is particularly complex in people with ASPERGERS [23]. It is important to understand that aggressive behavior is not always associated with just one condition and can have highly varied sources. An array of theoretic models has been proposed to understand aggressive behavior in people with ASPERGERS [24]. There are promising biologic models that suggest the behavior arises from alterations in dopaminergic reward mechanisms [25], and cognitive models, suggesting that such acts are an outcome of conditioned learning [26], [27]. Tantrums and physical aggression are often responses to a variety of circumstances and occur in the context of diverse emotions [23]. It has become fashionable to consider aggression as prima facie evidence of bipolar disorder, particularly when ASPERGERS people are distractible, restless, and have chronically decreased need for sleep. It is increasingly important to consider, however, whether features of bipolar illness appear together and depart from chronic baseline functioning.
It is also relevant if they are associated with pharmacologic (eg, serotonin reuptake inhibitor) side effects. It is useful to know the circumstances preceding and following aggressive outbursts before selecting a pharmacologic agent. For example, when aggression is a response to anxiety or frustration, the most helpful interventions target those symptoms and the circumstances that produce them rather than exclusively focusing on aggressive behavior. Unfortunately, the request for treatment typically follows a crisis and the press for a rapid, effective end to the behaviors may not permit the gathering of much data or discussion. Nevertheless, it is not appropriate to “always” begin with one agent or another. Moving to a more “surefire” agent too quickly may mean that the patient takes on cardiovascular, endocrinologic, and cognitive risks that might be otherwise avoided. There are reports in support of using serotonin reuptake inhibitors (SRIs) [28], [29], [30], [31], [32], [33], [34] (Table 1), alpha-adrenergic agonists [35] (Table 2), beta-blocking agents [36], [37] (Table 3), “mood stabilizers,” (or anticonvulsants) [38] (Table 3), and neuroleptics [39], [40], [41], [42], [43], [44], [45] (Table 4) for aggressive behavior. When a clinician has the luxury of time, the support of family, and collaboration with staff where the individual is working or attending school (or living), then an agent that is safer, but perhaps takes a longer time to work or is a little less likely to help, can be tried. It does seem that those agents with a greater likelihood of success pose greater risks [22], [46]. The most evidence supports use of dopamine blocking agents (neuroleptics) for aggression [22] (Table 4), but the side effects and long-term risks from these agents are greater than others listed earlier.
Anxiety:
People with ASPERGERS are particularly vulnerable to anxiety [47], [48]. This vulnerability may be an intrinsic feature of ASPERGERS [49] through specific neurotransmitter system defects [50], a breakdown in circuitry related to extinguishing fear responses [51], or a secondary consequence of their inability to make social judgments [15], [16], [17] throughout development. The social limitations of ASPERGERS make it difficult for people with the disorder to develop coping strategies for soothing themselves and containing difficult emotions. Limitations in their ability to grasp social cues and their highly rigid style act in concert to create repeated social errors. They are frequently victimized and teased by their peers and cannot mount effective socially adaptive responses. Limitations in generalizing from one situation to another also may contribute to repeating the same social gaffs. Furthermore, the lack of empathy severely limits skills for autonomous social problem solving. For higher functioning people, there is sufficient grasp of situations to recognize that others “get it” when they do not. For others there is only the discomfort that comes from somatic responses that are disconnected from events and experience.
Several agents have been tried for treatment of anxiety. There is no reason to suspect that people with ASPERGERS are less likely to respond to the medications used for anxiety in people without ASPERGERS. Thus, SRIs [28], [29], [30], [31], [32], [33], [34], [52] (Table 1), buspirone [53] (Table 3), and alpha-adrenergic agonist medications such as clonidine or guanfacine all have been tried [35] (Table 2). The best evidence to date supports use of selective serotonin reuptake inhibitors (Table 1). It is also true that people with ASPERGERS may be more vulnerable to side effects and to exhibit unusual side effects. Disinhibition is particularly prominent and can be seen with any of the serotonin reuptake inhibitors; in some circles this is regarded as evidence of bipolar “switching,” although there are no studies to suggest that among people with ASPERGERS this reaction is a portent of later nonmedication-related mania. Similarly, excessive doses may produce an amotivational syndrome [54].
Depression:
Depression seems to be common among ASPERGERS people in adolescence and adulthood [55]. Many of the same deficits that produce anxiety may conspire to generate depression. The relationship between serotonin functioning and depression has been explored in detail [56], [57], [58], [59]. There is also good evidence that serotonin functions may be impaired in people with ASPERGERS [60] and which suggest that depression and ASPERGERS would be more likely. Another possibility is that the basic circuitry related to frontal lobe functions in depression may be affected in people with ASPERGERS [61]. In addition, deficits in social relationships and responses that permit one to compensate for disappointment and frustration may fuel a vulnerability to depression [15], [16], [17], [55]. There is some genetic evidence suggesting that depression and social anxiety are more common among first-degree relatives of autistic people [62], even when accounting for the subsequent effects of stress.
The medications that are useful for depression in typical kids and adolescents should be considered for people with ASPERGERS who display symptoms of depression. It exceeds the scope of this discussion to detail the diverse forms depression may take in people with ASPERGERS or the complexities of how one might make the diagnosis of depression in people with comorbid ASPERGERS. It should be pointed out, however, that because some features of depression and ASPERGERS overlap, it is important to track that the changes in mood are a departure from baseline functioning. Thus, the presence of social withdrawal in a person with ASPERGERS should not be considered a symptom of depression unless there is an acute decline from that person's baseline level of functioning.
A second important point is that the core symptoms of depression should arise together. Thus, the simultaneous appearance of symptoms such as sleep and appetite changes, irritability, sadness, loss of pleasure in activities, decreased energy, further withdrawal from interactions, and self-deprecating statements would point to depression. An additional important point is that individuals who display affective and vocal monotony are at higher risk for having their remarks minimized. Higher functioning people can make suicidal statements in a manner that suggests an off-hand remark, without emotional impact. When comments are made this way, therapists and others may underestimate them. In people with ASPERGERS, the content of such comments may be more crucial than the emotional emphasis with which they are delivered.
Agents that are useful for treatment of depression in people with ASPERGERS are serotonin reuptake inhibitors (Table 1). There also may be indications for considering tricyclic agents with appropriate monitoring of ECG, pulse, and blood pressure (Table 5). There are no agents that have been shown to be particularly more beneficial for depressive symptoms in people with ASPERGERS. Thus, the decision as to which agents to use is determined by side effect profiles, previous experience, and, perhaps, responses to these medications in other family members.
Hyperactivity and inattention:
Hyperactivity and inattention are common in ASPERGERS people, particularly in early childhood [5], [63], [64]. Differential diagnostic considerations are paramount, particularly in the context of ASPERGERS [63]. Hyperactivity and inattention is seen in a variety of other disorders, such as developmental receptive language disorders, anxiety, and depression. Thus, the appearance of inattention or hyperactivity does not point exclusively to attention deficit hyperactivity disorder (ADHD). The compatibility of the patient and his or her school curriculum is particularly important when evaluating symptoms of hyperactivity and inattention. There is a risk that a school program that is poorly matched to the individual's needs, by overestimating or underestimating a youngster's abilities, may be frustrating, boring, or unrewarding. If the verbal or social demands exceed what he or she can manage, they may produce anxiety or other problems that mimic inattention or induce hyperactivity.
Virtually every variety of medication has been tried to reduce hyperactive behavior and increase attention. The best evidence at this point supports dopamine blocking agents [39], [40], [41], [42], [43], [44], [45], [46] (Table 4), stimulants [65] (Table 6), alpha-adrenergic agonists [35] (Table 2), and naltrexone [66], [67], [68] (Table 3).
Inflexibility and behavioral rigidity:
Symptoms of inflexibility or behavioral rigidity are often difficult to quantify and yet often introduce some of the most disruptive chronic behaviors exhibited by individuals with ASPERGERS. These can be manifest by difficulties tolerating changes in routine, minor differences in the environment (such as changes in location for certain activities), or changes to plans that have been previously laid out. For some people this inflexibility can lead to aggression, or to extremes of frustration and anxiety that thwart activities. Families and school staff may find themselves “walking on eggshells” in an effort to circumvent any extreme reaction from brittle individuals. In addition, the individuals themselves may articulate their anxiety over fears that things will not go according to plan or that they will be forced to make changes that they cannot handle. Sometimes these behaviors are identified as “obsessive-compulsive” because of the patient's need for ritualized order or nonfunctional routine. This is a phenomenologic error, as OCD has features that can be differentiated from PDD spectrum disorders [69].
Nevertheless, the idea that OCD and these “needs for sameness” might share some biologic features is attractive. It is not known now whether these symptoms are produced by disturbances in the same cortico-striatal-thalamo-cortical circuitry that is believed to produce OCD [70]. The model of obsessive-compulsive disorder, however, has suggested that use of SRI agents might be useful in ameliorating this problem [28], [33]. Whether the effect of SRI agents on this symptom cluster is mediated by a general reduction in anxiety [48] or is specific for “needs for sameness” is not known. An alternative hypothesis suggests that the impairment might be located in circuitry subserving reward systems that rely on norepinephrine and dopamine [24], [71]. If so, this would point to study of other agents and systems in future investigations.
To add further support to this hypothesis, reports from studies of alpha-adrenergic agents like clonidine [35] and guanfacine also suggest a decrease in these rigid behaviors. These short-term trials do not establish whether the benefits were sustained over a longer time, however. Agents that have been most useful are SRIs (Table 1), but there may be a role for dopamine blocking agents for refractory symptoms [43], [44], [45] (Table 4).
Stereotypies and perseveration:
Stereotyped movements and repetitive behaviors are a common feature of ASPERGERS [64]. As with behavioral rigidity and inflexibility, similar models for stereotypy and obsessive-compulsive disorder have been proposed [72]. Stereotypy also may be closely related to tic disorders and Parkinson disease, however, in which repetitive behaviors emerge from impairment in dopaminergic [73] and glutamaturgic systems [74]. There are also interesting analogs to L-dopa toxicity in Parkinson disease [75].
The treatments for stereotyped movements and perseveration closely parallel those for behavioral inflexibility and the two clusters are often grouped together in studies of treatment efficacy. Thus, serotonin reuptake inhibitors (Table 1) and alpha-adrenergic agonists may be helpful (Table 2). In addition, the hypothesis that dopamine might play a role suggests that dopaminergic blocking agents should be added to the possibilities (Table 4). Reports from studies of olanzapine [41], risperidone [42], [43], [44], and ziprasidone [45] suggest this is warranted.
Complementary and alternative medicine:
The pharmacologic treatment of ASPERGERS people is in a very early stage. As a result of more organized and systematic investigation, the field is making advances in the discovery of more effective treatments [76]. A large gap remains, however, between the need for effective treatments and the effectiveness of the known agents. When there is such a disparity, opportunities for scientifically unfounded, anecdotal experience or highly biased efforts to capture the attention of moms/dads, physicians, and educators are great. In the case of ASPERGERS, one can cite many examples; the recent experience with secretin [77], [78], [79], [80] is one. This does not mean that everything about secretin in autism is now understood, only that is unreasonable to recommend secretin for ASPERGERS [81]. A similar point might be made for the variety of dietary and nutritional therapies—in the absence of carefully designed, scientifically valid, controlled studies, it is hard to justify recommending specific treatments.
Nevertheless, therapists still have to answer families who ask about trying novel treatments. Among investigators and concerned practitioners, broad guidelines have been suggested (Klin, personal communication). The first is that treatments should be safe. A variety of diets and mineral supplements are apparently safe, but some can be toxic; the frequency of toxic reactions should be spelled out and signs of toxicity should be thoroughly comprehended. More extraordinary interventions such as neurosurgery obviously are not reversible. The second guideline is that treatments should be affordable. At the height of the secretin rush, some practitioners were charging many hundreds of dollars for medication and supplies that totaled less than fifty dollars.
For most families, these treatments are not covered by insurance and money that goes to novel treatment is not available for other services. The third guideline is that novel treatments should not interfere with a youngster's participation in daily programs or treatments that are known to be helpful. Focusing on communication and social enhancement through education should be the first priority of every multimodal treatment plan. Attending school, having a detailed evaluation, and receiving behavioral supports that promote socialization and communication should not be curtailed by the pursuit of novel somatic, dietary, and complementary medical treatments.
Summary—
The treatment of complex, polymorphous disorders like ASPERGERS always brings a particular challenge to pharmacotherapy. Additionally, the specific characteristics presented by ASPERGERS introduce unique complications to patient care and place unusual demands on a clinician's skill and experience. To provide safe and effective treatment, the clinician must understand the core features of the disorder and the manifestations of the condition in his or her patient. Furthermore, a thorough understanding of the family, school, and community resources and limitations is necessary.
Once an assessment has been made, focusing on target symptoms provides a crucial framework for care. Knowing manifestations of symptoms and characterizing their distribution and behavior in that patient is most important. For individuals with ASPERGERS it is particularly essential to coordinate behavioral and pharmacologic objectives. The target symptoms should be tracked carefully and placed into a priority system that is based on the risks and disability they create for the patient. The skill of pharmacotherapy also means setting out realistic expectations, keeping track of the larger systems of care at school and home, and collaboration with moms/dads and care providers.
There is an expanding range and pace of biologic and intervention research into ASPERGERS. The genetic work has produced exciting leads that are likely to be helpful to future generations [82], [83], [84], but the task of therapists is to tend to today's individuals. As we discover more about the complex neural circuitry subserving repetitive behaviors, reward systems, and social cognition, there are good reasons to believe our treatments will become more sophisticated and specific. Psychopharmacology is also moving to design medications that target more specific populations of receptor and brain functions. This is likely to produce medicines that have fewer side effects, are more effective, and are more symptom-specific.
Pharmacotherapy is not the ultimate treatment for ASPERGERS but it has a definite place. Medication can be a critical element in a comprehensive treatment plan. There is a wider range of medications with more specific biologic effects than ever before. For individuals with ASPERGERS these newer agents are safer and less disruptive. When paired with therapists who are becoming more skilled at recognizing and managing symptoms, individuals have a greater opportunity to reach their potential and lead pleasurable lives.
My Aspergers Child: Preventing Meltdowns in Aspergers Children
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