The pharmacological treatment of autistic spectrum disorders

What role do medications play in the overall treatment of autistic spectrum disorders? In this review, the decision-making process involving identifying symptoms, initiating a pharmacological intervention, and monitoring that process is discussed. A review of the literature with an emphasis on controlled trials in autistic spectrum disorders is also undertaken.     

Pharmacological treatment effects on eye movement control

The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to learn about neurochemical systems relevant for identified disturbances, and to facilitate identification of oculomotor biomarkers of pharmacological effects. In this review, studies of pharmacologic treatment effects on eye movements in healthy individuals are summarized and the sensitivity of eye movements to a variety of pharmacological manipulations is established. Primary findings from these studies of healthy individuals involving mainly acute effects indicate that: (i) the most consistent finding across several classes of drugs, including benzodiazepines, first- and second- generation antipsychotics, anticholinergic agents, and anticonvulsant/mood stabilizing medications is a decrease in saccade and smooth pursuit velocity (or increase in saccades during pursuit); (ii) these oculomotor effects largely reflect the general sedating effects of these medications on central nervous system functioning and are often dose-dependent; (iii) in many cases changes in oculomotor functioning are more sensitive indicators of pharmacological effects than other measures; and (iv) other agents, including the antidepressant class of serotonergic reuptake inhibitors, direct serotonergic agonists, and stimulants including amphetamine and nicotine, do not appear to adversely impact oculomotor functions in healthy individuals and may well enhance aspects of saccade and pursuit performance. Pharmacological treatment effects on eye movements across several clinical disorders including schizophrenia, affective disorders, attention deficit hyperactivity disorder, Parkinson’s disease, and Huntington’s disease are also reviewed. While greater recognition and investigation into pharmacological treatment effects in these disorders is needed, both beneficial and adverse drug effects are identified. This raises the important caveat for oculomotor studies of neuropsychiatric disorders that performance differences from healthy individuals cannot be attributed to illness effects alone. In final sections of this review, studies are presented that illustrate the utility of eye movements for use as potential biomarkers in pharmacodynamic and pharmacogenetic studies. While more systematic studies are needed, we conclude that eye movement measurements hold significant promise as tools to investigate treatment effects on cognitive and sensorimotor processes in clinical populations and that their use may be helpful in speeding the drug development pathway for drugs targeting specific neural systems and in individualizing pharmacological treatments.     

Pharmacological treatment effects on eye movement control

The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to learn about neurochemical systems relevant for identified disturbances, and to facilitate identification of oculomotor biomarkers of pharmacological effects. In this review, studies of pharmacologic treatment effects on eye movements in healthy individuals are summarized and the sensitivity of eye movements to a variety of pharmacological manipulations is established. Primary findings from these studies of healthy individuals involving mainly acute effects indicate that: (i) the most consistent finding across several classes of drugs, including benzodiazepines, first- and second- generation antipsychotics, anticholinergic agents, and anticonvulsant/mood stabilizing medications is a decrease in saccade and smooth pursuit velocity (or increase in saccades during pursuit); (ii) these oculomotor effects largely reflect the general sedating effects of these medications on central nervous system functioning and are often dose-dependent; (iii) in many cases changes in oculomotor functioning are more sensitive indicators of pharmacological effects than other measures; and (iv) other agents, including the antidepressant class of serotonergic reuptake inhibitors, direct serotonergic agonists, and stimulants including amphetamine and nicotine, do not appear to adversely impact oculomotor functions in healthy individuals and may well enhance aspects of saccade and pursuit performance. Pharmacological treatment effects on eye movements across several clinical disorders including schizophrenia, affective disorders, attention deficit hyperactivity disorder, Parkinson’s disease, and Huntington’s disease are also reviewed. While greater recognition and investigation into pharmacological treatment effects in these disorders is needed, both beneficial and adverse drug effects are identified. This raises the important caveat for oculomotor studies of neuropsychiatric disorders that performance differences from healthy individuals cannot be attributed to illness effects alone. In final sections of this review, studies are presented that illustrate the utility of eye movements for use as potential biomarkers in pharmacodynamic and pharmacogenetic studies. While more systematic studies are needed, we conclude that eye movement measurements hold significant promise as tools to investigate treatment effects on cognitive and sensorimotor processes in clinical populations and that their use may be helpful in speeding the drug development pathway for drugs targeting specific neural systems and in individualizing pharmacological treatments.     

Review of State Medication Policies/Guidelines Regarding Psychotropic Medications in Public Schools

It is currently estimated that up to 6 million children take psychotropic medications for the treatment of mental health problems. The highest prevalence rates (50–76 %) are typically found among students with special needs, especially among those with ADHD and emotional disturbance. The Individuals with Disabilities Education Act (IDEA) and Section 504 of the Rehabilitation Act of 1973 require medications be administered by schools whenever it is deemed necessary for the child to have access to educational services. However, these requirements do not extend to all students, nor do they provide guidance regarding the safest and most efficacious manner in which psychotropic medications should be administered. The authors reviewed existing state medication policies and guidelines to assess the level of guidance currently provided to school staff. Results showed the vast majority of states (48) provided guidance related to the administration of medications to students, with slightly fewer (44) states discussing required documentation procedures. Surprisingly, only 15 states addressed monitoring students for adverse side effects of medications, and even fewer (11) states specifically discussed psychotropic medication in their policies/guidelines. The vast majority (42) of states also addressed requirements for the safe and proper storage of medications, while slightly more than half of all states (31) provided any guidance regarding training of unlicensed personnel (e.g., secretaries) who frequently administer medications to students. The authors highlight several model guidelines/policies and review recommendations for best practice.     

A review of the treatment for refractory obsessive-compulsive disorder: from medicine to deep brain stimulation

This article provides an overview of the etiology, epidemiology, and first-line treatment options for obsessive-compulsive disorder (OCD). The subject of treatment-resistant and treatment-refractory OCD is then discussed, including a definition of these often-debated terms, and the latest treatment options delineated. This includes a review of the latest research concerning the pharmacological agents that have been studied as monotherapy or augmenting agents for the treatment of OCD, the use of experimental medications and procedures, treatment with reversible, minimally invasive procedures, such as vagal nerve stimulation and transcranial magnetic stimulation, invasive but the potentially reversible deep brain stimulation, and irreversible lesioning with ablative psychosurgery. A discussion of the role of psychotherapy in the treatment of OCD is also included.     

Reassessing carbamazepine in the treatment of bipolar disorder: clinical implications of new data

This monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions. Panel discussants agree that current data confirm the utility of CBZ ERC as an effective treatment for acute manic and mixed episodes in bipolar disorder. Carbamazepine may also prove to be an option for maintenance treatment. Tolerability of the drug is related to dose and titration, and overall safety limitations regarding carbamazepine usage are comparable to other medications. For some patients, the main challenges to use of carbamazepine may be common drug-drug interactions and increased side effects related to aggressive introduction during treatment of acute manic and mixed episodes. Thus, carbamazepine may be a lower priority option for patients who are taking multiple medications, such as elderly individuals with medical comorbidity, due to the potential for drug interactions. Important benefits of carbamazepine include the low propensity toward weight gain and evidence of good tolerability with long-term treatment. (At present there are no available data from long-term, placebo-controlled studies evaluating the effects of carbamazepine or CBZ ERC on weight.) Thus, carbamazepine may be a good option for patients who are concerned about weight gain or who are intolerant of or respond poorly to other medications. Further efforts are needed to update physicians on the use of carbamazepine relative to other medications in the treatment of bipolar disorder.     

A critique of models and measures of treatment readiness in offenders

Assessing offender readiness for treatment has major implications in terms of determining program referrals, dropout rates and, hence, program efficiency and efficacy. To be treatment ready means that the offender is motivated, finds programming relevant and meaningful, and has the capacity to successfully engage in and complete treatment. The objective of this paper is to systematically review the current methods of defining and measuring the construct of offender treatment readiness. A review of 11 measures assessing treatment readiness is described. Commonalities and differences between the measures are discussed, as well as their psychometric properties and different theoretical models. This paper concludes that there is a lack of consensus regarding the construct of treatment readiness and highlights the need for its standardized assessment. While there are various instruments developed to examine treatment readiness, there have been few efforts in validating the variables and elements encompassed by this construct. The need for a solid theoretical model is identified. Implications regarding best practices are described, as well as future directions on how to develop a psychometrically sound measure.     

AEDs and psychotropic drugs in children with autism and epilepsy

The efficacy of antiepileptic drugs (AEDs) and psychotropic medications in children with autism is limited to the treatment of seizures or to specific behaviors such as irritability, impulsivity, hyperactivity, repetitive behaviors, or aggression. The reliability and value of the available data--to determine the efficacy of these medications in autism--are limited by lack of controlled clinical trials, the small number of subjects, the heterogeneity of the population studied, and the brief duration of most drug trials. Indeed, few controlled clinical trials using AEDs in autism, with or without seizures, have been conducted. Because some AEDs also have a positive effect on mood, the benefits that children with autism sometimes obtain from these medications may not be due to the treatment of the abnormal electrical activity or the seizures per se but to an effect on common neuronal systems responsible for both behavior and epilepsy. The relationship between epilepsy and autism, and specifically the effects that abnormal electrical activity may have on the developing brain, may provide some valuable insights into the type of studies that are needed to help us understand the pathophysiology of autism.     

Manualized Treatment of Panic Disorder in a Medical Setting: Two Illustrative Case Studies

People who experience panic attacks (PAs) typically present to medical settings, concerned that their symptoms signify a life-threatening condition. Despite the efficacy of cognitive-behavioral therapy (CBT) for panic disorder (PD), medical practitioners seldom provide this type of treatment. Physicians may lack the time or expertise to impart such behavioral medicine interventions, while patients may find group or individual CBT too costly even when available. Researchers have begun investigating manualized CBT as a cost-effective alternative when traditional forms of this intervention are prohibited. This article describes two case studies in which women presenting to a medical clinic with PD were treated with 6 weeks of manualized CBT after pharmacotherapy was unsuccessful or unpalatable. Both patients exhibited reductions in panic and depressive symptomatology over baseline levels, along with increases in self-efficacy regarding their ability to manage future PAs. Improvements were maintained over 12 months, supporting continued use of manualized CBT as a supplement or alternative to pharmacological methods of treating PD in the medical setting.     

Affect expression in prenatally psychotropic exposed and nonexposed mother–infant dyads

This prospective study examined infant, maternal, and dyadic affective profiles at three months postpartum in infant–mother dyads that were exposed to psychotropic medications in utero compared with nonexposed control dyads. Control dyads of nondepressed mothers and their infants showed many similarities in affect expression with mother–infant dyads who were exposed to selective serotonin reuptake inhibitors (SSRIs) alone for treatment of maternal depression. In contrast, mothers who received SSRIs and Rivotril (Benzodiazepine derivative) for treatment of depression and anxiety expressed both positive and negative affect towards their infants. Clinical implications regarding use of psychotropic medications such as SSRIs alone or in combination with other drugs for treatment of maternal anxiety and depression during pregnancy are discussed. Clinicians should be aware of the possible differential response in maternal–infant interaction in a mixed diagnosis group (i.e., depression and anxiety) regarding infant temperament, possibly suggesting latent behavioral teratogenicity with psychotropics. ©2002 Michigan Association for Infant Mental Health.     

Non-pharmacological treatment-related changes of molecular biomarkers in major depressive disorder: A systematic review and meta-analysis

BackgroundMajor depressive disorder (MDD) is a serious mood disorder and leading cause of disability. Despite treatment advances, approximately 30% of individuals with MDD do not achieve adequate clinical response. Better understanding the biological mechanism(s) underlying clinical response to specific psychopharmacological interventions may help fine tune treatments in order to further modulate their underlying mechanisms of action. However, little is known regarding the effect of non-pharmacological treatments (NPTs) on candidate molecular biomarker levels in MDD. This review aims to identify molecular biomarkers that may elucidate NPT response for MDD.MethodsWe performed a systematic review and a multilevel linear mixed-effects meta-analyses, and a meta-regression. Searches were performed in PubMed, Scopus, and PsycINFO in October 2020 and July 2021.ResultsFrom 1387 retrieved articles, 17 and six studies were included in the systematic review and meta-analyses, respectively. Although there was little consensus associating molecular biomarker levels with symptomology and/or treatment response, brain metabolites accessed via molecular biomarker-focused neuroimaging techniques may provide promising information on whether an individual with MDD would respond positively to NPTs. Furthermore, non-invasive brain stimulation interventions significantly increased the expression of neurotrophic factors (NTFs) compared to sham/placebo, regardless of add-on pharmacological treatment.ConclusionsNTFs are candidate biomarkers to fine-tune NIBS for MDD treatment.     

Developing treatments for impaired cognition in schizophrenia

Schizophrenia is one of the most debilitating of all common brain disorders, exacting a heavy toll on the afflicted and having a tremendous public health impact. Clinical outcome is more strongly predicted by cognitive deficits than psychotic symptoms, with no established treatment for these deficits. In this review, we discuss the status of treatment development for impaired cognition in schizophrenia. These treatments include a range of pharmacological targets within diverse neurotransmitter systems. New technologies, including transcranial magnetic stimulation and transcranial direct current stimulation, and psychological therapies, such as computer-based cognitive training, may also benefit cognition in schizophrenia. Each of these approaches shows promise and their integration may optimize benefits for patients in the future.     

Treatment with medications affecting dopaminergic and serotonergic mechanisms: effects on fluency and anxiety in persons who stutter

Medications with dopamine antagonist properties, such as haloperidol, and those with serotonin reuptake inhibitor properties, such as clomipramine, have been shown to improve fluency. To examine the degree to which each of these two pharmacological mechanisms might independently affect fluency, a selective serotonin reuptake inhibitor, paroxetine, and a selective dopamine (D-2) antagonist, pimozide, were evaluated. Both types of medications also affect mood and anxiety, factors that could influence fluency levels. Therefore, we also evaluated the medications’ effects on generalized and speech-related anxiety and the relationships between changes in anxiety and changes in fluency in 11 subjects with a history of developmental stuttering. The randomized, double blind, placebo-controlled crossover study that was designed had to be terminated prior to completion due to severe side effects following withdrawal from paroxetine. Even with a reduced sample size (n = 6), significant improvement in percent fluent speaking time (p = 0.02) was found using a telephone task between baseline and pimozide (n = 6), with average duration of dysfluencies significantly shorter (p = 0.04) but no significant difference in the estimated number of dysfluencies per minute. This significant improvement was associated with non-significant increases in generalized anxiety, but non-significant decreases in speech-related anxiety. No significant differences were found in fluency between baseline and paroxetine (n = 5). These preliminary results suggest that fluency improvement is more likely to be mediated by dopaminergic rather than serotonergic mechanisms. Due to its side effects, however, pimozide may be considered a risk for treatment of stuttering.

Educational objectives: As a result of reading this paper the reader will describe and explain: (1) how medications may affect fluency and the rationale for selecting medications for treatment trials; (2) the interrelationship between fluency and anxiety; and (3) factors important in developing clinical trials using medications.     

Drug Therapy of Post-Stroke Aphasia: A Review of Current Evidence

This review considers the role of drug therapy in the treatment of post-stroke aphasia, the evidence for efficacy of different agents, and the theory-based explanations of drug-related benefits for aphasia rehabilitation. Pharmacological interventions modulating stroke-induced disruption of diverse neurotransmitters may improve language and communication deficits in aphasic patients through facilitation of brain plasticity and long-term potentiation. However, benefits are not evident for all compounds and refinement in clinical trial designs is required. Some pharmacological trials have failed because drug treatment was not combined with speech-language therapy, while other trials combining drugs with intensive model-driven therapies also failed probably because of short-trial duration, inadequate sample selection, or lack of drug action. Preliminary data reveals that combining neuroscience-based intensive aphasia techniques (constraint-induced aphasia therapy) and drugs acting on cholinergic and glutamatergic neurotransmitter systems are associated with better outcomes than other strategies and long-term maintenance of benefits. Although further studies are needed, current state of the evidence suggests that drug therapy may play a key role in the treatment of post-stroke aphasia.     

Parent ADHD and Evidence-Based Treatment for Their Children: Review and Directions for Future Research

One fourth to one half of parents of children with attention-deficit/hyperactivity disorder (ADHD) have ADHD themselves, complicating delivery of evidence-based child behavioral and pharmacological treatments. In this article, we review the literature examining the relation between parent ADHD and outcomes following behavioral and pharmacological treatments for children with ADHD. We also review research that has incorporated treatment of parent ADHD (either alone or in combination with child treatment) with the goal of improving parenting and child outcomes. Finally, we offer recommendations for future research on the relation between parent ADHD and evidence-based treatment outcomes for their children, with the purpose of advancing the science and informing clinical care of these families.     

Pharmacological interventions in autism: theoretical and practical issues

Focused on issues of drug treatment in relation to autism. Pharmacological treatment studies in autism are complicated by various factors including a tremendous range of syndrome expression, a lack of robust animal models of the disorder, and various methodological problems. Theories have tended to follow treatments, and various neurochemical systems have been the focus of study. Neurochemical systems potentially implicated include those involving dopamine, norepinephrine, serotonin, and neuropeptides. The dopaminergic system has been the most extensively studied. Treatments developed are effective relative to certain disabling symptoms but "core" problems (e.g., in social relatedness and communication) appear less responsive to medications. The development of new approaches to assessment, including integration of behavioral and pharmacological approaches, is an important research priority.     

The role of culture in families' treatment decisions for children with autism spectrum disorders

There is little information available about how and why parents of children with autism spectrum disorders (ASD) make decisions regarding which of the many available treatments to implement with their children. Given the lack of available information regarding treatment efficacy, it is likely that parents' beliefs about child development, interpretation of the symptoms of ASD, its etiology and course, and their experiences with the health system influence treatment decisions. This article addresses these issues within the context of cultural influences. We review the small body of existing literature regarding cultural influences on decisions regarding ASD and draw implications for the study and treatment of ASD from the larger body of literature on culture and other health conditions of childhood. In addition to examining the potential for differences in clinical presentation by culture and different experiences with the healthcare system, we use Kleinman's framework of questions for understanding the role of culture in the interpretation and treatment of ASD. These questions address interpretation of symptoms and beliefs about their cause, course, and treatment. Finally, we present specific language for clinicians to use in discussion with families with different cultural beliefs about the use of less traditional treatment strategies.     

Characteristics of E-therapy Websites Involving Marriage and Family Therapists

This study described some of the common ethical and legal issues that mental health professionals practicing over the Internet or phone may encounter. It also explored how 83 e-therapy websites involving marriage and family therapists characterize their services. Results indicated that a majority of the websites lack information regarding crisis resources, terms of service, procedures for treatment of minors, and procedures for provision of therapy across borders. Further findings indicated that practitioners may have not properly considered the global nature of the Internet and its risks. Therapists are urged to give attention to e-therapy limitations, as well as ethical and legal problems, before attempting distance treatment.     

Metacognitive Interpersonal Therapy Improves Adherence to Antiretroviral Therapies in a Man with a Severe Personality Disorder: A Case Report

Treatment adherence by patients with HIV ensures they gain the full benefit of antiretroviral medications and extend their lives. One problem which may contribute to poor adherence is deficits in metacognition or the capacity to make sense of mental states. In particular, persons who struggle to notice and think about their thoughts and feelings may be less able to direct their own recovery by taking advantage of effective treatments. This raises the possibility that treatments which lead to improved metacognitive function may enhance treatment adherence. We describe the case of a man in an advanced stage of AIDS with Kaposi’s sarcoma. The patient was treated with Metacognitive Interpersonal Therapy combined with psychoeducation about pharmacological treatment for HIV. Primary medical outcomes were suppression of viral load, increase of CD4 count and control of AIDS related conditions such as Kaposi’s sarcoma. The primary psychological outcome was reduction of personality disorders criteria. The patient was able to understand what led him to discontinue medication and then later regain full adherence. He achieved suppression of viral load and restore of CD4 count. As regard severity of personality disorder, he achieved reliable change. Interventions such as Metacognitive Interpersonal Therapy may assist patients with HIV to gain the metacognitive capacities to make sense of their medical and psychological challenges and adhere to antiretroviral therapies leading to enhanced levels of health. Future studies are needed to explore these findings in larger controlled studies.     

Psychotherapy and (or) Medications for Depression in Youth? An Evidence-Based Review with Recommendations for Treatment

This article reviews existing research pertaining to antidepressant medications, psychotherapy, and their combined efficacy in the treatment of clinical depression in youth. Based on this review, we recommend that youth depression and its treatment can be readily understood from a social-psycho-bio model. We maintain that this model presents an alternative conceptualization to the dominant biopsychosocial model, which implies the primacy of biological contributors. Further, our review indicates that psychotherapy should be the frontline treatment for youth with depression and that little scientific evidence suggests that combined psychotherapy and medication treatment is more effective than psychotherapy alone. Due primarily to safety issues, selective serotonin reuptake inhibitors should be initiated only in conjunction with psychotherapy and/or supportive monitoring.