Drug treatment of obsessive-compulsive disorder

Knowledge of pharmacotherapeutic treatment options in obsessive-compulsive disorder (OCD) has grown considerably over the past 40 years. Serotonergic antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and clomipramine, are the established pharmacologic first-line treatment of OCD. Medium to large dosages and acute treatment for at least 3 months are recommended until efficacy is assessed. In case of significant improvement, maintenance treatment is necessary. Unfortunately, about half of the patients do not respond sufficiently to oral serotonergic antidepressants; augmentation with atypical antipsychotics is an established second-line drug treatment strategy. Alternatives include intravenous serotonergic antidepressants and combination with or switch to cognitive behavioral psychotherapy. Remarkably, a considerable proportion of OCD patients still do not receive rational drug treatment. Novel research approaches, such as preliminary treatment studies with glutamatergic substances, and trials with further drugs, as well as needed aspects of future research, are reviewed.     

Randomized, placebo-controlled trial of exposure and ritual prevention, clomipramine, and their combination in the treatment of obsessive-compulsive disorder

OBJECTIVE: The purpose of the study was to test the relative and combined efficacy of clomipramine and exposure and ritual prevention in the treatment of obsessive-compulsive disorder (OCD) in adults. Serotonin reuptake inhibitors (SRIs) and cognitive behavior therapy by exposure and ritual prevention are both established treatments for OCD, yet their relative and combined efficacy have not been demonstrated conclusively. METHOD: A double-blind, randomized, placebo-controlled trial comparing exposure and ritual prevention, clomipramine, their combination (exposure and ritual prevention plus clomipramine), and pill placebo was conducted at one center expert in pharmacotherapy, another with expertise in exposure and ritual prevention, and a third with expertise in both modalities. Participants were adult outpatients (N=122 entrants) with OCD. Interventions included intensive exposure and ritual prevention for 4 weeks, followed by eight weekly maintenance sessions, and/or clomipramine administered for 12 weeks, with a maximum dose of 250 mg/day. The main outcome measures were the Yale-Brown Obsessive Compulsive Scale total score and response rates determined by the Clinical Global Impression improvement scale. RESULTS: At week 12, the effects of all active treatments were superior to placebo. The effect of exposure and ritual prevention did not differ from that of exposure and ritual prevention plus clomipramine, and both were superior to clomipramine only. Treated and completer response rates were, respectively, 62% and 86% for exposure and ritual prevention, 42% and 48% for clomipramine, 70% and 79% for exposure and ritual prevention plus clomipramine, and 8% and 10% for placebo. CONCLUSIONS: Clomipramine, exposure and ritual prevention, and their combination are all efficacious treatments for OCD. Intensive exposure and ritual prevention may be superior to clomipramine and, by implication, to monotherapy with the other SRIs.     

Behavioral and psychological signs and symptoms of dementia: a practicing psychiatrist's viewpoint

Alzheimer's disease typically presents with two often overlapping syndromes, one cognitive, the other behavioral. The behavioral syndrome is characterized by psychosis, aggression, depression, anxiety, agitation, and other common if less well-defined symptoms subsumed under the umbrella entity "behavioral and psychological symptoms of dementia" (BPSD), itself divided into a number of subsyndromes: psychosis, circadian rhythm (sleepwake) disturbance, depression, anxiety, and agitation, it is BPSD with its impact on care providers that ultimately precipitates the chain of events resulting in long-term institutional care. The treatment challenge involves eliminating unmet medical needs (undiagnosed hip fracture and asymptomatic urinary tract infection or pneumonia). Pharmacologic intervention relies on risperidone and, increasingly cholinesterase inhibitors for the control of psychosis (but with response rates of only 65% at tolerable doses), olanzapine and risperidone for anxiety, and carbamazepine and valproic acid for agitation. However, evidence increasingly favors nonpharmacologic interventions, to the extent that these should now be considered as the foundation of BPSD treatment. Problem behaviors are viewed as meaningful responses to unmet needs in the therapeutic milieu. Because the progression and impact of BPSD varies between patients, interventions must be explored, designed, implemented, and assessed on an individual basis. They include: family support and education, psychotherapy reality orientation, validation therapy, reminiscence and life review, behavioral interventions, therapeutic activities and creative arts therapies, environmental considerations (including restraint-free facilities), behavioral intensive care units, and workplace design and practices that aid the ongoing management of professional caregiver stress.     

Nonpharmacological treatments for anxiety disorders

An evidence-based review of nonpharmacological treatments for anxiety disorders is presented. The vast majority of the controlled research is devoted to cognitive behavior therapy (CBT) and shows its efficiency and effectiveness in all the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) anxiety disorders in meta-analyses. Relaxation, psychoanalytic therapies, Rogerian nondirective therapy, hypnotherapy and supportive therapy were examined in a few controlled studies, which preclude any definite conclusion about their effectiveness in specific phobias, agoraphobia, panic disorder, obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD), CBT was clearly better than psychoanalytic therapy in generalized anxiety disorder (GAD) and performance anxiety Psychological debriefing for PTSD appeared detrimental to the patients in one high-quality meta-analysis. Uncontrolled studies of psychosurgery techniques for intractable OCD demonstrated a limited success and detrimental side effects. The same was true for sympathectomy in ereutophobia. Transcranial neurostimulation for OCD is under preliminary study. The theoretical and practical problems of CBT dissemination are discussed.     

NMDA receptors and fear extinction: implications for cognitive behavioral therapy

Based primarily on studies that employ Pavlovian fear conditioning, extinction of conditioned fear has been found to be mediated by N-methyi-D-aspartate (NMDA) receptors in the amygdala and medial prefrontal cortex. This led to the discovery that an NMDA partial agonist, D-cycloserine, could facilitate fear extinction when given systemically or locally into the amygdala. Because many forms of cognitive behavioral therapy depend on fear extinction, this led to the successful use of D-cycloserine as an adjunct to psychotherapy in patients with so-called simple phobias (fear of heights), social phobia, obsessive-compulsive behavior, and panic disorder. Data in support of these conclusions are reviewed, along with some of the possible limitations of D-cycloserine as an adjunct to psychotherapy.     

Long-term course and outcome of depression in later life

Depression in later life is usually a recurrent illness and often a chronic one, associated with increased health care utilization, amplification of the disability born of concurrent medical illness, decreased quality of life, increased risk for suicide, and cognitive impairment. The good news, however, is that maintenance treatments work and have a demonstrably positive impact on long-term illness course. Treatment response is especially variable, or brittle, in patients aged over 70; yet maintenance treatment with combined medication and psychotherapy is able to significantly reduce long-term treatment response variability, ensuring continued wellness. Further evaluation of cost-effectiveness is necessary in order to improve reimbursement for effective long-term treatment.     

Treatment-refractory anxiety; definition,risk factors,and treatment challenges

A sizable proportion of psychiatric patients will seek clinical evaluation and treatment for anxiety symptoms reportedly refractory to treatment. This apparent lack of response is either due to “pseudo-resistance” (a failure to have received and adhered to a recognized and effective treatment or treatments for their condition) or to true “treatment resistance.” Pseudo-resistance can be due to clinician errors in selecting and delivering an appropriate treatment effectively, or to patient nonadherence to a course of treatment. True treatment resistance can be due to unrecognized exogenous anxiogenic factors (eg, caffeine overuse, sleep deprivation, use of alcohol or marijuana) or an incorrect diagnosis (eg, atypical bipolar illness, occult substance abuse, attention deficit-hyperactivity disorder). Once the above factors are eliminated, treatment should focus on combining effective medications and cognitive behavioral therapy, combining several medications (augmentation), or employing novel medications or psychotherapies not typically indicated as first-line evidence-based anxiety treatments.     

How to treat the untreated: effectiveness of a self-help metacognitive training program (myMCT) for obsessive-compulsive disorder

Despite advances in the understanding and treatment of obsessive-compulsive disorder (OCD), many patients undergoing interventions display incomplete symptom reduction. Our research group has developed a self-help manual entitled “My Metacognitive Training for OCD” (myMCT) aimed at raising patients'' awareness about cognitive biases that seem to subserve OCD. The training is particularly intended for patients currently unable or unwilling to attend standard therapy, or in cases where such a treatment option is not available. For the present study, 86 individuals suffering from OCD were recruited over the Internet. Following the initial assessment participants were either immediately emailed the myMCT manual or allocated to a waitlist group. After 4 weeks, a second assessment was performed. The myMCT group showed significantly greater improvement for OCD symptoms according to the Y-BOCS total score compared with the waitlist group (d =.63), particularly for obsessions (d=.69). Medium to strong differences emerged for the OCI-R (d =.70) and the BDI-SF (d =.50). The investigation provides the first evidence for the effectiveness of the myMCT for OCD.     

Brief Report: Exposure and Response Prevention for Obsessive Compulsive Disorder in a 12-year-old with Autism

Obsessive Compulsive Disorder (OCD) involves exaggerated or excessive worry about threatening and non-threatening stimuli coupled with impairing rituals believed to reduce anxiety. Autism Spectrum Disorders (ASD) are characterized by impairment in social and communicative activities as well as restricted and repetitive behaviors. Approximately 2% of children with ASD are also diagnosed with OCD. Although there is extensive research demonstrating the effectiveness of behavioral interventions for pediatric OCD, little is known about how effective these treatments are for children who have a dual diagnosis of OCD and ASD. This report describes a 12-year-old male with Autism who was treated successfully with cognitive behavioral therapy with exposure and response prevention. This case study provides initial support that cognitive-behavioral therapy is effective in symptom reduction for children with comorbid autism and OCD.     

Psychosis in children: diagnosis and treatment

The diagnosis of childhood psychosis raises a host of unresolved problems, despite the Diagnostic and Statistical Manual Of Mental Disorders, 4th edition, Text Revision (DSM-IV-TR) giving identical symptoms and definitions for children, adolescents, and adults. The fantasy lives of children, and issues of developing language and cognition (including retardation), all impair diagnostic accuracy, particularly when differentiating between childhood-onset schizophrenia (COS) (≤12 years), bipolar affective disorder, major depressive disorder, and even obsessive-compulsive disorder and attention-deficit/hyperactivity disorder: the catch-all classification, psychosis not otherwise specified (PNOS), is always available for conundra that prove unsolvable. Typical if nonpathognomonic features include neurocognitive difficulties. Multiple screening instruments and specialized versions of semistructured diagnostic interviews are available. Although smooth-pursuit eye-tracking movements may prove a genetic marker for COS, etiologies are likely to be oligogenetic rather than related to a single gene. No specific biological markers or neuroimages have been identified. As such, psychoses may be indicative of a more general pattern of brain dysfunction. Drug treatments are largely based on the adult literature because of a dearth of controlled data below age 18. There are still no rigorous studies of psychosocial treatments and psychotherapy specific to childhood psychosis.     

Effects of different antidepressant treatments on the core of depression

Core symptoms of depression are a combination of psychological and somatic symptoms, often combined with psychomotor and cognitive disturbances. Diagnostic classification of depression including the concepts of melancholic, endogenous, or severe depression describe severely depressed patients suffering from most of the core symptoms, together with clinical characteristics of a cyclic unipolar or bipolar course, lower placebo response rates, higher response rates to electroconvulsive therapy, to antidepressant treatments with dually or mixed modes of action, or to lithium augmentation. Higher rates of hypothalamic-pituitary-adrenal axis hyperactivity and specific electroencephalographic patterns have also been shown in this patient group. Summarizing the symptomatology of depression in these patients, a broad overlap between the abovementioned subgroups can be suggested. Because the positive diagnosis of those core symptoms of depression may include clinical consequences, it would be of use to integrate all the mentioned concepts in the upcoming new versions of the diagnostic systems DSM-V and ICD-11.     

Behavioral, cognitive, and family therapy for obsessive-compulsive and related disorders.

Behavioral therapy and cognitive therapy, individually and combined, are a solid base in any therapy, the goal of which is to decrease the maladaptive behaviors associated with obsessive-compulsive spectrum disorders. Future research into this area involves two branches: (1) better resolution in what components of current treatments are effective and (2) a better understanding of the cause of OCD. The therapies of choice are behavioral therapy and cognitive therapy, but often what is described as behavioral therapy and cognitive therapy varies. Further refinement of the specific components of behavioral therapy and cognitive therapy that directly apply to OCD is needed. The specific components likely include the use of ERP and rational emotive behavioral therapy but often even these therapies can be parceled into smaller discrete parts. Many facets still have not been explored thoroughly (e.g., the extent of exposure to adverse situations needed, ideal length of therapy, time needed for exposure, and the use of virtual reality versus traditional exposures). A better understanding of the biological basis for OCD also would further the field. A better understanding of the basis of this disorder also would help clinicians to treat it with medication and behavioral therapy. Research into how behavioral therapy and cognitive therapy makes neurophysiologic changes would show the effectiveness of the treatment and a biological basis. Such studies could include the use of MR imaging during different stages in behavioral therapy and the use of functional during therapy to observe changes in the brain. Although OCD still is not fully understood, researchers are now beginning to understand how to treat it, and a solid base of empiric data now exists. The authors hope that investigators will continue research toward a better understanding of this disorder so that clinicians can better help their patients.     

Cognitive behavioral group therapy for anxiety: recent developments

Anxiety disorders occur frequently, and can have a negative impact on the quality of people''s lives. They often begin at an early age and can have some serious consequences. This article is an overview of the recent studies concerning group cognitive-behavioral interventions for anxiety disorders. In the last few years, anxiety disorder prevention for children and adolescents has become an important focus of research work. Group prevention programs are based on standard cognitive behavioral therapy (CBT) strategies and are aimed at preventing anxiety disorders as early as possible. Numerous cognitive behavioral group therapies for children as well as adults have been well studied. There are many CBT protocols that have been developed for treating specific anxiety disorders. Now, specialized CBT programs are available for individuals who suffer from different anxiety disorders, enabling them to be treated together in groups.     

Can premorbid and prodromal markers associated with psychosis be utilized for early detection and secondary prevention of schizophrenia?

The rationale for identifying markers of latent schizophrenia is the evidence that early treatment speeds remission and lessens long-term deterioration. Unfortunately hovever, although the childhood and adolescence of individual psychotics often reveal premorbid deviations from established norms, while epidemiological studies identify cognitive performance and social adjustment as potential premorbid markers, such signs vary widely and no typical prodrome has been identified. Illness-related events or behaviors are not the only factors precipitating the transition from premorbid to prodrome: educational and socioeconomic status are also involved, it follows that there is a controversy surrounding the secondary prevention of schizophrenia: because of the poor specificity of premorbid and prodromal markers, treating such patients implies thai an unacceptably high proportion of individuals who will not ultimately develop florid schizophrenia will be exposed to stigma of a provisional diagnosis of severe mental illness as well as to the adverse effects of treatment Schizophrenia, therefore, is an aggravated illustration of the dilemmas facing much preventive therapy.     

Cognitive-behavioral therapy as an adjunct to serotonin reuptake inhibitors in obsessive-compulsive disorder: an open trial.

BACKGROUND: We report the results of an open trial of cognitive-behavioral therapy (CBT) using exposure and ritual prevention as an adjunct to serotonin reuptake inhibitors (SRIs) in obsessive-compulsive disorder (OCD). We hypothesized that exposure and ritual prevention would significantly reduce OCD symptoms in patients who remained symptomatic despite an adequate trial of an SRI and enable patients to discontinue their medication. METHOD: OCD patients taking an adequate dose of an SRI > or = 12 weeks who remained symptomatic (i.e., a Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score > or = 16) were eligible. While taking a stable dose of an SRI, patients received 17 sessions of exposure and ritual prevention. For the intent-to-treat group, the paired t test was used to compare scores on the Y-BOCS, the National Institute of Mental Health (NIMH) Global OCD scale, the Clinical Global Impressions scale, and the Hamilton Rating Scale for Depression before and after exposure and ritual prevention. RESULTS: Six of 7 eligible patients entered the study, and 5 completed it. All 6 improved on all OCD measures. The mean +/- SD Y-BOCS score was 23.8 +/- 2.6 prior to exposure and ritual prevention and 12.2 +/- 4.3 after it (p < .001). The mean percentage decrease on the Y-BOCS was 49% (range, 26%-61%). Patients were rated by the therapist and rated themselves as much (N = 4) or very much (N = 2) improved. Blood drug levels did not change in most patients during exposure and ritual prevention; thus, the improvement was attributed to this type of therapy. No patients discontinued their medication. CONCLUSION: This open trial suggests that CBT using exposure and ritual prevention can lead to a significant reduction in OCD symptoms in patients who remain symptomatic despite an adequate trial of an SRI.     

Combination pharmacotherapy in Alzheimer's disease

Alzheimer's disease is a progressive, debilitating form of dementia affecting more than 18 million people worldwide. Without a cure, many patients and their families must turn to long-term care institutions during the later stages of the disease. Our current treatments only delay progression and help control behavioral symptoms. In recent years, research within this field has expanded to include many clinical trials on potential drug therapies. However, despite the numerous studies, the enigma of this disease remains. It is difficult yet necessary, to stay abreast of emerging information that may warrant changes in current therapy. Rationale for combination therapy becomes evident as we review the multiple neurochemical pathways common to the disease. This paper will review available information on Alzheimer's disease pharmacotherapy, and evaluate data on the use of combination drug therapy. Individual efficacy, possible synergistic effects, and the safety of combination therapy will also be addressed.     

Neuroimaging-based biomarkers for treatment selection in major depressive disorder

The use of neuroimaging approaches to identify likely treatment outcomes in patients with major depressive disorder is developing rapidly. Emerging work suggests that resting state pretreatment metabolic activity in the fronto-insular cortex may distinguish between patients likely to respond to psychotherapy or medication and may function as a treatment-selection biomarker. In contrast, high metabolic activity in the subgenual anterior cingulate cortex may be predictive of poor outcomes to both medication and psychotherapy, suggesting that nonstandard treatments may be pursued earlier in the treatment course. Although these findings will require replication before clinical adoption, they provide preliminary support for the concept that brain states can be measured and applied to the selection of a specific treatment most likely to be beneficial for an individual patient.     

Cognitive-behavioral therapy for anxiety disorders: an update on the empirical evidence

A large amount of research has accumulated on the efficacy and effectiveness of cognitive-behavioral therapy (CBT) for anxiety disorders including posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder, generalized anxiety disorder, social anxiety disorder, and specific phobia. The purpose of the current article is to provide an overview of two of the most commonly used CBT methods used to treat anxiety disorders (exposure and cognitive therapy) and to summarize and discuss the current empirical research regarding the usefulness of these techniques for each anxiety disorder. Additionally, we discuss the difficulties that arise when comparing active CBT treatments, and we suggest directions for future research. Overall, CBT appears to be both efficacious and effective in the treatment of anxiety disorders, but dismantling studies are needed to determine which specific treatment components lead to beneficial outcomes and which patients are most likely to benefit from these treatment components.     

中国强迫症研究的未来方向

强迫症是精神科的常见疾病之一。过去三十年,强迫症患者可以从药物治疗和心理治疗中获益,总体结局大为改善,但我国强迫症的基础与临床研究相对薄弱,未成体系,有效的认知行为治疗没有得到应有的普及和推广。因此,未来我国在建立高质量的中国强迫症研究数据库基础上,应重点强化强迫症的基础研究、核心症状、残留症状、临床亚型、共病机制和干预,及其心理治疗、心理治疗联合药物治疗或物理治疗等临床研究。