Combined Pharmacological Treatment Research Articles

The Cochrane Library and the treatment of childhood and adolescent anxiety disorders: an overview of reviews

AbstractBackgroundAnxiety disorders are among the most common psychiatric disorders diagnosed during childhood and adolescence. Reported lifetime prevalence of children or adolescents meeting criteria for at least one anxiety disorder in industrialized countries ranges from 8–27%. Current treatment includes psychotherapy (cognitive and behavioural therapies) as well as medication which is almost always used together with psychotherapy, rather than as a stand‐alone treatment.ObjectiveTo synthesize the evidence currently in the Cochrane Database of Systematic Reviews (CDSR) related to the question: ‘In the treatment of childhood and adolescent anxiety disorders, which pharmacologic or nonpharmacologic treatments are known to improve symptom response, response rates, functional capacity, adherence, persistence, and acceptability as well as increase diagnostic remission and decrease adverse events?’.MethodsThe CDSR was searched using the term ‘anxiety disorders’ in the title for all systematic reviews examining pharmacologic and nonpharmacologic interventions for the treatment of anxiety disorders in children and adolescents, including pharmacotherapy and psychotherapy. Data were extracted and entered into tables; data were synthesized using qualitative and quantitative methods.Main ResultsOf the studies included in the CDSR, treatment of childhood and adolescent anxiety disorders with cognitive behavioural therapy (CBT) led to significant reductions in anxiety symptoms and increased recovery. Treatment with CBT or behavioural therapy (BT) led to notable reductions in Obsessive–Compulsive Disorder (OCD) severity and a reduced risk of treatment failure. Use of selective serotonin reuptake inhibitors (SSRIs) and the selective norepinephrine reuptake inhibitor (SNRI) venlafaxine were superior to placebo in treating OCD and other anxiety disorders. There was no clear evidence that any particular SSRI or venlafaxine was most efficacious or best tolerated. While few studies were available, CBT combined with a SSRI or SNRI led to significant reductions in both anxiety and OCD symptoms. Psychotherapy (CBT/BT), used alone or in combination with medication, had a mixed impact on reducing risk of treatment failure for OCD.Author's ConclusionsFor childhood and adolescent anxiety disorders, including OCD, the CDSR reviews suggest that psychotherapy treatments are efficacious in reducing symptom severity. Although the CDSR does not include a number of recent research publications on CBT, these newer studies further reinforce CBT efficacy. Pharmacotherapy evidence from the CDSR supports using medication in treating anxiety disorders, and while few studies examined combined pharmacological and psychological treatment, results to date are also favourable for this combination. Clinicians should rely on expert consensus guidelines vis‐à‐vis this evidence as treatment decision‐making should be moderated by the patient's illness severity. Psychotherapy remains the first line treatment for mild to moderate symptoms, whereas pharmacotherapy is used for severe or treatment‐resistant disorders. In conclusion, there is a body of literature in the CDSR to support evidence‐based treatment decisions for pediatric anxiety disorders; however, as this is a field that is rapidly expanding its knowledge base, efforts must be made to ensure the most recent evidence is consistently incorporated. Copyright © 2010 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Adding Psychotherapy to Pharmacotherapy in the Treatment of Depressive Disorders in Adults

A considerable number of studies has examined whether adding psychotherapy to pharmacotherapy results in stronger effects than pharmacotherapy alone. However, earlier meta-analyses in this field have included only a limited number of available studies and did not conduct extended subgroup analyses to examine possible sources of heterogeneity. We used a database derived from a comprehensive literature search in PubMed, PsycINFO, EMBASE, and the Cochrane Central Register of Controlled Trials for studies published from 1966 to January 2008 that examined the psychological treatment of depression. The abstracts of these studies were identified by combining terms indicative of psychological treatment and depression. We included randomized trials in which the effects of a pharmacologic treatment were compared to the effects of a combined pharmacologic and psychological treatment in adults with a depressive disorder. For each of the studies, we calculated a standardized mean effect size indicating the difference between pharmacotherapy and the combined treatment at posttest. We also coded major characteristics of the population, the interventions, and the quality and design of the study. Twenty-five randomized trials, with a total of 2,036 patients, were included. A mean effect size of d = 0.31 (95% CI, 0.20 approximately 0.43) was found for the 25 included studies, indicating a small effect in favor of the combined treatment over pharmacotherapy alone. Studies aimed at patients with dysthymia resulted in significantly lower effect sizes compared to studies aimed at patients with major depression, a finding that suggests that the added value of psychotherapy is less in patients with dysthymia. The dropout rate was significantly lower in the combined treatment group compared to the pharmacotherapy only group (OR = 0.65; 95% CI, 0.50 approximately 0.83). Psychotherapy seems to have an additional value compared to pharmacotherapy alone for depression.

Electroconvulsive therapy‐associated Pisa syndrome in clozapine treatment

PISA SYNDROME is a rare type of truncal dystonia. It is characterized by sustained tonic flexion of the trunk with the head to one side. There have been several reports indicating that this movement side-effect is related to the use of classical or atypical antipsychotics.1 There have been no reports, however, of this movement disorder occurring in the patients who receive electroconvulsive therapy (ECT). We here report a schizophrenic patient whose refractory psychosis did not respond to 400 mg/day of clozapine and who developed Pisa syndrome when she received additional ECT. A 57-year-old female patient had chronic and treatment-refractory schizophrenia for 30 years. She had no past medical or surgical history, and there was no family history of psychiatric disorders. The patient has been hospitalized in the chronic ward at Armed Forces Beitou Hospital, Taipei, since 2003. On 4 April 2006 the patient's symptoms of paranoid thoughts, auditory hallucinations, and violent behavior became exacerbated and she was transferred to the acute ward. The patient was initially treated with clozapine and the dose was gradually titrated up to 400 mg/day, but her psychosis and violence did not respond to the clozapine therapy. As a result, the patient had her first bilateral ECT on 21 April 2006. After the patient had received the 10th ECT she was noted to have symptoms of sustained tonic flexion of her head and trunk, tilting to the right side. Due to the likelihood of ECT-associated Pisa syndrome, her ECT was discontinued. The clozapine dose was reduced from 400 mg/day down to 25 mg/day. Biperiden 2 mg three times a day was prescribed. On this regimen the patient's dystonic symptoms gradually remitted, and clozapine 300 mg/day was then resumed. Subsequent brain computed tomography and electroencephalography showed no abnormalities, and the patient remained in a relatively stable condition on clozapine. The present case suggests that not only classical or atypical antipsychotics can cause Pisa syndrome,1 but also ECT can lead to this unusual movement side-effect. Risk factors for developing Pisa syndrome during neuroleptic therapy include combined pharmacological treatment, old age, female gender, and the presence of organic brain disorder.1 In the present patient, potential risk factors for developing Pisa syndrome included (i) a relatively high dose of clozapine, (ii) old age, (iii) female gender, and (iv) bilateral ECT. Reductions in dose or discontinuation of antipsychotics, and use of anticholinergic agents have been suggested to resolve neuroleptic-associated Pisa syndrome.1 The present patient's Pisa syndrome gradually improved when ECT was stopped, clozapine was tapered and anticholinergic medication was added. We thus think that the Pisa syndrome in the present patient may have been triggered by ECT in the presence of clozapine therapy. Dopaminergic–cholinergic imbalances have been suggested to play a role in the development of antipsychotic-induced Pisa syndrome.1 This raises the possibility that such imbalances are also involved in the underlying mechanisms of ECT-associated Pisa syndrome. Last, we would like to advise that antipsychotic dose should be reduced before use of ECT in the treatment of refractory schizophrenic patients who have risk factors for Pisa syndrome.

Neuropsychological rehabilitation program and behavioral disturbances in early-stage Alzheimer patients.

Alzheimer’s disease (AD) is the most frequent cause of dementia and cholinesterase inhibitors are the available treatment in the mild stage. However cognitive rehabilitation has shown satisfactory results when combined with pharmacological treatment. Behavioral alteration is common in AD patients, which burdens caregivers and raises the risk of institutionalization. Providing caregivers guidance may enable them to assure better quality of life for patient and caregiver and lower institutionalization rates.ObjectiveTo evaluate the effects of a neuropsychological rehabilitation program (NRP) combined with pharmacological treatment in early stage AD patients.MethodsWe studied 12 AD patients (6 women), average age 75.42 (6.22) with 9.58 (5.6) years education in use of stable doses of cholinesterase inhibitors. Cognitive performance was evaluated using Mini-Mental State Examination (MMSE) and Alzheimer´s Disease Assessment Scale-cognitive (ADAS-Cog). Caregivers responded to Neuropsychiatric Inventory (NPI) and Functional Activities Questionnaire (FAQ) at initial evaluation (T1), and after 8 months of rehabilitation program (T2). The program comprised two sessions every week and family guidance every fortnight.ResultsMMSE (T1:23.25 (1.82)/T2:23.42 (2.81); ADAS-Cog (T1:17.11 (6.73)/T2:21.2 (8.59); NPI (T1:23.42 (23.38)/T2:19.83 (17.73); FAQ (T1:10.67 (7.24)/T2: 13.92 (6.92).ConclusionsThese results show the importance of providing guidance and support for caretakers. Study limitations were the small number of patients and absence of a control group with only drug treatment to compare with combined pharmacological and rehabilitation treatments.

Effectiveness of cognitive-analytic therapy (CAT) in major depression and systemic lupus erythematosus: a case report

Background A significant number of patients with systemic lupus erythematosus (SLE) suffer from depression. Most episodes of depression in SLE seem to be caused by non-organic factors i.e. patients' responses to the burden of disease and the social consequences of the disease. Therapeutic interventions should consist of a combined pharmacological and non-pharmacological treatment. Cognitive Analytic Psychotherapy (CAT) is a form of brief psychotherapy -its effectiveness has been showed in several studies with patients who manifested various psychological problems. The present study aims to present the appliance of CAT in a patient with SLE and depression.

Prevention of Recurrent Esophageal Variceal Hemorrhage

Variceal rebleeding is a very frequent and severe complication in cirrhotic patients; therefore, its prevention should be mandatory. Lately several studies demonstrated that the rate of rebleeding was decreased by 40% and overall survival is improved by 20% with beta-blockers. However, this treatment presents some problems, such as the number of nonresponders and contraindications for its use. Recent trials found that the combination of beta-blockers with mononitrate of isosorbide to be superior to beta-blockade alone. Furthermore, endoscopic band ligation also shown to decrease the frequency of rebleeding, complications, and death compared with sclerotherapy and should be the preferred endoscopic treatment. In addition, the comparison between combined pharmacologic treatment with endoscopic treatment present similar rebleeding and mortality rates. More recently, the addition of nadolol to endoscopic band ligation increased the efficacy of endoscopy alone in the prevention of variceal rebleeding. These studies suggest that banding plus drugs could be the treatment of choice for the prophylaxis of rebleeding. When these treatments fail, the recommendation is to use transjugular intrahepatic portosystemic shunt (TIPS) or surgical shunts. Both treatments are effective in preventing rebleeding; however, they are associated with a greater risk of encephalopathy. The comparison of portacaval shunts with TIPS demonstrated that TIPS patients presented higher rebleeding, treatment failure, and transplantation. Another randomized controlled trial comparing distal splenorenal shunt with TIPS shows that variceal rebleeding was similar in both groups without differences in encephalopathy and mortality. The only difference observed was the higher rate of reintervention observed in the TIPS group to maintain his patency.

Development of a parent training program for children with pervasive developmental disorders

AbstractParent delivered interventions based on applied behavior analysis (ABA) for children with Pervasive Developmental Disorders (PDDs) have been evaluated using primarily single‐subject design methodology or small case series. While the results of these evaluations are encouraging, an important next step is to standardize the interventions to allow for replication across sites, in studies with large samples and measures of long‐term, clinically meaningful outcomes such as improvements in children's functioning and their relationships with parents. Accordingly, the Research Units on Pediatric Psychopharmacology and Psychosocial Interventions (RUPP Autism Network) assembled a detailed manual for a structured behavioral parent training (PT) program, developed treatment fidelity and training procedures, and conducted a pilot, feasibility study. The PT program is part of a large scale, multisite study intended to determine the efficacy of combined pharmacological treatment and behavioral intervention to improve behavior and adaptive functioning in children with PDD. This paper discusses the rationale for this project. A companion paper provides the results of our feasibility study on the PT program. Copyright © 2007 John Wiley & Sons, Ltd.

Suboptimal Use of Cardioprotective Drugs in Newly Treated Elderly Individuals With Type 2 Diabetes

Cardiovascular disease is the main complication experienced by elderly individuals with diabetes (1). Despite randomized trials showing the benefits of individual (2–4) or combined (5) pharmacological treatments of cardiovascular risk factors in diabetes, observational studies have shown suboptimal use of medications (6–8). However, little is known about the use of cardioprotective medication among elderly individuals who were not already taking it before diabetes treatment was undertaken. We therefore studied a population of elderly individuals with type 2 diabetes in the province of Quebec, Canada, who had not been treated with any antihypertensive, lipid-lowering, or antiplatelet drugs in the year before oral antidiabetes drug initiation. We assessed whether they used a comprehensive cardioprotective regimen (CCR) of those three medications in the year following oral antidiabetic initiation. We also identified the determinants of a CCR use. We carried out a population-based inception cohort study using the Quebec Diabetes Surveillance System, which is the product of linking public health administrative databases managed by the Quebec Health Insurance Board. It includes information on patient demographics, physician and hospital services, and data from the public drug plan for individuals who had been diagnosed with diabetes. We selected individuals aged ≥66 years who had initiated an oral antidiabetes medication treatment between 1 January 1998 and 31 December 2002. The date of the first claim was the index date. We excluded individuals who had …

ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington's disease

Chromatin remodeling and transcription regulation are tightly controlled under physiological conditions. It has been suggested that altered chromatin modulation and transcription dysfunction may play a role in the pathogenesis of Huntington's disease (HD). Increased histone methylation, a well established mechanism of gene silencing, results in transcriptional repression. ERG-associated protein with SET domain (ESET), a histone H3 (K9) methyltransferase, mediates histone methylation. We show that ESET expression is markedly increased in HD patients and in transgenic R6/2 HD mice. Similarly, the protein level of trimethylated histone H3 (K9) was also elevated in HD patients and in R6/2 mice. We further demonstrate that both specificity protein 1 (Sp1) and specificity protein 3 (Sp3) act as transcriptional activators of the ESET promoter in neurons and that mithramycin, a clinically approved guanosine-cytosine-rich DNA binding antitumor antibiotic, interferes with the DNA binding of these Sp family transcription factors, suppressing basal ESET promoter activity in a dose dependent manner. The combined pharmacological treatment with mithramycin and cystamine down-regulates ESET gene expression and reduces hypertrimethylation of histone H3 (K9). This polytherapy significantly ameliorated the behavioral and neuropathological phenotype in the R6/2 mice and extended survival over 40%, well beyond any existing reported treatment in HD mice. Our data suggest that modulation of gene silencing mechanisms, through regulation of the ESET gene is important to neuronal survival and, as such, may be a promising treatment in HD patients.

Kombinierte pharmakologische und psychotherapeutische Behandlung im frühen Stadium einer Alzheimer-Demenz über 30 Monate

The present case delineates the results of a 30-month combined pharmacological and psychotherapeutic treatment in a mildly to moderately depressed patient with early Alzheimer's dementia. At onset and during following visits, clinical examination and standardized test procedures for measuring cognitive and emotional changes were completed. Treatment results reveal a consistent benefit to cognitive levels and emotional distress over time. The present example of a mildly demented, depressed Alzheimer's patient shows a therapeutic outcome which is markedly superior to usual expectations in Alzheimer's treatment and encourages combination of therapeutic strategies in early stages of the disease.

Benefits of Long-Term Fibromyalgia Syndrome Treatment with a Multidisciplinary Program

Objectives: To systematically assess the effectiveness of a combination of pharmacologic and nonpharmacologic long-term treatment interventions for the fibromyalgia syndrome [FMS].Methods: Participants involved in an outpatient, one year, multidisciplinary treatment program within a health care setting were studied. After being screened for eligibility, participants in the treatment sample took part in combined standard pharmacologic treatment and non-pharmacologic treatment [including cognitive behavioral therapy/psychoeducational classes, exercise, massage, auricular therapy, microcurrent therapy, and nutritional counseling] in a case controlled manner. A control sample received standard medical care in a rheumatologist's office. Pre- versus post-treatment outcome variables of psychological symptoms and personality features, as measured by the Multiaxial Diagnostic Inventory–Revised, overall impact of FMS as measured by the Fibromyalgia Impact Questionnaire, overall health status as measured by the Shor...

What Does the Future Hold for Irritable Bowel Syndrome and the Functional Gastrointestinal Disorders?

Our understanding of irritable bowel syndrome and the functional GI disorders has grown considerably over the last 15 years. In part this relates changes in their classification and definition from being due solely to motility disturbances, to being symptom based (eg, Rome criteria). This opened the door to the study of many other factors that contribute to the clinical expression of these disorders, including visceral hypersensitivity, sensitization, altered mucosal immunity, and dysfunction in brain-gut regulatory processes. New knowledge has been gained in areas of genetics, central nervous system and enteric nervous system neurotransmitters of motility, sensitivity and secretion, the effect of altered mucosal inflammation on cytokine and paracrine activation, and neural sensitization, postinfectious disorders, the influence of psychologic stress on gut functioning via alterations in regulatory pathways (eg, hypothalamic-pituitary adrenal axis, or pain regulatory system like the cingulate cortex), improved accuracy of diagnosis using Rome II criteria plus "red flags" the institution of behavioral treatments, and the use of new pharmacologic treatments both at the gut and brain level. Future research will improve upon this new knowledge via basic and translational studies of neuropeptide signaling with new neurotransmitters, new knowledge on the mechanisms for central nervous system-enteric nervous system communication and dysfunction, and more advanced clinical research on education, communication skills and their effects on outcome, genetics, pharmacogenetics and genetic epidemiology, better understanding as to how certain psychosocial domains (eg, catastrophizing, abuse) affect symptom behavior and outcome, newer pharmacologic treatments, and the use of combined pharmacologic and behavioral treatment packages. I am pleased to have the opportunity to provide a personal perspective on what the future will be for irritable bowel syndrome and the other functional GI disorders. Having been involved in this field for almost 30 years, I have been fortunate to witness tremendous changes. The focus of this presentation is to address the advances that have recently occurred that set the stage for proposing future research to help move the field along and ultimately to help our patients.

Perfil metabólico y deterioro de órganos diana en hipertensos esenciales según el control de la presión arterial en la consulta

To evaluate the degree of metabolic control and end-organ damage in a group of hypertensive patients with poor and good blood pressure (BP) control in primary health care centers. Observational study with diagnostic intervention, performed in 16 primary care centers of Burgos (Spain). 207 patients (120 with good BP control and 87 with poor BP control) with pharmacological treatment were included in the study. The following parameters were determined: clinic history, casual BP, 24-h ambulatory blood pressure monitoring (ABPM), electrocardiography, and clinic analysis in plasma and 24-hour urine. The 32% and 31% of patients respectively were receiving combined pharmacological treatment. No significant differences were detected between the two groups for the levels of c-HDL > 130 mg/dl (62% vs. 62%), microalbuminuria (5% vs. 10%) and basal glucose levels > 126 mg/dl (105 vs. 15%). There was a significant proportion of patients with poor clinical BP control with left ventricular hypertrophy (13% vs. 34%; p < 0,001), impaired renal function (3% vs. 11%; p < 0,05), mean hematocrit value (41,9 +/- 4,5 vs. 43,7 +/- 3,5; p < 0,01) and different degree on BP control by ABPM (1,6% vs. 16%: p < 0,01). Our hypertensive patients with poor BP clinical control showed more end-organ damage than those with good control, although they have a similar metabolic profile. The access to ABPM by primary health care centers could modify the therapeutic management in a significant subgroup of hypertensive patients with poor BP control.

Impact of combined pharmacologic treatment with clopidogrel and a statin on outcomes of patients with non-ST-segment elevation acute coronary syndromes: perspectives from a large multinational registry

To evaluate clinical outcomes associated with the combined use of clopidogrel and statins vs. clopidogrel alone on a background of aspirin therapy in patients with the spectrum of acute coronary syndromes (ACS). Utilizing data from the Global Registry of Acute Coronary Events, we studied 15 693 patients admitted with non-ST-segment elevation myocardial infarction (MI) or unstable angina, dividing them according to discharge medications: aspirin alone (group I); aspirin + clopidogrel (group II); aspirin + statin (group III); aspirin + clopidogrel + statin (group IV). Among the groups of patients in whom clopidogrel was used (groups II and IV), group II patients were older, more likely to have prior MI, but less likely to have a history of prior revascularization. In-hospital cardiac catheterization and revascularization rates were similar between groups II and IV. Importantly, Kaplan-Meier analysis showed that the 6 month mortality rate was lower in group IV (log-rank test 22.8, P<0.0001). The hazard ratio for the 6 month mortality rate was adjusted using the Cox proportional hazard model for confounding variables and for propensity score, and the 6 month mortality rate for patients in group IV remained lower compared with those in group II [0.59 (0.41-0.86), P<0.0001]. Our data suggest that the combination of clopidogrel with a statin has synergistic effects on the clinical outcomes of patients with non-ST-segment elevation ACS.

Comorbidity of obsessive-compulsive disorder and depression: prevalence, symptom severity, and treatment effect.

The goal of this study was to investigate the co-occurrence of depressive disorders in obsessive-compulsive disorder (OCD) and the effect of these disorders on combined pharmacologic and behavioral treatment for OCD. A retrospective chart analysis was performed on baseline ratings of 120 OCD patients and posttreatment ratings of 72 of these patients. For depressive symptoms, the Montgomery-Asberg Depression Rating Scale and the Self-Rating Depression Scale were applied; for obsessive-compulsive symptoms, the Yale-Brown Obsessive Compulsive Scale and the Maudsley Obsessive Compulsive Inventory were used; and for general anxiety symptoms, the Self-Rating Anxiety Scale, the Clinical Anxiety Scale, and the State-Trait Anxiety Inventory were given. One third of the OCD patients in our sample were found to be depressed. Symptom severity on OCD symptoms at baseline did not differ between depressed and nondepressed OCD patients; on general anxiety symptoms, the comorbid group was more severely affected. Both depressed and nondepressed OCD patients responded well to treatment, as reflected in assessments for depressive, obsessive-compulsive, and general anxiety symptoms. However, comorbid depression had a negative effect on treatment: depressed OCD patients showed less improvement than nondepressed OCD patients on most scales. Depression frequently accompanies OCD and appears to affect treatment outcome negatively. While both groups of patients improved with combination treatment, the OCD-alone group had more improvement than the group that had comorbid depression.

Fibromyalgia: diagnosis, pathogenesis, and treatment

Fibromyalgia is characterized by chronic widespread pain and the presence of tender points, often accompanied by several non-specific symptoms, such as fatigue, depressive mood, and sleep disturbances. The apparent overlap between fibromyalgia and other syndromes, such as chronic fatigue and irritable bowel, is not sufficient cause to consider all these syndromes as manifestations of a single syndrome. Fibromyalgia is a multifaceted problem. Central afferent pain amplification and perhaps also impaired descending pain inhibition are supposed to underlie widespread pain. Neuroendocrine perturbations, sleep disturbances, health beliefs, mood disorder, and physical deconditioning play a role in the modulation and perseverance of pain and other symptoms. It is extremely difficult to mitigate chronic generalized pain and to deal with other symptoms in fibromyalgia. A uniform intervention strategy is missing. Essential in the tailored management of fibromyalgia are an enhancement of functional capacities and quality of life, and the symptomatic treatment of individual symptoms such as pain, distress, and sleep disturbances. Rather than analysing monotherapy per se, the objective in future evaluations should be to try to find the combined pharmacological or non-pharmacological treatment of choice for specific subgroups of patients.

Pisa Syndrome (Pleurothotonus)

Pisa syndrome is usually regarded as a rare adverse event of neuroleptic medication. However, its frequency and predisposing factors have yet to be defined. Here, we investigated risk factors of Pisa syndrome occurring in a large population of psychiatric patients surveyed during a multicenter drug safety project. Twenty episodes of Pisa syndrome were documented in 17 patients within a population of 45,000 psychiatric patients monitored by a multicenter drug safety surveillance project (Projekt zur Uberwachung der Arzneimittelsicherheit in der Psychiatrie) between 1990 and 1997. All results were related to the epidemiologic data provided for this population and systematically analyzed regarding history of medication, current medication, comedication, and clinical course. A constellation of putative risk factors was found in the majority of patients: previous treatment with classical neuroleptics, combined pharmacologic treatment, female gender, old age, and the presence of an organic brain disorder. Given these risk factors, Pisa syndrome was also documented with atypical neuroleptic drugs such as clozapine, olanzapine, and sertindole. We conclude that Pisa syndrome is a very rare adverse event occurring with neuroleptic treatment. In patients exhibiting the reported constellation of risk factors, neuroleptic drugs should be administered with particular caution.

The Kleine-Levin Syndrome as a Neuropsychiatric Disorder: A Case Report

The Kleine-Levin syndrome (KLS) is characterized by periodic, sudden-onset episodes of hypersomnia, compulsive hyperphagia, and behavioral-emotional disorders (typically indiscriminate hypersexuality, irritability, impulsive behaviors), lasting from a few days to a few weeks, with almost complete remission in the intercritical periods. Depression, confusion, and thought disorders are frequently associated with the critical symptomatology, and they may suggest other psychiatric diagnoses (schizophrenia, mood disorder, conversion disorder) or a substance abuse. A diencephalic-hypothalamic dysfunction is suspected, even if this composite symptomatology cannot easily be linked to a simple mechanism. The aim of this article is to illustrate problems in differential diagnosis, using a case approach. History, course, and therapeutic intervention in a 21-year-old patient with KLS, associated with a clear psychiatric symptomatology and a critical affective pattern, is reported. Psychiatric correlates of KLS are discussed, including the relationship with affective disorders and the possible emotional impact of the attacks. Implications regarding a combined psychological and pharmacological treatment are also discussed.

Exposure and response prevention for obsessive thoughts

Although there have always been reports of people suffering from “ruminations,” “pure obsessions,” and similar phenomena where no overt compulsions are present, this group has traditionally been considered rare. The common belief was that this specific form, obsessive thoughts without overt-compulsions, was a rare but clinically interesting variant of OCD and was highly resistant to treatment. During the last 15 years there have been a number of significant advances that have culminated in the development of effective treatments. The treatment described here is based on a manual developed in the context of a controlled trial of cognitive-behavior therapy for obsessive thoughts (Freeston et al., 1997). After briefly addressing diagnostic issues and assessment, step-by-step guidelines describe how to present and conduct exposure and response prevention for obsessive thoughts. Other issues addressed include troubleshooting, terminating treatment, relapse prevention, and combined pharmacological and psychological treatment.

Recent advances regarding attention deficit-hyperactivity disorder in adolescence.

This paper reviews recent studies of attention deficit-hyperactivity disorder, focusing on research with implications for adolescents. Only 10 of the 31 recent investigations discussed employed an exclusively adolescent sample, necessitating considerable extrapolation from studies of children or adults or mixed samples with a wide range of ages. Significant advances include increased accuracy of predicting negative outcomes and the identification of adaptive skill dysfunction. Further information has become available on the long-term impact of attention deficit-hyperactivity disorder, and additional data have been reported on risk factors. Other reports have described typical services provided by pediatric and family medicine practices for attention deficit-hyperactivity disorder; beneficial effects of combined behavioral and pharmacologic treatment; absence of adverse effects of methylphenidate on cognitive constriction or tics; and disappointing results for nonstimulant pharmacotherapy. A National Institute of Mental Health multisite treatment study has recently been initiated.